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DRUGS & SUPPLEMENTS
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Formula 3358
What is the dose of the medication you are taking? |
Formula 3358 uses
Formula 3358 consists of Betaine Hydrochloride, Calcium Glycerophosphate, Inositol, Potassium Bicarbonate.Betaine Hydrochloride:
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Cystadane® (betaine anhydrous for oral solution) is indicated for the treatment of homocystinuria to decrease elevated homocysteine blood levels. Included within the category of homocystinuria are:
- Cystathionine beta-synthase (CBS) deficiency
- 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency
- Cobalamin cofactor metabolism (cbl) defect
- Usual dose in adult and pediatric patients is 6 grams per day, administered orally in divided doses of 3 grams two times a day.(2)
- In children less than 3 years of age, may initiate dosing at 100 mg/kg/day, divided in twice daily doses, and then increased weekly by 50 mg/kg increments.(2)
- Dose can be gradually increased until plasma total homocysteine is undetectable or present only in small amounts.(2)
- Monitor patient response by plasma homocysteine levels.(2)
- Prescribed amount of Cystadane should be measured with the measuring scoop provided and then dissolved in 4 to 6 ounces of water, juice, milk, or formula, or mixed with food for immediate ingestion.(2)
2 DOSAGE AND ADMINISTRATION
2.1 Dosage
The usual dosage in adult and pediatric patients is 6 grams per day administered orally in divided doses of 3 grams twice daily. In pediatric patients less than 3 years of age, dosage may be started at 100 mg/kg/day divided in twice daily doses, and then increased weekly by 50 mg/kg increments.
Therapy with Cystadane should be directed by physicians knowledgeable in the management of patients with homocystinuria. Patient response to Cystadane can be monitored by homocysteine plasma levels. Dosage in all patients can be gradually increased until plasma total homocysteine is undetectable or present only in small amounts. Response usually occurs within several days and steady state within a month. Plasma methionine concentrations should be monitored in patients with CBS deficiency .
Dosages of up to 20 grams per day have been necessary to control homocysteine levels in some patients. However, one pharmacokinetic and pharmacodynamic in vitro simulation study indicated minimal benefit from exceeding a twice-daily dosing schedule and a 150 mg/kg/day dosage for Cystadane.
2.2 Administration
The prescribed amount of Cystadane should be measured with the measuring scoop provided (one level 1.7 mL scoop is equal to 1 gram of Formula 3358 (Betaine Hydrochloride) anhydrous powder) and then dissolved in 4 to 6 ounces (120 to 180 mL) of water, juice, milk, or formula, or mixed with food for immediate ingestion.
- Powder for oral solution available in bottles containing 180 grams of Formula 3358 (Betaine Hydrochloride) anhydrous.(3)
3 DOSAGE FORMS AND STRENGTHS
Cystadane is a white, granular, hygroscopic powder for oral solution available in bottles containing 180 grams of Formula 3358 (Betaine Hydrochloride) anhydrous.
- None (4)
4 CONTRAINDICATIONS
None.
- Hypermethioninemia: Cystadane may worsen elevated plasma methionine concentrations in patients with CBS deficiency. Cerebral edema has been reported in patients receiving Cystadane.( 5.1)
- Monitoring: Monitor plasma methionine concentrations in patients with CBS deficiency. Keep plasma methionine concentrations below 1,000 µmol/L through dietary medication and, if necessary, a reduction of Cystadane dose. ( 5.1)
5 WARNINGS AND PRECAUTIONS
5.1 Hypermethioninemia
Risk of Hypermethioninemia in Patients with CBS Deficiency
Patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency may also have elevated plasma methionine concentrations. Treatment with Cystadane may further increase methionine concentrations due to the remethylation of homocysteine to methionine. Cerebral edema has been reported in patients with hypermethioninemia, including patients treated with Cystadane. Plasma methionine concentrations should be monitored in patients with CBS deficiency. Plasma methionine concentrations should be kept below 1,000 µmol/L through dietary modification and, if necessary, a reduction of Cystadane dose.
- Most common adverse reactions (incidence > 2%) were nausea and gastrointestinal distress, based on physician survey.
