Evaluation of Physician Knowledge of the Key Safety Information for Aflibercept in Canada: Evaluation of Risk-Minimization Measures.

BACKGROUND: As part of the risk-management plan (RMP) for aflibercept, materials have been developed to educate physicians in Canada on the key safety information and safe use for aflibercept. OBJECTIVE: The objectives of this study were to assess whether physicians in Canada received and reviewed the aflibercept educational materials (i.e. vial preparation instruction card, intravitreal injection procedure video, and product monograph) and to evaluate their knowledge of key safety information. METHODS: Retinal specialists and ophthalmologists who prescribe and/or administer aflibercept were recruited to complete a survey. Physicians could complete and return a paper questionnaire by mail or complete the questionnaire online via a study website. RESULTS: Of the 308 physicians invited to participate in the survey, 95 (31%) completed the questionnaire. Nearly all physicians (98%) reported receiving at least one of the educational materials. The proportion of correct responses to individual questions on storage and preparation of aflibercept ranged from 54 to 98%. Physician knowledge was high on the recommended dose of aflibercept (91%), dose preparation (91-96% on individual items), and dosing guidelines (75-95% on individual items). Most physicians knew the contraindications for aflibercept (89%) and that aflibercept should not be used in pregnancy unless clearly indicated by medical need in which benefits outweigh risks (60%); 21% responded more conservatively that aflibercept should never be used in pregnancy. Knowledge was high for most questions about injection procedures (91-99% on individual items); however, fewer physicians (24%) correctly reported that the eye should be covered with a sterile drape. Knowledge was high for possible side effects (89-100% on individual items) and actions to take in relation to the potential for increased intraocular pressure (86-93% on individual items). CONCLUSION: Nearly all physicians (98%) reported having received the product monograph, and most (82%) reported having received the vial preparation instruction card; nearly half (46%) reported having received the intravitreal injection procedure video. Physicians' knowledge of the most important topics was high. Knowledge varied for topics that are less frequently encountered (e.g. use in women of childbearing potential) and for recommendations that are not standard medical practice in Canada (e.g. use of sterile drape).

The effects of maternal supplementation of polyunsaturated Fatty acids on visual, neurobehavioural, and developmental outcomes of the child: a systematic review of the randomized trials.

Polyunsaturated fatty acid (PUFA) use in pregnancy has been promoted as beneficial for visual and neurobehavioural development in the fetus. However, no systematic review of the randomized trials has been conducted. The objective of this review was to evaluate potential advantages of this regiment by reviewing all randomized trials in pregnancy. Methods. Systematic review of randomized controlled studies comparing cognitive and visual achievements among infants whose mothers were treated and untreated with PUFA during gestation. Results. Nine studies met the inclusion criteria, three focusing on visual and six on neurobehavioural development. Due to differing outcome measurements in the infants, the studies could not be combined into a formal meta-analysis. Synthesizing the existing data, for both visual and neurobehavioural development, most studies could not show sustained benefits to infant cognition or visual development. Conclusion. At the present time a recommendation to change practice and supplement all expecting mothers with PUFA to improve offspring vision or neurobehavioural function is not supported by existing evidence.

Safety of infliximab use during pregnancy.

Infliximab is a chimeric IgG1 monoclonal antibody to tumor necrosis factor alpha (TNF)-α used in the treatment of inflammatory bowel disease and rheumatoid arthritis. Infliximab does not actively cross the placenta during the first trimester, but undergoes efficient placental transfer during the late second and third trimesters and is detectable in the infant's serum for several months after birth. This raises concerns about immunological risks of infection and response to vaccines. Available evidence from registry studies and case reports involving more than 300 pregnancy outcomes suggest that infliximab carries low fetal risk and is compatible with use during conception and the first two trimesters of pregnancy. The long-term effects of infliximab exposure on the developing immune system are yet unknown. Based on limited data from several case reports, infants born with detectable levels of infliximab do not seem to have an increased risk of infections in their first year of life and have normal responses to nonlive vaccines. However, a fatal case of disseminated mycobacterial infection has been reported in an infant who received BCG vaccine at 3 months of age, to a mother who had been treated with infliximab throughout her pregnancy. Vaccination with live viruses should be postponed in infants exposed to infliximab in utero, until serum levels are undetectable which may require more than 6 months. Discontinuing infliximab early in the third trimester should be considered in order to minimize late fetal exposure.

