Rx Update: February 2004
Joan Murhammer, R.Ph., Mary Ross, R.Ph., M.B.A., Kevin Bebout,
R.Ph.
Peer Review Status: Internally Reviewed
Eplerenone
Eplerenone (Inspra®) is an aldosterone receptor antagonist similar to spironolactone. It is indicated for the treatment of hypertension and to decrease mortality in patients with congestive heart failure after an acute myocardial infarction. Eplerenone acts as a potassium-sparing diuretic and is more selective than spironolactone for the aldosterone receptor.
Hyperkalemia is the principle risk with eplerenone. This risk can be minimized by patient selection, avoidance of certain concomitant treatments, and monitoring. Eplerenone is contraindicated in patients with baseline serum potassium >5.5 mEq/l, in patients with creatinine clearance <30 ml/minute, and in patients taking concomitant potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, nefazodone, clarithromycin, ritonavir, and nelfinavir). It is additionally contraindicated for the treatment of hypertension in patients with type 2 diabetes with microalbuminuria, serum creatinine >2.0 mg/dl in males or >1.8 mg/dl in females, creatinine clearance <50 ml/minute, and in patients taking concomitant potassium supplements or potassium-sparing diuretics (e.g., amiloride, spironolactone, or triamterene).
The most common adverse events with eplerenone therapy are dizziness, increase serum creatinine, fatigue, influenza-like symptoms, coughing, diarrhea, hypercholesteremia, hypertriglyceridemia, abdominal pain, and albuminuria.
The recommended starting dose of eplerenone for hypertension is 50 mg orally once daily. For patients with inadequate blood pressure response after 4 weeks, the dose can be increased to 50 mg twice daily. The initial dose should be 25 mg in patients who are concurrently taking weak CYP3A4 inhibitors (e.g., erythromycin, verapamil, or fluconazole). The recommended starting dose of eplerenone for congestive heart failure is 25 mg orally once daily. The dose should be titrated up to a target dose of 50 mg once daily, preferably within 4 weeks, as tolerated by the patient. Serum potassium should be measured at baseline, within the first week, and at one month after the start of treatment or a dose adjustment. The dose may need to be adjusted depending on potassium levels. Eplerenone can be administered with or without food.
Eplerenone is available in 25 mg and 50 mg tablets.
Daptomycin
Daptomycin (Cubicin®) is in a new class of antibiotics (cyclic lipopeptide) with activity limited to gram-positive organisms. It is indicated for the treatment of complicated skin and soft tissue infections. Daptomycin has a spectrum of activity similar to that of vancomycin, and includes methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, and penicillin-resistant Streptococcus pneumoniae. Additionally, it is similar in spectrum to linezolid (Zyvox®) and quinupristin/dalfopristin (Synercid®), with activity against vancomycin-resistant S. aureus and vancomycin-resistant Enterococcus faecium.
Reversible musculoskeletal toxicity has been reported with daptomycin therapy. Patients should be monitored for signs and symptoms of muscle pain or weakness, and creatinine phosphokinase (CPK) levels should be monitored weekly during daptomycin therapy. Daptomycin should be discontinued in patients with symptoms of muscle toxicity and elevation in CPK levels. If possible, it should not be used concurrently with other drugs that can also cause rhabdomyolysis (e.g., HMG-CoA reductase inhibitors like atorvastatin). Additional adverse reactions reported with daptomycin include constipation, nausea, diarrhea, headache, insomnia, and injection site reactions. It has rarely been reported to cause paresthesias.
The recommended dose of daptomycin is 4 mg/Kg intravenously once daily for 7 to 14 days. The interval should be extended to every 48 hours for patients with renal dysfunction (CrCl <30 ml/minute), including dialysis. The dose is diluted in 50 ml of 0.9% NaCl and infused over 30 minutes. The drug is not compatible with dextrose-containing solutions.
Daptomycin is available at UIHC as a protocol antibiotic with its use restricted to approval by the Infectious Diseases Service.