Simvastatin 4- Nelfinavir

Hare CB, Vu MP, Grunfeld C, Lampiris HW. Simvastatin-nelfinavir interaction implicated in rhabdomyolysis and death. Clin Infect Dis (20 2) 35, el 11-el 12. 

Hypersensitivity to any component of the product. Coadministration of nelfinavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (eg, amiodarone, quinidine, ergot derivatives, pimozide, midazolam, triazolam, lovastatin, simvastatin see Drug Interactions). 

Chemotherapy Cyclophosphamide, erlotlnlb, ifos-famide, paclitaxel, tamoxifen, vinblastine, vincristine HIV protease inhibitors Amprenavir, atazanavir, indinavir, nelfinavir, ritonavir, saquinavir HMG-CoA reductase inhibitors Atorvastatin, lovastatin, simvastatin... 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Healthy volunteers were given protease inhibitors and statins, and the authors concluded that simvastatin should be avoided and that atorvastatin could be used with caution in people taking ritonavir and saquinavir (111). Dosage adjustment of pravastatin may be necessary with co-administration of ritonavir and saquinavir. Pravastatin does not alter the pharmacokinetics of nelfinavir, and thus appears to be safe for co-administration. 

Isoniazid Avasimibe Bosentan Carbam- a2epine" Clotrimazole Cyproterone acetate Hyperforin Lovastatin Mifepristone Nelfinavir Nifedipine Omeprazole Paclitaxel Phenobarbital Phenytoin Rifabutin Rifampin"" Rifapentine Ritonavir Simvastatin Sulfinpyrazole Topotecan Troglitazone Troleandomycin Vitamin E Vitamin K2 Yin zhi wuang... 

A4/3A5 Midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, triazolam Atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin Rifampin, carbamazepine... 

Since HMG CoA reductase inhibitors (statins) are partially or completely metabolized by CYP3A4, drug interactions with protease inhibitors can be expected. When nelfinavir was combined with atorvastatin and simvastatin, their AUCs increased by 74 and 505% respectively (17). As myopathy and rhabdomyolysis are concentration-related, simvastatin is contraindicated with any protease inhibitor, not just nelfinavir. Based on the data, the starting dose of atorvastatin should be reduced by about 50%. 

Hsyu PH, Schultz-Smith MD, Lillibridge JH, Lewis RH, Kerr BM. Pharmacokinetic interactions between nelfinavir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and simvastatin. Antimicrob Agents Chemother 2001 45(12) 3445-50. 

There has been a study of the effects of ritonavir 400 mg bd plus saquinavir soft-gel capsules 400 mg bd on the pharmacokinetics of pravastatin, simvastatin, and atorvas-tatin (40 mg/day each), and of the effect of pravastatin on the pharmacokinetics of nelfinavir in a randomized, open study in 56 healthy HIV-negative adults (46). Ritonavir - -saquinavir reduced the steady-state AUC of pravastatin, markedly increased the AUC of simvastatin, and slightly increased the AUC of total active atorvastatin. The AUCs of nelfinavir and its active M8 metabolite were not altered by pravastatin. The authors concluded that simvastatin (and by implication lovastatin, which in... 

Nelfinavir (NFV) Yes Simvastatin, Atorvastatin, Delavirdine Product Monograph [48] Yes Methadone [49]... 

The levels of atorvastatin and simvastatin are markedly increased by lopinavir and saquinavir (with ritonavir), nelfinavir, and ritonavir alone. Pravastatin seems only moderately affected. Several cases of rhabdomyolysis have been attributed to this interaction. 

In an open label study, 31 healthy subjects were given either atorvastatin 10 mg daily or simvastatin 20 mg daily for 28 days, with nelfinavir 1.25 g twice daily for the last 14 days. Nelfinavir increased the maximum serum levels and AUC of atorvastatin approximately twofold and the maximum serum levels and AUC of simvastatin approximately sixfold. No significant adverse effects, or any signs of rhabdomyolysis were noted throughout the study. ... 

---