Concurrent Quinidine and Phenobarbital in the Treatment of a Patient with 2 KCNT1 Mutations.

Epilepsy of infancy with migrating focal seizures is a devastating pediatric neurologic disorder that often results in treatment-resistant seizure activity and developmental delay. The condition has been associated with mutations in the KCNT1 gene that cause a gain of function in neuronal sodium-activated potassium channels. Quinidine has been shown to reverse this gain of function and has recently been used to reduce seizure activity in patients with these mutations. We report the case of an infant with 2 KCNT1 mutations who experienced minor relief with quinidine and discuss the drug's important interaction with phenobarbital.

Role of Topical Oxymetazoline for Management of Erythematotelangiectatic Rosacea.

OBJECTIVE: To review and summarize topical oxymetazoline's pharmacology, pharmacokinetics, efficacy, safety, cost, and place in therapy for persistent redness associated with erythematotelangiectatic rosacea. DATA SOURCES: Literature searches of MEDLINE (1975 to September 2017), International Pharmaceutical Abstracts (1975 to September 2017), and Cochrane Database (publications through September 2017) using the terms rosacea, persistent redness, α -agonist, and oxymetazoline. STUDY SELECTION AND DATA EXTRACTION: Results were limited to studies of human subjects, English-language publications, and topical use of oxymetazoline. Relevant materials from government sources, industry, and reviews were also included. DATA SYNTHESIS: Data support the efficacy of oxymetazoline for persistent facial redness. Little study beyond clinical trials cited in the drug approval process has been conducted. Current data suggest that oxymetazoline is similar in safety and efficacy to brimonidine. Head-to-head comparisons of topical α-agonists for erythema caused by rosacea are needed. CONCLUSION: The topical α-agonist, oxymetazoline, is safe and effective for reducing persistent facial redness associated with erythematotelangiectatic subtype of rosacea. Health care practitioners selecting among treatments should consider not only the subtype of rosacea but also individual patient response, preference, and cost.

Association Between Prenatal Acetaminophen Exposure and Future Risk of Attention Deficit/Hyperactivity Disorder in Children.

OBJECTIVE: To evaluate the effect of prenatal acetaminophen exposure on the future development of attention deficit/hyperactivity disorder (ADHD) in children. DATA SOURCES: Literature searches of MEDLINE (1975 to June 2015), International Pharmaceutical Abstracts (1975 to June 2015), and Cochrane Database (publications through June 2015) for prospective clinical trials assessing the relationship of prenatal acetaminophen exposure and the development of attention deficit disorders or hyperactivity. STUDY SELECTION AND DATA EXTRACTION: Studies comparing self-reported maternal acetaminophen use during pregnancy to development of ADHD or ADHD-like behaviors in offspring between the ages of 3 and 12 years. DATA SYNTHESIS: Four studies examining the effects of prenatal acetaminophen exposure on subsequent ADHD behaviors were identified. Of these, one early study found no link to ADHD behaviors while the other studies found statistically significant correlations with the most prominent being a study finding a higher risk for using ADHD medications (hazard ratio = 1.29; 95% CI, 1.15-1.44) or having ADHD-like behaviors at age 7 years as determined by the Strengths and Difficulties Questionnaire (risk ratio = 1.13; 95% CI, 1.01-1.27) in children whose mothers used acetaminophen during pregnancy. CONCLUSION: While there does appear to be a mild correlation between prenatal acetaminophen use and the development of ADHD symptoms in children, current data do not provide sufficient evidence that prenatal acetaminophen exposure leads to development of ADHD symptoms late in life. Acetaminophen is a preferred option for pain management during pregnancy when compared with other medications such as nonsteroidal anti-inflammatory drugs or opioids for pyretic or pain relief.

Priapism associated with the use of stimulant medications and atomoxetine for attention-deficit/hyperactivity disorder in children.

