Valproic acid and congenital malformations. A case report.

An infant exposed in utero to valproic acid was born with multiple congenital malformations, including duodenal atresia, lumbar vertebral fusion, thoracolumbar scoliosis, renal abnormalities, diastasis recti abdominis, depigmentation of the eyebrows, and a large hemangioma. The child had neonatal hyperbilirubinemia and postnatal growth deficiency. This case report is an addition to the literature implicating valproic acid as a human teratogen.

A double-blind evaluation of skin test suppression produced by two doses of terfenadine.

For some patients, terfenadine, in the currently recommended dose of 60 mg twice daily (bid), may be only modestly effective in the treatment of allergic rhinitis. In a double-blind placebo-controlled crossover study of 12 patients, a larger dose (300 mg bid) was evaluated for its suppression of titrated skin tests to histamine and compound 48/80 to determine whether this regimen might result in greater suppression while it maintained the freedom from side effects of the presently recommended dose. In seven patients, skin test suppression by these two doses of terfenadine each administered for 3 days, was compared to that produced in an earlier study by 3 days of treatment with chlorpheniramine (8 mg three times a day). The 300 mg bid terfenadine regimen produced significantly greater skin test suppression (p less than 0.05) than the currently recommended 60 mg bid dose. There was no significant difference in side effects between the two doses, and neither active treatment regimen produced more side effects than placebo treatment. Both doses of terfenadine suppressed cutaneous reactivity significantly more than had chlorpheniramine. It is concluded that the presently recommended dose of terfenadine produces submaximal skin test suppression and that further studies are needed to investigate the clinical efficacy and safety of larger doses of terfenadine in the treatment of allergic rhinitis.

Chronic chlorpheniramine therapy: subsensitivity, drug metabolism, and compliance.

To investigate whether patients develop true subsensitivity to antihistamines during chronic therapy, we studied 14 adult subjects who received chlorpheniramine for 3-day and 3-week trials of therapy. Titrated skin tests to histamine and compound 48/80, chlorpheniramine blood levels (by HPLC), compliance, and side effects were monitored and compared during the two courses of therapy and their respective 72-hour washout periods. We found a significant correlation between chlorpheniramine blood levels and skin test suppression during both the 3-day and 3-week therapies. The 3-day chlorpheniramine therapy was more clinically effective (measured by skin test suppression corrected for serum chlorpheniramine concentration) than the 3-week therapy (P less than .01). Chlorpheniramine serum half-lives and 2-hour chlorpheniramine blood levels were not significantly different after the 3-day and 3-week trials. Compliance was significantly worse (P less than .01) during 3-week therapy. Medication side effects (particularly drowsiness) were frequently reported during both courses of therapy. We conclude that subsensitivity to chlorpheniramine does develop in adult patients receiving 3 weeks of therapy. This subsensitivity is not explained by changes in drug metabolism. In addition to subsensitivity, poor compliance may contribute to sub-therapeutic results during chronic antihistamine therapy. Side effects from antihistamines may also require individualization of therapy for certain patients.