Pack Emolan Bloqueador SPF 60

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Pack Emolan Bloqueador SPF 60 uses

Pack Emolan Bloqueador SPF 60 consists of 4-Methylbenzylidene Camphor, Avobenzone, C12-15 Alkyl Benzoate, Carbomer, Cethyl Alcohol, Ciclomethicone, Diazolidinyl Urea, Diethanolamine Cetyl Phosphate, Dimethicone, Edetate Disodium, Ensulizole, Glycerol, Isopropyl Palmitate, Methylparaben, Perfume, Polypropylene Glycol Dicaprylate, Potassium Phosphate, Povidone Eicosene Copolymer, Propylene Glycol, Propylparaben, Sodium Phosphate Dibasic, Stearic Acid, Titanium Dioxide, Triethanolamine, Vitamin E (Tocopherol Acetate), Water.

Dimethicone:


This medication is used as a moisturizer to treat or prevent dry, rough, scaly, itchy skin and minor skin irritations (e.g., diaper rash, skin burns from radiation therapy). Emollients are substances that soften and moisturize the skin and decrease itching and flaking. Some products (e.g., zinc oxide, white petrolatum ) are used mostly to protect the skin against irritation (e.g., from wetness). Dry skin is caused by a loss of water in the upper layer of the skin. Emollients/moisturizers work by forming an oily layer on the top of the skin that traps water in the skin. Petrolatum, lanolin, mineral oil and Pack Emolan Bloqueador SPF 60 (Dimethicone) are common emollients. Humectants, including glycerin, lecithin, and propylene glycol, draw water into the outer layer of skin. Many products also have ingredients that soften the horny substance (keratin) that holds the top layer of skin cells together (e.g., urea, alpha hydroxy acids such as lactic/citric/glycolic acid, and allantoin ). This helps the dead skin cells fall off, helps the skin keep in more water, and leaves the skin feeling smoother and softer.

Edetate Disodium:


INDICATIONS AND USAGE

Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium is indicated for the reduction of blood levels and depot stores of lead in lead poisoning (acute and chronic) and lead encephalopathy, in both pediatric populations and adults.

Chelation therapy should not replace effective measures to eliminate or reduce further exposure to lead.

CONTRAINDICATIONS

Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium should not be given during periods of anuria, nor to patients with active renal disease or hepatitis.

WARNINGS

PRECAUTIONS

General Precautions

Pack Emolan Bloqueador SPF 60 calcium disodium may produce the same renal damage as lead poisoning, such as proteinuria and microscopic hematuria. Treatment-induced nephrotoxicity is dose-dependent and may be reduced by assuring adequate diuresis before therapy begins. Urine flow must be monitored throughout therapy which must be stopped if anuria or severe oliguria develop. The proximal tubule hydropic degeneration usually recovers upon cessation of therapy. Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium must be used in reduced doses in patients with pre-existing mild renal disease. Patients should be monitored for cardiac rhythm irregularities and other ECG changes during intravenous therapy.

Information for patients

Patients should be instructed to immediately inform their physician if urine output stops for a period of 12 hours.

Laboratory tests

Urinalysis and urine sediment, renal and hepatic function and serum electrolyte levels should be checked before each course of therapy and then be monitored daily during therapy in severe cases, and in less serious cases after the second and fifth day of therapy. Therapy must be discontinued at the first sign of renal toxicity. The presence of large renal epithelial cells or increasing number of red blood cells in urinary sediment or greater proteinuria call for immediate stopping of Pack Emolan Bloqueador SPF 60 calcium disodium administration. Alkaline phosphatase values are frequently depressed (possibly due to decreased serum zinc levels), but return to normal within 48 hours after cessation of therapy. Elevated erythrocyte protoporphyrin levels (> 35 mcg/dl of whole blood) indicate the need to perform a venous blood lead determination. If the whole blood lead concentration is between 25–55 mcg/dl a mobilization test can be considered.7,8 (See Diagnostic Test .) An elevation of urinary coproporphyrin (adults: > 250 mcg/day; pediatric patients under 80 lbs: > 75 mcg/day) and elevation of urinary delta aminolevulinic acid (ALA) (adults: > 4 mg/day; pediatric patients: > 3 mg/m2/day) are associated with blood lead levels > 40 mcg/dl. Urinary coproporphyrin may be falsely negative in terminal patients and in severely iron-depleted pediatric patients who are not regenerating heme.9 In growing pediatric patients long bone x-rays showing lead lines and abdominal x-rays showing radio-opaque material in the abdomen may be of help in estimating the level of exposure to lead.

Drug Interactions

There is no known drug interference with standard clinical laboratory tests. Steroids enhance the renal toxicity of Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium in animals.7 Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium interferes with the action of zinc insulin preparations by chelating the zinc.7

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term animal studies have not been conducted with Pack Emolan Bloqueador SPF 60 calcium disodium to evaluate its carcinogenic potential, mutagenic potential or its effect on fertility.

Pregnancy

Category B

One reproduction study was performed in rats at doses up to 13 times the human dose and revealed no evidence of impaired fertility or harm to the fetus due to Pack Emolan Bloqueador SPF 60.10 Another reproduction study performed in rats at doses up to about 25 to 40 times the human dose revealed evidence of fetal malformations due to Pack Emolan Bloqueador SPF 60 (Edetate Disodium), which were prevented by simultaneous supplementation of dietary zinc.11 There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery

Pack Emolan Bloqueador SPF 60 (Edetate Disodium) has no recognized use during labor and delivery, and its effects during these processes are unknown.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Pack Emolan Bloqueador SPF 60 is administered to a nursing woman.

Pediatric Use

Since lead poisoning occurs in pediatric populations and adults but is frequently more severe in pediatric patients, Pack Emolan Bloqueador SPF 60 (Edetate Disodium) is used in patients of all ages. The intramuscular route is preferred by some for young pediatric patients. In cases where the intravenous route is necessary, avoid rapid infusion. (See WARNINGS.) Urine flow must be monitored throughout therapy; Pack Emolan Bloqueador SPF 60 (Edetate Disodium) therapy must be stopped if anuria or severe oliguria develops. (See General Precautions .) At no time should the recommended daily dosage be exceeded. (See DOSAGE AND ADMINISTRATION .)

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ADVERSE REACTIONS

The following adverse effects have been associated with the use of Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium:

Body as a Whole: pain at intramuscular injection site, fever, chills, malaise, fatigue, myalgia, arthralgia.

Cardiovascular: hypotension, cardiac rhythm irregularities.

Renal: acute necrosis of proximal tubules (which may result in fatal nephrosis), infrequent changes in distal tubules and glomeruli.

Urinary: glycosuria, proteinuria, microscopic hematuria and large epithelial cells in urinary sediment.

Nervous System: tremors, headache, numbness, tingling.

Gastrointestinal: cheilosis, nausea, vomiting, anorexia, excessive thirst.

Hepatic: mild increases in SGOT and SGPT are common, and return to normal within 48 hours after cessation of therapy.

Immunogenic: histamine-like reactions (sneezing, nasal congestion, lacrimation), rash.

Hematopoietic: transient bone marrow depression, anemia.

Metabolic: zinc deficiency, hypercalcemia.

OVERDOSAGE

Symptoms

Inadvertent administration of 5 times the recommended dose, infused intravenously over a 24 hour period, to an asymptomatic 16 month old patient with a blood lead content of 56 mcg/dl did not cause any ill effects. Pack Emolan Bloqueador SPF 60 calcium disodium can aggravate the symptoms of severe lead poisoning, therefore, most toxic effects (cerebral edema, renal tubular necrosis) appear to be associated with lead poisoning. Because of cerebral edema, a therapeutic dose may be lethal to an adult or a pediatric patient with lead encephalopathy. Higher dosage of Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium may produce a more severe zinc deficiency.

Treatment

Cerebral edema should be treated with repeated doses of mannitol. Steroids enhance the renal toxicity of Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium in animals and, therefore, are no longer recommended.7 Zinc levels must be monitored. Good urinary output must be maintained because diuresis will enhance drug elimination. It is not known if Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium is dialyzable.

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DOSAGE AND ADMINISTRATION

When a source for the lead intoxication has been identified, the patient should be removed from the source, if possible. The recommended dose of Pack Emolan Bloqueador SPF 60 for asymptomatic adults and pediatric patients whose blood lead level is < 70 mcg/dl but > 20 mcg/dl (World Health Organization recommended upper allowable level) is 1000 mg/m2/day whether given intravenously or intramuscularly.

For adults with lead nephropathy, the following dosing regimen has been suggested: 500 mg/m2 every 24 hours for 5 days for patients with serum creatinine levels of 2–3 mg/dl, every 48 hours for 3 doses for patients with creatinine levels of 3–4 mg/dl, and once weekly for patients with creatinine levels above 4 mg/dl. These regimens may be repeated at one month intervals.12

Pack Emolan Bloqueador SPF 60 (Edetate Disodium), used alone, may aggravate symptoms in patients with very high blood lead levels. When the blood lead level is > 70 mcg/dl or clinical symptoms consistent with lead poisoning are present, it is recommended that Pack Emolan Bloqueador SPF 60 (Edetate Disodium) be used in conjunction with BAL (dimercaprol). Please consult published protocols and specialized references for dosage recommendations of combination therapy.14–18

Therapy of lead poisoning in adults and pediatric patients with Pack Emolan Bloqueador SPF 60 (Edetate Disodium) is continued over a period of five days. Therapy is then interrupted for 2 to 4 days to allow redistribution of the lead and to prevent severe depletion of zinc and other essential metals. Two courses of treatment are usually employed; however, it depends on severity of the lead toxicity and the patient's tolerance of the drug.

Pack Emolan Bloqueador SPF 60 (Edetate Disodium) is equally effective whether administered intravenously or intramuscularly. The intramuscular route is used for all patients with overt lead encephalopathy and this route is preferred by some for young pediatric patients.

Acutely ill individuals may be dehydrated from vomiting. Since Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium is excreted almost exclusively in the urine, it is very important to establish urine flow with intravenous fluid administration before the first dose of the chelating agent is given; however, excessive fluid must be avoided in patients with encephalopathy. Once urine flow is established, further intravenous fluid is restricted to basal water and electrolyte requirements. Administration of Pack Emolan Bloqueador SPF 60 (Edetate Disodium) should be stopped whenever there is cessation of urine flow in order to avoid unduly high tissue levels of the drug. Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium must be used in reduced doses in patients with pre-existing mild renal disease.

Intravenous Administration

Add the total daily dose of Pack Emolan Bloqueador SPF 60 (Edetate Disodium) (1000 mg/m2/day) to 250–500 ml of 5% dextrose or 0.9% sodium chloride injection. The total daily dose should be infused over a period of 8–12 hours. Pack Emolan Bloqueador SPF 60 (Edetate Disodium) injection is incompatible with 10% dextrose, 10% invert sugar in 0.9% sodium chloride, lactate Ringer's, Ringer's, one-sixth molar sodium lactate injections, and with injectable amphotericin B and hydralazine hydrochloride.

Intramuscular Administration

The total daily dosage should be divided into equal doses spaced 8–12 hours apart. Lidocaine or procaine should be added to the Pack Emolan Bloqueador SPF 60 (Edetate Disodium) injection to minimize pain at the injection site. The final lidocaine or procaine concentration of 5 mg/ml (0.5%) can be obtained as follows: 0.25 ml of 10% lidocaine solution per 5 ml concentrated Pack Emolan Bloqueador SPF 60 (Edetate Disodium); 1 ml of 1% lidocaine or procaine solution per ml of concentrated Pack Emolan Bloqueador SPF 60 (Edetate Disodium). When used alone, regardless of method of administration, Pack Emolan Bloqueador SPF 60 (Edetate Disodium) should not be given at doses larger than those recommended.

Diagnostic Test

Several methods have been described for lead mobilization tests using Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium to assess body stores.7, 9,12,13,18

These procedures have advantages and disadvantages that should be reviewed in current references. Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium mobilization tests should not be performed in symptomatic patients and in patients with blood lead levels above 55 mcg/dl for whom appropriate therapy is indicated.

Parenteral drugs should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

SURFACE AREA NOMOGRAM FIGURE

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HOW SUPPLIED

Pack Emolan Bloqueador SPF 60 (Edetate Disodium) injection, 5 mL ampul containing 200 mg of Pack Emolan Bloqueador SPF 60 (Edetate Disodium) calcium disodium per ml (1000 mg per ampul), in boxes containing 5 ampuls (NDC 99207-240-05).

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).

Rx Only

This product is non-returnable.

