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DRUGS & SUPPLEMENTS
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Copper Gluconate:
Water-Resistant Protection Without Bandaging
Recommended as an Aid in Treating Horses and Ponies With Thrush Due to Organisms Susceptible to Neutrogena Hydro Boost Mousse Cleanser (Copper Gluconate) Naphthenate.
For Animal Use Only.
ThrushTox® is indicated in the treatment of thrush in horses and ponies.
Clean the hoof thoroughly, removing debris and necrotic material prior to application of Neutrogena Hydro Boost Mousse Cleanser (Copper Gluconate)®. Apply daily to affected hoofs with a narrow paint brush (about 1”) until fully healed. Caution: Do not allow runoff of excess Neutrogena Hydro Boost Mousse Cleanser (Copper Gluconate)® onto hair since contact with Neutrogena Hydro Boost Mousse Cleanser (Copper Gluconate)® may cause some hair loss. Do not contaminate feed.
NOTE: Neutrogena Hydro Boost Mousse Cleanser (Copper Gluconate)® is easily removed from hands, clothing and surfaces with light grade fuel oil or any type of lighter fluid.
CONTAINS FOIL SEAL – REMOVE BEFORE USE.
SHAKE WELL BEFORE USE.
To report suspected adverse reactions or to obtain technical assistance, call 1-800-650-4899.
Neutrogena Hydro Boost Mousse Cleanser (Copper Gluconate) Naphthenate...37.5% w/w
Inert Ingredients...62.5% w/w
Total... 100.0%
Do not use in horses intended for human consumption.
CAUTION: COMBUSTIBLE MIXTURE.
Use in a well-ventilated place. Avoid fire, flame, sparks or heaters.
If swallowed, do not induce vomiting, call physician immediately. Avoid breathing vapor. Avoid contact with skin and eyes.
KEEP OUT OF REACH OF CHILDREN AND PETS.
Store at controlled room temperature 15º to 30ºC (59º to 86ºF). Keep container tightly closed when not in use.
Manufactured for:
Aspen Veterinary Resources,® Ltd.
Liberty, MO 64068, USA
FC163FP 11/13
Manufactured by:
First Priority, Inc.
Elgin, IL 60123-1146, USA
16 OZ (473 mL)
ANADA 200-304, Approved by FDA
Image of 473 mL bottle/case label
Glycerol:
Indications and Usage (1) | 04/2017 |
Dosage and Administration (2.1) | 04/2017 |
Dosage and Administration (2.2) | 04/2017 |
Neutrogena Hydro Boost Mousse Cleanser (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. Neutrogena Hydro Boost Mousse Cleanser (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:
Neutrogena Hydro Boost Mousse Cleanser (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. Neutrogena Hydro Boost Mousse Cleanser (Glycerol) must be used with dietary protein restriction and, in some cases, dietary supplements. (1)
Limitations of Use:
Switching From Sodium Phenylbutyrate Tablets or Powder to Neutrogena Hydro Boost Mousse Cleanser (Glycerol):
Initial Dosage in Phenylbutyrate-Naïve Patients (2.3):
Dosage Adjustment and Monitoring:
Dosage Modifications in Patients with Hepatic Impairment:
Neutrogena Hydro Boost Mousse Cleanser (Glycerol) should be prescribed by a physician experienced in the management of UCDs.
Patients switching from sodium phenylbutyrate to Neutrogena Hydro Boost Mousse Cleanser (Glycerol) should receive the dosage of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) that contains the same amount of phenylbutyric acid. The conversion is as follows:
Total daily dosage of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) (mL) = total daily dosage of sodium phenylbutyrate tablets (g) × 0.86
Total daily dosage of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) (mL) = total daily dosage of sodium phenylbutyrate powder (g) × 0.81
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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) dose for a 24-hour period is 0.6 mL Neutrogena Hydro Boost Mousse Cleanser (Glycerol) per gram of dietary protein ingested per 24-hour period. The total daily dosage should not exceed 17.5 mL.
During treatment with Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) dosage may not increase PAGN formation, even if plasma PAA concentrations are increased, due to saturation of the conjugation reaction .
