RELIS database 2000; spm.nr. 203, RELIS Nord-Norge
Dato for henvendelse: 01.08.2000
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SPØRSMÅL: Patient has occasionally been taking Somadril® as a muscle relaxant. She recently became pregnant and has estimated that she has been taking Somadril® 1-2 tablets a week for the first 6 weeks during her pregnancy. Are there any documented teratogenic side effects in the 1st trimester?
Carisoprodol (Somadril®) is a centrally acting muscle relaxant indicated for muscle spasms and back pain (1).
The drug is metabolized in the liver by cytochrome (CYP) 2C19 (2) and excreted in the urine as metabolites including meprobamate (1). Carisoprodol crosses the human placenta (3). The onset of action of carisoprodol is within 30 minutes; its half-life is 8 hours (4). In one volunteer study, 9 out of 10 adults given 700 mg carisoprodol had peak serum concentrations reached within 1 hour. Within 2.5 hours post-ingestion, meprobamate levels exceeded carisoprodol levels in the blood (5).
Meprobamate is widely distributed and also diffuses across the placenta (6). It is extensively metabolised in the liver and is excreted in the urine mainly as an inactive hydroxylated metabolite and its glucuronide conjugate (6).
Serum concentrations of meprobamate (15-25 micromols/L) were observed in one study after an oral dose of 700mg carisoprodol. This is close to the serum concentrations (20-100 micomols/L) found after intake of therapeutic doses (400-800mg) of meprobamate (5).
The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 14 of which were exposed in the 1st trimester to carisoprodol (7). No association of the drug with large classes of malformations or to individual defects was found.
In another study involving 229,101 completed pregnancies, 326 newborns had been exposed to carisoprodol during the first trimester (7). Twenty major (6.1%) birth defects were observed (14 expected), including 3 cardiovascular defects, 2 oral clefts, and 1 hypospadias. No anomalies were observed in three other categories of defects (spina bifida, polydactyly, and limb reduction defects). Only with the two cases of oral clefts is there a suggestion of a possible association, but other factors, including the mother's disease and concurrent drug usage, may be involved (7).
Human studies to examine the teratogenic effect of meprobamate have been divided in their findings. In one study during two periods that included 19,044 live births, 395 patients received meprobamate in which 8 defects were observed during the first 42 days (8):
Congenital heart disease (2 with multiple other defects) 5 cases
Down's syndrome 1 case
Deafness (partial) 1 case
Deformed elbows and joints 1 case
No differences in rates of severe congenital anomalies according to treatment group were evident for the gestational period, 43 days to termination of pregnancy (8).
Many women under-reported the drugs prescribed by physicians and many did not know the names of the drugs prescribed.
In another study, the Collaborative Perinatal Project monitored 50,282 pregnancies, 356 women who took meprobamate during the 1st trimester and 989 women who took the drug later (9). 141 women took the drug both early and late in the pregnancy. No association of meprobamate with large classes of malformations or to individual defects were found.
In the surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies, 75 newborns had been exposed to meprobamate during the 1st trimester (10). Three major birth defects were observed (three were expected), including 1 oral cleft and 2 polydactyly. No anamolies were observed in four other defect categories (cardiovascular defects, spina bifida, limb reduction defects, and hypospadias) for which specific data was available. Other factors such as the mother's disease, concurrent drug usage, and chance may be involved (10).
Only occasional doses of carisoprodol were consumed during the first 6 weeks of the pregnancy, and only small amounts of the metabolite meprobamate will be present in the serum.
It is unlikely that the drug in these doses will have any teratogenic effect on the foetus during the first trimester.