Drug Interactions between Cuprimine and pravastatin

ADJUST DOSING INTERVAL: Food may interfere with the gastrointestinal absorption of penicillamine. In a study of six healthy volunteers, administration of penicillamine (500 mg) following a standard breakfast reduced the mean peak plasma concentrations of penicillamine by 48% compared to administration in the fasting state.

MANAGEMENT: Penicillamine should be administered on an empty stomach, at least one hour before or two hours after meals, and at least one hour apart from any other drug, food, or milk. This permits maximum absorption and reduces the likelihood of inactivation by metal binding in the gastrointestinal tract.

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.

ADJUST DOSING INTERVAL: Oral administration of aluminum, copper, iron, zinc, magnesium, and possibly other minerals such as calcium may decrease the gastrointestinal absorption of penicillamine, and vice versa. The proposed mechanism involves chelation of penicillamine to polyvalent cations, which leads to formation of a nonabsorbable complex. In a study of six healthy volunteers, administration of penicillamine (500 mg) following a single dose of ferrous sulfate (300 mg) or antacid (Maalox Plus 30 mL) reduced the mean peak plasma concentration of penicillamine by 65% and 34%, respectively, compared to administration in the fasting state. In addition to chelation, some investigators suggest that antacids may also reduce penicillamine bioavailability by increasing gastric pH, which favors the oxidation of penicillamine to its poorly absorbed disulfide form. These changes could result in diminished therapeutic effects of penicillamine.

MANAGEMENT: Mineral supplements or other products containing polyvalent cations (e.g., antacids or preparations containing antacids such as didanosine buffered tablets or pediatric oral solution) should be administered at least two hours before or two hours after the penicillamine dose. In addition, pharmacologic response to penicillamine should be monitored more closely whenever these products are added to or withdrawn from therapy, and the penicillamine dosage adjusted as necessary. When penicillamine is coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering penicillamine at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium.