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Database of Antiretroviral Drug Interactions

All Interactions with Ritonavir (Norvir)

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Alfuzosin55
(Uroxatral)
------

Do not coadminister

Alprazolam55
(Xanax)
1 mg x 1500 mg BID x 10 dAlprazolam AUC: no significant change; Cmax: decreased 16%- - -

Avoid combination; consider alternative agents

Alternative Agents:
Lorazepam

Alprazolam55, 178, 255
(Xanax)
1 mg x 1 dose200 mg BIDAlprazolam clearance: decreased 59%; half-life: increased 122%- Increased alprazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by ritonavir

Avoid combination; consider alternative agents

Alternative Agents:
Lorazepam

Amiodarone55
(Cordarone)
--Not studied; may increase amiodarone levels-Increased amiodarone effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by ritonavir

Do not coadminister

Amitriptyline55
(Elavil)
- - Increased amitriptyline levels- Increased amitriptyline effects (eg, dry mouth, hypotension, confusion)Inhibition of CYP450 3A4 and 2D6 by ritonavir

Monitor and adjust amitriptyline as indicated

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir63, 53
(APV)(Agenerase)
--Increased amprenavir levelsNot studiedIncreased amprenavir effectsInhibition of CYP450 3A4 by ritonavir

Dose adjustment not established

Amprenavir112
(APV)(Agenerase)
1200 mg BID200 mg BIDAmprenavir AUC: increased 127%; Cmin: increased 395%;Not studiedIncreased amprenavir effectsInhibition of CYP450 3A4 by ritonavir

No dose adjustment necessary

Amprenavir112
(APV)(Agenerase)
1200 mg BID500 mg BIDAmprenavir AUC: increased 143%; Cmin: increased 576%Not studiedIncreased amprenavir effectsInhibition of CYP450 3A4 by ritonavir

Dose adjustment not established

Amprenavir112
(APV)(Agenerase)
1200 mg BID with efavirenz 600 mg QD200 mg BIDNo significant changeNot studied-Inhibition of CYP450 3A4 by ritonavir and induction of CYP450 3A4 by efavirenz

No dose adjustment necessary

Amprenavir60
(APV)(Agenerase)
1200 mg QD200 mg BID x 2-4 weeksAmprenavir AUC: increased 62%; Cmin: increased 319%Not studiedIncreased amprenavir effectsInhibition of CYP450 3A4 by ritonavir

Dose adjustment not established

Amprenavir116
(APV)(Agenerase)
1200 mg QD on days 1-7100 mg on days 8-14, 200 mg QD on days 15-21Amprenavir AUC: increased 119%; Cmax: no significant change; Cmin: increased 840% (with 100 mg ritonavir); no significant change with 200 mg ritonavirNot studiedIncreased amprenavir effectsInhibition of CYP450 3A4 by ritonavir

Dose adjustment not established

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amprenavir60
(APV)(Agenerase)
600 mg BID100 mg BID x 2-4 weeksAmprenavir AUC: increased 64%; Cmax: decreased 30%; Cmin: increased 508%Not studiedIncreased amprenavir effectsInhibition of CYP450 3A4 by ritonavir

-

Amprenavir115
(APV)(Agenerase)
900 mg Q12H100 mg Q12HAmprenavir AUC: increased 109%; Cmax: no significant change; Cmin: increased 585%Ritonavir AUC: decreased 64%; Cmax: decreased 32%; Cmin: decreased 65%Increased amprenavir effectsInhibition of CYP450 3A4 by ritonavir and induction of CYP450 3A4 by amprenavir

Dose adjustment not established

Astemizole178, 55
(Hismanal)
--Not studied; may increase astemizole levels-Increased astemizole effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by ritonavir

Do not coadminister

Alternative Agents:
Cetirizine Fexofenadine Loratadine

Atazanavir99,
(ATV)(Reyataz)
300 mg QD on days 1-20100 mg QD on days 11-20Atazanavir AUC: increased 238%; Cmax: increased 86%; Cmin: increased 1089%Not studiedIncreased atazanavir effectsInhibition of CYP450 3A4 by ritonavir

