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Tindamax
Classes
Agents for Amoebiasis and Other Protozoal Diseases
Anaerobicides
Imidazole Derivative Antibiotics
Administration
Administer with food to minimize epigastric discomfort and other gastrointestinal side effects.
Oral Suspension Extemporaneous Preparation:
Grind four 500 mg tablets to a fine powder with a mortar and pestle.
Add approximately 10 mL of cherry syrup to the powder and mix until smooth.
Transfer the suspension to a graduated amber container. Use several small rinses of cherry syrup to transfer any remaining drug in the mortar to the final suspension for a final volume of 30 mL.
Shake well before each administration.
Storage: The suspension is stable for 7 days at room temperature.[29931]
Adverse Reactions
coma / Early / 0-1.0
seizures / Delayed / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
angioedema / Rapid / 0-1.0
erythema multiforme / Delayed / 0-1.0
bronchospasm / Rapid / 0-1.0
hepatic failure / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
candidiasis / Delayed / 4.7-4.7
vaginitis / Delayed / 4.7-4.7
constipation / Delayed / 0.4-1.4
stomatitis / Delayed / 0-1.0
peripheral neuropathy / Delayed / 0-1.0
depression / Delayed / 0-1.0
confusion / Early / 0-1.0
ataxia / Delayed / 0-1.0
palpitations / Early / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
dyspnea / Early / 0-1.0
neutropenia / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
superinfection / Delayed / Incidence not known
infertility / Delayed / Incidence not known
metallic taste / Early / 3.7-6.3
nausea / Early / 3.2-4.5
anorexia / Delayed / 1.5-2.5
malaise / Early / 1.1-2.1
fatigue / Early / 1.1-2.1
weakness / Early / 1.1-2.1
dyspepsia / Early / 1.4-1.8
vomiting / Early / 0.9-1.5
headache / Early / 0.7-1.3
dizziness / Early / 0.5-1.1
diarrhea / Early / 0-1.0
tongue discoloration / Delayed / 0-1.0
urine discoloration / Early / 0-1.0
insomnia / Early / 0-1.0
vertigo / Early / 0-1.0
drowsiness / Early / 0-1.0
paresthesias / Delayed / 0-1.0
rash / Early / 0-1.0
fever / Early / 0-1.0
diaphoresis / Early / 0-1.0
urticaria / Rapid / 0-1.0
pruritus / Rapid / 0-1.0
xerostomia / Early / 0-1.0
flushing / Rapid / 0-1.0
arthralgia / Delayed / 0-1.0
myalgia / Early / 0-1.0
pharyngitis / Delayed / 0-1.0
flatulence / Early / 2.0
infection / Delayed / 2.0
pelvic pain / Delayed / 2.0
menorrhagia / Delayed / 2.0
vaginal discharge / Delayed / Incidence not known
Boxed Warning
Although not reported with tinidazole, carcinogenicity has been seen in mice and rats treated chronically with nitroimidazole derivatives, which are structurally similar to tinidazole. It is unclear if the new primary malignancy findings in lifetime rodent studies indicate a risk to patients taking a short course or single dose of tinidazole. Limit tinidazole use to approved indications only, and avoid chronic use.[29931]
Common Brand Names
Tindamax
Dea Class
Rx
Description
Oral nitroimidazole antimicrobial
Used for trichomoniasis, giardiasis, amebiasis, and bacterial vaginosis
Limit use to approved indications and short-term only
Dosage And Indications
2 g PO as a single dose as an alternative. Sexual partners should be referred and evaluated for appropriate treatment.[29931]
2 g PO as a single dose as an alternative. Sexual partners should be referred and evaluated for appropriate treatment.
2 g PO once daily for 7 days for patients failing both the single dose and 7-day metronidazole regimens. If treatment failure occurs after this regimen, high-dose tinidazole 2 g PO once daily in combination with intravaginal tinidazole for 14 days may be used. If this regimen fails, high-dose tinidazole 1 g PO three times daily in combination with intravaginal paromomycin for 14 days may be considered. Sexual partners should be referred and evaluated for appropriate treatment.
