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Tequin (Gatifloxacin) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG-DRUG INTERACTIONS

Systemic exposure to TEQUIN (gatifloxacin) is increased following concomitant administration of TEQUIN and probenecid, and is reduced by concomitant administration of TEQUIN and ferrous sulfate or antacids containing aluminum or magnesium salts. TEQUIN (gatifloxacin) can be administered 4 hours before the administration of dietary supplements containing zinc, magnesium, or iron (such as multivitamins).

Probenecid: Concomitant administration of TEQUIN (single oral 200 mg dose) with probenecid (500 mg BID x 1 day) resulted in a 42% increase in AUC and a 44% longer half-life of gatifloxacin.

Iron: When TEQUIN (single oral 400 mg dose) was administered concomitantly with ferrous sulfate (single oral 325 mg dose), bioavailability of gatifloxacin was reduced (54% reduction in mean Cmax and 35% reduction in mean AUC). Administration of TEQUIN (single oral 400 mg dose) 2 hours after or 2 hours before ferrous sulfate (single oral 325 mg dose) did not significantly alter the oral bioavailability of gatifloxacin (see DOSAGE AND ADMINISTRATION).

Antacids: When TEQUIN (single oral 400 mg dose) was administered 2 hours before, concomitantly, or 2 hours after an aluminum/magnesium-containing antacid (1800 mg of aluminum oxide and 1200 mg of magnesium hydroxide single oral dose), there was a 15%, 69%, and 47% reduction in Cmax and a 17%, 64%, and 40% reduction in AUC of gatifloxacin, respectively. An aluminum/magnesium-containing antacid did not have a clinically significant effect on the pharmacokinetics of gatifloxacin when administered 4 hours after gatifloxacin administration (single oral 400 mg dose) (see DOSAGE AND ADMINISTRATION).

Milk, Calcium, and Calcium-containing Antacids: No significant pharmacokinetic interactions occur when milk or calcium carbonate is administered concomitantly with TEQUIN. Concomitant administration of 200 mL of milk or 1000 mg of calcium carbonate with TEQUIN (200 mg gatifloxacin dose for the milk study and 400 mg gatifloxacin dose for the calcium carbonate study) had no significant effect on the pharmacokinetics of gatifloxacin. TEQUIN can be administered 4 hours before the administration of dietary supplements containing zinc, magnesium, or iron (such as multivitamins).

Minor pharmacokinetic interactions occur following concomitant administration of gatifloxacin and digoxin; a priori dosage adjustments of either drug are not warranted.

Digoxin: Overall, only modest increases in Cmax and AUC of digoxin were noted (12% and 19% respectively) in 8 of 11 healthy volunteers who received concomitant administration of TEQUIN (400 mg oral tablet, once daily for 7 days) and digoxin (0.25 mg orally, once daily for 7 days). In 3 of 11 subjects, however, a significant increase in digoxin concentrations was observed. In these 3 subjects, digoxin Cmax increased by 18%, 29%, and 58% while digoxin AUC increased by 66%, 104%, and 79%, and digoxin clearance decreased by 40%, 51%, and 45%. Although dose adjustments for digoxin are not warranted with initiation of gatifloxacin treatment, patients taking digoxin should be monitored for signs and/or symptoms of toxicity. In patients who display signs and/or symptoms of digoxin intoxication, serum digoxin concentrations should be determined, and digoxin dosage should be adjusted as appropriate. The pharmacokinetics of gatifloxacin was not altered by digoxin.

No significant pharmacokinetic interactions occur when cimetidine, midazolam, theophylline, warfarin, or glyburide is administered concomitantly with TEQUIN (gatifloxacin). These results and the data from in vitro studies suggest that gatifloxacin is unlikely to significantly alter the metabolic clearance of drugs metabolized by CYP3A, CYP1A2, CYP2C9, CYP2C19, and CYP2D6 isoenzymes.

Cimetidine: Administration of TEQUIN (single oral dose of 200 mg) 1 hour after cimetidine (single oral dose of 200 mg) had no significant effect on the pharmacokinetics of gatifloxacin. These results suggest that absorption of gatifloxacin is expected to be unaffected by H2-receptor antagonists like cimetidine.

Midazolam: TEQUIN administration had no significant effect on the systemic clearance of intravenous midazolam. A single intravenous dose of midazolam (0.0145 mg/kg) had no effect on the steady-state pharmacokinetics of gatifloxacin (once daily oral doses of 400 mg for 5 days). These results are consistent with the lack of effect of TEQUIN in in vitro studies with the human CYP3A4 isoenzyme.

Theophylline: Concomitant administration of TEQUIN (once daily oral doses of 400 mg for 5 days) and theophylline (300 mg BID oral dose for 10 days) had no significant effect on the pharmacokinetics of either drug. These results are consistent with the lack of effect of TEQUIN in in vitro studies with the human CYP1A2 isoenzyme.

Warfarin: Concomitant administration of TEQUIN (once daily oral doses of 400 mg for 11 days) and warfarin (single oral dose of 25 mg) had no significant effect on the pharmacokinetics of either drug nor was the prothrombin time significantly altered. These results are consistent with the lack of effect of TEQUIN in in vitro studies with the human CYP2C9, CYP1A2, CYP3A4 and CYP2C19 isoenzymes (see PRECAUTIONS: Drug Interactions).

Glyburide: Pharmacodynamic changes in glucose homeostasis were seen with concomitant administration of TEQUIN (once daily oral doses of 400 mg for 10 days) and glyburide (steady-state once daily regimen) in patients with type 2 diabetes mellitus. This was not associated with significant effects on the pharmacokinetic disposition of either drug. These latter results are consistent with the lack of effect of TEQUIN in in vitro studies with the human CYP3A4 isoenzyme (see CLINICAL PHARMACOLOGY: Glucose Homeostasis and WARNINGS).

OVERDOSAGE

Gatifloxacin exhibits a low potential for acute toxicity in animal studies. The minimum lethal oral doses in rats and dogs were greater than 2000 mg/kg and 1000 mg/kg, respectively. The minimum lethal intravenous dose was 144 mg/kg in rats and greater than 45 mg/kg in dogs. Clinical signs observed included decreased activity and respiratory rate, vomiting, tremors, and convulsions.

In the event of acute oral overdose, the stomach should be emptied by inducing vomiting or by gastric lavage. The patient should be carefully observed (including ECG monitoring) and given symptomatic and supportive treatment. Adequate hydration should be maintained. Gatifloxacin is not efficiently removed from the body by hemodialysis (approximately 14% recovered over 4 hours) or by chronic ambulatory peritoneal dialysis (CAPD) (approximately 11% recovered over 8 days).

CONTRAINDICATIONS

TEQUIN (gatifloxacin) is contraindicated in persons with a history of hypersensitivity to gatifloxacin or any member of the quinolone class of antimicrobial agents.

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