OBJECTIVE: To review the association of priapism with stimulant medications and atomoxetine commonly used in the treatment of attention-deficit/hyperactivity disorder (ADHD). DATA SOURCES: A comprehensive literature search was conducted through PubMed (1966-May 15, 2014) using the search terms priapism, methylphenidate, amphetamine, atomoxetine, attention-deficit disorder with hyperactivity, and pediatrics. Google Scholar, Scopus, and the Food and Drug Administration (FDA) Web site were also searched. References from identified literature were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All identified literature focused on ADHD treatment. Literature regarding priapism caused by methylphenidate, amphetamines, and atomoxetine were included. DATA SYNTHESIS: Stimulant medications and atomoxetine have been linked to the occurrence of priapism in children. Specifically, methylphenidate has been implicated in a recent FDA safety announcement warning as a result of 15 case reports (mean age = 12.5 years), and thus, the drug label and medication guides have been updated to reflect this concern. Prolonged erections and priapism occurred with immediate- and long-acting products, dose increases, and drug withdrawal periods. Priapism has also occurred in 4 patients taking amphetamines and one 11-year-old patient taking atomoxetine for ADHD. CONCLUSIONS: Priapism has been associated with stimulants, amphetamines, and atomoxetine use for ADHD in children. Providers and health care practitioners should educate male patients prescribed these ADHD medications as well as caregivers regarding the signs, symptoms, and complications with priapism. Discontinuation and evaluation of the medication is warranted if this adverse drug reaction occurs. Depending on the priapism subtype, other products may be initiated or medications not associated with priapism may be utilized.

Effect of inhaled corticosteroids on long-term growth in pediatric patients with asthma and allergic rhinitis.

OBJECTIVE: To evaluate the effect of orally and nasally inhaled corticosteroids (ICS) on final adult height in pediatric patients with mild to moderate persistent asthma and allergic rhinitis. DATA SOURCES: MEDLINE (1975-April 2013), Cochrane Library (through 2012), and International Pharmaceutical Abstracts (1975-April 2013) were searched for prospective clinical trials assessing the effects of orally or intranasally ICS use on growth in pediatric patients with asthma or allergic rhinitis using the terms inhaled/intranasal corticosteroid, linear growth, height, and asthma or allergic rhinitis. STUDY SELECTION AND DATA EXTRACTION: Eligible articles included double-blind, randomized, placebo-controlled studies of at least 1 year with growth velocity or height as the primary outcome. DATA SYNTHESIS: Seven trials and 1 follow-up study analyzing the effects of orally ICSs were examined. Of these studies, 4 found a delay in growth in at least 1 subset of its participants of approximately 1 cm, 1 study found a decrease in final adult height of 1.2 cm, and 3 studies found no effect. Of the 4 studies examining nasally ICS, 1 found evidence of growth delay in a subgroup using supratherapeutic dosing. There are conflicting data on whether ICS use causes long-term growth reduction in pediatric patients. The concern surrounding their long-term use including a potential delay or decrease in growth may result in underuse and potential mismanagement of persistent asthma and/or allergic rhinitis. Patients should be treated with the lowest effective corticosteroid dose to achieve symptomatic control while minimizing excessive systemic effects. Orally ICS use may cause a delay in growth, but a decrease in final adult height (1.2 cm) has been documented in only one study. This single report should not preclude daily use of inhaled corticosteroids if needed to decrease the morbidity and mortality associated with pediatric reactive airway disease. CONCLUSIONS: Continued studies on the systemic effects of ICS are required before truly understanding the class's effect on growth in pediatric patients with asthma and allergic rhinitis. What is understood, however, is the detriment and potential danger of mismanaged asthma care.

Teratogenic risk of statins in pregnancy.

OBJECTIVE: To evaluate the teratogenic potential of statins in women of child-bearing age. DATA SOURCES: A PubMed search (1980-September 2012) was performed using the search terms statin and pregnancy, then repeated using statin and teratogenicity. Results were limited to articles published in English reporting on use of statins in humans. STUDY SELECTION AND DATA EXTRACTION: All articles presenting data on pregnancy outcomes after statin use during any trimester of pregnancy were included. Three case reports, 2 case series, 2 systematic reviews, 2 registry-based studies, and 1 prospective observational cohort study were reviewed. DATA SYNTHESIS: Since initial premarketing studies of lovastatin in animals, teratogenesis has been assumed to be a classwide function of statins' mechanism of action. Data from human exposure during pregnancy have been gathered and analyzed in a variety of study formats to formulate useable conclusions on statins' actual teratogenic risk and pattern of associated birth defects. Although the current trend is that actual risk is lower than once thought, the available literature is limited by potential reporting bias, contains overlap in the data, and frequently lacks numbers of total exposures to statins during pregnancy with reported malformations. Additionally, no human studies included data on the 2 newest statins (rosuvastatin, pitavastatin); the more lipophilic statins (lovastatin, simvastatin) have the most experience and thus have more evidence related to teratogenic potential. CONCLUSIONS: Human teratogenic risk has not been proven nor has it been ruled out by the available data on statin use in pregnancy. Possible differences in risk between individual statins require further evaluation. Additional data, including prospective observational cohorts with inadvertent maternal exposure to statins during early weeks of gestation, should further help to clarify appropriate recommendations for statin use in this population.