Dose adjustment not established

Beclomethasone583
160 mcg inhaled BID100 mg BIDBeclomethasone-17-monopriopionate AUC: increased 108%; Cmax: increased 67%Not studied--

Use lowest possible dose and titrate to effect

Bepridil55
(Vascor)
--Not studied; may increase bepridil levels-Increased bepridil effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by ritonavir

Do not coadminister

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Boceprevir569
(Victrelis)
400 mg TID x 15 days100 mg QD x 12 daysBoceprevir AUC: decreased 19%; Cmax: decreased 27%-Potentially decreased boceprevir effects; effect on ritonavir concentrations unknown-

Clinical significance unknown especially when combined with other protease inhibitors

Carbamazepine178, 292
(others)(Tegretol)
350 mg BID200 mg QD-TIDNot studied; May increase carbamazepine levelsDecreased ritonavir levelsIncreased carbamazepine effects; decreased ritonavir effectsInduction of CYP450 2C and 3A4

Avoid combination if possible; consider alternative agents;monitor carbamazepine levels and adjust as indicated

Alternative Agents:
Gabapentin Lamotrigine Tiagabine Topiramate

Cetirizine252
(Zyrtec)
10 mg QD600 mg BIDCetirizine AUC: increased 42%; half-life: increased 52%; clearance: decreased 29%; Cmax: no significant changeNot studied--

No dose adjustment necessary

Cisapride178, 55
(Propulsid)
--Increased cisapride levels-Increased cisapride effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by ritonavir

Do not coadminister

Alternative Agents:
Metoclopramide

Clarithromycin360, 56
(Biaxin)
500 mg BID200 mg TIDClarithromycin AUC: increased 77%; Cmax: increased 31%; Cmin: increased 182%AUC: no significant change; Cmax: increased 15%Increased clarithromycin effectsInhibition of CYP450 3A4 by ritonavir

No dose adjustment necessary

Co-trimoxazole55
(TMP/SMX, Trimethoprim/Sulfamethoxazole)(Bactrim, Septra)
160 mg/800 mg x 1 dose500 mg Q12H x 12 daysSulfamethoxazole AUC: decreased 20%; trimethoprim AUC: increased 20%- - Induction of CYP450 3A4 by ritonavir

No dose adjustment necessary

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Colchicine529
(Colcrys, Colcrys)
0.6 mg x 1100 mg BID x 5 daysColchicine AUC: increased 296%; Cmax: increased 184%-Increased colchicine effectsInhibition of P450 3A4 by ritonavir

For treatment of gout, reduce colchicine dosage to 0.6 mg x 1 then 0.3 mg one hour later. Dose not to be repeated no earlier than 3 days. For prophylaxis of gout, reduce colchicine dosage to 0.3 mg QD if on 0.6 mg BID prior to PI therapy or reduce colchicine dose to 0.3 mg QOD if on 0.6 mg QD prior to PI therapy.

Delavirdine88
(DLV)(Rescriptor)
400 or 600 mg BID300 mg BIDNo significant changeNo significant change- -

No dose adjustment necessary

Delavirdine59
(DLV)(Rescriptor)
600 mg BID x 10 days100 mg BID x 10 daysNo significant changeRitonavir AUC: increased 81%; Cmax: increased 50%; Cmin: increased 113%Increased ritonavir effectsInhibition of CYP450 3A4 by delavirdine

No dose adjustment necessary

Desipramine260
(Norpramin)
- - Desipramine clearance: decreased 59%- Increased desipramine effects (eg, dry mouth, dizziness, urinary retention)Inhibition of CYP450 2D6 by ritonavir

Monitor and adjust desipramine as indicated

Diazepam178, 55
(Valium)
--Increased diazepam levels-Increased diazepam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A by ritonavir

Do not coadminister

Alternative Agents:
Lorazepam Oxazepam Temazepam

Didanosine84
(ddI)(Videx)
200 mg (buffered formulation) Q12H x 4 days600 mg Q12H x 4 daysDidanosine AUC: no significant change; Cmax: decreased 16%No significant change--

