CLARIZED-500

Indications

• Bacterial respiratory tract infections
• Skin and soft tissue infections
• Sinusitis
• Otitis media
• Chlamydia infections
• Mycobacterial infections

Dosage

Adults: Refer to the BNF for specific dosing

Mechanism of action

Clarithromycin is first metabolized to 14-OH clarithromycin, which is active and works synergistically with its parent compound. It penetrates the bacterial cell wall and reversibly binds to domain V of the 23S ribosomal RNA of the 50S ribosomal subunit, blocking translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis. It also inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump.

Pharmacodynamics

Clarithromycin exhibits a broad spectrum of activity against many gram-positive bacteria such as Staphylococcus aureus, S. pneumoniae, and S. pyogenes, as well as gram-negative bacteria including Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis. It also shows activity against various anaerobic bacteria, some mycobacteria, and organisms like Mycoplasma, Ureaplasma, Chlamydia, Toxoplasma, and Borrelia. While generally bacteriostatic, it can be bactericidal at high concentrations or against highly susceptible organisms.

Pharmacokinetics

Clarithromycin is well-absorbed after oral administration, with peak plasma concentrations occurring within 2-3 hours. It is extensively metabolized in the liver, primarily by CYP3A4, with its metabolites including 14-OH clarithromycin. The drug has a half-life of approximately 3-4 hours and is eliminated predominantly through the urine. The presence of food can affect its absorption but does not significantly alter its overall bioavailability.

Contra-indications

• Hypersensitivity to clarithromycin, erythromycin, or any macrolide antibiotic
• History of cholestatic jaundice or hepatic dysfunction associated with previous use of clarithromycin

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Abdominal pain
• Altered taste
• Headache
• Dizziness
• Rash
• Liver enzyme elevation
• QT interval prolongation
• Rarely, severe allergic reactions (anaphylaxis)

Interactions

• Inhibits CYP3A4, potentially increasing plasma concentrations of drugs metabolized by this enzyme (e.g., certain statins, benzodiazepines, and calcium channel blockers)
• May enhance the effects of warfarin, increasing the risk of bleeding
• Concurrent use with ergotamine or dihydroergotamine can lead to ergot toxicity
• May increase plasma levels of midazolam when co-administered

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for signs of hepatic dysfunction during treatment
• Consider alternative therapy in individuals with known QT prolongation
• Use in pregnancy only if clearly needed

Pregnancy

Clarithromycin should be used in pregnancy only if the potential benefits justify the potential risk to the fetus. Risk category C.

Breast-feeding

Clarithromycin is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool and dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets (250 mg, 500 mg)
• Oral suspension (125 mg/5 mL, 250 mg/5 mL)

Mechanism of action

Clarithromycin is first metabolized to 14-OH clarithromycin, which is active and works synergistically with its parent compound. Like other macrolides, it then penetrates bacteria cell wall and reversibly binds to domain V of the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome, blocking translocation of aminoacyl transfer-RNA and polypeptide synthesis. Clarithromycin also inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump. Clarithromycin usually is bacteriostatic, although it may be bactericidal in high concentrations or against highly susceptible organisms. Bactericidal activity has been observed against Streptococcus pyogenes, S. pneumoniae, Haemophilus influenzae, and Chlamydia trachomatis. Clarithromycin inhibits protein synthesis in susceptible organisms by penetrating the cell wall and binding to 50S ribosomal subunits, thereby inhibiting translocation of aminoacyl transfer-RNA and inhibiting polypeptide synthesis. The site of action of clarithromycin appears to be the same as that of erythromycin, clindamycin, lincomycin, and chloramphenicol.

Pharmacodynamics

Clarithromycin is a macrolide antibiotic whose spectrum of activity includes many gram-positive (<i>Staphylococcus aureus, S. pneumoniae, and S. pyogenes</i>) and gram-negative aerobic bacteria (<i>Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis</i>), many anaerobic bacteria, some mycobacteria, and some other organisms including <i>Mycoplasma, Ureaplasma, Chlamydia, Toxoplasma</i>, and <i>Borrelia</i>. Other aerobic bacteria that clarithromycin has activity against include <i>C. pneumoniae and M. pneumoniae</i>. Clarithromycin has an in-vitro activity that is similar or greater than that of erythromycin against erythromycin-susceptible organisms. Clarithromycin is usually bacteriostatic, but may be bactericidal depending on the organism and the drug concentration.