Vitathion

Calcium (Inositocalcium):

• 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
• Vitathion (Calcium (Inositocalcium)) reviews

1 INDICATIONS AND USAGE

Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) acetate capsule.

- Capsule: 667 mg Vitathion (Calcium (Inositocalcium)) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting Vitathion ) acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)), including Vitathion (Calcium (Inositocalcium)) acetate. Avoid the use of Vitathion (Calcium (Inositocalcium)) supplements, including Vitathion (Calcium (Inositocalcium)) based nonprescription antacids, concurrently with Vitathion (Calcium (Inositocalcium)) acetate.

An overdose of Vitathion (Calcium (Inositocalcium)) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Vitathion (Calcium (Inositocalcium)) levels twice weekly. Should hypercalcemia develop, reduce the Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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, Vitathion (Calcium (Inositocalcium)) acetate has been generally well tolerated.

Vitathion (Calcium (Inositocalcium)) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Vitathion (Calcium (Inositocalcium)) 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.

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 Vitathion (Calcium (Inositocalcium)) concentration could reduce the incidence and severity of Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

The drug interaction of Vitathion ) acetate is characterized by the potential of Vitathion (Calcium (Inositocalcium)) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Vitathion (Calcium (Inositocalcium)) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.

There are no empirical data on avoiding drug interactions between Vitathion (Calcium (Inositocalcium)) acetate and most concomitant drugs. When administering an oral medication with Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

Vitathion ) acetate capsules contains Vitathion (Calcium (Inositocalcium)) acetate. Animal reproduction studies have not been conducted with Vitathion (Calcium (Inositocalcium)) acetate, and there are no adequate and well controlled studies of Vitathion (Calcium (Inositocalcium)) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Vitathion (Calcium (Inositocalcium)) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Vitathion (Calcium (Inositocalcium)) 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. Vitathion (Calcium (Inositocalcium)) acetate treatment, as recommended, is not expected to harm a fetus if maternal Vitathion (Calcium (Inositocalcium)) levels are properly monitored during and following treatment.

8.2 Labor and Delivery

The effects of Vitathion (Calcium (Inositocalcium)) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

Vitathion ) Acetate Capsules contains Vitathion (Calcium (Inositocalcium)) acetate and is excreted in human milk. Human milk feeding by a mother receiving Vitathion (Calcium (Inositocalcium)) acetate is not expected to harm an infant, provided maternal serum Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Vitathion (Calcium (Inositocalcium)) acetate acts as a phosphate binder. Its chemical name is Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) acetate USP (anhydrous; Ca(CH₃COO)₂; MW=158.17 grams) equal to 169 mg (8.45 mEq) Vitathion (Calcium (Inositocalcium)), 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.

Vitathion (Calcium (Inositocalcium)) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.

Chemical Structure

12 CLINICAL PHARMACOLOGY

Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum Vitathion ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

Vitathion (Calcium (Inositocalcium)) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Vitathion (Calcium (Inositocalcium)) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) acetate.

14 CLINICAL STUDIES

Effectiveness of Vitathion (Calcium (Inositocalcium)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Vitathion (Calcium (Inositocalcium)) levels are also presented.

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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) acetate is shown in the Table 3.

Overall, 2 weeks of treatment with Vitathion (Calcium (Inositocalcium)) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Vitathion (Calcium (Inositocalcium)) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.

16 HOW SUPPLIED/STORAGE AND HANDLING

Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Vitathion (Calcium (Inositocalcium)) 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 Vitathion (Calcium (Inositocalcium)) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Vitamin C (Ascorbic Acid):

• Pharmacological action
• Pharmacokinetics
• Why is Vitathion ) prescribed?
• Dosage and administration
• Vitathion (Vitamin C (Ascorbic Acid)) side effects, adverse reactions
• Vitathion ) contraindications
• Using during pregnancy and breastfeeding
• Special instructions
• Vitathion ) drug interactions
• Vitathion ) in case of emergency / overdose
• Vitathion (Vitamin C (Ascorbic Acid)) reviews

Pharmacological action

Vitathion ) (vitamin c) is essential for the formation of intracellular collagen, is required to strengthen the structure of teeth, bones, and the capillary walls. Vitathion (Vitamin C (Ascorbic Acid)) participates in redox reactions, the metabolism of tyrosine, converting folic acid into folinic acid, metabolism of carbohydrates, the synthesis of lipids and proteins, iron metabolism, processes of cellular respiration. Reduces the need for vitamins B1, B2, A, E, folic acid, pantothenic acid, enhances the body's resistance to infections; enhances iron absorption, contributing to its sequestration in reduced form. Vitathion (Vitamin C (Ascorbic Acid)) has antioxidant properties.