No dose adjustment necessary

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Didanosine54, 55
(ddI)(Videx)
200 mg (tablets) BID600 mg BIDDidanosine AUC: decreased 15%; Cmax: decreased 15%Not studiedDecreased didanosine effectsFormulation incompatibility

Separate didanosine and ritonavir administration by at least 2.5 hours

Digoxin385, 386
(others)(Lanoxin)
0.4 mg x 1 dose200 mg BID x 15 daysDigoxin AUC (0-8 hr): increased 29%; AUC (0-72 hr): increased 22%; clearance: decreased 30%; half-life: increased 43%Not studiedIncreased digoxin effectsPossible inhibition of P-gp by ritonavir

Monitor digoxin concentrations closely

Disulfiram55
(Antabuse)
--Oral solution (contains alcohol) and capsules-Disulfiram reaction (eg, headache, hypotension, flushing, vomiting)Inhibition of aldehyde dehydrogenase by disulfiram

Do not coadminister

Efavirenz56
(EFV)(Sustiva)
600 mg QDDay 1: 300 mg Q12H; Day 2: 400mg Q12H; Days 3-10: 500 mg Q12HEfavirenz AUC: increased 21%Ritonavir AUC: increased 18%Possible increased effects of both drugsInhibition of CYP450 3A4 by both drugs

May dose ritonavir at 500 mg BID when given with efavirenz; no dose adjustment required for efavirenz

Efavirenz90
(EFV)(Sustiva)
600 mg x 10 days500 mg Q12H x 8 daysEfavirenz AUC: increased 21%; Cmax: no significant changeRitonavir AUC: increased 18% after AM dose; Cmax: increased 24% after AM dose; AUC: no significant change after PM dose; Cmax: no significant change after PM doseIncreased efavirenz and ritonavir effectsInhibition of CYP450 3A4 by both drugs

No dose adjustment necessary

Enfuvirtide6, 7
(ENF)(Fuzeon)
90 mg SQ BID on days 1-7200 mg BID on days 4-7Enfuvirtide Cmax: increased 24%; Cmin: no significant change; AUC: increased 22%No significant change--

No dose adjustment necessary

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Ergotamine178, 318, 319, 320, 321, 55
(Cafergot, Ergot derivatives)(Cafergot, others)
--Not studied; may increase ergotamine levels-Increased ergotamine effects (eg, ergotism)Inhibition of CYP450 3A4 by ritonavir

Do not coadminister

Alternative Agents:
5-HT agonists ("triptans")

Escitalopram387
(Lexapro)
20 mg x 1 dose600 mg x 1 doseNo significant changeNo significant change--

No dose adjustment necessary

Ethinyl estradiol/norethindrone acetate368, 55
(others)(Ortho-Novum)
50 mcg x 2 doses500 mg Q12HEthinyl estradiol Cmax: decreased 32%; AUC: decreased 41%- Decreased oral contraceptive effectivenessInduction CYP450 3A4 by ritonavir

Use alternative contraceptive method

Alternative Agents:
Barrier devices; Condoms

Etravirine405
(ETR)(Intelence)
-600 mg BIDEtravirine AUC: decreased 46%; Cmax: decreased 32%-- Induction of CYP450 by ritonavir

-

Fentanyl179
(Duragesic)
5 mcg/kgDay 1: 200 mg TID; Day 2: 300 mg TID; Day 3: 300 mg QAMFentanyl clearance: decreased 67%- Increased fentanyl effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by ritonavir

Monitor closely when using together; start with low dose and titrate to pain response as indicated

Flecainide55
(Tambocor)(Tambocor)
--Not studied; may increase flecainide levels-Increased flecainide effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by ritonavir

Do not coadminister

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Fluconazole273
(Diflucan)(Diflucan)
400 mg x 1 day, then 200 mg days 2-5200 mg Q6H x 4 days- Cmax: increased 14.5%; AUC: increased 12%; Cmin: increased 14%- Inhibition of CYP450 3A4 by fluconazole

