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Journal: The Annals of pharmacotherapy


OBJECTIVE:To present a series of cases demonstrating successful reversal of mifepristone effects in women who chose to reverse the medical abortion process.CASE REPORTS:Four of 6 women who took mifepristone were able to carry their pregnancies to term after receiving intramuscular progesterone 200 mg.DISCUSSION:Mifepristone has been available in the US since 2000. By 2008, approximately 25% of abortions prior to 9 weeks were accomplished with mifepristone. Some women who take mifepristone wish to reverse the medical abortion process. Progesterone competes with mifepristone for the progesterone receptor and may reverse the effects of mifepristone. A PubMed literature search from 1996 to May 2012 did not reveal any trials or case studies evaluating the efficacy of progesterone use to reverse the effects of mifepristone.CONCLUSIONS:Health care professionals should be aware of the possible use of progesterone to reverse mifepristone in women who have begun the medical abortion process by taking mifepristone and then change their minds.

Concepts: Pregnancy, Fetus, Obstetrics, Fertility, Abortion, Progesterone, Abortifacient, Medical abortion


OBJECTIVE:To report a case of accidental amphotericin B overdose that was treated with plasmapheresis.CASE SUMMARY:A 60-year-old woman with a history of kidney transplant 4 years prior to presentation for a congenital abnormality was admitted for a suspected systemic fungal infection. The patient inadvertently received intravenous amphotericin B deoxycholate 250 mg (4.3 mg/kg) over 2 hours instead of prescribed liposomal amphotericin B. The medication error was discovered 16 hours after administration. She had normal vital signs at that time and reported abdominal pain and general malaise. Results of a metabolic panel were significant for a creatinine level of 2.1 mg/dL and CO(2) of 17 mg/dL. Her serum amphotericin B concentration 33 hours after the initial dose was 4.9 μg/mL. She subsequently received 5 courses of plasmapheresis and 3 courses of hemodialysis and ultimately did not develop any further renal injury, as well as hemolysis, cardiovascular collapse, dysrhythmias, or severe electrolyte abnormalities.DISCUSSION:The dosing differences between nonliposomal and liposomal preparations of amphotericin B can be as high as 50-fold. Reported adverse events from overdose in both animal models and human case reports include renal insufficiency, hemolysis, thrombocytopenia, electrolyte abnormality, and cardiac dysrhythmias. There have been previous reports of similar errors that have led to death. Furthermore, amphotericin B has been shown to be poorly dialyzable. Our patient’s serum amphotericin B concentration decreased after she received plasmapheresis, and she did not develop severe complications.CONCLUSIONS:We describe a patient who survived a 4-fold overdose of amphotericin because of a medication error. The use of plasmapheresis may have enhanced the elimination of amphotericin and may have contributed to the positive outcome. However, the role of plasmapheresis in amphotericin overdose is not fully understood.

Concepts: Chronic kidney disease, Kidney, Nephrology, Dialysis, Report, Vital signs, Amphotericin B, Thrombocytopenia


OBJECTIVE:To evaluate the efficacy of bioidentical progesterone cream in the treatment of menopause-related vasomotor symptoms.DATA SOURCES:A systematic search (from time of inception to September 2012) of PubMed, EMBASE, International Pharmaceutical Abstracts, International Journal of Pharmaceutical Compounding, Cochrane, and CINAHL was conducted using the terms progesterone, vasomotor symptoms, night sweats, hot flash or flush, and randomized controlled trials (RCTs). Hand-searching of citations from relevant articles was also performed.STUDY SELECTION AND DATA EXTRACTION:Articles selected for inclusion described RCTs evaluating the use of bioidentical progesterone cream for the treatment of menopause-related vasomotor symptoms. Studies included were placebo controlled and participants were postmenopausal women experiencing vasomotor symptoms.DATA SYNTHESIS:Searching identified 3 published RCTs. Only one study, which used a bioidentical progesterone cream specifically compounded for the trial, found that the bioidentical progesterone was more effective than placebo in relieving menopause-related vasomotor symptoms. The 2 studies using manufactured bioidentical progesterone creams found that the creams were no more effective than placebo. Vaginal bleeding and headaches were the most commonly reported adverse effects in the studies.CONCLUSIONS:Available evidence from RCTs does not support the efficacy of bioidentical progesterone cream for the management of menopause-related vasomotor symptoms. Adverse effects appear to be mild and self-limiting.