Guidelines for maternal codeine use during breastfeeding.

QUESTION: In light of the recent evidence of adverse events in infants whose mothers use codeine medication, we have been struggling with the issue of how to manage codeine analgesia in our postpartum patients. What are some guidelines for the safe use of codeine during breastfeeding? ANSWER: Motherisk has summarized recent scientific evidence into suggested guidelines for the safe use of codeine during breastfeeding.

In utero exposure to therapeutic radiation for Hodgkin lymphoma.

QUESTION: One of my patients was incidentally found to be pregnant after completion of radiotherapy for Hodgkin lymphoma. What are the possible effects that I should discuss with her before she makes a final decision regarding continuation of her pregnancy? ANSWER: Radiotherapy might not be an absolute contraindication in pregnant women who are diagnosed with cancer located in areas remote from the pelvis. However, the fetal exposure should be carefully estimated, and the known dose-response information has to be discussed individually to allow informed decisions to be made.

Use of hypoglycemic drugs during lactation.

QUESTION: My patient was taking glipizide (an oral sulfonylurea) for type 2 diabetes. Now she is pregnant and taking insulin instead. She is very anxious to return to her previous treatment immediately after delivery because of the pain and hurdles associated with the administration of insulin. Can sulfonylureas cross into human milk and, if so, is it safe for her to breastfeed her infant? ANSWER: The exposure of infants to second-generation sulfonylureas (eg, glipizide, glyburide) through breast milk is expected to be minimal, based on the limited data available. Women with type 2 diabetes treated with sulfonylureas should not be discouraged from breastfeeding. The benefits of breastfeeding greatly outweigh the risks of these medications, if any. The baby should, however, be monitored for signs of hypoglycemia.

H1N1 influenza in pregnancy: risks, vaccines, and antivirals.

When pregnant women are infected by the H1N1 influenza A virus, the consequences are more serious than they are in other groups of patients. It is imperative to vaccinate pregnant women against this virus. Unvaccinated women who come in contact with the virus should receive prophylactic antiviral therapy. The existing information on the safety of oseltamavir and zanamavir, the most used antivirals, is limited but reassuring.

Medications for restless legs syndrome in pregnancy.

According to epidemiological data, pregnant women have a two or three times higher risk of experiencing restless legs syndrome (RLS) than the general population. Current evidence suggests that dopaminergic dysfunction, impaired iron homeostasis, and genetic predisposition may be involved in the pathophysiology of RLS. Four classes of medications have been used for patients with RLS, but pregnancy elicits a therapeutic concern. Although two dopamine agonists, ropinirole and pramipexole, have been approved by the FDA for the treatment of RLS and are currently the first-line treatment for daily symptoms, there is very little information on the teratogenic risks of these new medications. Therefore, they are not currently recommended for use during pregnancy. Medications with a more extensive safety record in pregnancy include opioids; antiepileptics, such as carbamazepine and gabapentin; and certain benzodiazepines. Ruling out iron deficiency should be an integral part of a treatment plan for RLS in pregnancy. Before management with medication is introduced, every patient should be assessed for iron status with measurement of serum ferritin.

Does treatment with bisphosphonates endanger the human pregnancy?

Bisphosphonates are clinically used in the treatment of various bone diseases including corticosteroid-induced osteoporosis, hypercalcemia associated with malignancy, and osteogenesis imperfecta. They are therefore often used in women of childbearing age, but little is known about their possible effects on the human embryo and fetus. Animal studies have revealed unfavourable effects of bisphosphonate treatment on the fetus, mainly in the skeleton. Since bisphosphonates are retained for a long time in the human skeleton, concerns have been raised that even pre-pregnancy administration of bisphosphonates may result in embryofetal exposure and alter fetal bone modelling. To obtain current information on the risks and safety of bisphosphonate use in pregnancy, we performed a systematic search of the Medline and Embase databases, from 1950 and 1974, respectively, to September 2008. Fifty-one cases of exposure to bisphosphonates before or during pregnancy were identified; none of them described any skeletal abnormalities or other congenital malformations in the infants. The bisphosphonates used were alendronate (32 cases), pamidronate (11), etidronate (5), risedronate (2), and zoledronic acid (1). Although in theory bisphosphonates may affect bone modelling and development in the fetus, the 51 cases reported to date did not detect such pathology.