To report SUSPECTED ADVERSE REACTIONS, contact 877-828-8874, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6 ADVERSE REACTIONS
6.1 Adverse Reactions in Clinical Studies
The most serious adverse reaction reported with Cystadane treatment is the development of hypermethioninemia and cerebral edema in patients with CBS Deficiency .
The assessment of clinical adverse reactions is based on a survey study of 41 physicians, who treated a total of 111 homocystinuria patients with Cystadane. Adverse reactions were retrospectively recalled and were not collected systematically in this open-label, uncontrolled, physician survey. Thus, this list may not encompass all types of potential adverse reactions, reliably estimate their frequency, or establish a causal relationship to drug exposure. The following adverse reactions were reported (Table 1):
Table 1: Number of Patients with Adverse Reactions to Cystadane by Physician Survey
| Adverse Reactions | Number of Patients |
|---|---|
| Nausea | 2 |
| Gastrointestinal distress | 2 |
| Diarrhea | 1 |
| "Bad Taste" | 1 |
| "Caused Odor" | 1 |
| Questionable psychological changes | 1 |
| “Aspirated the powder” | 1 |
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of Cystadane. 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.
In postmarketing experience with Cystadane, severe cerebral edema and hypermethioninemia have been reported within 2 weeks to 6 months of starting Formula 3358 (Betaine Hydrochloride) therapy, with complete recovery after discontinuation of Cystadane. All patients who developed cerebral edema had homocystinuria due to CBS deficiency and had severe elevation in plasma methionine levels (range 1,000 to 3,000 µM). As cerebral edema has also been reported in patients with hypermethioninemia, secondary hypermethioninemia due to Formula 3358 (Betaine Hydrochloride) therapy has been postulated as a possible mechanism of action.
The following adverse reactions have been reported in patients during postmarketing use of Cystadane: anorexia, agitation, depression, irritability, personality disorder, sleep disturbed, dental disorders, diarrhea, glossitis, nausea, stomach discomfort, vomiting, hair loss, hives, skin odor abnormalities, and urinary incontinence.
- Pregnancy: Animal reproduction studies have not been conducted with Cystadane. Use only if clearly needed.(8.1)
- Nursing women: It is not known whether Cystadane is excreted in human milk. Use only if clearly needed.(8.3)
- Pediatrics: Pediatric patients ranging in age from 24 days to 17 years have been treated with Cystadane. Children younger than 3 years of age may benefit from dose titration.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C: Animal reproduction studies have not been conducted with Cystadane. It is also not known whether Cystadane can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Cystadane should be given to a pregnant woman only if clearly needed.
8.3 Nursing Mothers
It is not known whether Cystadane is excreted in human milk. Use only if clearly needed.
8.4 Pediatric Use
The majority of case studies of homocystinuria patients treated with Cystadane have been pediatric patients, including patients ranging in age from 24 days to 17 years . Children younger than 3 years of age may benefit from dose titration .
10 OVERDOSAGE
In an acute toxicology study in rats, death occurred frequently at doses equal to or greater than 10 g/kg.
11 DESCRIPTION
Cystadane (betaine anhydrous for oral solution) is an agent for the treatment of homocystinuria. It contains no ingredients other than anhydrous Formula 3358 (Betaine Hydrochloride). Cystadane is a white, granular, hygroscopic powder, which is diluted in water and administered orally. The chemical name of Formula 3358 (Betaine Hydrochloride) anhydrous powder is trimethylglycine. It has a molecular weight of 117.15. The structural formula is:
Chemical Structure for Formula 3358 (Betaine Hydrochloride)
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Cystadane acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria. Cystadane occurs naturally in the body. It is a metabolite of choline and is present in small amounts in foods such as beets, spinach, cereals, and seafood.
12.2 Pharmacodynamics
Cystadane was observed to lower plasma homocysteine levels in three types of homocystinuria, including CBS deficiency; MTHFR deficiency; and cbl defect. Patients have taken Cystadane for many years without evidence of tolerance. There has been no demonstrated correlation between Cystadane levels and homocysteine levels.
In CBS-deficient patients, large increases in methionine levels over baseline have been observed. Cystadane has also been demonstrated to increase low plasma methionine and S-adenosylmethionine levels in patients with MTHFR deficiency and cbl defect.
