Everolimus (Afinitor – Novartis) and pazopanib (Votrient – GlaxoSmithKline), two oral multikinase inhibitors, have been approved by the FDA for treatment of advanced renal cell carcinoma. Sunitinib (Sutent) and sorafenib (Nexavar), two other oral multikinase inhibitors, and temsirolimus (Torisel), an IV multikinase inhibitor, were approved earlier for the same indication.

The drugs of choice for treatment of some fungal infections are listed. Some of the indications and dosages recommended here have not been approved by the FDA. More detailed guidelines are available online from the Infectious Diseases Society of America (www.idsociety.org).

The FDA has approved the use of aliskiren (Tekturna), a direct renin inhibitor, with valsartan (Diovan), an angiotensin-receptor blocker (ARB), in a fixed-dose combination as Valturna (Novartis) for treatment of hypertension in patients already taking both drugs or not adequately controlled on monotherapy, and as initial therapy in those likely to need multiple drugs to control their blood pressure.

Silodosin (Rapaflo - Watson Pharmaceuticals), an alpha1a-adrenoreceptor selective antagonist, has been approved by the FDA for treatment of benign prostatic hyperplasia (BPH). Some medications for BPH are listed in the table on page 4. Alpha1 blockers are commonly used with 5a-reductase inhibitors such as finasteride, which can shrink the size of the prostate, but may take months to do so.

A recent letter to the editor of the Annals of Internal Medicine documented a single case of myopathy apparently due to an interaction between simvastatin (Zocor, and others) and green tea. Since it became available generically, simvastatin has surpassed atorvastatin (Lipitor) as the best selling statin. As such, it is probably the most common cause of statin-induced myopathy, which is often a result of drug interactions.

Aliskiren (Tekturna - Novartis), the first direct renin inhibitor for treatment of hypertension, has been approved for use in a fixed-dose combination with the diuretic hydrochlorothiazide (Tekturna HCT - Novartis). Many angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are also available in fixed-dose combinations with hydrochlorothiazide (HCTZ).

Nilotinib (Tasigna - Novartis), a tyrosine kinase inhibitor, has been approved by the FDA for treatment of Philadelphia chromosome-positive (Ph+) chronic or accelerated phase chronic myelogenous leukemia (CML) in patients resistant to or intolerant of imatinib (Gleevec).

The ability of grapefruit juice to increase serum concentrations of drugs was first discovered during a study of the effect of ethanol on felodipine (Plendil) pharmacokinetics. Double-strength grapefruit juice used to disguise the taste of ethanol resulted in higher than expected serum concentrations of felodipine (DG Bailey et al, Clin Invest Med 1989; 12:357).

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.