Cypon-L

Cypon-L

Manufacturer:

Geno

Distributor:

Nebula
Full Prescribing Info
Contents
Vitamin B Complex with Lysine.
Description
Each 5 ml contains: Thiamine Hydrochloride BP 2.5 mg, Riboflavin Sodium Phosphate BP 3.5 mg, Pyridoxine Hydrochloride BP 1 mg, Nicotinamide BP 25 mg, Lysine Hydrochloride USP 300 mg, Cyanocobalamin BP 3 mcg, Appropriate overages of vitamins added to compensate for loss on storage.
Excipients/Inactive Ingredients: Excipients Used in the formulation of CYPON-L SYRUP: Sorbitol Solution 70% (Non-crystallising) BP, Glycerol BP, Methyl Hydroxy Benzoate BP, Propyl Hydroxy Benzoate BP, Citric Acid Monohydrate BP, Saccharin Sodium BP, Sodium Citrate BP, Strawberry Flavour, Purified Water BP.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: THIAMINE HYDROCHLORIDE BP: Thiamine Hydrochloride is the hydrochloride salt form of thiamine, a vitamin essential for aerobic metabolism, cell growth, transmission of nerve impulses and acetylcholine synthesis. Upon hydrolysis, thiamine hydrochloride is phosphorylated by thiamine diphosphokinase to form active thiamine pyrophosphate (TPP), also known as cocarboxylase.
RIBOFLAVIN SODIUM PHOSPHATE BP: Riboflavin Sodium Phosphate the phosphate sodium salt form of riboflavin, a water-soluble and essential micronutrient that is the principal growth-promoting factor in naturally occurring vitamin B complexes. Riboflavin phosphate sodium is converted to 2 coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are necessary for energy production by aiding in the metabolism of fats, carbohydrates and proteins and are required for red blood cell formation and respiration, antibody production and for regulating human growth and reproduction. Riboflavin phosphate sodium is essential for healthy skin, nails and hair growth.
CYANOCOBALAMIN BP: MECHANISM OF ACTION: Vitamin B12 is a generic term for several cobalt-containing compounds, designated cobalamins, which consist of a macrocyclic tetrapyrrole group (corrin nucleus) linked to a dimethylbenzimidazolyl nucleotide. A variable R group attached to the central cobalt atom determines the type of vitamin B12 congener (cyano group in cyanocobalamin, hydroxy group in hydroxocobalamin, methyl group in methylcobalamin, deoxyadenosyl group in deoxyadenosylcobalamin).
Both vitamin B12 and folic acid are required for synthesis of purine nucleotides and metabolism of some amino acids. Each are essential for normal growth and replication.
A deficiency of either vitamin B12 or folate results in defective DNA synthesis and cellular maturation abnormalities; changes are most evident in tissues with high rates of cell turnover, such as the hematopoietic system. Cyanocobalamin and hydroxocobalamin are the pharmaceutical forms of vitamin B12 used clinically to treat vitamin B12 deficiency as they are stable during storage). After losing its cyanide adduct, cyanocobalamin is equally as active as hydroxocobalamin. The 2 active intracellular coenzyme forms of vitamin B12 are methylcobalamin and deoxyadenosylcobalamin, which are synthesized in vivo from hydroxocobalamin (or cyanocobalamin); the primary cobalamin present in plasma is methycobalamin. Only small amounts of cyanocobalamin are normally present in plasma, although higher concentrations of this form have been detectable in certain conditions (eg, patients with optic neuropathies, inborn errors of cobalamin metabolism, pernicious anemia). Conversion of hydroxocobalamin to cyanocobalamin has been observed as a result of cyanide release during sodium nitroprusside therapy. The ability of hydroxocobalamin to act as a cyanide antidote, by formation of readily excreted cyanocobalamin, has led to the use of hydroxocobalamin in cyanide poisoning and other cyanide-related disorders (eg, Leber's optic atrophy).
In the UK, hydroxocobalamin is the drug of choice for vitamin B12 deficiency because it binds more firmly to plasma proteins and is retained in the body longer. However, in the USA, cyanocobalamin is preferred because administration of hydroxocobalamin has resulted in the formation of antibodies to the transcobalamin II-vitamin B(12) complex in some patients.
LYSINE HYDROCHLORIDE USP: Lysine improves calcium assimilation. Lysine exerts antagonistic actions against arginine via several proposed mechanisms: serving as an antimetabolite of arginine, enhancing the excretion of arginine by competing for reabsorption at the renal tubule, competing for intestinal absorption, inducing arginase to breakdown arginine, and competing for transport into cells. Lysine supplementation may enhance protein nutrition to boost the immune response. Thus, to prevent and treat herpes simplex infections, increasing the intake of lysine and/or lysine-to-arginine may be beneficial.
Cardiovascular effects: Lysine may exert positive cardiovascular effects by blocking a lysine-binding domain on lipoprotein(a). Additionally, lysine can cause vasodilation.
Calcium absorption and osteoporosis: Lysine has been investigated for use in osteoporosis. Specifically, lysine increases the intestinal absorption and reduces the renal elimination of calcium. Additionally, lysine plays a role in the cross-linking process of bone collagen.
Anxiolytic effects: Lysine is believed to exert anxiolytic effects by acting as a partial serotonin receptor 4 antagonist and as a partial benzodiazepine agonist.
