Drug Twosome Protects Against Nausea and Vomiting

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Drug Twosome Protects Against Nausea and Vomiting

BALTIMORE – Starting treatment with a combination of doxylamine and pyridoxine before the onset of nausea and vomiting significantly reduced the incidence of severe nausea and vomiting of pregnancy, compared with starting treatment at the first sign of symptoms, in a study of 59 women with a history of severe nausea and vomiting of pregnancy, Caroline Maltepe reported.

In the prospective, randomized, open-label study of women with a history of nausea and vomiting of pregnancy (NVP), 30 women began taking the delayed-release combination of 10 mg of doxylamine and 10 mg of pyridoxine (vitamin B6) as soon as they learned they were pregnant, before they started to experience nausea and vomiting (at a mean of 4 weeks’ gestation). Another 29 pregnant women started taking the combination when they started to experience symptoms, Ms. Maltepe said at the annual meeting of the Teratology Society.

Women in both groups started to experience NVP symptoms at a mean of about 5 to almost 6 weeks, said Ms. Maltepe, the lead author of the study, who is with the Motherisk Program at the Hospital for Sick Children in Toronto. The program conducts research and provides information about the safety of maternal exposure to drugs, chemicals, diseases, radiation, and environmental agents to the developing fetus or infant.

The women (mean age, 31-32 years) had experienced severe NVP or hyperemesis gravidarum (HG) in their previous pregnancy, and enrolled when they were planning a pregnancy or in early pregnancy at a point when they had not yet experienced any symptoms. Women in both groups took 2-9 tablets of the doxylamine-pyridoxine combination a day, and received counseling and follow-up calls.

In Canada, the combination is approved and marketed as Diclectin, by Duchesnay, and is the only drug labeled for treating NVP in Canada. There it is considered a first-line treatment and is taken at a standard dose of four tablets a day, said Ms. Maltepe, the coordinator of the NVP helpline at Motherisk.

Diclectin is a generic form of the drug Bendectin, which was marketed in the United States until 1983, when it was voluntarily withdrawn by its manufacturer, Merrell Dow Pharmaceuticals, after a series of lawsuits claiming it caused birth defects. For several years, Duchesnay has been working toward Food and Drug Administration clearance to market Diclectin in the United States, but it would be premature to predict when it would become available in the United States, a spokesman for the company said.

In the study, symptoms were evaluated using the PUQE (Pregnancy–Unique Quantification of Emesis and Nausea) score, a validated scoring system that takes into account the frequency of vomiting; the frequency of retching, gagging, or dry heaves; and the number of hours spent feeling nauseous over a 24-hour period. The score was developed by Dr. Gideon Koren, director of Motherisk and coauthor of this study, and his associates. A score of 7-12 is considered moderate; a score of 13 or higher is considered severe.

In the study, preemptive treatment was associated with 70% fewer cases of moderate to severe NVP during the first 3 weeks women experienced symptoms: 4 of the 26 (15%) evaluable women had a PUQE score of 11 or more during the first 3 weeks of NVP symptoms, compared with 9 of the 23 (39%) evaluable women in the control group, a significant difference. Of the 19 women in the preemptively treated group who had HG during the previous pregnancy, 6 (32%) experienced HG, compared with 6 of the 11 (55%) in the control group, also a significant difference. Some women who enrolled were not evaluable for reasons that included having a miscarriage.

NVP resolved before labor in significantly more of the women in the preemptively treated group than in the control group (almost 80% vs. about 50%), and there was a negative correlation between PUQE scores and a well-being score, indicating that treatment is associated with improved quality of life for these patients, Ms. Maltepe said.

In women who have experienced severe NVP or HG in a previous pregnancy, preemptive treatment with doxylamine-pyridoxine events can reduce the recurrence of NVP in subsequent pregnancies, and improve their quality of life during pregnancy, as well as reduce time off from work and the need for enteral and parenteral therapy, hospitalization, and other costs associated with severe NVP, she concluded.

The NVP helpline at Motherisk is the only dedicated NVP helpline in the world, according to Ms. Maltepe, who provides evidence-based recommendations on pharmaceutical and nonpharmaceutical approaches to treating NVP for pregnant women, their family members, and clinicians via the helpline (800-436-8477 in North America).

 

 

The study was funded by Duchesnay. Ms. Maltepe and her coauthors said they had no relevant conflict of interest to disclose.

The Motherisk site is available at www.motherisk.org/women/index.jsp.

