Itraconazole (Sporanox - Janssen), an antifungal triazole, has been approved by the US Food and Drug Administration (FDA) for oral treatment of histoplasmosis and blastomycosis. These two endemic mycoses occur both in normal hosts and in immunocompromised patients, such as those with AIDS (RW Bradsher, Clin Infect Dis, 14:S82, 1992; LJ Wheat, Clin Infect Dis, 14:S91, 1992).

Carvedilol (Coreg - SmithKline Beecham and Boehringer-Mannheim), a betaadrenergic and alpha-adrenergic blocker approved by the FDA for treatment of hypertension in 1995, but not marketed at that time, has now been approved and marketed for treatment of mild or moderate (NYHA class II or III) heart failure stabilized on other drugs. It is being promoted as an add-on drug that reduces the morbidity and mortality of the disease.

Rofecoxib, a selective COX-2 inhibitor, has been approved by the FDA for treatment of osteoarthritis, acute pain and menstrual pain.

Serious adverse interactions between drugs continue to be reported. Many of these are due to inhibition or induction of cytochrome P450 (CYP) enzymes, particularly CYP3A4. CYP3A is thought to be involved in the metabolism of more than 50 percent of currently prescribed drugs.2 CYP3A4, which is more abundantly expressed than CYP3A5, accounts for most CYP3A activity in vivo.

The FDA has approved the marketing of tolvaptan (Samsca - Otsuka), an oral vasopressin receptor antagonist, for treatment of hypervolemic or euvolemic hyponatremia due to congestive heart failure (CHF), cirrhosis or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). A similar drug, conivaptan (Vaprisol) is already available for intravenous (IV) treatment of euvolemic hyponatremia in hospitalized patients. Tolvaptan was approved by the FDA for both inpatient and outpatient use, but it should be started in a hospital.

Leflunomide (Arava - Hoechst Marion Roussel), which inhibits pyrimidine synthesis, and etanercept (Enbrel - Immunex/Wyeth-Ayerst), which blocks the action of tumor necrosis factor (TNF), have been approved by the FDA for treatment of rheumatoid arthritis. A third drug, infliximab (Remicade - Centocor), which also blocks TNF and has been used to treat rheumatoid arthritis, was approved earlier for treatment of Crohn's disease. Its use in Crohn's disease will be reviewed in a future issue.

Amprenavir is the fifth protease inhibitor to become available for treatment of HIV infection. It was approved by the FDA for use with other drugs in the treatment of HIV-infected adults and children at least four years old.

Regorafenib (Stivarga – Bayer), a multikinase inhibitor, has been approved by the FDA for treatment of patients with metastatic colorectal cancer previously treated with multiple other regimens specified in the labeling. It has also been approved for use in treatment-refractory, locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST).

A fixed-dose combination of atovaquone and proguanil hydrochloride has been approved by the FDA for oral prophylaxis and treatment of malaria due to Plasmodium falciparum, including choloroquine-resistant strains.

Erlotinib (Tarceva) is the second oral epidermal growth factor receptor (EGFR) inhibitor to become available in the US for treatment of advanced refractory NSCLC. In clinical trials, erlotinib produced a response rate of only 8.9%, but increased median survival from 4.7 to 6.7 months. Patients who had never smoked and those with EGFR-positive tumors survived longer. Erlotinib is generally well tolerated; diarrhea and rash are the most common adverse effects.