Azithromycin/Fluconazole/Tinidazole

Azithromycin extended-release granules are indicated for the treatment of patients with mild to moderate infections caused by susceptible strains of designated microorganisms in the specific conditions listed as follows.

Adults: Acute uncomplicated bacterial sinusitis due to Haemophilus influenzae, Moraxella catarrhalis or Streptococcus pneumoniae.

Mild to moderate community-acquired pneumonia (CAP) due to Chlamydia pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Mycoplasma pneumoniae or Streptococcus pneumoniae.

Pharyngitis/tonsillitis caused by Streptococcus pyogenes as an alternative to first-line therapy in individuals who cannot use first-line therapy. (Penicillin is the usual drug of choice in the treatment of Streptococcus pyogenes pharyngitis. Azithromycin is often effective in the eradication of susceptible strains of Streptococcus pyogenes from the nasopharynx. Because some strains are resistant to azithromycin, susceptibility tests should be performed when patients are treated with azithromycin). Data establishing efficacy of azithromycin in subsequent prevention of rheumatic fever are not available.

Pediatrics: Mild to moderate community-acquired pneumonia in pediatric patients 6 months of age or older due to Chlamydophila pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae or Streptococcus pneumoniae, in patients appropriate for oral therapy. Pediatric use in this indication is based on extrapolation of adult efficacy.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Azithromycin and other antibacterial drugs, Azithromycin should be used only to treat 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.

Appropriate culture and susceptibility tests should be performed before treatment to determine the causative organism and its susceptibility to Azithromycin. Therapy with Azithromycin may be initiated before results of these tests are known; once the results become available, antimicrobial therapy should be adjusted accordingly.

Fluconazole (fluconazole) is indicated for the treatment of:

1. Vaginal candidiasis (vaginal yeast infections due to Candida).
2. Oropharyngeal and esophageal candidiasis. In open noncomparative studies of relatively small numbers of patients, Fluconazole was also effective for the treatment of Candida urinary tract infections, peritonitis, and systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia.
3. Cryptococcal meningitis. Before prescribing Fluconazole (fluconazole) for AIDS patients with cryptococcal meningitis, please see Clinical Studies section. Studies comparing Fluconazole to amphotericin B in non-HIV infected patients have not been conducted.

Prophylaxis. Fluconazole is also indicated to decrease the incidence of candidiasis in patients undergoing bone marrow transplantation who receive cytotoxic chemotherapy and/or radiation therapy.

Specimens for fungal culture and other relevant laboratory studies (serology, histopathology) should be obtained prior to therapy to isolate and identify causative organisms. Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, anti-infective therapy should be adjusted accordingly.

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.

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.

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.

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.

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 Tinidazole Tablets and other antibacterial drugs, Tinidazole Tablets 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.

Azithromycin injection is used to treat bacterial infections in many different parts of the body. It is also used to prevent Mycobacterium avium complex (MAC) disease in patients infected with the human immunodeficiency virus (HIV).

Azithromycin belongs to the class of drugs known as macrolide antibiotics. It works by killing bacteria or preventing their growth. However, azithromycin will not work for colds, flu, or other virus infections. Azithromycin injection may be used for other problems as determined by your doctor.

azithromycin is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, azithromycin is used in certain patients with the following medical condition:

• Trachoma (treatment).

Fluconazole injection is used to treat serious fungal or yeast infections, such as vaginal candidiasis, oropharyngeal candidiasis (thrush, oral thrush), esophageal candidiasis (candida esophagitis), other candida infections (including urinary tract infections, peritonitis [inflammation of the lining of the abdomen or stomach], and infections that may occur in different parts of the body), or fungal (cryptococcal) meningitis. fluconazole works by killing the fungus or yeast, or preventing its growth.

Fluconazole injection is also used to prevent candidiasis in patients having bone marrow transplants, who receive cancer or radiation treatment.

fluconazole is to be given only by or under the direct supervision of a doctor.

Tinidazole (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.

Azithromycin for oral suspension (single dose 1 g packet) can be taken with or without food after constitution. However, increased tolerability has been observed when tablets are taken with food.

Azithromycin for oral suspension (single dose 1 g packet) is not for pediatric use. For pediatric suspension see the prescribing information for Azithromycin (azithromycin for oral suspension) 100 mg/5 mL and 200 mg/5 mL bottles.

Directions for administration of Azithromycin for oral suspension in the single dose packet (1 g): The entire contents of the packet should be mixed thoroughly with two ounces (approximately 60 mL) of water. Drink the entire contents immediately; add an additional two ounces of water, mix, and drink to ensure complete consumption of dosage. The single dose packet should not be used to administer doses other than 1000 mg of azithromycin.

Sexually Transmitted Diseases

The recommended dose of Azithromycin for the treatment of non-gonococcal urethritis and cervicitis due to C. trachomatis is a single 1 gram (1000 mg) dose of Azithromycin. This dose can be administered as one single dose packet (1 g).

Mycobacterial Infections

Prevention of Disseminated MAC Infections

The recommended dose of Azithromycin for the prevention of disseminated Mycobacterium avium complex (MAC) disease is: 1200 mg taken once weekly. This dose of Azithromycin may be combined with the approved dosage regimen of rifabutin.

Treatment of Disseminated MAC Infections

Azithromycin should be taken at a daily dose of 600 mg, in combination with ethambutol at the recommended daily dose of 15 mg/kg. Other antimycobacterial drugs that have shown in vitro activity against MAC may be added to the regimen of azithromycin plus ethambutol at the discretion of the physician or health care provider.

How supplied

Dosage Forms And Strengths

Azithromycin 600 mg tablets (engraved on front with “PFIZER” and on back with “308”) are supplied as white, modified oval-shaped, film-coated tablets containing azithromycin dihydrate equivalent to 600 mg azithromycin. These are packaged in bottles of 30 tablets.

Azithromycin for oral suspension 1000 mg/5 mL is supplied in single-dose packets containing azithromycin dihydrate equivalent to 1 gram of azithromycin.

Storage And Handling

Azithromycin 600 mg tablets (engraved on front with “PFIZER” and on back with “308”) are supplied as white, modified oval-shaped, film-coated tablets containing azithromycin dihydrate equivalent to 600 mg azithromycin. These are packaged in bottles of 30 tablets. Azithromycin tablets are supplied as follows:

Bottles of 30 NDC 0069-3080-30

Tablets should be stored at or below 30°C (86°F).

