Drug Interactions between Cipro I.V. and rasagiline

ADJUST DOSING INTERVAL: Concurrent ingestion of dairy products (milk, yogurt) or calcium-fortified foods (i.e., cereal, orange juice) may decrease the activity of certain oral fluoroquinolone antibiotics. The mechanism is chelation of calcium and the quinolone, resulting in decreased bioavailability. In the case of orange juice, inhibition of intestinal transport mechanisms (P-glycoprotein or organic anion-transporting polypeptides) by flavones may also be involved. One study reported an average 41% decrease in maximum plasma concentrations and a 38% decrease in AUC when ciprofloxacin was given with calcium-fortified orange juice instead of water. Administration of ciprofloxacin tablets with enteral nutrition may reduce its bioavailability and maximum serum concentrations. Data have been conflicting and variable by the type of enteral nutrition product, location of the feeding tube, and patient characteristics. Decreased absorption is expected if ciprofloxacin is given by jejunostomy tube.

MANAGEMENT: Oral ciprofloxacin should not be taken with dairy products or calcium-fortified foods alone, but may be taken with meals that contain these products. When taken alone, dairy products or calcium-fortified foods should be ingested at least 2 hours before or after ciprofloxacin administration. When ciprofloxacin tablets are administered to patients receiving continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for at least 1 hour before and 2 hours after the dose of ciprofloxacin is given. Patients should be monitored for altered antimicrobial efficacy and switched to intravenous ciprofloxacin if necessary. If no enteral route besides a jejunostomy tube is available, it is also recommended to switch to intravenous ciprofloxacin. According to the manufacturer, ciprofloxacin oral suspension should not be administered via nasogastric or feeding tubes due to its physical characteristics.

GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with monoamine oxidase (MAO) inhibitors. The mechanism involves inhibition of MAO-A, the enzyme responsible for metabolizing exogenous amines such as tyramine in the gut and preventing them from being absorbed intact. Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules. Although rasagiline is a selective inhibitor of MAO-B at the recommended dosages of 0.5 or 1 mg/day, selectivity is not absolute and may diminish with increasing dosage. There were no cases of hypertensive crisis in the clinical development program associated with rasagiline treatment at 1 mg/day, in which most patients did not follow dietary tyramine restriction. However, rare cases of hypertensive crisis have been reported during the postmarketing period in patients who ingested unknown amounts of tyramine-rich foods while taking recommended dosages of rasagiline or selegiline, another MAO-B inhibitor.

Rasagiline peak plasma concentration (Cmax) and systemic exposure (AUC ) are decreased by approximately 60% and 20%, respectively, during coadministration with a high-fat meal. The time to peak concentration (Tmax) is not affected by food.

MANAGEMENT: Dietary restriction is not ordinarily required during rasagiline treatment with respect to most foods and beverages that may contain tyramine such as air-dried and fermented meats or fish, aged cheeses, most soybean products, yeast extracts, red wine, beer, and sauerkraut. However, certain foods like some of the aged cheeses (e.g., Boursault, Liederkrantz, Mycella, Stilton) may contain very high amounts of tyramine and could potentially cause a hypertensive reaction in patients taking rasagiline even at recommended dosages due to increased sensitivity to tyramine. Patients should be advised to avoid ingesting very high levels of tyramine (e.g., greater than 150 mg), and to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, confusion, stupor or coma, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. Rasagiline should not be used at dosages exceeding 1 mg/day (0.5 mg/day for patients with mild hepatic impairment or concomitant use of ciprofloxacin or other CYP450 1A2 inhibitors), as it can increase the risk of hypertensive crisis and other adverse reactions associated with nonselective inhibition of MAO. Rasagiline can be administered with or without food.

ADJUST DOSING INTERVAL: Oral preparations that contain magnesium, aluminum, or calcium may significantly decrease the gastrointestinal absorption of quinolone antibiotics. Absorption may also be reduced by sucralfate, which contains aluminum, as well as other polyvalent cations such as iron and zinc. The mechanism is chelation of quinolones by polyvalent cations, forming a complex that is poorly absorbed from the gastrointestinal tract. The bioavailability of ciprofloxacin has been reported to decrease by as much as 90% when administered with antacids containing aluminum or magnesium hydroxide.

MANAGEMENT: When coadministration cannot be avoided, quinolone antibiotics should be dosed either 2 to 4 hours before or 4 to 6 hours after polyvalent cation-containing products to minimize the potential for interaction. When coadministered with Suprep Bowel Prep (magnesium/potassium/sodium sulfates), the manufacturer recommends administering fluoroquinolone antibiotics at least 2 hours before and not less than 6 hours after Suprep Bowel Prep to avoid chelation with magnesium. Please consult individual product labeling for specific recommendations.

MONITOR: Coadministration with certain quinolones may increase the plasma concentrations and pharmacologic effects of caffeine due to inhibition of the CYP450 1A2 metabolism of caffeine. Quinolones that may inhibit CYP450 1A2 include ciprofloxacin, enoxacin, grepafloxacin, nalidixic acid, norfloxacin, pipemidic acid, and pefloxacin (not all commercially available). In healthy volunteers, enoxacin (100 to 400 mg twice daily) increased systemic exposure (AUC) of caffeine by 2- to 5-fold and reduced its clearance by approximately 80%. Pipemidic acid (400 to 800 mg twice daily) increased AUC of caffeine by 2- to 3-fold and reduced its clearance by approximately 60%. Ciprofloxacin (250 to 750 mg twice daily) increased AUC and elimination half-life of caffeine by 50% to over 100%, and reduced its clearance by 30% to 50%. Norfloxacin 400 mg twice daily increased caffeine AUC by 16%, while 800 mg twice daily increased caffeine AUC by 52% and reduced its clearance by 35%. Pefloxacin (400 mg twice daily) has been shown to reduce caffeine clearance by 47%.

MANAGEMENT: Patients using caffeine-containing products should be advised that increased adverse effects such as headache, tremor, restlessness, nervousness, insomnia, tachycardia, and blood pressure increases may occur during coadministration with quinolones that inhibit CYP450 1A2. Caffeine intake should be limited when taking high dosages of these quinolones. If an interaction is suspected, other quinolones such as gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, and ofloxacin may be considered, since they are generally believed to have little or no effect on CYP450 1A2 or have been shown not to interact with caffeine.