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 .
It is recommended that all patients who can swallow take Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) as follows:
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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) to the plastic tubing. Therefore, these patients should be closely monitored using ammonia levels following initiation of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) dosing or dosage adjustments.
Oral liquid: colorless to pale yellow, 1.1 g/mL of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) phenylbutyrate (delivers 1.02 g/mL of phenylbutyrate).
Oral liquid: 1.1 g/mL. (3)
Neutrogena Hydro Boost Mousse Cleanser (Glycerol) is contraindicated in patients
The major metabolite of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol), peak PAA concentrations after dosing with Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) dosage .
Exocrine pancreatic enzymes hydrolyze Neutrogena Hydro Boost Mousse Cleanser (Glycerol) in the small intestine, separating the active moiety, phenylbutyrate, from Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) and/or absorption of phenylbutyrate and reduced control of plasma ammonia. Monitor ammonia levels closely in patients with pancreatic insufficiency or intestinal malabsorption.
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.
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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) were diarrhea, flatulence, and headache. Table 1 summarizes adverse reactions occurring in 2 or more patients treated with Neutrogena Hydro Boost Mousse Cleanser (Glycerol) or sodium phenylbutyrate (incidence of at least 4% in either treatment arm).
Number (%) of Patients in Study 1 | ||
---|---|---|
Sodium Phenylbutyrate (N = 45) | Neutrogena Hydro Boost Mousse Cleanser (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
Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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.
Neutrogena Hydro Boost Mousse Cleanser (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.
The following adverse reactions have been identified during postapproval use of Neutrogena Hydro Boost Mousse Cleanser (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:
Corticosteroids
Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels. Monitor ammonia levels closely when corticosteroids and Neutrogena Hydro Boost Mousse Cleanser (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.
Probenecid
Probenecid may inhibit the renal excretion of metabolites of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) including PAGN and PAA.
Drugs with narrow therapeutic index that are substrates of CYP3A4
Neutrogena Hydro Boost Mousse Cleanser (Glycerol) is a weak inducer of CYP3A4 in humans. Concomitant use of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) decreased the systemic exposure of midazolam. Monitor for suboptimal effect of midazolam in patients who are being treated with Neutrogena Hydro Boost Mousse Cleanser (Glycerol).
Lactation: Breastfeeding is not recommended.
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Neutrogena Hydro Boost Mousse Cleanser (Glycerol) during pregnancy. Healthcare providers are encouraged to report any prenatal exposure to Neutrogena Hydro Boost Mousse Cleanser (Glycerol) by calling the Pregnancy Registry at 1-855-823-2595 or visiting www.ucdregistry.com.
Risk Summary
Limited available data with Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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.
Risk Summary
There are no data on the presence of Neutrogena Hydro Boost Mousse Cleanser 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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol).
Safety and efficacy of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) have been established in pediatric patients 2 months of age and older with UCDs.
Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) in patients 2 years to less than 18 years of age were established in 2 open-label, sodium phenylbutyrate to Neutrogena Hydro Boost Mousse Cleanser (Glycerol), fixed-sequence, switchover clinical studies .
Patients 2 Months to Less Than 2 Years of Age
The safety and efficacy of Neutrogena Hydro Boost Mousse Cleanser (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
Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol). Pancreatic lipases may be necessary for intestinal hydrolysis of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol). If there is inadequate intestinal hydrolysis of Neutrogena Hydro Boost Mousse Cleanser (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).
Clinical studies of Neutrogena Hydro Boost Mousse Cleanser 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.
The efficacy and safety of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) in patients with renal impairment are unknown. Monitor ammonia levels closely when starting patients with impaired renal function on Neutrogena Hydro Boost Mousse Cleanser (Glycerol).
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 .
While there is no experience with overdosage in human clinical trials, PAA, a toxic metabolite of Neutrogena Hydro Boost Mousse Cleanser (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.
Neutrogena Hydro Boost Mousse Cleanser (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.