REFERENCES

  • Thomas DJ, Chisolm JJ. Lead, zinc and copper decorporation during calcium disodium ethylenediamine tetraacetate treatment of lead-poisoned children. J Pharmacol Exp Therapeu 1986; 239: 829–835.
  • The Pharmacological Basis of Therapeutics, 7th edition, Goodman and Gilman, editors. MacMillan Publishing Company, New York, 1985, pp. 1619–1622.
  • Hammond PB, Aronson AL, Olson WC. The mechanism of mobilization of lead by ethylenediaminetetraacetate. J Pharmacol Exp Therapeu 1967; 157: 196–206.
  • Van deVyver FL, D'Haese PC, Visser WJ, et al. Bone lead in dialysis patients. Kidney Intl 1988; 33: 601–607.
  • Cory-Slecta DA, Weiss B, Cox C. Mobilization and redistribution of lead over the course of calcium disodium ethylenediamine tetraacetate chelation therapy. J Pharmacol Exp Therapeu 1987; 243: 804–813.
  • Chisolm JJ. Mobilization of lead by calcium disodium Pack Emolan Bloqueador SPF 60 (Edetate Disodium). Am J Dis Child 1987; 141: 1256–1257.
  • Drug Evaluations, 6th Edition, American Medical Association, Saunders, Philadelphia, 1986, pp. 1637–1639.
  • Centers for Disease Control: Preventing lead poisoning in young children. Atlanta, GA, Department of Health and Human Services, 1985 Jan.
  • Finberg L, Rajagopal V. Diagnosis and treatment of lead poisoning in children. J Family Med 1985 April: 3–12.
  • Schardein JL, Sakowski R, Petrere J, et al. Teratogenesis studies with EDTA and its salts in rats. Toxicol Appl Pharmacol 1981; 61: 423–428.
  • Swenerton H, Hurley LS. Teratogenic effects of a chelating agent and their prevention by zinc. Science 1971; 173: 62–64.
  • American Hospital Formulary Service, Drug Information, 1988, pp. 1695–1698.
  • Markowitz ME, Rosen JF. Assessment of lead stores in children: Validation of an 8-hour CaNa2EDTA (Calcium Disodium Versenate) provocative test. J Pediatrics 1984; 104: 337–341.
  • Piomelli S, Rosen JF, Chisolm JJ, et al. Management of childhood lead poisoning. J Pediatrics 1984; 105: 523–532.
  • Sachs HK, Blanksma LA, Murray EF, et al. Ambulatory treatment of lead poisoning: Report of 1,155 cases. Pediatrics 1970; 46: 389.
  • Chisolm JJ. The use of chelating agents in the treatment of acute and chronic lead intoxication in childhood. J Pediatrics 1968; 73: 1.
  • Coffin R, Phillips JL, Staples WI, et al. Treatment of lead encephalopathy in children. J Pediatrics 1966; 69: 198–206.
  • Chisolm JJ. Increased lead absorption and acute lead poisoning. Current Pediatric Therapy 12, Gillis and Kagan, editors, WB Saunders, Philadelphia, 1986, pp. 667–671.

Manufactured for:

Medicis, The Dermatology Company

Scottsdale, AZ 85256

By: CP Pharmaceuticals, Ltd.

Wrexham LL13 9UF, U.K.

Product of UK

106055/1

Rev. 10/12

MEDICIS Logo

Glycerol:


Indications and Usage (1) 04/2017
Dosage and Administration (2.1) 04/2017
Dosage and Administration (2.2) 04/2017

Pack Emolan Bloqueador SPF 60 (Glycerol) is indicated for use as a nitrogen-binding agent for chronic management of patients 2 months of age and older with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Pack Emolan Bloqueador SPF 60 (Glycerol) must be used with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements).

Limitations of Use:

  • Pack Emolan Bloqueador SPF 60 (Glycerol) is not indicated for the treatment of acute hyperammonemia in patients with UCDs because more rapidly acting interventions are essential to reduce plasma ammonia levels.
  • The safety and efficacy of Pack Emolan Bloqueador SPF 60 (Glycerol) for the treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established.

Pack Emolan Bloqueador SPF 60 (Glycerol) is a nitrogen-binding agent indicated for chronic management of patients 2 months of age and older with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Pack Emolan Bloqueador SPF 60 (Glycerol) must be used with dietary protein restriction and, in some cases, dietary supplements. (1)

Limitations of Use:

  • Pack Emolan Bloqueador SPF 60 (Glycerol) is not indicated for treatment of acute hyperammonemia in patients with UCDs. (1)
  • Safety and efficacy for treatment of N-acetylglutamate synthase (NAGS) deficiency has not been established. (1)
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2 DOSAGE AND ADMINISTRATION

  • Pack Emolan Bloqueador SPF 60 should be prescribed by a physician experienced in management of UCDs. For administration and preparation, see full prescribing information. (2.1, 2.6)

Switching From Sodium Phenylbutyrate Tablets or Powder to Pack Emolan Bloqueador SPF 60 (Glycerol):

  • Patients should receive the dosage of Pack Emolan Bloqueador SPF 60 (Glycerol) that contains the same amount of phenylbutyric acid, see full prescribing information for conversion. (2.2)

Initial Dosage in Phenylbutyrate-Naïve Patients (2.3):

  • Recommended dosage range is 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day).
  • For patients with some residual enzyme activity not adequately controlled with dietary restriction, the recommended starting dose is 4.5 mL/m2/day.
  • Take into account patient's estimated urea synthetic capacity, dietary protein intake, and diet adherence.

Dosage Adjustment and Monitoring:

  • Follow plasma ammonia levels to determine the need for dosage titration. (2.4)

Dosage Modifications in Patients with Hepatic Impairment:

  • Start dosage at lower end of range. (2.5, 8.6)

2.1 Important Administration Instructions

Pack Emolan Bloqueador SPF 60 (Glycerol) should be prescribed by a physician experienced in the management of UCDs.

  • Instruct patients to take Pack Emolan Bloqueador SPF 60 (Glycerol) with food or formula and to administer directly into the mouth via oral syringe or dosing cup.
  • For patients who cannot swallow, see the instructions on administration of Pack Emolan Bloqueador SPF 60 (Glycerol) by nasogastric tube or gastrostomy tube .
  • For patients who require a volume of less than 1 mL per dose via nasogastric or gastrostomy tube, the delivered dose may be less than anticipated. Closely monitor these patients using ammonia levels .
  • The recommended dosages for patients switching from sodium phenylbutyrate to Pack Emolan Bloqueador SPF 60 (Glycerol) and patients naïve to phenylbutyric acid are different . For both subpopulations:
    • Patients 2 years of age and older: Give Pack Emolan Bloqueador SPF 60 (Glycerol) in 3 equally divided dosages, each rounded up to the nearest 0.5 mL
    • Patients 2 months of age to less than 2 years: Give Pack Emolan Bloqueador SPF 60 (Glycerol) in 3 or more equally divided dosages, each rounded up to the nearest 0.1 mL.
    • The maximum total daily dosage is 17.5 mL (19 g).
    • Pack Emolan Bloqueador SPF 60 (Glycerol) must be used with dietary protein restriction and, in some cases, dietary supplements (e.g., essential amino acids, arginine, citrulline, protein-free calorie supplements).

2.2 Switching From Sodium Phenylbutyrate to Pack Emolan Bloqueador SPF 60

Patients switching from sodium phenylbutyrate to Pack Emolan Bloqueador SPF 60 (Glycerol) should receive the dosage of Pack Emolan Bloqueador SPF 60 (Glycerol) that contains the same amount of phenylbutyric acid. The conversion is as follows:

Total daily dosage of Pack Emolan Bloqueador SPF 60 (Glycerol) (mL) = total daily dosage of sodium phenylbutyrate tablets (g) × 0.86

Total daily dosage of Pack Emolan Bloqueador SPF 60 (Glycerol) (mL) = total daily dosage of sodium phenylbutyrate powder (g) × 0.81

2.3 Initial Dosage in Phenylbutyrate-Naïve Patients

The recommended dosage range, based upon body surface area, in patients naïve to phenylbutyrate is 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day). For patients with some residual enzyme activity who are not adequately controlled with protein restriction, the recommended starting dosage is 4.5 mL/m2/day.

In determining the starting dosage of Pack Emolan Bloqueador SPF 60 (Glycerol) in treatment-naïve patients, consider the patient's residual urea synthetic capacity, dietary protein requirements, and diet adherence. Dietary protein is approximately 16% nitrogen by weight. Given that approximately 47% of dietary nitrogen is excreted as waste and approximately 70% of an administered PBA dose will be converted to urinary phenylacetylglutamine (U-PAGN), an initial estimated Pack Emolan Bloqueador SPF 60 (Glycerol) dose for a 24-hour period is 0.6 mL Pack Emolan Bloqueador SPF 60 (Glycerol) per gram of dietary protein ingested per 24-hour period. The total daily dosage should not exceed 17.5 mL.

2.4 Dosage Adjustment and Monitoring

During treatment with Pack Emolan Bloqueador SPF 60 (Glycerol), patients should be followed clinically and with plasma ammonia levels to determine the need for dosage titration. Closely monitor ammonia levels after changing the dosage of Pack Emolan Bloqueador SPF 60 (Glycerol).

Normal Ammonia Levels

If patients experience symptoms of vomiting, nausea, headache, somnolence or confusion in the absence of high ammonia levels or other intercurrent illnesses, reduce the Pack Emolan Bloqueador SPF 60 (Glycerol) dosage and monitor patients clinically. If available, obtain measurements of plasma phenylacetate (PAA) concentrations and the ratio of plasma PAA to PAGN to guide dosing. A high PAA to PAGN ratio may indicate the saturation of the conjugation reaction to form PAGN. The PAA to PAGN ratio has been observed to be generally less than 1 in patients with UCDs without significant PAA accumulation .

Elevated Ammonia Levels

When plasma ammonia is elevated, increase the Pack Emolan Bloqueador SPF 60 (Glycerol) dosage to reduce the fasting ammonia level to less than half the upper limit of normal (ULN) in patients 6 years and older. In infants and pediatric patients (generally below 6 years of age), where obtaining fasting ammonia is problematic due to frequent feedings, adjust the dosage to keep the first ammonia of the morning below the ULN.

Urinary Phenylacetylglutamine: If available, U-PAGN measurements may be used to help guide Pack Emolan Bloqueador SPF 60 (Glycerol) dosage adjustment. Each gram of U-PAGN excreted over 24 hours covers waste nitrogen generated from 1.4 grams of dietary protein. If U-PAGN excretion is insufficient to cover daily dietary protein intake and the fasting ammonia is greater than half the ULN, the Pack Emolan Bloqueador SPF 60 (Glycerol) dosage should be adjusted upward. The amount of dosage adjustment should factor in the amount of dietary protein that has not been covered, as indicated by the 24-hour U-PAGN level and the estimated Pack Emolan Bloqueador SPF 60 (Glycerol) dose needed per gram of dietary protein ingested and the maximum total daily dosage (i.e., 17.5 mL).

Consider a patient's use of concomitant medications, such as probenecid, when making dosage adjustment decisions based on U-PAGN. Probenecid may result in a decrease of the urinary excretion of PAGN .

Plasma Phenylacetate and Phenylacetylglutamine: If available, the ratio of PAA to PAGN in plasma may provide additional information to assist in dosage adjustment decisions. In patients with a high PAA to PAGN ratio, a further increase in Pack Emolan Bloqueador SPF 60 (Glycerol) dosage may not increase PAGN formation, even if plasma PAA concentrations are increased, due to saturation of the conjugation reaction .

2.5 Dosage Modifications in Patients with Hepatic Impairment

For patients with moderate to severe hepatic impairment, the recommended starting dosage is at the lower end of the recommended dosing range and kept at the lowest dose necessary to control the patient's ammonia levels .

2.6 Preparation for Nasogastric Tube or Gastrostomy Tube Administration

It is recommended that all patients who can swallow take Pack Emolan Bloqueador SPF 60 (Glycerol) orally, even those with nasogastric and/or gastrostomy tubes. However, for patients who cannot swallow, a nasogastric tube or gastrostomy tube may be used to administer Pack Emolan Bloqueador SPF 60 (Glycerol) as follows:

  • Utilize an oral syringe to withdraw the prescribed dosage of Pack Emolan Bloqueador SPF 60 (Glycerol) from the bottle.
  • Place the tip of the syringe into the nasogastric/gastrostomy tube.
  • Utilizing the plunger of the syringe, administer Pack Emolan Bloqueador SPF 60 (Glycerol) into the tube.
  • Flush once with 10 mL of water or formula and allow the flush to drain.
  • If needed, flush a second time with an additional 10 mL of water or formula to clear the tube.

For patients who require a volume of less than 1 mL per dose via nasogastric or gastrostomy tube, the delivered dosage may be less than anticipated due to adherence of Pack Emolan Bloqueador SPF 60 (Glycerol) to the plastic tubing. Therefore, these patients should be closely monitored using ammonia levels following initiation of Pack Emolan Bloqueador SPF 60 (Glycerol) dosing or dosage adjustments.

