The following Structured Product Label (SPL) was submitted to the FDA by U.s. Pharmaceutical Corporation for the product Integra Plus (NDC 52747-712). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding description, clinical pharmacology, clinical studies, contraindications, warnings and precautions, adverse reactions, overdosage, dosage & administration, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
DESCRIPTION: Each capsule contains: Ferrous Fumarate (anhydrous) ......191.1 mg Polysaccharide Iron Complex... 135.9 mg (Equivalent to about 125 mg of elemental iron) Vitamin C (from ProAscorb C‡)....210 mg Folic Acid .....1 mg Thiamine Mononitrate (B1)...5 mg Riboflavin (B2)....5 mg Niacin (B3) . 20 mg d-Calcium Pantothenate (B5)..7 mg Pyridoxine HCl (B6) ...25 mg Biotin (B7)......300 mcg Cyanocobalamin (B12) .. 10 mcg
CLINICAL PHARMACOLOGY: Integra PlusTM is unique in that it utilizes two (2) different forms of iron, i.e., Ferrous Fumarate and Polysaccharide Iron Complex (as cell-contracted akaganèite), making available a total of 125 mg of elemental iron per capsule as follows:
Ferrous Fumarate (anhydrous) 191.1 mg Polysaccharide iron complex (PIC) 135.9 mg
Subclinical B-Group vitamin deficiencies have greatly increased in recent years, due to changes in dietetic habits, increase in the use of sugar, and the excessive milling of flour and cereals. With thiamine deficiencies in a healthy populous, it is self-evident that the unwell person is particularly prone to thiamine avitaminosis. This is true of the anemic individual with his/her poor appetite and disturbed digestive functions. Folic acid is best known for its role in megaloblastic anemias. Zinc has been recognized in the nutrition of animals and humans, even though the evidence for an uncomplicated zinc deficiency in humans is limited.
Ferrous Fumarate: Provides about 62.5 mg of elemental iron per dose. Ferrous Fumarate is an anhydrous salt of a combination of ferrous iron and fumaric acid, containing 33% of iron per weight. The acute toxicity in experimental animals is low and Ferrous Fumarate is well tolerated clinically. As a ferrous salt, it is more efficiently absorbed in the duodenum. Ferrous Fumarate contrasts very favorably with the availability of the 20% of elemental iron of ferrous sulfate, and the 13% of elemental iron of ferrous gluconate.
Polysaccharide Iron Complex: Provides about 62.5 mg elemental iron, as a cell-contracted akaganèite. It is a product of ferric iron complexed to a low molecular weight polysaccharide. This polysaccharide is produced by the extensive hydrolysis of starch and is a dark brown powder that dissolves in water to form a very dark brown solution, which is virtually odorless and tasteless.
Folic Acid: Folic Acid is one of the important hematopoetic agents necessary for proper regeneration of the blood-forming elements and their function. Folic acid is a precursor of a large family of compounds which serve as coenzymes in carbon transfer reactions. These reactions are required for the synthesis of purine and pyrimidine bases, inter-conversion of glycine and serine, biosynthesis of methionine methyl groups and degradation of histidine. Additionally, folic acid increases jejunal glycolytic enzymes and is involved in the desaturation and hydroxylation of long-chain fatty acids in the brain. A deficiency in folic acid results in megaloblastic anemia.
All IntegraTM products include a unique patented source of iron, e.g. Ferrous Fumarate and Polysaccharide Iron Complex (U.S. Patent No: 11/243,043 Pending). "An increase in tolerability is observed with the (patented formulation) and is believed to occur as the result of distributing the total iron content in the composition among compounds that provide iron to the patient's blood stream via two different mechanisms. The ferrous salts are readily absorbed in the upper gut, by direct dissolution and absorption of the ferrous iron by the bloodstream. However, the iron available from PIC is absorbed in the lower gut, via an active protein transport mechanism".
