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Interactions between specific vitamins in Cernevit and other agents should be managed accordingly.
Such interactions include: Agents that can cause pseudotumor cerebri (including certain tetracyclines): Increased risk for pseudotumor cerebri by concomitant administration of Vitamin A.
Alcohol (chronic excessive consumption): Increases the risk of vitamin A hepatotoxicity.
Anticonvulsants (phenytoin, fosphenytoin, phenobarbital, primidone): Folic acid supplementation can decrease the anticonvulsant serum concentration and increase seizure risk.
Antiplatelet agents (e.g., aspirin): Vitamin E can add to the inhibition of platelet function.
Aspirin (high dose therapy): Can reduce folic acid levels by increasing urinary excretion.
Certain anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital, valproate): Can cause folate, pyridoxine and vitamin D deficiencies.
Certain antiretroviral agents: Decreased vitamin D levels have been associated with, e.g., efavirenz and zidovudine. Decreased formation of the active vitamin D metabolite has been associated with protease inhibitors.
Chloramphenicol: Can inhibit the haematological response to vitamin B12 therapy.
Deferoxamine: Increased risk of iron-induced cardiac failure due to increased iron mobilization by supraphysiologic vitamin C supplementation. For specific precautions, refer to deferoxamine product information.
Ethionamide: Can cause pyridoxine deficiency.
Fluoropyrimidines (5-fluorouracil, capecitabine, tegafur): Increased cytotoxicity when combined with folic acid.
Folate antagonists, e.g., methotrexate, sulfasalazine, pyrimethamine, triamterene, trimethoprim, and high doses of tea catechins: Block the conversion of folate to its active metabolites and reduce the effectiveness of supplementation.
Folate antimetabolites (methotrexate, raltitrexed): Folic acid supplementation can decrease the antimetabolite effects.
Levodopa: The content of pyridoxine may interfere with the effects of concurrent levodopa therapy.
Pyridoxine antagonists, including cycloserine, hydralazine, isoniazid, penicillamine, phenelzine: Can cause pyridoxine deficiency.
Retinoids, including bexarotene: Increase the risk of toxicity when used concomitantly with vitamin A (see Hypervitaminosis A under Warnings).
Theophylline: Can cause pyridoxine deficiency.
Tipranavir oral solution: Contains 116 IU/mL of vitamin E, which is in excess of the daily recommended intake.
Vitamin K antagonists (e.g., warfarin): Enhanced anticoagulant effect by vitamin E.
Drugs that Bind to alpha1-Acid Glycoprotein (AAG): In an in vitro study using human serum, concentrations of glycocholic acid approximately 4 times higher than the glycocholic acid serum concentration that would result from a bolus injection of Cernevit in adults, increased the unbound fraction of selected drugs known to bind to alpha1-acid glycoprotein (AAG) by 50-80%.
It is not known whether this effect is clinically relevant if the amount of glycocholic acid contained in a standard Cernevit dose (as a component of the mixed micelles) is administered by slow intravenous injection, intramuscular injection, or infused over a longer period of time.
Patients receiving Cernevit as well as drugs that bind to AAG should be closely monitored for increases in response of these drugs. These include propranolol, prazosin, and numerous others.
Interactions with Additional Vitamin Supplementation: Some medications can interact with certain vitamins at doses markedly higher than those provided with Cernevit. This should be taken into consideration in patients receiving vitamins from multiple sources, and when applicable, patients should be monitored for such interactions and managed accordingly.
Such interactions include: Amiodarone: Concomitant use of vitamin B6 can enhance amiodarone-induced photosensitivity.
Agents with anticoagulant effects (e.g., such as abciximab, clopidogrel, heparin, warfarin): Increased bleeding risk due to additional risk of bleeding associated with high vitamin A doses.
Carbamazepine: Inhibition of metabolism associated with large nicotinamide doses.
Chemotherapeutic agents that rely on the production of reactive oxygen species for their activity: Possible inhibition of chemotherapy activity by the antioxidant effects of high doses of vitamin E.
Insulin, antidiabetic agents: Decreased insulin sensitivity associated with large nicotinamide doses.
Iron: High dose-supplementation with vitamin E may reduce the haematological response to iron in anaemic patients.
Oral contraceptives (combination hormone types): High doses of vitamin C have been associated with breakthrough bleeding and contraceptive failure.
Phenobarbital: Increased metabolism/lower serum levels and reduced effect associated with large pyridoxine doses.
Phenytoin, fosphenytoin: Lower serum levels associated with large pyridoxine doses.
Primidone: Decreased metabolism to phenobarbital and increased primidone levels associated with large nicotinamide doses.
Pernicious anaemia: The folic acid in Cernevit may obscure pernicious anaemia.