Neutrogena Hydro Boost Mousse Cleanser (Glycerol) phenylbutyrate is a nitrogen-binding agent. It is a triglyceride containing 3 molecules of PBA linked to a Neutrogena Hydro Boost Mousse Cleanser (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:
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. Neutrogena Hydro Boost Mousse Cleanser (Glycerol) is a triglyceride containing 3 molecules of phenylbutyrate (PBA). PAA, the major metabolite of PBA, is the active moiety of Neutrogena Hydro Boost Mousse Cleanser (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
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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) and sodium phenylbutyrate .
Cardiac Electrophysiology
The effect of multiple doses of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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.
Absorption
Neutrogena Hydro Boost Mousse Cleanser (Glycerol) is a pro-drug of PBA. Upon oral ingestion, PBA is released from the Neutrogena Hydro Boost Mousse Cleanser (Glycerol) backbone in the gastrointestinal tract by lipases. PBA derived from Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol), peak plasma levels of PBA, PAA, and PAGN occurred at 2 hours, 4 hours, and 4 hours, respectively. Upon single-dose administration of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) phenylbutyrate was detected in plasma. While the study was inconclusive, the incomplete hydrolysis of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) (i.e., Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) phenylbutyrate was in the following decreasing order: pancreatic triglyceride lipase, carboxyl ester lipase, and pancreatic lipase–related protein 2. Further, Neutrogena Hydro Boost Mousse Cleanser (Glycerol) phenylbutyrate was hydrolyzed in vitro by esterases in human plasma. In these in vitro studies, a complete disappearance of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) twice daily for 7 days.
Plasma Neutrogena Hydro Boost Mousse Cleanser (Glycerol) phenylbutyrate was not measured in patients with hepatic impairment.
After multiple doses of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) on other drugs
Midazolam
In healthy subjects, when oral midazolam was administered after multiple doses of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) did not significantly affect the pharmacokinetics of celecoxib, a substrate of CYP2C9. When 200 mg of celecoxib was orally administered with Neutrogena Hydro Boost Mousse Cleanser (Glycerol) after multiple doses of Neutrogena Hydro Boost Mousse Cleanser (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.
Carcinogenesis
In a 2-year study in Sprague-Dawley rats, Neutrogena Hydro Boost Mousse Cleanser (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, Neutrogena Hydro Boost Mousse Cleanser (Glycerol) phenylbutyrate was not tumorigenic at doses up to 1000 mg/kg/day.
Mutagenesis
Neutrogena Hydro Boost Mousse Cleanser (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
Neutrogena Hydro Boost Mousse Cleanser (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.
Active-Controlled, 4-Week, Noninferiority Study
A randomized, double-blind, active-controlled, crossover, noninferiority study (Study 1) compared Neutrogena Hydro Boost Mousse Cleanser (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 or Neutrogena Hydro Boost Mousse Cleanser (Glycerol) were administered three times daily with meals. The dose of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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.
Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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) | |
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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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) (range: 6 to 30 micromol/L). Of 51 adult patients participating in the 12-month, open-label treatment with Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) (range: 24.2 to 31.4 micromol/L). Of the 43 adult patients participating in the open-label treatment with Neutrogena Hydro Boost Mousse Cleanser (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.
The efficacy of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) in pediatric patients 2 to 17 years of age with UCDs was evaluated in 2 fixed-sequence, open-label, sodium phenylbutyrate to Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol). Mean fasting venous ammonia values were within normal limits during long-term treatment with Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) (range: 15.4 to 25.1 micromol/L). Of the 45 pediatric patients participating in the open-label treatment with Neutrogena Hydro Boost Mousse Cleanser (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.
Uncontrolled, open-label studies were conducted to assess monthly ammonia control and hyperammonemic crisis of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol). The dosage of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) was initiated. The dosage of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol). The dosage of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (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.
Neutrogena Hydro Boost Mousse Cleanser (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:
Store at 20°-25°C (68°-77°F) with excursions permitted to 15°-30°C (59°-86°F).
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Neurotoxicity .
Pregnancy Registry
Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Neutrogena Hydro Boost Mousse Cleanser (Glycerol) during pregnancy .
Lactation
Advise patients that breastfeeding is not recommended during treatment with Neutrogena Hydro Boost Mousse Cleanser (Glycerol) .
