DRUG INTERACTIONS
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.
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.
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.
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.
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