Effects on muscle mass: Lysine in combination with other targeted nutritional supplements has been evaluated for its effects on age-associated changes in muscle mass, protein metabolism, and functionality in elderly patients.
PYRIDOXINE HYDROCHLORIDE BP: Pyridoxine Hydrochloride is water-soluble and used in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). It has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension. Human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities.
NICOTINAMIDE BP: MECHANISM OF ACTION: The use of niacin in the treatment of hyperlipoproteinemia is based on its ability to reduce serum lipids. Several possible modes of action have been proposed including, inhibition of hepatic synthesis of lipoproteins containing apolipoprotein B-100; promotion of lipoprotein lipase activity, and reduction of free fatty acid mobilization from adipose tissue with an increase in fecal output of sterols. Niacin also has a vasodilation effect when administered in large doses, identified by flushing of the skin while plasma niacin levels are rising. The normal, physiologic role of niacin is as a component of the coenzymes NAD and NADP which are essential for oxidation-reduction reactions in tissue respiration. Niacin is thought to counteract the effect of enterotoxins, as in cholera, by suppressing the action of camp key messenger involved in secretory stimulation in the intestinal mucosa. Nicotinamide, a metabolite of niacin, possesses similar function as a vitamin but has no pharmacological value in reducing lipids.
Pharmacokinetics: THIAMINE HYDROCHLORIDE BP: ABSORPTION: Thiamine is a water-soluble vitamin. It is absorbed by both diffusion and active transport mechanisms. Absorption following IM administration is rapid and complete.
DISTRIBUTION: Thiamine is widely distributed in all tissues, with highest concentrations in liver, brain, kidney, and heart. When thiamine intake exceeds needs, tissue stores increase more than 2 to 3 times. If intake is insufficient, tissues become depleted of their vitamin content.
METABOLISM: Thiamine undergoes rapid metabolism. Thiamine + ATP → thiamine pyrophosphate (cocarboxylase) coenzyme.
ELIMINATION: Excess thiamine is excreted in urine. Depletion of vitamin B1 occurs about 3 wk with absence of thiamine in diet.
RIBOFLAVIN SODIUM PHOSPHATE BP.
PYRIDOXINE HYDROCHLORIDE BP: ABSORPTION: BIOAVAILABILITY: Readily absorbed from the GI tract.
DISTRIBUTION: Stored mainly in liver with lesser amounts in muscle and brain.
Crosses the placenta; plasma concentrations in the fetus 5 times greater than maternal plasma concentrations. Distributed into milk.
Plasma Protein Binding.
Highly protein bound.
METABOLISM: Metabolized to 4-pyridoxic acid in the liver.
ELIMINATION ROUTE: Metabolite excreted in urine.
NICOTINAMIDE BP: ABSORPTION: Bioavailability: Oral, extended release: 60% to 76%.
According to single-dose bioavailability studies, niacin extended-release 500 milligram (mg) and 1000 mg tablets are dosage form equivalent, meaning, two 500 mg extended-release tablets are equivalent to one 1000 mg extended-release tablet. The 750-mg extended-release tablets are not dosage form equivalent.
Effects of Food: Food minimizes gastrointestinal upset: Administration with a low-fat meal or snack is recommended.
METABOLISM: Metabolism Sites and Kinetics: Liver, rapid (Prod Info NIASPAN(R), 2005).
Metabolites: Nicotinamide adenine dinucleotide (NAD), active (Prod Info NIASPAN(R), 2005).
Nicotinamide, inactive (Prod Info NIASPAN(R), 2005).
Nicotinuric acid, inactive (Prod Info NIASPAN(R), 2005).
EXCRETION: Kidney: Renal Excretion (%): 60% to 76% (Prod Info NIASPAN(R), 2005).
LYSINE HYDROCHLORIDE USP: Oral administration is the preferred route for lysine supplementation. Upon ingestion, it is absorbed from the lumen of the small intestine into the enterocytes via active transport and moves from the gut to the liver via the portal circulation. Once in the liver, lysine joins other amino acids to facilitate protein synthesis. Catabolism of lysine also occurs in the liver, where it undergoes condensation with ketoglutarate to form saccharopine. Saccharopine is converted to L-alpha-aminoadipic acid semialdehyde, which eventually becomes acetoacetyl-CoA. Unlike other amino acids, lysine does not undergo transamination. Lysine is both glycogenic and ketogenic, and thus can aid in the formation of D-glucose, glycogen, lipids, and consequently energy production. Human absorption studies have demonstrated lysine supplements have absorption rates similar to those from digestion of proteins, suggesting supplementation is an effective and efficient means of correcting a dietary lysine deficiency. Lysine is rapidly transported into muscle tissue, within 5-7 hours after ingestion, and is more concentrated in the intracellular space of muscle tissue compared to other essential amino acids. This suggests that muscle may serve as a reservoir for free lysine in the body. Lysine is the most strongly conserved of the essential amino acids.
CYANOCOBALAMIN BP: ONSET AND DURATION: ONSET: INITIAL RESPONSE: Megaloblastic anemia, intramuscular: 8 hours.
Conversion of megaloblastic to normoblastic erythroid hyperplasia within the bone marrow is evident within 8 hours of an intramuscular cyanocobalamin dose in patients with megaloblastic anemia. An increase in reticulocytes usually begins after 2 to 5 days of therapy, followed by rises in hemoglobin, hematocrit, and erythrocyte count.
