Metronidazole + Ofloxacin + Racecadotril

Usage

This combination medication is primarily prescribed for acute diarrhea, particularly when a bacterial infection or mixed bacterial and protozoal infection is suspected. It is effective against various types of diarrhea, including traveler’s diarrhea.

• Pharmacological Classification: This combination includes drugs from multiple classes:

  • Metronidazole: Antibiotic and antiprotozoal.
  • Ofloxacin: Fluoroquinolone antibiotic.
  • Racecadotril: Antisecretory agent.

• Mechanism of Action: The components work synergistically:

  • Ofloxacin inhibits bacterial DNA gyrase and topoisomerase IV, essential enzymes for bacterial DNA replication and repair, effectively halting bacterial growth.
  • Metronidazole disrupts DNA synthesis and causes DNA damage in both bacteria and protozoa, leading to cell death.
  • Racecadotril inhibits enkephalinase, an enzyme that degrades enkephalins. This action reduces intestinal hypersecretion of water and electrolytes, decreasing the frequency and volume of diarrhea without affecting normal gut motility.

Alternate Names

This combination often goes by various names since a globally recognized single brand name is lacking. It is frequently identified using a combination of generic names or abbreviations, such as “Ofloxacin-Metronidazole-Racecadotril.” Brand names vary according to the manufacturer and region. Avof OZ Plus is an example of a commercial name mentioned in one of the sources.

How It Works

• Pharmacodynamics: The combination exerts its therapeutic effect by targeting different aspects of diarrhea. Ofloxacin and metronidazole act as antimicrobials, eliminating the causative pathogens. Racecadotril reduces fluid loss by decreasing intestinal secretions.

• Pharmacokinetics:

  • Ofloxacin: Well-absorbed orally, reaching peak plasma concentrations within 1-2 hours. Primarily eliminated through renal excretion.
  • Metronidazole: Also well-absorbed orally, with peak concentrations reached in 1-3 hours. Metabolized in the liver and excreted in urine and feces.
  • Racecadotril: Rapidly absorbed after oral administration. Its active metabolite, thiorphan, is responsible for the antisecretory effect. Primarily excreted in urine.

• Mode of Action: The individual components work through distinct mechanisms:

  • Ofloxacin and metronidazole target bacterial and protozoal DNA, leading to their destruction.
  • Racecadotril modulates enkephalinase activity, impacting intestinal water and electrolyte balance.

• Elimination Pathways:

  • Ofloxacin: Primarily renal excretion.
  • Metronidazole: Hepatic metabolism followed by renal and fecal excretion.
  • Racecadotril: Primarily renal excretion of its active metabolite.

Dosage

Dosage information for this specific combination is limited in the provided sources. Determining the appropriate dosage requires a physician’s assessment considering patient factors such as age, weight, infection severity, and renal function. It is generally recommended for adults and adolescents over 18. Consult additional resources or a pharmacist for comprehensive dosage information. It’s crucial to emphasize that pediatric dosing information is not found within the provided resources. It is vital to consult reliable dosage resources or seek expert advice before administering this combination to pediatric patients.

Standard Dosage

Adults:

Specific adult dosage information for this particular fixed-dose combination is not available within the sources. Clinical judgment guided by authoritative references is required.

Children:

The sources do not provide pediatric dosage guidelines for the combined formulation of these drugs. Prescribing to children should be done with extreme caution, referencing appropriate resources for individual drug dosages and considering potential interactions.

Special Cases:

Dosage adjustments in the elderly, patients with renal or hepatic impairments, and those with comorbid conditions necessitate careful medical evaluation and are not explicitly defined within the provided sources. Rely on clinical judgment and consult relevant resources for accurate dosage recommendations.

Clinical Use Cases

Dosage recommendations for specific clinical scenarios (intubation, surgical procedures, mechanical ventilation, ICU use, emergencies) aren’t available in the provided sources. Such uses should be determined on a case-by-case basis by a healthcare professional.

Dosage Adjustments

Specific dosage adjustments are not available in the provided source material.

Side Effects

Common Side Effects

Nausea, vomiting, abdominal pain, headache, dizziness, dry mouth, metallic taste.

Rare but Serious Side Effects

Severe allergic reactions (rash, itching, swelling, difficulty breathing), seizures, peripheral neuropathy (numbness, tingling, pain in hands and feet), tendon rupture (especially Achilles tendon), QT interval prolongation (a heart rhythm problem), Clostridium difficile-associated diarrhea (severe diarrhea caused by disruption of normal gut flora).

Long-Term Effects

The long-term effects of this combination are not explicitly mentioned in the provided sources.

