In pregnant women, mefloquine appears to pose minimal risk to the fetus, and is not associated with increased risk of birth defects or miscarriages. Compared to other malaria chemoprophylaxis regimens, however, mefloqinone may produce more side effects in non-pregnant travelers. Mefloquine is also safe and effective for use during breastfeeding, though it appears in breast milk in low concentrations. : 9  The World Health Organization (WHO) gives approval for the use of mefloquine in the second and third trimesters of pregnancy and use in the first trimester does not mandate termination of pregnancy. Pharmacology
Elimination
Mefloquine is metabolized primarily through the liver. Its elimination in persons with impaired liver function may be prolonged, resulting in higher plasma levels and an increased risk of adverse reactions. The mean elimination plasma half-life of mefloquine is between two and four weeks. Total clearance is through the liver, and the primary means of excretion is through the bile and feces, as opposed to only 4% to 9% excreted through the urine. During long-term use, the plasma half-life remains unchanged.Liver function tests should be performed during long-term administration of mefloquine. Alcohol use should be avoided during treatment with mefloquine. Chemistry
Specifically it is used as mefloquine hydrochloride. Mefloquine is a chiral molecule with two asymmetric carbon centres, which means it has four different stereoisomers. The drug is currently manufactured and sold as a racemate of the (R,S)- and (S,R)-enantiomers by Hoffman-LaRoche, a Swiss pharmaceutical company. Essentially, it is two drugs in one.
The two drugs bind the same enzymatic targets as the drugs trimethoprim and sulfamethoxazole - dihydrofolate reductase and dihydropteroate synthase, respectively.Pyrimethamine has also been used in several trials to treat retinochoroiditis. Pregnancy consideration
Pyrimethamine is labeled as pregnancy category C in the United States. To date,  not enough evidence on its risks in pregnancy or its effects on the fetus is available. Malaria
It is primarily active against Plasmodium falciparum, but also against Plasmodium vivax. Due to the emergence of pyrimethamine-resistant strains of P. falciparum, pyrimethamine alone is seldom used now. In combination with a long-acting sulfonamide such as sulfadiazine, it was widely used, such as in Fansidar, though resistance to this combination is increasing. Contraindications
Pyrimethamine is contraindicated in people with folate-deficiency anaemia. Side effects
When higher doses are used, as in the treatment of toxoplasmosis, pyrimethamine can cause gastrointestinal symptoms such as nausea, vomiting, glossitis, anorexia, and diarrhea. A rash, which can be indicative of a hypersensitivity reaction, is also seen, particularly in combination with sulfonamides. Central nervous system effects include ataxia, tremors, and seizures. Hematologic side effects such as thrombocytopenia, leukopenia, and anemia can also occur. Interactions
Other antifolate agents such as methotrexate and trimethoprim may potentiate the antifolate actions of pyrimethamine, leading to potential folate deficiency, anaemia, and other blood dyscrasias. Mechanism of action
Pyrimethamine interferes with the regeneration of tetrahydrofolic acid from dihydrofolate by competitively inhibiting the enzyme dihydrofolate reductase. Tetrahydrofolic acid is essential for DNA and RNA synthesis in many species, including protozoa.