2 g PO once daily for 7 days for patients failing both the single dose and 7-day metronidazole regimens. If treatment failure occurs after this regimen, high-dose tinidazole 2 g PO once daily in combination with intravaginal tinidazole for 14 days may be used. If this regimen fails, high-dose tinidazole 1 g PO three times daily in combination with intravaginal paromomycin for 14 days may be considered. Sexual partners should be referred and evaluated for appropriate treatment.
500 mg intravaginally 2 to 3 times daily in combination with high-dose tinidazole 2 g PO once daily for 14 days has been used after treatment failure with high-dose metronidazole/tinidazole. Sexual partners should be referred and evaluated for appropriate treatment.
500 mg intravaginally 2 to 3 times daily in combination with high-dose tinidazole 2 g PO once daily for 14 days has been used after treatment failure with high-dose metronidazole/tinidazole. Sexual partners should be referred and evaluated for appropriate treatment.
2 g PO as a single dose.
50 mg/kg/dose (Max: 2 g/dose) PO as a single dose.
2 g PO once daily for 3 to 5 days followed by either iodoquinol or paromomycin.
50 mg/kg/dose (Max: 2 g/dose) PO once daily for 3 to 5 days followed by either iodoquinol or paromomycin.
2 g PO once daily for 3 days followed by either iodoquinol or paromomycin.
50 mg/kg/dose (Max: 2 g/dose) PO once daily for 3 days followed by either iodoquinol or paromomycin.
NOTE: Rule out other commonly associated pathogens such as Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhea, Candida albicans, and Herpes simplex virus before treatment.[29931]
For the initial treatment of bacterial vaginosis. Oral dosage Adults
2 g PO once daily for 2 days or 1 g PO once daily for 5 days as an alternative.
2 g PO once daily for 2 days or 1 g PO once daily for 5 days as alternative therapy.
500 mg PO twice daily for 7 days, followed by intravaginal boric acid with suppressive metronidazole gel.
500 mg PO twice daily for 7 days, followed by intravaginal boric acid with suppressive metronidazole gel.
2 g PO as a single dose for males who have sex with females in areas where T. vaginalis is prevalent.
500 mg PO twice daily in combination with clarithromycin, amoxicillin, and a proton pump inhibitor (PPI) for 10 to 14 days.
500 mg PO 2 to 3 times daily in combination with clarithromycin, amoxicillin, and a proton pump inhibitor (PPI) for 10 to 14 days.
500 mg PO twice daily in combination with levofloxacin and a proton pump inhibitor (PPI) for 5 to 7 days after initial 5 to 7-day therapy with amoxicillin and a PPI.
500 mg PO twice daily in combination with clarithromycin, amoxicillin, and a proton pump inhibitor (PPI) for 7 days after initial 7-day therapy with amoxicillin and a PPI.
500 mg PO twice daily in combination with clarithromycin and a proton pump inhibitor (PPI) for 5 to 7 days after initial 5 to 7-day therapy with amoxicillin and a PPI.
†Indicates off-label use
Dosing Considerations
No data are available on tinidazole pharmacokinetics in patients with hepatic impairment. Reduced elimination of metronidazole, a chemically-related nitroimidazole, has been reported to be reduced in patients with hepatic impairment. Use typical tinidazole doses cautiously in patients with hepatic impairment.[29931]
Renal ImpairmentNo dosage adjustment needed.[29931]
Intermittent hemodialysis
Approximately 43% of the amount of tinidazole present in the body is eliminated during a 6-hour hemodialysis session. If tinidazole is administered on the same day and before dialysis, give an additional dose equivalent to one-half the recommended dose after the end of the hemodialysis session.[29931]
Peritoneal dialysis
The pharmacokinetics of tinidazole in patients undergoing routine continuous peritoneal dialysis have not been studied.[29931]
Drug Interactions
Adagrasib: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with adagrasib is necessary. Concurrent use may increase the exposure of tinidazole. Tinidazole is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor.
Apalutamide: (Moderate) Monitor for decreased efficacy of tinidazole if coadministration with apalutamide is necessary. Tinidazole is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Concomitant use may accelerate the elimination of tinidazole, decreasing plasma concentrations.
