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Year in review: drug use in pregnant and breastfeeding women.

The Food and Drug Administration approved 41 new drug preparations in 2014. At the present time, three of these agents are not yet available: finafloxacin otic suspension (Xtoro) for acute otitis externa, naloxegol (Movantik) for opioid-induced constipation in adults with chronic noncancer pain, and peginterferon beta-la (Plegridy) for relapsing multiple sclerosis.

Four of the approvals involved drug combinations: Zerbaxa (ceffolozane, a cephalosporin; and tazobactam, a beta-lactamase inhibitor) for complicated intra-abdominal or urinary tract infections; Viekira Pak (ombitasvir, paritaprevir, and ritonavir copackaged with dasabuvir) for treatment of chronic hepatitis C virus genotype 1 infection; Akynzeo (netupitant and palonosetron) for nausea and vomiting due to cancer chemotherapy; and Harvoni (ledipasvir and sofosbuvir) for chronic hepatitis C virus genotype 1 infection. These four products do not appear to be a risk to the embryo and fetus. Although there are no human pregnancy data, the maternal benefit probably outweighs the unknown embryo/fetal risk.

Most of the remaining agents can be classified into the following categories: anti-infectives, antineoplastics, central nervous system, endocrine/ metabolic, hematologic, immunologic, and respiratory. Except for peramivir, there is no reported human pregnancy experience with any of these agents. All probably will cross the placenta at least in some part of pregnancy.


The seven new anti-infectives and their indications are dalbavancin (Dalvance) for treatment of skin infections caused by gram-positive organisms; efinaconazole (Jublia), for treatment of fungal infections of the toenails; miltefosine (Impavido) for treatment of visceral, cutaneous, and mucosal infections by various Leishmania species; oritavancin (Orbactiv) for skin infections caused by gram-positive bacteria; peramivir (Rapivab), for acute uncomplicated influenza; tavaborole (Kerydin) for treatment of fungal infections of the toenails; and tedizolid (Sivextro) for treatment of bacterial skin infections.

Only peramivir has human pregnancy experience. Two pregnant women who were successfully treated gave birth to healthy infants (Clin. Infect. Dis. 2011;52:695-706; Clin. Infect. Dis. 2011;52:707-9). Two of these agents (efinaconazole and tavaborole) are administered topically so relatively small amounts enter the systemic circulation. Although miltefosine caused severe toxicity in two animal species, visceral and cutaneous leishmaniasis may be life-threatening for the mother and can cause severe developmental toxicity in the embryo and fetus, so the drug should not be withheld in pregnancy. Overall, none of these agents appear to represent a significant risk to the embryo and/or fetus.


The nine new antineoplastic agents and their indications are belinostat (Beleodaq) for peripheral T-cell lymphoma; blinatumomab (Blincyto) for acute lymphoblastic leukemia; ceritinib (Zykadia) for non-small cell lung cancer; idelalisib (Zydelig) for some types of leukemia and lymphoma; nivolumab (Opdivo) for metastatic melanoma; olaparib (Lynparza) for ovarian cancer; pembrolizumab (Keytruda) for unresectable or metastatic melanoma; ramucirumab (Cyramza) for gastric or gastroesophageal adenocarcinoma and metastatic non-small cell lung cancer; and siltuximab (Sylvant) for multicentric Castleman disease.

Based on their mechanisms of action, all of these agents may represent a risk to the embryo and / or fetus. Moreover, some of these drugs are combined with other antineoplastics, thereby increasing the risk. Thus, withholding treatment until after the mother gives birth is the safest choice but, if the mother's condition requires immediate treatment, they should not be withheld.

Central nervous system

Suvorexant (Belsomra) and tasimelteon (Hetlioz) are oral drugs given for treatment of insomnia and the treatment of non-24-hour sleep-wake disorder, respectively. The animal data for both drugs suggest low risk but, based on the molecular weight (about 451 and 245), both will cross to the embryo and/or fetus throughout gestation.

