Pravastatin Itraconazole

The effects of itraconazole, a potent inhibitor of CYP3A4, on the pharmacokinetics of atorvastatin, ceri-vastatin, and pravastatin have been evaluated in an open, randomized, crossover study in 18 healthy subjects who took single doses of atorvastatin 20 mg, cerivastatin 0.8 mg, or pravastatin 40 mg, with and without itraconazole 200 mg (72). Itraconazole markedly raised atorvastatin plasma concentrations (2.5-fold) and produced modest rises in the plasma concentrations of cerivastatin (1.3-fold) and pravastatin (1.5-fold). These results suggest that in patients taking itraconazole, cerivastatin or pravastatin may be preferable to atorvastatin. 

Physicians should check for lipid-lowering drugs before treating elderly individuals with itraconazole (73). Susceptibility to this interaction varies from statin to statin, in that simvastatin is more affected than pravastatin (74). Concomitant use of simvastatin with itraconazole should be avoided, and the same holds true for atorvastatin (75). In another study, the blood concentration of fluvastatin was not significantly increased, whereas that of lovastatin was (76). 

Mazzu AL, Lasseter KC, Shamblen EC, Agarwal V, Lettieri J, Sundaresen P. Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin. Clin Pharmacol Ther 2000 68(4) 391 100. 

Neuvonen PJ, Kantola T, Kivisto KT. Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 1998 63(3) 332-41. 

The effects of itraconazole 200 mg on the pharmacokinetics of pravastatin have been studied in a randomized, double-blind, crossover study in 10 healthy volunteers (12). Itraconazole slightly increased the AUC and Cmax of pravastatin, but the changes were not statistically significant the half-life was not altered. 

Abacavir Adinazolam 5-Aminosalicylic acid Atorvastatin Avitriptan Bromazepam Bumetanide Celecoxib CGP 43371 Clodronate Cyclosporin Danazol Didanosine Erythromycin Fexofenadine Furosemide Ganciclovir Halofantrine Inidnavir Itraconazole Levofloxacin Methotrexate Nifedipine Pravastatin Rifabutin Stavudine Tacrine... 

Itraconazole increases the risk of skeletal muscle toxicity of some statins by increasing their serum concentrations, but not all statins are equally affected. Concomitant use of atorvastatin, lovastatin, and simvastatin with itraconazole should be avoided or the doses should be reduced fluvastatin and pravastatin have much less potential than other statins for chnically significant interactions with itraconazole and other CYP3A4 inhibitors the effects of cerivastatin are intermediate. 

In a randomized, open, three-way, crossover study, 18 healthy subjects took single doses of cerivastatin 0.8 mg, atorvastatin 20 mg, or pravastatin 40 mg without or with itraconazole 200 mg (111). Concomitant cerivastatin - - itraconazole and pravastatin -I- itraconazole produced small increases in AUC, Cmax, and half-Ufe (up to 51%, 25%, and 23% respectively). However, itraconazole markedly increased atorvastatin AUC (150%),... 

Clinically important, potentially hazardous interactions with alfentanil, aminophylline, amisulpride, amoxicillin, ampicillin, anticonvulsants, astemizole, atorvastatin, benzodiazepines, bromocriptine, buprenorphine, bupropion, carbamazepine, cilostazol, ciprofloxacin, cisapride, clindamycin, colchicine, cyclosporine, dasatinib, digoxin, dihydroergotamine, diltiazem, disopyramide, enoxacin, eplerenone, ergotamine, eszopiclone, everolimus, fluconazole, fluoxetine, fluvastatin, gatifloxacin, HMG-CoA reductase inhibitors, imatinib, itraconazole, ketoconazole, lomefloxacin, lorazepam, lovastatin, methadone, methylprednisolone, methysergide, midazolam, mizolastine, moxifloxacin, nitrazepam, norfloxacin, ofloxacin, paroxetine, pimozide, pravastatin, quinolones, ranolazine, repaglinide, rupatadine, sertraline, sildenafil, simvastatin, sparfloxacin, sulpiride, tacrolimus, terfenadine, triazolam, troleandomycin, vardenafil, verapamil, vinblastine, warfarin, zaleplon, zolpidem, zuclopenthixol... 

Clinically important, potentially hazardous interactions with amlodipine, anisindione, anticoagulants, aprepitant, atorvastatin, barbiturates, benzodiazepines, butabarbital, carbamazepine, chlordiazepoxide, clarithromycin, clonazepam, dorazepate, corticosteroids, cyclosporine, dexamethasone, diazepam, dicumarol, erythromycin, ethotoin, felodipine, flurazepam, fluvastatin, fosphenytoin, isradipine, itraconazole, ketoconazole, lorazepam, lovastatin, mephenytoin, mephobarbital, midazolam, nicardipine, nifedipine, nimodipine, nisoldipine, oxazepam, pentobarbital, phenobarbital, pimozide, pravastatin, primidone, quazepam, rifampin, secobarbital, simvastatin, St John s wort, temazepam, warfarin... 

Figure 11.9 Different effects of itraconazole and obtained from the previous literature. The details cyclosporin A on the plasma AUC of pravastatin, are described in the Section 11.7.1. BA simvastatin, and atorvastatin [210, 221-224], bioavailability, Fa Fg fraction of dose absorbed The fold-increase in the plasma AUC of statins from the small intestine to the portal vein, Fh was expressed after coadministration of hepatic availability,...

The AUC of a single 40-mg dose of pravastatin was increased by 71% in 10 healthy subjects who took itraconazole 200 mg daily for 4 days, although this did not reach statistical significance. In a similar study, the same dosage of itraconazole caused a modest 51% increase in the AUC of pravastatin. In contrast, one study in 104 subjects found that itraconazole had no effect on pravastatin pharmacokinetics. ... 

HMG Co-A reductase inhibitors A 58-year-old man who was taking simvastatin was given itraconazole for onychomycosis, and the simvastatin was replaced by pravastatin to prevent drug interactions [18 ]. He ran out of pravastatin and started to take simvastatin again. He developed myalgia and muscle weakness after 1 week, with a greatly raised serum creatine kinase activity, and then severe rhabdomyolysis. 

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