Rhabdomyolysis triggered by azithromycin.

A 17-year-old male with uneventful previous history developed generalized myalgias, exercise intolerance, and general fatigue after two dosages of azithromycin (500 mg/d) during 3 d for febrile infection. Neurologic exam revealed generally reduced tendon reflexes. Serum creatine kinase (CK) was elevated to 25000 U/L. Needle-EMG showed short and small, polyphasic motor-units and abnormal spontaneous activity, being interpreted as myositis. Azithromycin was discontinued and he was advised to avoid the fitness studio and to drink plenty of liquids. Myalgias disappeared within two days and CK continuously declined. Azithromycin may trigger rhabdomyolysis in the context of exercise and infection. Azithromycin may be myotoxic and should be prescribed with caution in exercising and infected patients.

Left ventricular hypertrabeculation/noncompaction, cardiac phenotype, and neuromuscular disorders.

BACKGROUND: The prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT) and its association with neuromuscular disorders (NMDs) is a controversial topic. The aim of this study was to assess whether the prognosis of LVHT patients is dependent on cardiac phenotype and the presence of NMDs. METHODS: Consecutive patients who were diagnosed with LVHT between 1995 and 2016 were included in the study. Cardiac phenotype was classified according to the recommendations of the European Society of Cardiology as: "dilated" if the left ventricular end-diastolic diameter (LVEDD) was >57 mm and left ventricular fractional shortening (FS) was ≤25%; "hypertrophic" if LVEDD was ≤57 mm, FS > 25%, and left ventricular posterior wall (LVPWT) and interventricular septal thickness (IVST) were both >13 mm; "intermediate" if LVEDD was >57 mm and FS > 25% or if LVEDD was ≤57 mm and FS ≤ 25%; and "normal" if LVEDD was ≤57 mm, FS > 25%, and IVST and LVPWT ≤ 13 mm. Therapy was carried out by the treating physicians. RESULTS: LVHT was diagnosed in 273 patients (80 females, 53 ± 16 years). The phenotype was assessed as dilated in 46%, hypertrophic in 8%, intermediate in 17%, and normal in 29% of the patients. Of these patients, 72% underwent neurological examinations, and an NMD was found in 76%. Over a period of 7.4 years (±5.7), 84 patients died and six underwent cardiac transplantation. The highest mortality rate was observed in the dilated and the lowest in the hypertrophic cardiac phenotype groups. Among the dilated phenotype, mortality was higher in patients with than without NMDs. CONCLUSION: Patients with LVHT and dilated cardiac phenotype have a worse prognosis than patients with a hypertrophic or intermediate/normal cardiac phenotype, especially if they suffer from NMDs.

Relevance of P-glycoprotein in stroke prevention with dabigatran, rivaroxaban, and apixaban.

BACKGROUND: The new oral anticoagulants (NOAC) dabigatran etexilate, rivaroxaban, and apixaban show similar efficacy for stroke prevention in patients with atrial fibrillation (AF) as the vitamin K antagonist warfarin. Absorption of NOACs is dependent on the intestinal P-glycoprotein (P-gp) system and P-gp activity is modulated by a variety of drugs and food components. OBJECTIVE: The aim of this review is to give an overview of P-gp-associated drug-drug and drug-food interactions with NOACs in AF patients. METHODS: A literature search was carried out by screening MEDLINE for the terms dabigatran, rivaroxaban, apixaban, P-glycoprotein, and atrial fibrillation from 1998 to 2013. Randomized clinical trials, longitudinal studies, case series, and case reports were included. RESULTS: Concomitant medication with proton pump inhibitors, amiodarone, clarithromycin, and verapamil increased bioavailability whereas rifampicin decreased the bioavailability of dabigatran. Coadministration of erythromycin, clarithromycin, fluconazole, ketoconazole, and ritonavir increased rivaroxaban plasma concentrations. No data were found on apixaban and P-gp-modulating drugs or on NOACs and food components modulating P-gp. The clinical relevance of interactions between NOACs and P-gp-modulating drugs or food components is largely unknown as bleeding complications under NOACs and P-gp-inhibiting drugs are mainly reported from patients with concomitant renal failure. CONCLUSION: There is an urgent need to investigate the role of P-gp-modulating substances as potential sources of drug-drug and drug-food interactions. A thorough analysis of the data accumulated in the three large NOAC trials regarding the role of P-gp-modulating drugs in bleeding and embolic events is desirable. Pharmacological studies should investigate the influence of P-gp-modulating drugs and food on NOAC plasma concentrations and coagulation parameters. When prescribing NOACs, patients should be informed about the potential interactions with drugs and herbal drugs. Patients who develop bleeding or embolic events under treatment with NOACs should be investigated for co-medications as well as for over-the-counter drugs and dietary habits. In post-marketing surveillance of NOACs, the association with drug or food intake with complications, bleeding, and embolic events should be registered.

Gastrointestinal bleeding under dabigatran.

Dabigatran-absorption is dependent on the intestinal P-glycoprotein (P-gp)-system, and P-gp activity is modulated by several drugs. We report an 83-old female with atrial fibrillation who developed gastrointestinal bleeding. She was under a therapy with non-steroidal anti-inflammatory drugs (NSAID) and P-gp-modulating drugs and renal function was impaired. We conclude that NSAID and P-gp-modulating drugs should be avoided in dabigatran-treated patients. If renal function deteriorates the dabigatran-dosage should be reduced or the therapy should be stopped. There is an urgent need to increase knowledge about drug interactions with dabigatran.

Beneficial effect of ivabradine in dilated cardiomyopathy from Becker muscular dystrophy.

OBJECTIVES: The I(f) blocker ivabradine reduces heart rate and improves systolic function without causing arterial hypotension. Ivabradine has not been reported to improve cardiac involvement in Becker muscular dystrophy (BMD). CASE REPORT: In a 22-year-old Vietnamese male with BMD, cardiac involvement became apparent at age 19 years with reduced systolic function, which was treated with ramipril. At the age of 20 years, he developed sinus tachycardia, leg edema, coughing, and arterial hypotension. Dilated cardiomyopathy was diagnosed and ramipril was successfully replaced by candesartan, ivabradine, and furosemide. An attempt to discontinue ivabradine and increase candesartan was followed by recurrence of sinus tachycardia and reduction of blood pressure. Under ivabradine, candesartan, and spironolactone, which replaced furosemide, he achieved heart rates between 60 and 80 beats/min and systolic blood pressure values between 85 and 105 mmHg without heart failure. CONCLUSION: Ivabradine normalizes sinus tachycardia and resolves heart failure in patients with dilated cardiomyopathy from BMD. In addition to normalization of the heart rate and remodeling of the left ventricle, ivabradine seems to also have a positive inotropic effect in dilated cardiomyopathy of BMD patients.