No dose adjustment necessary

Fluoxetine262, 55
(Prozac)
30 mg Q12H600 mg x 1 dose days 1 and 10-AUC: increased 19%; Cmax: no significant changeIncreased ritonavir effects; possibly increased fluoxetine effectsInhibition of CYP450 2D6 by both drugs

No dose adjustment necessary

Fluticasone55
(Flonase, Aerobid)(Advair, Flonase, Aerobid)
--Fluticasone AUC: increased 350-fold; Cmax: increased 25-fold-Decreased plasma cortisol concentrations (eg, Cushing's syndrome, adrenal suppression)-

Avoid if possible

Fluticasone392
(Flonase, Aerobid)(Advair, Flonase, Aerobid)
200 mcg once daily x 7 d100 mg BID x 7 dFluticasone Cmax: increased 2572%; AUC: increased 36697%-Increased fluticasone effects (eg, Cushing's syndrome, adrenal suppression)Inhibition of CYP450 3A4 by ritonavir

Dose adjustment not established; use caution

Fosamprenavir129
(FPV)(Lexiva)
1400 mg QD with efavirenz 600 mg QD300 mg QDAmprenavir AUC: no significant change; Cmax: increased 18%; Cmin: no significant changeNot studied-Inhibition of CYP450 3A4 by ritonavir

No dose adjustment necessary

Indinavir119
(IDV)(Crixivan)
400 mg BID x 14 days400 mg BID x 14 daysIndinavir AUC: increased 62%; Cmax: no significant change; Cmin: increased 929% (compared to indinavir 800 mg Q8H)Not studiedIncreased indinavir effectsInhibition of CYP450 3A4 by ritonavir

No dose adjustment necessary

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Indinavir254, 33, 34, 35, 36, 37, 38, 39, 40, 41
(IDV)(Crixivan)
400 mg Q12H x 15 days400 mg Q12H x 15 daysIndinavir Cmin: increased 400%Not studied-Inhibition of CYP450 3A4 by ritonavir

May consider indinavir/ritonavir combination as follows (BID dosing): 800/100; 800/200; 400/400

Indinavir119
(IDV)(Crixivan)
800 mg BID x 14 days100 mg BID x 14 daysIndinavir AUC: increased 170%; Cmax: increased 60%; Cmin: increased 1000% (compared to indinavir 800 mg Q8H)Not studiedIncreased indinavir effectsInhibition of CYP450 3A4 by ritonavir

No dose adjustment necessary

Indinavir119
(IDV)(Crixivan)
800 mg BID x 14 days200 mg BID x 14 daysIndinavir AUC: increased 254%; Cmax: increased 77%; Cmin: increased 2356% (compared to indinavir 800 mg Q8H)Not studiedIncreased indinavir effectsInhibition of CYP450 3A4 by ritonavir

No dose adjustment necessary

Indinavir119
(IDV)(Crixivan)
800 mg BID x 14 days400 mg BID x 14 daysIndinavir AUC: increased 209%; Cmax: increased 49%; Cmin: increased 2344% (compared to indinavir 800 mg Q8H)Not studiedIncreased indinavir effectsInhibition of CYP450 3A4 by ritonavir

No dose adjustment necessary

Itraconazole278
(Sporanox)(Sporanox)
---Increased ritonavir levelsIncreased ritonavir effectsInhibition of CYP450 3A4 by itraconazole

Dose adjustment not established

Ketoconazole278
(Nizoral)
---Increased ritonavir levelsIncreased ritonavir effectsInhibition of CYP450 3A4 by ketoconazole

Dose adjustment not established

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Levothyroxine364
(Synthroid, Levoxyl)
0.125 mg600 mg BID- - Increased TSH levels (eg, Signs and symptoms of hypothyroidism)Induction of glucuronosyl transferases by ritonavir

