What are the effects of Quinine (an antimalarial medication) on pregnancy?

From the Guidelines

Quinine can be used to treat malaria in pregnant women, but it is not the first-line treatment, and its use should be carefully considered due to potential side effects and the availability of more effective and safer alternatives like artemether-lumefantrine 1.

Recommended Regimen

The recommended regimen for uncomplicated malaria in pregnancy is:

• First trimester: Quinine 10 mg/kg three times daily for 7 days, plus clindamycin 300 mg three times daily for 7 days.
• Second and third trimesters: Artemether-lumefantrine is preferred, but quinine can be used if necessary, as supported by the CDC recommendations 1.

Considerations for Quinine Use in Pregnancy

When using quinine in pregnancy:

• Monitor for hypoglycemia, as quinine can stimulate insulin release.
• Be aware of potential side effects like tinnitus, headache, and nausea.
• Ensure adequate dosing, as pregnancy can alter drug metabolism. Quinine crosses the placenta but has not been associated with increased risk of birth defects, as noted in studies on its use in pregnancy 1. Its use in pregnancy is justified by the high risks of untreated malaria to both mother and fetus. However, newer artemisinin-based combinations are generally preferred when available due to their efficacy and better side effect profile.

Important Considerations

Always confirm the diagnosis of malaria before treatment and consider local resistance patterns when selecting antimalarial drugs. The choice of treatment should be guided by the most recent and highest quality evidence, prioritizing the safety and efficacy of the treatment for both the mother and the fetus 1.

From the FDA Drug Label

Prolonged experience with quinine in pregnant women over several decades, based on published prospective and retrospective observational studies, surveys, safety and efficacy studies, review articles, case reports and case series have not identified a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes In animal reproduction studies, administration of quinine by multiple routes of administration to pregnant rabbits, dogs, guinea pigs, rats, and monkeys during the period of organogenesis at doses of 0. 25 to 2 times the maximum recommended human dose (MRHD) based on body surface area (BSA), produced embryo-fetal toxicity including malformations. An increased incidence of hypoglycemia, due to increased pancreatic secretion of insulin, has been reported with quinine use, in pregnant women, especially during the third trimester Tinnitus, vomiting, dizziness, and nausea are commonly reported adverse reactions in pregnant women taking quinine Pregnant women are also at risk for a rare triad of complications: massive hemolysis, hemoglobinemia, and hemoglobinuria

The effects of quinine on pregnancy include:

• No increased risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes based on prolonged experience with quinine in pregnant women
• Embryo-fetal toxicity and malformations in animal reproduction studies
• Hypoglycemia due to increased pancreatic secretion of insulin, especially during the third trimester
• Common adverse reactions such as tinnitus, vomiting, dizziness, and nausea
• Rare triad of complications: massive hemolysis, hemoglobinemia, and hemoglobinuria 2

From the Research

Effects of Quinine on Pregnancy

• Quinine has traditionally been the treatment drug of choice for severe malaria in pregnancy 3
• However, recent studies suggest that artemisinins, such as artesunate, may be more efficacious and safe for use in pregnant women 3, 4
• Quinine treatment has been associated with a high rate of gametocyte carriage and adverse effects such as tinnitus 5
• Some studies have found no increased risk of miscarriage, stillbirth, or congenital anomalies associated with quinine treatment in the first trimester 5, 6, 7
• However, other studies have found that quinine exposure in the first trimester may be associated with an increased risk of miscarriage, stillbirth, and premature birth 7

Comparison with Artemisinins

• Artemisinins, such as artemether-lumefantrine, may be a safer and more effective alternative to quinine for treating malaria in pregnancy 4, 6, 7
• Some studies have found no evidence of embryotoxicity or teratogenicity associated with artemisinin-based treatments in the first trimester 4, 6
• Artemether-lumefantrine has been found to have a lower risk of adverse pregnancy outcomes compared to quinine 4, 7

Pregnancy Outcomes

• The risk of adverse pregnancy outcomes, such as miscarriage, stillbirth, and congenital anomalies, may be lower with artemisinin-based treatments compared to quinine 4, 6, 7
• Quinine exposure in the first trimester may be associated with an increased risk of miscarriage, stillbirth, and premature birth 7
• However, some studies have found no increased risk of adverse pregnancy outcomes associated with quinine treatment in the first trimester 5, 6