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BALTIMORE – Starting treatment with a combination of doxylamine and pyridoxine before the onset of nausea and vomiting significantly reduced the incidence of severe nausea and vomiting of pregnancy, compared with starting treatment at the first sign of symptoms, in a study of 59 women with a history of severe nausea and vomiting of pregnancy, Caroline Maltepe reported.

In the prospective, randomized, open-label study of women with a history of nausea and vomiting of pregnancy (NVP), 30 women began taking the delayed-release combination of 10 mg of doxylamine and 10 mg of pyridoxine (vitamin B6) as soon as they learned they were pregnant, before they started to experience nausea and vomiting (at a mean of 4 weeks’ gestation). Another 29 pregnant women started taking the combination when they started to experience symptoms, Ms. Maltepe said at the annual meeting of the Teratology Society.

Women in both groups started to experience NVP symptoms at a mean of about 5 to almost 6 weeks, said Ms. Maltepe, the lead author of the study, who is with the Motherisk Program at the Hospital for Sick Children in Toronto. The program conducts research and provides information about the safety of maternal exposure to drugs, chemicals, diseases, radiation, and environmental agents to the developing fetus or infant.

The women (mean age, 31-32 years) had experienced severe NVP or hyperemesis gravidarum (HG) in their previous pregnancy, and enrolled when they were planning a pregnancy or in early pregnancy at a point when they had not yet experienced any symptoms. Women in both groups took 2-9 tablets of the doxylamine-pyridoxine combination a day, and received counseling and follow-up calls.

In Canada, the combination is approved and marketed as Diclectin, by Duchesnay, and is the only drug labeled for treating NVP in Canada. There it is considered a first-line treatment and is taken at a standard dose of four tablets a day, said Ms. Maltepe, the coordinator of the NVP helpline at Motherisk.

Diclectin is a generic form of the drug Bendectin, which was marketed in the United States until 1983, when it was voluntarily withdrawn by its manufacturer, Merrell Dow Pharmaceuticals, after a series of lawsuits claiming it caused birth defects. For several years, Duchesnay has been working toward Food and Drug Administration clearance to market Diclectin in the United States, but it would be premature to predict when it would become available in the United States, a spokesman for the company said.

In the study, symptoms were evaluated using the PUQE (Pregnancy–Unique Quantification of Emesis and Nausea) score, a validated scoring system that takes into account the frequency of vomiting; the frequency of retching, gagging, or dry heaves; and the number of hours spent feeling nauseous over a 24-hour period. The score was developed by Dr. Gideon Koren, director of Motherisk and coauthor of this study, and his associates. A score of 7-12 is considered moderate; a score of 13 or higher is considered severe.

In the study, preemptive treatment was associated with 70% fewer cases of moderate to severe NVP during the first 3 weeks women experienced symptoms: 4 of the 26 (15%) evaluable women had a PUQE score of 11 or more during the first 3 weeks of NVP symptoms, compared with 9 of the 23 (39%) evaluable women in the control group, a significant difference. Of the 19 women in the preemptively treated group who had HG during the previous pregnancy, 6 (32%) experienced HG, compared with 6 of the 11 (55%) in the control group, also a significant difference. Some women who enrolled were not evaluable for reasons that included having a miscarriage.

NVP resolved before labor in significantly more of the women in the preemptively treated group than in the control group (almost 80% vs. about 50%), and there was a negative correlation between PUQE scores and a well-being score, indicating that treatment is associated with improved quality of life for these patients, Ms. Maltepe said.

In women who have experienced severe NVP or HG in a previous pregnancy, preemptive treatment with doxylamine-pyridoxine events can reduce the recurrence of NVP in subsequent pregnancies, and improve their quality of life during pregnancy, as well as reduce time off from work and the need for enteral and parenteral therapy, hospitalization, and other costs associated with severe NVP, she concluded.

The NVP helpline at Motherisk is the only dedicated NVP helpline in the world, according to Ms. Maltepe, who provides evidence-based recommendations on pharmaceutical and nonpharmaceutical approaches to treating NVP for pregnant women, their family members, and clinicians via the helpline (800-436-8477 in North America).

 

 

The study was funded by Duchesnay. Ms. Maltepe and her coauthors said they had no relevant conflict of interest to disclose.

The Motherisk site is available at www.motherisk.org/women/index.jsp.

BALTIMORE – Starting treatment with a combination of doxylamine and pyridoxine before the onset of nausea and vomiting significantly reduced the incidence of severe nausea and vomiting of pregnancy, compared with starting treatment at the first sign of symptoms, in a study of 59 women with a history of severe nausea and vomiting of pregnancy, Caroline Maltepe reported.