Aprepitant, Fosaprepitant: (Moderate) Use caution if tinidazole and aprepitant, fosaprepitant are used concurrently and monitor for an increase in tinidazole-related adverse effects for several days after administration of a multi-day aprepitant regimen. Tinidazole is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of tinidazole. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Atazanavir: (Major) The plasma concentrations of tinidazole may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate.
Atazanavir; Cobicistat: (Major) The plasma concentrations of tinidazole may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate. (Moderate) The plasma concentrations of tinidazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate.
Berotralstat: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with berotralstat is necessary. Concurrent use may increase the exposure of tinidazole. Tinidazole is a CYP3A4 substrate and berotralstat is a moderate CYP3A inhibitor.
Ceritinib: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with ceritinib is necessary. Tinidazole is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Cholestyramine: (Moderate) Administer tinidazole at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine. Separate dosing of cholestyramine and tinidazole to minimize any potential effect on the bioavailability of tinidazole. Cholestyramine was shown to decrease the bioavailability of another nitroimidazole by 21%.
Cimetidine: (Major) Coadministration may result in increased tinidazole concentrations. Cimetidine is an enzyme inhibitor that can decrease the hepatic metabolism of tinidazole.
Cobicistat: (Moderate) The plasma concentrations of tinidazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate.
Conivaptan: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with conivaptan is necessary. Concurrent use may increase the exposure of tinidazole. Tinidazole is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with crizotinib is necessary. Tinidazole is a CYP3A4 substrate and crizotinib is a moderate CYP3A inhibitor. Inhibitors of CYP3A4 inhibitors may prolong the half-life and decrease the plasma clearance of tinidazole, increasing the plasma concentrations of tinidazole.
Cyclosporine: (Moderate) Monitor for signs of calcineurin-inhibitor associated toxicities during coadministration of tinidazole and cyclosporine. Data suggest that another nitroimidazole has the potential to increase cyclosporine concentrations.
Darunavir: (Major) The plasma concentrations of tinidazole may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate.
Darunavir; Cobicistat: (Major) The plasma concentrations of tinidazole may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate. (Moderate) The plasma concentrations of tinidazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) The plasma concentrations of tinidazole may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate. (Moderate) The plasma concentrations of tinidazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate.
Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Disulfiram: (Major) Do not use tinidazole in patients who have taken disulfiram within the last 2 weeks. Psychotic reactions have been reported in patients with alcoholism using another nitroimidazole and disulfiram concurrently.
Dronabinol: (Major) The use of tinidazole within 14 days of beginning therapy with dronabinol oral solution is contraindicated, due to the risk of a disulfiram-like reaction. Do not administer tinidazole within 7 days of completing therapy with the oral solution. Dronabinol oral solution contains 50% (w/w) dehydrated alcohol and 5% (w/w) propylene glycol, which can produce disulfiram-like reactions (e.g., abdominal cramps, nausea/vomiting, headaches, and flushing) with drugs such as tinidazole. Ethanol competitively inhibits the metabolism of propylene glycol; however, the contribution of propylene glycol to these reactions is unknown. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations (e.g., capsules).
Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A. Tinidazole is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Elbasvir; Grazoprevir: (Moderate) Administering tinidazole with elbasvir; grazoprevir may result in elevated tinidazole plasma concentrations. Tinidazole is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of tinidazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of tinidazole may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Cobicistat is a strong CYP3A4 inhibitor, while tinidazole is a CYP3A4 substrate.
Enzalutamide: (Moderate) Monitor for decreased efficacy of tinidazole if coadministration with enzalutamide is necessary. Tinidazole is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Concomitant use may accelerate the elimination of tinidazole, decreasing plasma concentrations.
Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethanol: (Major) Avoid alcohol and preparations containing alcohol or propylene glycol during tinidazole therapy and for 3 days after because abdominal cramps, nausea, vomiting, headaches, and flushing may occur.
Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Fedratinib: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with fedratinib is necessary. Concurrent use may prolong the half-life and decrease the plasma clearance of tinidazole, increasing the plasma concentrations of tinidazole. Tinidazole is a CYP3A4 substrate and fedratinib is a moderate CYP3A inhibitor.
Fluorouracil, 5-FU: (Moderate) Monitor for fluorouracil-related toxicities if concomitant use of tinidazole and fluorouracil cannot be avoided. Another nitroimidazole was shown to decrease fluorouracil clearance resulting in an increase in side effects without an increase in therapeutic benefits.
