Tinidazole (tinidazole)

No dosing information is available for this tab.

Tinidazole is administered orally with food.

Although food does not affect oral bioavailability of tinidazole, the drug should be given with meals to reduce the incidence of epigastric discomfort and other adverse GI effects.

Alcohol should be avoided during tinidazole treatment and for 3 days after the last dose of the drug. (See Drug Interactions: Alcohol and Propylene Glycol.)

Tinidazole is commercially available as tablets containing 250 or 500 mg of the drug. For children and other patients unable to swallow tablets, the 500-mg tablets can be used to prepare an extemporaneous oral suspension.

Formal drug interaction studies have not been performed to date with tinidazole; however, interactions reported with metronidazole, a nitroimidazole anti-infective chemically related to tinidazole, may also occur in patients receiving tinidazole. For further information on interactions associated with metronidazole, see Drug Interactions, in Metronidazole 8:30.92.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

Metronidazole; Tinidazole/Propylene Glycol

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Metronidazole(1) and tinidazole(2) inhibit the alcohol and aldehyde dehydrogenase pathway, which is responsible for the metabolism of propylene glycol.(1,2)

CLINICAL EFFECTS: The concurrent administration of metronidazole(1) and tinidazole(2) may result in the accumulation of propylene glycol, which may result in adverse effects such as seizures, stupor, tachycardia, hyperosmolality, lactic acidosis, renal toxicity, and hemolysis.

PREDISPOSING FACTORS: Certain ethnic populations (Asians, Eskimos, and Native Americans) and women may have a decreased ability to metabolize propylene glycol.(1,2)

PATIENT MANAGEMENT: Patients should be advised of the possible affects that may result from ingestion or application of products that contain propylene glycol while taking metronidazole or tinidazole.(1,2) Patients receiving metronidazole or tinidazole should be instructed to avoid products containing propylene glycol during and for 3 days after taking metronidazole or tinidazole.(1,2) Patients should be informed about unsuspected sources of propylene glycol such as elixirs and topical preparations. Caution is also warranted when using intravenous preparations containing propylene glycol solvents in patients receiving metronidazole or tinidazole.

DISCUSSION: Concurrent use of products that contain propylene glycol may cause a disulfiram-like reaction to alcohol when used with metronidazole or tinidazole.

Selected Nitroimidazole Antimicrobials/Disulfiram

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Since disulfiram has been associated with psychotic behavior in some patients, this interaction has been attributed to a combined toxicity with metronidazole or benznidazole.(1)

CLINICAL EFFECTS: May observe psychotic reactions of confusional states.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturers of benznidazole,(2) fexinidazole,(3) metronidazole,(4) and tinidazole(5) state that these agents should not be administered to patients who have received disulfiram in the previous two weeks.

DISCUSSION: In a study in hospitalized alcoholics, six of 29 patients receiving concurrent disulfiram and metronidazole developed acute psychosis or confusion. Of these six, five had paranoid delusions and three experienced visual and auditory hallucinations. These reactions were not reported in any of the 29 patients who received placebo with disulfiram.(6,7) An increased central effect of ethyl alcohol was observed in a single patient during concurrent disulfiram and metronidazole.(8) Psychotic symptoms were reported during concurrent use in another case report.(9)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Fexinidazole;Metronidazole;Tinidazole/Ethyl Alcohol

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: In vitro studies show that metronidazole produces an inhibition of aldehyde dehydrogenase and other alcohol-oxidizing enzymes.(1-5) This results in the accumulation of acetaldehyde, which is responsible for the disulfiram-like reaction. A similar process may occur with fexinidazole(6) and tinidazole.(7)

CLINICAL EFFECTS: Concurrent use of oral metronidazole with alcohol has been associated with a disulfiram-type reaction resulting in symptoms of hypotension, tachycardia, nausea, sweating, facial flushing, headache, and vomiting.(7-10) It has been suggested that some patients find this combination of agents a pleasant experience, citing giddiness and excitement as rationale for abuse.(11)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving fexinidazole should be instructed to avoid alcohol during and for at least 48 hours after taking fexinidazole.(6) Patients should be advised of the possible affects that may result from ingestion or application of products that contain alcohol while taking metronidazole. Patients receiving tinidazole should be instructed to avoid alcohol during and for 3 days after taking tinidazole.(7) Patients should be informed about unsuspected sources of alcohol such as elixirs and topical preparations. Caution is also warranted when using intravenous preparations containing alcohol solvents in patients receiving metronidazole or tinidazole. Alcohol is used to improve docetaxel and paclitaxel solubility. - The quantity of alcohol in paclitaxel injection formulations (0.385-0.396 grams/mL) is similar across manufacturers. A paclitaxel 200 mg dose contains approximately 13 grams of alcohol. - The quantity of alcohol in docetaxel formulations varies approximately 3-fold depending upon the manufacturer. FDA data on alcohol content (22): Product Manufacturer Alcohol/200 mg dose Docetaxel Inj. Pfizer 6.4 grams Docetaxel Inj. Sandoz 5.5 grams Docetaxel Inj. Accord 4.0 grams Taxotere-one vial Sanofi 4.0 grams formulation Docetaxel Inj. Hospira 3.7 grams Docefrez Sun Pharma 2.9 grams Taxotere-two vial Sanofi 2.0 grams formulation