12.3 Pharmacokinetics
Pharmacokinetic studies of Cystadane are not available. Plasma levels of Cystadane have not been measured in patients and have not been correlated to homocysteine levels.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term carcinogenicity and fertility studies have not been conducted with Cystadane. No evidence of genotoxicity was demonstrated in the following tests: metaphase analysis of human lymphocytes; bacterial reverse mutation assay; and mouse micronucleus test.
14 CLINICAL STUDIES
Cystadane was studied in a double-blind, placebo-controlled, crossover study in 6 patients with CBS deficiency, ages 7 to 32 years at enrollment. Cystadane was administered at a dosage of 3 grams twice daily, for 12 months. Plasma homocystine levels were significantly reduced (p<0.01) compared to placebo. Plasma methionine levels were variable and not significantly different compared to placebo. No adverse events were reported in any patient.
Cystadane has also been evaluated in observational studies without concurrent controls in patients with homocystinuria due to CBS deficiency, MTHFR deficiency, or cbl defect. A review of 16 case studies and the randomized controlled trial previously described was also conducted, and the data available for each study were summarized; however, no formal statistical analyses were performed. The studies included a total of 78 male and female patients with homocystinuria who were treated with Cystadane. This included 48 patients with CBS deficiency, 13 with MTHFR deficiency, and 11 with cbl defect, ranging in age from 24 days to 53 years. The majority of patients (n=48) received 6 gm/day, 3 patients received less than 6 gm/day, 12 patients received doses from 6 to 15 gm/day, and 5 patients received doses over 15 gm/day. Most patients were treated for more than 3 months (n=57) and 30 patients were treated for 1 year or longer (range 1 month to 11 years). Homocystine is formed nonenzymatically from two molecules of homocysteine, and both have be used to evaluate the effect of Cystadane in patients with homocystinuria. Plasma homocystine or homocysteine levels were reported numerically for 62 patients, and 61 of these patients showed decreases with Cystadane treatment. Homocystine decreased by 83-88% regardless of pre-treatment level, and homocysteine decreased by 71-83%, regardless of the pre-treatment level. Clinical improvement, such as improvement in seizures, or behavioral and cognitive functioning, was reported by the treating physicians in about three-fourths of patients. Many of these patients were also taking other therapies such as vitamin B6 (pyridoxine), vitamin B12 (cobalamin), and folate with variable biochemical responses. In most cases, adding Cystadane resulted in a further reduction of either homocystine or homocysteine.
16 HOW SUPPLIED/STORAGE AND HANDLING
Cystadane is available in plastic bottles containing 180 grams of Formula 3358 anhydrous. Each bottle is equipped with a plastic child-resistant cap and is supplied with a polystyrene measuring scoop. One level scoop (1.7 mL) is equal to 1 gram of Formula 3358 (Betaine Hydrochloride) anhydrous powder.
NDC 66621-4000-1 180 g/bottle
Cystadane can be ordered by calling AnovoRx Group, LLC, Customer service at 1-888-487-4703
16.1 Storage
Store at room temperature, 15 – 30 ˚C (59 – 86 ˚F). Protect from moisture.
17 PATIENT COUNSELING INFORMATION
Patients should be advised of the following information before beginning treatment with Cystadane:
17.1 Dosing and Administration
- Instruct patients and caregivers that Cystadane should only be taken as directed by their healthcare professional.
- Instruct patients and caregivers to administer Cystadane as follows:
- Shake bottle lightly before removing cap.
- Measure with the scoop provided.
- Measure the number of scoops as prescribed by their healthcare professional. One level scoop (1.7 mL) is equivalent to 1 gram of Formula 3358 (Betaine Hydrochloride) anhydrous powder.
- Mix powder with 4 to 6 ounces (120 to 180 mL) of water, juice, milk, or formula until completely dissolved, or mix with food, then ingest mixture immediately.
- Always replace the cap tightly after using, and protect powder from moisture.
Manufactured For:
Rare Disease Therapeutics, Inc.