Fosamprenavir: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with fosamprenavir is necessary. Concurrent use may increase the exposure of tinidazole. Tinidazole is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor.
Fosphenytoin: (Moderate) Tinidazole may decrease the clearance of hydantoins resulting in an increase in hydantoin plasma concentrations. Hydantoin levels should be checked regularly when tinidazole therapy is undertaken. Additionally, hydantoins are inducers of hepatic cytochrome P450 enzymes and may accelerate the elimination of tinidazole and decrease plasma concentrations of tinidazole.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tinidazole, a CYP3A substrate, as tinidazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Isavuconazonium: (Moderate) The plasma concentrations of tinidazole may be elevated when administered concurrently with isavuconazonium. Clinical monitoring for adverse effects, such as GI effects, is recommended during coadministration. Tinidazole is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor for decreased efficacy of tinidazole if coadministration with rifampin is necessary. Concomitant use may accelerate the elimination of tinidazole, decreasing plasma concentrations. Tinidazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
Isoniazid, INH; Rifampin: (Moderate) Monitor for decreased efficacy of tinidazole if coadministration with rifampin is necessary. Concomitant use may accelerate the elimination of tinidazole, decreasing plasma concentrations. Tinidazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
Ketoconazole: (Major) Ketoconazole is an enzyme inhibitor that can decrease the hepatic metabolism of tinidazole. As a result, elimination can be delayed and serum tinidazole concentrations can increase.
Lefamulin: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with oral lefamulin is necessary. Concurrent use may prolong the half-life and decrease the plasma clearance of tinidazole, increasing the plasma concentrations of tinidazole. Tinidazole is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A inhibitor; an interaction is not expected with intravenous lefamulin.
Lenacapavir: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with lenacapavir is necessary. Concurrent use may increase the exposure of tinidazole. Tinidazole is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of tinidazole; monitor for potential reduction in efficacy. Tinidazole is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of tinidazole; monitor for potential reduction in efficacy. Tinidazole is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Letermovir: (Moderate) An increase in the plasma concentration of tinidazole may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Tinidazole is primarily metabolized by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levoketoconazole: (Major) Ketoconazole is an enzyme inhibitor that can decrease the hepatic metabolism of tinidazole. As a result, elimination can be delayed and serum tinidazole concentrations can increase.
Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Lithium: (Moderate) Consider monitoring serum lithium and creatinine concentrations after several days of concomitant lithium and tinidazole treatment to detect potential lithium intoxication. Another nitroimidazole has been reported to increase serum lithium concentrations.
Lonafarnib: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with lonafarnib is necessary. Concurrent use may increase the exposure of tinidazole. Tinidazole is a CYP3A4 substrate and lonafarnib is a strong CYP3A inhibitor.
Lopinavir; Ritonavir: (Major) Medications with significant alcohol content should not be ingested during therapy with tinidazole and should be avoided for 3 days after therapy is discontinued. Oral solutions of lopinavir; ritonavir contain ethanol. Administration of lopinavir; ritonavir oral solution to patients receiving or who have recently received tinidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations of lopinavir; ritonavir (e.g., tablets). (Moderate) Coadministration of tinidazole with ritonavir may accelerate the elimination of tinidazole, decreasing the plasma concentration of tinidazole, or may prolong the half-life of tinidazole, increasing the plasma concentration of tinidazole. Tinidazole is a CYP3A4 substrate, and ritonavir is a CYP3A4 inhibitor and strong CYP3A4 inducer. Additionally, ritonavir oral solution and capsules contain ethanol. Medications with significant alcohol content should not be ingested during therapy with tinidazole and should be avoided for 3 days after therapy is discontinued. Administration of ritonavir oral solution and capsules to patients receiving or who have recently received tinidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations of ritonavir (e.g., tablets or oral powder).
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may reduce the efficacy of tinidazole by decreasing its systemic exposure; if concomitant use is necessary, monitor for decreased antimicrobial effect. Tinidazole is primarily metabolized by CYP3A4, and lumacaftor is a strong CYP3A inducer.
