QUININE

Fetal Risk Summary

Nishimura and Tanimura (1) summarized the human case reports of teratogenic effects linked with quinine in 21 infants who were exposed during the 1st trimester after unsuccessful abortion attempts (some infants had multiple defects and are listed more than once): Central nervous system (CNS) anomalies (6 with hydrocephalus) (10 cases) Limb defects (3 dysmelias) (8 cases) Facial defects (7 cases) Heart defects (6 cases) Digestive organ anomalies (5 cases) Urogenital anomalies (3 cases) Hernias (3 cases) Vertebral anomaly (1 case) The malformations noted are varied, although CNS anomalies and limb defects were the most frequent. Auditory defects and optic nerve damage have also been reported (1,2,3,4 and 5). These reports usually concern the use of quinine in toxic doses as an abortifacient. Quinine has also been used for the induction of labor in women with intrauterine fetal death (6). Epidemiologic observations do not support an increased teratogenic risk or increased risk of congenital deafness over non-quinine-exposed patients (1,7). Neonatal and maternal thrombocytopenia purpura and hemolysis in glucose-6-phosphate dehydrogenase–deficient newborns has been reported (8,9).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 35 newborns had been exposed to quinine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Two (5.7%) major birth defects were observed (one expected). No anomalies were observed in six defect categories (cardiovascular defects, oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias) for which specific data were available.

Quinine has effectively been replaced by newer agents for the treatment of malaria. Although no increased teratogenic risk can be documented, its use during pregnancy should be avoided. One manufacturer considers the drug to be contraindicated in pregnancy (10). However, some investigators believe quinine should be used for the treatment of chloroquine-resistant Plasmodium falciparum malaria (11).

[*Risk Factor X according to manufacturer—Merrell Dow, 1993.]

Breast Feeding Summary

Quinine is excreted into breast milk. Following 300- and 640-mg oral doses in six patients, milk concentrations varied up to 2.2 µg/mL with an average level of 1 µg/mL at 3 hours (12). No adverse effects were reported in the nursing infants. Patients at risk for glucose-6-phosphate dehydrogenase deficiency should not be breast-fed until this disease can be ruled out. The American Academy of Pediatrics considers quinine to be compatible with breast feeding (13).

References

1. Nishimura H, Tanimura T. Clinical Aspects of The Teratogenicity of Drugs. New York, NY: American Elsevier, 1976:140–3.
2. Robinson GC, Brummitt JR, Miller JR. Hearing loss in infants and preschool children. II. Etiological considerations. Pediatrics 1963;32:115–24.
3. West RA. Effect of quinine upon auditory nerve. Am J Obstet Gynecol 1938;36:241–8.
4. McKinna AJ. Quinine induced hypoplasia of the optic nerve. Can J Ophthalmol 1966;1:261.
5. Morgon A, Charachon D, Brinquier N. Disorders of the auditory apparatus caused by embryopathy or foetopathy. Prophylaxis and treatment. Acta Otolaryngol (Stockh) 1971;291(Suppl):5.
6. Mukherjee S, Bhose LN. Induction of labor and abortion with quinine infusion in intrauterine fetal deaths. Am J Obstet Gynecol 1968;101:853–4.
7. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977:299,302,333.
8. Mauer MA, DeVaux W, Lahey ME. Neonatal and maternal thrombocytopenic purpura due to quinine. Pediatrics 1957;19:84–7.
9. Glass L, Rajegowda BK, Bowne E, Evans HE. Exposure to quinine and jaundice in a glucose-6-phosphate dehydrogenase-deficient newborn infant. Pediatrics 1973;82:734–5.
10. Product information. Quinamm. Merrell Dow, 1990.
11. Strang A, Lachman E, Pitsoe SB, Marszalek A, Philpott RH. Malaria in pregnancy with fatal complications: case report. Br J Obstet Gynaecol 1984;91:399–403.
12. Terwilliger WG, Hatcher RA. The elimination of morphine and quinine in human milk. Surg Gynecol Obstet 1934;58:823–6.
13. Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:137–50.