Roxithromycin

Usage

Roxithromycin is a macrolide antibiotic prescribed for bacterial infections such as:

• Respiratory tract infections (e.g., tonsillitis, sinusitis, bronchitis, pneumonia)
• Skin and soft tissue infections (e.g., impetigo, cellulitis)
• Urinary tract infections
• Nongonococcal urethritis
• Atypical pneumonia

Pharmacological Classification: Macrolide antibiotic

Mechanism of Action: Roxithromycin inhibits bacterial protein synthesis by reversibly binding to the 50S ribosomal subunit of susceptible bacteria, thereby blocking transpeptidation and translocation reactions. This action prevents bacterial growth and replication.

Alternate Names

Roxithromycin is also known as roxithromycinum.

Brand Names: Rulide, Surlid, Roximycin, Roxithromycin Sandoz, APO-Roxithromycin, Roxithromycin-RL, Roxithromycin GH.

How It Works

Pharmacodynamics: Roxithromycin exerts its bacteriostatic effect by binding to the 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis. It is effective against a broad spectrum of Gram-positive and some Gram-negative bacteria.

Pharmacokinetics:

• Absorption: Roxithromycin is well-absorbed orally. It should be taken on an empty stomach as food can decrease absorption.
• Distribution: It distributes widely into tissues and fluids, achieving high concentrations in lung tissue, tonsils, and prostate tissue. Roxithromycin is highly protein-bound (92-96%), primarily to alpha-1-acid glycoprotein.
• Metabolism: It is metabolized in the liver, primarily by CYP3A4, to both active and inactive metabolites.
• Elimination: Roxithromycin is excreted primarily in feces (via bile) and a small amount via urine.

Mode of Action: Roxithromycin’s primary mode of action is through inhibition of protein synthesis by binding to the 50S ribosomal subunit of susceptible bacteria. This action is generally bacteriostatic but can be bactericidal at higher concentrations against some organisms.

Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Roxithromycin binds to the 50S ribosomal subunit.

Elimination Pathways: Roxithromycin is eliminated primarily via hepatic metabolism and biliary excretion with a small portion excreted renally.

Dosage

Standard Dosage

Adults:

• 150 mg twice daily or 300 mg once daily for 5-10 days.
• The duration may be extended depending on the indication and clinical response (e.g., streptococcal throat infections require at least 10 days).

Children:

• 6-40 kg: 5-8 mg/kg/day divided into two doses.
• ≥40 kg: 150 mg twice daily.
• Roxithromycin is generally not recommended for children under 40 kg, although some sources mention sachets for younger children (2 months-14 years) at dosages of 2.5-5 mg/kg/12h.
• The maximum duration of treatment in children is generally limited to 10 days.

Special Cases:

• Elderly Patients: No dose adjustment is usually necessary.
• Patients with Renal Impairment: No dose adjustment is necessary.
• Patients with Hepatic Dysfunction:
  • Mild to moderate impairment: Use with caution, dose reduction may be considered.
  • Severe impairment: Contraindicated, or if essential, consider half the usual dose (150 mg once daily).
• Patients with Comorbid Conditions: Use with caution in patients with:
  • QT prolongation risk factors (e.g., congenital long QT syndrome, hypokalemia, hypomagnesemia)
  • Cardiac arrhythmias
  • Myasthenia gravis

Clinical Use Cases

Dosages for specific clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are not explicitly defined for roxithromycin and would follow standard dosing with consideration for renal/hepatic function and drug interactions.

Dosage Adjustments

Dose adjustments may be needed for hepatic impairment as described above. Therapeutic drug monitoring may be useful for certain drug interactions (e.g., theophylline).

Side Effects

Common Side Effects:

• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Loss of appetite
• Skin rash
• Headache
• Vaginal thrush

Rare but Serious Side Effects:

• Severe or persistent diarrhea (especially if bloody), abdominal cramps
• Oral or vaginal candidiasis, or new infections (signs of superinfection)
• Allergic reactions (difficulty breathing, swelling, severe skin rash)
• Hepatitis (with or without jaundice)
• QT prolongation, cardiac arrhythmias
• Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)

Long-Term Effects:

• Superinfection with resistant organisms.
• Long-term effects are not well-studied.

Adverse Drug Reactions (ADR):

Clinically significant ADRs include severe allergic reactions, hepatitis, severe skin reactions (SJS/TEN), Clostridium difficile associated diarrhea (CDAD), and cardiac arrhythmias (including QT prolongation and torsades de pointes). These require immediate medical attention.

Contraindications

• Hypersensitivity to roxithromycin or other macrolides.
• Severe hepatic impairment.
• Concomitant use with vasoconstrictive ergot alkaloids (ergotamine, dihydroergotamine).
• Concomitant use with CYP3A4 substrates with narrow therapeutic windows (astemizole, cisapride, pimozide, terfenadine).
• Congenital or acquired long QT syndrome.