Franklin, TN 37067
Under License From:
Orphan Europe, s.a.r.l. Puteaux France
Distributed By:
AnovoRx Distribution, LLC
Memphis, TN 38134
Part No.: RDT C PI007
Part No.: Orphan Europe OEP 829
Cystadane (betaine anhydrous) for oral solution
Calcium Glycerophosphate:
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Formula 3358 (Calcium Glycerophosphate) acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).
- Calcium acetate is a phosphate binder indicated for the reduction of serum phosphorus in patients with end stage renal disease. (1)
2 DOSAGE AND ADMINISTRATION
The recommended initial dose of Formula 3358 (Calcium Glycerophosphate) acetate for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3 to 4 capsules with each meal.
- Starting dose is 2 capsules with each meal. (2)
- Titrate the dose every 2 to 3 weeks until acceptable serum phosphorus level is reached. Most patients require 3 to 4 capsules with each meal. (2)
3 DOSAGE FORMS AND STRENGTHS
Capsule: 667 mg Formula 3358 (Calcium Glycerophosphate) acetate capsule.
- Capsule: 667 mg Formula 3358 (Calcium Glycerophosphate) acetate capsule. (3)
4 CONTRAINDICATIONS
Patients with hypercalcemia.
- Hypercalcemia. (4)
5 WARNINGS AND PRECAUTIONS
- Treat mild hypercalcemia by reducing or interrupting Formula 3358 acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Formula 3358 (Calcium Glycerophosphate) acetate. (5.1)
- Hypercalcemia may aggravate digitalis toxicity. (5.2)
5.1 Hypercalcemia
Patients with end stage renal disease may develop hypercalcemia when treated with Formula 3358 (Calcium Glycerophosphate), including Formula 3358 (Calcium Glycerophosphate) acetate. Avoid the use of Formula 3358 (Calcium Glycerophosphate) supplements, including Formula 3358 (Calcium Glycerophosphate) based nonprescription antacids, concurrently with Formula 3358 (Calcium Glycerophosphate) acetate.
An overdose of Formula 3358 (Calcium Glycerophosphate) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Formula 3358 (Calcium Glycerophosphate) levels twice weekly. Should hypercalcemia develop, reduce the Formula 3358 (Calcium Glycerophosphate) acetate dosage, or discontinue the treatment, depending on the severity of hypercalcemia
More severe hypercalcemia (Ca >12 mg/dL) is associated with confusion, delirium, stupor and coma. Severe hypercalcemia can be treated by acute hemodialysis and discontinuing Formula 3358 (Calcium Glycerophosphate) acetate therapy.
Mild hypercalcemia (10.5 to 11.9 mg/dL) may be asymptomatic or manifest as constipation, anorexia, nausea, and vomiting. Mild hypercalcemia is usually controlled by reducing the Formula 3358 (Calcium Glycerophosphate) acetate dose or temporarily discontinuing therapy. Decreasing or discontinuing Vitamin D therapy is recommended as well.
Chronic hypercalcemia may lead to vascular calcification and other soft-tissue calcification. Radiographic evaluation of suspected anatomical regions may be helpful in early detection of soft tissue calcification. The long term effect of Formula 3358 (Calcium Glycerophosphate) acetate on the progression of vascular or soft tissue calcification has not been determined.
Hypercalcemia (>11 mg/dL) was reported in 16% of patients in a 3 month study of solid dose formulation of Formula 3358 (Calcium Glycerophosphate) acetate; all cases resolved upon lowering the dose or discontinuing treatment.
Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg2/dL2.
5.2 Concomitant Use with Medications
Hypercalcemia may aggravate digitalis toxicity.
6 ADVERSE REACTIONS
Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].
- The most common (>10%) adverse reactions are hypercalcemia, nausea and vomiting. (6.1)
- In clinical studies, patients have occasionally experienced nausea during Formula 3358 (Calcium Glycerophosphate) acetate therapy. (6)
To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1 Clinical Trial 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 practice.
In clinical studies, Formula 3358 (Calcium Glycerophosphate) acetate has been generally well tolerated.