3 DOSAGE FORMS AND STRENGTHS

Oral liquid: colorless to pale yellow, 1.1 g/mL of Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate (delivers 1.02 g/mL of phenylbutyrate).

Oral liquid: 1.1 g/mL. (3)

4 CONTRAINDICATIONS

Pack Emolan Bloqueador SPF 60 (Glycerol) is contraindicated in patients

  • Less than 2 months of age. Pediatric patients less than 2 months of age may have immature pancreatic exocrine function, which could impair hydrolysis of Pack Emolan Bloqueador SPF 60 (Glycerol), leading to impaired absorption of phenylbutyrate and hyperammonemia .
  • With known hypersensitivity to phenylbutyrate. Signs of hypersensitivity include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.
  • Patients less than 2 months of age. (4)
  • Known hypersensitivity to phenylbutyrate. (4)

5 WARNINGS AND PRECAUTIONS

  • Neurotoxicity: Phenylacetate, the active moiety of Pack Emolan Bloqueador SPF 60 (Glycerol), may be toxic; reduce dosage for symptoms of neurotoxicity. (5.1)
  • Reduced Phenylbutyrate Absorption in Pancreatic Insufficiency or Intestinal Malabsorption: Monitor ammonia levels closely. (5.2)

5.1 Neurotoxicity

The major metabolite of Pack Emolan Bloqueador SPF 60 (Glycerol), PAA, is associated with neurotoxicity. Signs and symptoms of PAA neurotoxicity, including somnolence, fatigue, lightheadedness, headache, dysgeusia, hypoacusis, disorientation, impaired memory, and exacerbation of preexisting neuropathy, were observed at plasma PAA concentrations of 500 micrograms/mL in a study of adult cancer patients who were administered PAA intravenously. In this study, adverse reactions were reversible.

In healthy subjects, after administration of 4 mL and 6 mL Pack Emolan Bloqueador SPF 60 (Glycerol) 3 times daily for 3 days, a dose-dependent increase in all-grade nervous system adverse reactions was observed, even at exposure levels of PAA less than 100 micrograms/mL.

In clinical trials in patients with UCDs who had been on sodium phenylbutyrate prior to administration of Pack Emolan Bloqueador SPF 60 (Glycerol), peak PAA concentrations after dosing with Pack Emolan Bloqueador SPF 60 (Glycerol) ranged from 1.6 to 178 micrograms/mL (mean: 39 micrograms/mL) in adult patients, from 1 to 410 micrograms/mL (mean: 70 micrograms/mL; median: 50 micrograms/mL) in pediatric patients ages 2 years and older, and from 1 to 1215 micrograms/mL (mean: 142 micrograms/mL; median: 35 micrograms/mL) in pediatric patients ages 2 months to less than 2 years. Some patients with UCDs experienced headache, fatigue, symptoms of peripheral neuropathy, seizures, tremor and/or dizziness. No correlation between PAA levels and neurotoxicity symptoms was identified but PAA levels were generally not measured at the time of neurotoxicity symptoms.

If symptoms of vomiting, nausea, headache, somnolence or confusion, are present in the absence of high ammonia or other intercurrent illnesses, reduce the Pack Emolan Bloqueador SPF 60 (Glycerol) dosage .

5.2 Reduced Phenylbutyrate Absorption in Pancreatic Insufficiency or Intestinal Malabsorption

Exocrine pancreatic enzymes hydrolyze Pack Emolan Bloqueador SPF 60 (Glycerol) in the small intestine, separating the active moiety, phenylbutyrate, from Pack Emolan Bloqueador SPF 60 (Glycerol). This process allows phenylbutyrate to be absorbed into the circulation. Low or absent pancreatic enzymes or intestinal disease resulting in fat malabsorption may result in reduced or absent digestion of Pack Emolan Bloqueador SPF 60 (Glycerol) and/or absorption of phenylbutyrate and reduced control of plasma ammonia. Monitor ammonia levels closely in patients with pancreatic insufficiency or intestinal malabsorption.

6 ADVERSE REACTIONS

Most common adverse reactions in adults are: diarrhea, flatulence, and headache. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Horizon Therapeutics at 1-855-823-7878 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Assessment of adverse reactions was based on exposure of 45 adult patients (31 female and 14 male) with UCD subtype deficiencies of ornithine transcarbamylase (OTC, n=40), carbamyl phosphate synthetase (CPS, n=2), and argininosuccinate synthetase (ASS, n=1) in a randomized, double-blind, active-controlled (RAVICTI vs sodium phenylbutyrate), crossover, 4-week study (Study 1) that enrolled patients 18 years of age and older . One of the 45 patients received only sodium phenylbutyrate prior to withdrawing on day 1 of the study due to an adverse reaction.

The most common adverse reactions (occurring in at least 10% of patients) reported during short-term treatment with Pack Emolan Bloqueador SPF 60 (Glycerol) were diarrhea, flatulence, and headache. Table 1 summarizes adverse reactions occurring in 2 or more patients treated with Pack Emolan Bloqueador SPF 60 (Glycerol) or sodium phenylbutyrate (incidence of at least 4% in either treatment arm).

Number (%) of Patients in Study 1
Sodium Phenylbutyrate

(N = 45)

Pack Emolan Bloqueador SPF 60 (Glycerol)

(N = 44)

Diarrhea 3 (7) 7 (16)
Headache 4 (9) 6 (14)
Flatulence 1 (2) 6 (14)
Abdominal pain 2 (4) 3 (7)
Vomiting 2 (4) 3 (7)
Decreased appetite 2 (4) 3 (7)
Fatigue 1 (2) 3 (7)
Dyspepsia 3 (7) 2 (5)
Nausea 3 (7) 1 (2)
Dizziness 4 (9) 0
Abdominal discomfort 3 (7) 0

Other Adverse Reactions

Pack Emolan Bloqueador SPF 60 (Glycerol) has been evaluated in 77 patients with UCDs (51 adult and 26 pediatric patients ages 2 years to 17 years) in 2 open-label long-term studies, in which 69 patients completed 12 months of treatment with Pack Emolan Bloqueador SPF 60 (Glycerol) (median exposure = 51 weeks). During these studies there were no deaths.

Adverse reactions occurring in at least 10% of adult patients were nausea, vomiting, diarrhea, decreased appetite, dizziness, headache, and fatigue.

Adverse reactions occurring in at least 10% of pediatric patients ages 2 years to 17 years were upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite, and headache.

Pack Emolan Bloqueador SPF 60 (Glycerol) has also been evaluated in 17 patients with UCDs ages 2 months to less than 2 years in 3 open-label studies. The median exposure was 6 months (range 0.2 to 18 months). Adverse reactions occurring in at least 10% of pediatric patients aged 2 months to less than 2 years were neutropenia, vomiting, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash and papule.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Pack Emolan Bloqueador SPF 60 (Glycerol). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

  • Abnormal body odor, including from skin, hair and urine
  • Retching and gagging
  • Dysgeusia or burning sensation in mouth

7 DRUG INTERACTIONS

  • Corticosteroids, valproic acid, or haloperidol: May increase plasma ammonia level; monitor ammonia levels closely.
  • Probenecid: May affect renal excretion of metabolites of Pack Emolan Bloqueador SPF 60 (Glycerol), including phenylacetylglutamine (PAGN) and PAA. (7.2)
  • CYP3A4 Substrates with narrow therapeutic index (e.g., alfentanil, quinidine, cyclosporine): Pack Emolan Bloqueador SPF 60 (Glycerol) may decrease exposure; monitor for decreased efficacy of the narrow therapeutic index drug. (7.3)
  • Midazolam: Decreased exposure; monitor for suboptimal effect of midazolam. (7.3)

7.1 Potential for Other Drugs to Affect Ammonia

Corticosteroids

Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels. Monitor ammonia levels closely when corticosteroids and Pack Emolan Bloqueador SPF 60 (Glycerol) are used concomitantly.

Valproic Acid and Haloperidol

Hyperammonemia may be induced by haloperidol and by valproic acid. Monitor ammonia levels closely when use of valproic acid or haloperidol is necessary in patients with UCDs.

7.2 Potential for Other Drugs to Affect Pack Emolan Bloqueador SPF 60

Probenecid

Probenecid may inhibit the renal excretion of metabolites of Pack Emolan Bloqueador SPF 60 (Glycerol) including PAGN and PAA.

7.3 Potential for Pack Emolan Bloqueador SPF 60 to Affect Other Drugs

Drugs with narrow therapeutic index that are substrates of CYP3A4

Pack Emolan Bloqueador SPF 60 (Glycerol) is a weak inducer of CYP3A4 in humans. Concomitant use of Pack Emolan Bloqueador SPF 60 (Glycerol) may decrease the systemic exposure to drugs that are substrates of CYP3A4. Monitor for decreased efficacy of drugs with narrow therapeutic index (e.g., alfentanil, quinidine, cyclosporine) .

Midazolam

Concomitant use of Pack Emolan Bloqueador SPF 60 (Glycerol) decreased the systemic exposure of midazolam. Monitor for suboptimal effect of midazolam in patients who are being treated with Pack Emolan Bloqueador SPF 60 (Glycerol).

8 USE IN SPECIFIC POPULATIONS

Lactation: Breastfeeding is not recommended.

8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Pack Emolan Bloqueador SPF 60 (Glycerol) during pregnancy. Healthcare providers are encouraged to report any prenatal exposure to Pack Emolan Bloqueador SPF 60 (Glycerol) by calling the Pregnancy Registry at 1-855-823-2595 or visiting www.ucdregistry.com.

Risk Summary

Limited available data with Pack Emolan Bloqueador SPF 60 (Glycerol) use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. In an animal reproduction study, administration of oral Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate to pregnant rabbits during organogenesis at doses up to 2.7–times the dose of 6.87 mL/m2/day in adult patients resulted in maternal toxicity, but had no effects on embryo-fetal development. In addition, there were no adverse developmental effects with administration of oral Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate to pregnant rats during organogenesis at 1.9 times the dose of 6.87 mL/m2/day in adult patients; however, maternal toxicity, reduced fetal weights, and variations in skeletal development were observed in pregnant rats administered oral Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate during organogenesis at doses greater than or equal to 5.7 times the dose of 6.87 mL/m2/day in adult patients [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Oral administration of Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate during the period of organogenesis up to 350 mg/kg/day in rabbits produced maternal toxicity, but no effects on embryo-fetal development. The dose of 350 mg/kg/day in rabbits is approximately 2.7 times the dose of 6.87 mL/m2/day in adult patients, based on combined area under the plasma concentration-time curve [AUCs] for PBA and PAA. In rats, at an oral dose of 300 mg/kg/day of Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate (1.9 times the dose of 6.87 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA) during the period of organogenesis, no effects on embryo-fetal development were observed. Doses of 650 mg/kg/day or greater produced maternal toxicity and adverse effects on embryo-fetal development including reduced fetal weights and cervical ribs at the 7th cervical vertebra. The dose of 650 mg/kg/day in rats is approximately 5.7 times the dose of 6.87 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA. No developmental abnormalities, effects on growth, or effects on learning and memory were observed through maturation of offspring following oral administration in pregnant rats with up to 900 mg/kg/day of Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate (8.5 times the dose of 6.87 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA) during organogenesis and lactation.

8.2 Lactation

Risk Summary

There are no data on the presence of Pack Emolan Bloqueador SPF 60 in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including neurotoxicity and tumorigenicity in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with Pack Emolan Bloqueador SPF 60 (Glycerol).

8.4 Pediatric Use

Safety and efficacy of Pack Emolan Bloqueador SPF 60 (Glycerol) have been established in pediatric patients 2 months of age and older with UCDs.

Pack Emolan Bloqueador SPF 60 (Glycerol) is contraindicated in pediatric patients less than 2 months of age .

Patients 2 Years to Less Than 18 Years of Age

The safety and efficacy of Pack Emolan Bloqueador SPF 60 (Glycerol) in patients 2 years to less than 18 years of age were established in 2 open-label, sodium phenylbutyrate to Pack Emolan Bloqueador SPF 60 (Glycerol), fixed-sequence, switchover clinical studies .

Patients 2 Months to Less Than 2 Years of Age

The safety and efficacy of Pack Emolan Bloqueador SPF 60 (Glycerol) in patients with UCDs, 2 months to less than 2 years of age were established in 3 open-label studies. Pharmacokinetics and pharmacodynamics (plasma ammonia), and safety were studied in 17 patients between 2 months and less than 2 years of age .

