Can Artemether-Lumefantrine (ACT SP) be given to pregnant women?

Artemether-Lumefantrine (ACT SP) Use in Pregnant Women

Artemether-Lumefantrine (AL) can be safely given to pregnant women during the second and third trimesters of pregnancy at the same doses recommended for non-pregnant women, but should only be used in the first trimester when other treatment options (mefloquine or quinine plus clindamycin) are unavailable. 1

Treatment Recommendations by Trimester

First Trimester

• First-line treatment options:
  • Mefloquine
  • Quinine plus clindamycin
• When first-line options are unavailable:
  • Artemether-Lumefantrine may be considered 1

Second and Third Trimesters

• Artemether-Lumefantrine is recommended as a safe and effective option
• Same dosing as for non-pregnant women 1

Safety Evidence

Second and Third Trimester Safety

The CDC guidelines clearly state that AL is safe during the second and third trimesters based on substantial evidence from multiple studies 1. This recommendation is consistent with World Health Organization (WHO) treatment guidelines.

Key findings supporting second/third trimester safety:

• Multiple trials comparing ACTs with quinine-based regimens found no differences in pregnancy outcomes 1
• Fewer maternal adverse events occurred with ACTs compared to non-ACTs 1
• A prospective cohort study in Zambia showed similar rates of perinatal mortality between AL (4.2%) and sulfadoxine-pyrimethamine (5.0%) groups 2

First Trimester Considerations

First trimester use requires more caution due to limited data, though emerging evidence suggests AL may be safer than previously thought:

• A meta-analysis of five observational studies found no significant increase in miscarriage or stillbirth risk with artemisinin exposure compared to quinine (adjusted hazard ratio for stillbirth and miscarriage: 0.58,95% CI = 0.36–1.02) 1
• A Zambian observational study of 294 first-trimester exposures found similar rates of perinatal mortality between AL (4.4%) and SP/quinine (3.9%) groups 3
• A small Sudanese study of 62 women exposed to artemisinins in early pregnancy reported no congenital malformations and only two miscarriages (which occurred during quinine treatment for second malaria episodes) 4

Common Pitfalls and Caveats

1. First trimester restrictions: The most important caveat is to remember that AL should not be first-line therapy in the first trimester. Only use AL in the first trimester when mefloquine or quinine plus clindamycin are unavailable 1.

2. Malaria risks during pregnancy: Untreated malaria in pregnancy can result in serious maternal and fetal complications. The risks of untreated malaria may outweigh the potential risks of antimalarial medication 1.

3. Monitoring requirements: Women treated with AL during pregnancy should be followed up through delivery to monitor for any adverse outcomes.

4. Resistance patterns: Consider local resistance patterns when selecting antimalarial treatment, as chloroquine resistance affects treatment choices 1.

5. Drug availability: Limited availability of quinine and increasing resistance to mefloquine may restrict treatment options in some settings, making AL an important alternative 1.

Developmental and Reproductive Toxicity

Animal studies have shown that:

• Lumefantrine has developmental no-effect levels of 300 mg/kg/day in rats and 1000 mg/kg/day in rabbits 5
• Artemether has developmental no-effect levels of 3 mg/kg/day in rats and 25 mg/kg/day in rabbits 5
• While artemisinin derivatives can cause embryotoxicity in animals, lumefantrine did not show teratogenicity in animal studies 5

In human studies, no significant increase in congenital malformations has been observed with AL exposure during pregnancy 1, 3, 2.

In summary, Artemether-Lumefantrine is a safe and effective option for treating malaria during the second and third trimesters of pregnancy, and can be considered in the first trimester when other recommended treatments are unavailable.