Monitor and adjust levothyroxine as indicated

Lopinavir/ritonavir78
(LPV/r)(Kaletra)
400 mg/100 mg BID x 3-4 weeks100 mg BID x 3-4 weeksLopinavir AUC: increased 46%; Cmax: increased 28%; Cmin: increased 116%- Increased lopinavir/ritonavir effectsInhibition of CYP450 3A4 by ritonavir

Dose adjustment not established

Maraviroc2
(MVC)(Selzentry)
100 mg BID100 mg BIDMaraviroc AUC: increased 161%; Cmin: increased 355%; Cmax: increased 28%- Increased maraviroc effectsInhibition of CYP450 3A4 by ritonavir

-

Mefloquine375
(Larium)(Larium)
250 mg QD x 3 days, then once weekly for 3 weeks200 mg BID x 7 daysNo significant changeAUC: decreased 31%; Cmax: increased 36%; Cmin: decreased 43%-Unknown

Dose adjustment not established

Meperidine180
(Demerol)(Demerol)
50 mg PO x 1 dose500 mg BID x 10 daysMeperidine AUC: decreased 67%; normeperidine AUC: increased 47%-Increased normeperidine effectsInduction of CYP450 1A2 by ritonavir; inhibition of p-glycoprotein reducing first-pass metabolism of meperidine

Avoid combination

Alternative Agents:
Morphine

Methadone198
(Dolophine)(Dolophine)
-400 mg BID combined with 400 mg BID saquinavirS-methadone AUC: decreased 25%; R-methadone AUC: decreased 20%-Not clinically significantInduction of CYP450 by ritonavir and saquinavir

Monitor and adjust methadone as indicated

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Methadone196, 197
(Dolophine)(Dolophine)
90 mg QD x 2 years400 mg BID x 7 daysMethadone AUC: decreased- Decreased methadone effects (eg, methadone withdrawal)Possible induction of CYP450 2C9, 3A4 and 2D6 by ritonavir

Monitor and adjust methadone as indicated

Methadone187
(Dolophine)(Dolophine)
Stable methadone dose100 mg BID x 7 daysNo significant effect---

Monitor and adjust methadone as indicated

Metronidazole55
(Flagyl)(Flagyl)
-Oral solution (contains alcohol) and capsules--Disulfiram-like reaction (eg, headache, hypotension, flushing, vomiting)Inhibition of alcohol and aldehyde dehydrogenase by metronidazole

Do not coadminister

Midazolam178
(Versed)(Versed)
- - Increased midazolam levels- Increased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by ritonavir

Single dose intravenous midazolam may be used; chronic midazolam administration (oral or intravenous) should be avoided

Alternative Agents:
Lorazepam

Nelfinavir107
(NFV)(Viracept)
1250 mg BID on days 1-31100 mg or 200 mg BID on days 15-31Nelfinavir AUC: increased 17-27% (on ritonavir 100 mg BID); M8 AUC: increased 67-82% (on ritonavir 100 mg BID); nelfinavir AUC: increased 20-53% (on ritonavir 200 mg BID); M8 AUC: increased 69-87% (on ritonavir 200 mg BID)Not studied-Inhibition of CYP450 3A4 by both ritonavir and nelfinavir

Dose adjustment not established

Nelfinavir77
(NFV)(Viracept)
2000 mg/ritonavir 200 mg, 2000 mg/ritonavir 400 mg, or 2500 mg/200 mg QD with food x 15 days200 mg or 400 mg QD with food x 15 daysNelfinavir 2000 mg/ritonavir 200 mg AUC: increased 100%; Cmax: increased 95%; Cmin: increased 92% (all values are compared to nelfinavir 1250 mg BID)--Inhibition of CYP450 3A4 by ritonavir

Using nelfinavir 2000 mg/ritonavir 200 mg QD with food may allow for QD dosing

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Nelfinavir24
(NFV)(Viracept)
750 mg Q8H x 5 dose500 mg x 1 dose-No significant change--

No dose adjustment necessary

Nelfinavir24
(NFV)(Viracept)
750 mg x 1 dose500 mg Q12H x 3 dosesNelfinavir AUC: increased 152%; Cmax: increased 44%Not studiedIncreased nelfinavir effectsInhibition of CYP450 3A4 by ritonavir