Patients Less Than 2 Months of Age

Pack Emolan Bloqueador SPF 60 (Glycerol) is contraindicated in patients less than 2 months of age . Pediatric patients less than 2 months of age may have immature pancreatic exocrine function, which could impair hydrolysis of Pack Emolan Bloqueador SPF 60 (Glycerol). Pancreatic lipases may be necessary for intestinal hydrolysis of Pack Emolan Bloqueador SPF 60 (Glycerol), allowing release of phenylbutyrate and subsequent formation of PAA, the active moiety. It is not known whether pancreatic and extrapancreatic lipases are sufficient for hydrolysis of Pack Emolan Bloqueador SPF 60 (Glycerol). If there is inadequate intestinal hydrolysis of Pack Emolan Bloqueador SPF 60 (Glycerol), impaired absorption of phenylbutyrate and hyperammonemia could occur.

Juvenile Animal Toxicity Data

In a juvenile rat study with daily oral dosing performed on postpartum day 2 through mating and pregnancy after maturation, terminal body weight was dose-dependently reduced by up to 16% in males and 12% in females at 900 mg/kg/day or higher (3 times the dose of 6.87 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA). Learning, memory, and motor activity endpoints were not affected. However, fertility (number of pregnant rats) was decreased by up to 25% at 650 mg/kg/day or higher (2.6 times the dose of 6.87 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA).

8.5 Geriatric Use

Clinical studies of Pack Emolan Bloqueador SPF 60 did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.6 Renal Impairment

The efficacy and safety of Pack Emolan Bloqueador SPF 60 (Glycerol) in patients with renal impairment are unknown. Monitor ammonia levels closely when starting patients with impaired renal function on Pack Emolan Bloqueador SPF 60 (Glycerol).

8.7 Hepatic Impairment

No studies were conducted in patients with UCDs and hepatic impairment. Because conversion of PAA to PAGN occurs in the liver, patients with hepatic impairment may have reduced conversion capability and higher plasma PAA and PAA to PAGN ratio . Therefore, dosage for patients with moderate to severe hepatic impairment should be started at the lower end of the recommended dosing range and should be kept on the lowest dose necessary to control their ammonia levels .

10 OVERDOSAGE

While there is no experience with overdosage in human clinical trials, PAA, a toxic metabolite of Pack Emolan Bloqueador SPF 60 (Glycerol), can accumulate in patients who receive an overdose .

If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

11 DESCRIPTION

Pack Emolan Bloqueador SPF 60 (Glycerol) (glycerol phenylbutyrate) is a clear, colorless to pale yellow oral liquid. It is insoluble in water and most organic solvents, and it is soluble in dimethylsulfoxide (DMSO) and greater than 65% acetonitrile.

Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate is a nitrogen-binding agent. It is a triglyceride containing 3 molecules of PBA linked to a Pack Emolan Bloqueador SPF 60 (Glycerol) backbone, the chemical name of which is benzenebutanoic acid, 1', 1' ' –(1,2,3-propanetriyl) ester with a molecular weight of 530.67. It has a molecular formula of C33H38O6. The structural formula is:

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

UCDs are inherited deficiencies of enzymes or transporters necessary for the synthesis of urea from ammonia. Absence of these enzymes or transporters results in the accumulation of toxic levels of ammonia in the blood and brain of affected patients. Pack Emolan Bloqueador SPF 60 (Glycerol) is a triglyceride containing 3 molecules of phenylbutyrate (PBA). PAA, the major metabolite of PBA, is the active moiety of Pack Emolan Bloqueador SPF 60 (Glycerol). PAA conjugates with glutamine (which contains 2 molecules of nitrogen) via acetylation in the liver and kidneys to form PAGN, which is excreted by the kidneys (Figure 1). On a molar basis, PAGN, like urea, contains 2 moles of nitrogen and provides an alternate vehicle for waste nitrogen excretion.

Figure 1: RAVICTI Mechanism of Action

12.2 Pharmacodynamics

Pharmacological Effects

In clinical studies, total 24-hour area under the plasma concentration-time curve (AUC) of ammonia concentration was comparable at steady state during the switchover period between Pack Emolan Bloqueador SPF 60 (Glycerol) and sodium phenylbutyrate .

Cardiac Electrophysiology

The effect of multiple doses of Pack Emolan Bloqueador SPF 60 (Glycerol) 13.2 g/day and 19.8 g/day (approximately 69% and 104% of the maximum recommended daily dosage) on QTc interval was evaluated in a randomized, placebo- and active-controlled (moxifloxacin 400 mg), four-treatment-arm, crossover study in 57 healthy subjects. The upper bound of the one-sided 95% CI for the largest placebo-adjusted, baseline-corrected QTc, based on individual correction method (QTcI) for Pack Emolan Bloqueador SPF 60 (Glycerol), was below 10 ms. However, assay sensitivity was not established in this study because the moxifloxacin time-profile was not consistent with expectation. Therefore, an increase in mean QTc interval of 10 ms cannot be ruled out.

12.3 Pharmacokinetics

Absorption

Pack Emolan Bloqueador SPF 60 (Glycerol) is a pro-drug of PBA. Upon oral ingestion, PBA is released from the Pack Emolan Bloqueador SPF 60 (Glycerol) backbone in the gastrointestinal tract by lipases. PBA derived from Pack Emolan Bloqueador SPF 60 (Glycerol) is further converted by β-oxidation to PAA.

In healthy, fasting adult subjects receiving a single oral dose of 2.9 mL/m2 of Pack Emolan Bloqueador SPF 60 (Glycerol), peak plasma levels of PBA, PAA, and PAGN occurred at 2 hours, 4 hours, and 4 hours, respectively. Upon single-dose administration of Pack Emolan Bloqueador SPF 60 (Glycerol), plasma concentrations of PBA were quantifiable in 15 of 22 participants at the first sample time postdose (0.25 hours). Mean maximum concentration (Cmax) for PBA, PAA, and PAGN was 37.0 micrograms/mL, 14.9 micrograms/mL, and 30.2 micrograms/mL, respectively. In healthy subjects, intact Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate was detected in plasma. While the study was inconclusive, the incomplete hydrolysis of Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate cannot be ruled out.

In healthy subjects, the systemic exposure to PAA, PBA, and PAGN increased in a dose-dependent manner. Following 4 mL of Pack Emolan Bloqueador SPF 60 (Glycerol) 3 times a day for 3 days, the mean Cmax and AUC were 66 micrograms/mL and 930 micrograms∙h/mL for PBA and 28 micrograms/mL and 942 micrograms∙h/mL for PAA, respectively. In the same study, following 6 mL of Pack Emolan Bloqueador SPF 60 (Glycerol) three times a day for 3 days, mean Cmax and AUC were 100 micrograms/mL and 1400 micrograms∙h/mL for PBA and 65 µg/mL and 2064 micrograms∙h/mL for PAA, respectively.

In adult patients with UCDs receiving multiple doses of Pack Emolan Bloqueador SPF 60 (Glycerol), maximum plasma concentrations at steady state (Cmax,ss) of PBA, PAA, and PAGN occurred at 8 hours, 12 hours, and 10 hours, respectively, after the first dose in the day. Intact Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate was not detectable in plasma in patients with UCDs.

Distribution

In vitro, the extent of plasma protein binding for 14C-labeled metabolites was 81% to 98% for PBA (over 1 to 250 micrograms/mL), and 37% to 66% for PAA (over 5 to 500 micrograms/mL). The protein binding for PAGN was 7% to 12% and no concentration effects were noted.

Elimination

Metabolism

Upon oral administration, pancreatic lipases hydrolyze Pack Emolan Bloqueador SPF 60 (Glycerol) (i.e., Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate), and release PBA. PBA undergoes β-oxidation to PAA, which is conjugated with glutamine in the liver and in the kidney through the enzyme phenylacetyl-CoA: L-glutamine-N-acetyltransferase to form PAGN. PAGN is subsequently eliminated in the urine.

Saturation of conjugation of PAA and glutamine to form PAGN was suggested by increases in the ratio of plasma PAA to PAGN with increasing dose and with increasing severity of hepatic impairment.

In healthy subjects, after administration of 4 mL, 6 mL, and 9 mL 3 times daily for 3 days, the ratio of mean AUC0-23h of PAA to PAGN was 1, 1.25, and 1.6, respectively. In a separate study, in patients with hepatic impairment (Child-Pugh B and C), the ratios of mean Cmax values for PAA to PAGN among all patients dosed with 6 mL and 9 mL twice daily were 3 and 3.7.

In in vitro studies, the specific activity of lipases for Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate was in the following decreasing order: pancreatic triglyceride lipase, carboxyl ester lipase, and pancreatic lipase–related protein 2. Further, Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate was hydrolyzed in vitro by esterases in human plasma. In these in vitro studies, a complete disappearance of Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate did not produce molar equivalent PBA, suggesting the formation of mono- or bis-ester metabolites. However, the formation of mono- or bis-esters was not studied in humans.

Excretion

The mean (SD) percentage of administered PBA excreted as PAGN was approximately 69% (17) in adults and 66% (24) in pediatric patients with UCDs at steady state. PAA and PBA represented minor urinary metabolites, each accounting for less than 1% of the administered dose of PBA.

Specific Populations

Age: Pediatric Population

Population pharmacokinetic modeling and dosing simulations suggest body surface area to be the most significant covariate explaining the variability of PAA clearance. PAA clearance was 10.9 L/h, 16.4 L/h, and 24.4 L/h, respectively, for patients ages 3 to 5, 6 to 11, and 12 to 17 years with UCDs.

In pediatric patients with UCDs (n = 14) ages 2 months to less than 2 years, PAA clearance was 6.8 L/h.

Sex

In healthy adult subjects, a gender effect was found for all metabolites, with women generally having higher plasma concentrations of all metabolites than men at a given dose level. In healthy female subjects, mean Cmax for PAA was 51 and 120% higher than in male volunteers after administration of 4 mL and 6 mL 3 times daily for 3 days, respectively. The dose normalized mean AUC0-23h for PAA was 108% higher in females than in males.

Renal Impairment

The pharmacokinetics of Pack Emolan Bloqueador SPF 60 (Glycerol) in patients with impaired renal function, including those with end-stage renal disease (ESRD) or those on hemodialysis, have not been studied .

Hepatic Impairment

The effects of hepatic impairment on the pharmacokinetics of Pack Emolan Bloqueador SPF 60 (Glycerol) were studied in patients with mild, moderate and severe hepatic impairment of (Child-Pugh class A, B, and C, respectively) receiving 100 mg/kg of Pack Emolan Bloqueador SPF 60 (Glycerol) twice daily for 7 days.

Plasma Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate was not measured in patients with hepatic impairment.

After multiple doses of Pack Emolan Bloqueador SPF 60 (Glycerol) in patients with hepatic impairment of Child-Pugh A, B, and C, geometric mean AUCt of PBA was 42%, 84%, and 50% higher, respectively, while geometric mean AUCt of PAA was 22%, 53%, and 94% higher, respectively, than in healthy subjects.

In patients with hepatic impairment of Child-Pugh A, B, and C, geometric mean AUCt of PAGN was 42%, 27%, and 22% lower, respectively, than that in healthy subjects.

The proportion of PBA excreted as PAGN in the urine in Child-Pugh A, B, and C was 80%, 58%, and 85%, respectively, and, in healthy volunteers, was 67%.

In another study in patients with moderate and severe hepatic impairment (Child-Pugh B and C), mean Cmax of PAA was 144 micrograms/mL (range: 14 to 358 micrograms/mL) after daily dosing of 6 mL of Pack Emolan Bloqueador SPF 60 (Glycerol) twice daily, while mean Cmax of PAA was 292 micrograms/mL (range: 57 to 655 micrograms/mL) after daily dosing of 9 mL of Pack Emolan Bloqueador SPF 60 (Glycerol) twice daily. The ratio of mean Cmax values for PAA to PAGN among all patients dosed with 6 mL and 9 mL twice daily were 3 and 3.7, respectively.

After multiple doses, a PAA concentration greater than 200 micrograms/mL was associated with a ratio of plasma PAA to PAGN concentrations higher than 2.5 .

Drug Interaction Studies

In vitro PBA or PAA did not induce CYP1A2, suggesting that in vivo drug interactions via induction of CYP1A2 is unlikely.

In in vitro studies, PBA at a concentration of 800 micrograms/mL caused greater than 60% reversible inhibition of cytochrome P450 isoenzymes CYP2C9, CYP2D6, and CYP3A4/5 (testosterone 6β-hydroxylase activity). The in vitro study suggested that in vivo drug interactions with substrates of CYP2D6 cannot be ruled out. The inhibition of CYP isoenzymes 1A2, 2C8, 2C19, and 2D6 by PAA at the concentration of 2.8 mg/mL was observed in vitro. Clinical implication of these results is unknown.

