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Database of Antiretroviral Drug Interactions

All Interactions with Lopinavir/ritonavir (Kaletra)

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Amiodarone78
(Cordarone)
- - Not studied; may increase amiodarone levels- Increased amiodarone effects (eg, cardiac arrhythmias, hypotension)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Monitor and adjust amiodarone as indicated

Amprenavir78, 79
(APV)(Agenerase)
450 mg BID x 5 days, 750 mg BID x 5 days400 mg/100 mg BID x 22 daysNo significant changeLopinavir AUC: decreased 15%; lopinavir Cmax: no significant change; Cmin: decreased 19%--

No dose adjustment necessary

Amprenavir65
(APV)(Agenerase)
600 mg BID400 mg/100 mg BIDAmprenavir Cmin: decreased 37% (when compared to standard curve obtained from amprenavir and ritonavir at same doses)Not studiedDecreased amprenavir levelsNot established

Dose adjustment not established

Amprenavir151
(APV)(Agenerase)
750 mg BID533mg/133 mg BID with and without efavirenz 600 mg QHSAmprenavir AUC: no significant change; Cmax: decreased 34%; Cmin: increased 22%(when compared to amprenavir, lopinavir/ritonavir with efavirenz)Lopinavir AUC: no significant change; Cmax: no significant change; Cmin: no significant change; half-life: decreased 32%(when compared to amprenavir, lopinavir/ritonavir with efavirenz)--

No dose adjustment necessary

Amprenavir64
(APV)(Agenerase)
Group 2: 1200 mg amprenavir/200 mg ritonavir BID; Group 4: 1200 mg amprenavir/400 mg ritonavir BID x weeks 1-26400 mg/100 mg BID x weeks 2-26Amprenavir Cmin: decreased 42% (in Group 2); Cmin decreased 69% (in Group 4)Not studiedDecreased amprenavir levels-

Dose adjustment not established

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Astemizole78
(Hismanal)
- - Not studied; may increase astemizole levels- Increased astemizole effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

Alternative Agents:
Cetirizine Fexofenadine Loratadine

Atazanavir160
(ATV)(Reyataz)
300 mg QD on d 11-24400 mg/100 mg BID on d 11-24Atazanavir AUC: no significant change; Cmin: increased 45%; Cmax: no significant change (compared to 300 mg atazanavir with 100 mg ritonavir QD)No significant changeIncreased atazanavir effectsInhibition of CYP450 3A4 by ritonavir, lopinavir and atazanavir

No dose adjustment necessary

Atazanavir160
(ATV)(Reyataz)
300 mg with 100 mg QD ritonavir on d 25-34400 mg/100 mg BID on d 25-34Atazanavir AUC: no significant change; Cmin: increased 64% (compared to 300 mg atazanavir with 100 mg ritonavir QD)--Inhibition of CYP450 3A4 by ritonavir, lopinavir and atazanavir

No dose adjustment necessary

Atorvastatin216, 78
(Lipitor)
20 mg QD x 4 days400 mg/100 mg BID x 14 daysAtorvastatin AUC: increased 488%; Cmax: increased 367%; Cmin: increased 128%No significant changeIncreased atorvastatin effects (eg, myopathy, rhabdomyolysis)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Avoid combination if possible; may consider low dose atorvastatin or alternative agents; monitor for myopathy

Alternative Agents:
Pravastatin

Atovaquone78
(Mepron)
- - May decrease atovaquone levels- Decreased atovaquone effects-

No dose adjustment necessary

Atovaquone487
(Mepron)
250 mg with 100 mg proguanil x 1400/100 mg BIDAtovaquone AUC: decreased 74%; Cmax: decreased 44%-Potentially compromised antimalarial activityIncreased atovaquone glucuronidation; induction of CYP450 3A4 by lopinavir/ritonavir

Dose adjustment not established

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Bepridil78
(Vascor)
--Not studied; may increase bepridil levels-Increased bepridil effects (hypotension, cardiac arrhythmias)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

Boceprevir599
(Victrelis)
800 mg TID400/100 mg BIDBoceprevir AUC: decreased 32%; Cmin: decreased 35%Lopinavir AUC: decreased 44%; Cmax: decreased 36%; Cmin: decreased 59%Decreased HIV and HCV treatment efficacy-