Azithromycin for oral suspension is supplied in single-dose packets containing azithromycin dihydrate equivalent to 1 gram of azithromycin as follows:

Boxes of 10 single-dose packets (1 g) NDC 0069-3051-07

Boxes of 3 single-dose packets (1 g) NDC 0069-3051-75

Store single-dose packets between 5° and 30°C (41° and 86°F).

Distributed by: Pfizer Labs Division of Pfizer Inc., NY, NY 10017. Revised: Dec 2015

Dosage and Administration in Adults

Single Dose: Vaginal Candidiasis: The recommended dosage of fluconazole for vaginal candidiasis is 150 mg as a single oral dose.

Multiple Dose: SINCE ORAL ABSORPTION IS RAPID AND ALMOST COMPLETE, THE DAILY DOSE OF FLUCONAZOLE IS THE SAME FOR ORAL (TABLETS AND SUSPENSION) AND INTRAVENOUS ADMINISTRATION. In general, a loading dose of twice the daily dose is recommended on the first day of therapy to result in plasma concentrations close to steady-state by the second day of therapy.

The daily dose of fluconazole for the treatment of infections other than vaginal candidiasis should be based on the infecting organism and the patient’s response to therapy. Treatment should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse.

Oropharyngeal Candidiasis: The recommended dosage of fluconazole for oropharyngeal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Clinical evidence of oropharyngeal candidiasis generally resolves within several days, but treatment should be continued for at least 2 weeks to decrease the likelihood of relapse.

Esophageal Candidiasis: The recommended dosage of fluconazole for esophageal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Doses up to 400 mg/day may be used, based on medical judgment of the patient’s response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least two weeks following resolution of symptoms.

Systemic Candida Infections: For systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia, optimal therapeutic dosage and duration of therapy have not been established. In open, noncomparative studies of small numbers of patients, doses of up to 400 mg daily have been used.

Urinary Tract Infections and Peritonitis: For the treatment of Candida urinary tract infections and peritonitis, daily doses of 50 to 200 mg have been used in open, noncomparative studies of small numbers of patients.

Cryptococcal Meningitis: The recommended dosage for treatment of acute cryptococcal meningitis is 400 mg on the first day, followed by 200 mg once daily. A dosage of 400 mg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. The recommended dosage of fluconazole for suppression of relapse of cryptococcal meningitis in patients with AIDS is 200 mg once daily.

Prophylaxis in Patients Undergoing Bone Marrow Transplantation: The recommended fluconazole daily dosage for the prevention of candidiasis in patients undergoing bone marrow transplantation is 400 mg, once daily. Patients who are anticipated to have severe granulocytopenia (less than 500 neutrophils per cu mm) should start fluconazole prophylaxis several days before the anticipated onset of neutropenia, and continue for 7 days after the neutrophil count rises above 1000 cells per cu mm.

Dosage and Administration in Children

The following dose equivalency scheme should generally provide equivalent exposure in pediatric and adult patients:

Experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns. Based on the prolonged half-life seen in premature newborns (gestational age 26 to 29 weeks), these children, in the first two weeks of life, should receive the same dosage (mg/kg) as in older children, but administered every 72 hours. After the first two weeks, these children should be dosed once daily. No information regarding fluconazole pharmacokinetics in full-term newborns is available.

Oropharyngeal Candidiasis: The recommended dosage of fluconazole for oropharyngeal candidiasis in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Treatment should be administered for at least 2 weeks to decrease the likelihood of relapse.

Esophageal Candidiasis: For the treatment of esophageal candidiasis, the recommended dosage of fluconazole in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Doses up to 12 mg/kg/day may be used based on medical judgment of the patient’s response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least 2 weeks following the resolution of symptoms.

Systemic Candida Infections: For the treatment of candidemia and disseminated Candida infections, daily doses of 6 to 12 mg/kg/day have been used in an open, noncomparative study of a small number of children.

Cryptococcal Meningitis: For the treatment of acute cryptococcal meningitis, the recommended dosage is 12 mg/kg on the first day, followed by 6 mg/kg once daily. A dosage of 12 mg/kg once daily may be used, based on medical judgment of the patient’s response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. For suppression of relapse of cryptococcal meningitis in children with AIDS, the recommended dose of fluconazole is 6 mg/kg once daily.

Dosage in Patients with Impaired Renal Function

Fluconazole is cleared primarily by renal excretion as unchanged drug. There is no need to adjust single dose therapy for vaginal candidiasis because of impaired renal function. In patients with impaired renal function who will receive multiple doses of fluconazole, an initial loading dose of 50 to 400 mg should be given. After the loading dose, the daily dose (according to indication) should be based on the following table:

Patients on regular dialysis should receive 100% of the recommended dose after each dialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.

These are suggested dose adjustments based on pharmacokinetics following administration of multiple doses. Further adjustment may be needed depending upon clinical condition.

When serum creatinine is the only measure of renal function available, the following formula (based on sex, weight, and age of the patient) should be used to estimate the creatinine clearance in adults:

Females: 0.85 x above value

Although the pharmacokinetics of fluconazole has not been studied in children with renal insufficiency, dosage reduction in children with renal insufficiency should parallel that recommended for adults. The following formula may be used to estimate creatinine clearance in children:

(Where K=0.55 for children older than 1 year and 0.45 for infants.)

Administration

Fluconazole for

Oral Suspension USP is administered orally. Fluconazole can be taken with or without food.

Directions for Mixing the

Oral Suspension

Prepare a suspension at time of dispensing as follows: tap bottle until all the powder flows freely. To reconstitute, add 24 mL of distilled water or Purified Water (USP) to fluconazole bottle and shake vigorously to suspend powder. Each bottle will deliver 35 mL of suspension. The concentrations of the reconstituted suspensions are as follows:

Note: Shake oral suspension well before using. Before Reconstitution: Store at 20° to 25°C (68° to 77°F). After Reconstitution: Store suspension at 5° to 25°C (41° to 77°F). Discard unused portion after 2 weeks. Protect from freezing.

Usual Adult Dose for Trichomoniasis

2 g orally once with food

The sexual partners should be treated with the same dose at the same time.

Usual Adult Dose for Giardiasis

2 g orally once with food

Usual Adult Dose for Amebiasis

Intestinal: 2 g orally once a day with food for 3 days

Amebic liver abscess: 2 g orally once a day with food for 3 to 5 days

Usual Adult Dose for Bacterial Vaginosis

Nonpregnant, adult women: 2 g orally once a day with food for 2 days or 1 g orally once a day with food for 5 days

Usual Pediatric Dose for Trichomoniasis

2 g orally once with food

The sexual partners should be treated with the same dose at the same time.