Concepts: Pharmacology, Hormone replacement therapy, Clinical trial, Randomized controlled trial, Effectiveness, Menopause, Efficacy, Bioidentical hormone replacement therapy


To determine whether thiazides have a chronic antihypertensive effect, in the absence of diuresis, in patients with severe renal disease (creatinine clearance <30 mL/min) or in those receiving dialysis.

Concepts: Renal failure, Nephrology, Thiazide


To review the available evidence regarding dosing conversion between glargine and detemir in an effort to assist clinicians in performing dosing conversion.

Concepts: Insulin therapies, Insulin pump


OBJECTIVE:To review the place in therapy of mirabegron, a new oral β3-adrenergic receptor agonist, for the treatment of overactive bladder (OAB).DATA SOURCES:A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-April 2013) was conducted using the key words mirabegron, receptor, adrenergic, beta-3; adrenergic beta-3 receptor; beta-3 receptor, and overactive bladder; urinary bladder; overactive. All published articles regarding mirabegron were included. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed.STUDY SELECTION AND DATA EXTRACTION:Available English-language data from reviews, abstracts, presentations, and clinical trials of mirabegron in humans were reviewed; relevant clinical data were selected and included.DATA SYNTHESIS:Mirabegron is the newest option for treatment of OAB with symptoms of urge incontinence. As a β3-receptor agonist, it reduces bladder muscle contractions. In two 12-week, randomized, double-blind, placebo-controlled Phase 3 studies, mirabegron significantly reduced the number of incontinence episodes per 24 hours from baseline (-1.47, -1.63, and -1.13; p < 0.05; and -1.57, -1.46, and -1.17; p < 0.05; all values for mirabegron 50 mg, 100 mg, and placebo). Micturitions per 24 hours were also reduced from baseline (-1.66, -1.75, and -1.05; p < 0.05; and -1.93, -1.77, and -1.34; p < 0.05; all values for mirabegron 50 mg, 100 mg, and placebo). A 12-month trial found mirabegron to have a safety and efficacy profile similar to that of tolterodine.CONCLUSIONS:Treatment of OAB initially includes lifestyle and nonpharmacologic intervention; for patients with persistent symptoms despite these treatments, drug therapy represents a next-step approach for symptom control. Mirabegron alleviates symptoms of OAB while having a mechanism of action that provides an alternative for patients who are intolerant of or who have contraindications to anticholinergic agents. The place in therapy of mirabegron relative to anticholinergics in the treatment of urge incontinence has not yet been established.

Concepts: Pharmacology, Clinical trial, Medical terms, Urinary incontinence, Symptoms, Urinary bladder, Urinary system, Adrenergic receptor


OBJECTIVE:To review clinical data on the use of the long-acting anticholinergic agent tiotropium in patients with asthma.DATA SOURCES:A literature search was performed via EMBASE and MEDLINE (1966-November 2012). The search was limited to human data published in the English language. Search terms included asthma, tiotropium, and long-acting anticholinergics.STUDY SELECTION AND DATA EXTRACTION:Relevant information related to the use of tiotropium in patients with asthma was reviewed. Randomized controlled trials and open-label trials were included. The references of published articles identified in the search were also examined for additional studies appropriate to include in the review. Data were prioritized if they originated from human studies, especially if derived from randomized, placebo-controlled trials. Trials and case reports involving the use of long-acting anticholinergic tiotropium in asthma patients were included; conversely, trials involving ipratropium were not.DATA SYNTHESIS:Two large randomized controlled trials support the safety and efficacy of adding tiotropium to the treatment regimen of select patients with poorly controlled asthma already receiving combination high-dose glucocorticosteroid/long-acting β-agonist (LABA) therapy. Pharmacogenomic studies have shown that patients with polymorphisms of the β2-adrenoreceptor (ADRB2; 16 Arg/Arg and 16 Arg/Gly) are particularly responsive to treatment with tiotropium. Smaller studies indicate that the advantages may be most pronounced in patients with a predominance of sputum neutrophils and that tiotropium can assist with decreasing the inhaled corticosteroid (ICS) dose. An increased risk of cardiovascular events was not identified.CONCLUSIONS:Tiotropium should be considered in patients with asthma who remain symptomatic while receiving high-dose ICS and LABA therapy. Specifically, patients with high sputum neutrophil levels or with 16 Arg/Arg or 16 Arg/Gly polymorphism of the ADRB2 gene appear to respond best.