With intravaginal application of Vitathion (Vitamin C (Ascorbic Acid)) lowers the vaginal pH, inhibiting the growth of bacteria and helps to restore and maintain normal pH and vaginal flora (Lactobacillus acidophilus, Lactobacillus gasseri).

Pharmacokinetics

After oral administration Vitathion (Vitamin C (Ascorbic Acid)) is completely absorbed from the gastrointestinal tract. Widely distributed in body tissues.

The concentration of Vitathion (Vitamin C (Ascorbic Acid)) in blood plasma in normal amounts to approximately 10-20 mg / ml.

The concentration of Vitathion (Vitamin C (Ascorbic Acid)) in white blood cells and platelets is higher than in erythrocytes and plasma. When deficient state of concentration in leucocytes is reduced later and more slowly and is regarded as the best criterion for evaluating the deficit than the concentration in plasma.

Plasma protein binding is about 25%.

Vitathion (Vitamin C (Ascorbic Acid)) is reversibly oxidized to form dehydroascorbic acid, is metabolized with the formation of ascorbate-2-sulphate which is inactive and oxalic acid which is excreted in the urine.

Vitathion (Vitamin C (Ascorbic Acid)) taken in excessive quantities is rapidly excreted unchanged in urine, it usually happens when exceeding a daily dose is 200 mg.

Why is Vitathion ) prescribed?

For systemic use of Vitathion (Vitamin C (Ascorbic Acid)) RiteMED Phils: prevention and treatment of hypo- and avitaminosis of vitamin C; providing increased need for vitamin C during growth, pregnancy, lactation, with heavy loads, fatigue and during recovery after prolonged severe illness; in winter with an increased risk of infectious diseases.

For intravaginal use: chronic or recurrent vaginitis (bacterial vaginosis, nonspecific vaginitis) caused by the anaerobic flora (due to changes in pH of the vagina) in order to normalize disturbed vaginal microflora.

Dosage and administration

This medication administered orally, IM, IV, intravaginally.

For the prevention of deficiency conditions Vitathion ) dose is 25-75 mg / day, for the treatment - 250 mg / day or more in divided doses.

For intravaginal used Vitathion (Vitamin C (Ascorbic Acid)) drugs in appropriate dosage forms.

Vitathion (Vitamin C (Ascorbic Acid)) side effects, adverse reactions

CNS: headache, fatigue, insomnia.

Digestive system: stomach cramps, nausea and vomiting.

Allergic reaction: describes a few cases of skin reactions and manifestations of the respiratory system.

Urinary system: when used in high doses - hyperoxaluria and the formation of kidney stones of calcium oxalate.

Local reactions: with intravaginal application - a burning or itching in the vagina, increased mucous discharge, redness, swelling of the vulva. Other: sensation of heat.

Vitathion ) contraindications

Increased sensitivity to Vitathion (Vitamin C (Ascorbic Acid)).

Using during pregnancy and breastfeeding

The minimum daily requirement of Vitathion ) in the II and III trimester of pregnancy is about 60 mg.

Vitathion (Vitamin C (Ascorbic Acid)) crosses the placental barrier. It should be borne in mind that the fetus can adapt to high doses of Vitathion (Vitamin C (Ascorbic Acid)), which takes a pregnant woman, and then a newborn baby may develop the ascorbic disease as the reaction of cancel. Therefore, during pregnancy should not to take Vitathion (Vitamin C (Ascorbic Acid)) in high doses, except in cases where the expected benefit outweighs the potential risk.