In the prospective, randomized, open-label study of women with a history of nausea and vomiting of pregnancy (NVP), 30 women began taking the delayed-release combination of 10 mg of doxylamine and 10 mg of pyridoxine (vitamin B6) as soon as they learned they were pregnant, before they started to experience nausea and vomiting (at a mean of 4 weeks’ gestation). Another 29 pregnant women started taking the combination when they started to experience symptoms, Ms. Maltepe said at the annual meeting of the Teratology Society.

Women in both groups started to experience NVP symptoms at a mean of about 5 to almost 6 weeks, said Ms. Maltepe, the lead author of the study, who is with the Motherisk Program at the Hospital for Sick Children in Toronto. The program conducts research and provides information about the safety of maternal exposure to drugs, chemicals, diseases, radiation, and environmental agents to the developing fetus or infant.

The women (mean age, 31-32 years) had experienced severe NVP or hyperemesis gravidarum (HG) in their previous pregnancy, and enrolled when they were planning a pregnancy or in early pregnancy at a point when they had not yet experienced any symptoms. Women in both groups took 2-9 tablets of the doxylamine-pyridoxine combination a day, and received counseling and follow-up calls.

In Canada, the combination is approved and marketed as Diclectin, by Duchesnay, and is the only drug labeled for treating NVP in Canada. There it is considered a first-line treatment and is taken at a standard dose of four tablets a day, said Ms. Maltepe, the coordinator of the NVP helpline at Motherisk.

Diclectin is a generic form of the drug Bendectin, which was marketed in the United States until 1983, when it was voluntarily withdrawn by its manufacturer, Merrell Dow Pharmaceuticals, after a series of lawsuits claiming it caused birth defects. For several years, Duchesnay has been working toward Food and Drug Administration clearance to market Diclectin in the United States, but it would be premature to predict when it would become available in the United States, a spokesman for the company said.

In the study, symptoms were evaluated using the PUQE (Pregnancy–Unique Quantification of Emesis and Nausea) score, a validated scoring system that takes into account the frequency of vomiting; the frequency of retching, gagging, or dry heaves; and the number of hours spent feeling nauseous over a 24-hour period. The score was developed by Dr. Gideon Koren, director of Motherisk and coauthor of this study, and his associates. A score of 7-12 is considered moderate; a score of 13 or higher is considered severe.

In the study, preemptive treatment was associated with 70% fewer cases of moderate to severe NVP during the first 3 weeks women experienced symptoms: 4 of the 26 (15%) evaluable women had a PUQE score of 11 or more during the first 3 weeks of NVP symptoms, compared with 9 of the 23 (39%) evaluable women in the control group, a significant difference. Of the 19 women in the preemptively treated group who had HG during the previous pregnancy, 6 (32%) experienced HG, compared with 6 of the 11 (55%) in the control group, also a significant difference. Some women who enrolled were not evaluable for reasons that included having a miscarriage.

NVP resolved before labor in significantly more of the women in the preemptively treated group than in the control group (almost 80% vs. about 50%), and there was a negative correlation between PUQE scores and a well-being score, indicating that treatment is associated with improved quality of life for these patients, Ms. Maltepe said.

In women who have experienced severe NVP or HG in a previous pregnancy, preemptive treatment with doxylamine-pyridoxine events can reduce the recurrence of NVP in subsequent pregnancies, and improve their quality of life during pregnancy, as well as reduce time off from work and the need for enteral and parenteral therapy, hospitalization, and other costs associated with severe NVP, she concluded.

The NVP helpline at Motherisk is the only dedicated NVP helpline in the world, according to Ms. Maltepe, who provides evidence-based recommendations on pharmaceutical and nonpharmaceutical approaches to treating NVP for pregnant women, their family members, and clinicians via the helpline (800-436-8477 in North America).

 

 

The study was funded by Duchesnay. Ms. Maltepe and her coauthors said they had no relevant conflict of interest to disclose.

The Motherisk site is available at www.motherisk.org/women/index.jsp.

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Early Data Find No Adalimumab Teratogenicity

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Early Data Find No Adalimumab Teratogenicity

BALTIMORE – Exposure to adalimumab was not associated with any specific pattern of minor or major birth defects in women with rheumatoid arthritis taking the biologic drug during pregnancy, according to preliminary data from an ongoing prospective cohort study.

Between November 2004 and January 2012, 312 pregnant women in the United States and Canada – 69 women with RA exposed to adalimumab, 80 women with RA who had not taken adalimumab, and 163 healthy controls – were enrolled before 20 weeks’ gestation. Their mean age was 32-33 years, and about two-thirds were white.