Psychiatric sequelae of vitamin B12 deficiency: 24 hours.
Psychiatric sequelae of vitamin B12 deficiency may subside within 24 hours of initiation of therapy, while neurologic complications require substantially longer periods (several months); in patients with long-standing neurologic sequelae (months to years) prior to therapy, damage may be irreversible.
Thrombocytopenia: 10 days.
Leukopenia: 2 weeks.
DURATION: MULTIPLE DOSE: Vitamin B12 deficiency, intramuscular: 2 to 4 weeks.
Serum vitamin B12 levels are maintained above 200 pg/mL in most patients with intramuscular cyanocobalamin doses of 100 mcg every 2 to 4 weeks.
Slower rates of decline in vitamin B12 serum levels have been reported with hydroxocobalamin as compared with cyanocobalamin with equivalent parenteral doses (AMA, 1991; Chalmers & Shinton, 1965; Glass et al, 1963). However, in other reports, reductions in plasma concentration of vitamin B12 over a 10- to 30-day period have been similar with each preparation.
A depot cyanocobalamin formulation (cyanocobalamin-tannate complex in sesame oil; Betolvex(R)) is available in some countries and has been effective in maintaining adequate vitamin B12 levels when administered every 2 to 3 months.
Pernicious anemia, parenteral: 6 months to 5 years.
The wide range in time to relapse is attributed to variability in the period required to deplete liver stores of vitamin B12. Because low serum vitamin B12 levels can precede relapse for several years in pernicious anemia, without evidence of deleterious effects, some investigators have suggested a longer interval between injections of cyanocobalamin.
DRUG CONCENTRATION LEVELS: THERAPEUTIC: THERAPEUTIC DRUG CONCENTRATION: Healthy adult, 200 to 900 pg/mL.
Intramuscular doses of cyanocobalamin 100 mcg every 2 to 4 weeks are adequate to maintain therapeutic plasma levels of vitamin B12 (greater than 200 pg/mL).
Serum vitamin B12 levels following administration of intramuscular hydroxocobalamin have been higher than those achieved with equivalent doses of cyanocobalamin. However, this is of doubtful significance clinically. Recommended maintenance doses of cyanocobalamin and hydroxocobalamin are similar.
Total vitamin B12 levels refer to methylcobalamin, adenosylcobalamin, hydroxocobalamin, and cyanocobalamin.
Limited evidence suggests that increases in serum cyanocobalamin concentrations following a single 400 mg intranasal dose of Ener-B(R) (intranasal cyanocobalamin gel formulation) are similar to those achieved after a single dose of intramuscular cyanocobalamin 100 mcg.
TIME TO PEAK CONCENTRATION: Intramuscular, injection: 30 minutes to 2 hours.
Subcutaneous, injection: 30 minutes to 2 hours.
ADME: ABSORPTION: BIOAVAILABILITY (F): Oral, tablet: poor.
The presence of intrinsic factor, calcium and the proper pH influence the absorption of vitamin B12. Binding to intrinsic factor occurs during passage through the gastrointestinal tract, and the intrinsic factor-vitamin B12 complex is absorbed in the ileum in the presence of calcium. Intrinsic factor, bile, and sodium bicarbonate are required for ileal transport of vitamin B12.
Small amounts of vitamin B12 can also be absorbed independent of intrinsic factor via simple diffusion.
The average US diet supplies 5 to 30 micrograms of vitamin B12 daily, of which 1 to 5 micrograms is absorbed in the presence of gastric intrinsic factor.
In the absence of intrinsic factor (pernicious anemia), large oral doses of cyanocobalamin (1000 mcg or more) have been effective in achieving therapeutic vitamin B12 plasma levels as sufficient vitamin is absorbed via passive diffusion. The oral bioavailability of cyanocobalamin in pernicious anemia is reportedly 1.2%
DISTRIBUTION: DISTRIBUTION SITES: Vitamin B12 binds in plasma to transcobalamin II, a beta-globulin, and this complex is transported to tissues (Donaldson et al, 1977; Gilman et al, 1990). Hydroxocobalamin is more tightly bound than cyanocobalamin.
OTHER DISTRIBUTION SITES: LIVER, 90%: Preferential distribution to hepatic parenchymal cells is observed, and the liver serves as a storage site for other tissues. Up to 90% of body stores are in the liver (1 to 10 mg), where the vitamin is stored as the active coenzyme with a turnover rate of 0.5 to 8 micrograms daily.
TISSUES: Vitamin B12 bound to transcobalamin II is rapidly cleared from plasma and transported to tissues (liver, bone marrow, endocrine glands, kidney).
EXCRETION: BREAST MILK: BREASTFEEDING: Safe.
Vitamin B12 is excreted into breast milk, and megaloblastic anemia has been described in some infants breast-fed by vitamin B12-deficient mothers; many of the mothers were vegetarians. Supplementation of the diet with vitamin B12 should be considered during lactation in vegetarians.
For breast-feeding women with adequate nutritional intake, dietary supplementation is not necessary.
KIDNEY: RENAL EXCRETION: 50% to 98%.
Between 50% and 98% of an intramuscular or subcutaneous dose (100 to 1000 mcg) of cyanocobalamin is excreted unchanged in the urine, most within the first 8 hours post injection.
Doses higher than 100 mcg will not result in greater retention of the vitamin, although stores may be replenished more quickly. Renal clearance is more rapid with intravenous administration.