Endocrine/ metabolic

There are six new drugs belonging to the endocrine/metabolic pharmacologic class: albiglutide (Tanzeum), dapagliflozin (Farxiga), dulaglutide (Trulicity), eliglustat (Cerdelga), elosulfase alfa (Vimizim), and empagliflozin (Jardiance). Four of these agents are indicated to reduce blood glucose levels in patients with type 2 diabetes: albiglutide, dapagliflozin, dulaglutide, and empagliflozin. Based on their MW, only dapagliflozin and empagliflozin should cross the placenta early in gestation, but all may cross in the second half of pregnancy.

Eliglustat is given orally for the treatment of Gaucher disease. The animal data in one of two species suggest risk, but the disease itself may also cause severe problems in the mother. Thus, if required, the drug should not be withheld because of pregnancy.

Elosulfase alfa, given as an IV infusion, is indicated for patients with mucopolysaccharidosis type IVA. The MW (55,000) suggests that it will not cross the human placenta, at least in the first half of pregnancy. There were no effects on embryo-fetal development in rats and rabbits but, when given during organogenesis through lactation, there was an increase in stillbirths and pup mortality.


The hematologic agent vorapaxar (Zontivity) is an oral agent indicated for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. The animal reproduction data suggest low risk but the drug should cross the placenta (MW about 591).


The three drugs in the immunologic pharmaceutical class are apremilast (Otezla), metreleptin (Myalept), and vedolizumab (Entyvio). Apremilast is an oral drug indicated for the treatment of active psoriatic arthritis. The drug caused no malformations in monkeys or mice, but in monkeys there was a dose-related increase in spontaneous abortions and embryo-fetal death. Based on its MW (about 461), it probably crosses the placenta.

Metreleptin is given subcutaneously for the complications of leptin deficiency. The animal data suggest low risk. Exposure of the human embryo or fetus is probably very low, at least during the first half of pregnancy (MW 16,150).

Vedolizumab is indicated for ulcerative colitis. It is given as an IV infusion. No adverse effects were observed in rabbits and monkeys. The very high MW (147,000) suggests that it will not cross the placenta during the first half of pregnancy.


Three drugs are classified as respiratory agents: nintedanib (Ofev), olodaterol (Striverdi Respimat), and pirfenidone (Esbriet). The MWs of these agents (about 650,423, and 185, respectively) suggest that all three will cross the placenta throughout gestation.

Nintedanib is an oral drug used for the treatment of pulmonary fibrosis. The drug caused embryo-fetal death and teratogenic effects in two animal species. Depending upon the maternal condition, avoiding pregnancy may be the safest course.

Olodaterol is a long-acting beta-adrenergic agonist for use in patients with chronic obstructive pulmonary disease including chronic bronchitis and/or emphysema. The animal data suggest low risk.

Pirfenidone is indicated for the treatment of idiopathic pulmonary fibrosis. No evidence of impaired fertility or harm to the fetus was observed in rats and rabbits. Depending on the maternal condition, it would be best to avoid these drugs in pregnancy but, if required, they should not be withheld.


There are no data on the use of any of the above drugs during lactation. Nearly all will be excreted into breast milk, but the amount in milk and potential effect on a nursing infant are unknown. If a mother is breastfeeding and taking one of these drugs, referral to the list of the most common adverse reactions (typically on the first page of the package insert) observed with the drug might be helpful in monitoring the nursing infant.


Mr. Briggs is a pharmacist clinical specialist at the outpatient clinics of Memorial Care Center for Women at Miller Children's Hospital in Long Beach, Calif; clinical professor of pharmacy at the University of California, San Francisco; and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He had no relevant financial disclosures. Contact him at imnews@


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Title Annotation:WOMEN'S HEALTH
Author:Briggs, Gerald G.
Publication:Internal Medicine News
Article Type:Medical condition overview
Date:Mar 15, 2015
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