Diloxanide

Usage

Diloxanide, specifically its furoate ester (Diloxanide furoate), is a luminal amebicide used to treat asymptomatic intestinal amebiasis caused by Entamoeba histolytica. It is effective against the non-invasive luminal forms of the parasite, primarily cysts, which are responsible for transmission. Although Diloxanide itself has no extraintestinal activity, it is frequently used in combination therapy with tissue amebicides like Metronidazole or Tinidazole to eradicate both luminal and invasive forms in symptomatic amebiasis. Diloxanide is classified as an antiprotozoal agent. Its mechanism of action involves disruption of protein synthesis within the amoeba, leading to the destruction of its outer cell wall (cyst).

Alternate Names

Diloxanide furoate is the most common form. It’s marketed under various brand names like Furamide and Entamide.

How It Works

Pharmacodynamics: Diloxanide furoate is a prodrug hydrolyzed in the gut to release the active metabolite, diloxanide. The exact mechanism is not fully understood, but it’s believed to interfere with the parasite’s protein synthesis within the intestinal lumen, causing cell death. Diloxanide exhibits minimal systemic absorption, concentrating its effects within the gut.

Pharmacokinetics: Diloxanide furoate is orally administered. After hydrolysis, diloxanide is absorbed from the GI tract and rapidly metabolized, primarily via glucuronidation. It is then excreted mainly in the urine, with a small amount eliminated in feces.

Dosage

Standard Dosage

Adults: 500 mg three times a day for 10 days. The course may be repeated if necessary.

Children: 20 mg/kg of body weight per day, divided into three doses for 10 days. (For children weighing more than 25kg). Diloxanide is not recommended for children weighing less than 25kg.

Special Cases:

• Elderly Patients: No specific dose adjustments are typically required but caution is advised due to potential age-related decline in organ function.
• Patients with Renal Impairment: No specific dose adjustment is required, as minimal drug is renally excreted.
• Patients with Hepatic Dysfunction: Use with caution. Dose adjustment may be necessary in severe hepatic impairment.
• Patients with Comorbid Conditions: Assess on a case-by-case basis.

Clinical Use Cases

Diloxanide is not indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary role is limited to the eradication of intestinal E. histolytica cysts.

Dosage Adjustments

Dosage adjustments may be necessary in cases of severe hepatic impairment. Monitor liver function tests.

Side Effects

Common Side Effects:

Flatulence, nausea, vomiting, abdominal cramps, diarrhea, anorexia, itching, dizziness, headache.

Rare but Serious Side Effects:

Severe skin rash (urticaria), angioedema (swelling of face, lips, tongue, or throat), difficulty breathing (signs of an allergic reaction).

Long-Term Effects:

No significant long-term adverse effects are known to be associated with the recommended course of diloxanide treatment.

Adverse Drug Reactions (ADR):

Allergic reactions as mentioned above require immediate discontinuation of the drug and appropriate medical management.

Contraindications

• Known hypersensitivity to diloxanide furoate.
• Pregnancy (unless absolutely necessary, under strict medical supervision).
• Breastfeeding (unless absolutely necessary, under strict medical supervision).
• Severe hepatic impairment.

Drug Interactions

No clinically significant drug interactions are well documented.

Pregnancy and Breastfeeding

Diloxanide is generally contraindicated during pregnancy and breastfeeding due to the potential for adverse effects on the fetus or neonate. Safety in these populations has not been established. If absolutely necessary, it may be used under strict medical supervision.

Drug Profile Summary

• Mechanism of Action: Disrupts protein synthesis in E. histolytica within the intestinal lumen.
• Side Effects: Flatulence, nausea, vomiting, abdominal cramps, diarrhea, allergic reactions (rare).
• Contraindications: Hypersensitivity, pregnancy, breastfeeding, severe hepatic impairment.
• Drug Interactions: No well-documented clinically significant interactions.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: Adults: 500 mg TID for 10 days; Children (>25 kg): 20 mg/kg/day divided TID for 10 days.
• Monitoring Parameters: Monitor for signs of allergic reactions. Liver function tests may be considered in patients with pre-existing liver disease.

Popular Combinations

Diloxanide is often combined with metronidazole or tinidazole for treating invasive amebiasis. This combination ensures the elimination of both the invasive and luminal forms of E. histolytica.

Precautions

• General Precautions: Hypersensitivity, liver disease.
• Specific Populations:
  • Pregnant Women: Avoid unless absolutely necessary.
  • Breastfeeding Mothers: Avoid unless absolutely necessary.
  • Children & Elderly: Use with caution in children weighing less than 25kg and elderly.
• Lifestyle Considerations: Alcohol consumption may increase the risk of gastrointestinal side effects.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Diloxanide?

A: Adults: 500mg three times daily for 10 days. Children (>25 kg): 20mg/kg/day in three divided doses for 10 days.

Q2: How does Diloxanide work?

A: Diloxanide disrupts the protein synthesis within the Entamoeba histolytica parasite, leading to its destruction, primarily affecting the luminal cyst form.

Q3: What are the common side effects of Diloxanide?

A: Common side effects include flatulence, nausea, vomiting, diarrhea, and abdominal discomfort.

Q4: Can Diloxanide be used during pregnancy?

A: Diloxanide is generally contraindicated during pregnancy. Use only if potential benefits outweigh risks, under strict medical supervision.

Q5: What is Diloxanide primarily used for?

A: Diloxanide is primarily used for treating asymptomatic intestinal amebiasis, targeting the cyst form of E. histolytica.

Q6: How should Diloxanide be taken?

A: Diloxanide furoate should be taken orally, with food, three times a day for the prescribed duration (usually 10 days).

Q7: Is Diloxanide effective against all forms of amebiasis?

A: Diloxanide primarily targets luminal amebiasis (cysts). It’s often combined with other amebicides for treating invasive disease.

Q8: Are there any drug interactions with Diloxanide?

A: No clinically significant drug interactions are well documented.

Q9: What should I do if I miss a dose of Diloxanide?

A: Take the missed dose as soon as you remember. If it is near the time of the next dose, skip the missed dose and continue your regular dosing schedule. Do not double the dose to catch up.

Q10: What should I do if I experience side effects while taking Diloxanide?

A: If you experience mild side effects, such as flatulence or nausea, they may resolve on their own. However, if the side effects are bothersome, persistent, or if you experience severe side effects like an allergic reaction, contact your doctor immediately.