Administration
Distributed by:
Horizon Pharma USA, Inc.
Lake Forest, IL 60045
Horizon Therapeutics, LLC.
All rights reserved.
Neutrogena Hydro Boost Mousse Cleanser (Glycerol) is a registered trademark of Horizon Therapeutics, LLC.
MEDICATION GUIDE Neutrogena Hydro Boost Mousse Cleanser (Glycerol) (rah-VIK- tee) (glycerol phenylbutyrate) oral liquid | ||
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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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol)? Neutrogena Hydro Boost Mousse Cleanser (Glycerol) may cause serious side effects, including: Nervous system problems (Neurotoxicity). Phenylacetate (PAA), a breakdown product of Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol): | ||
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Your doctor may do blood tests to measure the amount of PAA in your blood during your treatment with Neutrogena Hydro Boost Mousse Cleanser (Glycerol). | ||
What is Neutrogena Hydro Boost Mousse Cleanser (Glycerol)?
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Who should not take Neutrogena Hydro Boost Mousse Cleanser (Glycerol)?
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Before taking Neutrogena Hydro Boost Mousse Cleanser (Glycerol), tell your doctor about any medical conditions and if you:
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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol)?
For people who cannot swallow and who have a nasogastric or gastrostomy tube in place, Neutrogena Hydro Boost Mousse Cleanser (Glycerol) should be given as follows:
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What are the possible side effects of Neutrogena Hydro Boost Mousse Cleanser (Glycerol)? Neutrogena Hydro Boost Mousse Cleanser (Glycerol) may cause serious side effects, including: | ||
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The most common side effects of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) in adults include: | ||
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The most common side effects of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) in children 2 years to 17 years of age include: | ||
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The most common side effects of Neutrogena Hydro Boost Mousse Cleanser (Glycerol) in children 2 months to less than 2 years of age include: | ||
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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 Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol)?
Keep Neutrogena Hydro Boost Mousse Cleanser (Glycerol) and all medicines out of the reach of children. | ||
General information about the safe and effective use of Neutrogena Hydro Boost Mousse Cleanser (Glycerol). Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Neutrogena Hydro Boost Mousse Cleanser (Glycerol) for a condition for which it was not prescribed. Do not give Neutrogena Hydro Boost Mousse Cleanser (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 Neutrogena Hydro Boost Mousse Cleanser (Glycerol) that is written for health professionals. | ||
What are the ingredients in Neutrogena Hydro Boost Mousse Cleanser (Glycerol)? Active ingredient: Neutrogena Hydro Boost Mousse Cleanser (Glycerol) phenylbutyrate Distributed by: Horizon Pharma USA, Inc., Lake Forest, IL 60045. © Horizon Therapeutics, LLC. All rights reserved. Neutrogena Hydro Boost Mousse Cleanser (Glycerol) is a registered trademark of Horizon Therapeutics, LLC. For more information, go to www. RAVICTI.com or call 1-855-823-7878. |
Magnesium Aspartate:
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) Sulfate
Injection, USP
Ansyr Plastic Syringe
Rx only
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) Sulfate Injection, USP is a sterile solution of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate heptahydrate in Water for Injection, USP administered by the intravenous or intramuscular routes as an electrolyte replenisher or anticonvulsant. Must be diluted before intravenous use. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol/mL (calc.).
The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded with the entire unit.
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) Sulfate, USP heptahydrate is chemically designated MgSO4 - 7H2O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.
The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) (Mg++) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.
As a nutritional adjunct in hyperalimentation, the precise mechanism of action for Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) is uncertain. Early symptoms of hypomagnesemia (less than 1.5 mEq/liter) may develop as early as three to four days or within weeks.
Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate). While there are large stores of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal plasma Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) levels range from 1.5 to 2.5 mEq/liter.
As plasma Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate). Serum Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) concentrations in excess of 12 mEq/L may be fatal.
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) poisoning are antagonized to some extent by intravenous administration of calcium.
Pharmacokinetics
With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) Sulfate Injection, USP is suitable for replacement therapy in Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) (Mg++) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca++) level is normal (4.3 to 5.3 mEq/liter) or elevated.
