Novel drugs approved in 2016

Nusinersen (Spinraza), a survival motor neuron 2 directed–antisense oligonucleotide, is given as an intrathecal dose. It is indicated for the treatment of spinal muscular atrophy. Subcutaneous doses in two animal species caused no developmental toxicity. The molecular weight of 7,501 suggests that the drug will not cross the human placenta, at least not in the first half of pregnancy. The mean terminal elimination half-life in cerebrospinal fluid was 135-177 days and 63-87 days in plasma.

Ophthalmic agents

Lifitegrast (Xiidra) is an ophthalmic solution of a lymphocyte function-associated–antigen-1 antagonist. It is indicated for the treatment of the signs and symptoms of dry eye disease. The animal reproduction data suggest low risk. The molecular weight is about 616, suggesting that the drug would cross the placenta. However, in a Phase III trial conducted before FDA approval, 47 patients with dry eye disease were given 1 drop twice daily for periods up to 360 days. Nine patients (19%) had plasma predose (trough) concentrations above 0.5 ng/mL, the lower limit of quantitation. Trough plasma concentrations in these patients ranged from 0.55 ng/mL to 3.74 ng/mL. These amounts do not appear to represent an embryo-fetal risk.

Respiratory agents

Reslizumab (Cinqair), an interleukin-5 antagonist monoclonal antibody, is given intravenously. It is indicated for add-on maintenance treatment of severe asthma in patients with an eosinophilic phenotype. Animal data in two species suggest low risk. The molecular weight is about 147,000, and the elimination half-life is about 24 days. This suggests that exposure of the embryo and fetus will be minimal, at least in the first half of pregnancy. The maternal benefit appears to outweigh the unknown embryo-fetal risk.

Lactation

None of the above drugs have been studied during breastfeeding. Many drugs, regardless of their molecular weight, will cross into milk in small amounts during the first postpartum week. The effects of this exposure on a nursing infant are unknown. Based on the potential for nursing infant harm, the drugs that probably should not be given during breastfeeding include the four antineoplastics, the atypical antipsychotic pimavanserin, and the diabetes injection lixisenatide.

Mr. Briggs is a clinical professor of pharmacy at the University of California, San Francisco, and an adjunct professor of pharmacy at the University of Southern California, Los Angeles, and at Washington State University, Spokane. He coauthored “Drugs in Pregnancy and Lactation,” and coedited “Diseases, Complications, and Drug Therapy in Obstetrics.” He reported having no relevant financial disclosures.