Usual Pediatric Dose for Giardiasis

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

Usual Pediatric Dose for Amebiasis

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.

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

No data available for dosing adjustments for tinidazole. However, caution should be used in dosing patients with severe hepatic dysfunction due to reduction of metabolic elimination of metronidazole in this patient population.

Dose Adjustments

No adjustment recommended

Precautions

Convulsive seizures and peripheral neuropathy have been reported. The drug should be discontinued if patient experiences abnormal neurological symptoms. Tinidazole should be administered cautiously to patients with diseases of the central nervous system.

Tinidazole may produce transient leukopenia and neutropenia, However no persistent hematological abnormalities attributable to tinidazole have been observed clinically. If retreatment is necessary, total and differential leukocyte counts are recommended.

Alcoholic beverages should be avoided during and for 3 days after tinidazole therapy.

Animal studies have revealed carcinogenicity with another agent in the nitroimidazole class (metronidazole). Therefore, unnecessary use of tinidazole should be avoided.

Tinidazole is contraindicated during the first trimester of pregnancy.

Tinidazole is contraindicated in women who are breastfeeding. Interruption of breastfeeding is recommended for the duration of treatment and for 72 hours following the last dose.

To reduce the risk of development of drug resistant organisms, antibiotics should only be used to treat or prevent proven or suspected infections caused by bacteria. Culture and susceptibility information should be considered when selecting treatment or, if no data are available, local epidemiology and susceptibility patterns may be considered when selecting empiric therapy. Patients should be advised to avoid missing doses and to complete the entire course of therapy.

Dialysis

Hemodialysis: On the day of hemodialysis, if tinidazole is administered prior to hemodialysis, an additional dose equivalent to one-half of the original dose should be administered after the end of hemodialysis.

Peritoneal dialysis: Data not available

Other Comments

Bioavailability is not affected by food.

For patients unable to swallow tablets, tinidazole tablets may be crushed in artificial cherry syrup and administered with food. The oral suspension may be prepared as follows:

1. Crush four 500 mg oral tablets to a powder with mortar and pestle.

2. Add about 10 mL cherry syrup to the powder and mix until smooth.

3. Transfer the suspension to a graduated amber container.

4. Use several small rinses of cherry syrup to transfer any remaining drug in the mortar to the final suspension for a total volume of 30 mL.

The oral suspension should be shaken well before each administration. The oral suspension of crushed tablets in artificial cherry syrup is stable for 7 days at room temperature.

See also:
What is the most important information I should know about Azithromycin?

You should not use this medication if you have ever had jaundice or liver problems caused by taking azithromycin. You should not use azithromycin if you are allergic to it or to similar drugs such as erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), clarithromycin (Biaxin), telithromycin (Ketek), or troleandomycin (Tao).

There are many other medicines that can interact with azithromycin. 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. Keep a list of all your medicines and show it to any healthcare provider who treats you.

Take this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Azithromycin will not treat a viral infection such as the common cold or flu.

Avoid taking an antacid within 2 hours before or after you take azithromycin. Some antacids can make it harder for your body to absorb azithromycin.

See also:
What is the most important information I should know about Fluconazole?

Fluconazole (fluconazole) is contraindicated in patients who have shown hypersensitivity to fluconazole or to any of its excipients. There is no information regarding cross-hypersensitivity between fluconazole and other azole antifungal agents. Caution should be used in prescribing Fluconazole to patients with hypersensitivity to other azoles. Coadministration of terfenadine is contraindicated in patients receiving Fluconazole (fluconazole) at multiple doses of 400 mg or higher based upon results of a multiple dose interaction study. Coadministration of other drugs known to prolong the QT interval and which are metabolized via the enzyme CYP3A4 such as cisapride, astemizole, erythromycin, pimozide, and quinidine are contraindicated in patients receiving fluconazole.

See also:
What is the most important information I should know about Tinidazole?

Hypersensitivity to tinidazole, other 5-nitroimidazole derivatives or to any of the excipients of Tinidazole.

As with other drugs of similar structure, tinidazole is also contraindicated in patients having or with a history of blood dyscrasias, although no persistent hematologic abnormalities have been noted in clinical or animal studies.

Use in pregnancy: Tinidazole crosses the placental barrier. Since the effects of compounds of this class on fetal development are unknown, the use of tinidazole during the 1st trimester is contraindicated. There is no evidence that tinidazole is harmful during the latter stages of pregnancy, but its use during the 2nd and 3rd trimesters requires that the potential benefits be weighed against possible hazards to the mother or fetus.

Use in lactation: Tinidazole is distributed in breast milk. Tinidazole may be present in breast milk for >72 hrs after administration. Women should not nurse during and for at least 3 days after having discontinued taking tinidazole.

Use Azithromycin as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Azithromycin. Talk to your pharmacist if you have questions about this information.
• Azithromycin is for use in the eye only. Do not swallow it.
• Wash your hands immediately before you use Azithromycin.
• To use Azithromycin, turn the bottle upside down and shake once before each use. Remove the cap while the bottle is still upside down. Tilt your head back. Using your index finger, pull the lower eyelid away from the eye to form a pouch. Gently squeeze the bottle to drop the medicine into the pouch, then gently close your eyes. Immediately use your finger to apply pressure to the inside corner of the eye for 1 to 2 minutes. Do not blink. Remove excess medicine around your eye with a clean, dry tissue, being careful not to touch your eye. Wash your hands to remove any medicine that may be on them.
• If a drop does not come out of the bottle when using your dose, repeat these steps.
• To prevent germs from contaminating your medicine, do not touch the applicator tip to any surface, including the eye. Keep the container tightly closed.
• Do not wear contact lenses while you are using Azithromycin. Take care of your contact lenses as directed by the manufacturer. Check with your doctor before you use them.
• To clear up your infection completely, use Azithromycin for the full course of treatment. Keep using it even if you feel better in a few days.
• If you miss a dose of Azithromycin, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Azithromycin.

Use Fluconazole as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Fluconazole is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Fluconazole at home, a health care provider will teach you how to use it. Be sure you understand how to use Fluconazole. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Do not use Fluconazole if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• To clear up your infection completely, use Fluconazole for the full course of treatment. Keep using it even if you feel better in a few days. Do not miss any doses.
• Fluconazole works best if it is taken at the same time each day.
• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Fluconazole, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Fluconazole.

