Alicia B. Forinash

The Use of Galactogogues in the Breastfeeding Mother

Objective: To review data regarding the efficacy of galactogogues available in the US to increase breast milk production in postpartum mothers. Data Sources: Literature was sought using PubMed (1966-June 2012) and EMBASE (1973-June 2012). Search terms included breastfeeding, breast milk, Lactation, galactogogue, motoctopramide, oxytocin, fenugreek, milk thistle, Silymarin, growth hormone, thyroid releasing hormone, medroxyprogesterone, domperidono. goats rue, beer, Asparagus racemosus, shatavari, Medicago sativa, alfalfa. Onicus bonedictus. blessed thistle, Galoga officinalis, brewers yeast, and herbals. Study Selection and Data Extraction: All studies including humans and published in English with data assessing the efficacy of galactogogues for increasing breast milk production were evaluated. Data Synthesis: Breast milk is considered the optimal food source for newborns through 1 year of age. Many factors influence overall maternal production, including maternal pain, illness, balance of time when returning to work, anxiety, or emotional stress. Although a variety of herbal and pharmaceutical options have anecdotal evidence of their ability to improve breast milk production, peer-reviewed studies proving their efficacy are lacking. Metoclopramide, oxytocin, fenugreek, and milk thistle have shown mixed results in improving milk production; however, the trials were small and had a variety of limitations. Conclusions: Nonpharmacologic recommendations should be exhausted before adding therapy. Although anecdotal evidence encourages the use of metoclopramide, fenugreek, asparagus, and milk thistle for their galactogogue properties, efficacy and safety data in the literature are lacking. Oxytocin and domperidono are potentially available for compounding purposes, but safety data are limited. More studies are needed to evaluate the effects of available galactogogues on breast milk production.

Impact of Online Lecture-capture on Student Outcomes in a Therapeutics Course

Objectives. To examine the correlation between students accessing recorded lecture files (audio and slides) online and course grades and class attendance. Methods. Second professional year (of 6-year program) students in a therapeutics course had access to recorded online lectures for 72 hours following live lectures. The number and duration of lecture accessions were compared to final course grades and class attendance. Course grades were compared to those of a historical control group. At the end of the semester, students completed a brief survey instrument regarding their use and perceptions of online lectures. Results. No correlation was found between final course grades and the number of lecture accessions (r = 0.0014) or total number of minutes lectures were viewed (r = 0.033), nor between class attendance and minutes viewed (r = 0.2158). Students with access to recorded lectures outperformed the historical control group on the final examination (p < 0.002). Seventy-two percent of students reported no influence of online files on class attendance. Conclusions. Posting lectures online did not affect student outcomes, but students did score higher on the final examination.

Nicotine Replacement Therapy Effect on Pregnancy Outcomes

Objective: To review data assessing the effects of nicotine replacement therapy (NRT) during pregnancy on fetal, neonatal, and maternal outcomes. Data Sources: A literature search of PubMed (1966-Jufy 2010) was performed using the terms smoking, smoking cessation, pregnancy, and nicotine replacement therapy. Bibliographies and the Cochrane Database were reviewed to identify additional relevant articles. Study Selection and Data Extraction: All studies including humans and published in English with data describing NRT effects on pregnancy outcomes or malformations as a primary or secondary outcome were evaluated. Data Synthesis: Currently, behavior modification therapy is recommended for smoking cessation in pregnancy as first-line treatment, but NRT should be offered to patients who are not successful. NRT is currently a pregnancy category D medication. Pregnancy outcomes and malformation rates for NRT in pregnancy were evaluated as either primary or secondary outcomes in several trials. Four studies examined pregnancy outcomes after a full course of nicotine gum or patch therapy. NRT use significantly decreased the risk of preterm delivery and low birth weight compared to that of smokers. Only 1 study evaluated the risk of malformations after exposure to the NRT patch during the first trimester. In a retrospective analysis, NRT users had an increased risk for any fetal malformation but not for major or musculoskeletal ones. However, no adjustments were made for many known factors associated with malformations. Conclusions: Behavior modification therapy should always be the first method tried for smoking cessation in the pregnant population. If behavior modification therapy is attempted without success, NRT should be offered because of decreased risk for low birth weight and preterm delivery compared to continued smoking. Additionally, NRT does not appear to increase the risk for malformations.