Mitotane: (Major) Use caution if mitotane and tinidazole are used concomitantly, and monitor for decreased efficacy of tinidazole and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and tinidazole is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of tinidazole.
Nirmatrelvir; Ritonavir: (Moderate) Coadministration of tinidazole with ritonavir may accelerate the elimination of tinidazole, decreasing the plasma concentration of tinidazole, or may prolong the half-life of tinidazole, increasing the plasma concentration of tinidazole. Tinidazole is a CYP3A4 substrate, and ritonavir is a CYP3A4 inhibitor and strong CYP3A4 inducer. Additionally, ritonavir oral solution and capsules contain ethanol. Medications with significant alcohol content should not be ingested during therapy with tinidazole and should be avoided for 3 days after therapy is discontinued. Administration of ritonavir oral solution and capsules to patients receiving or who have recently received tinidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations of ritonavir (e.g., tablets or oral powder).
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concu
Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Oritavancin: (Minor) Tinidazole is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of tinidazole may be reduced if these drugs are administered concurrently.
Phenobarbital: (Moderate) Monitor for decreased efficacy of tinidazole if coadministration with phenobarbital is necessary. Concomitant use may accelerate the elimination of tinidazole, decreasing plasma concentrations. Tinidazole is a CYP3A substrate and phenobarbital is a strong CYP3A inducer.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Monitor for decreased efficacy of tinidazole if coadministration with phenobarbital is necessary. Concomitant use may accelerate the elimination of tinidazole, decreasing plasma concentrations. Tinidazole is a CYP3A substrate and phenobarbital is a strong CYP3A inducer.
Phenytoin: (Moderate) Although not reported with tinidazole, oral metronidazole, has been shown to decrease the clearance of intravenous phenytoin resulting in an increase in phenytoin plasma concentrations. Phenytoin levels should be checked regularly when tinidazole therapy is undertaken. Additionally, phenytoin is an inducer of hepatic cytochrome P450 enzymes and may accelerate the elimination of tinidazole and decrease plasma concentrations of tinidazole.
Posaconazole: (Major) Posaconazole and tinidazole should be coadministered with caution due to an increased potential for tinidazole-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of tinidazole. These drugs used in combination may result in elevated tinidazole plasma concentrations, causing an increased risk for tinidazole-related adverse events.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Ribociclib: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with ribociclib is necessary. Tinidazole is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with ribociclib is necessary. Tinidazole is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Rifampin: (Moderate) Monitor for decreased efficacy of tinidazole if coadministration with rifampin is necessary. Concomitant use may accelerate the elimination of tinidazole, decreasing plasma concentrations. Tinidazole is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer.
Rifapentine: (Moderate) Monitor for decreased efficacy of tinidazole if coadministration with rifapentine is necessary. Concomitant use may accelerate the elimination of tinidazole, decreasing plasma concentrations. Tinidazole is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer.
Ritlecitinib: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with ritlecitinib is necessary. Concurrent use may increase the exposure of tinidazole. Tinidazole is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Moderate) Coadministration of tinidazole with ritonavir may accelerate the elimination of tinidazole, decreasing the plasma concentration of tinidazole, or may prolong the half-life of tinidazole, increasing the plasma concentration of tinidazole. Tinidazole is a CYP3A4 substrate, and ritonavir is a CYP3A4 inhibitor and strong CYP3A4 inducer. Additionally, ritonavir oral solution and capsules contain ethanol. Medications with significant alcohol content should not be ingested during therapy with tinidazole and should be avoided for 3 days after therapy is discontinued. Administration of ritonavir oral solution and capsules to patients receiving or who have recently received tinidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations of ritonavir (e.g., tablets or oral powder).
Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Tacrolimus: (Moderate) Monitor for signs of calcineurin-inhibitor associated toxicities during coadministration of tinidazole and tacrolimus. Data suggest that another nitroimidazole has the potential to increase tacrolimus concentrations.
Tucatinib: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with tucatinib is necessary. Concurrent use may increase the exposure of tinidazole. Tinidazole is a CYP3A4 substrate and tucatinib is a strong CYP3A inhibitor.
Vemurafenib: (Minor) Vemurafenib is an inducer of CYP3A4 and decreased plasma concentrations of drugs metabolized by this enzyme, such as tinidazole, could be expected with concurrent use. Use caution, and monitor therapeutic effects of tinidazole when coadministered with vemurafenib.
