Drugs for Treating Alcohol Use Disorder During Lactation

Approved Drugs

Only three drugs are approved by the U.S. Food and Drug Administration for treatment of AUD: acamprosate, disulfiram, and naltrexone. Very little information is available on these drugs in lactation. American Psychiatric Association (APA) guidelines recommend naltrexone or acamprosate be offered first line to patients with moderate-to-severe AUD and that disulfiram, topiramate, and gabapentin are second-line options for patients who prefer one of these agents and are intolerant to or have not responded to first-line drugs. ⁶

The APA guidelines also recommend avoiding pharmacotherapy in nursing mothers unless a co-occurring disorder exists that warrants pharmacological treatment. This strictness may not be justified for some of the drugs used to treat AUD. For example, topiramate is recommended as an initial treatment option in the Department of Veterans Affairs/Department of Defense practice guideline.

Acamprosate is an oral centrally acting taurine analog that has a structure similar to γ-amino butyric acid (GABA). Acamprosate is thought to work by modulating glutamatergic activity, but its exact mechanism in AUD is not known. It is most useful in promoting complete abstinence. ⁵ No information exists on acamprosate's use during breastfeeding in humans. Based on its chemical properties (small molecule with negligible protein binding), it is likely to enter milk. However, the oral bioavailability of acamprosate is only 11%, so systemic effects in the breastfed infant are unlikely. Diarrhea is the most common side effect and the breastfed infant should be monitored for this side effect. Although acamprosate is not contraindicated during breastfeeding, other drugs may be preferred.

Naltrexone is an opioid antagonist that is metabolized to β-naltrexol, which is active. Alcohol releases endogenous opioids and naltrexone can block their reinforcing effects after alcohol consumption. Naltrexone is effective in reducing alcohol consumption in heavy users and in promoting complete abstinence. ⁵ Naltrexone has been studied in one woman who was 1.5 months postpartum and took naltrexone during pregnancy and lactation for opiate use disorder in an oral dose of 50 mg daily, the same dose used in AUD. Naltrexone milk levels were undetectable by 8 hours after the dose, whereas β-naltrexol milk levels remained detectable throughout the study period and averaged 46 mcg/L.

The authors estimated that an exclusively breastfed infant would receive ∼7 mcg/kg daily of naltrexone plus β-naltrexol, equivalent to 0.86% of the maternal weight-adjusted dosage. Oral bioavailability of naltrexone is 5–40%, which would further minimize systemic exposure in the infant. The infant in the study had undetectable plasma levels of both naltrexone and β-naltrexol 9.5 hours after the maternal dose. The infant was reportedly healthy with no naltrexone-related adverse effects. Naltrexone is also available as a once-monthly injection, but this product has not been studied during breastfeeding. Naltrexone is not contraindicated during breastfeeding and may be a good choice.

Disulfiram blocks the metabolism of the alcohol metabolite acetaldehyde, causing acetaldehyde buildup and consequently a number of uncomfortable reactions when alcohol is ingested. No information is available on the clinical use of disulfiram during breastfeeding. Drug labeling recommends that disulfiram not be given to nursing mothers. An alternative drug such as naltrexone is preferred in nursing mothers.

Drugs Used Off Label

A number of drugs have been repurposed for use in the treatment of AUD. The amount of information on efficacy is variable. The most well-accepted drugs are discussed hereunder.

Baclofen is a GABA_B agonist that is a muscle relaxant approved for treatment of AUD in France. It might be particularly useful for treating AUD in patients who have generalized muscle spasticity, Tourette syndrome, or tardive dyskinesia. ⁵ Limited information indicates that orally administered baclofen appears in low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Monitoring newborn infants for sedation is recommended.

Gabapentin modulates GABA activity. It may be most useful in AUD patients with comorbid conditions that are treated with gabapentin, such as restless leg syndrome, neuropathic pain, anxiety, or insomnia. It can also help alleviate alcohol withdrawal symptoms. ⁵ Limited information indicates that maternal doses of gabapentin up to 2.1 g daily produce relatively low levels in infant serum. A single oral dose of either 300 or 600 mg given to the mother before cesarean section appeared to have no effect on breastfeeding initiation. ⁷

An expert consensus guideline indicates that gabapentin is an acceptable choice for refractory restless leg syndrome during lactation, indicating their comfort with its use in nursing mothers. Monitor the infant for drowsiness, adequate weight gain, and developmental milestones, especially in younger exclusively breastfed infants.

Nalmefene is an opioid receptor antagonist and partial agonist that is approved as an oral dosage form in the European Union for reduction of drinking. In the United States, it is only available as an injection for opioid overdose. The oral drug has been studied as an “as needed” drug 2 hours before the person perceives the risk of drinking alcohol. No information is available about the excretion of nalmefene in milk or its effect on nursing infants, but interestingly, it can increase serum prolactin in men and nonlactating women. Nalmefene has a low order of toxicity, similar to naltrexone and naloxone, so it would be unlikely to adversely affect the nursing infant.

Ondansetron is a serotonin antagonist that may lower dopamine release in the central nervous system (CNS). It seems to be most effective in early-onset AUD in patients <25 years of age. ⁵ No adverse infant effects were reported in a pharmacokinetic study of women who received ondansetron during cesarean section or postpartum for prevention of nausea and vomiting. Use of ondansetron in nursing mothers beyond the immediate postpartum setting has not been studied well, but the drug is labeled for use in infants as young as 1 month of age. A computer model demonstrated that the amounts in milk are much less than the labeled infant dose.

Sodium oxybate is the pharmaceutical name for γ-hydroxybutyric acid (GHB). GHB is an endogenous substance that modulates GABA activity. Sodium oxybate is approved in Italy and Austria for the treatment of AUD. Low amounts of GHB are normally found in breast milk and infants have been successfully breastfed by mothers taking sodium oxybate therapeutically for narcolepsy. With the typical narcolepsy treatment regimen of two doses per night, nursing is usually withheld from the time of the first dose to 4–6 hours after the second dose with breastfeeding continued during the day.

For treatment of AUD, sodium oxybate is given three or four times daily, making it difficult to follow the nursing regimen used in narcolepsy. However, the doses used for AUD are 30–50% of those used for narcolepsy, so the risk to the infant, if any, would be lower.

Topiramate inhibits glutamatergic activity, increases GABA activity, and reduces dopamine levels in the CNS. It may be especially useful in patients with comorbid migraine headaches or binge eating disorder. ⁵ Used as an anticonvulsant, maternal doses of topiramate up to 200 mg daily produce relatively low levels of the serum of their breastfed infants. Sedation and diarrhea have been reported occasionally in breastfed infants, but most infants tolerate the drug in milk well. In a few infants who were followed, no long-term adverse effects on growth and development were seen. Monitoring the infant for diarrhea, drowsiness, irritability, adequate weight gain, and developmental milestones is advisable, especially in younger exclusively breastfed infants.

Summary

Most drugs used to treat AUD have not been adequately studied during breastfeeding and some sources recommend against pharmacotherapy during nursing. However, naltrexone is unlikely to harm the breastfed infant and is probably the drug of choice. Other drugs used off-label that are probably acceptable during breastfeeding are baclofen, gabapentin, ondansetron, and topiramate.