TINILOX-MPS SUSPENSION

Indications

• Intestinal amoebiasis
• Urogenital trichomoniasis
• Giardiasis

Dosage

Children: For children aged 1 month to 11 years, the dosage is 50–75 mg/kg once, with a maximum of 2 g per dose. For children aged 12 to 17 years, the dosage is 2 g for a single dose, which may be repeated once if necessary.

Adults: The usual adult dosage is 2 g taken orally as a single dose for urogenital trichomoniasis or giardiasis, and 1.5 g to 2 g once daily for 3 to 6 days for intestinal amoebiasis.

Mechanism of action

Tinidazole acts as a prodrug and antiprotozoal agent. Its nitro group is reduced in Trichomonas by a ferredoxin-mediated electron transport system, generating free nitro radicals that covalently bind to DNA, causing DNA damage and cell death. The exact mechanism of action against Giardia and Entamoeba species is not fully understood but is believed to be similar to that of Trichomonas.

Pharmacodynamics

Tinidazole demonstrates in vitro and clinical activity against Trichomonas vaginalis, Giardia duodenalis (also known as G. lamblia), and Entamoeba histolytica. It does not exhibit significant activity against most strains of vaginal lactobacilli, which are beneficial bacteria in the vaginal flora.

Pharmacokinetics

Tinidazole is well absorbed following oral administration, with peak plasma concentrations occurring within 0.5 to 3 hours. It is extensively distributed throughout body tissues and fluids. The drug undergoes hepatic metabolism and is eliminated primarily through the urine, with a half-life of approximately 12 to 14 hours. Clinical and laboratory monitoring is advised if treatment extends beyond 10 days.

Adverse effects

• Abdominal pain
• Decreased appetite
• Diarrhoea
• Headache
• Nausea
• Skin reactions
• Vertigo
• Vomiting

Precautions

• Clinical and laboratory monitoring is advised if treatment exceeds 10 days

Pregnancy

Manufacturer advises avoiding use in the first trimester.

Breast-feeding

Present in milk; the manufacturer advises avoiding breastfeeding during and for 3 days after stopping treatment.

Storage

Store below 25°C, protect from moisture.

Formulations

• Tinidazole 500 mg tablets
• Tinidazole oral suspension

Indications

• Asymptomatic intestinal amebiasis
• Amebic dysentery (as part of combination therapy)

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidelines.

Adults: Refer to the BNF for specific adult dosing guidelines.

Mechanism of action

The exact mechanism of action of diloxanide is unknown. It may inhibit protein synthesis, which contributes to its efficacy against the trophozoites of E. histolytica.

Pharmacodynamics

Diloxanide acts as a luminal amebicide, effectively destroying the trophozoites of Entamoeba histolytica. The drug's action helps in reducing the load of the organism in the intestinal lumen, thereby preventing the formation of cysts and subsequent transmission of the infection.

Pharmacokinetics

Diloxanide is administered orally and is hydrolyzed in the gastrointestinal tract to release the active ingredient. The pharmacokinetics, including absorption, distribution, metabolism, and excretion specifics, are not well-documented, indicating a need for further research in these areas.

Pregnancy

There is limited data on the use of diloxanide during pregnancy. It should only be used if clearly needed.

Breast-feeding

Diloxanide is excreted in breast milk, caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• tablets

Indications

• Asymptomatic intestinal amebiasis
• Amoebic dysentery (mild cases)

Dosage

Children: Refer to the relevant prescribing information or guidelines.

Adults: Refer to the relevant prescribing information or guidelines.

Mechanism of action

Diloxanide furoate works by inhibiting the growth of the Entamoeba histolytica trophozoites in the intestines. The active metabolite, diloxanide, disrupts the cellular function of the protozoa, leading to cell lysis and death. It is thought to interfere with the protozoan's ability to utilize glucose and other nutrients, thereby inhibiting their metabolic processes.

Pharmacodynamics

Diloxanide furoate's effectiveness against Entamoeba histolytica is due to its ability to alter the protozoan's metabolic pathways, particularly affecting glucose metabolism. This results in a reduction of the organism's viability and ability to replicate. The drug's action is primarily localized to the intestinal lumen, minimizing systemic exposure and associated side effects.