New hormonal contraceptives : A comprehensive review of the literature

Over 16 million women in the United States take oral hormonal contraceptives, yet approximately 5% experience an unintended pregnancy during the first year of use. Compliance with the regimen is important in maintaining cycle control and preventing pregnancy. New hormonal contraceptive agents, norelgestromin‐ethinyl estradiol patch, etonogestrel‐ethinyl estradiol vaginal ring, and medroxyprogesterone‐estradiol cypionate injection, were designed to increase compliance and decrease adverse effects while maintaining efficacy. Each one has potential advantages for women seeking alternatives to traditional oral contraceptives or for those who have trouble remembering to take a daily pill. Each agent also may have its own disadvantages, including application site reactions, need for monthly injections, and device‐related events; however, all have similar efficacy and adverse‐effect profiles compared with current oral hormonal contraceptives.

Changing oral contraceptives from prescription to over-the-counter status: an opinion statement of the Women's Health Practice and Research Network of the American College of Clinical Pharmacy.

Addressing the issue of unintended pregnancy is a national priority. One proposed strategy to reduce unintended pregnancy is to improve access to oral contraceptives by changing them to over‐the‐counter (OTC) status. Existing data indicate that oral contraceptives meet safety criteria required of OTC products. Available literature demonstrates that women can self‐screen for contraindications to oral contraceptives and can do this as well as clinicians, and experience with OTC emergency contraception suggests that OTC oral contraceptives would not increase sexual risk‐taking behavior. Women support OTC access to oral contraceptives, but express an interest in accessing pharmacist counseling. On the basis of these data, the Womens Health Practice and Research Network of the American College of Clinical Pharmacy supports changing oral contraceptives to OTC status under two conditions: that they are sold where a pharmacist is on duty and that there are mechanisms in place to cover OTC contraceptives through Medicaid. Future research should address the issues of out‐of‐pocket costs to individuals, label‐comprehension studies, and models for pharmacist reimbursement for time spent counseling on contraception.

Levetiracetam Use in Pregnancy

Objective: To review data evaluating levetiracetam management of epilepsy during pregnancy. Data Sources: A literature search of PubMed (1966–June 2009) was performed using the terms pregnancy, epilepsy, levetiracetam, and anticonvulsants. Bibliographies of all articles retrieved were reviewed to identify additional relevant articles. Study Selection and Data Extraction: All studies including humans and published in English with data describing levetiracetam management during pregnancy were included. Data Synthesis: The pharmacokinetic studies included in this review demonstrate that the clearance of levetiracetam increases during pregnancy, particularly during the third trimester, which subsequently leads to decreased serum levetiracetam concentrations. The increase in clearance is most likely due to an increase in renal blood flow. The teratogenic studies included in this review included a total of 147 patients. Of these patients, 2% experienced a major congenital malformation (MCM) and 4.8% experienced a minor anomaly. All of the patients who had either an MCM or a minor anomaly were receiving antiepileptic drug (AED) polytherapy. It was unknown whether 10.9% of the 147 patients discussed were receiving levetiracetam monotherapy or AED polytherapy. None of the published literature assessed adherence to AED therapy. Folic acid supplementation was addressed in only one of the case series presented. Conclusions: If levetiracetam is used during pregnancy, women should receive adequate amounts of folic acid (0.4–5 mg/day) and serum concentrations of levetiracetam should be determined before conception if possible and during each trimester, especially during the middle of the third trimester, to assess therapeutic concentrations. The dose may need to be increased during the third trimester to provide concentrations consistent with those before conception. Patients should be informed that there appears to be a small chance of malformations with levetiracetam, but that the data are limited.

Should pregnant women be included in phase IV clinical drug trials

Relatively few drugs, especially those recently approved by the US Food and Drug Administration, have published human pregnancy experience. Although all drugs contain animal reproduction data, these are usually not predictive of human risk. Clinical trials in pregnant women are rarely conducted because of ethical and legal concerns, and it may be many years before sufficient observational data are collected to guide clinical treatment decisions. Because many of these drugs will be used in pregnancy, human data are needed shortly after the drugs come to the market. Lack of human data leads to uncertainty over whether a drug can be safely prescribed for a pregnant patient. Unless there are compelling scientific and ethical reasons to exclude them, pregnant women should be included in phase IV clinical trials (postmarketing studies to obtain additional information, including the risks, benefits, and optimal use of a drug). This paper examines how physicians currently counsel pregnant women when there are no human data and proposes an alternative method in which knowledge regarding risks associated with the use of drugs during pregnancy can be enhanced in a clinical trial setting.

