Usage
Diloxanide + Metronidazole is prescribed for the treatment of intestinal amoebiasis caused by Entamoeba histolytica. It is also effective against Giardia lamblia and Clostridium difficile infections, which can cause diarrhea. This combination may also be used for trichomoniasis and bacterial vaginosis.
It’s pharmacological classifications are:
- Diloxanide: Antiamoebic, Luminal amoebicide
- Metronidazole: Antibiotic, Antiprotozoal
Mechanism of Action: Diloxanide acts within the lumen of the intestine to kill amoebae, particularly the cyst form responsible for transmission. Metronidazole, a nitroimidazole antibiotic, disrupts DNA synthesis and other cellular processes in anaerobic bacteria and protozoa. Together, they provide comprehensive coverage against E. histolytica.
Alternate Names
While “Diloxanide + Metronidazole” is the generic name, some sources refer to this combination as “Diloxanide Furoate + Metronidazole.” Brand names vary depending on the manufacturer and region, and may include names like Dyrade M, Eflorn Plus, and others.
How It Works
Pharmacodynamics: Diloxanide acts primarily in the gut lumen, targeting intraluminal amoebae, especially cysts. Metronidazole has broader systemic activity against anaerobic bacteria and protozoa, including E. histolytica trophozoites.
Pharmacokinetics: Diloxanide furoate is orally administered. It is hydrolyzed in the gut to the active form, diloxanide. Diloxanide is minimally absorbed and excreted primarily in feces. Metronidazole is well-absorbed orally. It is metabolized in the liver, and its metabolites are excreted in urine and feces.
Mode of Action: Diloxanide’s precise mechanism is unclear but likely involves disrupting amoebic protein synthesis. Metronidazole enters microbial cells and forms cytotoxic radicals that damage DNA, inhibiting cell growth.
Elimination Pathways: Diloxanide is primarily eliminated in feces. Metronidazole undergoes hepatic metabolism; its metabolites are excreted in urine and feces.
Dosage
Standard Dosage
Adults:
The typical dosage is one tablet containing 250 mg diloxanide furoate and 200 mg (or 400 mg) metronidazole, three times daily for 5-10 days. Treatment duration depends on the severity and type of infection.
Children:
Dosage is adjusted based on weight, generally 20-30mg/kg of metronidazole daily, divided into three doses, often combined with diloxanide furoate based on weight. Pediatric safety considerations include monitoring for gastrointestinal side effects and adjusting the dose based on age, weight, and clinical response.
Special Cases:
- Elderly Patients: Dosage adjustments may be necessary in patients with hepatic impairment. Monitor for potential neurological side effects.
- Patients with Renal Impairment: Dosage adjustments may be needed for severe renal dysfunction due to metabolite accumulation. Hemodialysis removes metronidazole and metabolites.
- Patients with Hepatic Dysfunction: Metronidazole is metabolized in the liver. Dosage adjustment may be necessary in patients with severe hepatic impairment.
- Patients with Comorbid Conditions: Caution should be exercised in patients with central nervous system disorders, blood disorders, or those taking anticoagulants or disulfiram.
Clinical Use Cases
Diloxanide + Metronidazole is typically used in outpatient settings for treating intestinal amoebiasis and giardiasis. Its use in other clinical situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations is limited, as other agents are typically preferred.
Dosage Adjustments
Adjustments should be considered for hepatic and renal impairment. Always follow clinical guidelines and individualize dosage based on patient-specific factors.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, metallic taste, headache, dizziness.
Rare but Serious Side Effects:
Peripheral neuropathy (numbness, tingling), seizures, encephalopathy, leukopenia (low white blood cell count), Stevens-Johnson syndrome.
Long-Term Effects:
Long-term use can rarely cause chronic peripheral neuropathy.
Adverse Drug Reactions (ADR):
Severe skin reactions, neurological effects, or blood dyscrasias require immediate attention.
Contraindications
Hypersensitivity to diloxanide, metronidazole, or nitroimidazoles. Neurological disorders (e.g., epilepsy, multiple sclerosis). Severe hepatic impairment. Active or chronic severe peripheral and central nervous system disease. First trimester of pregnancy. Use with caution in patients with blood disorders. Do not take with disulfiram. Do not consume alcohol during and shortly after treatment.
Drug Interactions
Alcohol (disulfiram-like reaction), disulfiram, coumarin anticoagulants (increased anticoagulant effect), lithium (increased lithium levels), phenytoin and phenobarbital (decreased metronidazole levels), cimetidine (increased metronidazole levels).
Pregnancy and Breastfeeding
Diloxanide + Metronidazole should be avoided, especially in the first trimester. Limited data suggests potential risk, and safer alternatives may be considered. The drug can pass into breast milk. A single dose might necessitate withholding breastfeeding for 12–24 hours, while longer-term use’s safety during breastfeeding is debated.
Drug Profile Summary
- Mechanism of Action: Diloxanide is a luminal amoebicide, while metronidazole disrupts DNA in anaerobes.
- Side Effects: Nausea, metallic taste, diarrhea, rarely neuropathy or seizures.
- Contraindications: Hypersensitivity, neurological disorders, severe liver disease, first trimester of pregnancy.
- Drug Interactions: Alcohol, disulfiram, anticoagulants, lithium, anticonvulsants.
- Pregnancy & Breastfeeding: Avoid during pregnancy, especially the first trimester. Exercise caution during breastfeeding.
- Dosage: Refer to detailed dosage section.
- Monitoring Parameters: Liver function tests, complete blood count (if prolonged use), neurological examination.
Popular Combinations
Metronidazole is often combined with diloxanide furoate for comprehensive treatment of amoebiasis.
Precautions
Assess for allergies, hepatic/renal function, and neurological status. Caution in pregnancy/breastfeeding, children, and elderly. Avoid alcohol.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Diloxanide + Metronidazole?
A: Refer to the dosage section above.
Q2: What are the common side effects?
A: Common side effects include nausea, vomiting, diarrhea, metallic taste, and headache.
Q3: Can this drug be used in pregnant or breastfeeding women?
A: It is generally contraindicated, especially in the first trimester of pregnancy. Use with caution during breastfeeding and consult available guidelines.
Q4: What are the drug interactions I should be aware of?
A: Significant interactions occur with alcohol, disulfiram, anticoagulants (e.g., warfarin), lithium, and certain anticonvulsants.
Q5: What is the mechanism of action?
A: Diloxanide acts within the gut lumen to kill amoebae. Metronidazole inhibits DNA synthesis in susceptible organisms.
Q6: Are there any contraindications?
A: Contraindications include hypersensitivity to the drug components, certain neurological conditions, and severe liver disease.
Q7: Should the dosage be adjusted for renal or hepatic impairment?
A: Yes, adjustments may be necessary in cases of severe renal or hepatic dysfunction.
Q8: What are the signs of an overdose?
A: Overdose may manifest as severe nausea, vomiting, ataxia, seizures, or peripheral neuropathy.
Q9: What should I do if a dose is missed?
A: Take the missed dose as soon as remembered, unless it is close to the next scheduled dose. Do not double the dose.
Q10: How should Diloxanide + Metronidazole be stored?
A: Store in a cool, dry place away from direct sunlight.
