Central Nervous System Agent (Smoking Deterrent)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of varenicline in human pregnancy have been located. The animal data suggest low risk, but the absence of human pregnancy experience prevents a more complete assessment of embryo–fetal risk. However, smoking is known to cause significant developmental toxicity (as well as toxicity in the smoker) (see Cigarette Smoking). Thus, the benefit to the woman and her pregnancy appears to outweigh the unknown risk to the embryo and/or fetus. If nonpharmacologic methods to stop smoking have failed, and the use of varenicline is indicated, it should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Varenicline is a partial agonist selective for α4β2 nicotinic acetylcholine receptor subtypes. This binding is thought to prevent nicotine from binding to these receptors. Varenicline is indicated as an aid in smoking cessation treatment. Oral bioavailability is nearly complete and metabolism of a dose is about 8%. Binding to plasma proteins also is low (≤20%), but the elimination half-life is long (about 24 hours) (1).
Reproduction studies have been conducted in rats and rabbits. In these species, no teratogenicity was observed with daily oral doses ≤36 and 50 times the maximum recommended human daily exposure based on AUC at 1 mg twice daily (MRHDE), respectively. However, in the offspring of pregnant rats given the highest dose there was an increased incidence of auditory startle response. In pregnant rabbits, the highest dose resulted in decreased fetal weights. The no-effect dose in rabbits was 23 times the MRHDE (1).
In 2-year carcinogenicity studies, there was no evidence of carcinogenic effects in mice given daily doses up to 47 times the MRHDE. In male rats, but not females, tumors of the brown fat (hibernoma) were observed at daily doses that were 23 and 67 times, respectively, the MRHDE. Various studies for mutagenicity were negative. No effects on fertility were observed in male and female rats given daily doses up to 67 and 36 times, respectively, the MRHDE. However, a decrease in fertility was noted in the offspring of pregnant rats given a daily dose that was 36 times, but not at 9 times, the MRHDE (1).
It is not known if varenicline crosses the human placenta. The molecular weight (about 361), high oral bioavailability, low metabolism and plasma protein binding, and the long elimination half-life suggest that the drug will pass to the embryo and fetus.
BREASTFEEDING SUMMARY
No reports describing the use of varenicline during human lactation have been located. The molecular weight (about 361), high oral bioavailability, low metabolism (about 8%) and plasma protein binding (≤20%), and the long elimination half-life (about 24 hours) suggest that the drug will be excreted into breast milk. The effects of this exposure on a nursing infant are unknown. However, smoking during breastfeeding is known to represent a significant risk to the nursing infant, as well as to the mother. (See Cigarette Smoking.) Thus, the benefit to the woman and her infant appears to outweigh the unknown risk to the infant. If a woman uses this drug while breastfeeding, she should closely monitor her infant for the adverse effects commonly observed in adults: nausea and vomiting, sleep disturbance, constipation, and flatulence.
Reference
1.Product information. Chantix. Pfizer, 2007.