Effects of Pack Emolan Bloqueador SPF 60 (Glycerol) on other drugs

Midazolam

In healthy subjects, when oral midazolam was administered after multiple doses of Pack Emolan Bloqueador SPF 60 (Glycerol) (4 mL three times a day for 3 days) under fed conditions, the mean Cmax and AUC for midazolam were 25% and 32% lower, respectively, compared to administration of midazolam alone. In addition the mean Cmax and AUC for 1-hydroxy midazolam were 28% and 58% higher, respectively, compared to administration of midazolam alone .

Celecoxib

Concomitant administration of Pack Emolan Bloqueador SPF 60 (Glycerol) did not significantly affect the pharmacokinetics of celecoxib, a substrate of CYP2C9. When 200 mg of celecoxib was orally administered with Pack Emolan Bloqueador SPF 60 (Glycerol) after multiple doses of Pack Emolan Bloqueador SPF 60 (Glycerol) (4 mL three times a day for 6 days) under fed conditions (a standard breakfast was consumed 5 minutes after celecoxib administration), the mean Cmax and AUC for celecoxib were 13% and 8% lower than after administration of celecoxib alone.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

In a 2-year study in Sprague-Dawley rats, Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate caused a statistically significant increase in the incidence of pancreatic acinar cell adenoma, carcinoma, and combined adenoma or carcinoma at a dose of 650 mg/kg/day in males (4.7 times the dose of 6.9 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA) and 900 mg/kg/day in females (8.4 times the dose of 6.9 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA). The incidence of the following tumors was also increased in female rats at a dose of 900 mg/kg/day: thyroid follicular cell adenoma, carcinoma and combined adenoma or carcinoma, adrenal cortical combined adenoma or carcinoma, uterine endometrial stromal polyp, and combined polyp or sarcoma. The dose of 650 mg/kg/day in male rats is 3 times the dose of 7.5 mL/m2/day in pediatric patients, based on combined AUCs for PBA and PAA. The dose of 900 mg/kg/day in female rats is 5.5 times the dose of 7.5 mL/m2/day in pediatric patients, based on combined AUCs for PBA and PAA. In a 26-week study in transgenic (Tg.rasH2) mice, Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate was not tumorigenic at doses up to 1000 mg/kg/day.

Mutagenesis

Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate was not genotoxic in the Ames test, the in vitro chromosomal aberration test in human peripheral blood lymphocytes, or the in vivo rat micronucleus test. The metabolites PBA, PAA, PAGN, and phenylacetylglycine were not genotoxic in the Ames test or in vitro chromosome aberration test in Chinese hamster ovary cells.

Impairment of Fertility

Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate had no effect on fertility or reproductive function in male and female rats at oral doses up to 900 mg/kg/day. At doses of 1200 mg/kg/day (approximately 7 times the dose of 6.9 mL/m2/day in adult patients, based on combined AUCs for PBA and PAA), maternal toxicity was observed and the number of nonviable embryos was increased.

14 CLINICAL STUDIES

14.1 Clinical Studies in Adult Patients with UCDs

Active-Controlled, 4-Week, Noninferiority Study

A randomized, double-blind, active-controlled, crossover, noninferiority study (Study 1) compared Pack Emolan Bloqueador SPF 60 (Glycerol) to sodium phenylbutyrate by evaluating venous ammonia levels in patients with UCDs who had been on sodium phenylbutyrate prior to enrollment for control of their UCD. Patients were required to have a confirmed diagnosis of UCD involving deficiencies of CPS, OTC, or ASS, confirmed via enzymatic, biochemical, or genetic testing. Patients had to have no clinical evidence of hyperammonemia at enrollment and were not allowed to receive drugs known to increase ammonia levels (e.g., valproate), increase protein catabolism (e.g., corticosteroids), or significantly affect renal clearance (e.g., probenecid).

The primary endpoint was the 24-hour AUC (a measure of exposure to ammonia over 24 hours) for venous ammonia on days 14 and 28 when the drugs were expected to be at steady state. Statistical noninferiority would be established if the upper limit of the 2-sided 95% CI for the ratio of the geometric means (RAVICTI/sodium phenylbutyrate) for the endpoint was 1.25 or less.

Forty-five patients were randomized 1:1 to 1 of 2 treatment arms to receive either

  • Sodium phenylbutyrate for 2 weeks → Pack Emolan Bloqueador SPF 60 (Glycerol) for 2 weeks; or
  • Pack Emolan Bloqueador SPF 60 (Glycerol) for 2 weeks → sodium phenylbutyrate for 2 weeks.

Sodium phenylbutyrate or Pack Emolan Bloqueador SPF 60 (Glycerol) were administered three times daily with meals. The dose of Pack Emolan Bloqueador SPF 60 (Glycerol) was calculated to deliver the same amount of PBA as the sodium phenylbutyrate dose the patients were taking when they entered the study. Forty-four patients received at least 1 dose of Pack Emolan Bloqueador SPF 60 (Glycerol) in the study.

Patients adhered to a low-protein diet and received amino acid supplements throughout the study. After 2 weeks of dosing, by which time patients had reached steady state on each treatment, all patients had 24 hours of ammonia measurements.

Demographic characteristics of the 45 patients enrolled in Study 1 were as follows: mean age at enrollment was 33 years (range: 18 to 75 years); 69% were female; 33% had adult-onset disease; 89% had OTC deficiency; 7% had ASS deficiency; 4% had CPS deficiency.

Pack Emolan Bloqueador SPF 60 (Glycerol) was non-inferior to sodium phenylbutyrate with respect to the 24-hour AUC for ammonia. Forty-four patients were evaluated in this analysis. Mean 24-hour AUCs for venous ammonia during steady-state dosing were 866 micromol∙h/L and 977 micromol∙h/L with Pack Emolan Bloqueador SPF 60 (Glycerol) and sodium phenylbutyrate, respectively. The ratio of geometric means was 0.91 [95% CI 0.8, 1.04].

The mean venous ammonia levels over 24-hours after 2 weeks of dosing (on day 14 and 28) in the double-blind short-term study (Study 1) are displayed in Figure 2 below. The mean and median maximum venous ammonia concentration (Cmax) over 24 hours and 24-hour AUC for venous ammonia are summarized in Table 2. Ammonia values across different laboratories were normalized to a common normal range of 9 to 35 micromol/L using the following formula after standardization of the units to micromol/L:

Normalized ammonia (micromol/L) = ammonia readout in micromol/L × (35/ULN of a laboratory reference range specified for each assay)

Figure 2: Venous Ammonia Response in Adult Patients with UCDs in Short-Term Treatment Study 1

Timepoint Ammonia (n=44)
Mean (SD) Median (min, max)
Daily Cmax (micromol/L)
RAVICTI 61 (46) 51 (12, 245)
Sodium phenylbutyrate 71 (67) 46 (14, 303)
24-Hour AUC (micromol∙h/L)
RAVICTI 866 (661) 673 (206, 3351)
Sodium phenylbutyrate 977 (865) 653 (302, 4666)

Open-Label, Uncontrolled, Extension Study in Adults

A long-term (12-month), uncontrolled, open-label study (Study 2) was conducted to assess monthly ammonia control and hyperammonemic crisis over a 12-month period. A total of 51 adults were in the study and all but 6 had been converted from sodium phenylbutyrate to Pack Emolan Bloqueador SPF 60 (Glycerol). Venous ammonia levels were monitored monthly. Mean fasting venous ammonia values in adults in Study 2 were within normal limits during long-term treatment with Pack Emolan Bloqueador SPF 60 (Glycerol) (range: 6 to 30 micromol/L). Of 51 adult patients participating in the 12-month, open-label treatment with Pack Emolan Bloqueador SPF 60 (Glycerol), 7 patients (14%) reported a total of 10 hyperammonemic crises. The fasting venous ammonia measured during Study 2 is displayed in Figure 3. Ammonia values across different laboratories were normalized to a common normal range of 9 to 35 micromol/L.

Figure 3: Venous Ammonia Response in Adult Patients with UCDs in Long-Term Treatment Study 2

Open-Label, Long-Term Study in Adults

An open-label long-term, study (Study 5) was conducted to assess ammonia control in adult patients with UCDs. The study enrolled patients with UCDs who had completed the safety extensions of Study 1, Study 3 or Study 4 (Study 2, 3E and 4E, respectively). A total of 43 adult patients between the ages of 19 and 61 years were in the study. The median length of study participation was 1.9 years (range 0 to 4.5 years). Venous ammonia levels were monitored at a minimum of every 6 months. Mean fasting venous ammonia values in adult patients in Study 5 were within normal limits during long-term (24 months) treatment with Pack Emolan Bloqueador SPF 60 (Glycerol) (range: 24.2 to 31.4 micromol/L). Of the 43 adult patients participating in the open-label treatment with Pack Emolan Bloqueador SPF 60 (Glycerol), 9 patients (21%) reported a total of 21 hyperammonemic crises. Ammonia values across different laboratories were normalized to a common normal range of 10 to 35 micromol/L.

14.2 Clinical Studies in Pediatric Patients Ages 2 to 17 Years with UCDs

The efficacy of Pack Emolan Bloqueador SPF 60 (Glycerol) in pediatric patients 2 to 17 years of age with UCDs was evaluated in 2 fixed-sequence, open-label, sodium phenylbutyrate to Pack Emolan Bloqueador SPF 60 (Glycerol) switchover studies (Studies 3 and 4). Study 3 was 7 days in duration and Study 4 was 10 days in duration.

These studies compared blood ammonia levels of patients on Pack Emolan Bloqueador SPF 60 (Glycerol) to venous ammonia levels of patients on sodium phenylbutyrate in 26 pediatric patients between 2 months and 17 years of age with UCDs. Four patients less than 2 years of age are excluded for this analysis due to insufficient data. The dose of Pack Emolan Bloqueador SPF 60 (Glycerol) was calculated to deliver the same amount of PBA as the dose of sodium phenylbutyrate patients were taking when they entered the trial. Sodium phenylbutyrate or Pack Emolan Bloqueador SPF 60 (Glycerol) were administered in divided doses with meals. Patients adhered to a low-protein diet throughout the study. After a dosing period with each treatment, all patients underwent 24 hours of venous ammonia measurements, as well as blood and urine pharmacokinetic assessments.

UCD subtypes included OTC (n=12), argininosuccinate lyase (ASL) (n=8), and ASS deficiency (n=2), and patients received a mean Pack Emolan Bloqueador SPF 60 (Glycerol) dose of 8 mL/m2/day (8.8 g/m2/day), with doses ranging from 1.4 to 13.1 mL/m2/day (1.5 to 14.4 g/m2/day). Doses in these patients were based on previous dosing of sodium phenylbutyrate.

The 24-hour AUCs for blood ammonia (AUC0-24h) in 11 pediatric patients 6 to 17 years of age with UCDs (Study 3) and 11 pediatric patients 2 years to 5 years of age with UCDs (Study 4) were similar between treatments. In children 6 to 17 years of age, the ammonia AUC0-24h was 604 micromol∙h/L vs 815 micromol∙h/L on Pack Emolan Bloqueador SPF 60 (Glycerol) vs sodium phenylbutyrate. In the patients between 2 years and 5 years of age with UCDs, the ammonia AUC0-24h was 632 micromol∙h/L vs 720 micromol∙h/L on Pack Emolan Bloqueador SPF 60 (Glycerol) versus sodium phenylbutyrate.

The mean venous ammonia levels over 24 hours in open-label, short-term Studies 3 and 4 at common time points are displayed in Figure 4. Ammonia values across different laboratories were normalized to a common normal range of 9 to 35 micromol/L using the following formula after standardization of the units to micromol/L:

Normalized ammonia (micromol/L) = ammonia readout in micromol/L × (35/ULN of a laboratory reference range specified for each assay)

Figure 4: Venous Ammonia Response in Pediatric Patients Ages 2 to 17 Years with UCDs in Short-Term Treatment Studies 3 and 4

Open-Label, Uncontrolled, Extension Studies in Children Ages 2 to 17 Years

Long-term (12-month), uncontrolled, open-label studies were conducted to assess monthly ammonia control and hyperammonemic crisis over a 12-month period. In two studies (Study 2, which also enrolled adults, and an extension of Study 3, referred to here as Study 3E), a total of 26 children ages 6 to 17 were enrolled and all but 1 had been converted from sodium phenylbutyrate to Pack Emolan Bloqueador SPF 60 (Glycerol). Mean fasting venous ammonia values were within normal limits during long-term treatment with Pack Emolan Bloqueador SPF 60 (Glycerol) (range: 17 to 23 micromol/L). Of the 26 pediatric patients 6 to 17 years of age participating in these two trials, 5 patients (19%) reported a total of 5 hyperammonemic crises. The fasting venous ammonia measured during these two extension studies in patients 6 to 17 years is displayed in Figure 5. Ammonia values across different laboratories were normalized to a common normal range of 9 to 35 micromol/L.

