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Liver function impairment –The pharmacokinetics are altered. No dosage adjustment is required in patients with hepatic function impairment, unless there is also concurrent severe renal function impairment. |
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Renal function impairment (severe) –The elimination of Klarithranis reduced in patients with renal function impairment, especially those with a creatinine clearance of <30 mL/min. The dose of Klarithranshould be halved or the dosing interval doubled in patients with a creatinine clearance of <30 mL/min. |
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Rhabdomyolysis has been reported with concomitant use of Klarithranand the HMGCoA reductase inhibitors e.g. simvastatin (See Interactions). |
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Rifabutin and rifampicin –May decrease serum concentration of Klarithranby >50%. Co-administration has been reported to cause a higher incidence of uveitis compared to rifabutin alone (See Interactions). |
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Theophylline – The area under the plasma concentration-time curve is increased. Monitoring of theophylline serum concentrations is recommended (See Interactions). |
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Cross-resistance between Klarithranand other macrolides, lincomycin and clindamycin have been reported. |
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Astemizole, cisapride, pimozide and terfenadine – Has resulted in cardiac arrhythmias, including QTc-interval prolongation, ventricular arrhythmia, ventricular tachycardia, ventricular fibrillation and torsade de pointes. Fatalities have occurred. The most likely cause is the inhibition of metabolism of these medicines by Klarithran. Concurrent use is contra-indicated. See Contra-indications. |
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Anticoagulants such as warfarin –Klarithranmay result in the potentiation of the effects of warfarin. Prothrombin time should be monitored closely. |
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Digoxin –Klarithran has been shown to increase serum digoxin concentrations. Monitoring of digoxin serum concentrations is recommended. |
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Carbamazepine or other medicines metabolised by the cytochrome P450 enzyme system for example, alprazolam, cyclosporine, disopyramide, ergot alkaloids, methylprednisolone, midazolam, omeprazole, quinidine, sildenafil, simvastatin, tacrolimus, triazolam, vinblastine, phenytoin, and valproate –Klarithran may be associated with increased levels of these medicines. Serum concentrations of these medicines may require monitoring. Rhabdomyolysis has been reported with concomitant use of Klarithran and the HMGCoA reductase inhibitors e.g. simvastatin (See Warnings). |
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Rifabutin and rifampicin –May decrease serum concentration of Klarithranby >50%. Co-administration has been reported to cause a higher incidence of uveitis compared to rifabutin alone (SeeWarnings). |
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Theophylline –The area under the plasma concentration-time curve is increased. Monitoring of theophylline serum concentrations is recommended (See Warnings) |
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Zidovudine – A decrease in the steady-state concentration of zidovudine may occur. Doses of zidovudine and Klarithranshould be taken at least 4 hours apart. |
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Ritonavir –The metabolism of Klarithranis inhibited. No dosage reduction of Klarithranis needed in patients with normal renal function. Patients with renal function impairment require a reduction in the dosage of Klarithranas follows: |
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Creatinine clearance 30 to 60 mL/min –Reduce dose by 50%. |
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Creatinine clearance of <30 mL/min –Reduce dose by 75%. |
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Do not exceed a dose of 1 g/day during concurrent administration of Klarithranwith ritonavir. |
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It has been suggested that other HIV-protease inhibitors and non-nucleoside reverse transcriptase inhibitors may have a similar effect on Klarithran. |
KLARITHRAN 250 Tablets