Adverse Drug Reactions (ADR)

Clinically significant ADRs include severe allergic reactions, cardiac arrhythmias, tendon rupture, and C. difficile-associated diarrhea, requiring immediate medical attention.

Contraindications

Hypersensitivity to any component of the medication, history of tendon disorders related to fluoroquinolone use, epilepsy or other seizure disorders, severe renal or hepatic impairment, pregnancy (especially the first trimester), breastfeeding.

Drug Interactions

Antacids can reduce ofloxacin absorption. Ofloxacin can interact with QT interval-prolonging drugs (e.g., antiarrhythmics, antipsychotics), increasing the risk of cardiac arrhythmias. Metronidazole can interact with alcohol, causing a disulfiram-like reaction (flushing, nausea, vomiting). Metronidazole can enhance warfarin’s anticoagulant effect. Consult a comprehensive drug interaction resource for complete information.

Pregnancy and Breastfeeding

This combination is generally contraindicated in pregnancy, especially during the first trimester, and breastfeeding. Metronidazole is excreted in breast milk and may affect the infant. Ofloxacin should be used cautiously during pregnancy if benefits outweigh risks. Racecadotril use during pregnancy and breastfeeding must be individually assessed by a healthcare professional.

Drug Profile Summary

• Mechanism of Action: See Usage section.
• Side Effects: See Side Effects section.
• Contraindications: See Contraindications section.
• Drug Interactions: See Drug Interactions section.
• Pregnancy & Breastfeeding: Generally contraindicated.
• Dosage: Determined by a physician based on individual patient factors.
• Monitoring Parameters: Monitor for signs of superinfection (e.g., C. difficile infection), allergic reactions, and neurological symptoms.

Popular Combinations

Specific popular combinations with metronidazole, ofloxacin, and racecadotril as a fixed-dose combination are not provided in the sources. However, the sources do include information about other antimicrobial combinations for acute gastroenteritis.

Precautions

Screen patients for allergies, metabolic disorders, and organ dysfunction. Exercise caution in pregnant and breastfeeding women. Consider age-related adjustments in children and elderly patients. Advise patients against alcohol consumption during treatment due to potential interaction with metronidazole. Driving or operating machinery should be avoided if dizziness or other central nervous system effects occur.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Metronidazole + Ofloxacin + Racecadotril?

A: The recommended dosage requires physician determination based on individual patient factors (age, weight, infection severity, renal function). Specific dosage information is not found within the provided sources. Refer to authoritative drug resources for detailed dosage guidance.

Q2: What are the primary uses of this combination?

A: It is primarily prescribed for acute diarrhea, especially cases suspected to be of bacterial or mixed bacterial and protozoal origin.

Q3: What are the common side effects?

A: Common side effects include nausea, vomiting, abdominal pain, headache, dizziness, dry mouth, and a metallic taste.

Q4: Are there any serious side effects to watch out for?

A: Yes, rare but serious side effects include severe allergic reactions, seizures, peripheral neuropathy, tendon rupture, QT interval prolongation, and C. difficile-associated diarrhea. These warrant immediate medical attention.

Q5: Can this medication be used during pregnancy or breastfeeding?

A: This combination is generally contraindicated during pregnancy, particularly in the first trimester, and breastfeeding. Consult a healthcare professional for individualized risk-benefit assessment.

Q6: What are the major drug interactions?

A: Important drug interactions include antacids (reduce ofloxacin absorption), QT interval-prolonging drugs (risk of arrhythmias with ofloxacin), alcohol (disulfiram-like reaction with metronidazole), and warfarin (enhanced anticoagulant effect with metronidazole).

Q7: What are the key contraindications to the use of this combination?

A: Key contraindications include hypersensitivity to any component, history of tendon disorders related to fluoroquinolones, epilepsy, severe renal or hepatic impairment, pregnancy, and breastfeeding.

Q8: How is this combination eliminated from the body?

A: Ofloxacin primarily via renal excretion; metronidazole through hepatic metabolism followed by renal and fecal excretion; racecadotril mainly via renal excretion of its active metabolite.

Q9: Should patients avoid any specific substances while taking this medication?

A: Patients should avoid alcohol due to the potential for a disulfiram-like reaction with metronidazole. Dairy products should be taken separately from Ofloxacin as they might interfere with the absorption.

Q10: Can this medication be given to children?

A: While use in children is not contraindicated, determining the appropriate dosage for pediatric patients must be done with caution, as specific dosage information for the fixed-dose combination is not found within the provided sources. Individual components need careful dosing based on age, weight, and clinical condition, accounting for potential interactions. Always consult authoritative pediatric resources.