The minimum daily requirement during lactation (breastfeeding) is 80 mg. Vitathion (Vitamin C (Ascorbic Acid)) is excreted in breast milk. A mother's diet that contains adequate amounts of Vitathion (Vitamin C (Ascorbic Acid)), is sufficient to prevent deficiency in an infant. It is unknown whether dangerous to the child's mother use of Vitathion (Vitamin C (Ascorbic Acid)) in high doses. Theoretically it is possible. Therefore, it is recommended not to exceed the maximum daily nursing mother needs to Vitathion (Vitamin C (Ascorbic Acid)), except when the expected benefit outweighs the potential risk.

Special instructions

Vitathion (Vitamin C (Ascorbic Acid)) is used with caution in patients with hyperoxaluria, renal impairment, a history of instructions on urolithiasis. Because Vitathion (Vitamin C (Ascorbic Acid)) increases iron absorption, its use in high doses can be dangerous in patients with hemochromatosis, thalassemia, polycythemia, leukemia, and sideroblastic anemia.

Patients with high content body iron should apply Vitathion (Vitamin C (Ascorbic Acid)) in minimal doses.

Vitathion (Vitamin C (Ascorbic Acid)) is used with caution in patients with deficiency of glucose-6-phosphate dehydrogenase.

The use of Vitathion (Vitamin C (Ascorbic Acid)) in high doses can cause exacerbation of sickle cell anemia.

Data on the diabetogenic action of Vitathion (Vitamin C (Ascorbic Acid)) are contradictory. However, prolonged use of Vitathion (Vitamin C (Ascorbic Acid)) should periodically monitor your blood glucose levels.

It is believed that the use of Vitathion (Vitamin C (Ascorbic Acid)) in patients with rapidly proliferating and widely disseminated tumors may worsen during the process. It should therefore be used with caution in Vitathion (Vitamin C (Ascorbic Acid)) in patients with advanced cancer.

Absorption of Vitathion (Vitamin C (Ascorbic Acid)) decreased while use of fresh fruit or vegetable juices, alkaline drinking.

Vitathion ) drug interactions

In an application with barbiturates, primidone increases the excretion of Vitathion (Vitamin C (Ascorbic Acid)) in the urine.

With the simultaneous use of oral contraceptives reduces the concentration of Vitathion (Vitamin C (Ascorbic Acid)) in blood plasma.

In an application of Vitathion (Vitamin C (Ascorbic Acid)) with iron preparations Vitathion (Vitamin C (Ascorbic Acid)), due to its regenerative properties, transforms ferric iron in the bivalent, which improves its absorption.

Vitathion (Vitamin C (Ascorbic Acid)) in high doses can decrease urine pH that while the application reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.

With the simultaneous use of aspirin reduces the absorption of Vitathion (Vitamin C (Ascorbic Acid)) by about a third.

Vitathion (Vitamin C (Ascorbic Acid)) in an application with warfarin may decrease effects of warfarin.

With the simultaneous application of Vitathion (Vitamin C (Ascorbic Acid)) increases the excretion of iron in patients receiving deferoxamine. In the application of Vitathion (Vitamin C (Ascorbic Acid)) at a dose of 500 mg / day possibly left ventricular dysfunction.

In an application with tetracycline is increased excretion of Vitathion (Vitamin C (Ascorbic Acid)) in the urine.

There is a described case of reducing the concentration of fluphenazine in plasma in patients treated with Vitathion (Vitamin C (Ascorbic Acid)) 500 mg 2 times / day.

May increase the concentration of ethinyl estradiol in the blood plasma in its simultaneous application in the oral contraceptives.

Vitathion ) in case of emergency / overdose

Symptoms: long-term use of large doses (more than 1 g) - headache, increased CNS excitability, insomnia, nausea, vomiting, diarrhea, gastritis giperatsidnyh, ultseratsiya gastrointestinal mucosa, inhibition of the function insular apparatus of the pancreas (hyperglycemia, glycosuria), hyperoxaluria, nephrolithiasis (calcium oxalate), damage to the glomerular apparatus of the kidneys, moderate thamuria (when receiving a dose of 600 mg / day).

Decrease capillary permeability (possibly deteriorating trophic tissues, increased blood pressure, hypercoagulability, the development of microangiopathy).

When IV administration in high doses - the threat of termination of pregnancy (due to estrogenemia), hemolysis of red blood cells.