John Erramouspe

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. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-04-014-H01

Treatment and Prevention of Otitis Media

OBJECTIVE: To review and summarize recent advances in the treatment and prevention of otitis media (OM). DATA SOURCES: A MEDLINE search (1996–March 2000) was performed to identify relevant primary and review articles. References from these articles were also reviewed if deemed important. STUDY SELECTION AND DATA EXTRACTION: English-language primary and review articles focusing on the treatment and prevention of acute otitis media (AOM) were included. Studies focusing exclusively on OM with effusion or serous OM and chronic suppurative OM were excluded. Information regarding prevention and drug therapy was reviewed, with an emphasis placed on advances made in the last two years. DATA SYNTHESIS: Recently, an expert panel of the Centers for Disease Control and Prevention recommended use of only three of 16 systemic antibiotics approved by the Food and Drug Administration for treatment of AOM: amoxicillin, cefuroxime axetil, and ceftriaxone. Controversy exists over the importance of key selection factors used by the expert panel in determining which antibiotics to recommend in a two-step treatment algorithm, that is, in vitro data, pharmacodynamic profiles, and necessity for coverage of drug-resistant Streptococcus pneumoniaeat all steps of empiric treatment. Additional antibiotic and patient selection factors useful for individualizing therapy include clinical efficacy, adverse effects, frequency and duration of administration, taste, cost, comorbid infections, and ramifications should bacterial resistance develop to the chosen antibiotic. Presumed or past patient/caregiver adherence (especially when antibiotic failure has occurred) is also paramount in selecting antibiotic therapy. A three-step treatment algorithm for refractory AOM that employs amoxicillin, trimethoprim/sulfamethoxazole (TMP/SMX), or high-dose amoxicillin/ clavulanate (depending on the prior dose of and adherence to amoxicillin therapy), and ceftriaxone or tympanocentesis at steps 1, 2, and 3, respectively, appears rational and cost-effective. The recent upsurge in antimicrobial resistance is highlighted, and recommendations are presented for the treatment of AOM and prevention of recurrent otitis media (rAOM). CONCLUSIONS: Amoxicillin remains the antibiotic of choice for initial empiric treatment of AOM, although the traditional dosage should be increased in patients at risk for drug-resistant S. pneumoniae. In cases refractory to high-dose amoxicillin, TMP/SMX should be prescribed if adherence to prior therapy seemed good or complete, or high-dose amoxicillin/clavulanate if adherence was incomplete or questionable. Ceftriaxone should be reserved as third-line treatment. The increasing prevalence of drug-resistant S. pneumoniaeemphasizes the importance of alternative medical approaches for the prevention of OM, as well as judicious antibiotic use in established cases. Removal of modifiable risk factors should be first-line therapy for prevention of rAOM. We support the use of conjugate pneumococcal vaccine per guidelines for prevention of rAOM from the Advisory Committee on Immunization Practice of the Centers for Disease Control and Prevention, with consideration given to influenza vaccine for cases of rAOM that historically worsen during the flu season. Sulfisoxazole prophylaxis should be reserved for children who are immunocompromised, have concurrent disease states exacerbated by AOM, or meet the criteria of rAOM despite conjugate pneumococcal and influenza vaccination. Therapy should be intermittent, beginning at the first sign of an upper respiratory infection, and should continue for 10 days. The invasive nature and risks of anesthesia relegate myringotomy, tympanostomy tubes, and adenoidectomy to last-line therapies for rAOM.

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 manufacturers list price of

Extrapyramidal Symptoms following Accidental Ingestion of Risperidone in a Child

58/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.

