Pis Drug Interaction
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Protease Inhibitors (PIs)-Drug Interactions Drugs Affected
Indinavir* (Crixivan®, IDV)
Ritonavir* (Norvir®, RTV)
Saquinavir* (Fortovase®, SQV)
Nelfinavir* (Viracept®, NFV)
Amprenavir* (Agenerase®, APV)
Lopinavir/Ritonavir* (Kaletra®, LPV/RTV)
IDV ↑ 68% Dose: IDV 600mg tid
Keto. ↑ 3X Dose: NTE keto dose 200mg/day
SQV ↑ 3X No dose adjustment
No dose adjustment
APV ↑ 31%, Keto ↑ 44% Dose: Combo. Use under investigation
LPV AUC ↓ 13% Keto ↑ 3-fold
Rifampin
IDV ↓ 89% Contraindicated
RTV ↓ 35% Dose: no data, possible ↑ liver toxicity
NFV ↓ 82% Contraindicated
APV AUC ↓ 82% No change in rifampin AUC Avoid concomitant use
LPV ↓ 75% Avoid concomitant use
Rifabutin
IDV ↓ 32% rifabutin ↑ 2X Dose: ↓ rifabutin 150mg qd or 300mg 2-3x/wk IDV 1000mg tid
Rifabutin ↑ 4X Dose: ↓ rifabutin dose to 150mg qod or 3x/wk RTV std dose
SQV ↓ 84% Contraindicated unless using with RTV+SQV→use rifampin dose 600mg qd or 23X/wk SQV ↓ 40% No dose adjustment unless use with SQV+RTV→ rifabutin 150mg 2-3x/wk
NFV ↓ 32% Rifabutin ↑ 2X Dose: rifabutin ↓ 150mg qd or 300mg 2-3x/wk NFV ↑ 1000mg tid
APV AUC ↓ 15% Rifabutin ↑ 193% Dose: Rifabutin ↓ 150mg qd or 300mg 2-3x/wk APV std dose
Rifabutin AUC ↑ 3-fold Dose: Rifabutin ↓ 150mg qod & LPV/RTV std dose
Clarithromycin
Clarithro ↑ 53% No dose adjustment
Clarithro ↑ 77% Dose adjust for renal impairment
No data
APV AUC ↑ 18% No dose adjustment
No data
Oral Contraceptives
Norethindrone ↑ 26% Ethinyl estradiol ↑ 24% No dsoe adjustment
Ethinyl estradiol ↓ 40% Use alternative/additional methods
Clarithro ↑ 45% SQV ↑ 177% No dose adjustment No data
Norethindrone ↓ 18% Ethinyl estradiol ↓ 47% Use alternative/additional methods
Potential for interaction Use alternative/additional methods
Ethinyl estradiol ↓ 42% Use alternative/additional methods
Potential for large increase in statin level Avoid concomitant use
Potential for large increase in statin level Avoid concomitant use
Potential for large increase in statin level Avoid concomitant use
Potential for large increase in statin level Avoid concomitant use
Potential for large increase in statin level Avoid concomitant use
Potential for large increase in statin level Avoid concomitant use
_____
_____
_____
Antifungal Ketoconazole
Anti-mycobacterials
Lipid Lowering Agents Simvastatin Lovastatin Atorvastatin Pravastatin
_____
______
Atorvastatin AUC ↑ 5.88fold→ use w/caution Pravastatin AUC ↑ 33%→ no dose adjustment
Anticonvulsants Phenobarbitol Phenytoin Carbamazepine
Carbamazepine ↓ IDV AUC Consider alternative agent
Unknown Use w/caution, monitor anticonvulsant levels
Unknown, may ↓ SQV levels Monitor anticonvulsant level
Unknown, may ↓ NFV levels Monitor anticonvulsant levels
Methadone
No change in methadone levels
Methadone ↓ 37% May need to ↑ methadone dose
No data
NFV may ↓ methadone levels May need to ↑ methadone dose
Miscellaneous
GJ§ ↓ IDV by 26% Sildenafil AUC ↑ 2-11 fold. NTE 25mg in 48 hr
Sildenafil AUC ↑ 2-11 fold. NTE 25mg in 48 hr Desipramine ↑ 145%, ↓ dose Theophylline ↓ 47%, monitor level
GJ§ ↑ SQV levels Sildenafil AUC ↑ 2-11 fold. Use 25mg starting dose of sildenafil
Sildenafil AUC ↑ 2-11 fold NTE 25mg in 48 hr
*Inhibitor of CYP3A4 isoenzyme § Grapefruit Juice
Unknown, may ↓ APV levels substantially Monitor anticonvulsant level No data
Unknown, may ↓ LPV levels substantially Monitor anticonvulsant levels
Sildenafil AUC ↑ 2-11 fold NTE 25mg in 48 hr
Possible substantial ↑ in sildenafil AUC. NTE 25mg in 48 hr
