Gerald G. Briggs, Bpharm

It is best to avoid any new drug in women of childbearing potential or during pregnancy if an older agent with human pregnancy experience exists. However, this is not always possible, because the new drug may be a major breakthrough or is the only or most efficacious drug for the indication. So, how do you counsel the patient about a drug’s risk to the embryo or fetus when there is little or no human pregnancy data?

Fortunately, the package insert provides data for three factors that can be used to give some estimate of risk: pharmacologic class, potential to cross the placenta, and animal reproduction data. Although all of the factors are important, the animal data are often the best source for estimating human risk. The book "Drugs in Pregnancy and Lactation," which I coauthored, defines the levels of risk (low-moderate-high) that I use to evaluate the animal data.

In 2011, the Food and Drug Administration approved 30 new drugs and biologics. Because they are unlikely to be used during pregnancy or lactation, the following 10 new drugs will not be reviewed here: abiraterone (Zytiga; pregnancy risk category X) for prostate cancer; adenovirus type 4 and type 7 live virus vaccine (X), for prevention of febrile acute respiratory disease; azficel-T (LaViv; C), for nasolabial fold wrinkles; centruroides (Anascorp; C), for scorpion envenomation; Coccidioides immitis skin test antigen (Spherusol; C); gabapentin enacarbil (Horizant; C), prodrug of the antiepileptic gabapentin for restless legs syndrome; gadobutrol (Gadavist; C), a contrast agent for MRI of the central nervous system; ioflupane I¹²³ (DaTscan; B), for single-photon emission computed tomography (SPECT) brain imaging; and two drugs for chronic obstructive pulmonary disease: indacaterol (Arcapta Neohaler; C) and roflumilast (Daliresp; C).

Of the remaining 20 drugs, only one has human pregnancy data: factor XIII concentrate human (Corifact; C). The new drugs can be categorized into 10 pharmacologic classes: 2 anticoagulants, 1 anticonvulsant, 1 antidepressant, 1 antidiabetic, 1 antihypertensive, 4 anti-infectives, 5 antineoplastics, 1 dermatologic, 2 hematologics, and 2 immunologic agents.

Rivaroxaban (Xarelto; C), a factor Xa inhibitor, is used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and to prevent deep vein thrombosis in patients undergoing knee or hip replacement surgery. The drug crosses the human placenta, and the animal data suggest risk. Ticagrelor (Brilinta; C) is a platelet inhibitor indicated for reducing the rate of thrombotic events in patients with acute coronary syndrome. The animal data suggest risk, and the drug probably crosses the placenta. Although both of these agents are best avoided in pregnancy, the maternal benefit in some cases may outweigh the unknown embryo-fetal risk.

The animal data suggest risk if ezogabine (Potiga; C), an oral anticonvulsant indicated as adjunctive treatment of partial-onset seizures, is used in pregnancy. If used in pregnancy, the woman should be advised of the absence of human data. Pregnant women taking ezogabine are encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 888-233-2334.

The new antidepressant is vilazodone (Viibryd; C), a selective serotonin reuptake inhibitor. As with other SSRIs, the potential developmental toxicity includes spontaneous abortion, low birth weight, preterm delivery, neonatal serotonin syndrome, neonatal withdrawal, abnormal behavior beyond the neonatal period, and persistent pulmonary hypertension of the newborn. However, the benefits of vilazodone may outweigh the risks and must be evaluated on a case by case basis.

Linagliptin (Tradjenta; B), a dipeptidyl peptidase-4 inhibitor taken orally, is indicated for type 2 diabetes. Although the animal data suggest low risk, the lack of human pregnancy data prevents an assessment of its effect in a condition requiring tight control of glucose. Insulin remains the gold standard, but other oral agents, such as glipizide, glyburide, and metformin, have been effective in selected cases.

Azilsartan (Edarbi; D) is an angiotensin II receptor blocker used for hypertension. As with all agents in this class, severe fetal toxicity, including death, is a potential complication if it is used in the second half of pregnancy.

Two of the new anti-infectives are protease inhibitors used for chronic hepatitis C infection: boceprevir (Victrelis; B) and telaprevir (Incivek; B). Although both drugs carry an FDA rating of B, they must be used in combination with ribavirin (contraindicated in pregnancy) and peginterferon alfa. Thus, they should not be used in pregnancy.

