PROKLAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROKLAR (PROKLAR).
PROKLAR (clarithromycin) is a macrolide antibiotic that inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, blocking peptide chain elongation.
| Metabolism | Primarily hepatic via CYP3A4; major metabolites include 14-hydroxyclarithromycin, which is active. Undergoes extensive first-pass metabolism. |
| Excretion | Renal: 20-30% unchanged; fecal: 15-30%; biliary: 5-10%; total renal excretion of metabolites: ~70% |
| Half-life | Terminal elimination half-life: 2-4 hours (prolonged to 6-8 hours in hepatic impairment); context: requires q8-12h dosing in normal renal function |
| Protein binding | 42-50% bound to serum albumin (primarily) and alpha-1-acid glycoprotein |
| Volume of Distribution | 3-4 L/kg; indicates extensive tissue penetration (e.g., lung, prostate, bone) |
| Bioavailability | Topical: 0.5-2% (minimal systemic); oral: 15-30% (first-pass effect); IM: 90-100% |
| Onset of Action | Oral: 30-60 minutes; IV: 15-30 minutes; topical: 2-4 hours (antimicrobial effect) |
| Duration of Action | Oral/IV: 6-8 hours (bacteriostatic levels); clinical note: tissue concentrations persist beyond serum half-life up to 24 hours |
500 mg orally every 12 hours for 7-14 days.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-89 mL/min: no adjustment; CrCl 15-29 mL/min: 250 mg every 12 hours; CrCl <15 mL/min: 250 mg every 24 hours. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% or every 12 hours to every 24 hours; Child-Pugh C: 250 mg every 24 hours. |
| Pediatric use | 15 mg/kg/day divided every 12 hours, not to exceed 500 mg per dose. |
| Geriatric use | No specific dose adjustment; monitor renal function and adjust accordingly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROKLAR (PROKLAR).
| Breastfeeding | Excreted in human milk; M/P ratio not established. Contraindicated in breastfeeding due to risk of infant gastrointestinal bleeding and interference with platelet function. |
| Teratogenic Risk | Pregnancy Category C: Animal studies have shown teratogenic effects at high doses. First trimester: Potential risk of cardiac malformations and neural tube defects. Second and third trimesters: Risk of premature ductus arteriosus closure and pulmonary hypertension; avoid use after 32 weeks. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to clarithromycin or any macrolide antibiotic","Concomitant use with ergot derivatives (ergotamine, dihydroergotamine)","Concomitant use with HMG-CoA reductase inhibitors that are CYP3A4 substrates (e.g., lovastatin, simvastatin)","History of cholestatic jaundice or hepatic dysfunction with prior clarithromycin use","Concomitant use with ticagrelor or ranolazine","Prolonged QT interval or concurrent use with other QT-prolonging drugs"]
| Precautions | ["Prolongs QT interval, risk of cardiac arrhythmias (including torsades de pointes)","Exacerbation of myasthenia gravis","Hepatotoxicity (elevated liver enzymes, hepatitis)","Clostridioides difficile infection","Increased risk of cardiovascular events in patients with coronary artery disease","Potential for drug interactions with CYP3A4 substrates/inducers (e.g., statins, warfarin, colchicine)"] |
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| Monitor fetal ductus arteriosus via ultrasound after 32 weeks if used. Assess maternal platelet count and bleeding time. Monitor fetal growth and amniotic fluid volume. |
| Fertility Effects | Reversible interference with ovulation via prostaglandin synthesis inhibition. May impair implantation and increase risk of spontaneous abortion. Discontinuation restores normal fertility. |