OTHER EXCRETION: BILE: Between 1 and 3 mcg of vitamin B12 is excreted daily in the bile. Up to 50% of this amount is reabsorbed, establishing an enterohepatic recirculation of the vitamin. In patients with pernicious anemia (or following total gastrectomy), enterohepatic recirculation is impaired due to lack of intrinsic factor which results in continuous depletion of hepatic stores of vitamin B12.]
Toxicology: Preclinical Safety Data: Preclinical data reveal no special hazard for humans based on conventional studies of pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.
Indications/Uses
Indicated in anorexia, fatigue, weakness, co-therapy with Antibiotics, convalescence, Ideal for children with loss of appetite, underweight children and children with B complex deficiency
Dosage/Direction for Use
RECOMMENDED POSOLOGY: Children: One teaspoonful once a day.
Adults: One teaspoonful twice a day or as directed by the Physician.
METHOD OF ADMINISTRATIONS: Oral Route of Administration.
Overdosage
THIAMINE HYDROCHLORIDE BP: Very large doses of thiamine administered parenterally may produce neuromuscular and ganglionic blockade and neurologic symptoms. Treatment is supportive.
CYANOCOBALAMIN BP: Even in large doses, vitamin B12 isn't usually toxic.
LYSINE HYDROCHLORIDE USP: Overdose of L-lysine could increase cholesterol levels and cause gallstones. High L-lysine intake can also cause diarrhea and stomach cramps.
PYRIDOXINE HYDROCHLORIDE BP: Usually nontoxic; adverse neurologic effects, nausea, headache, paresthesia, somnolence, increased serum AST, decreased serum folic acid concentrations, Ataxia, sensory neuropathy.
Contraindications
Hypersensitivity to any of its ingredients of Cypon-L.
Warnings
Apart from possibility of allergic reactions no other precautions or warnings are warranted.
Special Precautions
Effects on Ability to Drive and Use Machine: NONE REPORTED.
Use In Pregnancy & Lactation
THIAMINE HYDROCHLORIDE BP: Thiamine Hydrochloride has to be used with caution during lactation.
PYRIDOXINE HYDROCHLORIDE BP: Pyridoxine is likely safe for pregnant women when taken under the supervision of their healthcare provider. It is sometimes used in pregnancy to control morning sickness. High doses are unsafe. High doses can cause newborns to have seizures. Pyridoxine is likely safe for breast-feeding women when used in amounts not larger than 2 mg per day. Avoid using higher amounts. Not enough is known about the safety of pyridoxine at higher doses in breast-feeding women.
NICOTINAMIDE BP: Teratogenicity/Effects in Pregnancy: U.S. Food and Drug Administration's Pregnancy Category: Category C (All Trimesters): Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
Australian Drug Evaluation Committee's (ADEC) Category: B2 (Batagol, 1996): Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.
Crosses Placenta: Yes.
Clinical Management: It is not known whether doses of niacin used in treating lipid disorders can cause fetal harm when given to pregnant women or whether it affects fertility. If a woman being treated for hypercholesterolemia (Type IIa or IIb) becomes pregnant, niacin should be discontinued. If a woman being treated for hypertriglyceridemia (Types IV or V) conceives, the benefits and risks of continuation should be determined on an individual basis. Nutritional supplement doses of vitamins and minerals are generally considered safe during pregnancy. Daily dietary niacin requirements are increased during pregnancy to a recommended dietary reference intake of 18 nanograms niacin equivalents, an amount almost 30% over nonreproducing adult women.
Breastfeeding: Thomson Lactation Rating: Infant risk cannot be ruled out: Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during breastfeeding.
Clinical Management: Niacin, in the extended release formulation, has been reported to appear in human milk. The recommended daily intake of niacin during lactation is 18 to 20 mg of the standard release formulation. It is not known if higher doses would result in clinically significant consequences for the nursing infant. It is not known if niacin affects the quantity or composition of breastmilk.
Literature Reports: Information is limited with regard to the safety of high-dose niacin, used in the treatment of hypercholesterolemia or hypertriglyceridemia, in the nursing infant. Until additional data are available, an attempt should be made to control cholesterol and triglycerides with dietary measures if the patient plans to breastfeed her infant.
LYSINE HYDROCHLORIDE USP: Lysine supplementation in combination with vitamins and iron supplementation increased hemoglobin levels in pregnant women.
CYANOCOBALAMIN BP: TERATOGENICITY: U.S. Food and Drug Administration's Pregnancy Category C.
There is no evidence that low levels of vitamin B12 are associated with congenital malformations.
EFFECTS IN PREGNANCY: The recommended dietary allowance (RDA) of vitamin B12 during pregnancy is 2.2 micrograms/day, and this is usually provided by an adequate diet (USPDI, 1993). However, dietary supplementation may be required during pregnancy in strict vegetarians (AMA, 1991).
Adverse Reactions
Apart from possibility of allergic reactions no other precautions or warnings are warranted.
Drug Interactions
THIAMINE HYDROCHLORIDE BP: Thiamine is unstable in neutral or alkaline solutions; do not use with substances that yield alkaline solutions, such as citrates, barbiturates, carbonates, or erythromycin lactobionate IV.