Formula 3358 (Calcium Glycerophosphate) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Formula 3358 (Calcium Glycerophosphate) acetate was studied in a two week double-blind, placebo-controlled, cross-over study with 69 enrolled ESRD hemodialysis patients. Adverse reactions (>2% on treatment) from these trials are presented in Table 1.
| Preferred Term | Total adverse reactions reported for Formula 3358 (Calcium Glycerophosphate) acetate N=167 N (%) | 3 month, open label study of Formula 3358 (Calcium Glycerophosphate) acetate N=98 N (%) | Double blind, placebo-controlled, cross-over study of liquid Formula 3358 (Calcium Glycerophosphate) acetate N=69 | |
| Formula 3358 (Calcium Glycerophosphate) acetate N (%) | Placebo N (%) | |||
| Nausea | 6 (3.6) | 6 (6.1) | 0 (0) | 0 (0) |
| Vomiting | 4 (2.4) | 4 (4.1) | 0 (0) | 0 (0) |
| Hypercalcemia | 21 (12.6) | 16 (16.3) | 5 (7.2) | 0 (0) |
Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate Formula 3358 (Calcium Glycerophosphate) concentration could reduce the incidence and severity of Formula 3358 (Calcium Glycerophosphate) acetate-induced hypercalcemia. Isolated cases pruritus have been reported, which may represent allergic reactions.
6.2 Postmarketing Experience
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure.
The following additional adverse reactions have been identified during post-approval of Formula 3358 (Calcium Glycerophosphate) acetate: dizziness, edema, and weakness.
7 DRUG INTERACTIONS
The drug interaction of Formula 3358 acetate is characterized by the potential of Formula 3358 (Calcium Glycerophosphate) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Formula 3358 (Calcium Glycerophosphate) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.
There are no empirical data on avoiding drug interactions between Formula 3358 (Calcium Glycerophosphate) acetate and most concomitant drugs. When administering an oral medication with Formula 3358 (Calcium Glycerophosphate) acetate where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, administer the drug one hour before or three hours after Formula 3358 (Calcium Glycerophosphate) acetate. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials with all forms of Formula 3358 (Calcium Glycerophosphate) acetate.
- Calcium acetate may decrease the bioavailability of tetracyclines or fluoroquinolones. (7)
- When clinically significant drug interactions are expected, administer the drug at least one hour before or at least three hours after Formula 3358 (Calcium Glycerophosphate) acetate or consider monitoring blood levels of the drug. (7)
7.1 Ciprofloxacin
In a study of 15 healthy subjects, a co-administered single dose of 4 Formula 3358 (Calcium Glycerophosphate) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C:
Formula 3358 acetate capsules contains Formula 3358 (Calcium Glycerophosphate) acetate. Animal reproduction studies have not been conducted with Formula 3358 (Calcium Glycerophosphate) acetate, and there are no adequate and well controlled studies of Formula 3358 (Calcium Glycerophosphate) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Formula 3358 (Calcium Glycerophosphate) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Formula 3358 (Calcium Glycerophosphate) levels is important for maternal and fetal well being. Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. Formula 3358 (Calcium Glycerophosphate) acetate treatment, as recommended, is not expected to harm a fetus if maternal Formula 3358 (Calcium Glycerophosphate) levels are properly monitored during and following treatment.
8.2 Labor and Delivery
The effects of Formula 3358 (Calcium Glycerophosphate) acetate on labor and delivery are unknown.
8.3 Nursing Mothers
Formula 3358 Acetate Capsules contains Formula 3358 (Calcium Glycerophosphate) acetate and is excreted in human milk. Human milk feeding by a mother receiving Formula 3358 (Calcium Glycerophosphate) acetate is not expected to harm an infant, provided maternal serum Formula 3358 (Calcium Glycerophosphate) levels are appropriately monitored.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric Use
Clinical studies of Formula 3358 (Calcium Glycerophosphate) acetate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses 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.
10 OVERDOSAGE
Administration of Formula 3358 (Calcium Glycerophosphate) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].