Voriconazole: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with voriconazole is necessary. Tinidazole is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor.
Voxelotor: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with voxelotor is necessary. Concurrent use may increase the exposure of tinidazole. Tinidazole is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Moderate) The warfarin dose may need to be adjusted during tinidazole coadministration and for up to 8 days after stopping therapy. Tinidazole may enhance the effect of warfarin resulting in a prolongation of prothrombin time.
How Supplied
Tindamax/Tinidazole Oral Tab: 250mg, 500mg
Maximum Dosage
2 g/day PO.
Geriatric2 g/day PO.
Adolescents50 mg/kg/dose (Max: 2 g/dose) PO.
Children4 to 12 years: 50 mg/kg/dose (Max: 2 g/dose) PO.
1 to 3 years: Safety and efficacy have not been established.
Safety and efficacy have not been established.
NeonatesSafety and efficacy have not been established.
Mechanism Of Action
Tinidazole is an antiprotozoal, antibacterial agent. The nitro- group of tinidazole is reduced by cell extracts of Trichomonas. The free nitro radical generated as a result of this reduction may be responsible for the antiprotozoal activity. Chemically reduced tinidazole was shown to release nitrites and cause damage to purified bacterial DNA in vitro. Additionally, the drug causes DNA base changes in bacterial cells and DNA strand breakage in mammalian cells. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is unknown.[29931]
Pharmacokinetics
Tinidazole is administered orally. Tinidazole is distributed into essentially all tissues and body fluids and crosses the blood-brain barrier. Plasma protein binding is approximately 12%. Tinidazole is significantly metabolized before being excreted. Metabolism is partly by oxidation, hydroxylation, and conjugation. Tinidazole is the major drug-related constituent in plasma along with a minor amount of the 2-hydroxymethyl metabolite. Tinidazole is excreted by the liver and kidneys. Approximately 20% to 25% of the administered dose is excreted unchanged in the urine. About 12% of the drug is excreted in the feces. The plasma half-life of tinidazole is about 12 to 14 hours.[29931]
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
Tinidazole is biotransformed mainly by CYP3A4. In an in vitro metabolic drug interaction study, tinidazole concentrations of up to 75 mcg/mL did not inhibit the enzyme activities of CYP1A2, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4.[29931]
Tinidazole is absorbed rapidly and completely. A bioavailability study was done in healthy adult volunteers receiving a single oral dose of tinidazole 2 g after an overnight fast. Mean peak plasma concentration (Cmax) was 47.7 mcg/mL with a mean time to peak concentration (Tmax) of 1.6 hours. Mean plasma concentration decreased to 14.3 mcg/mL at 24 hours, 3.8 mcg/mL at 48 hours, and 0.8 mcg/mL at 72 hours after dosing. Steady-state concentrations are reached in 2.5 to 3 days of multiday dosing. Food delays the Tmax by about 2 hours and reduces the Cmax by approximately 10% compared to fasted conditions; food did not affect the AUC or half-life. Administration of an extemporaneous preparation using crushed tinidazole tablets and artificial cherry syrup after an overnight fast did not alter the pharmacokinetics of tinidazole compared to tablets swallowed whole under fasted conditions.[29931]
Pregnancy And Lactation
Available published data with tinidazole use during pregnancy are insufficient to identify a risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks associated with untreated lower genital tract infections during pregnancy. In animal reproduction studies, oral administration of tinidazole at 6 times the maximum recommended human dose (based on body surface area comparison) showed a slight increase in fetal mortality.[29931]
Advise nursing mothers that breast-feeding is not recommended during tinidazole therapy and for 72 hours after administration to minimize exposure to the breast-feeding infant. A breast-feeding mother may choose to pump and discard her breast milk during and for 72 hours after tinidazole administration. Tinidazole is present in human breast milk. There are no reports of adverse effects on the breast-fed infant and no information on the effects of tinidazole on milk production.[29931] Previous American Academy of Pediatrics (AAP) recommendations considered tinidazole to be of concern due to potential mutagenesis and suggested if a single oral dose is given that breast-feeding may be resumed in 12 to 24 hours.[27500]