Tinidazole

Mechanism of Action

Antiprotozoal; may cause cytotoxicity by damaging DNA and preventing further DNA synthesis

Pharmacokinetics

Half-life: 12-14 hr

Metabolism: Mainly by CYP3A4

Vd: 50L

Protein binding: 12%

Peak plasma time: 1.6 hr

Metabolites: Undergoes oxidation, hydroxylation & conjugation

Excretion: Mainly in urine (20-25% as unchanged drug); feces: 12%

Tinidazole is an antibiotic that fights bacteria in the body.

Tinidazole is used to treat certain infections caused by bacteria, such as infection of the intestines or vagina. It is also used to treat certain sexually transmitted infections.

Tinidazole may also be used for purposes other than those listed in this medication guide.

Do not drink alcohol while taking tinidazole and for at least 3 days after your treatment ends. You may have unpleasant side effects such as fast heartbeats, severe nausea, vomiting, sweating, and warmth or tingling under your skin.

Check the label of the products and other medicines you use, such as mouthwash or cough and cold medicines. Alcohol in these products can also cause a reaction if you use them while taking tinidazole.

You should not use this medication if you are allergic to tinidazole or metronidazole (Flagyl), or if you are in the first 3 months of pregnancy.

You should not breast-feed a baby while you are taking tinidazole. However, you may begin nursing again 3 days after you take the last dose. Do not keep any milk you collect with a breast pump while you are taking tinidazole.

Before you take tinidazole, tell your doctor if you have kidney disease (or if you are on dialysis), epilepsy or other seizure disorder, a blood cell disorder such as anemia or low platelets, or a weak immune system.

Take this medication for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Tinidazole will not treat a viral infection such as the common cold or flu.

Do not drink alcohol while taking tinidazole and for at least 3 days after your treatment ends.

A medicine similar to tinidazole has caused cancer in laboratory animals. It is not known if tinidazole would have the same effect in animals, or in humans. Talk with your doctor about your individual risk.

You should not use this medication if you are allergic to tinidazole or metronidazole (Flagyl), or if you are in the first 3 months of pregnancy.

Tinidazole can pass into breast milk and may harm a nursing baby. Do not breast-feed while you are taking tinidazole and for at least 3 days after your last dose.

You may begin nursing again 3 days after your last dose or tinidazole. If you use a breast pump during treatment, throw out any milk you collect while taking tinidazole. Do not feed it to your baby.

To make sure you can safely take tinidazole, tell your doctor if you have any of these other conditions:

• kidney disease (or if you are on dialysis);

• epilepsy or other seizure disorder;

• a blood cell disorder such as anemia or low platelets; or

• a weak immune system.

FDA pregnancy category C. Do not take tinidazole during the first 3 months of pregnancy. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

A medicine similar to tinidazole has caused cancer in laboratory animals. It is not known if tinidazole would have the same effect in animals, or in humans. Talk with your doctor about your individual risk.

Usual Adult Dose for Trichomoniasis:

2 g orally once

Comments:
-Appropriate diagnostic procedures should be used to identify organism.
-The patient's sexual partner(s) should be treated with the same dose at the same time to prevent reinfection.
-Current guidelines should be consulted for additional information.

Use: For the treatment of trichomoniasis due to Trichomonas vaginalis

Usual Adult Dose for Giardiasis:

2 g orally once

Use: For the treatment of giardiasis due to Giardia lamblia

Usual Adult Dose for Amebiasis:

2 g orally once a day

Duration of Therapy:
-Intestinal: 3 days
-Amebic liver abscess: 3 to 5 days

Comments:
-This drug is not indicated to treat asymptomatic cyst passage.

Use: For the treatment of intestinal amebiasis and amebic liver abscess due to Entamoeba histolytica

Some Experts Recommend: 2 g orally once a day

Duration of Therapy:
-Mild to moderate intestinal disease: 3 days
-Severe intestinal and extraintestinal disease: 5 days

Comments:
-Treatment with a luminal amebicide should follow this 3- or 5-day therapy.
-Current guidelines should be consulted for additional information.

Usual Adult Dose for Bacterial Vaginosis:

2 g orally once a day for 2 days OR 1 g orally once a day for 5 days

Comments:
-Formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis
-Should rule out other pathogens commonly associated with vulvovaginitis (e.g., T vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans, Herpes simplex virus)
-Use of this drug in pregnant women has not been studied.

Use: For the treatment of bacterial vaginosis in nonpregnant women

Usual Adult Dose for STD Prophylaxis:

US CDC Recommendations: 2 g orally in a single dose

Comments:
-Recommended as part of a regimen for prophylaxis after sexual assault
-Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Giardiasis:

3 years or older: 50 mg/kg orally once
Maximum dose: 2 g/dose

Use: For the treatment of giardiasis due to G lamblia

Usual Pediatric Dose for Amebiasis:

3 years or older: 50 mg/kg orally once a day
Maximum dose: 2 g/day

Duration of Therapy:
-Intestinal: 3 days
-Amebic liver abscess: 3 to 5 days

Comments:
-This drug is not indicated to treat asymptomatic cyst passage.
-Limited pediatric data on use beyond 3 days; small number of children treated for 5 days had no additional reported side effects. Close monitoring is recommended when duration of therapy exceeds 3 days.