DISCUSSION: In a case report,(13) a patient developed disulfiram-like reactions after receiving concurrent metronidazole and intravenous sulfamethoxazole-trimethoprim, which is solubilized in a 10% alcohol base. In another case report, a female patient using vaginal inserts containing metronidazole once daily at bedtime ingested two or three drinks containing 30ml of vodka on the fifth day of metronidazole therapy.(14) About a half hour later, the patient inserted the metronidazole vaginal tablet and awoke one hour later with a severe burning sensation in her stomach, a severe headache, and nausea accompanied by a cold sweat. These symptoms resolved in about four hours. Other studies have failed to observe a disulfiram-like reaction between alcohol and metronidazole.(15-21)

Metronid; Secnidazole; Tinidazole/Slt Anticoag (Vit K Antag)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Possible inhibition of anticoagulant metabolism by metronidazole, secnidazole, or tinidazole. Metronidazole is a weak CYP2C9 inhibitor and may inhibit the metabolism of the more potent warfarin isomer, S-warfarin.(1)

CLINICAL EFFECTS: Concurrent use of anticoagulants with metronidazole, secnidazole, or tinidazole may increase the risk for bleeding.

PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). Patients with a CYP2C9 intermediate metabolizer genotype, and/or 1-2 copies of a reduced function VKORC1 gene are expected to be most susceptible to this interaction. Patients with a pre-existing CYP2C9 poor metabolizer genotype would be less susceptible to this interaction. However, patients with reduced function genotypes (e.g. CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3) have an inherently higher risk for bleeding at usual anticoagulant doses and thus generally require lower doses to achieve effective and safe anticoagulation. In addition, CYP2C9 poor metabolizers may require more time (>2 to 4 weeks) to achieve maximum INR effect for a given dosage regimen than patients without these CYP2C9 variants.

PATIENT MANAGEMENT: INR values should be closely monitored during and for several days after the conclusion of concurrent metronidazole, secnidazole, or tinidazole. Anticoagulant dosage may need to be adjusted up to 10 days after concurrent therapy ends. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug.

DISCUSSION: In two studies, metronidazole significantly enhanced the hypoprothrombinemic effect of warfarin.(2,3) The onset of the interaction occurred within four(2) to ten days(3) and appeared as excessive bruising of the legs. In eight normal subjects, metronidazole significantly increased the half-life of racemic warfarin and the S-enantiomer of warfarin. The R-enantiomer of warfarin, which is metabolized primarily by the reduction of side chains, was unaffected by metronidazole.(4) In an animal study, metronidazole preferentially inhibited the S-enantiomer of warfarin.(5) This interaction should also be considered during concurrent administration and for eight days after concurrent anticoagulants and tinidazole.(6)

Metronidazole;Tinidazole/Fluorouracil & Fluorouracil Prodrug

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Metronidazole(1) and tinidazole(2) may decrease the clearance of fluorouracil.

CLINICAL EFFECTS: Concurrent use of metronidazole(1) or tinidazole with fluorouracil may result in elevated levels of fluorouracil and toxicity, including severe and fatal myelosuppression including neutropenia, thrombocytopenia, or anemia, severe diarrhea, cardiotoxicity, or neurotoxicity.

PREDISPOSING FACTORS: Patients who are intermediate or poor dihydropyrimidine dehydrogenase (DPYD) metabolizers have diminished or no DPYD function. Since DPYD is the rate-limiting enzyme involved in fluoropyrimidine metabolism, these patients may be more susceptible to the effects of this interaction.(3)

PATIENT MANAGEMENT: Avoid using metronidazole as an adjunct agent to fluorouracil therapy. If possible, also avoid treating infections with metronidazole or tinidazole in patients receiving fluorouracil. If concurrent therapy for the treatment of infection is required, the dosage of fluorouracil may need to be reduced. Patients receiving concurrent therapy should be closely monitored for signs of fluorouracil toxicity.

