QUIOFIC - Solubiomix, LLC

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.

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 pentamidine, antacids, cholestyramine, colestipol, and H ₂ blockers impair gastrointestinal folate uptake through pH elevation, transporter inhibition, or binding of dietary folate. Nitrous oxide indirectly decreases folate activity by inactivating vitamin B12 and downstream methylation pathways, while oral contraceptives increase folate turnover and urinary loss.

While on QUIOFIC treatment, if patients are concomitantly using any of the drugs or drug classes mentioned above, then monitor for reduced efficacy and adjust the dose of QUIOFIC as needed.

Risk Summary
Available data from published studies over decades of use of folic acid in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Pregnant women should follow the U.S. Recommended Daily Allowances for pregnancy because their folic acid requirements may exceed those of nonpregnant women. Pregnant women with folic acid deficiency during the first trimester are at increased risk of neural tube defects in the developing fetus. Animal studies to evaluate the potential reproductive and developmental toxicity have not been conducted.
The background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Risk Summary
Available data from published studies over decades of use of folic acid supplementation in lactating women have found that folic acid is present in human milk. Lactating women should follow the U.S. Recommended Dietary Allowances for their condition, because their folic acid requirements may exceed those of nonlactating women. At recommended supplementation doses, there have been no reports of adverse events in breastfed infants over decades of use. There are no data regarding the effect of folic acid on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for folic acid and any potential adverse effects on the breastfed child from supplemental folic acid or from the underlying maternal condition.

QUIOFIC is approved for treatment of megaloblastic anemias due to folic acid deficiency in pediatric patients [see Dosage and Administration (2)].

Folic acid supplementation restores tetrahydrofolate-dependent activity, with reticulocytosis in 2–5 days and hematologic normalisation within 1–2 weeks. Serum folate reflects recent intake, red blood cell folate reflects long-term stores, and plasma homocysteine serves as a functional biomarker.