Do not coadminister

Bosentan467
(Tracleer)
125 mg BID400/100 mg BIDBosentan AUC: increased 422%; Cmax: increased : 512%Lopinavir AUC: decreased 14%; Ritonavir AUC:decreased 17%Increased bosentan effectsInhibition of CYP450 3A4 by lopinavir/ritonavir

Start low and titrate bosentan to effect

Buprenorphine453
(Suboxone)(Buprenex)
paitents on stable buprenorphine/naloxoneLopinavir/ritonavir 800 mg/200 mg QDBuprenorphine: no significant change; Norbuprenorphine Cmax: decreased 41%Lopinavir Cmax: decreased 22-32% (when compared to historical controls)No significant change-

No dose adjustment necessary

Bupropion533
(Wellbutrin, Zyban)(Wellbutrin)
100 mg x 1400/100 mg BIDBupropion AUC: decreased 57%; Cmax: decreased 57%Ritonavir AUC: decreased 15%Decreased bupropion effectsPossible induction of CYP450 2B6 and UGT enzymes

-

Carbamazepine78
(others)(Tegretol)
---Not studied; may decrease lopinavir levelsDecreased lopinavir/ritonavir effects-

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

Alternative Agents:
Gabapentin Lamotrigine Tiagabine Topiramate

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Cerivastatin78
(Baycol)
--Not studied; may increase cerivastatin levels-Increased cerivastatin effects (eg, myopathy, rhabdomyolysis)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

Alternative Agents:
Atorvastatin Pravastatin

Cisapride78
(Propulsid)
- - Not studied; may increase cisapride levels- Increased cisapride effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

Alternative Agents:
Metoclopramide

Clarithromycin78
(Biaxin)
- - May increase clarithromycin levels- Increased clarithromycin effectsInhibition of CYP450 3A4 by lopinavir/ritonavir

No dose adjustment necessary

Colchicine555
(Colcrys, Colcrys)
----Increased colchicine effectsInhibition of P450 3A4 by lopinavir/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.

Cyclosporine78
(Neoral, Sandimmune)
- - May increase cyclosporine levels- Increased cyclosporine effects (increased immunosuppression, renal toxicity)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Monitor and adjust cyclosporine as indicated

Darunavir164
(DRV)(Prezista)
1200 mg BID with ritonavir 100 mg BID400/100 mg BIDDarunavir AUC: decreased 38%; Cmax: decreased 21%; Cmin: decreased 51% (compared to DRV/r 600/100 mg BID)Lopinavir Cmin: increased 23%Decreased darunavir/ritonavir effects; increased lopinavir/ritonavir effectsPossible induction of CYP450 3A4

Do not coadminister

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Darunavir161
(DRV)(Prezista)
300 mg BID with ritonavir 100 mg BID400/100 mg BIDDarunavir AUC: decreased 53%; Cmax: decreased 39%; Cmin: decreased 65%Lopinavir AUC: increased 37%; Cmax: increased 22%; Cmin: increased 72%Decreased darunavir/ritonavir effects; increased lopinavir/ritonavir effects-

Do not coadminister

Delavirdine78
(DLV)(Rescriptor)
---Not studied; may increase lopinavir/ritonavir levelsIncreased lopinavir/ritonavir effects-

Dose adjustment not established

Dexamethasone78
(Decadron)
- - - Not studied; may decrease lopinavir levelsDecreased lopinavir/ritonavir effects-

No dose adjustment necessary

Didanosine78
(ddI)(Videx)
-----Decreased lopinavir/ritonavir absorption

Take didanosine 1 hour before or 2 hours after lopinavir/ritonavir

Disulfiram78
(Antabuse)
- Oral solution (contains alcohol)- - Disulfiram reaction (eg, nausea, vomiting, hypotension, headache)Inhibition of alcohol and aldehyde dehydrogenase by disulfiram

Do not coadminister; consider lopinavir/ritonavir capsules

Dolutegravir641
(Tivicay)
30 mg QD400/100 mg BIDNo significant change ---

No dose adjustment necessary

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Echinacea527
(Purple coneflower)
500 mg TID x 28 days400/100 mg BID x 29.5 days-No significant change--