Fidaxomicin (Dificid; B) is an oral macrolide used for Clostridium difficile–associated diarrhea. Only minimal amounts are absorbed and, like other macrolides, such as erythromycin, the drug is probably compatible with pregnancy. Rilpivirine (Edurant; B) is a non-nucleoside reverse transcriptase inhibitor used in combination with other agents for HIV-1 infections. Animal data suggest low risk, but there are no human pregnancy data. However, the maternal benefit appears to outweigh embryo-fetal risk.

The five antineoplastics are: brentuximab (Adcetris; D), approved for Hodgkin’s disease and systemic anaplastic large cell lymphoma; crizotinib (Xalkori; D), for metastatic non–small cell lung cancer; ipilimumab (Yervoy; C), for metastatic melanoma; vandetanib (Caprelsa; D), for metastatic medullary thyroid cancer; and vemurafenib (Zelboraf; D) for metastatic melanoma. The properties (molecular weight, plasma elimination half-life) of these agents suggest that they will probably cross the placenta. The combination of these properties, their mechanisms of action, and/or their animal reproduction data suggests that all should be avoided in pregnancy.

Spinosad (Natroba; B) is an insecticide used for head lice infection. The pediculicide is not absorbed systemically, so it is compatible with pregnancy.

Factor XIII Concentrate (Human) (Corifact; C) is a hematologic agent used for the prophylactic treatment of congenital factor XIII deficiency. The product is made from pooled human plasma that has been checked for hepatitis B surface antigen and antibodies to HIV-1/2 and HCV. The limited human data suggest that it is low risk in pregnancy. In contrast, the animal data for icatibant (Firazyr; C), the other hematologic agent that is indicated for the treatment of acute attacks of hereditary angioedema, suggest risk. Currently, plasma-derived human C1 inhibitor concentrate is preferred for acute treatment and short- or long-term prophylaxis of hereditary angioedema (J. Allergy Clin. Immunol. 2012;129:308-20). Until human data are available, icatibant is best avoided in pregnancy.

The first of the two immunologic agents is the immunosuppressant belatacept (Nulojix; C), indicated to prevent rejection of a kidney transplant. Although the animal data suggest low risk, it is given in combination with basiliximab induction and two agents known to be teratogenic, mycophenolate and corticosteroids. The absolute risk for major defects with corticosteroids is low, but the risk magnitude is thought to be much higher for mycophenolate. If possible, belatacept should be avoided in pregnancy. The other agent is the immunomodulator belimumab (Benlysta; C), which is indicated for the treatment of systemic lupus erythematosus. The animal data for this monoclonal antibody are reassuring, and the agent is probably compatible with pregnancy.

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.; 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 Washington State University, Spokane. He also is coauthor of "Drugs in Pregnancy and Lactation," and coeditor of "Diseases, Complications, and Drug Therapy in Obstetrics." He said he had no relevant financial disclosures.

It is best to avoid any new drug in women of childbearing potential or during pregnancy if an older agent with human pregnancy experience exists. However, this is not always possible, because the new drug may be a major breakthrough or is the only or most efficacious drug for the indication. So, how do you counsel the patient about a drug’s risk to the embryo or fetus when there is little or no human pregnancy data?

Fortunately, the package insert provides data for three factors that can be used to give some estimate of risk: pharmacologic class, potential to cross the placenta, and animal reproduction data. Although all of the factors are important, the animal data are often the best source for estimating human risk. The book "Drugs in Pregnancy and Lactation," which I coauthored, defines the levels of risk (low-moderate-high) that I use to evaluate the animal data.

In 2011, the Food and Drug Administration approved 30 new drugs and biologics. Because they are unlikely to be used during pregnancy or lactation, the following 10 new drugs will not be reviewed here: abiraterone (Zytiga; pregnancy risk category X) for prostate cancer; adenovirus type 4 and type 7 live virus vaccine (X), for prevention of febrile acute respiratory disease; azficel-T (LaViv; C), for nasolabial fold wrinkles; centruroides (Anascorp; C), for scorpion envenomation; Coccidioides immitis skin test antigen (Spherusol; C); gabapentin enacarbil (Horizant; C), prodrug of the antiepileptic gabapentin for restless legs syndrome; gadobutrol (Gadavist; C), a contrast agent for MRI of the central nervous system; ioflupane I¹²³ (DaTscan; B), for single-photon emission computed tomography (SPECT) brain imaging; and two drugs for chronic obstructive pulmonary disease: indacaterol (Arcapta Neohaler; C) and roflumilast (Daliresp; C).