CYANOCOBALAMIN BP: DRUG-DRUG COMBINATIONS: AMINOSALICYLIC ACID: Summary: Long-term therapy with aminosalicylic acid may reduce the absorption of cyanocobalamin from the gastrointestinal tract, possibly resulting in cyanocobalamin deficiency. This may be related to an aminosalicylic acid-induced malabsorption syndrome. Theoretically, higher doses of oral cyanocobalamin may be required in patients treated with aminosalicylic acid. However, this interaction is of doubtful clinical relevance unless large doses of aminosalicylic acid are taken for prolonged periods.
Adverse Effect: reduced cyanocobalamin absorption.
Clinical Management: Patients receiving aminosalicylic acid for more than one month may require supplemental cyanocobalamin.
Severity: minor.
Onset: delayed.
Documentation: fair.
Probable Mechanism: unknown, possibly due to a malabsorption syndrome.
Literature Reports: Cyanocobalamin absorption has been reduced 55% by aminosalicylic acid 5 grams as a result of competition. Clinically significant erythrocyte abnormalities developed after the depletion of cyanocobalamin.
ASCORBIC ACID: Summary: Herbert & Jacob (1974) have reported that ascorbic acid in doses as low as 250 mg may destroy up to 81% of the cyanocobalamin in a moderate vitamin B12-containing meal, and up to 25% in a high vitamin B12-containing meal. The degree of destruction appears to be dependent on the various other ingredients in the meal, such as iron in moderate amounts and nitrates, which may counteract ascorbic acid's effect on cyanocobalamin. To diminish the possibility and magnitude of such destruction, it is suggested that ascorbic acid be taken two or more hours after meals. While ascorbic acid may still destroy a substantial amount of the normally excreted vitamin B12 and possibly lower vitamin B12 in serum and body stores, frank megaloblastic anemia would require megadoses of ascorbic acid ingested over several years.
Adverse Effect: reduced amounts of cyanocobalamin available for serum and body stores.
Clinical Management: Ascorbic acid should be administered two or more hours after a meal or vitamin B12 supplements.
Severity: minor.
Onset: delayed.
Documentation: poor.
Probable Mechanism: unknown.
CHLORAMPHENICOL: Summary: The use chloramphenicol in vitamin B12-deficient patients treated with cyanocobalamin may result in a suboptimal clinical response to cyanocobalamin.
Adverse Effect: decreased hematologic response.
Clinical Management: In the rare event that this interaction occurs, monitor for an adequate hematologic response with a periodic CBC.
Severity: minor.
Onset: delayed.
Documentation: poor.
Probable Mechanism: antagonism.
CIMETIDINE: Severity: not specified.
Onset: not specified.
Documentation: poor.
Literature Reports: Cimetidine may inhibit the absorption of dietary cyanocobalamin. Cyanocobalamin (vitamin B12) supplementation may be necessary for patients on long-term cimetidine therapy or those with depleted body stores.
Oral cimetidine (300 and 600 mg single doses) has been reported to reduce absorption of food-bound cyanocobalamin (Vitamin B 12) in patients with peptic ulcer disease. The food source employed in this study was egg yolk. The authors indicate that the standard Schilling test would not detect cimetidine-induced cyanocobalamin malabsorption. In contrast, orally administered crystalline cyanocobalamin (in solution) was unaffected by concurrent cimetidine administration in these patients. These data suggest that cyanocobalamin deficiency is possible during prolonged oral cimetidine therapy. However, this was a single-dose study and further investigations with daily cimetidine administration for several weeks in peptic ulcer patients are warranted to determine the clinical significance of the interaction.
COLESTIPOL: Summary: In vitro data has shown that colestipol may bind to cyanocobalamin/intrinsic factor complex, folic acid, and iron citrate. Concurrent administration may decrease the bioavailability of vitamin and mineral preparations.
Severity: not specified.
Onset: not specified.
Documentation: poor.
ETHINYL ESTRADIOL: Severity: not specified.
Onset: not specified.
Documentation: poor.
Literature Reports: A decrease in vitamin B12 serum levels has been reported in women taking combination oral contraceptives, possibly related to a reduction in serum vitamin B12 binding capacity. However, the interaction was not felt to be clinically relevant in most women, and the authors indicate that routine vitamin B12 determinations are not justified during oral contraceptive administration. Similarly, oral contraceptives would appear to have minimal effect on the response to cyanocobalamin.
MESTRANOL: Severity: not specified.
Onset: not specified.
Documentation: poor.
Literature Reports: A decrease in vitamin B12 serum levels has been reported in women taking combination oral contraceptives, possibly related to a reduction in serum vitamin B12 binding capacity. However, the interaction was not felt to be clinically relevant in most women, and the authors indicate that routine vitamin B12 determinations are not justified during oral contraceptive administration. Similarly, oral contraceptives would appear to have minimal effect on the response to cyanocobalamin.
OMEPRAZOLE: Summary: A prospective study involving 10 healthy volunteers demonstrated that omeprazole therapy for 2 weeks' duration resulted in a decrease of 90% (p=0.031) in protein-bound cyanocobalamin absorption. It is not known to what degree absorption of an oral cyanocobalamin supplement would be affected if taken with a protein meal under similar conditions. Cyanocobalamin by intramuscular or subcutaneous route would therefore be preferred in patients receiving long-term omeprazole therapy.
Adverse Effect: decreased cyanocobalamin absorption.