Figure 5: Venous Ammonia Response in Pediatric Patients Ages 2 to 17 Years with UCDs in Long-Term Treatment Studies 2 and 3E

In an extension of Study 4, after a median time on study of 4.5 months (range: 1 to 5.7 months), 2 of 16 pediatric patients ages 2 to 5 years had experienced three hyperammonemic crises.

Open-Label, Long-Term Study in Children Ages 1 to 17 Years of Age

An open-label, long-term study (Study 5) was conducted to assess ammonia control in pediatric patients with UCD. The study enrolled patients with UCD who had completed the safety extensions of Study 1, Study 3 or Study 4 (Study 2, 3E and 4E, respectively). A total of 45 pediatric patients between the ages of 1 and 17 years were in the study. The median length of study participation was 1.7 years (range 0.2 to 4.6 years). Venous ammonia levels were monitored at a minimum of every 6 months. Mean venous ammonia values in pediatric patients in Study 5 were within normal limits during long-term (24 months) treatment with Pack Emolan Bloqueador SPF 60 (Glycerol) (range: 15.4 to 25.1 micromol/L). Of the 45 pediatric patients participating in the open-label treatment with Pack Emolan Bloqueador SPF 60 (Glycerol), 11 patients (24%) reported a total of 22 hyperammonemic crises. Ammonia values across different laboratories were normalized to a common normal range of 10 to 35 micromol/L.

14.3 Clinical Studies in Pediatric Patients Ages 2 Months to Less Than 2 Years with UCDs

Uncontrolled, open-label studies were conducted to assess monthly ammonia control and hyperammonemic crisis of Pack Emolan Bloqueador SPF 60 (Glycerol) in pediatric patients with UCDs 2 months to less than 2 years of age (Study 4/4E, Study 5, and Study 6). Patients in Study 5 previously participated in Study 4/4E. A total of 17 pediatric patients with UCDs aged 2 months to less than 2 years participated in the studies.

Uncontrolled, Open-Label Study in Children Under 2 Years of Age (Study 6)

A total of 10 pediatric patients with UCDs aged 2 months to less than 2 years participated in Study 6, of which 7 patients converted from sodium phenylbutyrate to Pack Emolan Bloqueador SPF 60 (Glycerol). The dosage of Pack Emolan Bloqueador SPF 60 (Glycerol) was calculated to deliver the same amount of PBA as the sodium phenylbutyrate dosage the patients were taking when they entered the trial. Two patients were treatment naïve and received Pack Emolan Bloqueador SPF 60 (Glycerol) dosage of 7.5 mL/m2/day and 9.4 mL/m2/day, respectively. One additional patient was gradually discontinued from intravenous sodium benzoate and sodium phenylacetate while Pack Emolan Bloqueador SPF 60 (Glycerol) was initiated. The dosage of Pack Emolan Bloqueador SPF 60 (Glycerol) after transition was 8.5 mL/m2/day.

In Study 6, there were 9, 7 and 3 pediatric patients who completed 1, 3 and 6 months, respectively (mean and median exposure of 4 and 5 months, respectively).

Patients received a mean Pack Emolan Bloqueador SPF 60 (Glycerol) dose of 8 mL/m2/day (8.8 g/m2/day), with doses ranging from 4.8 to 11.5 mL/m2/day (5.3 to 12.6 g/m2/day). Patients were dosed three times a day (n=6), four times a day (n = 2), or five or more times a day (n=2).

The primary efficacy endpoint was successful transition to Pack Emolan Bloqueador SPF 60 (Glycerol) within a period of 4 days followed by 3 days of observation for a total of 7 days, where successful transition was defined as no signs and symptoms of hyperammonemia and a venous ammonia value less than 100 micromol/L. Venous ammonia levels were monitored for up to 4 days during transition and on day 7. Nine patients successfully transitioned as defined by the primary endpoint. One additional patient developed hyperammonemia on day 3 of dosing and experienced surgical complications (bowel perforation and peritonitis) following jejunal tube placement on day 4. This patient developed hyperammonemic crisis on day 6, and subsequently died of sepsis from peritonitis unrelated to drug. Although two patients had day 7 ammonia values of 150 micromol/L and 111 micromol/L respectively, neither had associated signs and symptoms of hyperammonemia.

During the extension phase, venous ammonia levels were monitored monthly. Ammonia values across different laboratories were normalized (transformed) to a common normal pediatric range of 28 to 57 micromol/L for comparability. The mean normalized venous ammonia values in pediatric patients at month 1, 2, 3, 4, 5 and 6 were 67, 53, 78, 99, 56 and 61 micromol/L during treatment with Pack Emolan Bloqueador SPF 60 (Glycerol), respectively. Three patients reported a total of 7 hyperammonemic crises defined as having signs and symptoms consistent with hyperammonemia (such as frequent vomiting, nausea, headache, lethargy, irritability, combativeness, and/or somnolence) associated with high venous ammonia levels and requiring medical intervention. Hyperammonemic crises were precipitated by vomiting, upper respiratory tract infection, gastroenteritis, decreased caloric intake or had no identified precipitating event (3 events). There were three additional patients who had one venous ammonia level that exceeded 100 micromol/L which was not associated with a hyperammonemic crisis.

Uncontrolled, Open-Label Studies in Children Under 2 Years of Age (Studies 4/4E, 5)

A total of 7 patients with UCDs aged 2 months to less than 2 years participated in Studies 4/4E and 5. In these studies, there were 7, 6, 6, 6 and 3 pediatric patients who completed 1, 6, 9, 12 and 18 months, respectively (mean and median exposure of 15 and 17 months, respectively). Patients were converted from sodium phenylbutyrate to Pack Emolan Bloqueador SPF 60 (Glycerol). The dosage of Pack Emolan Bloqueador SPF 60 (Glycerol) was calculated to deliver the same amount of PBA as the sodium phenylbutyrate dosage the patients were taking when they entered the study.

Patients received a mean Pack Emolan Bloqueador SPF 60 (Glycerol) dose of 7.5 mL/m2/day (8.2 g/m2/day), with doses ranging from 3.3 to 12.3 mL/m2/day (3.7 to 13.5 g/m2/day). Patients were dosed three times a day (n=3) or four times a day (n = 4).

Venous ammonia levels were monitored on days 1, 3 and 10 in Study 4 and at week 1 in Study 4E. Two patients had day 1 ammonia values of 122 micromol/L and 111 micromol/L respectively, neither had associated signs and symptoms of hyperammonemia. At day 10/week 1, six of the 7 patients had venous ammonia levels less than 100 micromol/L the remaining patient had a day 10 ammonia value of 168 micromol/L and was asymptomatic.

During the extension period, venous ammonia levels were monitored monthly. Ammonia values across different laboratories were normalized (transformed) to a common normal pediatric range of 28 to 57 micromol/L for comparability. The mean venous ammonia values in pediatric patients at month 1, 3, 6, 9 and 12 were 58, 49, 34, 65, and 31 micromol/L during treatment with Pack Emolan Bloqueador SPF 60 (Glycerol), respectively.

Three patients reported a total of 3 hyperammonemic crises, as defined in Study 6. Hyperammonemic crises were precipitated by gastroenteritis, vomiting, infection or no precipitating event (one patient). There were 4 patients who had one venous ammonia level that exceeded 100 micromol/L which was not associated with a hyperammonemic crisis.

16 HOW SUPPLIED/STORAGE AND HANDLING

Pack Emolan Bloqueador SPF 60 (Glycerol) ® (glycerol phenylbutyrate) oral liquid 1.1 g/mL is supplied in multi-use, 25-mL glass bottles. The bottles are supplied in the following configurations:

  • NDC 75987-050-06: Single 25-mL bottle per carton
  • NDC 75987-050-07: Four 25-mL bottles per carton

Store at 20°-25°C (68°-77°F) with excursions permitted to 15°-30°C (59°-86°F).

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Neurotoxicity .

  • Inform patients/caregivers that adverse reactions of Pack Emolan Bloqueador SPF 60 (Glycerol) are sometimes the same as symptoms of high blood ammonia. Neurological adverse events may also be associated with the major metabolite of Pack Emolan Bloqueador SPF 60 (Glycerol), PAA, and may be reversible. Blood tests for PAA may be done to measure the amount of PAA in the blood. Instruct the patient/caregiver to contact the healthcare provider immediately if the patient experiences: nausea, vomiting, headache, fatigue, somnolence, lightheadedness, confusion, exacerbation of preexisting neuropathy, disorientation, impaired memory, dysgeusia, or hypoacusis.

Pregnancy Registry

Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Pack Emolan Bloqueador SPF 60 (Glycerol) during pregnancy .

Lactation

Advise patients that breastfeeding is not recommended during treatment with Pack Emolan Bloqueador SPF 60 (Glycerol) .

Administration

  • Instruct patients to take Pack Emolan Bloqueador SPF 60 (Glycerol) with food or formula and to administer directly into the mouth via oral syringe or dosing cup.
  • Instruct patients to take Pack Emolan Bloqueador SPF 60 (Glycerol) orally, even if they have a nasogastric and/or gastrostomy tube. For patients who cannot swallow and who have a nasogastric tube or gastrostomy tube in place, instruct patients/caregivers to administer Pack Emolan Bloqueador SPF 60 (Glycerol) as follows:
    • Utilize an oral syringe to withdraw the prescribed dosage of Pack Emolan Bloqueador SPF 60 (Glycerol) from the bottle.
    • Place the tip of the syringe into the gastrostomy/nasogastric tube.
    • Utilizing the plunger of the syringe, administer Pack Emolan Bloqueador SPF 60 (Glycerol) into the tube.
    • Flush once with 10 mL of water or formula and allow the flush to drain.
    • If needed, flush a second time with an additional 10 mL of water or formula to clear the tube.

Distributed by:

Horizon Pharma USA, Inc.

Lake Forest, IL 60045

Horizon Therapeutics, LLC.

All rights reserved.

Pack Emolan Bloqueador SPF 60 (Glycerol) is a registered trademark of Horizon Therapeutics, LLC.

MEDICATION GUIDE

Pack Emolan Bloqueador SPF 60 (Glycerol) (rah-VIK- tee)

(glycerol phenylbutyrate)

oral liquid

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 04/2017
What is the most important information I should know about Pack Emolan Bloqueador SPF 60 (Glycerol)?

Pack Emolan Bloqueador SPF 60 (Glycerol) may cause serious side effects, including:

Nervous system problems (Neurotoxicity). Phenylacetate (PAA), a breakdown product of Pack Emolan Bloqueador SPF 60 (Glycerol), may cause nervous system side effects. Call your doctor or get medical help right away if you get any of these symptoms while taking Pack Emolan Bloqueador SPF 60 (Glycerol):

  • sleepiness
  • lightheadedness
  • change in taste
  • problems with hearing
  • confusion
  • problems with memory
  • worsening of numbness, tingling, or burning in your hands or feet
  • headache
  • feeling very tired (fatigue)
  • nausea
  • vomiting

Your doctor may do blood tests to measure the amount of PAA in your blood during your treatment with Pack Emolan Bloqueador SPF 60 (Glycerol).


What is Pack Emolan Bloqueador SPF 60 (Glycerol)?

  • Pack Emolan Bloqueador SPF 60 (Glycerol) is a prescription medicine used in adults and in children 2 months of age and older for long-term management of high blood levels of ammonia (hyperammonemia) caused by a condition called a urea cycle disorder (UCD). Pack Emolan Bloqueador SPF 60 (Glycerol) should be used if the UCD cannot be managed with a low protein diet and dietary supplements alone. Pack Emolan Bloqueador SPF 60 (Glycerol) must be used along with a low protein diet and in some cases dietary supplements.
  • Pack Emolan Bloqueador SPF 60 (Glycerol) is not used for the acute treatment of hyperammonemia in people with UCD.
  • It is not known if Pack Emolan Bloqueador SPF 60 (Glycerol) is safe and effective for the treatment of N-acetylglutamate synthase (NAGS) deficiency.

Who should not take Pack Emolan Bloqueador SPF 60 (Glycerol)?

  • Children less than 2 months of age should not take Pack Emolan Bloqueador SPF 60 (Glycerol) because it may not be digested in children less than 2 months of age.
  • Do not take Pack Emolan Bloqueador SPF 60 (Glycerol) if you are allergic to phenylbutyrate. Call your doctor or go to the nearest hospital emergency room if you have wheezing, shortness of breath, cough, low blood pressure, flushing, nausea or a rash while taking Pack Emolan Bloqueador SPF 60 (Glycerol).

