Tindamax

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Tinidazole may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• sharp, unpleasant metallic taste
• upset stomach
• vomiting
• loss of appetite
• constipation
• stomach pain or cramps
• headache
• tiredness or weakness
• dizziness

Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, call your doctor immediately:

• seizures
• numbness or tingling of hands or feet
• rash
• hives
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• difficulty swallowing or breathing

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

• fever, chills, body aches, flu symptoms;
• numbness, burning pain, or tingly feeling; or
• seizure (convulsions).

Less serious side effects may include:

• vaginal itching or discharge;
• nausea, vomiting, loss of appetite, indigestion;
• constipation, diarrhea, stomach cramps;
• feeling weak or tired;
• headache, dizziness; or
• a metallic or bitter taste in your mouth;

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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.

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.

Tinidazole is a synthetic antiprotozoal and antibacterial agent. It is 1-[2-(ethylsulfonyl)ethyl]-2-methyl- 5-nitroimidazole, a second-generation 2-methyl-5-nitroimidazole, which has the following chemical structure:

Tindamax pink oral tablets contain 250 mg or 500 mg of tinidazole. Inactive ingredients include croscarmellose sodium, FD&C Red 40 lake, FD&C Yellow 6 lake, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized corn starch, titanium dioxide, and triacetin.

Trichomoniasis

Tinidazole is indicated for the treatment of trichomoniasis caused by Trichomonas vaginalis. The organism should be identified by appropriate diagnostic procedures. Because trichomoniasis is a sexually transmitted disease with potentially serious sequelae, partners of infected patients should be treated simultaneously in order to prevent re-infection[see Clinical Studies].

Giardiasis

Tinidazole is indicated for the treatment of giardiasis caused by Giardia duodenalis (also termed G. lamblia) in both adults and pediatric patients older than three years of age [see Clinical Studies]. Sections or subsections omitted from the full prescribing information are not listed.

Amebiasis

Tinidazole is indicated for the treatment of intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica in both adults and pediatric patients older than three years of age. It is not indicated in the treatment of asymptomatic cyst passage [see Clinical Studies].

Bacterial Vaginosis

Tinidazole is indicated for the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis) in non-pregnant women [see Use in Specific Populations and Clinical Studies].

Other pathogens commonly associated with vulvovaginitis such as Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans and Herpes simplex virus should be ruled out.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tindamax and other antibacterial drugs, Tindamax should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

• Mission Pharmacal Company

Serious side effects have been reported with Tindamax. See the “Drug Precautions” section.

Common side effects of Tindamax include the following:

• metallic or bitter taste
• nausea
• weakness
• upset stomach
• vomiting
• headache
• dizziness
• constipation

This is not a complete list of Tindamax side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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.

• Amebicidal, trichomonacidal, and bactericidal.1 32 58 59 63 64 65 68

• Cell extracts of Trichomonas appear to reduce the nitroimidazole group of tinidazole and generate the free nitro radical, which may be responsible for the drug’s anti-infective activity.1 32 59 65 Mechanism of activity against Giardia and Entamoeba histolytica not known.1

• Protozoa: Active in vitro and in clinical infections against Trichomonas vaginalis, G. duodenalis (also known as G. lamblia or G. intestinalis), and E. histolytica.1 58 59 65

• Anaerobes: Active in vitro against many anaerobic bacteria including some Bacteroides58 64 (e.g., B. fragilis,32 59 63 64 65 68 B. melaninogenicus63 ), some Clostridium32 59 63 (e.g., C. difficile,32 C. perfringens63 64 ), Prevotella,32 Fusobacterium,63 64 68 Peptococcus,32 58 59 63 and Peptostreptococcus.32 58 59 63

• Other organisms: Active against Helicobacter pylori 32 and Gardnerella vaginalis.32 59 65 Inactive against most Lactobacillus normally resident in vagina.1 32

• Potential for development of resistance in Giardia, E. histolytica, or bacteria associated with bacterial vaginosis not evaluated.1

• Although clinical importance unclear,61 some T. vaginalis with reduced susceptibility to metronidazole also have reduced susceptibility to tinidazole in vitro.1 61 62 61

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Change in consciousness
• cough
• difficulty breathing
• loss of consciousness
• noisy breathing
• shortness of breath
• tightness in chest
• wheezing

• Black, tarry stools
• bleeding gums
• blood in urine or stools
• burning, numbness, tingling, or painful sensations
• chest pain
• chills
• difficulty swallowing
• fast, irregular, pounding, or racing heartbeat or pulse
• fever
• hives
• increased transaminase levels
• large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• lower back or side pain
• nausea
• painful or difficult urination
• pale skin
• pinpoint red spots on skin
• reddening of the skin, especially around ears
• seizures
• sore throat
• sores, ulcers, or white spots on lips or in mouth
• swelling of eyes, face, or inside of nose
• swollen glands
• ulcers
• unsteadiness or awkwardness
• unusual bleeding or bruising
• unusual tiredness or weakness
• weakness in arms, hands, legs, or feet