Of the remaining 20 drugs, only one has human pregnancy data: factor XIII concentrate human (Corifact; C). The new drugs can be categorized into 10 pharmacologic classes: 2 anticoagulants, 1 anticonvulsant, 1 antidepressant, 1 antidiabetic, 1 antihypertensive, 4 anti-infectives, 5 antineoplastics, 1 dermatologic, 2 hematologics, and 2 immunologic agents.

Rivaroxaban (Xarelto; C), a factor Xa inhibitor, is used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and to prevent deep vein thrombosis in patients undergoing knee or hip replacement surgery. The drug crosses the human placenta, and the animal data suggest risk. Ticagrelor (Brilinta; C) is a platelet inhibitor indicated for reducing the rate of thrombotic events in patients with acute coronary syndrome. The animal data suggest risk, and the drug probably crosses the placenta. Although both of these agents are best avoided in pregnancy, the maternal benefit in some cases may outweigh the unknown embryo-fetal risk.

The animal data suggest risk if ezogabine (Potiga; C), an oral anticonvulsant indicated as adjunctive treatment of partial-onset seizures, is used in pregnancy. If used in pregnancy, the woman should be advised of the absence of human data. Pregnant women taking ezogabine are encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 888-233-2334.

The new antidepressant is vilazodone (Viibryd; C), a selective serotonin reuptake inhibitor. As with other SSRIs, the potential developmental toxicity includes spontaneous abortion, low birth weight, preterm delivery, neonatal serotonin syndrome, neonatal withdrawal, abnormal behavior beyond the neonatal period, and persistent pulmonary hypertension of the newborn. However, the benefits of vilazodone may outweigh the risks and must be evaluated on a case by case basis.

Linagliptin (Tradjenta; B), a dipeptidyl peptidase-4 inhibitor taken orally, is indicated for type 2 diabetes. Although the animal data suggest low risk, the lack of human pregnancy data prevents an assessment of its effect in a condition requiring tight control of glucose. Insulin remains the gold standard, but other oral agents, such as glipizide, glyburide, and metformin, have been effective in selected cases.

Azilsartan (Edarbi; D) is an angiotensin II receptor blocker used for hypertension. As with all agents in this class, severe fetal toxicity, including death, is a potential complication if it is used in the second half of pregnancy.

Two of the new anti-infectives are protease inhibitors used for chronic hepatitis C infection: boceprevir (Victrelis; B) and telaprevir (Incivek; B). Although both drugs carry an FDA rating of B, they must be used in combination with ribavirin (contraindicated in pregnancy) and peginterferon alfa. Thus, they should not be used in pregnancy.

Fidaxomicin (Dificid; B) is an oral macrolide used for Clostridium difficile–associated diarrhea. Only minimal amounts are absorbed and, like other macrolides, such as erythromycin, the drug is probably compatible with pregnancy. Rilpivirine (Edurant; B) is a non-nucleoside reverse transcriptase inhibitor used in combination with other agents for HIV-1 infections. Animal data suggest low risk, but there are no human pregnancy data. However, the maternal benefit appears to outweigh embryo-fetal risk.

The five antineoplastics are: brentuximab (Adcetris; D), approved for Hodgkin’s disease and systemic anaplastic large cell lymphoma; crizotinib (Xalkori; D), for metastatic non–small cell lung cancer; ipilimumab (Yervoy; C), for metastatic melanoma; vandetanib (Caprelsa; D), for metastatic medullary thyroid cancer; and vemurafenib (Zelboraf; D) for metastatic melanoma. The properties (molecular weight, plasma elimination half-life) of these agents suggest that they will probably cross the placenta. The combination of these properties, their mechanisms of action, and/or their animal reproduction data suggests that all should be avoided in pregnancy.

Spinosad (Natroba; B) is an insecticide used for head lice infection. The pediculicide is not absorbed systemically, so it is compatible with pregnancy.

