Azithromycin + Ofloxacin

Usage

Azithromycin + Ofloxacin is a combination antibiotic used to treat various bacterial infections. Specifically, this combination is effective against infections susceptible to both azithromycin and ofloxacin.

• Pharmacological Classification: Antibiotic

• Mechanism of Action: Azithromycin, a macrolide antibiotic, inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. Ofloxacin, a fluoroquinolone antibiotic, inhibits bacterial DNA gyrase and topoisomerase IV, enzymes essential for bacterial DNA replication and repair. The combination of these two antibiotics with different mechanisms of action provides a broader spectrum of coverage and can enhance efficacy against certain bacterial infections.

Alternate Names

There is no officially recognized alternate name for the combination of Azithromycin + Ofloxacin. The individual drugs are sometimes referred to by their generic names or alternative brand names.

• Brand Names: A number of brand names exist for formulations containing this drug combination, although brand availability varies regionally. It’s essential to confirm the active ingredients as formulations and brand names vary.

How It Works

• Pharmacodynamics: Azithromycin accumulates within cells, including phagocytes, which transport the drug to the site of infection. It exhibits activity against a wide range of bacteria, including gram-positive, gram-negative, and atypical organisms. Ofloxacin, also broadly active, disrupts bacterial DNA replication and repair, leading to bacterial cell death.

• Pharmacokinetics: Azithromycin is well absorbed orally and distributes widely into tissues, achieving high intracellular concentrations. It has a long half-life (up to 68 hours), allowing for once-daily dosing. Ofloxacin is also well-absorbed orally, achieving peak serum concentrations within 1 to 2 hours. It is primarily eliminated via renal excretion.

• Mode of Action: Azithromycin binds to the 50S ribosomal subunit of bacteria, blocking protein synthesis. Ofloxacin inhibits bacterial DNA gyrase and topoisomerase IV.

• Elimination Pathways: Azithromycin is primarily excreted in bile, with a small portion eliminated renally. Ofloxacin is predominantly excreted in the urine.

Dosage

Standard Dosage

Adults: Dosing varies depending on the infection being treated. Typical doses range from 500mg of azithromycin once daily for 3 days plus 200-400 mg of ofloxacin twice daily for 7-14 days. Some infections may require different durations of treatment or higher doses of ofloxacin (up to 400 mg twice daily).

Children: Due to the risk of musculoskeletal adverse effects, ofloxacin is generally avoided in children and pregnant women unless other treatment options are unsuitable. Azithromycin dosing in children is weight-based (10 mg/kg on day 1, followed by 5 mg/kg daily for 4 days), but the combination of azithromycin and ofloxacin is not typically recommended for pediatric use.

Special Cases:

• Elderly Patients: Dose adjustments for azithromycin are not typically required in elderly patients with normal renal and hepatic function. Ofloxacin dosage may need adjustment based on renal function.

• Patients with Renal Impairment: Ofloxacin dosage needs to be reduced in patients with renal impairment. Azithromycin dose adjustments may not be necessary in mild to moderate renal impairment, but caution is advised in severe cases.

• Patients with Hepatic Dysfunction: Cautious use is recommended in patients with hepatic impairment. Dosage adjustments of both azithromycin and ofloxacin may be considered in severe hepatic dysfunction.

• Patients with Comorbid Conditions: Patients with certain comorbid conditions, like cardiac arrhythmias, or those taking medications that prolong the QT interval, should be closely monitored for adverse effects when taking this combination due to the increased risk of QT interval prolongation.

Clinical Use Cases

The use of this specific combination for the clinical use cases listed is not routinely indicated, and other antibiotic regimens are typically preferred. Dosage and duration of therapy would need to be determined based on the specific infection and patient factors.

Dosage Adjustments

Dose modifications may be necessary depending on the infection being treated, patient age, renal and hepatic function, and potential drug interactions.

Side Effects

Common Side Effects:

Nausea, vomiting, diarrhea, abdominal pain, headache, dizziness.

Rare but Serious Side Effects:

QTc prolongation and torsades de pointes, tendonitis or tendon rupture, peripheral neuropathy, seizures, Clostridium difficile-associated diarrhea.

Long-Term Effects:

Peripheral neuropathy and tendon damage can persist even after discontinuation of the drugs.