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bitter taste
• metallic taste

• Acid or sour stomach
• belching
• cramps
• difficulty having a bowel movement (stool)
• dizziness
• general feeling of discomfort or illness
• headache
• heartburn
• indigestion
• loss of appetite
• pain or discomfort in chest, upper stomach, or throat
• vomiting
• weight loss

• Body aches or pain
• coating on tongue
• congestion
• depression
• dryness or soreness of throat
• hoarseness
• mood or mental changes
• runny nose
• tender, swollen glands in neck
• voice changes

• Abnormal liver
• darkened urine
• diarrhea
• difficulty in moving
• feeling of constant movement of self or surroundings
• giddiness
• lightheadedness
• muscle pain or stiffness
• pain, swelling, or redness in joints
• sensation of spinning
• shakiness and unsteady walk
• sleepiness
• sleeplessness
• swelling or inflammation of the mouth
• tongue discoloration
• trembling, or other problems with muscle control or coordination
• trouble sleeping
• unable to sleep
• white or brownish vaginal discharge
• white patches in the mouth or throat or on the tongue

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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 Tindamax 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.

The use of tinidazole is contraindicated:

• In patients with a previous history of hypersensitivity to tinidazole or other nitroimidazole derivatives. Reported reactions have ranged in severity from urticaria to Stevens-Johnson syndrome [see Adverse Reactions ( 6.1, 6.2)].
• During first trimester of pregnancy [see Use in Specific Populations ( 8.1)].
• In nursing mothers: Interruption of breast-feeding is recommended during tinidazole therapy and for 3 days following the last dose [see Use in Specific Populations ( 8.3)].

Trichomoniasis

Tinidazole (2 g single oral dose) use in trichomoniasis has been well documented in 34 published reports from the world literature involving over 2,800 patients treated with tinidazole. In four published, blinded, randomized, comparative studies of the 2 g tinidazole single oral dose where efficacy was assessed by culture at time points post-treatment ranging from one week to one month, reported cure rates ranged from 92% (37/40) to 100% (65/65) (n=172 total subjects). In four published, blinded, randomized, comparative studies where efficacy was assessed by wet mount between 7-14 days post-treatment, reported cure rates ranged from 80% (8/10) to 100% (16/16) (n=116 total subjects). In these studies, tinidazole was superior to placebo and comparable to other anti-trichomonal drugs. The single oral 2 g tinidazole dose was also assessed in four open-label trials in men (one comparative to metronidazole and 3 single-arm studies). Parasitological evaluation of the urine was performed both pre- and post-treatment and reported cure rates ranged from 83% (25/30) to 100% (80/80) (n=142 total subjects).

Giardiasis

Tinidazole (2 g single dose) use in giardiasis has been documented in 19 published reports from the world literature involving over 1,600 patients (adults and pediatric patients). In eight controlled studies involving a total of 619 subjects of whom 299 were given the 2 g × 1 day (50 mg/kg × 1 day in pediatric patients) oral dose of tinidazole, reported cure rates ranged from 80% (40/50) to 100% (15/15). In three of these trials where the comparator was 2 to 3 days of various doses of metronidazole, reported cure rates for metronidazole were 76% (19/25) to 93% (14/15). Data comparing a single 2 g dose of tinidazole to usually recommended 5-7 days of metronidazole are limited.

Intestinal Amebiasis

Tinidazole use in intestinal amebiasis has been documented in 26 published reports from the world literature involving over 1,400 patients. Most reports utilized tinidazole 2 g/day × 3 days. In four published, randomized, controlled studies (1 investigator single-blind, 3 open-label) of the 2 g/day × 3 days oral dose of tinidazole, reported cure rates after 3 days of therapy among a total of 220 subjects ranged from 86% (25/29) to 93% (25/27).

Amebic Liver Abscess

Tinidazole use in amebic liver abscess has been documented in 18 published reports from the world literature involving over 470 patients. Most reports utilized tinidazole 2 g/day × 2-5 days. In seven published, randomized, controlled studies (1 double-blind, 1 single-blind, 5 open-label) of the 2 g/day × 2-5 days oral dose of tinidazole accompanied by aspiration of the liver abscess when clinically necessary, reported cure rates among 133 subjects ranged from 81% (17/21) to 100% (16/16). Four of these studies utilized at least 3 days of tinidazole.