Concepts: Pharmacology, Asthma, Randomized controlled trial, Chronic obstructive pulmonary disease, Corticosteroid, Tiotropium, Anticholinergic, Clinical data acquisition


To assess the literature that evaluates how variations in metered-dose inhaler (MDI) technique affect lung distribution for inhaled corticosteroids (ICSs) formulated as MDI suspensions and solutions.

Concepts: Asthma, Metered-dose inhaler, Dosage forms, Inhaler


OBJECTIVE:To present a case of nebulized tissue plasminogen activator (t-PA) treatment for symptomatic plastic bronchitis in a pediatric patient years after a Fontan procedure.CASE SUMMARY:A 13-year-old boy with a history of corrected congenital heart disease was admitted to the pediatric intensive care unit after 2 weeks of worsening respiratory distress. A chest radiograph and subsequent bronchoscopy revealed extensive mucus plugging due to plastic bronchitis. Casts reaccumulated quickly after manual removal of the mucus and a regimen of aerosolized t-PA was initiated to break down the casts and prevent further cast formation over the 17-day hospital course. The treatment was successful and the patient was discharged home without evidence of bronchial casts.DISCUSSION:Plastic bronchitis is a potentially devastating condition in which pulmonary infiltrates line the bronchial tree, forming casts and prohibiting effective oxygen exchange. There are few effective treatment options for this condition. The use of aerosolized t-PA for the treatment of plastic bronchitis has been reported to be safe and effective in 4 cases but no consistent regimen, dose, or duration of treatment has been established.CONCLUSIONS:t-PA can be nebulized and inhaled for successful inhibition of bronchial cast formation. More information to determine the most effective dose and duration of therapy is needed to effectively improve the lives of people with plastic bronchitis.

Concepts: Asthma, Lung, Heart, Respiratory system, Mucus, Tissue plasminogen activator, Plasmin


BACKGROUND:The introduction of the health care-associated pneumonia (HCAP) categorization expanded recommendations for broad-spectrum empiric antibiotics to pneumonia patients presenting from the community with recent health care-system exposure. However, the efficacy of such regimens in improving clinical outcomes in these patients has not been well established.OBJECTIVE:To compare the clinical outcomes of HCAP patients treated initially with HCAP guideline-concordant antibiotic regimens to those treated initially with community-acquired pneumonia (CAP) guideline-concordant antibiotic regimens.METHODS:This retrospective study included HCAP patients presenting from home and admitted to general medical wards. HCAP regimen patients were treated empirically with at least 1 antipseudomonal agent. All other patients were assigned to the CAP regimen group. The primary end point was clinical cure at 30 days postdischarge. Subgroup analysis was performed in patients hospitalized 1-30 days and 31-90 days before the HCAP admission.RESULTS:Of 228 HCAP admissions, 122 patients received CAP regimens and 106 received HCAP regimens. The 2 groups were similar at baseline, including Pneumonia Severity Index scores. Attributable clinical cure occurred in 75.4% of CAP regimen patients and 69.8% of HCAP regimen patients (p = 0.34). Overall clinical cure occurred in 59.8% of CAP regimen patients and 54.7% of HCAP regimen patients (p = 0.44). The CAP regimen group used fewer days of intravenous antibiotics (4.39 vs 7.75, p < 0.0001) and had shorter lengths of stay (6.36 vs 8.58 days, p < 0.0001). For patients hospitalized 31-90 days earlier, clinical cure was higher in the CAP regimen group (attributable, 82.9% vs 60.0%, p = 0.0090; overall, 67.1% vs 47.5%, p = 0.044).CONCLUSIONS:Compared to CAP guideline-concordant regimens, treatment of HCAP with HCAP guideline-concordant regimens did not increase clinical cure rates and was associated with lower clinical cure rates in patients hospitalized 31-90 days prior to the HCAP admission. This study suggests that broad-spectrum empiric antibiotics may not be necessary in all HCAP patient groups.

Concepts: Medicine, Bacteria, Pneumonia, Hospital, Antibiotic, Empiric therapy, Antibiotics, Healthcare-associated pneumonia