Clinical Management: If possible, switch to another anti-ulcer medication (eg, ranitidine, famotidine, or sucralfate) and separate the doses by at least two hours. However, if long term omeprazole therapy is required, cyanocobalamin by the intramuscular or subcutaneous route would be preferred.
Severity: minor.
Onset: delayed.
Documentation: poor.
Probable Mechanism: altered gastric pH.
RANITIDINE: Summary: Ranitidine, like cimetidine, has been reported to decrease absorption of vitamin B12 (cyanocobalamin). Malabsorption of cyanocobalamin did not appear to be due to an alteration of gastric intrinsic factor.
Severity: not specified.
Onset: not specified.
Documentation: poor.
SIMVASTATIN: Severity: none.
Onset: not specified.
Documentation: fair.
Literature Reports: A pilot study was conducted by MacMahon et al (2000) to evaluate whether any clinically meaningful interaction between simvastatin and folic acid/vitamin B12 exists. The double-blind, placebo-controlled, parallel study enrolled 141 patients with increased triglycerides and LDL-C. A two-week placebo/diet run-in period was followed by six weeks of active treatment. Active treatment groups included those patients randomized to either daily simvastatin 80 mg and folic acid 2 mg/vitamin B12 0.8 mg (combination product); or simvastatin 80 mg and placebo vitamins; or placebo simvastatin and folic acid 2mg/vitamin B12 0.8 mg. Significant reductions (p less than 0.001) in homocysteine of 23.1% and 25.3% occurred in those patients receiving vitamins alone or in combination with simvastatin, respectively. Similar reductions in LDL-C occurred in the combination group (55.2%) and the simvastatin alone group (51.5%). There was no measurable antagonistic effect when the combinations of simvastatin and homocysteine-lowering vitamins, such as folic acid/vitamin B12, were administered concomitantly.
INTRAVENOUS ADMIXTURES: COMPATIBILITIES - SOLUTIONS: DEXTRAN: DEXTRAN IN DEXTROSE: Cyanocobalamin 1 mg/L with dextran 70 6% in Dextrose 5% in water, physically compatible for 24 hours; conditions not specified.
Cyanocobalamin 1 mg/L and vitamin B complex with C with dextran 70 6% in Dextrose 5% in water, physically compatible for 24 hours; conditions not specified.
DEXTRAN IN SODIUM CHLORIDE: Cyanocobalamin 1 mg/L with dextran 70 6% in Sodium chloride 0.9%, physically compatible for 24 hours; conditions not specified.
Cyanocobalamin 1 mg/L with vitamin B complex with C with dextran 70 6% in Sodium chloride 0.9%, physically compatible for 24 hours; conditions not specified (Kirkland et al, 1961; Smith, 1965).
DEXTROSE IN LACTATED RINGER'S: Dextrose 2.5% in half-strength lactated Ringer's injection (with cyanocobalamin 1000 mcg/L physically compatible; conditions not specified).
Dextrose 5% in lactated Ringer's injection (with cyanocobalamin 1000 mcg/L physically compatible; conditions not specified).
Dextrose 10% in lactated Ringer's injection (with cyanocobalamin 1000 mcg/L physically compatible; conditions not specified).
DEXTROSE IN RINGER'S: Dextrose 2.5% in half-strength Ringer's injection (with cyanocobalamin 1000 mcg/L physically compatible; conditions not specified).
Dextrose 5% in Ringer's injection (with cyanocobalamin 1000 mcg/L physically compatible; conditions not specified).
Dextrose 10% in Ringer's injection (with cyanocobalamin 1000 mcg/L physically compatible; conditions not specified).
INCOMPATIBILITIES - SOLUTIONS: PROTEIN HYDROLYSATE: Protein hydrolysate (incompatible with cyanocobalamin; conditions not specified).
INCOMPATIBILITIES - DRUGS: CHLORPROMAZINE: Chlorpromazine hydrochloride incompatible with cyanocobalamin; conditions not specified.
HYDROCORTISONE: Hydrocortisone sodium succinate (250 mg/L with cyanocobalamin 1000 mcg/L in IONOSOL(R) DCM IN DEXTROSE 5%, haze or precipitate formation reported between 6 and 24 hours; conditions not specified).
PHENYTOIN: Cyanocobalamin (Rubramin(R)) stated to be physically incompatible with phenytoin (diphenylhydantoin sodium - Dilantin(R)); conditions not specified.
PROCHLORPERAZINE: Cyanocobalamin incompatible with prochlorperazine; conditions not specified.
WARFARIN: Warfarin (100 mg/L with cyanocobalamin 100 mcg/L physically incompatible in Dextrose 5% in water; conditions not specified).
NICOTINAMIDE BP: ATORVASTATIN: Interaction Effect: an increased risk of myopathy or rhabdomyolysis.
Summary: The risk of myopathy is increased when niacin is administered concurrently with HMG-CoA reductase inhibitors such as atorvastatin. Caution is warranted if concurrent administration is deemed necessary.
Severity: major.
Onset: delayed.
Substantiation: theoretical.
Clinical Management: If concurrent therapy is required, monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, o weakness). Monitor creatine kinase (CK) levels and discontinue use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected.
Probable Mechanism: unknown.
CERIVASTATIN: Interaction Effect: an increased risk of myopathy or rhabdomyolysis.
Summary: The risk of myopathy is increased when lipid-lowering doses of niacin (greater than 1 gram daily) are administered concurrently with HMG-CoA reductase inhibitors such as cerivastatin. Caution is warranted if concurrent administration is deemed necessary.
