Many readers have asked the Medical Letter to evaluate St. John's wort, an herbal extract now widely sold in health food stores and pharmacies, for its effectiveness and safety in the treatment of depression. St. John's wort is licensed in Germany for treatment of anxiety, depression and insomnia. In the USA, it is considered a dietary supplement and has not been evaluated by the FDA.

Even though its effectiveness has not been established, many patients take St. John's Wort (Hypericum perforatum), an over-the-counter herbal extract, to treat symptoms of depression, often without the knowledge of their physicians. Recent reports indicate that St. John's wort interacts adversely with a number of drugs.

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.

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.

Tipranavir (Aptivus - Boehringer Ingelheim), a new protease inhibitor, has received accelerated approval from the FDA. It must be given with ritonavir (Norvir). The combination is indicated for use with other antiretrovirals to treat HIV infection in highly treatment-experienced adults who have ongoing viral replication or in those with HIV strains known to be resistant to multiple protease inhibitors.

Five different selective serotonin reuptake inhibitors (SSRIs) are promoted for treatment of depression and a sixth (fluvoxamine) for use in obsessive compulsive disorder. Which one should we prescribe for our patients?

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.

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.

Mifepristone (RU 486; Mifeprex - Danco), an antiprogestin, has been approved by the FDA for termination of intrauterine pregnancies of 49 days or less. It is generally used with misoprostol (Cytotec - Searle), an E₁ prostaglandin analog marketed in the USA only for prevention of gastric ulcers.

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.