Use tinidazole as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take tinidazole by mouth with food.
• If you have trouble swallowing the tablets, check with your doctor or pharmacist.
• If you take cholestyramine, do not take it at the same time you take tinidazole. Talk with your doctor about how you should take cholestyramine with tinidazole.
• If more than one dose of tinidazole is required, continue using tinidazole for the full course of treatment in order to clear up your infection completely, even if you feel better in a few days. Do not miss any doses.
• If you miss a dose of tinidazole, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use tinidazole.

Use: Labeled Indications

Oral, IV:

Chancroid: Treatment of genital ulcer disease (in men) due to Haemophilus ducreyi (chancroid)

Chronic obstructive pulmonary disease, acute exacerbation: Treatment of acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD) due to Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae

Mycobacterium avium complex: Prevention of Mycobacterium avium complex (MAC) in patients with advanced HIV infection; treatment of disseminated MAC (in combination with ethambutol) in patients with advanced HIV infection

Otitis media, acute: Treatment of acute otitis media due to H. influenzae, M. catarrhalis, or S. pneumoniae

Pneumonia, community-acquired: Treatment of community-acquired pneumonia (CAP) due to Chlamydophila pneumoniae, H. influenzae, Legionella pneumophila, M. catarrhalis, Mycoplasma pneumoniae, or S. pneumoniae

Skin and skin structure infection, uncomplicated: Treatment of uncomplicated skin and skin structure infections due to Staphylococcus aureus, Streptococcus pyogenes, or Streptococcus agalactiae

Streptococcal pharyngitis (group A): Treatment of pharyngitis/tonsillitis due to S. pyogenes as an alternative to first-line therapy

Urethritis/cervicitis: Treatment of urethritis and cervicitis due to Chlamydia trachomatis or Neisseria gonorrhoeae

Off Label Uses

Acne vulgaris

Data from controlled trials support the use of azithromycin in the treatment of acne vulgaris in adults with moderate to severe acne.

Based on the American Academy of Dermatology guidelines of care for the management of acne vulgaris, azithromycin, in combination with topical therapy, may be considered as a treatment option for moderate and severe acne and forms of inflammatory acne that are resistant to topical treatments. However, its use should be limited to patients who cannot receive a tetracycline (ie, pregnant women). Concomitant topical therapy with benzoyl peroxide or a retinoid should be administered with systemic antibiotic therapy (eg, azithromycin) and continued for maintenance after the antibiotic course is completed.

Babesiosis

Data from a prospective, nonblinded, randomized trial in patients with non-life-threatening babesiosis, support the use of azithromycin (in combination with atovaquone) for the treatment of this condition.

Based on the CDC Yellow Book, the ACG guideline for the diagnosis, treatment, and prevention of acute diarrheal infections in adults, and the IDSA practice guidelines for the diagnosis and management of infectious diarrhea, azithromycin is effective and recommended treatment for patients with travelers' diarrhea. Due to increased levels of resistance to fluoroquinolones, azithromycin may be a recommended first-line treatment, especially in regions with a high prevalence of Campylobacter (eg, Southeast Asia, India) or in geographical areas with suspected fluoroquinolone-resistant pathogens or enterotoxigenic Escherichia coli.

Use: Labeled Indications

Treatment of candidiasis (esophageal, oropharyngeal, peritoneal, urinary tract, vaginal); systemic candida infections (eg, candidemia, disseminated candidiasis, pneumonia); and cryptococcal meningitis; and antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients

Off Label Uses

Blastomycosis

Data from a randomized, multicenter, open-label study comparing fluconazole 400 mg versus 800 mg suggest that the use of fluconazole at each of these doses is effective for the treatment of non-life-threatening blastomycosis.

Use: Labeled Indications

Amebiasis: Treatment of intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica in adults and pediatric patients older than 3 years.

Limitations of use: Not indicated for the treatment of asymptomatic cyst passage.

Bacterial vaginosis: Treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis) in adult women.

Giardiasis: Treatment of giardiasis caused by Giardia duodenalis (also termed Giardia lamblia) in adults and pediatric patients older than 3 years.

Trichomoniasis: Treatment of trichomoniasis caused by Trichomonas vaginalis; treat partners of infected patients simultaneously to prevent reinfection.

Off Label Uses

Helicobacter pylori eradication

Based on the American College of Gastroenterology Clinical Guideline for the Treatment of Helicobacter pylori Infection, tinidazole is an effective and recommended component of a multiple-drug regimen for the treatment of this condition.

Prophylaxis against sexually transmitted diseases following sexual assault

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, tinidazole, in combination with ceftriaxone and Tinidazole, is a recommended regimen for prophylaxis against sexually transmitted diseases following sexual assault in adolescents and adults.

Urethritis, nongonococcal (persistent and recurrent)

Based on the CDC sexually transmitted diseases treatment guidelines, tinidazole is effective and recommended as treatment for recurrent and persistent urethritis for men who have sex with women and who live in areas where T. vaginalis is prevalent. Compliance with initial regimen and lack of reexposure to an untreated sex partner should be excluded prior to use. Sex partners should be referred for evaluation and appropriate treatment.

See also:
What other drugs will affect Azithromycin?

Antacids: In a pharmacokinetic study investigating the effects of simultaneous administration of antacid with azithromycin, no effect on overall bioavailability was seen, although peak serum concentrations were reduced by approximately 24%. In patients receiving both azithromycin and antacids, the drugs should not be taken simultaneously. Co-administration of azithromycin extended-release granules for oral suspension with a single dose of 20 mL co-magaldrox (aluminum hydroxide and magnesium hydroxide) did not affect the rate and extent of azithromycin absorption.

Cetirizine: In healthy volunteers, co-administration of a 5-day regimen of azithromycin with 20 mg cetirizine at steady-state resulted in no pharmacokinetic interaction and no significant changes in the QT interval.

Didanosine (Dideoxyinosine): Co-administration of 1,200 mg/day azithromycin with 400 mg/day didanosine in six HIV-positive subjects did not appear to affect the steady-state pharmacokinetics of didanosine as compared to placebo.

Digoxin: Concomitant administration of macrolide antibiotics, including azithromycin, with P-glycoprotein substrates such as digoxin, has been reported to result in increased serum levels of the P-glycoprotein substrate. Therefore, if azithromycin and P-glycoprotein substrates such as digoxin are administered concomitantly, the possibility of elevated serum digoxin concentrations should be considered. Clinical monitoring, and possibly serum digoxin levels, during treatment with azithromycin and after its discontinuation are necessary.

Ergot: There is a theoretical possibility of interaction between azithromycin and ergot derivatives.