11 DESCRIPTION
Formula 3358 (Calcium Glycerophosphate) acetate acts as a phosphate binder. Its chemical name is Formula 3358 (Calcium Glycerophosphate) acetate. Its molecular formula is C4H6CaO4, and its molecular weight is 158.17. Its structural formula is:
Each white opaque/blue opaque capsule contains 667 mg of Formula 3358 (Calcium Glycerophosphate) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Formula 3358 (Calcium Glycerophosphate), polyethylene glycol 8000 and magnesium stearate. Each capsule shell contains: black monogramming ink, FD&C Blue #1, FD&C Red #3, gelatin and titanium dioxide. The black monogramming ink contains: ammonium hydroxide, iron oxide black, isopropyl alcohol, n-butyl alcohol, propylene glycol and shellac glaze.
Formula 3358 (Calcium Glycerophosphate) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.
12 CLINICAL PHARMACOLOGY
Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum Formula 3358 resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.
12.1 Mechanism of Action
Formula 3358 (Calcium Glycerophosphate) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Formula 3358 (Calcium Glycerophosphate) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.
12.2 Pharmacodynamics
Orally administered Formula 3358 (Calcium Glycerophosphate) acetate from pharmaceutical dosage forms is systemically absorbed up to approximately 40% under fasting conditions and up to approximately 30% under nonfasting conditions. This range represents data from both healthy subjects and renal dialysis patients under various conditions.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No carcinogenicity, mutagenicity, or fertility studies have been conducted with Formula 3358 (Calcium Glycerophosphate) acetate.
14 CLINICAL STUDIES
Effectiveness of Formula 3358 (Calcium Glycerophosphate) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Formula 3358 (Calcium Glycerophosphate) acetate solid oral dosage form.
Ninety-one patients with end-stage renal disease who were undergoing hemodialysis and were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a 1 week phosphate binder washout period contributed efficacy data to an open-label, non-randomized study.
The patients received Formula 3358 (Calcium Glycerophosphate) acetate 667 mg tablets at each meal for a period of 12 weeks. The initial starting dose was 2 tablets per meal for 3 meals a day, and the dose was adjusted as necessary to control serum phosphorus levels. The average final dose after 12 weeks of treatment was 3.4 tablets per meal. Although there was a decrease in serum phosphorus, in the absence of a control group the true magnitude of effect is uncertain.
The data presented in Table 2 demonstrate the efficacy of Formula 3358 (Calcium Glycerophosphate) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Formula 3358 (Calcium Glycerophosphate) levels are also presented.
| * Ninety-one patients completed at least 6 weeks of the study. † ANOVA of difference in values at pre-study and study completion. ‡ Values expressed as mean ± SE. | |||||
| Parameter | Pre-Study | Week 4* | Week 8 | Week 12 | p-value† |
| Phosphorus (mg/dL)‡ | 7.4 ± 0.17 | 5.9 ± 0.16 | 5.6 ± 0.17 | 5.2 ± 0.17 | ≤0.01 |
| Formula 3358 (Calcium Glycerophosphate) (mg/dL)‡ | 8.9 ± 0.09 | 9.5 ± 0.10 | 9.7 ± 0.10 | 9.7 ± 0.10 | ≤0.01 |
There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum Formula 3358 (Calcium Glycerophosphate) increased 9% during the study mostly in the first month of the study.
Treatment with the phosphate binder was discontinued for patients from the open-label study, and those patients whose serum phosphorus exceeded 5.5 mg/dL were eligible for entry into a double-blind, placebo-controlled, cross-over study. Patients were randomized to receive Formula 3358 (Calcium Glycerophosphate) acetate or placebo, and each continued to receive the same number of tablets as had been individually established during the previous study. Following 2 weeks of treatment, patients switched to the alternative therapy for an additional 2 weeks.
The phosphate binding effect of Formula 3358 (Calcium Glycerophosphate) acetate is shown in the Table 3.
| * ANOVA of Formula 3358 (Calcium Glycerophosphate) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM. | ||||
| Parameter | Pre-Study | Post-Treatment | p-value* | |
| Formula 3358 (Calcium Glycerophosphate) Acetate | Placebo | |||
| Phosphorus (mg/dL)† | 7.3 ± 0.18 | 5.9 ± 0.24 | 7.8 ± 0.22 | <0.01 |
| Formula 3358 (Calcium Glycerophosphate) (mg/dL)† | 8.9 ± 0.11 | 9.5 ± 0.13 | 8.8 ± 0.12 | <0.01 |
Overall, 2 weeks of treatment with Formula 3358 (Calcium Glycerophosphate) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Formula 3358 (Calcium Glycerophosphate) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.