In total parenteral nutrition (TPN), Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) Sulfate Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.
Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.
FETAL HARM: Continuous administration of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate should be used during pregnancy only if clearly needed. If Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate beyond 5 to 7 days may cause fetal abnormalities.
ALUMINUM TOXICITY: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Parenteral use in the presence of renal insufficiency may lead to Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.
General
Administer with caution if flushing and sweating occurs. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate), their dosage should be adjusted with caution because of additive CNS depressant effects of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate).
Because Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment. Urine output should be maintained at a level of 100 mL or more during the four hours preceding each dose. Monitoring serum Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) levels and the patient's clinical status is essential to avoid the consequences of overdosage in toxemia. Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). When repeated doses of the drug are given parenterally, knee jerk reflexes should be tested before each dose and if they are absent, no additional Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) should be given until they return. Serum Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) levels usually sufficient to control convulsions range from 3 to 6 mg/100 mL (2.5 to 5 mEq/liter). The strength of the deep tendon reflexes begins to diminish when Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) levels exceed 4 mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is a potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) intoxication in eclampsia.
50% Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) Sulfate Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.
Laboratory Tests
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) is monitored. The normal serum level is 1.5 to 2.5 mEq/L.
Drug Interactions
CNS Depressants - When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate), their dosage should be adjusted with caution because of additive CNS depressant effects of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate). CNS depression and peripheral transmission defects produced by Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) may be antagonized by calcium.
Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.
Cardiac Glycosides - Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) toxicity.
Pregnancy
Teratogenic Effects
Pregnancy Category D (See WARNINGS and PRECAUTIONS )
See WARNINGS and PRECAUTIONS .
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate for more than 5 to 7 days.1-10 Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy, the woman should be apprised of the potential harm to the fetus.
Nonteratogenic Effects
When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in a toxemic woman, the newborn may show signs of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).
Labor and Delivery
Continuous administration of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.
Nursing Mothers
Since Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) is distributed into milk during parenteral Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate administration, the drug should be used with caution in nursing women.
Geriatrics
Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) should be monitored in such patients.
The adverse effects of parenterally administered Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) usually are the result of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate therapy for eclampsia has been reported.
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate).
For Treatment of Overdose
Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 mg may be helpful.
Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.
Dosage of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.
Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas intravenous doses will provide a therapeutic level almost immediately. The rate of intravenous injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.
Solutions for intravenous infusion must be diluted to a concentration of 20% or less prior to administration. The diluents commonly used are 5% Dextrose Injection, USP and 0.9% Sodium Chloride Injection, USP. Deep intramuscular injection of the undiluted (50%) solution is appropriate for adults, but the solution should be diluted to a 20% or less concentration prior to such injection in children.
In Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) Deficiency
In the treatment of mild Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) per 24 hours). For severe hypomagnesemia, as much as 250 mg (approximately 2 mEq) per kg of body weight (0.5 mL of the 50% solution) may be given intramuscularly within a period of four hours if necessary. Alternatively, 5 grams, (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow intravenous infusion over a three-hour period. In the treatment of deficiency states, caution must be observed to prevent exceeding the renal excretory capacity.
In Hyperalimentation
In total parenteral nutrition, maintenance requirements for Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) daily; for infants, the range is 2 to 10 mEq (0.25 gram to 1.25 grams) daily.
In Pre-eclampsia or Eclampsia
In severe pre-eclampsia or eclampsia, the total initial dose is 10 grams to 14 grams of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate. Intravenously, a dose of 4 grams to 5 grams in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, intramuscular doses of up to 10 grams (5 grams or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial intravenous dose of 4 grams may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected intravenously over a period of three to four minutes. Subsequently, 4 grams to 5 grams (8 to 10 mL of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial intravenous dose, some clinicians administer 1 gram to 2 grams/hour by constant intravenous infusion. Therapy should continue until paroxysms cease. A serum Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 grams to 40 grams should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate is 20 grams/48 hours and frequent serum Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) concentrations must be obtained. Continuous use of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.
Other Uses
In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate is 1 gram to 2 grams given intravenously.