Severity: major.
Onset: delayed.
Substantiation: probable.
Clinical Management: If concurrent therapy is required, monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness). Monitor creatine kinase (CK) levels and discontinue use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected.
Probable Mechanism: unknown.
CHOLESTYRAMINE: Interaction Effect: decreased niacin absorption.
Summary: Concurrent administration of niacin and cholestyramine may affect the absorption of niacin. In an in vitro study, 10% to 30% of available niacin was bound to cholestyramine.
Severity: moderate.
Onset: rapid.
Substantiation: theoretical.
Clinical Management: If used concurrently, at least four to six hours should elapse between the ingestion of cholestyramine and niacin.
Probable Mechanism: binding of niacin to cholestyramine.
COLESTIPOL: Interaction Effect: decreased niacin absorption.
Summary: Concurrent administration of niacin and colestipol may affect the absorption of niacin. In an in vitro study, about 98% of available niacin was bound to colestipol.
Severity: moderate.
Onset: rapid.
Substantiation: theoretical.
Clinical Management: If used concurrently, at least four to six hours should elapse between the ingestion of colestipol and niacin.
Probable Mechanism: binding of niacin to colestipol.
FLUVASTATIN: Interaction Effect: an increased risk of myopathy or rhabdomyolysis.
Summary: The concomitant administration of fluvastatin and niacin has no effect on the bioavailability of fluvastatin. Myopathy and rhabdomyolysis have been observed in patients treated with HMG-CoA reductase inhibitors. Concomitant administration of fluvastatin with niacin may increase the risk of these conditions. However, results from a short-term clinical trial involving 74 patients indicated that combination therapy with fluvastatin and niacin may be safe. Careful monitoring of patients is still advised.
Severity: moderate.
Onset: delayed.
Substantiation: theoretical.
Clinical Management: If concurrent therapy is required, monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness). Monitor creatine phosphokinase (CPK) levels and discontinue use if CPK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected.
Probable Mechanism: unknown.
LOVASTATIN: Interaction Effect: myopathy or rhabdomyolysis.
Summary: The concurrent use of lovastatin and niacin in lipid-lowering doses (greater than 1 gram daily) has resulted in reversible myopathy and rhabdomyolysis (Malloy et al, 1987a; Reaven & Witztum, 1988a; Norman et al, 1988a; Cooke, 1994). The incidence of myopathy which occurred during coadministration of lovastatin and niacin was 2% in early clinical studies (Prod Info Altocor(TM), 2003; Prod Info Mevacor(R), 2002). However, two short-term studies have found that the combination of low-dose lovastatin plus niacin resulted in no reports of myopathy or rhabdomyolysis (Vacek et al, 1995a; Gardner et al, 1996a). The dose of lovastatin should not exceed 20 milligrams daily when given concomitantly with lipid lowering doses of niacin (greater than or equal to 1 g/day).
Severity: major.
Onset: delayed.
Substantiation: probable.
Clinical Management: The combined use of HMG-CoA reductase inhibitors and niacin should be generally be avoided unless the benefit of further alteration in lipid levels is likely to outweigh the increased risk of this drug combination. The dose of lovastatin should not exceed 20 mg daily in patients receiving concomitant lipid lowering doses of niacin (greater than or equal to 1 g/day). If concurrent therapy is required, monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness). Monitor creatine kinase (CK) levels and discontinue use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected.
Probable Mechanism: unknown.
NICOTINE: Interaction Effect: flushing and dizziness.
Summary: A case of a woman experienced flushing and dizziness when transdermal nicotine 20 mg daily was added to her drug regimen that consisted of niacin 250 mg twice daily, nifedipine 30 mg daily, ranitidine 150 mg twice daily, and ferrous sulfate 300 mg three times daily. She experienced flushing after every niacin dose for three days. Niacin was withheld for a day and no adverse effects were reported; niacin was restarted and within 30 min the patient was flushed and dizzy. Niacin was discontinued and the flushing episodes stopped.
Severity: minor.
Onset: rapid.
Substantiation: probable.
Clinical Management: If niacin and transdermal nicotine are used concurrently, the patient should be advised of the potential for this interaction.
Probable Mechanism: unknown.
PRAVASTATIN: Interaction Effect: an increased risk of myopathy and rhabdomyolysis.
Summary: Rare cases of rhabdomyolysis have been reported with the use of pravastatin. The risk of myopathy during treatment with another HMG-CoA reductase inhibitor is increased with concurrent niacin therapy. Therefore, coadministration of niacin in lipid-lowering doses and pravastatin is not recommended. However, in clinical trials involving a small number of patients, there were no reports of myopathy in patients receiving concurrent niacin and pravastatin therapy.
Severity: moderate.
Onset: delayed.
Substantiation: theoretical.
Clinical Management: The concurrent use of niacin in lipid-lowering doses and pravastatin is generally not recommended. If concurrent therapy is required, monitor the patient for signs and symptoms of myopathy and rhabdomyolysis (muscle pain, tenderness, or weakness). Monitor creatine kinase (CK) levels and discontinue use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected.
Probable Mechanism: unknown.
ROSUVASTATIN: Interaction Effect: an increased risk of myopathy or rhabdomyolysis.