Factor XIII Concentrate (Human) (Corifact; C) is a hematologic agent used for the prophylactic treatment of congenital factor XIII deficiency. The product is made from pooled human plasma that has been checked for hepatitis B surface antigen and antibodies to HIV-1/2 and HCV. The limited human data suggest that it is low risk in pregnancy. In contrast, the animal data for icatibant (Firazyr; C), the other hematologic agent that is indicated for the treatment of acute attacks of hereditary angioedema, suggest risk. Currently, plasma-derived human C1 inhibitor concentrate is preferred for acute treatment and short- or long-term prophylaxis of hereditary angioedema (J. Allergy Clin. Immunol. 2012;129:308-20). Until human data are available, icatibant is best avoided in pregnancy.

The first of the two immunologic agents is the immunosuppressant belatacept (Nulojix; C), indicated to prevent rejection of a kidney transplant. Although the animal data suggest low risk, it is given in combination with basiliximab induction and two agents known to be teratogenic, mycophenolate and corticosteroids. The absolute risk for major defects with corticosteroids is low, but the risk magnitude is thought to be much higher for mycophenolate. If possible, belatacept should be avoided in pregnancy. The other agent is the immunomodulator belimumab (Benlysta; C), which is indicated for the treatment of systemic lupus erythematosus. The animal data for this monoclonal antibody are reassuring, and the agent is probably compatible with pregnancy.

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.; 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 Washington State University, Spokane. He also is coauthor of "Drugs in Pregnancy and Lactation," and coeditor of "Diseases, Complications, and Drug Therapy in Obstetrics." He said he had no relevant financial disclosures.

It is best to avoid any new drug in women of childbearing potential or during pregnancy if an older agent with human pregnancy experience exists. However, this is not always possible, because the new drug may be a major breakthrough or is the only or most efficacious drug for the indication. So, how do you counsel the patient about a drug’s risk to the embryo or fetus when there is little or no human pregnancy data?

Fortunately, the package insert provides data for three factors that can be used to give some estimate of risk: pharmacologic class, potential to cross the placenta, and animal reproduction data. Although all of the factors are important, the animal data are often the best source for estimating human risk. The book "Drugs in Pregnancy and Lactation," which I coauthored, defines the levels of risk (low-moderate-high) that I use to evaluate the animal data.

In 2011, the Food and Drug Administration approved 30 new drugs and biologics. Because they are unlikely to be used during pregnancy or lactation, the following 10 new drugs will not be reviewed here: abiraterone (Zytiga; pregnancy risk category X) for prostate cancer; adenovirus type 4 and type 7 live virus vaccine (X), for prevention of febrile acute respiratory disease; azficel-T (LaViv; C), for nasolabial fold wrinkles; centruroides (Anascorp; C), for scorpion envenomation; Coccidioides immitis skin test antigen (Spherusol; C); gabapentin enacarbil (Horizant; C), prodrug of the antiepileptic gabapentin for restless legs syndrome; gadobutrol (Gadavist; C), a contrast agent for MRI of the central nervous system; ioflupane I¹²³ (DaTscan; B), for single-photon emission computed tomography (SPECT) brain imaging; and two drugs for chronic obstructive pulmonary disease: indacaterol (Arcapta Neohaler; C) and roflumilast (Daliresp; C).

Of the remaining 20 drugs, only one has human pregnancy data: factor XIII concentrate human (Corifact; C). The new drugs can be categorized into 10 pharmacologic classes: 2 anticoagulants, 1 anticonvulsant, 1 antidepressant, 1 antidiabetic, 1 antihypertensive, 4 anti-infectives, 5 antineoplastics, 1 dermatologic, 2 hematologics, and 2 immunologic agents.

Rivaroxaban (Xarelto; C), a factor Xa inhibitor, is used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and to prevent deep vein thrombosis in patients undergoing knee or hip replacement surgery. The drug crosses the human placenta, and the animal data suggest risk. Ticagrelor (Brilinta; C) is a platelet inhibitor indicated for reducing the rate of thrombotic events in patients with acute coronary syndrome. The animal data suggest risk, and the drug probably crosses the placenta. Although both of these agents are best avoided in pregnancy, the maternal benefit in some cases may outweigh the unknown embryo-fetal risk.

The animal data suggest risk if ezogabine (Potiga; C), an oral anticonvulsant indicated as adjunctive treatment of partial-onset seizures, is used in pregnancy. If used in pregnancy, the woman should be advised of the absence of human data. Pregnant women taking ezogabine are encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 888-233-2334.

