Fergon Iron Plus Calcium

Calcium Carbonate:

• 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
• Fergon Iron Plus Calcium (Calcium Carbonate) reviews

1 INDICATIONS AND USAGE

Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) acetate capsule.

- Capsule: 667 mg Fergon Iron Plus Calcium (Calcium Carbonate) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

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

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

Fergon Iron Plus Calcium (Calcium Carbonate) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) concentration could reduce the incidence and severity of Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

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

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of Fergon Iron Plus Calcium (Calcium Carbonate) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

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

11 DESCRIPTION

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

Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

Orally administered Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) acetate.

14 CLINICAL STUDIES

Effectiveness of Fergon Iron Plus Calcium (Calcium Carbonate) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) acetate is shown in the Table 3.

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

16 HOW SUPPLIED/STORAGE AND HANDLING

Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Fergon Iron Plus Calcium (Calcium Carbonate) 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 Fergon Iron Plus Calcium (Calcium Carbonate) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Ferrous Fumarate:

• Indications and usage
• Contraindications
• Precaution
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Storage
• Fergon Iron Plus Calcium (Ferrous Fumarate) reviews

INDICATIONS AND USAGE

Non-pregnant Adults

For the treatment of iron deficiency and prevention of concomitant folic acid deficiency.

Pregnant Females

For the prevention and treatment of iron deficiency and to supply a maintenance dosage of folic acid.

CONTRAINDICATIONS

Contraindicated in patients with pernicious anemia and in the rare instance of hypersensitivity to folic acid. Hemochromatosis and hemosiderosis are contraindications to iron therapy.

PRECAUTION

Anemia is a manifestation that requires appropriate investigation to determine its cause or causes. Folic acid alone is unwarranted in the treatment of vitamin B₁₂ deficiency states such as pernicious anemia. Folic acid, especially in doses above 100 mcg daily may obscure pernicious anemia in that hematological remission may occur while neurological manifestations remain progressive. Concomitant parenteral therapy with vitamin B₁₂ may be necessary for adequate treatment of patients with a deficiency of vitamin B₁₂. Pernicious anemia is rare in women of childbearing age, and the likelihood of its occurrence along with pregnancy is reduced by the impairment of fertility associated with vitamin B₁₂ deficiency. In older patients and those with conditions tending to lead to vitamin B₁₂ depletion, serum B₁₂ levels should be regularly assessed during treatment.

Drug Interactions

Absorption of iron is inhibited by magnesium trisilicate and antacids containing carbonates. Since oral iron products interfere with absorption of oral tetracycline antibiotics, these products should not be taken within two hours of each other. Iron absorption may also be inhibited by the ingestion of milk or eggs.

Carcinogenesis

Adequate data are not available on long-term potential for carcinogenesis in animals and humans.

Pregnancy

Pregnancy Category A

Studies in pregnant women have not shown that the ingredients in Fergon Iron Plus Calcium caplets formula increase the risk of fetal abnormalities if administered during pregnancy. If this product is used during pregnancy, the possibility of fetal harm appears remote. Because studies cannot rule out the possibility of harm, however, Fergon Iron Plus Calcium (Ferrous Fumarate) caplets should be used during pregnancy only if clearly needed.

Nursing Mothers

Folic acid and ascorbic acid are excreted in breast milk.

ADVERSE REACTIONS

Rarely, controlled-release iron produces gastrointestinal reactions, such as diarrhea or constipation. Administering the dose with meals will minimize these effects in the iron-sensitive patient. Allergic sensitization has been reported with both oral and parenteral administration of folic acid.

OVERDOSAGE

Signs and symptoms of iron toxicity, which may be delayed because the iron is in a controlled-release form, may include pallor and cyanosis, vomiting of blood, diarrhea, passage of dark-colored stool, shock, drowsiness and coma. In overdosage, efforts should be made to hasten the elimination of the caplets ingested. An emetic should be administered as soon as possible, followed by gastric lavage if indicated. Immediately following emesis, a large dose of saline cathartic should be used to speed passage through the intestinal tract. X-ray examination may then be considered to determine the position and number of caplets remaining in the gastrointestinal tract.

DOSAGE AND ADMINISTRATION

Adults, including Pregnant Females

The recommended dose is one (1) caplet daily on an empty stomach.

HOW SUPPLIED

Fergon Iron Plus Calcium (Ferrous Fumarate) is supplied in bottles of 30 caplets.

Product Code: 13811-051-30

STORAGE

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

Call your doctor about side effects. You may report side effects by calling 888 9 TRIGEN (888-987-4436).

KEEP OUT OF THE REACH OF CHILDREN.

R_x Only

All prescriptions using this product shall be pursuant to statutes as applicable. This is not an Orange Book product. There are no implied or explicit claims on therapeutic equivalence.

Manufactured for:

TRIGEN Laboratories, Inc., Sayreville, NJ 08872

www.trigenlab.com

Rev. 05/13

13811-051-30

R_x Only

Fergon Iron Plus Calcium (Ferrous Fumarate)

Caplets

30 CAPLETS

TRIGEN

LABORATORIES