No dose adjustment necessary

Nevirapine95
(NVP)(Viramune)
200 mg QD x 2 weeks then 200 mg BID x 28 days600 mg BIDNo significant changeNo significant change- -

No dose adjustment necessary

Olanzapine175
(Zyprexa)(Zyprexa)
10 mg QD500 mg BIDOlanzapine AUC: decreased 53%; half-life: decreased 50%; clearance: increased 115%; Cmax: decreased 40%Not studiedDecreased olanzapine effectsInduction of CYP450 1A2 by ritonavir

Monitor and adjust olanzapine as indicated

Phenytoin225
(Dilantin)(Dilantin)
--Increased phenytoin levels-Increased phenytoin effects-

Avoid combination if possible; consider alternative agents; monitor phenytoin levels and adjust as indicated

Alternative Agents:
Gabapentin Lamotrigine Tiagabine Topiramate

Pimozide178
(Orap)(Orap)
--Not studied; may increase pimozide levels-Increased pimozide effects (eg, hypotension, cardiac arrhythmias)Inhibition of CYP450 3A4 by ritonavir

Do not coadminister

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Posaconazole503, 424
(Noxafil)
400 mg BID100 mg QD-Ritonavir AUC: increased 80%; Cmax: increased 49%Possibly increased ritonavir effectsInhibition of CYP450 3A4 by posaconazole; potential inhibition of UGT 1A1 by atazanavir

Dose adjustment not necessary

Prednisone396
(others)(Deltasone)
20 mg x 1 dose200 mg BID for 4 and 14 daysPrednisolone AUC: increased 30%; clearance: decreased 23%-Possibly increased prednisolone effects-

No dose adjustment necessary

Propafenone55
(Rythmol)(Rythmol)
--Not studied; may increase propafenone levels-Increased propafenone effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by ritonavir

Do not coadminister

Quinidine55
(Quindex, others)(Quindex)
--Not studied; may increase quinidine levels-Increased quinidine effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by ritonavir

Do not coadminister

Quinine547
600 mg x 1200 mg Q12 h x 9 daysQuinine AUC: increased 341%; Cmax: increased 284%Ritonavir AUC: increased 21%; Cmax: increased 15%Increased quinine effectsPotential competitive displacement from CYP450 3A4 and inhibition of 2D6

Avoid combination if possible; if combination must be used a potential four-fold reduction in quinine dosage may be needed

Raltegravir3
(RAL)(Isentress)
400 mg x 1100 mg BIDRaltegravir AUC: decreased 16%; Cmax: decreased 24%---

No dose adjustment necessary

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Raltegravir436
(RAL)(Isentress)
400 mg x 1100 mg BID x 16 dRaltegravir AUC: decreased 16%; Cmax: decreased 24%-- Induction of UGT1A1 by ritonavir

No dose adjustment necessary

Rifabutin344, 55
(Mycobutin)(Mycobutin)
150 mg QD x 24 days300 mg on day 15; 400 mg on day 16; 500 mg on days 17-24Rifabutin AUC: increased 400%; Cmax: increased 250%-Increased rifabutin effects (eg, uveitis)Inhibition of CYP450 3A4 by ritonavir

Decrease rifabutin to 150 mg QOD or 300 mg 3 times/week

Rifampin197, 55
(Rifampicin)(Rifadin)
300 mg or 600 mg x 10 days500 mg Q12H x 20 days-Ritonavir AUC: decreased 35%; Cmax: decreased 25%Decreased ritonavir effectsInduction of CYP450 3A4 by rifampin

Do not coadminister

Alternative Agents:
Rifabutin

Saquinavir118
(SQV)(Fortovase, Invirase)
1600 mg QD x 13 days100 mg QDSaquinavir AUC: increased 592%; Cmax: increased 566%; Cmin: increased 424% (compared to saquinavir 1200 mg TID)-Increased saquinavir effectsInhibition of CYP450 3A4 by ritonavir

