Betaine (Cystadane - Orphan Medical), an orphan drug, has recently been marketed for treatment of homocystinuria, a genetic disorder. Patients with homocystinuria frequently have premature atherosclerosis and thromboembolism, and may also have lens dislocations, skeletal abnormalities and mental retardation (SH Mudd et al in CR Scriver et al, eds, The Metabolic and Molecular Bases of Inherited Disease, 7th ed, New York:McGraw Hill, 1995, page 1279).

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.

Cysteamine bitartrate (Cystagon - Mylan), an orphan drug, has been approved by the US Food and Drug Administration for oral treatment of nephropathic cystinosis, an autosomal recessive metabolic disorder that affects only a few hundred people in the USA (WA Gahl et al, in The Metabolic Basis of Inherited Disease, 7th ed., CR Scriver et al, eds, New York:McGraw-Hill, 1995, p 3763).

Donepezil hydrochloride (Aricept - Eisai), a piperidine-based acetylcholinesterase inhibitor, is now being marketed for oral treatment of cognitive symptoms in patients with mild to moderate dementia due to Alzheimer's disease. Donepezil is the second drug approved for this indication; tacrine hydrochloride (Cognex), also an acetylcholinesterase inhibitor, has been available in the USA for four years (Medical Letter, 35:87, 1993).

Terfenadine (Seldane - Marion Merrell Dow) and astemizole (Hismanal - Janssen) are nonsedating antihistamines widely used to treat symptoms of allergic rhinitis (Medical Letter, 27:65, 1985; 31:43, 1989). Both are available without a prescription in Canada, and the US Food and Drug Administration is apparently considering terfenadine for over-the-counter availability in the USA.

Gabapentin (Neurontin - Parke-Davis), a cyclohexane acetic acid derivative, has been approved by the US Food and Drug Administration for use in addition to other antiepileptic drugs in patients with partial (focal) seizures with or without secondary generalization. Since this diagnostic category includes the largest number of patients with intractable epilepsy, new drugs with antiepileptic activity are generally tried first for this indication.

The FDA has approved deutetrabenazine (Austedo – Teva), a vesicular monoamine transporter 2 (VMAT2) inhibitor, for treatment of chorea associated with Huntington's disease and, more recently, for treatment of tardive dyskinesia in adults. It is the second VMAT2 inhibitor to be approved for each of these indications; tetrabenazine (Xenazine, and generics) was approved earlier for Huntington's chorea and valbenazine (Ingrezza) was recently approved for treatment of adults with tardive dyskinesia.

Paroxetine (Paxil - SmithKline Beecham), a new selective serotonin reuptake inhibitor (SSRI), is now available in the USA. Two other SSRIs, fluoxetine (Prozac - Medical Letter, 30:45, 1988; 32:83, 1990) and sertraline (Zoloft - Medical Letter, 34:47, 1992), were approved previously.

The FDA has approved the antiprogestin mifepristone (Korlym – Corcept Therapeutics) for control of hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing’s syndrome who have type 2 diabetes/ glucose intolerance and have not responded to, or are not candidates for, surgery. Formerly known as RU 486, mifepristone is also available in a lower strength as Mifeprex for use in terminating an early intrauterine pregnancy.

The FDA has approved tramadol hydrochloride extended-release (Ryzolt – Purdue) for treatment of moderate to moderately severe chronic pain in adults. Tramadol is already available in another extended-release formulation (Ultram ER) and in immediate-release tablets alone (Ultram, and others) and combined with acetaminophen (Ultracet, and others).