Pharmacokinetics

After oral administration, diloxanide furoate is rapidly absorbed and metabolized to its active form, diloxanide. The drug is extensively metabolized in the liver, with a half-life of approximately 12 hours. It is excreted mainly in the feces, with minimal renal excretion. The bioavailability of diloxanide is enhanced when taken with food, leading to improved therapeutic outcomes.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Dizziness
• Headache

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor liver function tests in patients with pre-existing liver conditions.

Pregnancy

There is limited data on the use of diloxanide furoate in pregnancy. It should be used only if clearly needed and the potential benefits justify the potential risks to the fetus.

Breast-feeding

It is not known whether diloxanide furoate is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Oral tablet
• Oral suspension

Indications

• Flatulence
• Bloating
• Gastroesophageal reflux disease
• Functional dyspepsia

Dosage

Children: For children, refer to the BNF for Children for specific dosing recommendations.

Adults: The usual adult dose is 40 to 125 mg taken after meals and at bedtime, as needed.

Mechanism of action

Simethicone is a surfactant that decreases the surface tension of gas bubbles in the gastrointestinal tract, facilitating their expulsion. It acts by forming a film of low surface tension that promotes the coalescence of mucus-surrounded gas bubbles, allowing for easier passage of gas.

Pharmacodynamics

Simethicone decreases the surface tension of gas bubbles in the gastrointestinal tract, facilitating their expulsion. Its effects are generally short-lived, as it is typically administered as needed. The therapeutic index is wide since it is not absorbed systemically, making it safe for use in various patient populations.

Pharmacokinetics

Simethicone is not systemically absorbed following oral administration, which contributes to its safety profile. Due to its lack of systemic absorption, specific pharmacokinetic parameters such as half-life, clearance, and volume of distribution are not applicable.

Pregnancy

Simethicone can be used during pregnancy as there are no known risks associated with its use.

Breast-feeding

Simethicone is considered safe to use during breastfeeding, as it is not absorbed systemically.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Oral suspension
• Chewable tablets
• Soft gels

Mechanism of action

Tinidazole is a prodrug and antiprotozoal agent. The nitro group of tinidazole is reduced in <i>Trichomonas</i> 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 <i>Giardia</i> and <i>Entamoeba</i> species is not known, though it is probably similar. The nitro group of tinidazole is reduced by cell extracts of Trichomonas. As a result of this reduction a free nitro radical is generated which may be responsible for the antiprotozoal activity. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known.

Pharmacodynamics

Tinidazole is a synthetic antiprotozoal agent. Tinidazole demonstrates activity both in vitro and in clinical infections against the following protozoa: <i>Trichomonas vaginalis</i>, <i>Giardia duodenalis</i> (also termed <i>G. lamblia</i>), and <i>Entamoeba histolytica</i>. Tinidazole does not appear to have activity against most strains of vaginal lactobacilli.

Mechanism of action

Unknown. Diloxanide may inhibit protein synthesis.

Pharmacodynamics

Diloxanide is a luminal amebicide, however the mechanism of action of diloxanide is unknown. Diloxanide destroys the trophozoites of E. histolytica that eventually form into cysts. The cysts are then excreted by persons infected with asymptomatic amebiasis. Diloxanide furoate is a prodrug, and is hydrolyzed in the gastrointestinal tract to produce diloxanide, the active ingredient.

Mechanism of action

Simethicone is a surfactant that decreases the surface tension of gas bubbles in the gastrointestinal tract, more easily allowing gas to exit the body. The clinical use of simethicone is based on its antifoam properties. Silicone antifoams spread on the surface of aqueous liquids, forming a film of low surface tension and thus causing collapse of foam bubbles. Simethicone reportedly allows mucus-surrounded gas bubbles in the GI tract to coalesce and be expelled.

Pharmacodynamics

Simethicone decreases the surface tension of gas bubbles in the gastrointestinal tract, facilitating their expulsion. It has a short duration of action as it is generally given as needed, and a wide therapeutic index as it is not systemically absorbed.