Skeletal Muscle Relaxant
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
No reports describing the use of tizanidine in human pregnancy have been located. The animal data suggest toxicity but not congenital defects. The absence of human pregnancy experience prevents an assessment of the embryo–fetal risk. However, dose-related hypotension has been observed in humans and this could be a potentially serious adverse effect in pregnant women. Single doses of the recommended dose (8 mg) have caused a 20% reduction in either the systolic or the diastolic blood pressure in two-thirds of patients. This effect may be minimized by titration of the dose, but close monitoring of the maternal blood pressure is required. In addition, if the drug must be used in pregnancy, avoidance in the 1st trimester is recommended.
FETAL RISK SUMMARY
Tizanidine is a centrally acting α2-adrenergic agonist structurally related to clonidine that is used for the management of spasticity. Based on animal studies, tizanidine has no direct effect on skeletal muscle fibers or the neuromuscular junction. Although, in animals the drug has a small fraction (2%–10%) of the potency of clonidine in lowering blood pressure, dose-related hypotension has been observed in humans. The terminal elimination half-life is about 2.5 hours (1).
Reproduction studies have been conducted in rats and rabbits. In rats, a dose equal to the maximum recommended human dose based on BSA (MRHD) revealed no evidence of teratogenicity. At doses up to 8 times the MRHD, increased duration of gestation, increased prenatal and postnatal pup mortality and slow development were noted. In rabbits, no evidence of structural defects was evident at a dose 16 times the MRHD. However, postimplantation loss was increased at a dose equal to or greater than 0.5 times the MRHD (1).
It is not known if tizanidine crosses the human placenta. The relatively low molecular weight (about 254 for the free base) and lipid solubility suggest that passage to the embryo or fetus should be expected.
No reports describing the use of tizanidine during human lactation have been located. The molecular weight (about 254 for the free base) and lipid solubility suggest that excretion into breast milk will occur. The effect of this exposure on a nursing infant is unknown, but serious toxicity (e.g., sedation, hypotension, liver injury, and hallucinations/psychotic-like symptoms as seen in adults) is a potential complication. Because of these potential adverse effects, breastfeeding is not recommended.
1.Product information. Zanaflex. Elan Biopharmaceuticals, 2004.