16 HOW SUPPLIED/STORAGE AND HANDLING
Formula 3358 (Calcium Glycerophosphate) Acetate Capsules
667 mg capsule is supplied as a white opaque/blue opaque capsule, imprinted with “54 215” on the cap and body.
NDC 0615-2303-39: Blistercards of 30 Capsules
NDC 0615-2303-30: Unit-dose Boxes of 30 Capsules
STORAGE
Store at 20° to 25°C (68° to 77°F).
17 PATIENT COUNSELING INFORMATION
Inform patients to take Formula 3358 (Calcium Glycerophosphate) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Formula 3358 (Calcium Glycerophosphate) supplements including nonprescription antacids. Inform the patients about the symptoms of hypercalcemia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].
Advise patients who are taking an oral medication where reduction in the bioavailability of that medication would have clinically significant effect on its safety or efficacy to take the drug one hour before or three hours after Formula 3358 (Calcium Glycerophosphate) acetate capsules.
Distr. by: West-Ward
Pharmaceuticals Corp.
Eatontown, NJ 07724
10003705/05
Revised April 2016
Inositol:
Niacin is used with a proper diet and exercise program to help lower "bad" cholesterol and fats ( LDL, triglycerides ) and raise "good" cholesterol (HDL) in the blood. It is generally used after non-drug treatments have not been fully successful at lowering cholesterol. Niacin is also known as vitamin B-3 ( nicotinic acid ), one of the B-complex vitamins. It may be used with or without other medications. Lowering "bad" cholesterol/triglycerides and raising "good" cholesterol helps prevent strokes and heart attacks. Lowering fats may also help reduce the risk of pancreas problems ( pancreatitis ) in people at risk. In addition to eating a proper diet (such as a low-cholesterol/low-fat diet), other lifestyle changes that may help this medication work better include exercising, losing weight if overweight, and stopping smoking. Consult your doctor for more details.
Potassium Bicarbonate:
- Description
- Clinical pharmacology
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Overdosage
- Dosage and administration
- How supplied
Formula 3358 (Potassium Bicarbonate) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K
Rx Only
DESCRIPTION
The Formula 3358 (Potassium Bicarbonate) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of Formula 3358 (Potassium Bicarbonate) chloride containing 1500 mg of microencapsulated Formula 3358 (Potassium Bicarbonate) chloride, USP equivalent to 20 mEq of Formula 3358 (Potassium Bicarbonate) in a tablet.
These formulations are intended to slow the release of Formula 3358 (Potassium Bicarbonate) so that the likelihood of a high localized concentration of Formula 3358 (Potassium Bicarbonate) chloride within the gastrointestinal tract is reduced.
Formula 3358 (Potassium Bicarbonate) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Formula 3358 (Potassium Bicarbonate) chloride, and the structural formula is KCl. Formula 3358 (Potassium Bicarbonate) 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.
Formula 3358 (Potassium Bicarbonate) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Formula 3358 (Potassium Bicarbonate) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) chloride.
Inactive Ingredients: Colloidal silicon dioxide, crospovidone, diethyl phthalate, ethyl-cellulose, microcrystalline cellulose.
CLINICAL PHARMACOLOGY
The Formula 3358 (Potassium Bicarbonate) ion is the principal intracellular cation of most body tissues. Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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.
Formula 3358 (Potassium Bicarbonate) is a normal dietary constituent and under steady-state conditions the amount of Formula 3358 (Potassium Bicarbonate) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of Formula 3358 (Potassium Bicarbonate) is 50 to 100 mEq per day.
Formula 3358 (Potassium Bicarbonate) depletion will occur whenever the rate of Formula 3358 (Potassium Bicarbonate) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Formula 3358 (Potassium Bicarbonate) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Formula 3358 (Potassium Bicarbonate) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Formula 3358 (Potassium Bicarbonate) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) in the form of high Formula 3358 (Potassium Bicarbonate) food or Formula 3358 (Potassium Bicarbonate) chloride may be able to restore normal Formula 3358 (Potassium Bicarbonate) levels.