Dr. Christina Chambers

Major birth defects among the live births were identified in 5% of the babies born to women exposed to adalimumab, compared with about 4% among disease-matched controls who did not take adalimumab, and about 7% among healthy controls, Christina Chambers, Ph.D., of the University of California, San Diego, reported at the annual meeting of the Teratology Society.

The rate of minor structural abnormalities was similar in the three groups, at about 22%-24%, and there was no pattern of major or minor structural defects noted among the adalimumab-exposed group. (The three major malformations in the adalimumab-exposed group were one ventricular septal defect, one unilateral cryptorchidism, and one case of microcephaly.)

There were no stillbirths. The rate of spontaneous abortions was not significantly different between the three groups, nor were the rates of preterm delivery or birth weights, said Dr. Chambers, director of the California Teratogen Information Service and Clinical Research Program.

Through 1-year of follow-up, there were no malignancies among the infants and the rates of serious infections in the three groups were similar (about 3% in the two RA groups and 2% in the healthy comparison group).

The teratogenic effects of adalimumab, a tumor necrosis factor blocker, are being evaluated in the pregnancy registry, which is part of the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project.

Adalimumab, marketed as Humira by Abbott Laboratories, was first approved in the United States in 2002 as a treatment for people with moderately to severely active RA, and has since been approved for other autoimmune diseases, including psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, and psoriasis.

The registry study is comparing outcomes in women with RA who are treated with adalimumab during pregnancy, in women with RA not treated with adalimumab during pregnancy, and in women who do not have an autoimmune disease and have not been exposed to adalimumab or any known teratogenic drug during pregnancy. The study includes medical record reviews, examination of infants for major and minor structural abnormalities, and follow-up for 1 year post partum. It is expected to continue through 2017; the pregnant women are recruited from OTIS member services and from rheumatologists, and other clinicians who care for these patients.

Although little to no placental transfer of adalimumab is expected during early pregnancy, limited information on the safety of adalimumab during pregnancy has been published, Dr. Chambers said.

Abbott Laboratories is among the sponsors of the OTIS Autoimmune Diseases in Pregnancy Project, which is also evaluating safety of medications in women with ankylosing spondylitis, psoriasis and psoriatic arthritis, and Crohn’s disease. Dr. Chambers and her coauthors have received or receive grant funding for research on medications for autoimmune diseases from Abbott and other manufacturers: Amgen, Bristol Myers Squibb, Roche Genentech, Sanofi, Teva, Par, Sandoz, and Apotex.

Information for women and clinicians interested in enrolling in the OTIS Autoimmune Diseases in Pregnancy Project is available at www.otispregnancy.org/autoimmune-studies-s13049.

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BALTIMORE – Exposure to adalimumab was not associated with any specific pattern of minor or major birth defects in women with rheumatoid arthritis taking the biologic drug during pregnancy, according to preliminary data from an ongoing prospective cohort study.

Between November 2004 and January 2012, 312 pregnant women in the United States and Canada – 69 women with RA exposed to adalimumab, 80 women with RA who had not taken adalimumab, and 163 healthy controls – were enrolled before 20 weeks’ gestation. Their mean age was 32-33 years, and about two-thirds were white.

Dr. Christina Chambers

Major birth defects among the live births were identified in 5% of the babies born to women exposed to adalimumab, compared with about 4% among disease-matched controls who did not take adalimumab, and about 7% among healthy controls, Christina Chambers, Ph.D., of the University of California, San Diego, reported at the annual meeting of the Teratology Society.

The rate of minor structural abnormalities was similar in the three groups, at about 22%-24%, and there was no pattern of major or minor structural defects noted among the adalimumab-exposed group. (The three major malformations in the adalimumab-exposed group were one ventricular septal defect, one unilateral cryptorchidism, and one case of microcephaly.)

There were no stillbirths. The rate of spontaneous abortions was not significantly different between the three groups, nor were the rates of preterm delivery or birth weights, said Dr. Chambers, director of the California Teratogen Information Service and Clinical Research Program.

Through 1-year of follow-up, there were no malignancies among the infants and the rates of serious infections in the three groups were similar (about 3% in the two RA groups and 2% in the healthy comparison group).

The teratogenic effects of adalimumab, a tumor necrosis factor blocker, are being evaluated in the pregnancy registry, which is part of the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project.

Adalimumab, marketed as Humira by Abbott Laboratories, was first approved in the United States in 2002 as a treatment for people with moderately to severely active RA, and has since been approved for other autoimmune diseases, including psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, and psoriasis.