Before taking Pack Emolan Bloqueador SPF 60 (Glycerol), tell your doctor about any medical conditions and if you:

  • Have liver or kidney problems.
  • Have pancreas or bowel (intestine) problems.
  • Are pregnant or plan to become pregnant. It is not known if Pack Emolan Bloqueador SPF 60 (Glycerol) will harm your unborn baby.
  • Pregnancy Registry: There is a Pregnancy Registry for women who take Pack Emolan Bloqueador SPF 60 (Glycerol) just before becoming pregnant or who become pregnant during treatment with Pack Emolan Bloqueador SPF 60 (Glycerol). The purpose of this registry is to collect information about the health of you and your baby. Talk to your doctor about how you can join the Pregnancy Registry. For more information about this registry, call 1-855-823-2595 or visit www.ucdregistry.com.
  • Are breastfeeding or plan to breastfeed. It is not known if Pack Emolan Bloqueador SPF 60 (Glycerol) passes into your breast milk. Breastfeeding is not recommended during treatment with Pack Emolan Bloqueador SPF 60 (Glycerol). Talk to your doctor about the best way to feed your baby if you take Pack Emolan Bloqueador SPF 60 (Glycerol).

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, dietary and herbal supplements.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.


How should I take Pack Emolan Bloqueador SPF 60 (Glycerol)?

  • Take Pack Emolan Bloqueador SPF 60 (Glycerol) exactly as your doctor tells you.
  • Your doctor will tell you how much Pack Emolan Bloqueador SPF 60 (Glycerol) to take and when to take it.
  • Your doctor may change your dose if needed.
  • Take Pack Emolan Bloqueador SPF 60 (Glycerol) with food or formula.
  • Pack Emolan Bloqueador SPF 60 (Glycerol) is an oral liquid that is taken by mouth using an oral syringe or dosing cup. Ask your pharmacist for an oral syringe or dosing cup if you do not have one.
  • If you have a nasogastric or gastrostomy tube in place and can swallow, you should take Pack Emolan Bloqueador SPF 60 (Glycerol) by mouth.
  • Stay on the diet that your doctor gives you.
  • If you take too much Pack Emolan Bloqueador SPF 60 (Glycerol), call your doctor or your poison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away.

For people who cannot swallow and who have a nasogastric or gastrostomy tube in place, Pack Emolan Bloqueador SPF 60 (Glycerol) should be given as follows:

  • Use an oral syringe to withdraw the prescribed dose of Pack Emolan Bloqueador SPF 60 (Glycerol) from the bottle.
  • Place the tip of the syringe into the nasogastric or gastrostomy tube and push the plunger of the syringe to give Pack Emolan Bloqueador SPF 60 (Glycerol) into the tube.
  • Add 10 mL of water or formula to the syringe and push the plunger of the syringe to flush any remaining medicine from the nasogastric or gastrostomy tube into the stomach.
  • If needed, flush the nasogastric or gastrostomy tube again with 10 mL of water or formula to clear the nasogastric or gastrostomy tube.

What are the possible side effects of Pack Emolan Bloqueador SPF 60 (Glycerol)?

Pack Emolan Bloqueador SPF 60 (Glycerol) may cause serious side effects, including:

  • See " What is the most important information I should know about Pack Emolan Bloqueador SPF 60 (Glycerol)? "

The most common side effects of Pack Emolan Bloqueador SPF 60 (Glycerol) in adults include:

  • diarrhea
  • gas
  • headache
  • abdomen (stomach) pain
  • vomiting
  • tiredness
  • decreased appetite
  • indigestion or heartburn

The most common side effects of Pack Emolan Bloqueador SPF 60 (Glycerol) in children 2 years to 17 years of age include:

  • upper abdomen (stomach) pain
  • rash
  • nausea
  • vomiting
  • diarrhea
  • decreased appetite
  • headache

The most common side effects of Pack Emolan Bloqueador SPF 60 (Glycerol) in children 2 months to less than 2 years of age include:

  • low white blood cell count (neutropenia)
  • vomiting
  • diarrhea
  • fever
  • reduced food intake
  • cough
  • stuffy nose
  • runny nose
  • skin rash
  • small round bumps on the skin

Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of Pack Emolan Bloqueador SPF 60 (Glycerol).

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.


How should I store Pack Emolan Bloqueador SPF 60 (Glycerol)?

  • Store Pack Emolan Bloqueador SPF 60 (Glycerol) between 68ºF to 77ºF (20°C to 25°C).

Keep Pack Emolan Bloqueador SPF 60 (Glycerol) and all medicines out of the reach of children.


General information about the safe and effective use of Pack Emolan Bloqueador SPF 60 (Glycerol).

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Pack Emolan Bloqueador SPF 60 (Glycerol) for a condition for which it was not prescribed. Do not give Pack Emolan Bloqueador SPF 60 (Glycerol) to other people, even if they have the same symptoms you have. It may harm them.

You can ask your doctor or pharmacist for information about Pack Emolan Bloqueador SPF 60 (Glycerol) that is written for health professionals.


What are the ingredients in Pack Emolan Bloqueador SPF 60 (Glycerol)?

Active ingredient: Pack Emolan Bloqueador SPF 60 (Glycerol) phenylbutyrate

Distributed by: Horizon Pharma USA, Inc., Lake Forest, IL 60045.

© Horizon Therapeutics, LLC. All rights reserved. Pack Emolan Bloqueador SPF 60 (Glycerol) is a registered trademark of Horizon Therapeutics, LLC.

For more information, go to www. RAVICTI.com or call 1-855-823-7878.

Isopropyl Palmitate:



Active Ingredients Purpose

Pack Emolan Bloqueador SPF 60 (Isopropyl Palmitate) alcohol 62% by weight Antiseptic

Benzyl Alcohol 6.1% Bacteriacide

Tannic Acid 1.5% Astringent

Picric Acid 0.2% Bacteriacide

Uses

Pack Emolan Bloqueador SPF 60 (Isopropyl Palmitate) is a highly effective germicide, formulated expressly for minor wounds and burns. Its four-way action reduces pain, checks capillary bleeding, promotes healing, and aids in the prevention of infection.

Warnings

For external use only.

FLAMMABLE. Do not spray while smoking or near fire. Contents under pressure. Do not puncture or incinerate container or place where temperature exceeds 120 F. Use only as directed. Intentional misuse by concentrating and inhaling the contents can be harmful or fatal. In case of accidental ingestion, seek professional assistance or contact a Poison Control Center immediately. If irritation occurs or if there is no improvement within 2 weeks, discontinue use and consult a doctor. Keep this and all drugs out of the reach of children.

Directions

Cleanse wound with Cinder Suds® soap. Saturate sterile dressing with Pack Emolan Bloqueador SPF 60 (Isopropyl Palmitate). Leave in place at least five minutes; add Nitrotan® to keep dressing wet. Remove dressing, allow to dry, and apply antiseptic dressing. Renew at least once daily.

Inactive Ingredients

Isobutane and propane

Mfd. by Cramer Products, Inc. Gardner, Kansas 66030

QUESTIONS? (800) 345-2231 (M-F 8:00AM-5:00PM CST)

Purpose

Antiseptic

Bacteriacide

Astringent

Bacteriacide

Keep this and all drugs out of the reach of children.

Germicidal Wound Care Spray

Prevents Infection

Promotes Healing

Reduces Pain

Checks Capillary Bleeding

WARNING:

EXTREMELY FLAMMABLE

CONTENTS UNDER PRESSURE

READ WARNINGS ON BACK PANEL

NET WT 8 OZ (226 g)

Potassium Phosphate:



Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

The Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride containing 1500 mg of microencapsulated Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride, USP equivalent to 20 mEq of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) in a tablet.

These formulations are intended to slow the release of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) so that the likelihood of a high localized concentration of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride within the gastrointestinal tract is reduced.

Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride, and the structural formula is KCl. Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride, USP occurs as a white, granular powder or as colorless crystals. It is odorless and has a saline taste. Its solutions are neutral to litmus. It is freely soluble in water and insoluble in alcohol.

Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablets USP, 20 mEq begin disintegrating into microencapsulated crystals within seconds and completely disintegrates within 1 minute. The microencapsulated crystals are formulated to provide an extended release of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride.

Inactive Ingredients: Colloidal silicon dioxide, crospovidone, diethyl phthalate, ethyl-cellulose, microcrystalline cellulose.

CLINICAL PHARMACOLOGY

The Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) ion is the principal intracellular cation of most body tissues. Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity; the transmission of nerve impulses; the contraction of cardiac, skeletal, and smooth muscle; and the maintenance of normal renal function.

The intracellular concentration of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane.

Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) is a normal dietary constituent and under steady-state conditions the amount of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) is 50 to 100 mEq per day.

Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) depletion will occur whenever the rate of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) depletion may produce weakness, fatigue, disturbances or cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine.

If Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, eg, where the patient requires long-term diuretic therapy, supplemental Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) in the form of high Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) food or Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride may be able to restore normal Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) levels.

In rare circumstances (eg, patients with renal tubular acidosis) Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) replacement should be accomplished with Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) salts other than the chloride, such as Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) bicarbonate, Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) citrate, Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) acetate, or Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) gluconate.

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) PREPARATIONS OR FOR PATIENTS IN WHOM THERE IS A PROBLEM OF COMPLIANCE WITH THESE PREPARATIONS.

1. For the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxication, and in patients with hypokalemic familial periodic paralysis. If hypokalemia is the result of diuretic therapy, consideration should be given to the use of a lower dose of diuretic, which may be sufficient without leading to hypokalemia.

2. For the prevention of hypokalemia in patients who would be at particular risk if hypokalemia were to develop, eg, digitalized patients or patients with significant cardiac arrhythmias.

The use of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) salts in patients receiving diuretics for uncomplicated essential hypertension is often unnecessary when such patients have a normal dietary pattern and when low doses of the diuretic are used. Serum Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) should be checked periodically, however, and if hypokalemia occurs, dietary supplementation with potassium-containing foods may be adequate to control milder cases. In more severe cases, and if dose adjustment of the diuretic is ineffective or unwarranted, supplementation with Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) salts may be indicated.

CONTRAINDICATIONS

Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) concentration in such patients can produce cardiac arrest. Hyperkalemia may complicate any of the following conditions: chronic renal failure, systemic acidosis, such as diabetic acidosis, acute dehydration, extensive tissue breakdown as in severe burns, adrenal insufficiency, or the administration of a potassium-sparing diuretic (eg, spironolactone, triamterene, amiloride) (see OVERDOSAGE ).

Controlled-release formulations of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride are contraindicated in any patient in whom there is structural, pathological (eg, diabetic gastroparesis), or pharmacologic (use of anticholinergic agents or other agents with anticholinergic properties at sufficient doses to exert anticholinergic effects) cause for arrest or delay in tablet passage through the gastrointestinal tract.

WARNINGS

Hyperkalemia (see OVERDOSAGE )

In patients with impaired mechanisms for excreting Pack Emolan Bloqueador SPF 60 (Potassium Phosphate), the administration of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) by the intravenous route but may also occur in patients given Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) salts in patients with chronic renal disease, or any other condition which impairs Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) excretion, requires particularly careful monitoring of the serum Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) salts and a potassium-sparing diuretic (eg, spironolactone, triamterene, or amiloride) since the simultaneous administration of these agents can produce severe hyperkalemia.

Interaction with Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, enalapril) will produce some Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) retention by inhibiting aldosterone production. Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride are associated with an increased frequency of small bowel lesions (40-50 per 100,000 patient years) compared to sustained release wax matrix formulations (less than one per 100,000 patient years). Because of the lack of extensive marketing experience with microencapsulated products, a comparison between such products and wax matrix or enteric-coated products is not available. Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride and thus to minimize the possibility of a high local concentration of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) near the gastrointestinal wall.

Prospective trials have been conducted in normal human volunteers in which the upper gastrointestinal tract was evaluated by endoscopic inspection before and after 1 week of solid oral Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride therapy. The ability of this model to predict events occurring in usual clinical practice is unknown. Trials which approximated usual clinical practice did not reveal any clear differences between the wax matrix and microencapsulated dosage forms. In contrast, there was a higher incidence of gastric and duodenal lesions in subjects receiving a high dose of a wax matrix controlled-release formulation under conditions which did not resemble usual or recommended clinical practice (ie, 96 mEq per day in divided doses of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride administered to fasted patients, in the presence of an anticholinergic drug to delay gastric emptying). The upper gastrointestinal lesions observed by endoscopy were asymptomatic and were not accompanied by evidence of bleeding (Hemoccult testing). The relevance of these findings to the usual conditions (ie, non-fasting, no anticholinergic agent, smaller doses) under which controlled-release Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride products are used is uncertain; epidemiologic studies have not identified an elevated risk, compared to microencapsulated products, for upper gastrointestinal lesions in patients receiving wax matrix formulations. Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablets USP, 20 mEq should be discontinued immediately and the possibility of ulceration, obstruction, or perforation should be considered if severe vomiting, abdominal pain, distention, or gastrointestinal bleeding occurs.

Metabolic Acidosis

Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) salt such as Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) bicarbonate, Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) citrate, Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) acetate, or Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) gluconate.