Zidovudine: Single 1,000 mg doses and multiple 1,200 mg or 600 mg doses of azithromycin had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells. The clinical significance of this finding is unclear, but it may be of benefit to patients.

Azithromycin does not interact significantly with the hepatic cytochrome P450 system. It is not believed to undergo the pharmacokinetic drug interactions as seen with erythromycin and other macrolides. Hepatic cytochrome P450 induction or inactivation via cytochrome-metabolite complex does not occur with azithromycin.

Pharmacokinetic studies have been conducted between azithromycin and the following drugs known to undergo significant cytochrome P450-mediated metabolism.

Atorvastatin: Co-administration of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not alter the plasma concentrations of atorvastatin (based on a HMG CoA-reductase inhibition assay). However, post-marketing cases of rhabdomyolysis in patients receiving azithromycin with statins have been reported.

Carbamazepine: In a pharmacokinetic interaction study in healthy volunteers, no significant effect was observed on the plasma levels of carbamazepine or its active metabolite in patients receiving concomitant azithromycin.

Cimetidine: In a pharmacokinetic study investigating the effects of a single dose of cimetidine, given 2 hours before azithromycin, on the pharmacokinetics of azithromycin, no alteration of azithromycin pharmacokinetics was seen.

Coumarin-Type

Oral Anticoagulants:

Cyclosporin: In a pharmacokinetic study with healthy volunteers who were administered a 500 mg/day oral dose of azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of cyclosporin, the resulting cyclosporin C_max and AUC_0-5 were found to be significantly elevated. Consequently, caution should be exercised before considering concurrent administration of these drugs. If co-administration of these drugs is necessary, cyclosporin levels should be monitored and the dose adjusted accordingly.

Efavirenz: Co-administration of a single dose of 600 mg azithromycin and 400 mg efavirenz daily for 7 days did not result in any clinically significant pharmacokinetic interactions.

Fluconazole: Co-administration of a single dose of 1,200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. Total exposure and half-life of azithromycin were unchanged by the co-administration of fluconazole; however, a clinically insignificant decrease in C_max (18%) of azithromycin was observed.

Indinavir: Co-administration of a single dose of 1,200 mg azithromycin had no statistically significant effect on the pharmacokinetics of indinavir administered as 800 mg three times daily for 5 days.

Methylprednisolone: In a pharmacokinetic interaction study in healthy volunteers, azithromycin had no significant effect on the pharmacokinetics of methylprednisolone.

Midazolam: In healthy volunteers, co-administration of 500 mg/day azithromycin for 3 days did not cause clinically significant changes in the pharmacokinetics and pharmacodynamics of a single dose of 15 mg midazolam.

Nelfinavir: Co-administration of azithromycin (1,200 mg) and nelfinavir at steady-state (750 mg three times daily) resulted in increased azithromycin concentrations. No clinically significant adverse effects were observed and no dose adjustment was required. Although no dosage adjustment of Azithromycin is recommended when administered with nelfinavir, close monitoring for known side effects of azithromycin, such as liver enzyme abnormalities and hearing impairment, is warranted.

Rifabutin: Co-administration of azithromycin and rifabutin did not affect the serum concentrations of either drug.

Neutropenia was observed in subjects receiving concomitant treatment of azithromycin and rifabutin. Although neutropenia has been associated with the use of rifabutin, a causal relationship to combination with azithromycin has not been established.

Sildenafil: In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500 mg daily for 3 days) on the AUC and C_max of sildenafil or its major circulating metabolite.

Terfenadine: Pharmacokinetic studies have reported no evidence of an interaction between azithromycin and terfenadine. There have been rare cases reported where the possibility of such an interaction could not be entirely excluded; however, there was no specific evidence that such an interaction had occurred.

Theophylline: There is no evidence of a clinically significant pharmacokinetic interaction when azithromycin and theophylline are co-administered to healthy volunteers.

Triazolam: In 14 healthy volunteers, co-administration of 500 mg azithromycin on Day 1 and 250 mg on Day 2 with 0.125 mg triazolam on Day 2 had no significant effect on any of the pharmacokinetic variables for triazolam compared to triazolam and placebo.

Trimethoprim/Sulfamethoxazole: Co-administration of trimethoprim/sulfamethoxazole DS (160 mg/800 mg) for 7 days with 1,200 mg azithromycin on Day 7 had no significant effect on peak concentrations, total exposure or urinary excretion of either trimethoprim or sulfamethoxazole. Azithromycin serum concentrations were similar to those seen in other studies.

Incompatibilities: Not applicable.

See also:
What other drugs will affect Fluconazole?

Anticoagulants: Bleeding events (bruising, epistaxis, gastrointestinal bleeding, hematuria, and melena), have been reported, in association with increases in prothrombin time in patients receiving fluconazole concurrently with warfarin. Prothrombin time in patients receiving coumarin-type anticoagulant should be carefully monitored.

Fluconazole: There was no significant pharmacokinetic interaction between fluconazole and Fluconazole.

Benzodiazepines (Short Acting): Following oral administration of midazolam, fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects. This effect on midazolam appears to be more pronounced following oral administration of fluconazole than with fluconazole administered intravenously. If concomitant benzodiazepine therapy is necessary in patients being treated with fluconazole, consideration should be given to decreasing the benzodiazepine dosage, and the patients should be appropriately monitored.

Cisapride: Cisapride increased risk of ventricular arrhythmia troubles notably torsades de pointes. The interaction between fluconazole and cisapride yielded significant increase in cisapride plasma levels and prolongation of QTc interval. Coadministration of cisapride is contraindicated in patients receiving fluconazole.

Cyclosporin: Fluconazole slowly increase cyclosporin concentrations in renal transplant patients. Fluconazole did not affect cyclosporine levels in patients with bone marrow transplants. Cyclosporin plasma concentration monitoring in patients receiving fluconazole is recommended.

Hydrochlorothiazide: Interaction between multiple-dose hydrochlorothiazide and fluconazole has increased plasma concentrations of fluconazole by 40%. An effect of this magnitude should not necessitate a change in the fluconazole dose regimen in subjects receiving concomitant diuretics, although the prescriber should bear it in mind.

Oral Contraceptives:

Phenytoin: Concomitant administration of fluconazole and phenytoin may increase the levels of phenytoin to a clinically significant degree. If it is necessary to administer both drugs concomitantly, phenytoin levels should be monitored and the phenytoin dose adjusted to maintain therapeutic levels.

Pimozide: Combination of fluconazole will increase the risk of ventricular arrhythmia troubles notably torsades de pointes.

