New drugs approved in 2012


In 2012, the Food and Drug Administration approved 39 new molecular entities (i.e., drugs). This was the highest number of approvals in the 2003 to 2012 period. Of the 39, 2 have not yet come onto the market, 3 are highly unlikely to be used in women of reproductive age, and 1 is a four-drug combination for HIV-1 infection.

The remaining 33 agents are classified as anorexiant (1), anticoagulant (1), anticonvulsant (1), antidote (1), antilipemic (1), antineoplastic (11), antituberculosis (1), dermatologic (1), endocrine/metabolic (3), gastrointestinal (4), hematologic (1), immunologic (2), impotence (1), ophthalmic (2), respiratory (1), and urinary tract agent (1).

There is no reported human pregnancy experience for any of these agents. Consequently, the potential risk to the embryo and/or fetus must be estimated based on the indication, mechanism of action, other drugs with a similar mechanism, route of administration, molecular weight, elimination half-life, and animal reproduction data. Some of these drugs have been included in the quarterly updates to the 9th edition of my book "Drugs in Pregnancy and Lactation." The remainder will appear in the 10th edition, scheduled to be released in the spring of 2014.

Lorcaserin (Belviq) is an anorexiant. Because weight loss in pregnancy usually offers no benefit to a pregnant woman, the manufacturer classifies the drug as contraindicated in pregnancy.

A new anticoagulant, apixaban (Eliquis), is used to reduce the risk of stroke in patients with atrial fibrillation. The animal data suggest low risk and, when combined with the indication, the drug should not be withheld because of pregnancy.

The animal data for the anticonvulsant perampanel (Fycompa) suggest risk, but the absence of human pregnancy experience prevents a full assessment of the embryo-fetal risk. If the drug is used in pregnancy, physicians are encouraged to recommend that their patients enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334.

The antidote, glucarpidase (Voraxaze), is used to treat toxic levels of methotrexate. Because methotrexate is contraindicated in pregnancy, it appears that there will be few opportunities for use of this drug in a pregnant woman. The same can be said for the antilipemic agent, lomitapide (Juxtapid). Decreasing the levels of lipids and cholesterol offers no benefit in pregnancy. The manufacturer classifies the agent as contraindicated because of the toxicity observed in three animal species.

Among the new antineoplastic agents approved, six are kinase inhibitors. Of these, five are in the subclass of tyrosine kinase inhibitors (trade name; indication): Axitinib (Inlyta; renal cancer), bosutinib (Bosulif; leukemia), cabozantinib (Cometriq; thyroid cancer), ponatinib (Iclusig; leukemia), and ziv-aflibercept (Zaltrap; colorectal cancer). The sixth kinase inhibitor is a multikinase inhibitor: regorafenib (Stivarga; colorectal cancer).

Other new antineoplastics are the antiandrogen enzalutamide (Xtandi; prostate cancer but could be used for other cancers), the proteasome inhibitor carfilzomib (Kyprolis; multiple myeloma), and the protein synthesis inhibitor omacetaxine (Synribo; leukemia). Pertuzumab (Perjeta; breast cancer) is a monoclonal antibody that is given in combination with trastuzumab and docetaxel. Vismodegib (Erivedge; basal cell cancer) is a miscellaneous antineoplastic that has been associated with amenorrhea in clinical trials. Animal data suggest risk of embryo-fetal harm.

All of the above antineoplastics are contraindicated in pregnancy because their mechanisms suggest the potential for embryo-fetal harm. However, if a drug is the best choice for a woman with a severe or a potentially fatal disease, it should not be withheld because the maternal benefit should far outweigh the unknown embryo-fetal risk.

Bedaquiline (Sirturo) is a new antituberculosis agent that can be used in pregnancy because of the low risk in animal studies and its indication. The dermatologic agent, ingenol mebutate (Picato) is used topically for actinic keratosis and appears to be compatible in pregnancy, because blood levels of the drug and two of its metabolites were below the lower limit of quantification (0.1 ng/mL).

The three endocrine/metabolic agents are ivacaftor (Kalydeco; cystic fibrosis), taliglucerase alfa (Elelyso; Gaucher disease), and pasireotide (Signifor; Cushing’s disease). The animal data for ivacaftor suggest low risk. Taliglucerase alfa appears to be compatible in pregnancy because it might reduce the risk of spontaneous abortion and bleeding complications. However, based on animal data, if a pregnant woman takes pasireotide, she should be informed of the potential risk, including abortion, to her embryo and/or fetus.

There are four gastrointestinal agents: crofelemer (Fulyzaq; antidiarrheal), linaclotide (Linzess; laxative), teduglutide (Gattex; short bowel syndrome), and the combination of sodium picosulfate, magnesium oxide, and citric acid (Prepopik; osmotic laxative). All appear to be compatible in pregnancy because of limited, if any, absorption (crofelemer, linaclotide, and sodium picosulfate) or because it is an analogue of a naturally occurring peptide (teduglutide).


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