Bacterial Vaginosis

A randomized, double-blind, placebo-controlled clinical trial in 235 non-pregnant women was conducted to evaluate the efficacy of tinidazole for the treatment of bacterial vaginosis. A clinical diagnosis of bacterial vaginosis was based on Amsel's criteria and defined by the presence of an abnormal homogeneous vaginal discharge that (a) has a pH of greater than 4.5, (b) emits a "fishy" amine odor when mixed with a 10% KOH solution, and (c) contains ≥20% clue cells on microscopic examination. Clinical cure required a return to normal vaginal discharge and resolution of all Amsel's criteria. A microbiologic diagnosis of bacterial vaginosis was based on Gram stain of the vaginal smear demonstrating (a) markedly reduced or absent Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few white blood cells, with quantification of these bacterial morphotypes to determine the Nugent score, where a score ≥4 was required for study inclusion and a score of 0-3 considered a microbiologic cure. Therapeutic cure was a composite endpoint, consisting of both a clinical cure and microbiologic cure. In patients with all four Amsel's criteria and with a baseline Nugent score ≥4, tinidazole oral tablets given as either 2 g once daily for 2 days or 1 g once daily for 5 days demonstrated superior efficacy over placebo tablets as measured by therapeutic cure, clinical cure, and a microbiologic cure.

1Modified Intent-to-Treat defined as all patients randomized with a baseline
  Nugent score of at least 4
2Difference in cure rates (Tindamax-placebo)
3CI: confidence interval
  p-values for both Tindamax regimens vs. placebo for therapeutic, clinical and
  Nugent score cure rates for both 2 and 5 days <0.001

The therapeutic cure rates reported in this clinical study conducted with Tindamax were based on resolution of 4 out of 4 Amsel's criteria and a Nugent score of <4. The cure rates for previous clinical studies with other products approved for bacterial vaginosis were based on resolution of either 2 or 3 out of 4 Amsel's criteria. At the time of approval for other products for bacterial vaginosis, there was no requirement for a Nugent score on Gram stain, resulting in higher reported rates of cure for bacterial vaginosis for those products than for those reported here for tinidazole.

Applies to tinidazole: compounding powder, oral tablet

General

Reported side effects were typically mild, infrequent, and self-limiting. Gastrointestinal side effects were reported most often.[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, dyspepsia/cramps/epigastric discomfort, vomiting, constipation, diarrhea, abdominal pain, flatulence
Rare (less than 0.1%): Furry tongue
Frequency not reported: Tongue discoloration, stomatitis, dryness of mouth, salivation, oral candidiasis, glossitis[Ref]

Nervous system

Common (1% to 10%): Metallic/bitter taste, headache, dizziness, vertigo
Rare (less than 0.1%): Coma
Frequency not reported: Convulsions, peripheral neuropathy, ataxia, giddiness, drowsiness, burning sensation, paresthesia, hypoesthesia/numbness, sensory disturbances, dysgeusia[Ref]

Other

Common (1% to 10%): Weakness/fatigue/malaise
Frequency not reported: Flushing, fever/pyrexia, thirst, Candida overgrowth, fatigue, malaise[Ref]

Dermatologic

In a study involving 450 patients with fixed drug eruptions, 8 patients were found to have this oral drug as the probable causative agent. The fixed drug eruptions varied as to duration, shape and size, symptoms, number of lesions, and body site(s) affected. The study did not break these factors down for each individual causative agent.[Ref]

Common (1% to 10%): Allergic dermatitis, pruritus
Frequency not reported: Urticaria, rash, sweating, angioedema, fixed drug eruption[Ref]

Metabolic

Common (1% to 10%): Anorexia, decreased appetite

Genitourinary

Common (1% to 10%): Urinary tract infection, dysuria/painful urination, urine abnormality, pelvic pain, vulvovaginal discomfort, vaginal odor, menorrhagia
Frequency not reported: Darkened urine/chromaturia, increased vaginal discharge, female genital pruritus, Candida vaginitis[Ref]

Respiratory

Common (1% to 10%): Upper respiratory tract infection
Rare (less than 0.1%): Bronchospasm, dyspnea, pharyngitis[Ref]

Psychiatric

Rare (less than 0.1%): Confusion, depression
Frequency not reported: Insomnia[Ref]

Hematologic

Rare (less than 0.1%): Reversible thrombocytopenia
Frequency not reported: Neutropenia, leukopenia, increased eosinophil count, decreased hemoglobin[Ref]

Hypersensitivity

Severe acute hypersensitivity reactions have been reported during initial or subsequent exposure to this drug.[Ref]

Frequency not reported: Drug hypersensitivity
Postmarketing reports: Severe acute hypersensitivity reactions, hypersensitivity reactions (included urticaria, pruritus, rash, flushing, sweating, dryness of mouth, fever, burning sensation, thirst, salivation, angioedema, Stevens-Johnson syndrome, erythema multiforme)[Ref]

Hepatic

Frequency not reported: Hepatic abnormalities (included raised transaminase level), increased AST, increased blood bilirubin[Ref]

Renal

Frequency not reported: Increased blood urea[Ref]

Cardiovascular

Frequency not reported: Palpitations[Ref]

Musculoskeletal

Frequency not reported: Arthralgias, myalgias, arthritis[Ref]

Some side effects of Tindamax may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Tinidazole has been detected in breast milk in concentrations similar to those seen in serum. Measurable levels have been detected for up to 72 hours after discontinuation of therapy.

Tinidazole is excreted into human milk. The effects in the nursing infant are unknown. Breast-feeding is not recommended during therapy and for 72 hours following the last dose.