No dose adjustment necessary

Efavirenz80
(EFV)(Sustiva)
- 400 mg/100 mg BIDNo significant changeLopinavir AUC: decreased 20-25%; Cmin: decreased 40-45%- -

Increase dose of lopinavir/ritonavir to 533 mg/133 mg (4 capsules) BID with food

Efavirenz120
(EFV)(Sustiva)
600 mg QD on days 1-35400/100 mg BID on days 1-14, then increased to 533/133 mg BID on 15-35Not studiedLopinavir AUC: increased 46%; Cmax: increased 33%; Cmin: increased 141%; Ritonavir AUC: increased 48%; Cmax: increased 46%; Cmin: increased 63% (compared to lopinavir/ritonavir 400/100 mg BID)Increased lopinavir/ritonavir effectsInhibition of CYP450 3A4 by lopinavir/ritonavir

Increase lopinavir/ritonavir to 533/133 mg BID when used with efavirenz

Efavirenz158
(EFV)(Sustiva)
600 mg QHS on days 11-25400/100 mg BID (tablet formulation) on days 1-15, then 600/150 mg BID on days 15-25Not studiedLopinavir AUC: increased 36%; Cmax: increased 36%; Cmin: increased 35% (compared to lopinavir 400/100 mg BID tablets without efavirenz)Ritonavir AUC: increased 78%; Cmax: increased 92%; Cmin: increased 60% (compared to ritonavir 150 mg BID without efavirenz)-Increased levels due to formulation

No dose adjustment necessary

Efavirenz681, 78
(EFV)(Sustiva)
600 mg QHS x 9 days400 mg/100 mg BID x 9 daysEfavirenz AUC: decreased 16%; Cmax: no significant change; Cmin: decreased 16%Lopinavir AUC: decreased 19%; Cmax: no significant change; Cmin: decreased 39%;Ritonavir AUC: no significant change; Cmax: no significant changeDecreased lopinavir effectsInduction of CYP450 3A4 by efavirenz

Increase dose of lopinavir/ritonavir to 533 mg/133 mg (4 capsules) BID with food

Elvitegravir/cobicistat649, 639
(Stribild)
Elvitegravir 125 mg QD400/100 mg BIDElvitegravir AUC; increased 75%; Cmax: increased 52%; Cmin: increased 139%No significant changePotentially decreased or increased elvitegravir, cobicistat and/or lopinavir effects-

Do not coadminister

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Ergotamine78
(Cafergot, Ergot derivatives)(Cafergot, others)
--Not studied; may increase ergotamine levels-Increased ergotamine effects (eg, ergotism)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

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

Ethinyl estradiol/norethindrone acetate78
(others)(Ortho-Novum)
Ethinyl estradiol 35 mcg QD x 21 days400 mg/100 mg BID x 14 daysEthinyl estradiol AUC: decreased 42%; Cmax: decreased 41%; Cmin: decreased 58%- Decreased ethinyl estradiol effects (eg, contraceptive failure)Induction of CYP450 3A4 by ritonavir

Use alternative contraceptive method

Alternative Agents:
Barrier devices Condoms

Ethinyl estradiol/norethindrone acetate78
(others)(Ortho-Novum)
Norethindrone 1 mg QD x 21 days400 mg/100 mg BID x 14 daysNorethindrone AUC: decreased 17%; Cmax: decreased 16%; Cmin: decreased 32%- Decreased norethindrone effects (eg, contraceptive failure)Induction of CYP450 3A4 by ritonavir

Use alternative contraceptive method

Alternative Agents:
Barrier devices Condoms

Etravirine405, 434
(ETR)(Intelence)
200 mg BID400/100 mg BIDEtravirine AUC: decreased 35%; Cmax: decreased 30%; Cmin: decreased 45%Lopinavir Cmin: decreased 20%; Ritonavir Cmax: decreased19%Potentially decreased etravirine effectsPotential induction of CYP450 3A4, 2C9 and 2C19 by lopinavir/ritonavir

No dose adjustment necessary

Felodipine78
(Plendil)(Plendil)
- - Not studied; may increase felodipine levels- Increased felodipine effects (hypotension, bradycardia)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Monitor and adjust felodipine as indicated