Safety of the HPV Bivalent and Quadrivalent Vaccines During Pregnancy

OBJECTIVE: To evaluate the safety of the human papillomavirus (HPV) bivalent and quadrivalent vaccines in pregnancy. DATA SOURCE: PubMed (1966-August 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, and pregnancy. References were reviewed for relevant information. STUDY SELECTION AND DATA EXTRACTION: All studies including humans that were published in English with data describing HPV vaccine administration in pregnancy were evaluated. DATA SYNTHESIS: Two combined analyses of 7 Phase 3 efficacy trials have retrospectively evaluated the safety of unintentional administration of either the bivalent (n = 1786) or quadrivalent (n = 2085) HPV vaccine during pregnancy. In addition, postmarketing pregnancy registry surveillance data (prospective, n = 787; retrospective, n = 76) for the quadrivalent HPV vaccine have been published. However, only 279 pregnancies from the studies and 90 pregnancies from the registry occurred within 30 days of receiving the vaccination. Overall, the vaccine does not appear to be associated with an increased risk of spontaneous abortion, fetal malformations, or adverse pregnancy outcomes beyond that found in the general population. Although the data are limited, neither HPV vaccine appears to be associated with an increased risk of adverse pregnancy outcomes. However, limitations of the data include small patient populations, minimal to no adjustments for factors known to influence pregnancy outcomes or malformations, and the majority of the available pregnancy data are from retrospective analysis of Phase 3 efficacy trials. CONCLUSIONS: Neither HPV vaccine should be routinely administered during pregnancy. If a pregnancy occurs midseries, the remaining vaccines should be given after pregnancy completion. Further studies are required to determine actual risk.

The Prophylactic Role for the Human Papillomavirus Quadrivalent Vaccine in Males

Objective: To determine the role of human papillomavirus (HPV) quadrivalent vaccine in males. Data Source: PubMed (1966–March 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, quadrivalent, males, cancer, and genital warts. Reference citations were reviewed for relevant information. Study Selection and Data Extraction: All studies including humans and published in English with data describing HPV quadrivalent vaccine administration in males were evaluated. Data Synthesis: The HPV quadrivalent vaccine is currently recommended in females, but its role in males is still being defined. Three clinical trials evaluated the immunogenicity and tolerability of the vaccine in more than 1100 males 9–26 years of age. Greater than 99.5% of males seroconverted for HPV 6, 11, 16, and 18 at 1 month post-completion and titers were found to be numerically higher than those in females 16–26 years old. One study found that immune response persisted in >92.5% of males at 1 year. The results show high efficacy against detection of new anogenital lesions in males 29 months after receiving the quadrivalent HPV vaccine. In addition, the quadrivalent HPV vaccine appears to be well tolerated, with the most common adverse effects being syncope, fever, local site reactions, dizziness, nausea, and headache. Conclusions: The HPV quadrivalent vaccine appears to be safe and induces an effective immune response in males. It may also decrease the incidence of anogenital and penile cancer, although current data are limited in number and duration of follow-up. Further analysis of the long-term immunogenicity and effects on HPV-associated complications is needed.

Buprenorphine Versus Methadone for Opioid Dependence in Pregnancy.

Objective: To evaluate maternal and neonatal safety outcomes for methadone and buprenorphine in the obstetric population. Data Sources: A literature search of PubMed (1966 to March 2016) and EMBASE (1973 to March 2016) was completed using the search terms buprenorphine, methadone, pregnancy, opioid, and neonatal abstinence syndrome. Priority was given to randomized controlled trials and trials directly comparing buprenorphine and methadone during pregnancy. The bibliographies were reviewed for other relevant articles. Study Selection and Data Extraction: All human studies published in English, that compared methadone and buprenorphine use in pregnancy were evaluated. Because of the limited number of obstetric studies, only 5 critical studies were found. Data Synthesis: Buprenorphine significantly improved or had similar outcomes to methadone for development of neonatal abstinence syndrome (NAS), percentage of infants requiring treatment for NAS (20%-47% vs 45.5%-57%, respectively), total amount of morphine used to treat NAS (0.472-3.4 vs 1.862-10.4 mg, respectively), duration of NAS (4.1-5.6 vs 5.3-9.9 days, respectively), peak NAS (3.9-11 vs 4.9-12.8 score, respectively), infant hospital stay (6.8-10.6 vs 8.1-17.5 days, respectively), and gestational age at delivery (38.8-39.7 vs 37.9-38.8 weeks, respectively). No difference was found with other neonatal or maternal outcomes. Conclusions: Both methadone and buprenorphine are effective agents, with improved safety compared with continued nonmedical opioid use during pregnancy. There is evidence to suggest that buprenorphine should be considered as an equivalent option to methadone for use in pregnancy; however, larger studies are still needed to fully evaluate buprenorphine safety and advantages over methadone in the obstetric population.