Usage
Clioquinol + Metronidazole is a combination medication used to treat various infections, including:
- Amebiasis: An infection caused by the parasite Entamoeba histolytica.
- Giardiasis: An infection of the small intestine caused by the parasite Giardia lamblia.
- Bacterial vaginosis: An overgrowth of bacteria in the vagina.
- Trichomoniasis: A sexually transmitted infection caused by the parasite Trichomonas vaginalis.
- Certain skin infections caused by bacteria or fungi.
Pharmacological Classification: Antibiotic, Antiprotozoal, Antifungal.
Mechanism of Action: Clioquinol has antifungal and antiprotozoal activity, while metronidazole is effective against anaerobic bacteria and some parasites. The combination provides broad-spectrum coverage. Metronidazole enters microbial cells and forms toxic free radicals that damage DNA, thus disrupting microbial growth. Clioquinol inhibits certain microbial enzymes, further contributing to its antimicrobial effects.
Alternate Names
Clioquinol + Metronidazole; Iodochlorhydroxyquin + Metronidazole. No popular brand names were found in the provided sources.
How It Works
Pharmacodynamics: Metronidazole disrupts DNA synthesis and causes cell death in susceptible anaerobic bacteria and protozoa. Clioquinol affects energy production and membrane stability in fungi and some protozoa.
Pharmacokinetics:
- Metronidazole: Well-absorbed orally, with bioavailability greater than 90%. Metabolized in the liver by CYP enzymes, primarily CYP2C9 and CYP3A4, and excreted mainly in the urine.
- Clioquinol: Absorbed from the gastrointestinal (GI) tract. Its metabolic pathway is not well-characterized.
Elimination Pathways: Primarily renal for both drugs.
Mode of Action: Metronidazole is a prodrug that is activated within anaerobic microorganisms. The nitro group of metronidazole is reduced by microbial nitroreductases, forming reactive cytotoxic metabolites. These metabolites damage DNA and other macromolecules, leading to cell death. Clioquinol’s antifungal and antiprotozoal mechanism is not fully elucidated but involves chelation of metal ions and disruption of microbial enzyme systems.
Receptor Binding, Enzyme Inhibition, Neurotransmitter Modulation: Not well-characterized for this combination.
Dosage
Dosage varies depending on the infection being treated, patient age, and other factors. Always consult a physician for appropriate dosage recommendations.
Standard Dosage
Adults:
Dosages provided in the sources vary significantly and require clinical judgement. For amebiasis, one suggested dose is 750 mg three times a day for 5-10 days. For giardiasis, single doses of 2g have been mentioned, as well as split doses over several days. For bacterial vaginosis, common regimens include 500 mg twice daily for 7 days, a single 2g dose, or 1g daily for two days. For trichomoniasis, common regimens include a single 2g dose or 250 mg three times a day for 7 days.
Children:
Dosage is weight-based and must be determined by a physician. Sources mention doses ranging from 15 mg/kg daily in 3 divided doses for amoebiasis, up to 35-50 mg/kg daily in 3 divided doses for other infections.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary due to age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Dose adjustment may be necessary in severe renal impairment or end-stage renal disease. Hemodialysis removes metronidazole, so supplementation may be required.
- Patients with Hepatic Dysfunction: Close monitoring and dose reduction may be necessary.
- Patients with Comorbid Conditions: Dosage adjustments should be made based on the specific comorbidity.
Clinical Use Cases
Dosage for these clinical scenarios is not well-defined in the provided sources and would be at the discretion of the treating physician.
- Intubation
- Surgical Procedures (Pre-operative prophylaxis doses have been mentioned.)
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
Dose modifications may be necessary based on patient-specific factors such as renal/hepatic dysfunction, metabolic disorders, or genetic polymorphisms affecting drug metabolism.
Side Effects
Common Side Effects:
Nausea, vomiting, diarrhea, abdominal pain/cramps, metallic taste, headache, dizziness.
Rare but Serious Side Effects:
Seizures, peripheral neuropathy, encephalopathy, aseptic meningitis, liver injury, severe skin reactions (Stevens-Johnson syndrome), blood dyscrasias (leukopenia, thrombocytopenia), anaphylaxis.
Long-Term Effects:
Peripheral neuropathy can occur with prolonged use.
