Drug Interactions between colchicine and Sumycin

GENERALLY AVOID: Coadministration with grapefruit juice may increase the serum concentrations of colchicine. Clinical toxicity including myopathy, neuropathy, multiorgan failure, and pancytopenia may occur. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism and P-glycoprotein efflux in the gut wall by certain compounds present in grapefruits. A published case report describes an eight-year-old patient with familial Mediterranean fever who developed acute clinical colchicine intoxication after ingesting approximately one liter of grapefruit juice per day for two months prior to hospital admission while being treated with colchicine 2 mg/day. Her condition progressed to circulatory shock and multiorgan failure, but she recovered with supportive therapy after 24 days in the hospital. In a study of 21 healthy volunteers, administration of 240 mL grapefruit juice twice a day for 4 days was found to have no significant effect on the pharmacokinetics of a single 0.6 mg dose of colchicine. However, significant interactions have been reported with other CYP450 3A4 inhibitors such as clarithromycin, diltiazem, erythromycin, ketoconazole, ritonavir, and verapamil.

MANAGEMENT: Patients treated with colchicine should be advised to avoid the consumption of grapefruit and grapefruit juice, and to contact their physician if they experience symptoms of colchicine toxicity such as abdominal pain, nausea, vomiting, diarrhea, fatigue, myalgia, asthenia, hyporeflexia, paresthesia, and numbness.

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ADJUST DOSING INTERVAL: Administration with food, particularly dairy products, significantly reduces tetracycline absorption. The calcium content of these foods forms nonabsorbable chelates with tetracycline.

MANAGEMENT: Tetracycline should be administered one hour before or two hours after meals.

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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.

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