Clinical Studies: Because Ferrous Fumarate is an organic complex, it contains no free ions, either ferric or ferrous. Polysaccharide Iron Complex is clinically non-toxic. Prior studies in rats demonstrated that Polysaccharide Iron Complex (PIC), administered as a single oral dose to Sprague Dawley rats did not produce evidence of toxicity at a dosage level of 5000 mg Iron/kg: (An Acute Oral Toxicity Study in Rats with Polysaccharide-Iron Complex. T.N.Merriman, M. Aikman and R.E. Rush, Springborn Laboratories. Inc. Spencerville, Ohio Study No. 3340.1 March - April 1994). Other clinical studies had demonstrated that Polysaccharide Iron gives a good hematopoietic response with an almost complete absence of the side effects usually associated with oral iron therapy. Picinni and Ricciotti suggested in 1982, that "the therapeutic effectiveness of Polysaccharide Iron Complex when compared with iron fumarate in the treatment of iron deficiency anemia, appears to be as active as the iron fumarate and as well tolerated, however, it exerted a greater influence on the level of hemoglobin and on the number of red cells..." and that, "it has been exceptionally well tolerated by all patients" (Picinni, L.-Ricciotti, M. 1982. Therapeutic effectiveness of an iron-polysaccharide complex in comparison with iron fumarate in the treatment of iron deficiency anemias): PANMINERVA MEDICA-EUROPA MEDICA, Vol. 24, No. 3, pp. 213-220 (July-September 1982).
As mentioned above, the patented source of iron used in Integra PlusTM (Ferrous Fumarate and Polysaccharide Iron Complex) provides a high level of elemental iron with a low incidence of gastric distress.
CONCLUSION: Based on the results of this study, the oral combination of Ferrous Fumarate and Polysaccharide Iron Complex was better tolerated and safer than the oral administration of Ferrous Fumarate alone. The conclusion of this research stated, that the addition of PIC to Ferrous Fumarate surprisingly allows the same concentration of Ferrous Fumarate to be better tolerated than the Ferrous Fumarate alone.
CONTRAINDICATIONS: Integra PlusTM is contraindicated in patients with a known hypersensitivity to any of its ingredients; also, all iron compounds are contraindicated in patients with hemosiderosis, hemochromatosis, or hemolytic anemias. Pernicious anemia is a contraindication, as folic acid may obscure its signs and symptoms.
WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately.
WARNING: Folic acid alone is improper therapy in the treatment of pernicious anemia and other megaloblastic anemias where Vitamin B12 is deficient.
PRECAUTIONS: General: Folic acid in doses above 0.1 mg - 0.4 mg daily may obscure pernicious anemia, in that hematological remission can occur while neurological manifestations remain progressive. Pediatric Use: Safety and effectiveness of this product have not been established in pediatric patients. Geriatric Use: No clinical studies have been performed in patients age 65 and over to determine whether older persons respond differently from younger persons. Dosage should always begin at the low end of the dosage scale and should consider that elderly persons may have decreased hepatic, renal, or cardiac function and or concomitant diseases.
Adverse Reactions: Folic Acid: Allergic sensitizations have been reported following both oral and parenteral administration of folic acid. Ferrous Fumarate: Gastrointestinal disturbances (anorexia, nausea, diarrhea, constipation) occur occasionally, but are usually mild and may subside with continuation of therapy. Although the absorption of iron is best when taken between meals, giving Integra PlusTM after meals may control occasional G.I. disturbances. Integra PlusTM is best absorbed when taken at bedtime.
OVERDOSE: Iron: Signs and Symptoms: Iron is toxic. Acute overdosage of iron may cause nausea and vomiting and, in severe cases, cardiovascular collapse and death. Other symptoms include pallor and cyanosis, melena, shock, drowsiness and coma. The estimated overdose of orally ingested iron is 300-mg/kg body weight. When overdoses are ingested by children, severe reactions, including fatalities, have resulted. Integra PlusTM should be stored beyond the reach of children to prevent against accidental iron poisoning. Keep this and all other drugs out of the reach of children.
Treatment: For specific therapy, exchange transfusion and chelating agents should be used. For general management, perform gastric lavage with sodium bicarbonate solution or milk. Administer intravenous fluids and electrolytes and use oxygen.
DOSAGE AND ADMINISTRATION: Adults (persons over 12 years of age), One (1) capsule daily, between meals, or as prescribed by a physician. Do not exceed recommended dosage. Do not administer to children under the age of 12.
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HOW SUPPLIED: Integra PlusTM are bright yellow (body) and maroon (cap) capsules imprinted "US" logo in maroon and "Integra Plus" in bright yellow. Child resistant bottles of 90 capsules NDC# 52747-712-60. Dispense in a tight, light-resistant container as defined in the USP/NF with a child resistant closure. Store at controlled room temperature 15 ̊ to 30 ̊C (59 ̊ to 86 ̊ F). Keep in a cool, dry place. Capsules are not USP.
CAUTION: Rx only.
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