Flecainide78
(Tambocor)(Tambocor)
- - Not studied; may increase flecainide levels- Increased flecainide effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Fluticasone78
(Flonase, Aerobid)(Advair, Flonase, Aerobid)
--Increased fluticasone concentrations-Decreased plasma cortisol concentrations (eg, Cushing's syndrome, adrenal suppression)-

Avoid if possible

Fosamprenavir140, 130
(FPV)(Lexiva)
1400 mg BID x 14 days533/133 mg BID x 14 daysAmprenavir AUC: decreased 26%; Cmax: no significant change; Cmin: decreased 42%No significant changeDecreased amprenavir effectsInduction of CYP450 3A4 by lopinavir/ritonavir

Avoid coadministration

Fosamprenavir133
(FPV)(Lexiva)
700 mg BID with 100 mg ritonavir BID x 2-4 weeks400/100 mg BIDAmprenavir AUC: decreased 64%; Cmin: decreased 69%Lopinavir AUC: decreased 48%; Cmin: decreased 61%Decreased lopinavir and amprenavir effectsInduction of CYP450 3A4 by lopinavir and amprenavir

Do not coadminister

Fosamprenavir140, 130
(FPV)(Lexiva)
700 mg BID with ritonavir 100 mg BID x 14 days400/100 mg BID x 14 daysAmprenavir AUC: decreased 63%; Cmax: decreased 58%; Cmin: decreased 65%Lopinavir AUC: increased 37%; Cmax: increased 30%; Cmin: increased 52%Decreased amprenavir effects; increased lopinavir effectsInduction of CYP450 3A4 by lopinavir/ritonavir and inhibition of CYP450 3A4 by amprenavir/ritonavir

Avoid coadministration

Fosamprenavir139
(FPV)(Lexiva)
700 mg BID x 10 days taken simultaneously, 4 hours or 12 hours away from lopinavir/ritonavir dose400/100 mg BID x 10 daysNot studiedLopinavir AUC (12 hours apart and compared to simultaneous dosing): increased 187%; Cmax: increased 53%; Cmin: increased 69%;Amprenavir AUC: increased 53%; Cmax: increased 56%; Cmin: decreased 71%Decreased amprenavir and increased lopinavir effectsInduction of CYP450 3A4 by lopinavir and amprenavir

Avoid coadministration; Despite separating doses by 12 hours, significant induction still exists when amprenavir and lopinavir levels are compared to historical controls

Gemfibrozil521
(Lopid)
600 mg x 1400/100 mg BIDGemfibrozil AUC: decreased 41%; Cmax: decreased 33%-Decreased gemfibrozil effectsReduced gemfibrozil absorption due to lopinavir/ritonavir

Potential option includes utilizing alternative antiretrovirals; unknown if fenofibrate has same interaction as gemfibrozil

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Ginkgo biloba621
120 mg BID400/100 mg BID-No significant change--

No dose adjustment necessary

Indinavir13
(IDV)(Crixivan)
400 mg BID x 14 days400/100 mg BIDIndinavir Cmax: no significant change; Cmin: increased 46%; AUC: increased 20%No significant change-Inhibition of P450 3A4 by lopinavir/ritonavir

No dose adjustment necessary

Indinavir78
(IDV)(Crixivan)
600 mg x 1 dose400 mg/100 mg BID x 10 daysIndinavir AUC: no significant change; Cmax: decreased; Cmin: increasedNot studiedNo significant change-

Dose adjustment not established

Indinavir108
(IDV)(Crixivan)
800 mg TID on days 1-5, 600 mg BID on days 6-15400/100 mg BID on days 6-15Indinavir AUC: no significant change; Cmax: decreased 29%; Cmin: increased 247%No significant change-Inhibition of CYP450 3A4 by lopinavir/ritonavir

No dose adjustment necessary

Itraconazole279, 78
(Sporanox)(Sporanox)
- - Not studied; may increase itraconazole levelsNot studied; may increase ritonavir levelsIncreased lopinavir/ritonavir effects; increased itraconazole effectsInhibition of CYP450 3A4 by both drugs

Manufacturer recommends against using high doses of itraconazole (>200 mg daily)