-

Saquinavir44, 47, 48, 254
(SQV)(Fortovase, Invirase)
400 mg (hard gel caps) BID at steady state400 mg BID at steady stateSaquinavir AUC: increased 1587%; Cmax: increased 1277%Not studiedIncreased saquinavir effectsInhibition of CYP450 3A4 by ritonavir

Consider ritonavir-boosted saquinavir

Saquinavir44, 47, 48, 75, 254
(SQV)(Fortovase, Invirase)
400 mg (soft gel caps) BID x 14 days400 mg BID x 14 daysSaquinavir AUC: increased by 121%; Cmax: increased 64%-Increased saquinavir effectsInhibition of CYP450 3A4 by ritonavir

Consider ritonavir-boosted saquinavir

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Saquinavir55, 57
(SQV)(Fortovase, Invirase)
Multiple saquinavir hard gel caps doses studied; 200 mg, 400 mg, 600 mgMultiple doses studied; 200 mg, 300 mg, 600 mgSaquinavir AUC: increased 5000%; Cmax: increased 2100%Ritonavir AUC: no significant changeIncreased saquinavir effectsInhibition of CYP450 3A4 by ritonavir

Consider ritonavir-boosted saquinavir

Saquinavir51
(SQV)(Fortovase, Invirase)
Saquinavir soft gel caps 1000 mg/ritonavir 100 mg BID or saquinavir hard gel caps 1000 mg/ritonavir 100 mg BID, adminstered with food for at least 3 weeks100 mg BIDSaquinavir soft gel caps AUC: increased 30% (compared to hard gel caps/ritonavir AUC); Cmin: increased 17% (when compared to hard gel caps/ritonavir regimen Cmin)Not studiedIncreased saquinavir effects (AUC achieved with hard gel caps/ritonavir regimen is comparable, but not equivalent to, soft gel caps/ritonavir AUC)Inhibition of CYP450 3A4 by ritonavir

Consider ritonavir-boosted saquinavir

Sildenafil301, 55
(Viagra)
100 mg x 1 dose300 mg, 400 mg and 500 mg BID on days 2, 3 and 4-8Sildenafil AUC: increased 1000%; Cmax: increased 290%; Tmax: delayed 3 hours- Increased sildenafil effects (eg, hypotension, priapism)Inhibition of CYP450 3A4 by ritonavir

Initiate therapy at 25 mg dose; do not exceed 25 mg in 48 hour period

Simeprevir677
(Olysio)
200 mg QD x 7 days100 mg BID x 15 daysSimeprevir AUC: increased 618%; Cmax: increased 370%; Cmin: increased 1335% -Increased simeprevir effects Inhibition of P450 3A4 by ritonavir

Do not coadminister

St. John's Wort55
(Hypericum perforatum, hypericin, hyperforin)
- - - Not studied; may decrease ritonavir levelsDecreased ritonavir effectsInduction of CYP450 3A4 by St. John's Wort

Do not coadminister

Tacrolimus305
(Prograf)(Prograf)
4 mg BID- - - Increased tacrolimus effects (eg, bone marrow suppression)Inhibition of CYP450 3A4 by ritonavir

Monitor and adjust tacrolimus as indicated

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Tadalafil388
20 mg x 1200 mg BIDTadalafil AUC: increased 124%-Increased tadalafil effects (eg, hypotension, priapism)Inhibition of CYP450 3A4 by ritonavir

Do not exceed 10 mg tadalafil every 72 hours

Tadalafil388
20 mg x 1500 mg or 600 mg BIDTadalafil AUC: increased 32%, Cmax: decreased 30%-Increased tadalafil effects (eg, hypotension, priapism)Inhibition of CYP450 3A4 by ritonavir

Do not exceed 10 mg tadalafil every 72 hours

Telaprevir571
(Incivek)
750 mg Q12H x 14 days100 mg Q12H x 14 daysTelaprevir AUC: decreased 24%; Cmin: decreased 32%; Cmax: decreased 15%---

