Tinidazoleinteractions

Although not specifically identified in studies with tinidazole, the following drug interactions were reported for metronidazole, a chemically-related nitroimidazole. Therefore, these drug interactions may occur with tinidazole. The following drug interactions were reported for metronidazole, a chemically-related nitroimidazole and may therefore occur with tinidazole: Warfarin and other oral coumarin anticoagulants: Anticoagulant dosage may need adjustment during and up to 8 days after tinidazole therapy Alcohol-containing beverages/preparations: Avoid during and up to 3 days after tinidazole therapy Lithium: Monitor serum lithium concentrations Cyclosporine, tacrolimus: Monitor for toxicities of these immunosuppressive drugs Fluorouracil: Monitor for fluorouracil-associated toxicities Phenytoin, fosphenytoin: Adjustment of anticonvulsant and/or tinidazole dose(s) may be needed CYP3A4 inducers/inhibitors: Monitor for decreased tinidazole effect or increased adverse reactions

7.1 Potential

Effects of Tinidazole on Other Drugs Warfarin and Other Oral Coumarin Anticoagulants: As with metronidazole, tinidazole may enhance the effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time. The dosage of oral anticoagulants may need to be adjusted during tinidazole co-administration and up to 8 days after discontinuation. Alcohols, Disulfiram: Alcoholic beverages and preparations containing ethanol or propylene glycol should be avoided during tinidazole therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur. Psychotic reactions have been reported in alcoholic patients using metronidazole and disulfiram concurrently. Though no similar reactions have been reported with tinidazole, tinidazole should not be given to patients who have taken disulfiram within the last two weeks.

Lithium: Metronidazole has been reported to elevate serum lithium levels. It is not known if tinidazole shares this property with metronidazole, but consideration should be given to measuring serum lithium and creatinine levels after several days of simultaneous lithium and tinidazole treatment to detect potential lithium intoxication. Phenytoin, Fosphenytoin: Concomitant administration of oral metronidazole and intravenous phenytoin was reported to result in prolongation of the half-life and reduction in the clearance of phenytoin. Metronidazole did not significantly affect the pharmacokinetics of orally-administered phenytoin. Cyclosporine, Tacrolimus: There are several case reports suggesting that metronidazole has the potential to increase the levels of cyclosporine and tacrolimus. During tinidazole co-administration with either of these drugs, the patient should be monitored for signs of calcineurin-inhibitor associated toxicities Fluorouracil: Metronidazole was shown to decrease the clearance of fluorouracil, resulting in an increase in side-effects without an increase in therapeutic benefits. If the concomitant use of tinidazole and fluorouracil cannot be avoided, the patient should be monitored for fluorouracil-associated toxicities.

7.2 Potential

Effects of Other Drugs on Tinidazole CYP3A4 Inducers and Inhibitors: Simultaneous administration of tinidazole with drugs that induce liver microsomal enzymes, i.e., CYP3A4 inducers such as phenobarbital, rifampin, phenytoin, and fosphenytoin (a pro-drug of phenytoin), may accelerate the elimination of tinidazole, decreasing the plasma level of tinidazole. Simultaneous administration of drugs that inhibit the activity of liver microsomal enzymes, i.e., CYP3A4 inhibitors such as cimetidine and ketoconazole, may prolong the half-life and decrease the plasma clearance of tinidazole, increasing the plasma concentrations of tinidazole.

Cholestyramine: Cholestyramine was shown to decrease the oral bioavailability of metronidazole by 21%. Thus, it is advisable to separate dosing of cholestyramine and tinidazole to minimize any potential effect on the oral bioavailability of tinidazole.

Oxytetracycline: Oxytetracycline was reported to antagonize the therapeutic effect of metronidazole.

7.3 Laboratory

Test Interactions Tinidazole, like metronidazole, may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD + ↔ NADH). Potential interference is due to the similarity of absorbance peaks of NADH and tinidazole. Tinidazole, like metronidazole, may produce transient leukopenia and neutropenia; however, no persistent hematological abnormalities attributable to tinidazole have been observed in clinical studies. Total and differential leukocyte counts are recommended if re-treatment is necessary.