Adverse Drug Reactions (ADR):

Allergic reactions, including anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, although rare, can occur.

Contraindications

Hypersensitivity to macrolides or fluoroquinolones, myasthenia gravis, history of QT prolongation, or use with other QT-prolonging medications.

Drug Interactions

This combination can interact with antacids containing aluminum or magnesium, warfarin, theophylline, digoxin, medications that prolong the QT interval, and certain antiarrhythmic drugs.

Pregnancy and Breastfeeding

Ofloxacin is contraindicated during pregnancy. Azithromycin is generally considered safe during pregnancy but should be used with caution. Both medications are excreted in breast milk. Consult a specialist regarding use during breastfeeding.

Drug Profile Summary

• Mechanism of Action: Azithromycin inhibits bacterial protein synthesis; ofloxacin inhibits bacterial DNA gyrase and topoisomerase IV.
• Side Effects: Nausea, vomiting, diarrhea, abdominal pain, QT prolongation, tendonitis, peripheral neuropathy.
• Contraindications: Hypersensitivity, myasthenia gravis, QT prolongation risk.
• Drug Interactions: Antacids, warfarin, theophylline, QT prolonging drugs.
• Pregnancy & Breastfeeding: Ofloxacin contraindicated in pregnancy; Azithromycin generally safe but use with caution. Consult specialist for breastfeeding.
• Dosage: Varies depending on infection; adult doses typically involve azithromycin 500mg once daily plus ofloxacin 200-400 mg twice daily. Pediatric use is generally avoided for ofloxacin.
• Monitoring Parameters: ECG (for QT interval), liver and kidney function tests, signs of tendonitis or neuropathy.

Popular Combinations

The combined use of Azithromycin and Ofloxacin is not a standard “popular” combination. They are often prescribed as standalone agents. Other antibiotic combinations may be preferred.

Precautions

Closely monitor patients for cardiac arrhythmias, tendonitis, and neuropathy. Perform baseline ECG in patients at risk of QT prolongation.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Azithromycin + Ofloxacin?

A: Dosing varies based on the infection and patient-specific factors. Adult doses commonly involve 500mg azithromycin once daily and 200-400mg ofloxacin twice daily. Consult treatment guidelines and consider renal/hepatic function and drug interactions. Pediatric use is generally avoided.

Q2: What are the major contraindications for this drug combination?

A: Hypersensitivity to macrolides or fluoroquinolones, myasthenia gravis, and a history of QT prolongation or concurrent use of QT-prolonging drugs.

Q3: Can Azithromycin + Ofloxacin be used in pregnant or breastfeeding women?

A: Ofloxacin is contraindicated during pregnancy. Azithromycin is generally considered safe during pregnancy but should be used cautiously. Consult a specialist regarding use during breastfeeding.

Q4: What are the most common side effects of Azithromycin + Ofloxacin?

A: Gastrointestinal disturbances such as nausea, vomiting, diarrhea, and abdominal pain are common. Headache and dizziness can also occur.

Q5: What are the serious side effects that doctors should monitor for?

A: Serious side effects include QT interval prolongation, torsades de pointes, tendonitis (including rupture), and peripheral neuropathy.

Q6: Are there any specific drug interactions that clinicians should be aware of?

A: Yes, interactions can occur with antacids containing aluminum or magnesium, warfarin, theophylline, digoxin, and other medications that prolong the QT interval.

Q7: How is Azithromycin + Ofloxacin eliminated from the body?

A: Azithromycin is primarily excreted in the bile, while ofloxacin is mainly eliminated via renal excretion.

Q8: How should renal or hepatic impairment influence dosing?

A: Ofloxacin dosage should be reduced in patients with renal impairment. Azithromycin dose adjustments may not be necessary in mild to moderate renal impairment but should be considered in severe renal or hepatic impairment.

Q9: Why is this combination prescribed?

A: This combination is used to treat infections where a broader spectrum of coverage or enhanced efficacy against specific bacteria is desired. However, it’s essential to consider alternative therapies due to the risk of significant side effects associated with fluoroquinolones like ofloxacin.

Q10: What monitoring parameters are recommended for patients taking this combination?

A: Monitor for QT interval prolongation with ECG, especially in at-risk patients. Assess liver and kidney function tests. Watch for clinical signs of tendonitis and peripheral neuropathy.