Gastronorm-d

Uses

Diloxanide is used alone as a primary agent in the treatment of asymptomatic (cyst passers) intestinal amebiasis caused by Entamoeba histolytica. Diloxanide may also be used concurrently, or sequentially, with other agents such as the nitroimidazoles (eg. metronidazole) in the treatment of invasive or extraintestinal forms of amebiasis.

Trichomoniasis: Tinidazole is used 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 used for the treatment of giardiasis caused by Giardia duodenalis in both adults and pediatric patients older than three years of age. Sections or subsections omitted from the full prescribing information are not listed.

Amebiasis: Tinidazole is used 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 used for the treatment of asymptomatic cystpassage.

Bacterial Vaginosis: Tinidazole is used 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 and other antibacterialdrugs, Tinidazole 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.

Gastronorm-d is also used to associated treatment for these conditions: Amebiasis, Bacterial Vaginosis (BV), Candidal Vulvovaginitis, Giardiasis, Mixed Vaginal Infections, Nongonococcal urethritis, Sexually Transmitted Disease (STD), Trichomonas Vaginalis Infection, Trichomoniasis

How Gastronorm-d works

Unknown. Diloxanide may inhibit protein synthesis.

Tinidazole is a prodrug and antiprotozoal agent. The nitro group of tinidazole is reduced in Trichomonas by a ferredoxin-mediated electron transport system. The free nitro radical generated as a result of this reduction is believed to be responsible for the antiprotozoal activity. It is suggested that the toxic free radicals covalently bind to DNA, causing DNA damage and leading to cell death. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known, though it is probably similar.

Dosage

Gastronorm-d dosage

Prevention of Postoperative Infections :

• Adult: A single oral dose of 2g approximately 12 hours before surgery.
• Children less than 12 years: Data are not available to allow dosage recommendations for children below the age of 12 years in the prophylaxis of anaerobic infections.

Trichomoniasis: a single 2 g oral dose taken with food. Treat sexual partners with the same dose and at the same time Giardiasis:

• Adults: a single 2 g dose taken with food.
• Pediatric patients older than three years of age: a single dose of 50 mg/kg (up to 2 g) with food

Amebiasis, Intestinal:

• Adults: 2 g per day for 3 days with food.
• Pediatric patients older than three years of age: 50 mg/kg/day (up to 2 g per day) for 3 days with food

Amebic liver abscess:

• Adults: 2 g per day for 3-5 days with food.
• Pediatric patients older than three years of age: 50 mg/kg/day (up to 2 g per day) for 3-5 days with food

Bacterial vaginosis: Non-pregnant, adult women: 2 g once daily for 2 days taken with food, or 1 g once daily for 5 days taken with food.

Should be taken with food. Take during or immediately after meals.

Side Effects

Reported side effects have generally been infrequent, mild and self-limiting. Side effects from the gastrointestinal tract include nausea, vomiting, anorexia, diarrhoea and metallic taste. Hypersensitivity reactions, occasionally severe, may occur in rare cases in the form of skin rash, pruritis, urticaria and angioneurotic oedema. As with related compounds, tinidazole may produce transient leukopenia. Other rarely reported side-effects are headache, tiredness, furry tongue and dark urine.

Toxicity

There are no reported overdoses with tinidazole in humans. In acute studies with mice and rats, the LD 50 for mice was generally > 3,600 mg/kg for oral administration and was > 2,300 mg/kg for intraperitoneal administration. In rats, the LD 50 was > 2,000 mg/kg for both oral and intraperitoneal administration.

Precaution

Compounds of similar chemical structure have produced various neurological disturbances such as dizziness, vertigo, uncoordination, and ataxia. If, during therapy with tinidazole, abnormal neurological signs develop, therapy should be discontinued. Use in Pregnancy & Lactation: Tinidazole is contraindicated during the first trimester of pregnancy. While there is no evidence that tinidazole is harmful during the late stages of pregnancy, its use during the last two trimesters requires that the potential benefits outweigh the possible risk to mother and foetus. Tinidazole is excreted in breast milk in concentrations similar to those seen in serum. Tinidazole can be detected in breast milk for up to 72 hours following administration. Interruption of breast-feeding is recommended during tinidazole therapy and for 3 days following the last dose.

Interaction

The following interactions were reported with metronidazole, which is chemically-related to tinidazole.

Alcohol, disulfiram: Avoid during tinidazole use and for 3 days afterward because cramps, nausea, vomiting, headaches, and flushing may occur.

Anticoagulants, oral (eg, warfarin): Anticoagulant effects may be increased. Anticoagulant dose may need to be adjusted during coadministration and for up to 8 days after discontinuation.

Cholestyramine: Bioavailability of tinidazole may be decreased. Cyclosporine, lithium, tacrolimus: Levels may be elevated by tinidazole, increasing the risk of toxicity.

Drugs that induce CYP3A4 (eg, fosphenytoin, phenobarbital, phenytoin, rifampin): May increase metabolism of tinidazole, decreasing plasma levels and therapeutic effect.

Drugs that inhibit CYP3A4 (eg, cimetidine, ketoconazole): May prolong t½ and decrease tinidazole Cl, increasing plasma levels and risk of adverse reactions.

Fluorouracil: Cl may be decreased by tinidazole, increasing the risk of adverse reactions

Fosphenytoin, phenytoin: The t½ may be prolonged and Cl reduced by tinidazole, increasing the risk of adverse reactions.

Oxytetracycline: Therapeutic effect of tinidazole may be decreased.

Volume of Distribution

• 50 L

Elimination Route

Bioavailability is 90% (in diloxanide parental form), however diloxanide furoate is slowly absorbed from the gastrointestinal tract.

Rapidly and completely absorbed under fasting conditions. Administration with food results in a delay in T_max of approximately 2 hours and a decline in C_max of approximately 10% and an AUC of 901.6 ± 126.5 mcg hr/mL.

Half Life

3 hours

The elimination half-life is 13.2±1.4 hours and the plasma half-life is 12 to 14 hours.

Elimination Route

Renal (90%, rapidly excreted as glucuronide metabolite). 10% is excreted in the feces as diloxanide.

Tinidazole crosses the placental barrier and is secreted in breast milk. Tinidazole is excreted by the liver and the kidneys. Tinidazole is excreted in the urine mainly as unchanged drug (approximately 20-25% of the administered dose). Approximately 12% of the drug is excreted in the feces.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

As with other compounds of similar structure, tinidazole, is contraindicated in patients having, or with a history of, blood dyscrasias although no persistent haematological abnormalities have been noted in clinical or animal studies. Tinidazole should be avoided in patients with organic neurological disorders. Tinidazole should not be administered to patients with known hypersensitivity to the compound.

Special Warning

Renal Impairment: Haemodialysis: Additional dose equal to half the usual dose at the end of haemodialysis.

Storage Condition

Store at room temperature & protected from light.

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