Adverse Drug Reactions (ADR):
Anaphylaxis, severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Contraindications
Hypersensitivity to metronidazole, clioquinol, other nitroimidazoles, or any component of the formulation. First trimester of pregnancy (metronidazole). Patients with Cockayne syndrome (metronidazole). Active or history of blood dyscrasias (metronidazole). Porphyria (metronidazole). Certain neurological conditions. Clioquinol is contraindicated in children under 2 years old and in those with hypersensitivity to hydroxyquinolines, iodine, or other quinoline derivatives.
Drug Interactions
Alcohol (disulfiram-like reaction), disulfiram, warfarin, lithium, phenytoin, phenobarbital, busulfan, drugs that prolong the QT interval (e.g., certain antipsychotics, some antibiotics), domperidone, famotidine, ciprofloxacin, azithromycin, formoterol, olanzapine, alfuzosin, escitalopram, ondansetron.
Pregnancy and Breastfeeding
Pregnancy: Metronidazole is generally avoided in the first trimester. Use in later trimesters should be carefully considered. Clioquinol has limited safety data in pregnancy and is generally avoided.
Breastfeeding: Metronidazole is excreted in breast milk. While generally considered compatible with breastfeeding, a decision should be made to discontinue breastfeeding or the drug, considering its importance to the mother. Monitor infants for loose stools, diaper rash, or thrush.
Drug Profile Summary
- Mechanism of Action: Metronidazole disrupts DNA synthesis in anaerobes; clioquinol disrupts energy production and membrane stability in fungi and some protozoa.
- Side Effects: Nausea, vomiting, diarrhea, metallic taste, headache, seizures, peripheral neuropathy.
- Contraindications: Hypersensitivity, first trimester of pregnancy (metronidazole), Cockayne syndrome (metronidazole), blood dyscrasias (metronidazole). Clioquinol is contraindicated in those under 2 years old.
- Drug Interactions: Alcohol, disulfiram, warfarin, lithium, phenytoin.
- Pregnancy & Breastfeeding: Avoid in the first trimester; use with caution during breastfeeding.
- Dosage: Varies depending on the infection and patient factors.
- Monitoring Parameters: Liver function tests, complete blood count, neurological exam.
Popular Combinations
No popular combinations mentioned in the provided sources.
Precautions
- General Precautions: Pre-screening for allergies, metabolic disorders, organ dysfunction.
- Pregnant Women: Avoid in the first trimester, use cautiously thereafter.
- Breastfeeding Mothers: Monitor infant for potential side effects; consider interrupting breastfeeding briefly after high doses.
- Children & Elderly: Age-specific dosage adjustments are necessary.
- Lifestyle Considerations: Avoid alcohol during treatment and for 3 days after.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Clioquinol + Metronidazole?
A: The dosage varies depending on the infection, patient age, and other factors. A physician should always determine the proper dosage.
Q2: What are the common side effects?
A: Common side effects include nausea, metallic taste, headache, diarrhea, and abdominal discomfort.
Q3: What are the serious side effects?
A: Serious side effects are rare but can include seizures, peripheral neuropathy, and severe skin reactions.
Q4: Can this medication be used during pregnancy?
A: Metronidazole should generally be avoided during the first trimester of pregnancy. Use during later trimesters should be carefully assessed. Clioquinol is typically avoided during pregnancy.
Q5: Can this medication be used while breastfeeding?
A: Metronidazole is excreted in breast milk and may cause side effects in infants. A decision should be made to discontinue breastfeeding or the drug, taking into account the importance of the drug to the mother.
Q6: What are the contraindications for this medication?
A: Contraindications include hypersensitivity to either drug or their components, certain neurological conditions, and Cockayne syndrome for metronidazole. Clioquinol is contraindicated in children under 2.
Q7: What are the major drug interactions?
A: This medication interacts with alcohol (disulfiram-like reaction), disulfiram, warfarin, and other drugs metabolized by the liver.
Q8: What should patients avoid while taking this medication?
A: Patients should avoid alcohol during and for three days after treatment with this medication.
Q9: How does metronidazole work against anaerobic bacteria?
A: Metronidazole is a prodrug activated within anaerobic microorganisms. Its metabolites damage microbial DNA, leading to cell death.
Q10: How does clioquinol work against fungi and protozoa?
A: Clioquinol’s mechanism involves the chelation of metal ions and disruption of microbial enzyme systems.