Methadone AUC ↓ 53% May need to ↑ methadone dose
(2001)
Indinavir* (Crixivan®, IDV)
Ritonavir* (Norvir®, RTV)
Saquinavir* (Fortovase®, SQV)
Nelfinavir* (Viracept®, NFV)
Amprenavir* (Agenerase®, APV)
Lopinavir/Ritonavir* (Kaletra®, LPV/RTV)
IDV ↑ 68% Dose: IDV 600mg tid
Keto. ↑ 3X Dose: NTE keto dose 200mg/day
SQV ↑ 3X No dose adjustment
No dose adjustment
APV ↑ 31%, Keto ↑ 44% Dose: Combo. Use under investigation
LPV AUC ↓ 13% Keto ↑ 3-fold
Rifampin
IDV ↓ 89% Contraindicated
RTV ↓ 35% Dose: no data, possible ↑ liver toxicity
NFV ↓ 82% Contraindicated
APV AUC ↓ 82% No change in rifampin AUC Avoid concomitant use
LPV ↓ 75% Avoid concomitant use
Rifabutin
IDV ↓ 32% rifabutin ↑ 2X Dose: ↓ rifabutin 150mg qd or 300mg 2-3x/wk IDV 1000mg tid
Rifabutin ↑ 4X Dose: ↓ rifabutin dose to 150mg qod or 3x/wk RTV std dose
SQV ↓ 84% Contraindicated unless using with RTV+SQV→use rifampin dose 600mg qd or 23X/wk SQV ↓ 40% No dose adjustment unless use with SQV+RTV→ rifabutin 150mg 2-3x/wk
NFV ↓ 32% Rifabutin ↑ 2X Dose: rifabutin ↓ 150mg qd or 300mg 2-3x/wk NFV ↑ 1000mg tid
APV AUC ↓ 15% Rifabutin ↑ 193% Dose: Rifabutin ↓ 150mg qd or 300mg 2-3x/wk APV std dose
Rifabutin AUC ↑ 3-fold Dose: Rifabutin ↓ 150mg qod & LPV/RTV std dose
Clarithromycin
Clarithro ↑ 53% No dose adjustment
Clarithro ↑ 77% Dose adjust for renal impairment
No data
APV AUC ↑ 18% No dose adjustment
No data
Oral Contraceptives
Norethindrone ↑ 26% Ethinyl estradiol ↑ 24% No dsoe adjustment
Ethinyl estradiol ↓ 40% Use alternative/additional methods
Clarithro ↑ 45% SQV ↑ 177% No dose adjustment No data
Norethindrone ↓ 18% Ethinyl estradiol ↓ 47% Use alternative/additional methods
Potential for interaction Use alternative/additional methods
Ethinyl estradiol ↓ 42% Use alternative/additional methods
Potential for large increase in statin level Avoid concomitant use
Potential for large increase in statin level Avoid concomitant use
Potential for large increase in statin level Avoid concomitant use
Potential for large increase in statin level Avoid concomitant use
Potential for large increase in statin level Avoid concomitant use
Potential for large increase in statin level Avoid concomitant use
_____
_____
_____
Antifungal Ketoconazole
Anti-mycobacterials
Lipid Lowering Agents Simvastatin Lovastatin Atorvastatin Pravastatin
_____
______
Atorvastatin AUC ↑ 5.88fold→ use w/caution Pravastatin AUC ↑ 33%→ no dose adjustment
Anticonvulsants Phenobarbitol Phenytoin Carbamazepine
Carbamazepine ↓ IDV AUC Consider alternative agent
Unknown Use w/caution, monitor anticonvulsant levels
Unknown, may ↓ SQV levels Monitor anticonvulsant level
Unknown, may ↓ NFV levels Monitor anticonvulsant levels
Methadone
No change in methadone levels
Methadone ↓ 37% May need to ↑ methadone dose
No data
NFV may ↓ methadone levels May need to ↑ methadone dose
Miscellaneous
GJ§ ↓ IDV by 26% Sildenafil AUC ↑ 2-11 fold. NTE 25mg in 48 hr
Sildenafil AUC ↑ 2-11 fold. NTE 25mg in 48 hr Desipramine ↑ 145%, ↓ dose Theophylline ↓ 47%, monitor level
GJ§ ↑ SQV levels Sildenafil AUC ↑ 2-11 fold. Use 25mg starting dose of sildenafil
Sildenafil AUC ↑ 2-11 fold NTE 25mg in 48 hr
*Inhibitor of CYP3A4 isoenzyme § Grapefruit Juice
Unknown, may ↓ APV levels substantially Monitor anticonvulsant level No data
Unknown, may ↓ LPV levels substantially Monitor anticonvulsant levels
Sildenafil AUC ↑ 2-11 fold NTE 25mg in 48 hr
Possible substantial ↑ in sildenafil AUC. NTE 25mg in 48 hr
Methadone AUC ↓ 53% May need to ↑ methadone dose
(2001)
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