Newborn Renal Tubular Acidosis Associated with Prenatal Maternal Toluene Sniffing

OBJECTIVE: To describe the development of extrapyramidal symptoms (EPS) precipitated by an accidental overdose of risperidone in a 3.5-year-old boy. CASE SUMMARY: The boy presented to the emergency department with bilateral upward eye gaze, jerky movements of his extremities, and motor restlessness following an accidental ingestion of a single 4-mg risperidone tablet. Decontamination with NaCl 0.9% lavage and activated charcoal with sorbitol was performed. His symptoms responded immediately to intravenous diphenhydramine (on 3 different occasions) during his first 9.5 hours of hospitalization. He experienced no additional EPS, and was discharged home approximately 33 hours following initial presentation. At home, he received three oral doses of diphenhydramine in the 24 hours following hospital discharge because of hand tremor, total body shivering, and eye wandering. These signs resolved without further complications. DISCUSSION: Although the incidence of EPS associated with therapeutic risperidone use is low, its occurrence following overdose is less clearly defined. This represents the first published case, to our knowledge, of risperidone overdose in a child and highlights the potential for dystonic reactions at low doses in this population. Seven intentional overdoses of risperidone in adults (aged 21–68 y) have been reported in the literature and are reviewed. Amounts ingested ranged from 5 to 270 mg. All adult patients appeared to have a relatively benign course. Reported symptoms included drowsiness, slurred speech, altered levels of consciousness, hypertension, tachycardia, electrocardiogram abnormalities, atypical motor behavior, tremors, and other EPS (not specified). CONCLUSIONS: Accidental ingestion of low doses of risperidone can cause EPS in children that may respond well to an anticholinergic agent. Overdose management includes gastrointestinal lavage, activated charcoal with cathartic, cardiovascular monitoring, and supportive therapy.

Impact of Education by Clinical Pharmacists on Physician Ambulatory Care Prescribing of Generic versus Brand-Name Drugs

Sniffing of volatile organic solvents containing toluene, such as acrylic paints, glues, adhesives, paint thinners, varnishes and shoe polishes, has become increasingly frequent in recent years. Renal tubular acidosis is one of a number of human complications reported in the offspring of mothers inhaling toluene during pregnancy. This article reports a case of a premature newborn with renal tubular acidosis probably due to maternal sniffing of paint containing toluene. Characteristics of this condition are described as well as its medical management. With increasing frequency of maternal glue and paint sniffing, more cases of newborn renal tubular acidosis will likely appear. Physicians should be prepared to manage neonatal tubular acidosis that may accompany maternal toluene sniffing in order to lessen newborn morbidity and/or mortality.

Priapism Associated With the Use of Stimulant Medications and Atomoxetine for Attention-Deficit/Hyperactivity Disorder in Children

The physician prescribing of generic versus brand-name drugs to ambulatory care patients was compared between the time periods before and after rendering clinical pharmacist education. Copies of all written outpatient prescriptions were used for the comparison. Physicians significantly increased their generic prescribing after clinical pharmacist education.

Effect on Dissolution from Halving Methylphenidate Extended-Release Tablets

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.

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

OBJECTIVE: To determine the effect on in vitro dissolution from cutting methylphenidate extended-release tablets in half. DESIGN: Ritalin-SR (Ciba Pharmaceutical Co.) and generic methylphenidate extended-release (MD Pharmaceutical Inc.) tablets were dissolved in water according to the method prescribed by the US Pharmacopeia under two conditions: whole and halved. Samples were collected at 15, 30, and 45 minutes and at 1, 2, 3, 3.5, 4, 5, 6, and 7 hours. Methylphenidate content was determined by HPLC. RESULTS: Halving the tablets caused a statistically significant increase in cumulative dissolution as early as 15 minutes. The difference in cumulative dissolution reached its maximum for both Ritalin-SR and generic methylphenidate extended-release tablets at 2 hours. At this time point, the percent dissolution of the whole versus halved tablets was 57% versus 74% (Ritalin-SR), respectively, and 49% versus 67% (generic), respectively. The dissolution profiles of halved and whole extended-release methylphenidate tablets were parallel from this point through the 7-hour collection period. At 7 hours, however, there was no difference in the cumulative dissolution of halved versus whole tablets. CONCLUSIONS: While statistical differences during in vitro dissolution do exist and pharmacokinetic ramifications have not yet been determined, the absolute differences in dissolution between halved and whole tablets are not great. Halving methylphenidate extended-release tablets may be a clinically acceptable means of achieving a small increment/decrement in dose without converting to a regular-release tablet.

Intramuscular ceftriaxone in the treatment of childhood meningitis due to Haemophilus influenzae type F.

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.