The registry study is comparing outcomes in women with RA who are treated with adalimumab during pregnancy, in women with RA not treated with adalimumab during pregnancy, and in women who do not have an autoimmune disease and have not been exposed to adalimumab or any known teratogenic drug during pregnancy. The study includes medical record reviews, examination of infants for major and minor structural abnormalities, and follow-up for 1 year post partum. It is expected to continue through 2017; the pregnant women are recruited from OTIS member services and from rheumatologists, and other clinicians who care for these patients.

Although little to no placental transfer of adalimumab is expected during early pregnancy, limited information on the safety of adalimumab during pregnancy has been published, Dr. Chambers said.

Abbott Laboratories is among the sponsors of the OTIS Autoimmune Diseases in Pregnancy Project, which is also evaluating safety of medications in women with ankylosing spondylitis, psoriasis and psoriatic arthritis, and Crohn’s disease. Dr. Chambers and her coauthors have received or receive grant funding for research on medications for autoimmune diseases from Abbott and other manufacturers: Amgen, Bristol Myers Squibb, Roche Genentech, Sanofi, Teva, Par, Sandoz, and Apotex.

Information for women and clinicians interested in enrolling in the OTIS Autoimmune Diseases in Pregnancy Project is available at www.otispregnancy.org/autoimmune-studies-s13049.

BALTIMORE – Exposure to adalimumab was not associated with any specific pattern of minor or major birth defects in women with rheumatoid arthritis taking the biologic drug during pregnancy, according to preliminary data from an ongoing prospective cohort study.

Between November 2004 and January 2012, 312 pregnant women in the United States and Canada – 69 women with RA exposed to adalimumab, 80 women with RA who had not taken adalimumab, and 163 healthy controls – were enrolled before 20 weeks’ gestation. Their mean age was 32-33 years, and about two-thirds were white.

Dr. Christina Chambers

Major birth defects among the live births were identified in 5% of the babies born to women exposed to adalimumab, compared with about 4% among disease-matched controls who did not take adalimumab, and about 7% among healthy controls, Christina Chambers, Ph.D., of the University of California, San Diego, reported at the annual meeting of the Teratology Society.

The rate of minor structural abnormalities was similar in the three groups, at about 22%-24%, and there was no pattern of major or minor structural defects noted among the adalimumab-exposed group. (The three major malformations in the adalimumab-exposed group were one ventricular septal defect, one unilateral cryptorchidism, and one case of microcephaly.)

There were no stillbirths. The rate of spontaneous abortions was not significantly different between the three groups, nor were the rates of preterm delivery or birth weights, said Dr. Chambers, director of the California Teratogen Information Service and Clinical Research Program.

Through 1-year of follow-up, there were no malignancies among the infants and the rates of serious infections in the three groups were similar (about 3% in the two RA groups and 2% in the healthy comparison group).

The teratogenic effects of adalimumab, a tumor necrosis factor blocker, are being evaluated in the pregnancy registry, which is part of the Organization of Teratology Information Specialists (OTIS) Autoimmune Diseases in Pregnancy Project.

Adalimumab, marketed as Humira by Abbott Laboratories, was first approved in the United States in 2002 as a treatment for people with moderately to severely active RA, and has since been approved for other autoimmune diseases, including psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, and psoriasis.

The registry study is comparing outcomes in women with RA who are treated with adalimumab during pregnancy, in women with RA not treated with adalimumab during pregnancy, and in women who do not have an autoimmune disease and have not been exposed to adalimumab or any known teratogenic drug during pregnancy. The study includes medical record reviews, examination of infants for major and minor structural abnormalities, and follow-up for 1 year post partum. It is expected to continue through 2017; the pregnant women are recruited from OTIS member services and from rheumatologists, and other clinicians who care for these patients.

Although little to no placental transfer of adalimumab is expected during early pregnancy, limited information on the safety of adalimumab during pregnancy has been published, Dr. Chambers said.

Abbott Laboratories is among the sponsors of the OTIS Autoimmune Diseases in Pregnancy Project, which is also evaluating safety of medications in women with ankylosing spondylitis, psoriasis and psoriatic arthritis, and Crohn’s disease. Dr. Chambers and her coauthors have received or receive grant funding for research on medications for autoimmune diseases from Abbott and other manufacturers: Amgen, Bristol Myers Squibb, Roche Genentech, Sanofi, Teva, Par, Sandoz, and Apotex.

Information for women and clinicians interested in enrolling in the OTIS Autoimmune Diseases in Pregnancy Project is available at www.otispregnancy.org/autoimmune-studies-s13049.

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