Dose adjustment not established

Telaprevir571
(Incivek)
750 mg x 1100 mg x 1Telaprevir AUC: increased 100%; Cmax: increased 30%---

Dose adjustment not established

Terfenadine178, 55
(Seldane)(Seldane)
--Increased terfenadine levels-Increased terfenadine effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by ritonavir

Do not coadminister

Alternative Agents:
Cetirizine Fexofenadine Loratadine

Theophylline303
(Slo-Phyllin, Theo-Dur)
3 mg/kg Q8HDays 1-5 none; day 6 300 mg Q12H; day 7 400 mg Q12H; days 8-15 500 mg Q12HTheophylline AUC: decreased 43%; Cmax: decreased 32%; Cmin: decreased 57%; half-life: decreased 57%- Decreased theophylline effectsPossible induction of CYP450 1A2 by ritonavir

Monitor and adjust theophylline as indicated

Coadministered DrugDose of DrugDose of RitonavirEffect on Drug LevelsEffect on Ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Tinidazole328
(Tindamax)
- Oral solution (contains alcohol) and capsules- - Disulfiram-like reaction (eg, headache, hypotension, flushing, vomiting)Inhibition of alcohol and aldehyde dehydrogenase by tinidazole

Do not coadminister

Trazodone55
(Desyrel)(Desyrel)
--Trazodone AUC: increased 2.4-fold; Cmax: increased 34%-Increased trazodone effects (eg, nausea, dizziness, hypotension, syncope)Possible inhibition of trazodone metabolism

Use with caution; if benefits outweigh risk, initiate trazodone at lower dose

Trazodone259
(Desyrel)(Desyrel)
50 mg x 1 dose200 mg BID for 2 daysTrazodone AUC: increased 240%; Cmax: increased 34%; half-life: increased 220%Not studiedIncreased trazodone effects (eg, nausea, hypotension, syncope)Inhibition of CYP450 3A4 by ritonavir

Decrease trazodone dose or start low and titrate to effect

Triazolam55, 256
(Halcion)(Halcion)
0.125 mg x 1 dose200 mg BID x 2 daysTriazolam AUC: increased 1939%; half-life: increased 1267%; Cmax: increased 87%- Increased triazolam effects (eg, increased confusion, sedation, respiratory depression)Inhibition of CYP450 3A4 by ritonavir

Avoid combination; consider alternative agents

Alternative Agents:
Lorazepam, Oxazepam, Temazepam, Trazodone

Voriconazole507, 505, 378
(VFend)(VFend)
400 mg Q12H100 mg Q12H x 9 daysVoriconazole AUC: decreased 39%; Cmax: decreased 24%No significant changeDecreased voriconazole effectsInduction of CYP450 3A4 by ritonavir

Avoid coadministration; consider use of non-ritonavir containing antiretroviral regimens

Voriconazole507, 505
(VFend)(VFend)
400 mg Q12H400 mg Q12H x 9 daysVoriconazole AUC: decreased 83%; Cmax: decreased 68%No significant changeDecreased voriconazole effectsInduction of CYP450 3A4 by ritonavir

Do not coadminister

Warfarin324
(Coumadin)
12.5 mg QD400 mg BIDINR: decreased-Decreased warfarin effects (eg, decreased INR, increased risk of clotting)Possible inhibition of CYP450 3A4, 2C9 and 1A2 by ritonavir

Monitor INR and adjust warfarin as indicated

Zidovudine55, 58
(AZT, ZDV)(Retrovir)
200 mg Q8H300 mg Q6HZidovudine Cmax: decreased 27%; AUC: decreased 26%No significant changeDecreased zidovudine effectsUnknown

No dose adjustment necessary

Zolpidem256
(Ambien)(Ambien)
5 mg x 1 dose200 mg BID x 2 daysZolpidem AUC: increased 28%; Cmax: increased 22%-Increased zolpidem effects (eg, increased sedation, confusion)Inhibition of CYP450 3A4 by ritonavir

No dose adjustment necessary

"-" indicates that there are no data available
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