Drug Interactions between Cotempla XR-ODT and doxycycline

GENERALLY AVOID: Alcohol may exacerbate the adverse central nervous system effects of psychoactive drugs, including methylphenidate.

GENERALLY AVOID: Consumption of alcohol while taking certain sustained-release formulations of methylphenidate may cause rapid release of the drug, resulting in increased systemic levels of methylphenidate. In vitro studies have been conducted using Metadate CD 60 mg and Ritalin LA 40 mg capsules, as well as Concerta 18 mg tablet. At an alcohol concentration of 40%, an increase in the release rate of methylphenidate was observed in the first hour for Metadate CD and Ritalin LA, resulting in 84% and 98% of the methylphenidate being released, respectively. In contrast, there was no increased release of methylphenidate in the first hour for Concerta. These results are considered to be representative of the other available strengths of the corresponding product.

MANAGEMENT: Patients treated with methylphenidate should be advised to avoid alcohol or medications that contain alcohol.

GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.

Chronic alcohol consumption may enhance the elimination of doxycycline. The mechanism is induction of hepatic microsomal enzymes by alcohol. In one study, the half-life of doxycycline in six alcoholics was 10.5 hours, compared with 14.7 hours in six control patients. In addition, half the alcoholic patients had serum concentrations below what is generally considered the minimum therapeutic concentration (0.5 mcg/mL) at 12 to 24 hours after the dose. The investigators suggest that twice-a-day dosing may be indicated in these patients, especially if additional inducing drugs are used. The elimination of other tetracyclines probably is not affected by alcohol consumption.