Perceptions of practicing pharmacists in Idaho about a potential behind-the-counter drug program.

BACKGROUND: In late 2007, the Food and Drug Administration (FDA) held public hearings exploring the establishment of a new behind-the-counter (BTC) drug program. However, little is known about the views of pharmacists regarding such a program. OBJECTIVE: To assess the overall perceptions of Idaho's practicing pharmacists about the creation of a formal BTC drug program, the appropriateness of including certain drug categories, specific barriers to its adoption, and the impact of the new program on access to medicines. METHODS: A survey of practicing pharmacists in Idaho was conducted by mail, utilizing anonymous responses. Key questions exploring the views of pharmacists about the new BTC drug program utilized 5-point Likert scales. Data were also collected on respondent characteristics. RESULTS: A total of 357 practicing pharmacists in Idaho (31% response rate) returned the mail survey; 84% of pharmacists agreed that the FDA should be exploring an expanded BTC program, and 88% of pharmacists agreed that this program would improve access to some prescription-only products and convenience for patients. Almost 71% of pharmacists reported a personal willingness to both initiate and monitor certain BTC drug therapies. When focusing on specific drug categories for BTC status, the highest support was for selected agents within smoking cessation therapies (85%), nasal corticosteroids for allergies (81%), and vaccines (75%). Pharmacists who reported low barriers to the adoption of a new BTC program were significantly more likely to support this program than were those reporting high barriers. Only 39% of pharmacists agreed that adequate facilities were currently available for private evaluation and counseling of BTC patients. CONCLUSIONS: Pharmacists in a statewide survey of perceptions regarding a new BTC drug program overwhelmingly believe that patients would benefit. Pharmacists strongly support the development of the new program, and more than two thirds indicate that they would likely participate, given the necessary supporting institutional framework. Perceived barriers are related to willingness to participate and likely can be minimized through education and provision of private consulting areas.

Counter sampling combined with medical provider education: do they alter prescribing behavior?

OBJECTIVE: To observe if medical providers alter their prescribing patterns of three relatively expensive categories of medications provided as samples by manufacturers (focus medications) when they receive additional education from pharmacists concerning the appropriate use of lower cost alternatives (counter samples) that are made available to dispense. DESIGN: Pretest, post-test with a control group. SETTING: Two rural, private care clinics in southeastern Idaho providing immediate care services. PARTICIPANTS: Eight medical providers at a clinic where interventions were employed (active intervention group) and seven medical providers in a clinic where no interventions occurred (control group). INTERVENTIONS: Medical providers in the active intervention group had: 1) education from pharmacists concerning the appropriate use of lower-cost alternatives compared with expensive focus medications 2) counter samples and patient sample handouts available to dispense to patients at their own discretion. MAIN OUTCOME MEASURES: The percentage of the total yearly prescriptions for nonsteroidal anti-inflammatory drugs (NSAIDs), antihistamines, and acid-relief medications that consisted of focus-COX-2 NSAIDs, nonsedating antihistamines, and proton pump inhibitors (PPIs), respectively. RESULTS: The prescribing behavior of medical providers in the active intervention and control groups were significantly different at baseline in all three categories of focus medications. This suggested that the results should focus on changes across the two years of the study within the intervention and control groups rather than across the two groups. Medical providers in the intervention group significantly decreased the use of COX-2 NSAID prescriptions relative to total NSAID prescriptions following active intervention (38.9% in year 1 versus 23.7% in year 2, P < 0.05). Over the same two time periods, a nonstatistically significant decrease in COX-2 NSAID prescribing was seen at the control site (67.5% versus 62%, P > 0.05). Education and counter sampling did not stop medical providers from significantly increasing the total yearly prescriptions for antihistamines and acid-relief medications that consisted of focus-nonsedating antihistamines (86.7% versus 93.1%, P < 0.05) and PPIs (68.9% versus 86.2%, P < 0.05). Statistically significant increases in the prescribing of focus-nonsedating antihistamines (77.9% versus 98.3%, P < 0.05) and PPIs (77.5% versus 91.4%, P < 0.05) were also observed in the control group. CONCLUSIONS: Education by pharmacists, combined with access to counter samples, may or may not have an effect on medical provider prescribing, depending on the category of medication targeted for cost control.

Nitazoxanide treatment for giardiasis and cryptosporidiosis in children.