The new antidepressant is vilazodone (Viibryd; C), a selective serotonin reuptake inhibitor. As with other SSRIs, the potential developmental toxicity includes spontaneous abortion, low birth weight, preterm delivery, neonatal serotonin syndrome, neonatal withdrawal, abnormal behavior beyond the neonatal period, and persistent pulmonary hypertension of the newborn. However, the benefits of vilazodone may outweigh the risks and must be evaluated on a case by case basis.

Linagliptin (Tradjenta; B), a dipeptidyl peptidase-4 inhibitor taken orally, is indicated for type 2 diabetes. Although the animal data suggest low risk, the lack of human pregnancy data prevents an assessment of its effect in a condition requiring tight control of glucose. Insulin remains the gold standard, but other oral agents, such as glipizide, glyburide, and metformin, have been effective in selected cases.

Azilsartan (Edarbi; D) is an angiotensin II receptor blocker used for hypertension. As with all agents in this class, severe fetal toxicity, including death, is a potential complication if it is used in the second half of pregnancy.

Two of the new anti-infectives are protease inhibitors used for chronic hepatitis C infection: boceprevir (Victrelis; B) and telaprevir (Incivek; B). Although both drugs carry an FDA rating of B, they must be used in combination with ribavirin (contraindicated in pregnancy) and peginterferon alfa. Thus, they should not be used in pregnancy.

Fidaxomicin (Dificid; B) is an oral macrolide used for Clostridium difficile–associated diarrhea. Only minimal amounts are absorbed and, like other macrolides, such as erythromycin, the drug is probably compatible with pregnancy. Rilpivirine (Edurant; B) is a non-nucleoside reverse transcriptase inhibitor used in combination with other agents for HIV-1 infections. Animal data suggest low risk, but there are no human pregnancy data. However, the maternal benefit appears to outweigh embryo-fetal risk.

The five antineoplastics are: brentuximab (Adcetris; D), approved for Hodgkin’s disease and systemic anaplastic large cell lymphoma; crizotinib (Xalkori; D), for metastatic non–small cell lung cancer; ipilimumab (Yervoy; C), for metastatic melanoma; vandetanib (Caprelsa; D), for metastatic medullary thyroid cancer; and vemurafenib (Zelboraf; D) for metastatic melanoma. The properties (molecular weight, plasma elimination half-life) of these agents suggest that they will probably cross the placenta. The combination of these properties, their mechanisms of action, and/or their animal reproduction data suggests that all should be avoided in pregnancy.

Spinosad (Natroba; B) is an insecticide used for head lice infection. The pediculicide is not absorbed systemically, so it is compatible with pregnancy.

Factor XIII Concentrate (Human) (Corifact; C) is a hematologic agent used for the prophylactic treatment of congenital factor XIII deficiency. The product is made from pooled human plasma that has been checked for hepatitis B surface antigen and antibodies to HIV-1/2 and HCV. The limited human data suggest that it is low risk in pregnancy. In contrast, the animal data for icatibant (Firazyr; C), the other hematologic agent that is indicated for the treatment of acute attacks of hereditary angioedema, suggest risk. Currently, plasma-derived human C1 inhibitor concentrate is preferred for acute treatment and short- or long-term prophylaxis of hereditary angioedema (J. Allergy Clin. Immunol. 2012;129:308-20). Until human data are available, icatibant is best avoided in pregnancy.

The first of the two immunologic agents is the immunosuppressant belatacept (Nulojix; C), indicated to prevent rejection of a kidney transplant. Although the animal data suggest low risk, it is given in combination with basiliximab induction and two agents known to be teratogenic, mycophenolate and corticosteroids. The absolute risk for major defects with corticosteroids is low, but the risk magnitude is thought to be much higher for mycophenolate. If possible, belatacept should be avoided in pregnancy. The other agent is the immunomodulator belimumab (Benlysta; C), which is indicated for the treatment of systemic lupus erythematosus. The animal data for this monoclonal antibody are reassuring, and the agent is probably compatible with pregnancy.

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.; 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 Washington State University, Spokane. He also is coauthor of "Drugs in Pregnancy and Lactation," and coeditor of "Diseases, Complications, and Drug Therapy in Obstetrics." He said he had no relevant financial disclosures.