Use: For the treatment of intestinal amebiasis and amebic liver abscess due to E histolytica

Some Experts Recommend:
3 years or older: 50 mg/kg orally once a day
Maximum dose: 2 g/day

Duration of Therapy:
-Mild to moderate intestinal disease: 3 days
-Severe intestinal and extraintestinal disease: 5 days

Comments:
-Treatment with a luminal amebicide should follow this 3- or 5-day therapy.
-Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Trichomoniasis:

Some Experts Recommend: 50 mg/kg orally once
Maximum dose: 2 g/dose

Comments:
-Recommended for trichomoniasis due to T vaginalis
-The patient's sexual partner(s) should be treated with the same dose at the same time.
-Current guidelines should be consulted for additional information.

Usual Pediatric Dose for STD Prophylaxis:

American Academy of Pediatrics Recommendations: 2 g orally in a single dose

Comments:
-Recommended as part of a regimen for postpubertal adolescents as prophylaxis after sexual assault; recommended for trichomoniasis and bacterial vaginosis
-Current guidelines should be consulted for additional information.

Tell your doctor about all other medicines you use, especially:

• any other antibiotic;

• a blood thinner such as warfarin (Coumadin);

• cyclosporine (Gengraf, Neoral, Sandimmune);

• fluorouracil (Adrucil, Efudex, Carac, Flurorplex);

• isoniazid (for treating tuberculosis);

• lithium (Lithobid, Eskalith);

• St. John's wort;

• tacrolimus (Prograf);

• an antidepressant such as nefazodone;

• antifungal medication such as clotrimazole (Mycelex Troche), itraconazole (Sporanox), ketoconazole (Extina, Ketozole, Nizoral, Xolegal), or voriconazole (Vfend);

• a barbiturate such as phenobarbital (Solfoton) and others;

• heart or blood pressure medication such as diltiazem (Cartia, Cardizem), felodipine (Plendil), nifedipine (Nifedical, Procardia), verapamil (Calan, Covera, Isoptin, Verelan), and others;

• HIV medication such as atazanavir (Reyataz), delavirdine (Rescriptor), efavirenz (Sustiva), etravirine (Intelence), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), nevirapine (Viramune), saquinavir (Invirase), or ritonavir (Norvir); or

• seizure medication such as carbamazepine (Carbatrol, Tegretol), felbamate (Felbatol), oxcarbazepine (Trileptal), phenobarbital (Solfoton), phenytoin (Dilantin), or primidone (Mysoline).

This list is not complete and other drugs may interact with tinidazole. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Antiprotozoal and antibacterial; 1 58 59 63 64 65 68 nitroimidazole derivative.1 58 59 63 64 65 68

Administration

Oral Administration

Administer orally once daily with food.1

Administration with meals may reduce incidence of adverse GI effects.1

Do not consume alcohol during or for 3 days after completion of tinidazole therapy.1

For children and other patients unable to swallow tablets, an oral suspension may be prepared extemporaneously using the tablets.1

To prepare an oral suspension containing 66.7 mg/mL, grind 2 g (four 500-mg tablets) to a fine powder with a mortar and pestle.1 Add approximately 10 mL of cherry syrup to the powder and mix until smooth.1 Transfer suspension to a graduated amber container;1 use several small rinses of the cherry syrup to transfer any remaining drug in the mortar to provide a suspension with a final volume of 30 mL.1

Shake suspension well prior to administration of each dose.1

Dosage

Pediatric Patients

Children >3 years of age (intestinal amebiasis): 50 mg/kg (up to 2 g) once daily given for 3 days;1 17 follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).1 18 25 47

Children >3 years of age (amebic liver abscess): 50 mg/kg (up to 2 g) once daily given for 3–5 days;1 17 follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).1 18 25 47

Children >3 years of age: 50 mg/kg (up to 2 g) given as a single dose.1 17

Children >3 years of age†: 50 mg/kg (up to 2 g) given as a single dose.17

Adults

Intestinal amebiasis: 2 g once daily given for 3 days;1 17 follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).1 18 25 47

Amebic liver abscess: 2 g once daily for 3–5 days;1 17 follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).1 18 25 47

2 g given as a single dose.1 17

2 g given as a single dose.1 9 17

Treat sexual partners of the patient simultaneously using the same dosage.1 9 67

For treatment failure following a metronidazole regimen (e.g., single 2-g dose of metronidazole), CDC recommends retreatment with a single 2-g dose of tinidazole; if retreatment fails, CDC recommends tinidazole 2 g once daily for 5 days.9 If multiple-dose regimen fails, consult a specialist.9

