QUIOFIC

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE QUIOFIC is indicated for the treatment of megaloblastic anemias due to folic acid deficiency in adult and pediatric patients. QUIOFIC is a folate analog indicated for the treatment of megaloblastic anemias due to folic acid deficiency in adult and pediatric patients. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Recommended starting dosage in adults and pediatric patients (regardless of age) is up to 1 mg orally daily. ( 2 ) Maintenance dosage ( 2 ) - Pediatric patients birth to 23 months: 0.1 mg orally daily - Pediatric patients 2 years to less than 4 years: up to 0.3 mg orally daily - Adults and pediatric patients 4 years and older: 0.4 mg orally daily - Pregnant and Lactating Women: 0.8 mg orally daily; but never less than 0.1 mg orally per day 2.1 Important Administration Information Instruct patients or caregivers to use an oral dosing syringe to correctly measure the prescribed amount of medication. Inform patients that oral dosing syringes may be obtained from their pharmacy. 2.2 Recommended Dosing Initial Dosing The recommended starting dosage of QUIOFIC in pediatric and adult patients is up to 1 mg orally daily. QUIOFIC can be taken with or without food. Rule out pernicious anemia prior to use of any doses greater than 0.4 mg (except during pregnancy and lactation). Maintenance Dosing When clinical symptoms have subsided and the blood picture has become normal, use a daily maintenance level as follows: - Pediatric patients aged birth to 23 months: 0.1 mg orally daily - Pediatric patients aged 2 years to less than 4 years: up to 0.3 mg orally daily - Pediatric patients aged 4 years and older and adult patients: 0.4 mg orally daily - Pregnant and Lactating Women: 0.8 mg orally daily; but never less than 0.1 mg orally per day Higher maintenance doses may be needed in the presence of alcoholism, hemolytic anemia, anticonvulsant therapy, or chronic infection. Monitor patients frequently for relapse and adjust dose accordingly. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Folic acid in doses above 0.1 mg daily may obscure pernicious anemia in that hematologic remission can occur while neurologic manifestations remain progressive. This may result in severe nervous system damage before the correct diagnosis is made. ( 5.1 ) 5.1 Risk of Obscuring Diagnosis of Pernicious Anemia The use of single-agent QUIOFIC (without the use of vitamin B12) is not recommended for the treatment of pernicious anemia and other megaloblastic anemias in which vitamin B 12 is deficient. Folic acid in doses above 0.1 mg daily may obscure pernicious anemia in that hematologic remission can occur while neurologic manifestations remain progressive. There is a potential danger in administering folic acid to patients with undiagnosed anemia, since folic acid may obscure the diagnosis of pernicious anemia by alleviating the hematologic manifestations of the disease while allowing the neurologic complications to progress. This may result in severe nervous system damage before the correct diagnosis is made. Adequate doses of vitamin B 12 may prevent, halt, or improve the neurologic changes caused by pernicious anemia. Drug interactions 7 DRUG INTERACTIONS Anticonvulsant action of phenytoin is antagonized by folic acid. ( 7 ) Multiple drug classes, including anticonvulsants, antibiotic/antimicrobial agents, folate antagonists, GI-binding agents, and oral contraceptives, may reduce folic acid absorption or folate levels. ( 7 ) 7.1 Impact of Folic Acid on Other Drugs Folic acid may interfere with gastrointestinal absorption of methotrexate. Folic acid therapy in folate-deficient individuals may decrease serum levels of phenytoin. Folic acid may also interfere with the absorption and effectiveness of antibiotic tetracycline. Folic acid supplements are usually avoided on the day of oral methotrexate administration. Generally, the time of administration of these drugs should be separated from folic acid. 7.2 Impact of Other Drugs on Folic Acid A wide range of medications can affect folic acid levels through multiple mechanisms, including impaired absorption, accelerated metabolism, and direct inhibition of folate pathways. Enzyme-inducing anticonvulsants such as phenytoin, primidone, carbamazepine, phenobarbital, and the broader anticonvulsant class increase hepatic folate metabolism, inhibit intestinal folate-processing enzymes, raise gastrointestinal pH, or displace folate from serum proteins, collectively leading to decreased folate availability. Valproate and sulfasalazine primarily reduce intestinal folate absorption or interfere with folate-dependent metabolic pathways, while isoniazid and cycloserine reduce folate utilization through metabolic disruption. Several antifolate agents, including trimethoprim, pyrimethamine, methotrexate, and triamterene, directly inhibit dihydrofolate reductase, decreasing the formation of active folate derivatives. Additional agents such as