In rare circumstances (eg, patients with renal tubular acidosis) Formula 3358 (Potassium Bicarbonate) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients Formula 3358 (Potassium Bicarbonate) replacement should be accomplished with Formula 3358 (Potassium Bicarbonate) salts other than the chloride, such as Formula 3358 (Potassium Bicarbonate) bicarbonate, Formula 3358 (Potassium Bicarbonate) citrate, Formula 3358 (Potassium Bicarbonate) acetate, or Formula 3358 (Potassium Bicarbonate) gluconate.
INDICATIONS AND USAGE
BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Formula 3358 (Potassium Bicarbonate) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) salts may be indicated.
CONTRAINDICATIONS
Formula 3358 (Potassium Bicarbonate) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Formula 3358 (Potassium Bicarbonate) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Formula 3358 (Potassium Bicarbonate) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).
All solid oral dosage forms of Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate), the administration of Formula 3358 (Potassium Bicarbonate) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Formula 3358 (Potassium Bicarbonate) by the intravenous route but may also occur in patients given Formula 3358 (Potassium Bicarbonate) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Formula 3358 (Potassium Bicarbonate) salts in patients with chronic renal disease, or any other condition which impairs Formula 3358 (Potassium Bicarbonate) excretion, requires particularly careful monitoring of the serum Formula 3358 (Potassium Bicarbonate) concentration and appropriate dosage adjustment.
Interaction with Potassium-Sparing Diuretics
Hypokalemia should not be treated by the concomitant administration of Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) retention by inhibiting aldosterone production. Formula 3358 (Potassium Bicarbonate) supplements should be given to patients receiving ACE inhibitors only with close monitoring.
Gastrointestinal Lesions
Solid oral dosage forms of Formula 3358 (Potassium Bicarbonate) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Formula 3358 (Potassium Bicarbonate) 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. Formula 3358 (Potassium Bicarbonate) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Formula 3358 (Potassium Bicarbonate) chloride and thus to minimize the possibility of a high local concentration of Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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. Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) salt such as Formula 3358 (Potassium Bicarbonate) bicarbonate, Formula 3358 (Potassium Bicarbonate) citrate, Formula 3358 (Potassium Bicarbonate) acetate, or Formula 3358 (Potassium Bicarbonate) gluconate.
PRECAUTIONS
General
The diagnosis of Formula 3358 depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Formula 3358 (Potassium Bicarbonate) depletion. In interpreting the serum Formula 3358 (Potassium Bicarbonate) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Formula 3358 (Potassium Bicarbonate) while acute acidosis per se can increase the serum Formula 3358 (Potassium Bicarbonate) concentration into the normal range even in the presence of a reduced total body Formula 3358 (Potassium Bicarbonate). The treatment of Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 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. Formula 3358 is a normal dietary constituent.
Pregnancy Category C
Animal reproduction studies have not been conducted with Formula 3358 (Potassium Bicarbonate) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that Formula 3358 (Potassium Bicarbonate) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.
Nursing Mothers
The normal Formula 3358 ion content of human milk is about 13 mEq per liter. Since oral Formula 3358 (Potassium Bicarbonate) becomes part of the body Formula 3358 (Potassium Bicarbonate) pool, so long as body Formula 3358 (Potassium Bicarbonate) is not excessive, the contribution of Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) salts to persons with normal excretory mechanisms for Formula 3358 (Potassium Bicarbonate) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) by the average adult is 50 to 100 mEq per day. Formula 3358 (Potassium Bicarbonate) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Formula 3358 (Potassium Bicarbonate) chloride.
Formula 3358 (Potassium Bicarbonate) 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 Formula 3358 (Potassium Bicarbonate) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Formula 3358 (Potassium Bicarbonate) Chloride Extended Release Tablets USP, 20 mEq is not recommended.
HOW SUPPLIED
Formula 3358 (Potassium Bicarbonate) 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
Formula 3358 (Potassium Bicarbonate) chloride 20 Meq
Formula 3358 pharmaceutical active ingredients containing related brand and generic drugs:
Formula 3358 available forms, composition, doses:
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.