Urinary Tract Agent (Antispasmodic)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of trospium in human pregnancy have been located. The drug caused fetal death in two animal species but maternal toxicity was also evident. There was no evidence of malformations or developmental delays in surviving offspring. Although the absence of human pregnancy experience prevents a full assessment of the embryo–fetal risk, there is no evidence that other parasympatholytics (e.g., see Atropine), in the absence of maternal toxicity, cause developmental toxicity. Until human experience is available, the safest course is to avoid trospium in pregnancy. However, if inadvertent exposure in pregnancy does occur, the embryo–fetal risk is probably low.
FETAL RISK SUMMARY
Trospium, a quaternary ammonium compound, is an antispasmodic, antimuscarinic agent indicated for the treatment of overactive bladder with symptoms or urge urinary incontinence, urgency, and urinary frequency. The drug has negligible affinity for nicotinic receptors compared with muscarinic receptors. Trospium is in the same subclass as darifenacin, flavoxate, oxybutynin, solifenacin, and tolterodine. A mean 9.6% of an oral dose is absorbed under fasting conditions, but when ingested with a high fat meal, this limited systemic bioavailability is reduced by 70%–80%. Protein binding in serum ranges from 50% to 85% at therapeutic concentrations. The plasma elimination half-life is about 20 hours (1).
Reproduction studies have been conducted in rats and rabbits. In rats, a dose producing exposure about 10 times the human exposure (HE) caused maternal toxicity and a decrease in fetal survival. However, no impaired fertility, malformations, or developmental delays were observed. The no-effect levels for maternal and fetal toxicity were approximately equivalent to the HE. Neither malformations nor developmental delays were observed in pregnant rabbits. The no-effect levels for maternal and fetal toxicity were 5–6 times the HE. Trospium was not carcinogenic in long-term studies conducted in mice and rats and was not mutagenic in various assays (1).
It is not known if trospium crosses the human placenta. The molecular weight (about 428) and elimination half-life suggest that the drug will cross. However, trospium is a water-soluble quaternary ammonium compound that is ionized at physiologic pH. These characteristics should limit the amount of drug reaching the embryo–fetal compartment.
BREASTFEEDING SUMMARY
No reports describing the use of trospium during human lactation have been located. The molecular weight (about 428) and elimination half-life (about 20 hours) suggest that the drug will be excreted, especially into colostrum during the first 2–3 days after birth. Trospium is a water-soluble quaternary ammonium compound that is ionized at physiologic pH. This should limit the amount of drug reaching mature milk. Although neonates are particularly sensitive to anticholinergics, two other agents in this class (both tertiary amine compounds) are classified by the American Academy of Pediatrics as compatible with breastfeeding (see Atropine and Scopolamine). The effect of exposure to trospium on a nursing infant is unknown, but the risk of toxicity is probably low.
Reference
1.Product information. Sanctura. Odyssey Pharmaceuticals, 2005.