Alternative Agents:
Fluconazole

Ketoconazole78
(Nizoral)
200 mg x 1 dose400 mg/100 mg BID x 16 daysKetoconazole AUC: increased 204%; Cmax: no significant changeLopinavir AUC: no significant change; Cmax: no significant change; Cmin: decreased 25%Increased ketoconazole effects; decreased lopinavir/ritonavir effects-

Manufacturer recommends against using high doses of ketoconazole(>200 mg daily)

Alternative Agents:
Fluconazole

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Lamotrigine395
(Lamictal)(Lamictal)
50 mg QD on days 1 and 2, then 100 mg BID on days 3-20400/100 mg BID on days 11-20Lamotrigine AUC: decreased 50%; Cmax: decreased 46%; Cmin: decreased 56%; half-life: decreased 46%No significant changeDecreased lamotrigine effectsPossible induction of glucuronidation by lopinavir/ritonavir

Titrate to effect but may need to increase dose to 200 mg BID while patient is receiving lopinavir/ritonavir

Lidocaine78
(Xylocaine)
Systemic lidocaine- Not studied; may increase lidocaine levels- Increased lidocaine effectsInhibition of CYP450 3A4 by lopinavir/ritonavir

Monitor and adjust lidocaine as indicated

Lovastatin78
(Mevacor)(Mevacor)
- - Not studied; may increase lovastatin levels- Increased lovastatin effects (eg, myopathy, rhabdomyolysis)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

Alternative Agents:
Atorvastatin (low dose); Pravastatin

Maraviroc2
(MVC)(Selzentry)
300 mg BID400 mg/100 mg BIDMaraviroc AUC: increased 295%; Cmax: increased 97%; Cmin: increased 824%- Increased maraviroc effectsInhibition of CYP450 3A4 by lopinavir/ritonavir

Reduce maraviroc dose to 150 mg BID

Maraviroc2
(MVC)(Selzentry)
300 mg BID400 mg/100 mg BID with 600 mg efavirenz QDMaraviroc AUC: increased 153%; Cmax: increased 25%; Cmin: increased 529%- Increased maraviroc effectsInhibition of CYP450 3A4 by lopinavir/ritonavir

Decrease maraviroc dose to 150 mg BID

Medroxyprogesterone acetate683
(Depo-Provera)
150 mg400/100 mg BIDMedroxyprogesterone acetate AUC: increased 46%; Cmax: increased 65%Lopinavir: no significant change; Ritonavir: no significant change--

No dose adjustment necessary

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Methadone192
(Dolophine)(Dolophine)
-400/100 mg BID x 14 daysMethadone AUC: decreased 36%; Cmax: decreased 44%Not studiedDecreased methadone effects (eg, withdrawal)-

Monitor and adjust methadone as indicated

Methadone78
(Dolophine)(Dolophine)
5 mg x 1 dose400 mg/100 mg BID x 10 daysMethadone AUC: decreased 53%; Cmax: decreased 45%-Decreased methadone effects (eg, withdrawal)Possible induction of CYP450 3A4 by lopinavir/ritonavir

Monitor and adjust methadone as indicated

Methadone187
(Dolophine)(Dolophine)
Stable methadone dose400/100 mg BID x 7 daysMethadone AUC: decreased 26%; Cmax: decreased 28%; Cmin: decreased 28%-Decreased methadone effects (eg, withdrawal)Possible induction of methadone metabolism by lopinavir/ritonavir

Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dose

Metronidazole78
(Flagyl)(Flagyl)
- Oral solution (contains alcohol)- - Disulfiram reaction (hypotension, headache, nausea, vomiting)Inhibition of alcohol and aldehyde dehydrogenase by metronidazole

Do not coadminister; may consider lopinavir/ritonavir capsules

Midazolam78
(Versed)(Versed)
- - Not studied; may increase midazolam levels- Increased midazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by lopinavir/ritonavir

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

Alternative Agents:
Lorazepam

Naloxone451
(Narcan)
patients stable on buprenorphine/naloxone-No significant change-No significant change-