PRECAUTIONS

General

The diagnosis of Pack Emolan Bloqueador SPF 60 depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) depletion. In interpreting the serum Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) while acute acidosis per se can increase the serum Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) concentration into the normal range even in the presence of a reduced total body Pack Emolan Bloqueador SPF 60 (Potassium Phosphate). The treatment of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) depletion, particularly in the presence of cardiac disease, renal disease, or acidosis requires careful attention to acid-base balance and appropriate monitoring of serum electrolytes, the electrocardiogram, and the clinical status of the patient.

Information for Patients

Physicians should consider reminding the patient of the following: To take each dose with meals and with a full glass of water or other liquid. To take each dose without crushing, chewing, or sucking the tablets. If those patients are having difficulty swallowing whole tablets, they may try one of the following alternate methods of administration:

  • Break the tablet in half, and take each half separately with a glass of water.
  • Prepare an aqueous (water) suspension as follows:

    1. Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).

    2. Allow approximately 2 minutes for the tablet(s) to disintegrate.

    3. Stir for about half a minute after the tablet(s) has disintegrated.

    4. Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.

    5. Add another 1 fluid ounce of water, swirl, and consume immediately.

    6. Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.


Aqueous suspension of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

To take this medicine following the frequency and amount prescribed by the physician. This is especially important if the patient is also taking diuretics and/or digitalis preparations.

To check with the physician at once if tarry stools or other evidence of gastrointestinal bleeding is noticed.

Laboratory Tests

When blood is drawn for analysis of plasma Pack Emolan Bloqueador SPF 60 it is important to recognize that artifactual elevations can occur after improper venipuncture technique or as a result of in vitro hemolysis of the sample.

Drug Interactions

Potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (see WARNINGS ).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity, and fertility studies in animals have not been performed. Pack Emolan Bloqueador SPF 60 is a normal dietary constituent.

Pregnancy Category C

Animal reproduction studies have not been conducted with Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.

Nursing Mothers

The normal Pack Emolan Bloqueador SPF 60 ion content of human milk is about 13 mEq per liter. Since oral Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) becomes part of the body Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) pool, so long as body Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) is not excessive, the contribution of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride supplementation should have little or no effect on the level in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection; and it may be useful to monitor renal function.

ADVERSE REACTIONS

One of the most severe adverse effects is hyperkalemia (see CONTRAINDICATIONS , WARNINGS , and OVERDOSAGE ). There have also been reports of upper and lower gastrointestinal conditions including obstruction, bleeding, ulceration, and perforation (see CONTRAINDICATIONS and WARNINGS ). The most common adverse reactions to oral Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) salts are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea. These symptoms are due to irritation of the gastrointestinal tract and are best managed by diluting the preparation further, taking the dose with meals or reducing the amount taken at one time.

OVERDOSAGE

The administration of oral Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) salts to persons with normal excretory mechanisms for Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) is administered too rapidly intravenously, potentially fatal hyperkalemia can result (see CONTRAINDICATIONS and WARNINGS ). It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) concentration (6.5-8.0 mEq/L) and characteristic electrocardiographic changes (peaking of T-waves, loss of P-waves, depression of S-T segment, and prolongation of the QT-interval). Late manifestations include muscle paralysis and cardiovascular collapse from cardiac arrest (9-12 mEq/L).

Treatment measures for hyperkalemia include the following:

  • Patients should be closely monitored for arrhythmias and electrolyte changes.
  • Elimination of foods and medications containing Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) and of any agents with potassium-sparing properties such as potassium-sparing diuretics, ARBS, ACE inhibitors, NSAIDS, certain nutritional supplements and many others.
  • Intravenous calcium gluconate if the patient is at no risk of developing digitalis toxicity.
  • Intravenous administration of 300 to 500 mL/hr of 10% dextrose solution containing 10-20 units of crystalline insulin per 1,000 mL.
  • Correction of acidosis, if present, with intravenous sodium bicarbonate.
  • Use of exchange resins, hemodialysis, or peritoneal dialysis.

In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) concentration can produce digitalis toxicity.

The extended release feature means that absorption and toxic effects may be delayed for hours.

Consider standard measures to remove any unabsorbed drug.

DOSAGE AND ADMINISTRATION

The usual dietary intake of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) by the average adult is 50 to 100 mEq per day. Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) from the total body store.

Dosage must be adjusted to the individual needs of each patient. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40-100 mEq per day or more are used for the treatment of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose.

Each Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride.

Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablets USP, 20 mEq should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation (see WARNINGS ).

Patients having difficulty swallowing whole tablets may try one of the following alternate methods of administration:

  • Break the tablet in half, and take each half separately with a glass of water.
  • Prepare an aqueous (water) suspension as follows:
    • Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).
    • Allow approximately 2 minutes for the tablet(s) to disintegrate.
    • Stir for about half a minute after the tablet(s) has disintegrated.
    • Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.
    • Add another 1 fluid ounce of water, swirl, and consume immediately.
    • Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.

Aqueous suspension of Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) Chloride Extended Release Tablets USP, 20 mEq are available in bottles of 100 (NDC 62037-999-01), bottles of 500 (NDC 62037-999-05), and bottles of 1000 (NDC 62037-999-10). Potassium Chloride Extended Release Tablets USP, 20 mEq are capsule shaped, white to off-white tablets, with “ABRS-123” imprinted on one side and scored on the other side for flexibility of dosing.

Storage Conditions

Keep tightly closed. Store at controlled room temperature, 20°-25°C (68°-77°F).

Manufactured by:

Eurand, Inc.

Vandalia, OH 45377 USA

Distributed by:

Watson Pharma, Inc.

Rev. Date (01/09) 173714

Pack Emolan Bloqueador SPF 60 (Potassium Phosphate) chloride 20 Meq

Propylene Glycol:


This medication is used to relieve dry, irritated eyes. Common causes for dry eyes include wind, sun, heating/air conditioning, computer use/reading, and certain medications. This product may contain 1 or more of the following ingredients: carboxymethylcellulose, dextran, glycerin, hypromellose, polyethylene glycol 400 (PEG 400), polysorbate, polyvinyl alcohol, povidone, or Pack Emolan Bloqueador SPF 60 (Propylene Glycol), among others. Eye lubricants keep the eye moist, help to protect the eye from injury and infection, and decrease symptoms of dry eyes such as burning, itching, and feeling as if something is in the eye.

Stearic Acid:



Pack Emolan Bloqueador SPF 60 (Stearic Acid) ACID 12.00%

Cleansing

Excellent in deep cleansing and refines your skin clear

and clean by removing impurities from inside of the

skin.

Rub against the soap until bubbles appear and gently massage all over the skin and rinse off with water.

The soap contains moisturizing agents so it will easily become runny if it comes in contact with water. Keep it

away from water after use.

Hand-made soap may collect water bubbles on its surface if the air is humid, as the moisture in soap meets humidity and expanding. This is a natural phenomenon, so do not be concerned.

For external use only.

Do not eat, and do not use for purposes other than for skin cleansing.

Do not use on areas with wound, eczema, dermatitis...etc.

Immediately stop using in case of problems such as redness, swelling, itchiness, irritation…etc.

Immediately rinse with clean water if product gets in eyes.

Store away from UV rays.

Keep out of reach of children. If product is swallowed, get medical help or contact a Poison Control Center right away.

Mineral Water, Myristic Acid, Lauric Acid, Triethanolamine, Propylene Glycol, Germanium Ferment, Bentonite, Chrysanthemum Morifolium Flower Extract, Ricinus Communis (Castor) Seed Oil, Evening Primrose Oil, Citric Acid, Fragrance

image description

Titanium Dioxide:


Sunscreens are used to protect the skin from the harmful effects of the sun. They help to prevent sunburn and premature aging (e.g., wrinkles, leathery skin). Sunscreens also help to decrease the risk of skin cancer and also of sunburn-like skin reactions (sun sensitivity) caused by some medications (e.g., tetracyclines, sulfa drugs, phenothiazines such as chlorpromazine ). The active ingredients in sunscreens work either by absorbing the sun's ultraviolet (UV) radiation, preventing it from reaching the deeper layers of the skin, or by reflecting the radiation. Wearing sunscreen does not mean that you can stay out longer in the sun. Sunscreens cannot protect against all of the sun's radiation. There are various types of sunscreens available in many forms (e.g., cream, lotion, gel, stick, spray, lip balm). See the Notes section for information about selecting a sunscreen.

Triethanolamine:


Trolamine salicylate is used to treat minor aches and pains of the muscles/joints (such as arthritis, backache, sprains). It belongs to a class of drugs known as salicylates.

Vitamin E (Tocopherol Acetate):


A generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids.

Indication: Pack Emolan Bloqueador SPF 60 (Vitamin E (Tocopherol Acetate)), known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer's, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.

Pack Emolan Bloqueador SPF 60 (Vitamin E (Tocopherol Acetate)) has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. Pack Emolan Bloqueador SPF 60 (Vitamin E (Tocopherol Acetate)) is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. Pack Emolan Bloqueador SPF 60 (Vitamin E (Tocopherol Acetate)) is a fat-soluble vitamin and is an important antioxidant. It acts to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Pack Emolan Bloqueador SPF 60 (Vitamin E (Tocopherol Acetate)) is often used in skin creams and lotions because it is believed to play a role in encouraging skin healing and reducing scarring after injuries such as burns. There are three specific situations when a Pack Emolan Bloqueador SPF 60 (Vitamin E (Tocopherol Acetate)) deficiency is likely to occur. It is seen in persons who cannot absorb dietary fat, has been found in premature, very low birth weight infants (birth weights less than 1500 grams, or 3½ pounds), and is seen in individuals with rare disorders of fat metabolism. A Pack Emolan Bloqueador SPF 60 (Vitamin E (Tocopherol Acetate)) deficiency is usually characterized by neurological problems due to poor nerve conduction. Symptoms may include infertility, neuromuscular impairment, menstrual problems, miscarriage and uterine degradation. Preliminary research has led to a widely held belief that Pack Emolan Bloqueador SPF 60 (Vitamin E (Tocopherol Acetate)) may help prevent or delay coronary heart disease. Antioxidants such as Pack Emolan Bloqueador SPF 60 (Vitamin E (Tocopherol Acetate)) help protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. It also protects other fat-soluble vitamins (A and B group vitamins) from destruction by oxygen. Low levels of Pack Emolan Bloqueador SPF 60 (Vitamin E (Tocopherol Acetate)) have been linked to increased incidence of breast and colon cancer.

Water:


Active ingredient

Pack Emolan Bloqueador SPF 60 (Water) 99.8%

Purpose

Emergency eyewash

Uses

  • for flushing or irrigating the eye to reduce chances of severe injury caused by acid, alkali, or particulate contamination.

Warnings

For external use only

Do not use

  • if solution changes color or gets cloudy
  • with contact lenses
  • if twist-off top is broken or missing
  • in open wounds in or near the eyes

When using this product

  • avoid contamination, do not touch tip of container to any surface

When using this product

  • avoid contamination, do not touch tip of container to any surface

Stop use and consult a doctor if you have

  • changes in vision
  • eye pain
  • continued redness or irritation of the eye, or if the condition worsens or persists

Keep out of reach of children.

If swallowed, get medical help or contact a Poison Control Center right away.

Directions

  • remove contacts before using
  • twist top to remove
  • flush the affected eye as needed, controlling the rate of flow of the solution by pressure on the bottle

  • if necessary, continue flushing with emergency eyewash or shower

  • do not reuse
  • once opened, discard

  • obtain medical treatment

Other information

  • store at room temperature, 15o to 30o C (59o to 86o F)
  • do not freeze

Inactive ingredients

sodium chloride, sodium phosphate dibasic, sodium phosphate monobasic

Questions?

1-800 - 430-5490

Sperian Eye and Face Protection, Inc.

(a Honeywell Company)

825 East Highway 151

Platteville, WI 53818 USA

Pack Emolan Bloqueador SPF 60 pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Pack Emolan Bloqueador SPF 60 available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Pack Emolan Bloqueador SPF 60 destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Pack Emolan Bloqueador SPF 60 Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Pack Emolan Bloqueador SPF 60 pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."SPERIAN EYESALINE EYEWASH (WATER) LIQUID [SPERIAN EYE & FACE PROTECTION INC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."SYSTANE BALANCE (PROPYLENE GLYCOL) EMULSION [ALCON LABORATORIES, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."JINHWAGWANGSU BUBBLE (STEARIC ACID) SOAP [CPBIO CO., LTD]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Pack Emolan Bloqueador SPF 60?

Depending on the reaction of the Pack Emolan Bloqueador SPF 60 after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Pack Emolan Bloqueador SPF 60 not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Pack Emolan Bloqueador SPF 60 addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Pack Emolan Bloqueador SPF 60, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Pack Emolan Bloqueador SPF 60 consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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