2 g once daily for 2 days or 1 g once daily for 5 days.1

CDC recommends a single 2-g dose of tinidazole in conjunction with a single1-g dose of oral azithromycin (if azithromycin not used in the initial regimen) for treatment of recurrent and persistent urethritis in patients who previously received a recommended regimen. (See Nongonococcal Urethritis under Uses.)9

Prescribing Limits

Pediatric Patients

Children >3 years of age: Maximum 50 mg/kg (up to 2 g) daily or as a single dose.1 17

Special Populations

Hepatic Impairment

Data insufficient to make specific dosage recommendations.1 Use usual dosage with caution.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Dosage adjustments not needed, unless patient is undergoing hemodialysis.1 60

If given on a day that hemodialysis is performed, administer an additional dose (equivalent to 50% of the recommended dose) after the dialysis session.1 60

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

• Importance of taking with food to reduce the incidence of adverse GI effects (e.g., epigastric discomfort).1

• Advise patients to avoid alcoholic beverages and preparations containing alcohol or propylene glycol during and for at least 3 days after receiving tinidazole.1

• Advise patients to promptly discontinue tinidazole and contact clinician if abnormal neurologic signs occur.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of advising patients of other important precautionary information.1 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

If your symptoms do not improve within a few days, or if they become worse, check with your doctor.

You should not take tinidazole during the first trimester (3 months) of pregnancy. Using tinidazole while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away. Also, do not breastfeed while using tinidazole. Wait at least three days after you stop taking tinidazole before you breastfeed .

Tinidazole may cause a vaginal yeast infection. Check with your doctor right away if you are having itching of the vagina or outside genitals; pain during sexual intercourse; or thick, white curd-like vaginal discharge without odor or with mild odor .

Drinking alcoholic beverages or using preparations that contain propylene glycol while taking tinidazole may cause stomach pain, nausea, vomiting, headache, or flushing or redness of the face. Other alcohol-containing preparations (for example, elixirs, cough syrups, tonics) may also cause problems. These problems may last for at least 3 days after you stop taking tinidazole. Also, tinidazole may cause alcoholic beverages to taste different. Therefore, you should not drink alcoholic beverages or use other alcohol or propylene glycol-containing preparations while you are taking tinidazole and for at least 3 days after stopping it.

If you are taking tinidazole for trichomoniasis (an infection of the sex organs in males and females), your doctor may want to treat your sexual partner at the same time you are being treated, even if he or she has no symptoms. Also, it may be desirable to use a condom (prophylactic) during intercourse. These measures will help keep you from getting the infection back again from your partner. If you have any questions about this, check with your doctor.

Before you have any medical tests, tell the medical doctor in charge that you are taking tinidazole. The results of some tests may be affected by tinidazole .

• If you have an allergy to tinidazole, metronidazole, or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are pregnant or may be pregnant. Do not use tinidazole in the first 3 months of pregnancy.
• If you are breast-feeding. Do not breast-feed while you take this medicine and for at least 3 days after your last dose.
• If you have taken disulfiram within the past 2 weeks.

This is not a list of all drugs or health problems that interact with tinidazole.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with food to prevent an upset stomach.
• If you have trouble swallowing, talk with your doctor.
• To gain the most benefit, do not miss doses.
• Keep using tinidazole as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• For some infections, you will get a single dose.

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Amebiasis, intestinal: Oral: 2 g once daily for 3 days

Amebiasis, liver abscess: Oral: 2 g once daily for 3 to 5 days

Bacterial vaginosis: Oral: 2 g once daily for 2 days or 1 g once daily for 5 days

Bacterial vaginosis, recurrent (off-label dose): Oral: 500 mg twice daily for 7 days followed by intravaginal therapy with boric acid, followed by intravaginal metronidazole suppressive therapy (CDC [Workowski 2015])

Giardiasis: Oral: 2 g as a single dose

Prophylaxis against sexually transmitted diseases following sexual assault (off-label use): Oral: 2 g as a single dose in combination with azithromycin plus ceftriaxone (CDC [Workowski 2015])

Trichomoniasis: Oral: 2 g as a single dose; sexual partners should be treated at the same time

Trichomoniasis, persistent or recurrent (ie, treatment failure of nitroimidazole [eg, metronidazole]) (index case; treatment of sex partner; off-label dose): Oral: 2 g once daily for 7 days (CDC [Workowski 2015])

Urethritis, nongonococcal (recurrent or persistent urethritis in men who have sex with women and who live in regions where T. vaginalis is prevalent; off-label use): Oral: 2 g as a single dose. Note: Compliance with initial regimen and lack of reexposure to an untreated sex partner should be excluded prior to use (CDC [Workowski 2015])

2 g orally once with food

3 years or older: 50 mg/kg (up to 2 g) orally once with food

3 years or older:
Intestinal: 50 mg/kg (up to 2 g) orally once a day with food for 3 days
Amebic liver abscess: 50 mg/kg (up to 2 g) orally once a day with food for 3 to 5 days
Close monitoring is recommended when treatment durations exceed 3 days.

No adjustment recommended