DISCUSSION: In a study in 27 patients, metronidazole (750 mg/m2) was given one hour before fluorouracil (600 mg/m2) daily for five days. The regimen was repeated every 4 weeks. Fluorouracil toxicity was greatly enhanced, with 74% of patients experiencing granulocytopenia (less than 1500/ml). Pharmacokinetic studies showed that metronidazole decreased fluorouracil clearance by 26.9%. In vitro studies revealed no synergism with the two agents on the HCT-8 colon cancer cell line.(1)

There are no moderate interactions for this drug.

Tinidazole is contraindicated in patients with a history of hypersensitivity to tinidazole or other nitroimidazole derivatives.

Tinidazole is contraindicated during the first trimester of pregnancy. (See Pregnancy under Warnings/Precautions: Specific Populations, in Cautions.)

Tinidazole is contraindicated in breast-feeding women. (See Lactation under Warnings/Precautions: Specific Populations, in Cautions.)

• Cockayne syndrome
• Lactation

• Peripheral neuropathy
• Seizure disorder

• Neutropenic disorder

Adverse effects occurring in 1% or more of patients receiving a single 2-g dose of tinidazole include GI effects (metallic/bitter taste, nausea, anorexia, dyspepsia/cramps/epigastric discomfort, vomiting, constipation) and nervous system effects (weakness/fatigue/malaise, dizziness, headache).

Rare or Very Rare

• Abnormal hepatic function tests
• Acute cognitive impairment
• Angioedema
• Ataxia
• Bronchospastic pulmonary disease
• Candidiasis
• Coma
• Depression
• Dyspnea
• Erythema multiforme
• Hypersensitivity drug reaction
• Leukopenia
• Neutropenic disorder
• Oral candidiasis
• Peripheral neuropathy
• Seizure disorder
• Skin rash
• Stevens-johnson syndrome
• Thrombocytopenic disorder
• Tonic clonic seizure
• Urticaria
• Vertigo

More Frequent

• Abdominal pain with cramps
• Anorexia
• Constipation
• Dizziness
• Dysgeusia
• Dyspepsia
• Fatigue
• Headache disorder
• Malaise
• Nausea
• Vomiting

Less Frequent

• General weakness
• Vaginal discharge
• Vulvovaginal candidiasis

Rare or Very Rare

• Arthralgia
• Arthritis
• Diarrhea
• Drowsy
• Fever
• Flatulence
• Flushing
• Furred tongue
• Hyperhidrosis
• Insomnia
• Menorrhagia
• Myalgia
• Palpitations
• Paresthesia
• Pelvic pain
• Pharyngitis
• Polydipsia
• Pruritus of skin
• Sialorrhea
• Stomatitis
• Tongue discoloration
• Upper respiratory infection
• Urine discoloration
• Xerostomia

No enhanced messaging available.

Safety and efficacy of tinidazole have not been established in pediatric patients 3 years of age or younger. Some data are available regarding safety and efficacy of the drug for the treatment of giardiasis in pediatric patients younger than 3 years of age+.

Safety and efficacy of tinidazole in pediatric patients have been established only for the treatment of amebiasis or giardiasis in children older than 3 years of age.

Pediatric patients should be monitored closely when the duration of tinidazole treatment exceeds 3 days (e.g., for treatment of amebic liver abscess). Only limited data are available regarding tinidazole treatment exceeding 3 days in pediatric patients, although the drug has been used for 5 days in a small number of children without an increase in the severity and incidence of adverse effects.

Adverse effects reported in pediatric patients receiving tinidazole are similar in nature and frequency to those reported in adults and include nausea, vomiting, diarrhea, taste change, anorexia, and abdominal pain.

Safety and efficacy of tinidazole have not been evaluated in pregnant women, including use of the drug for the treatment of bacterial vaginosis in pregnant women.

Because tinidazole crosses the placenta and enters fetal circulation, the drug is contraindicated during the first trimester of pregnancy. The US Centers for Disease Control and Prevention (CDC) states that use of tinidazole for the treatment of trichomoniasis or bacterial vaginosis in pregnant women should avoided.

Tinidazole is distributed into human milk in concentrations similar to serum concentrations and can be detected in milk for up to 72 hours after administration.

Tinidazole is contraindicated in breast-feeding women. Breast-feeding should be interrupted during tinidazole treatment and for 3 days (72 hours) following the last dose.

Dosage of tinidazole in geriatric patients generally should be selected with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Clinical studies of tinidazole did not include a sufficient number of patients 65 years of age or older to determine whether geriatric adults respond differently than younger adults.

Dosage for geriatric patients should be selected with caution because of possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.