Summary: No cases of rosuvastatin and niacin adverse interactions have been reported to date. However, the concurrent use of niacin with lovastatin (a related member of the HMG-CoA reductase inhibitor class) in lipid-lowering doses (greater than 1 gram niacin daily) has resulted in reversible myopathy and rhabdomyolysis. The incidence of myopathy that occurred during co-administration of lovastatin and niacin was 2% in early clinical studies. The general risk of treatment-related myopathy is reported to increase with concomitant administration of niacin with drugs of the HMG-CoA reductase inhibitor class.
Severity: major.
Onset: delayed.
Substantiation: probable.
Clinical Management: Weigh the benefit of further alteration in lipid levels relative to the increased risk of this combination of agents. If concurrent therapy is required, monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness). Periodic CK determinations may be advisable in patients who are just starting or are increasing their dose of rosuvastatin, and in patients with complicated medical histories. Discontinue use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected.
Probable Mechanism: unknown.
SIMVASTATIN: Interaction Effect: an increased risk of myopathy or rhabdomyolysis.
Summary: The concomitant use of simvastatin and high-dose niacin (greater than or equal to 1 gram) may increase the risk of developing myopathy as both agents can cause myopathy when given alone. The benefit of using this combination in patients should be carefully weighed against the potential risks and use caution if these agents are prescribed together. Patients should be monitored for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness) and periodic CK determinations may be advisable. Discontinue simvastatin immediately if myopathy or rhabdomyolysis is suspected or diagnosed.
Severity: major.
Onset: delayed.
Substantiation: probable.
Clinical Management: Concurrent use of simvastatin and high-dose niacin (greater than or equal to 1 gram) may increase the risk of developing myopathy as both agents can cause myopathy when given alone. Carefully weigh the benefit of combination therapy against the potential risks and use caution if these agents are prescribed together (Prod Info simvastatin oral tablets, 2006). Monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness). Periodic CK determinations may be advisable. Discontinue simvastatin immediately if myopathy or rhabdomyolysis is suspected or diagnosed.
Probable Mechanism: additive risk of myopathy.
DRUG-FOOD COMBINATIONS: ETHANOL: Interaction Effect: increase in side effects of flushing and pruritus.
Summary: Concomitant alcohol may increase the side effects of flushing and pruritus and should be avoided around the time of niacin ingestion. In one case report, concomitant ethanol and niacin therapy resulted in delirium (paranoid ideation and asterixis) and lactic acidosis.
Severity: moderate.
Onset: unspecified.
Substantiation: probable.
Clinical Management: Alcohol may potentiate the adverse effects of niacin. Concomitant alcohol may increase the side effects of flushing and pruritus and should be avoided around the time of niacin ingestion.
Probable Mechanism: unknown.
Literature Reports: In one case report, concomitant ethanol and niacin therapy resulted in delirium (paranoid ideation and asterixis) and lactic acidosis. However, a causal relationship between the reaction and the interaction was not clearly established.
DRUG-LAB MODIFICATIONS: CATECHOLAMINE MEASUREMENT: Interaction Effect: falsely elevated plasma or urinary catecholamine levels.
Summary: Niacin use may result in false elevations of plasma or urinary catecholamine levels due to interference with the fluorescence test. Both plasma and urine catecholamine assay results should be interpreted with caution in patients receiving niacin.
Severity: moderate.
Onset: unspecified.
Substantiation: theoretical.
Clinical Management: Niacin may interfere with the fluorescence test for plasma or urinary catecholamines leading to falsely elevated levels. Interpret such assay results with caution in patients receiving niacin.
Probable Mechanism: interference with the fluorescence test.
URINALYSIS, GLUCOSE, QUALITATIVE: Interaction Effect: false-positive urine glucose measurements with cupric sulfate solution (Benedict's solution).
Summary: Niacin may lead to false-positive reactions for urinary glucose when tested using the cupric sulfate solution (Benedicts's reagent). Use caution when interpreting results of these tests in patients receiving niacin.
Severity: moderate.
Onset: unspecified.
Substantiation: theoretical.
Clinical Management: Niacin therapy may result in false-positive urine glucose measurements when assayed using cupric sulfate solution (Benedicts's reagent). Interpret results of such tests with caution in patients receiving niacin.
Probable Mechanism: mechanism unknown.
LYSINE HYDROCHLORIDE USP: CYCLOSERINE, ISONIAZID, HYDRALAZINE, ORAL CONTRACEPTIVES, PENICILLAMINE: Increased need for pyridoxine.
LEVODOPA: Decreased effect of levodopa. (Interaction does not occur with levodopa/carbidopa in combination with pyridoxine.)
PHENYTOIN: Phenytoin serum levels may be decreased.
INCOMPATIBILITY: Incompatible with alkaline solutions, iron salts and oxidizing agents (parenteral).
LABORATORY TEST INTERACTIONS: May result in false-positive urobilinogen in the spot test using Ehrlich reagent.
Caution For Usage
Incompatibilities: All excipients used in the formulation are inert materials which will not take part in stability of active ingredient used in the formulation.
Storage
Keep the cap tightly closed.
Store at a temperature not exceeding 30°C. Protect from light.
Shelf Life: 24 Months from the date of manufacturing.
ATC Classification
A11EX - Vitamin B-complex, other combinations ; Used as dietary supplements.
Presentation/Packing
Syrup 100 mL x 1's. 200 mL x 1's.
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