OBJECTIVE: To review the pharmacology, pharmacokinetics, adverse effects, drug interactions, dosing recommendations, and clinical efficacy of nitazoxanide, a new antiprotozoal/anthelmintic/antibacterial agent. DATA SOURCES: A MEDLINE search (1966-February 2004) of both human and animal research data published in the English language was conducted. STUDY SELECTION AND DATA EXTRACTION: All primary and review articles pertaining to the MEDLINE search were reviewed for inclusion. Emphasis was placed on randomized, double-blind, placebo-controlled trials. DATA SYNTHESIS: Nitazoxanide is approved for the treatment of giardiasis and cryptosporidiosis (first drug approved for the latter indication) in immune-competent children <12 years of age. Most studies in immune-competent patients have reported clinical and parasitologic response rates close to 80% and 70%, respectively, for both indications. Response rates have been lower in immune-compromised patients. CONCLUSIONS: Nitazoxanide should be available for patients unable to tolerate or adhere to first-line therapy employed for these intestinal protozoa.

Conjugated heptavalent pneumococcal vaccine.

OBJECTIVE: To review the immunogenicity, efficacy, and safety of the heptavalent conjugated pneumococcal vaccine (PCV7). DATA SOURCES: A MEDLINE search (1993-August 2001) of research limited to humans published in the English language was conducted. STUDY SELECTION: Findings from randomized, controlled, multicenter trials were reviewed. Literature regarding epidemiology, control, and treatment of invasive pneumococcal diseases in different populations and the Advisory Committee on Immunization Practices recommendations were also reviewed. DATA SYNTHESIS: PCV7 administered to infants aged 2, 4, and 6 months, with a booster dose at 12-15 months, has been shown to be immunogenic. It decreases the incidence of invasive pneumococcal disease; individual data on bacteremia and meningitis are unavailable. Findings from clinical trials showed that invasive pneumococcal disease caused by vaccine serotypes was reduced by 87%, 58%, and 62% for children <1 year, <2 years, and <5 years of age, respectively, after introduction of routine vaccine use. The overall incidence of acute otitis media did not decrease significantly. However, culture-confirmed episodes and episodes due to pneumococcal serotypes included in the vaccine were reduced. The vaccine was immunogenic in children with sickle cell disease, but its efficacy in preventing invasive pneumococcal diseases remains unclear. Although immunogenicity and efficacy trials are lacking, the vaccine is recommended for Alaskan Native or American Indian children between 24 and 59 months of age, and for children with underlying conditions such as HIV infection, AIDS, other immunocompromising conditions, and chronic illnesses. At the manufacturer's list price of 58 dollars/dose, PCV7 is not projected to be cost-effective after 4 doses. Postmarketing analysis evaluating immunogenicity and efficacy in the excluded population may favorably change this. CONCLUSIONS: Based on published efficacy and immunogenicity data, pharmacy formularies should include PCV7.

Veterinarian perception of the intentional misuse of veterinary medications in humans: a preliminary survey of Idaho-licensed practitioners.

The intentional administration of veterinary medications to humans is a form of medication misuse that has not been systematically studied. Veterinarians are the health practitioner group most likely to have knowledge about this problem and to be approached by the public for advice. For this preliminary study, questionnaires were mailed to 1,077 veterinarians registered with the Idaho Board of Veterinary Medicine regarding their knowledge and perceptions of this type of misuse; 392 (36.4%) completed surveys were returned. The most frequently reported veterinary medications misused in humans were analgesic, anti-inflammatory medications, anti-arthritis medications, or both; systemic antibiotics, topical anti-infectives; and topical corticosteroids. People involved with rodeo, horse racing, and health care; rural area residents; and those lacking health insurance were perceived to be the groups most likely to misuse veterinary drugs. Veterinarians rated the following as likely reasons for misuse: having an independent self-sufficient attitude, convenient availability of veterinary medications, lower cost, and belief that veterinary medications are stronger than comparable human medications. Human misuse of veterinary drugs may be more common than many health practitioners realize. Limitations of this study include the response rate, sampling of veterinarians licensed in only one rural state, and reliance on veterinarians' recall of relevant instances of misuse and their perceptions of groups most likely to misuse these drugs and why. These limitations make it difficult to determine if the problem is being under- or over-represented relative to the general population. However, regardless of the magnitude of the problem in the rural population, the general population, or both, the potential for harm is great. Patients with risk factors for this form of misuse should be questioned by their physician in a nonthreatening manner to detect use of veterinary medications and to provide an opportunity to inform them of the risks.