Rifabutin: An interaction exists when fluconazole is administered concurrently with rifabutin, leading to increased serum levels of rifabutin. There have been reports of uveitis in patients to whom fluconazole and rifabutin were coadministered. Patients receiving rifabutin and fluconazole concomitantly should be carefully monitored.

Rifampicin: Concomitant administration of fluconazole and rifampicin resulted in a 25% decrease in the AUC and a 20% shorter half-life of fluconazole. In patients receiving concomitant rifampicin, an increase of the fluconazole dose should be considered.

Sulfonylureas: Fluconazole has been shown to prolong the serum half-life of concomitantly administered oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide) in healthy volunteers. Fluconazole and oral sulfonylureas may be coadministered to diabetic patients, but the possibility of a hypoglycemic episode should be borne in mind.

Tacrolimus: An interaction exists when fluconazole is administered concomitantly with tacrolimus, leading to increased serum levels of tacrolimus. There have been reports of nephrotoxicity in patients also. Patients receiving tacrolimus and fluconazole concomitantly should be carefully monitored.

Terfenadine: Concomitant fluconazole and terfenadine causes palpitations, tachycardia, dizziness, and chest pain where the relationship of the adverse events to drug therapy or underlying medical condition was not clear. Because of the potential seriousness of such an interaction, it is recommended that terfenadine not be taken in combination with fluconazole.

Theophylline: Patients who are receiving high dose theophylline or who are otherwise at increased risk for theophylline toxicity should be observed for signs of theophylline toxicity while receiving fluconazole, and therapy modified appropriately it signs of toxicity develop.

Zidovudine: Increased levels of zidovudine most likely caused by the decreased conversion of zidovudine to its major metabolite. Patients receiving this combination of fluconazole and zidovudine should be monitored for the development of zidovudine-related adverse reaction.

Use of fluconazole in combination with astemizole or other drugs metabolized by the cytochrome P-450 system may be associated with elevations in serum levels of these drugs.

Oral fluconazole is coadministered with food, cimetidine, antacids or following total body irradiation for bone marrow transplantation. No clinically significant impairment of fluconazole absorption.

See also:
What other drugs will affect Tinidazole?

Although not specifically identified in studies with tinidazole, the following drug interactions were reported for metronidazole, a chemically-related nitroimidazole. Therefore, these drug interactions may occur with tinidazole.

Potential Effects Of Tinidazole On Other Drugs

Warfarin And Other

Oral Coumarin Anticoagulants

As with metronidazole, tinidazole may enhance the effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time. The dosage of oral anticoagulants may need to be adjusted during tinidazole co-administration and up to 8 days after discontinuation.

Alcohols, Disulfiram

Alcoholic beverages and preparations containing ethanol or propylene glycol should be avoided during tinidazole therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur. Psychotic reactions have been reported in alcoholic patients using metronidazole and disulfiram concurrently. Though no similar reactions have been reported with tinidazole, tinidazole should not be given to patients who have taken disulfiram within the last two weeks.

Lithium

Metronidazole has been reported to elevate serum lithium levels. It is not known if tinidazole shares this property with metronidazole, but consideration should be given to measuring serum lithium and creatinine levels after several days of simultaneous lithium and tinidazole treatment to detect potential lithium intoxication.

Phenytoin, Fosphenytoin

Concomitant administration of oral metronidazole and intravenous phenytoin was reported to result in prolongation of the half-life and reduction in the clearance of phenytoin. Metronidazole did not significantly affect the pharmacokinetics of orally-administered phenytoin.

Cyclosporine, Tacrolimus

There are several case reports suggesting that metronidazole has the potential to increase the levels of cyclosporine and tacrolimus. During tinidazole co-administration with either of these drugs, the patient should be monitored for signs of calcineurin-inhibitor associated toxicities.

Fluorouracil

Metronidazole was shown to decrease the clearance of fluorouracil, resulting in an increase in side-effects without an increase in therapeutic benefits. If the concomitant use of tinidazole and fluorouracil cannot be avoided, the patient should be monitored for fluorouracil-associated toxicities.

Potential Effects Of Other Drugs On Tinidazole

CYP3A4 Inducers And Inhibitors

Simultaneous administration of tinidazole with drugs that induce liver microsomal enzymes, i.e., CYP3A4 inducers such as phenobarbital, rifampin, phenytoin, and fosphenytoin (a pro-drug of phenytoin), may accelerate the elimination of tinidazole, decreasing the plasma level of tinidazole. Simultaneous administration of drugs that inhibit the activity of liver microsomal enzymes, i.e., CYP3A4 inhibitors such as cimetidine and ketoconazole, may prolong the half-life and decrease the plasma clearance of tinidazole, increasing the plasma concentrations of tinidazole.

Cholestyramine

Cholestyramine was shown to decrease the oral bioavailability of metronidazole by 21%. Thus, it is advisable to separate dosing of cholestyramine and tinidazole to minimize any potential effect on the oral bioavailability of tinidazole.

Oxytetracycline

Oxytetracycline was reported to antagonize the therapeutic effect of metronidazole.

Laboratory Test Interactions

Tinidazole, like metronidazole, may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD+↔ NADH). Potential interference is due to the similarity of absorbance peaks of NADH and tinidazole.

Tinidazole, like metronidazole, may produce transient leukopenia and neutropenia; however, no persistent hematological abnormalities attributable to tinidazole have been observed in clinical studies. Total and differential leukocyte counts are recommended if re-treatment is necessary.

See also:
What are the possible side effects of Azithromycin?

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adults:

The data described below reflect exposure to Azithromycin in 728 adult patients. All patients received a single 2 g oral dose of Azithromycin. The population studied had community-acquired pneumonia and acute bacterial sinusitis.

In controlled clinical trials with Azithromycin, the majority of the reported treatment-related adverse reactions were gastrointestinal in nature and mild to moderate in severity.

Overall, the most common treatment-related adverse reactions in adult patients receiving a single 2 g dose of Azithromycin were diarrhea/loose stools (12%), nausea (4%), abdominal pain (3%), headache (1%), and vomiting (1%). The incidence of treatment-related gastrointestinal adverse reactions was 17% for Azithromycin and 10% for pooled comparators.

