This drug should not be used during the first trimester of pregnancy unless there are no alternatives; this drug should be considered during the second and third trimesters of pregnancy only if the benefit to the mother outweighs the risk to the fetus.
-According to some experts: Use is contraindicated during the first trimester of pregnancy.

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned.

Risk summary: Published data from clinical trials and pharmacovigilance data have not associated use of this drug during pregnancy with major birth defects, miscarriage, or adverse maternal/fetal outcomes.

Comments:
-Disease-associated maternal and/or embryo/fetal risk should be considered.
-Use of this drug may reduce efficacy of hormonal contraceptives; patients using hormonal contraceptives should be advised to use an alternative nonhormonal contraceptive method of add a barrier method of contraception during therapy; according to some authorities, additional nonhormonal method of contraception should be used for about 1 month.
-According to some authorities, since this drug is contraindicated during the first trimester of pregnancy, patients of childbearing potential should not conceive while on this treatment for malaria; this includes those prescribed this drug for stand-by emergency treatment of malaria during travel; an effective form of contraception should be used during travel and until the start of the next menstruation after therapy.

Animal studies have revealed evidence of embryotoxicity, teratogenicity, and fetal loss. Increases in fetal loss, early resorptions, and postimplantation loss observed in pregnant rats given 50 mg/kg/day artemether-lumefantrine orally (corresponding to at least 7 mg/kg/day artemether), less than half the maximum recommended human dose (MRHD) of 1120 mg artemether-lumefantrine/day based on body surface area (BSA) comparisons; no adverse effects observed at 25 mg/kg/day artemether-lumefantrine (corresponding to 3.6 mg/kg/day of artemether), about one-third the MRHD based on BSA comparison. Abortions, preimplantation loss, postimplantation loss, and decreases in number of live fetuses observed in pregnant rabbits given 175 mg/kg/day orally (corresponding to 25 mg/kg/day artemether), about 3 times the MRHD based on BSA comparisons; no adverse reproductive effects detected in rabbits at 105 mg/kg/day artemether-lumefantrine (corresponding to 15 mg/kg/day artemether), about 2 times the MRHD. Artemether and other artemisinins are associated with maternal toxicity, embryotoxicity, and malformations in animals at clinically relevant exposures, while lumefantrine doses up to 1000 mg/kg/day showed no evidence of maternal toxicity, embryofetal toxicity, or teratogenicity in rats and rabbits. While absence of risk cannot be definitively established, a meta-analysis of observational studies including over 500 women exposed to this drug in their first trimester of pregnancy, data from observational, and open-label studies including over 1200 pregnant women in their second or third trimester exposed to this drug compared to other antimalarials, and pharmacovigilance data have not shown an increase in major birth defects, miscarriage, or adverse maternal/fetal outcomes; published epidemiologic studies have important methodological limitations which hinder data interpretation, including inability to control for confounders (such as underlying maternal disease and maternal use of concomitant drugs) and missing information on dose and duration of therapy.

Malaria during and after pregnancy increases the risk for adverse pregnancy and neonatal outcomes (including maternal anemia, severe malaria, spontaneous abortion, stillbirths, preterm delivery, low birth weight, intrauterine growth restriction, congenital malaria, maternal and neonatal mortality).

In animal fertility studies, repeated dosing of this drug to female rats (for 2 to 4 weeks) led to pregnancy rates reduced by half. Abnormal sperm cells, decreased sperm motility, and increased testes weight observed in male rats administered this drug for about 3 months.

AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

See references

US CDC: Use is considered acceptable in mothers nursing infants at least 5 kg; safety has not been established in breastfed infants less than 5 kg.
-According to some experts: Caution is recommended.
-According to some authorities: Breastfeeding is not recommended during use of this drug.

Excreted into human milk: Yes (in very low amounts [estimated])

Comments:
-The components of this drug have not been studied in nursing mothers.
-Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this drug.
-The effects in the nursing infant are unknown; potential side effects in the breastfed child due to this drug or the mother's underlying condition should be considered.
-According to some authorities: Due to the long elimination half-life of lumefantrine (2 to 6 days), breastfeeding should not resume until at least 1 to 4 weeks after the last dose, unless potential benefits to mother and child outweigh risks of therapy; local protocol should be consulted regarding nursing timing.

Estimates of excretion into breast milk suggest amounts in milk are very low. The excretion of each component in breast milk was estimated from average Cmax after a standard 6-dose regimen of artemether 40 mg and lumefantrine 240 mg per day; milk/plasma ratios of 1.04 for artemether and 1.3 for lumefantrine were assumed. According to author estimation, a fully breastfed infant would receive 0.03 mg/day of artemether (or less than 0.4% of the recommended dose for a 5 kg infant) and 5 mg/day of lumefantrine (or less than 10% of the recommended dose for a 5 kg infant).

See references