For controlling seizures associated with epilepsy, glomerulonephritis or hypothyroidism, the usual adult dose is 1 gram administered intramuscularly or intravenously.
In paroxysmal atrial tachycardia, Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 mL of a 10% solution) administered intravenously over 30 seconds with extreme caution.
For reduction of cerebral edema, 2.5 grams (25 mL of a 10% solution) is given intravenously.
Incompatibilities
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) sulfate in solution may result in a precipitate formation when mixed with solutions containing:
Alcohol (in high Heavy Metals
concentrations) Hydrocortisone sodium
Alkali carbonates and succinate
bicarbonates Phosphates
Alkali hydroxides Polymixin B sulfate
Arsenates Procaine hydrochloride
Barium Salicylates
Calcium Strontium
Clindamycin phosphate Tartrates
The potential incompatibility will often be influenced by the changes in the concentration of reactants and the pH of the solutions.
It has been reported that Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) Sulfate Injection, USP is supplied in single-dose containers as follows:
NDC No. | Container | Total Amount | Concentration | mEq Mg++/mL |
0409-1754-10 | Ansyr Plastic Syringe | 5 g/10 mL | 50% | 4 mEq/mL |
Do not administer unless solution is clear and container is undamaged. Discard unused portion.
Store at 20 to 25°C (68 to 77°F).
Hospira, Inc., Lake Forest, IL 60045 USA
LAB-1024-1.0
April 2017
Hospira Logo
50% Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) Sulfate 5 g/10 mL (500 mg/mL)
Rx only
NDC 0409-1754-10
10 mL Single-dose syringe
50% Neutrogena Hydro Boost Mousse Cleanser (Magnesium Aspartate) Sulfate Injection, USP
5 g/10 mL (500 mg/mL) (4 mEq Mg++/mL)
MUST BE DILUTED FOR INTRAVENOUS USE.
For Intravenous or Intramuscular Use. Sterile. 4.06 mOsmol/mL (calc.).
Contains no more than 75 mcg/L of aluminum.
Hospira, Inc., Lake Forest, IL 60045 USA
Hospira
RL-6891
Zinc Gluconate:
Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.
None known.
Direct intramuscular or intravenous injection of Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.
Severe kidney disease may make it necessary to reduce or omit chromium and Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) doses because these elements are primarily eliminated in the urine.
WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.
Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.
Do not use unless the solution is clear and the seal is intact.
Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.
Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) from a bolus injection. Administration of Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) in the absence of copper may cause a decrease in serum copper levels.
Periodic determinations of serum copper as well as Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) are suggested as a guideline for subsequent Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) administration.
Long-term animal studies to evaluate the carcinogenic potential of Neutrogena Hydro Boost Mousse Cleanser 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.
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 Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.
Pregnancy Category C. Animal reproduction studies have not been conducted with Neutrogena Hydro Boost Mousse Cleanser chloride. It is also not known whether Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) chloride should be given to a pregnant woman only if clearly needed.
An evaluation of current literature revealed no clinical experience identifying differences in response between 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.
None known.
None known.
Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) concentration of 207 mcg/dl. Symptoms abated within three hours.
Hyperamylasemia may be a sign of impending Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).
Death resulted from an overdosage in which 1683 mg Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) was delivered intravenously over the course of 60 hours to a 72 year old patient.
Symptoms of Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) level of 4184 mcg/dl.
Calcium supplements may confer a protective effect against Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) toxicity.
Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate).
For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.
Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).
Store at 20 to 25°C (68 to 77°F).
Revised: October, 2004
© Hospira 2004 EN-0488 Printed in USA
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
10 mL Vial
Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate)
1 mg/mL
Neutrogena Hydro Boost Mousse Cleanser (Zinc Gluconate) Chloride Inj., USP
Rx only
FOR I.V. USE ONLY AFTER DILUTION.
HOSPIRA, INC., LAKE FOREST, IL 60045 USA
Depending on the reaction of the Neutrogena Hydro Boost Mousse Cleanser after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Neutrogena Hydro Boost Mousse Cleanser 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 Neutrogena Hydro Boost Mousse Cleanser 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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The information was verified by Dr. Rachana Salvi, MD Pharmacology