Treatment-related adverse reactions following Azithromycin treatment that occurred with a frequency of <1% included the following:

Cardiovascular: Palpitations, chest pain

Gastrointestinal: Constipation, dyspepsia, flatulence, gastritis, oral moniliasis

Genitourinary: Vaginitis

Nervous system: Dizziness, vertigo

General: Asthenia

Allergic: Rash, pruritus, urticaria

Special senses: Taste perversion

Pediatric Patients:

The data described below reflect exposure to Azithromycin in 907 pediatric patients. The population was 3 months to 12 years of age. All patients received a single 60 mg/kg oral dose of Azithromycin.

As in adults, the most common treatment-related adverse reactions in pediatric subjects were gastrointestinal in nature. The pediatric subjects all received a single 60 mg/kg dose (equivalent to 27 mg/lb) of Azithromycin.

In a trial with 450 pediatric subjects (ages 3 months to 48 months), vomiting (11%), diarrhea (10%) loose stools (9%), and abdominal pain (2%) were the most frequently reported treatment-related gastrointestinal adverse reactions. Many treatment related gastrointestinal adverse reactions with an incidence greater than 1% began on the day of dosing in these subjects [43% (68/160)] and most [53% (84/160)] resolved within 48 hr of onset. Treatment-related adverse events that were not gastrointestinal, occurring with a frequency ≥ 1% were: rash (5%), anorexia (2%), fever (2%), and dermatitis (2%).

In a second trial of 337 pediatric subjects, ages 2 years to 12 years, the most frequently reported treatment-related adverse reactions also included vomiting (14%), diarrhea (7%), loose stools (2%), nausea (4%) and abdominal pain (4%).

A third trial investigated the tolerability of two different concentrations of azithromycin oral suspension in 120 pediatric subjects (ages 3 months to 48 months), all of whom were treated with azithromycin. The study evaluated the hypothesis that a more dilute, less viscous formulation (the recommended 27 mg/mL concentration of Azithromycin) is less likely to induce vomiting in young children than a more concentrated suspension used in other pediatric studies. The vomiting rate for subjects taking the dilute concentration azithromycin was 3% (2/61). The rate was numerically lower but not statistically different from the vomiting for the more concentrated suspension Across both treatment arms, the only treatment-related adverse events with a frequency of ≥ 1% were vomiting (6%, 7/120) and diarrhea (2%, 2/120).

Treatment-related adverse reactions with a frequency of < 1% following Azithromycin treatment in all 907 pediatric subjects in the Phase 3 studies were:

Body as a whole: Chills, fever, flu syndrome, headache;

Digestive: Abnormal stools, constipation, dyspepsia, flatulence, gastritis, gastrointestinal disorder, hepatitis;

Hematologic and lymphatic: Leukopenia;

Nervous system: Agitation, emotional liability, hostility, hyperkinesia, insomnia, irritability, paresthesia, Somnolence;

Respiratory: Asthma, bronchitis, cough, dyspnea, pharyngitis, rhinitis;

Skin and appendages: Dermatitis, fungal dermatitis, maculopapular rash, pruritus, urticaria;

Special senses: Otitis media, taste perversion;

Urogenital: Dysuria.

Postmarketing Experience with Other Azithromycin Products

Because these reactions are reported voluntarily from a population of uncertain size, reliably estimating their frequency or establishing a causal relationship to drug exposure is not always possible.

Adverse events reported with azithromycin immediate release formulations during the postmarketing period for which a causal relationship may not be established include:

Allergic: Arthralgia, edema, urticaria and angioedema

Cardiovascular: Palpitations and arrhythmias including ventricular tachycardia and hypotension

There have been reports of QT prolongation and torsades de pointes.

Gastrointestinal: Anorexia, constipation, dyspepsia, flatulence, vomiting/diarrhea, pseudomembranous colitis, pancreatitis, oral candidiasis, pyloric stenosis, and rare reports of tongue discoloration

General: Asthenia, paresthesia, fatigue, malaise and anaphylaxis

Genitourinary: Interstitial nephritis, acute renal failure and vaginitis

Hematopoietic: Thrombocytopenia, mild neutropenia

Liver/biliary: Adverse reactions related to hepatic dysfunction have been reported in postmarketing experience with azithromycin.

Nervous system: Convulsions, dizziness/vertigo, headache, somnolence, hyperactivity, nervousness, agitation and syncope

Psychiatric: Aggressive reaction and anxiety

Skin/appendages: Pruritus, rash, photosensitivity, serious skin reactions including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS.

Special senses: Hearing disturbances including hearing loss, deafness and/or tinnitus and reports of taste/smell perversion and/or loss

Laboratory Abnormalities

In subjects with normal baseline values, the following clinically significant laboratory abnormalities (irrespective of drug relationship) were reported in Azithromycin clinical trials in adults and pediatric patients:

Adults:

Laboratory abnormalities with an incidence of greater than or equal to 1%: reduced lymphocytes and increased eosinophils; reduced bicarbonate. Laboratory abnormalities with an incidence of less than 1%: leukopenia, neutropenia, elevated bilirubin, AST, ALT, BUN, creatinine, alterations in potassium. Where follow-up was provided, changes in laboratory tests appeared to be reversible.

Pediatric Patients:

Laboratory abnormalities with an incidence of greater than or equal to 1%: elevated eosinophils, BUN, and potassium; decreased lymphocytes; and alterations in neutrophils; with an incidence of less than 1%: elevated SGOT, SGPT and creatinine; decreased potassium; and alterations in sodium and glucose.

See also:
What are the possible side effects of Fluconazole?

Fluconazole is generally well tolerated.

In some patients, particularly those with serious underlying diseases such as AIDS and cancer, changes in renal and hematological function test results and hepatic abnormalities have been observed during treatment with fluconazole and comparative agents, but the clinical significance and relationship to treatment is uncertain.

In Patients Receiving A Single Dose For Vaginal Candidiasis

During comparative clinical studies conducted in the United States, 448 patients with vaginal candidiasis were treated with Fluconazole, 150 mg single dose. The overall incidence of side effects possibly related to Fluconazole was 26%. In 422 patients receiving active comparative agents, the incidence was 16%. The most common treatment-related adverse events reported in the patients who received 150 mg single dose fluconazole for vaginitis were headache (13%), nausea (7%), and abdominal pain (6%). Other side effects reported with an incidence equal to or greater than 1% included diarrhea (3%), dyspepsia (1%), dizziness (1%), and taste perversion (1%). Most of the reported side effects were mild to moderate in severity. Rarely, angioedema and anaphylactic reaction have been reported in marketing experience.

In Patients Receiving Multiple Doses For Other Infections

Sixteen percent of over 4000 patients treated with Fluconazole (fluconazole) in clinical trials of 7 days or more experienced adverse events. Treatment was discontinued in 1.5% of patients due to adverse clinical events and in 1.3% of patients due to laboratory test abnormalities.