Drug Interactions

Roxithromycin has a lower affinity for CYP450 than erythromycin, resulting in fewer interactions. However, clinically significant interactions can occur with:

• Ergot alkaloids: Increased risk of ergotism.
• CYP3A4 substrates: Increased serum levels of drugs like astemizole, cisapride, pimozide, and terfenadine (can lead to life-threatening cardiac arrhythmias, including QT interval prolongation).
• Theophylline: Increased theophylline levels.
• Warfarin: Increased risk of bleeding due to enhanced anticoagulant effect.
• Digoxin: Increased digoxin levels.
• Midazolam: Increased midazolam levels.
• Ciclosporin: Increased ciclosporin levels.
• Disopyramide: Increased disopyramide levels.
• Class IA and III antiarrhythmics: Increased risk of QT prolongation and cardiac arrhythmias.
• Some antipsychotics, fluoroquinolones, antifungals, and antiviral drugs: Increased risk of QT prolongation and cardiac arrhythmias.
• Alcohol: Concurrent use with alcohol is generally not recommended, although specific interactions are not well-documented. Alcohol may exacerbate gastrointestinal side effects.

Pregnancy and Breastfeeding

• Pregnancy: Roxithromycin is generally considered safe to use during pregnancy, however, it should be used with caution and only if clearly needed. No teratogenic effects have been observed in animal studies.
• Breastfeeding: Roxithromycin is excreted in breast milk in small amounts. Breastfeeding is generally considered safe while taking roxithromycin, but monitoring the infant for potential adverse effects is recommended.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.
• Side Effects: Common: Diarrhea, nausea, vomiting, abdominal pain, rash. Serious: Severe diarrhea, allergic reactions, hepatitis, QT prolongation, SJS/TEN.
• Contraindications: Hypersensitivity to macrolides, severe hepatic impairment, concomitant use with ergot alkaloids or certain CYP3A4 substrates, long QT syndrome.
• Drug Interactions: Ergot alkaloids, CYP3A4 substrates, theophylline, warfarin, digoxin.
• Pregnancy & Breastfeeding: Generally safe but use with caution and only if clearly needed. Monitor infant during breastfeeding.
• Dosage: Adults: 150 mg twice daily or 300 mg once daily. Children (6-40 kg): 5-8 mg/kg/day divided into two doses. Children (≥40 kg): 150 mg twice daily.
• Monitoring Parameters: Liver function tests (especially with long-term use), ECG (in patients at risk of QT prolongation), theophylline levels (if co-administered), INR (if co-administered with warfarin), complete blood count (CBC) (to monitor for neutropenia, especially in children).

Popular Combinations

Specific popular drug combinations for roxithromycin are not explicitly mentioned in the provided sources.

Precautions

• General Precautions: Assess for allergies, hepatic/renal function, and QT prolongation risk before starting treatment. Monitor for superinfection.
• Specific Populations: Roxithromycin is generally safe in pregnancy and breastfeeding but should be used with caution and if clearly needed. Monitor infants for potential adverse events while breastfeeding. No dose adjustment is needed in elderly patients or those with renal impairment. Use with caution in hepatic impairment. For pediatric use, dose adjustments are needed based on weight, and duration should be limited to 10 days.
• Lifestyle Considerations: Concurrent alcohol use may exacerbate gastrointestinal side effects, though specific interactions are not well documented.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Roxithromycin?

A: Adults: 150 mg twice daily or 300 mg once daily. Children (6-40 kg): 5-8 mg/kg/day divided into two doses. Children (≥40 kg): 150 mg twice daily.

Q2: What are the common side effects of Roxithromycin?

A: Common side effects include diarrhea, nausea, vomiting, abdominal pain, skin rash, headache, and vaginal thrush.

Q3: Is Roxithromycin safe to use during pregnancy?

A: Roxithromycin is generally considered safe to use during pregnancy, but it should be used with caution and only if clearly needed. Discuss the risks and benefits with your doctor.

Q4: Can I take Roxithromycin while breastfeeding?

A: Roxithromycin is excreted in breast milk in small amounts. It is generally considered safe to breastfeed while taking it, but monitoring the infant for any adverse effects is recommended. Consult your doctor for guidance.

Q5: How should Roxithromycin be administered?

A: Roxithromycin tablets should be taken on an empty stomach at least 15 minutes before food or on an empty stomach (more than 3 hours after a meal). Swallow the tablets whole with a glass of water. Do not crush or chew the tablets.

Q6: What are the contraindications for Roxithromycin use?

A: Contraindications include hypersensitivity to roxithromycin or other macrolides, severe hepatic impairment, concomitant use with ergot alkaloids or certain CYP3A4 substrates, and congenital or acquired long QT syndrome.

Q7: Does Roxithromycin interact with other medications?

A: Yes, Roxithromycin can interact with several medications, including ergot alkaloids, CYP3A4 substrates (e.g., astemizole, cisapride, pimozide, terfenadine), theophylline, warfarin, digoxin, and others. Consult your doctor about all medications you are taking, including over-the-counter drugs and supplements, before starting Roxithromycin.

Q8: What should I do if I miss a dose of Roxithromycin?

A: Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one.

Q9: Can Roxithromycin be used in elderly patients?

A: Yes, Roxithromycin can be used in elderly patients. No dose adjustment is usually required.

Q10: Does Roxithromycin require any special monitoring during treatment?

A: Monitoring parameters may include liver function tests, ECG (for patients at risk of QT prolongation), theophylline levels, INR (if co-administered with warfarin), and complete blood counts (especially in children to monitor for neutropenia).