Usage
This combination medication is prescribed for the treatment of diarrhea and dysentery, particularly amoebic dysentery and other intestinal amoebic infections caused by Entamoeba histolytica. It also addresses associated symptoms like gas, bloating, and abdominal cramps.
Pharmacological Classification: Antibiotic, antiamoebic, antiprotozoal, antiflatulent.
Mechanism of Action: This combination works through a multi-pronged approach:
- Metronidazole: Disrupts bacterial DNA and inhibits nucleic acid synthesis, acting against anaerobic bacteria and some protozoa.
- Diloxanide: A luminal amoebicide that targets Entamoeba histolytica within the intestinal lumen, mainly in its cyst form. It acts synergistically with metronidazole.
- Simethicone: Reduces the surface tension of gas bubbles, facilitating their expulsion and alleviating bloating and discomfort.
Alternate Names
There are no specific alternate names for this combination. However, individual components may have alternate names (e.g., Metronidazole is also known as Flagyl). Brand names include Aristogyl Plus, Dilomet, and Sprot Plus, among others.
How It Works
Pharmacodynamics: The combined effect of the three components targets both the infectious agent (Entamoeba histolytica) and the associated symptoms (bloating, gas). Metronidazole acts systemically, while diloxanide acts locally in the gut lumen. Simethicone works physically by reducing surface tension of gas bubbles.
Pharmacokinetics:
- Metronidazole: Well-absorbed orally. Metabolized in the liver, excreted in urine and feces.
- Diloxanide: Absorbed from the GI tract and rapidly hydrolyzed before absorption. Excreted primarily in feces.
- Simethicone: Not absorbed; acts locally in the GI tract and is eliminated unchanged in feces.
Mode of Action:
- Metronidazole: Inhibits nucleic acid synthesis by disrupting DNA, leading to bacterial and protozoal cell death.
- Diloxanide: Direct amoebicidal action on Entamoeba histolytica cysts in the intestinal lumen.
- Simethicone: Physically alters surface tension of gas bubbles, promoting their coalescence and expulsion.
Receptor Binding/Enzyme Inhibition: Metronidazole’s mechanism involves interaction with microbial DNA, not specific receptors or enzymes in human cells. Diloxanide’s precise mode of action is not fully elucidated. Simethicone does not bind to receptors or inhibit enzymes.
Elimination Pathways: Metronidazole is primarily excreted in the urine as metabolites, with some fecal excretion. Diloxanide is mostly excreted in feces. Simethicone, being unabsorbed, is eliminated unchanged in feces.
Dosage
Standard Dosage
Adults: One tablet containing 400 mg metronidazole, 500 mg diloxanide furoate, and 100 mg simethicone, taken three times daily with food for 10 days.
Children: Dosage is weight-based and should be determined by a doctor. Diloxanide furoate is not recommended for children weighing less than 25 kg when given as a single agent. For children above 25kg, it can be given 20mg/kg daily in 3 divided doses for 10 days, repeated if necessary.
Special Cases:
- Elderly Patients: Use with caution, especially at high doses, due to potential age-related decline in renal and hepatic function. Monitor for adverse effects closely.
- Patients with Renal Impairment: Dose adjustment may be necessary. Close monitoring of renal function is advised.
- Patients with Hepatic Dysfunction: Use with caution and monitor liver function tests. Dosage adjustments may be required.
- Patients with Comorbid Conditions: Evaluate for potential drug interactions. Consider conditions such as neurological disorders and blood dyscrasias.
Clinical Use Cases
This combination is specifically indicated for intestinal amoebiasis. It’s not typically used in settings like intubation, surgical procedures, mechanical ventilation, or ICU use. For specific infections requiring anaerobic coverage in these settings, metronidazole alone or in combination with other appropriate antibiotics might be considered.
Dosage Adjustments
Adjustments are based on patient-specific factors such as age, weight, renal function, and hepatic function. Always consult a doctor for appropriate dosage adjustments.
Side Effects
Common Side Effects
Nausea, dry mouth, headache, metallic taste in mouth, vomiting, flatulence, diarrhea, dizziness, and skin rash.
Rare but Serious Side Effects
Severe skin reactions (e.g., Stevens-Johnson syndrome), neurological side effects (peripheral neuropathy, seizures), and blood dyscrasias.
Long-Term Effects
Chronic use of metronidazole, a component of this combination, has been associated with potential neurotoxicity.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include severe allergic reactions, seizures, blood dyscrasias, and peripheral neuropathy.
Contraindications
Hypersensitivity to any of the components. Neurological disorders (e.g., epilepsy, multiple sclerosis), severe hepatic impairment, first trimester of pregnancy.
Drug Interactions
Alcohol (disulfiram-like reaction with metronidazole), anticoagulants (warfarin), lithium, anticonvulsants (phenytoin, phenobarbital), cimetidine, and other antibiotics.
Pregnancy and Breastfeeding
Use with caution during pregnancy and breastfeeding. Metronidazole is excreted in breast milk. Consult a doctor to assess benefit versus risk.
Drug Profile Summary
- Mechanism of Action: Metronidazole: Disrupts DNA synthesis. Diloxanide: Direct amoebicidal action. Simethicone: Reduces gas bubble surface tension.
- Side Effects: Nausea, headache, metallic taste, vomiting, diarrhea, dizziness.
- Contraindications: Hypersensitivity, neurological disorders, severe hepatic impairment, first trimester of pregnancy.
- Drug Interactions: Alcohol, anticoagulants, lithium, anticonvulsants, cimetidine.
- Pregnancy & Breastfeeding: Use with caution.
- Dosage: Adults: 400 mg metronidazole + 500 mg diloxanide furoate + 100 mg simethicone TID for 10 days. Children: weight-based, consult a doctor.
- Monitoring Parameters: Liver function tests, complete blood count (CBC) for long-term use.
Popular Combinations
This specific combination is commonly used as a comprehensive therapy for intestinal amoebiasis.
Precautions
Evaluate renal and hepatic function. Avoid alcohol. Monitor for neurological side effects. Counsel patients about potential side effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Diloxanide + Metronidazole + Simethicone?
A: Adults: One tablet containing 400 mg metronidazole, 500 mg diloxanide furoate, and 100 mg simethicone, three times daily with food for 10 days. Pediatric dosages are weight-based; consult a physician.
Q2: What are the common side effects?
A: Nausea, headache, metallic taste, vomiting, diarrhea, dizziness.
Q3: Can this medication be taken during pregnancy?
A: Use with caution. Consult a doctor to assess benefit versus risk.
Q4: What are the contraindications for this drug?
A: Hypersensitivity to any of the components, neurological disorders, severe hepatic impairment, first trimester of pregnancy.
Q5: How should this medication be stored?
A: Store in a cool, dry place away from direct sunlight and out of reach of children.
Q6: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember it. However, if it’s close to the time for your next dose, skip the missed dose and continue your regular dosing schedule. Don’t double the dose to catch up.
Q7: Can I drink alcohol while taking this medicine?
A: No. Metronidazole can cause a disulfiram-like reaction with alcohol.
Q8: How long does this medication take to work?
A: Symptom improvement may occur within a few days, but the full course of treatment is essential to eradicate the infection.
Q9: Should I stop taking the medicine if I feel better before completing the course?
A: No. Always complete the prescribed course of treatment, even if symptoms improve, to ensure complete eradication of the infection and prevent recurrence.