Clinical adverse events were reported more frequently in HIV infected patients (21%) than in non-HIV infected patients (13%); however, the patterns in HIV infected and non-HIV infected patients were similar. The proportions of patients discontinuing therapy due to clinical adverse events were similar in the two groups (1.5%).

The following treatment-related clinical adverse events occurred at an incidence of 1% or greater in 4048 patients receiving Fluconazole for 7 or more days in clinical trials: nausea 3.7%, headache 1.9%, skin rash 1.8%, vomiting 1.7%, abdominal pain 1.7%, and diarrhea 1.5%.

Hepatobiliary

In combined clinical trials and marketing experience, there have been rare cases of serious hepatic reactions during treatment with Fluconazole. The spectrum of these hepatic reactions has ranged from mild transient elevations in transaminases to clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities. Instances of fatal hepatic reactions were noted to occur primarily in patients with serious underlying medical conditions (predominantly AIDS or malignancy) and often while taking multiple concomitant medications. Transient hepatic reactions, including hepatitis and jaundice, have occurred among patients with no other identifiable risk factors. In each of these cases, liver function returned to baseline on discontinuation of Fluconazole.

In two comparative trials evaluating the efficacy of Fluconazole for the suppression of relapse of cryptococcal meningitis, a statistically significant increase was observed in median AST (SGOT) levels from a baseline value of 30 IU/L to 41 IU/L in one trial and 34 IU/L to 66 IU/L in the other. The overall rate of serum transaminase elevations of more than 8 times the upper limit of normal was approximately 1% in fluconazole-treated patients in clinical trials. These elevations occurred in patients with severe underlying disease, predominantly AIDS or malignancies, most of whom were receiving multiple concomitant medications, including many known to be hepatotoxic. The incidence of abnormally elevated serum transaminases was greater in patients taking Fluconazole concomitantly with one or more of the following medications: rifampin, phenytoin, isoniazid, valproic acid, or oral sulfonylurea hypoglycemic agents.

Post-Marketing Experience

In addition, the following adverse events have occurred during post-marketing experience.

Immunologic: In rare cases, anaphylaxis (including angioedema, face edema and pruritus) has been reported.

Body as a Whole: Asthenia, fatigue, fever, malaise.

Cardiovascular: QT prolongation, torsade de pointes.

Central Nervous System: Seizures, dizziness.

Hematopoietic and Lymphatic: Leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.

Metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Gastrointestinal: Cholestasis, dry mouth, hepatocellular damage, dyspepsia, vomiting.

Other Senses: Taste perversion.

Musculoskeletal System: myalgia.

Nervous System: Insomnia, paresthesia, somnolence, tremor, vertigo.

Skin and Appendages: Acute generalized exanthematous-pustulosis, drug eruption, increased sweating, exfoliative skin disorders including Stevens-Johnson syndrome and toxic epidermal necrolysis, alopecia.

Adverse Reactions In Children

The pattern and incidence of adverse events and laboratory abnormalities recorded during pediatric clinical trials are comparable to those seen in adults.

In Phase II/III clinical trials conducted in the United States and in Europe, 577 pediatric patients, ages 1 day to 17 years were treated with Fluconazole at doses up to 15 mg/kg/day for up to 1,616 days. Thirteen percent of children experienced treatment-related adverse events. The most commonly reported events were vomiting (5%), abdominal pain (3%), nausea (2%), and diarrhea (2%). Treatment was discontinued in 2.3% of patients due to adverse clinical events and in 1.4% of patients due to laboratory test abnormalities. The majority of treatment-related laboratory abnormalities were elevations of transaminases or alkaline phosphatase.

Percentage of Patients With Treatment-Related Side Effects

See also:
What are the possible side effects of Tinidazole?

Applies to tinidazole: oral tablet

As well as its needed effects, tinidazole (the active ingredient contained in Tinidazole) may cause unwanted side effects that require medical attention.

Major Side Effects

If any of the following side effects occur while taking tinidazole, check with your doctor immediately:

Rare

• 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

Minor Side Effects

Some tinidazole side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned about them:

More common:

• 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

Each capsule contains azithromycin dihydrate 262.05 mg equivalent to azithromycin base 250 mg. It also contains anhydrous lactose, maize starch, magnesium stearate and sodium lauryl sulfate as excipients. The capsule shell contains gelatin, titanium dioxide (E171) and up to 1,000 ppm sulfur dioxide.

Each tablet contains azithromycin dihydrate 262.05 mg equivalent to azithromycin base 250 mg. It also contains pre-gelatinized starch, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate and sodium lauryl sulfate as excipients. The film-coating contains hydroxypropyl cellulose, triacetin and titanium dioxide (E171).

Each 5 mL of powder for oral suspension contains azithromycin dihydrate 209.64 mg equivalent to azithromycin base 200 mg. It also contains sucrose (1.94 g/100 mg dose), anhydrous tribasic sodium phosphate, hydroxypropyl cellulose, xanthan gum, artificial cherry, creme de vanilla and banana flavors as excipients.

Each sachet contains azithromycin dihydrate 100.16 mg equivalent to azithromycin base 100 mg. It also contains sucrose (1.85 g/azithromycin 100-mg dose), anhydrous tribasic sodium phosphate, hydroxypropyl cellulose, xanthan gum, artificial cherry, creme de vanilla and banana flavors as excipients. It also contains a dry powder which yields, when added to water, a white to off-white suspension, cherry/banana with a slight vanilla odor.

Each vial contains azithromycin dihydrate 524.1 mg equivalent to azithromycin base 500 mg. It also contains anhydrous citric acid and sodium hydroxide as excipients. It is supplied in lyophilized form under a vacuum in a 10-mL vial for IV administration. Upon reconstitution, azithromycin powder yields a solution containing the equivalent of azithromycin 100 mg/mL.

Azithromycin is 9-deoxy-9a-aza-9a-methyl-9a-homoerythromycin A. The molecular weight is 749.

Fluconazole (Fluconazole) is designated chemically as 2,4-difluoro-α,α¹-bis(1H-1,2,4-triazol-l-ylmethyl) benzyl alcohol with an empirical formula of C₁₃H₁₂F₂N₆O and a molecular weight of 306.3.

Fluconazole is a white crystalline solid which is slightly soluble in water and saline.

Each vaginal suppository contains tioconazole 100 mg and tinidazole 150 mg. It also contains witepsol as excipient.