warnings
WARNINGS Hemolytic anemia and G6PD deficiency Due to the risk of hemolytic anemia in patients with G6PD deficiency, G6PD testing has to be performed before using primaquine. Due to the limitations of G6PD tests, physicians need to be aware of residual risk of hemolysis and adequate medical support and follow-up to manage hemolytic risk should be available. Primaquine should not be prescribed for patients with severe G6PD deficiency (see CONTRAINDICATIONS ). In case of mild to moderate G6PD deficiency, a decision to prescribe primaquine must be based on an assessment of the risks and benefits of using primaquine. If primaquine administration is considered, baseline hematocrit and hemoglobin must be checked before treatment and close hematological monitoring (e.g. at day 3 and 8) is required. Adequate medical support to manage hemolytic risk should be available. When the G6PD status is unknown and G6PD testing is not available, a decision to prescribe primaquine must be based on an assessment of the risks and benefits of using primaquine. Risk factors for G6PD deficiency or favism must be assessed. Baseline hematocrit and hemoglobin must be checked before treatment and close hematological monitoring (e.g. at day 3 and 8) is required. Adequate medical support to manage hemolytic risk should be available. Discontinue the use of primaquine phosphate promptly if signs suggestive of hemolytic anemia occur (darkening of the urine, marked fall of hemoglobin or erythrocytic count). Hemolytic reactions (moderate to severe) may occur in individuals with G6PD deficiency and in individuals with a family or personal history of favism. Areas of high prevalence of G6PD deficiency are Africa, Southern Europe, Mediterranean region, Middle East, South-East Asia, and Oceania. People from these regions have a greater tendency to develop hemolytic anemia (due to a congenital deficiency of erythrocytic G6PD) while receiving primaquine and related drugs. Usage in Pregnancy Safe usage of this preparation in pregnancy has not been established. Primaquine is contraindicated in pregnant women. Even if a pregnant woman is G6PD normal, the fetus may not be (see CONTRAINDICATIONS ). Animal data show toxicity to reproduction. Nonclinical data from studies conducted in bacteria and in animals treated with primaquine show evidence of gene mutations and chromosomal/DNA damage, teratogenicity, and injury to embryos and developing fetuses when primaquine is administered to pregnant animals. Patients must be informed of the potential for adverse genetic and reproductive effects associated with Primaquine treatment (See PRECAUTIONS , Carcinogenesis, Mutagenesis, and Impairment of fertility , and Animal Pharmacology and /or Animal Toxicology ). Use in Females and Males of Reproductive Potential Pregnancy Testing Sexually-active females of reproductive potential should have a pregnancy test prior to starting treatment with Primaquine. Contraception Patients should avoid pregnancy during treatment. The use of effective contraception is recommended during treatment and after the end of treatment as follows: Advise sexually-active females of child bearing potential to use effective contraception (methods that result in less than 1% pregnancy rates) when using Primaquine and after stopping treatment until completion of an on-going ovulatory cycle (e.g., up to next menses). Advise treated males whose partners may become pregnant, to use a condom while on treatment and for 3 months after stopping treatment with Primaquine. Lactation It is not known whether primaquine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from primaquine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.