No dose adjustment necessary

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Nelfinavir11
(NFV)(Viracept)
1250 mg BID400/100 mg BIDNelfinavir Cmax: no significant change; AUC: no significant change; Cmin: increased 113%Lopinavir Cmax: decreased 21%; AUC: decreased 27%; Cmin: decreased 33%. Ritonavir Cmax: decreased 26%; AUC: decreased 24%; Cmin: decreased 29%Decreased lopinavir/ritonavir effectsInduction of P450 3A4 by lopinavir/ritonavir and nelfinavir

Dose adjustment not established

Nevirapine78
(NVP)(Viramune)
200 mg QD x 14 days, 200 mg BID x 6 days400 mg/100 mg BID x 20 daysNevirapine AUC: no significant change; Cmax: no significant change; Cmin: increased 15%Lopinavir: no significant changeThough study does not suggest need to increase lopinavir/ritonavir dose, other evidence indicated decreased lopinavir/ritonavir effectsInduction of CYP450 3A4 by nevirapine

Increase dose of lopinavir/ritonavir to 533 mg/133 mg (4 capsules) BID with food

Nevirapine78
(NVP)(Viramune)
7 mg/kg or 4 mg/kg QD x 2 weeks; BID x 1 week300 mg/75 mg/square meter BID x 3 weeks-Lopinavir AUC: decreased 22%; Cmax: no significant change; Cmin: decreased 55%Decreased lopinavir/ritonavir effectsInduction of CYP450 3A4 by nevirapine

Increase dose of lopinavir/ritonavir to 6.5 mL BID with food

Nicardipine78
(Cardene)(Cardene)
- - Not studied; may increase nicardipine levels- Increased nicardipine effects (eg, hypotension, cardiac arrhythmias)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Monitor and adjust nicardipine as indicated

Nifedipine78
(Procardia, Adalat)(Adalat, Procardia)
- - Not studied; may increase nifedipine levels- Increased nifedipine effects (eg, hypotension, cardiac arrhythmias)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Monitor and adjust nifedipine as indicated

Omeprazole243
(Prilosec)(Prilosec)
40 mg QD on days 11-15800 mg/200 mg tabs QD on days 1-15Not studiedLopinavir: no significant change; Ritonavir: no significant change--

No dose adjustment necessary

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Omeprazole243
(Prilosec)(Prilosec)
40 mg QD on days 11-15400 mg/100 mg tabs BID on days 1-15Not studiedLopinavir: no significant change; Ritonavir: no significant change--

No dose adjustment necessary

Phenobarbital78
(Luminal, others)(Luminal)
---Not studied; may decrease lopinavir levelsDecreased lopinavir/ritonavir effectsInduction of CYP450 3A4 by phenobarbital

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

Alternative Agents:
Gabapentin Lamotrigine Tiagabine Topiramate

Phenytoin78
(Dilantin)(Dilantin)
---Not studied; may decrease lopinavir levelsDecreased lopinavir/ritonavir effectsInduction of CYP450 3A4 by phenytoin

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

Alternative Agents:
Gabapentin Lamotrigine Tiagabine Topiramate

Phenytoin224
(Dilantin)(Dilantin)
300 mg QHS for 10 days400/100 mg BID on days 1-22Phenytoin AUC: decreased 31%; Cmax: decreased 28%; Cmin: decreased 34%; half-life: decreased 38%Lopinavir AUC: decreased 33%; Cmax: decreased 24%; Cmin: decreased 46%; half-life: decreased 51%.Ritonavir AUC: decreased 28%; Cmax: decreased 20%; Cmin: decreased 47%; half-life: decreased 38%Decreased lopinavir/ritonavir and phenytoin effectsInduction of CYP450 3A4 by phenytoin; possible induction of CYP450 2C9 by lopinavir

Avoid combination if possible; consider alternative agents; monitor phenytoin levels and adjust as indicated; if combination cannot be avoided, possible options include increasing LPV/r to 4 caps BID or adding ritonavir 100 mg BID to regimen and monitoring levels. Neither option currently has any data.

Alternative Agents:
Gabapentin Lamotrigine Tiagabine Topiramate

Pimozide78
(Orap)(Orap)
--Not studied; may increase pimozide levels-Increased pimozide effects (eg, hypotension, cardiac arrhythmias)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

Pitavastatin573
(Livalo)
4 mg QD400/100 mg BIDPitavastatin AUC: decreased 20%No significant change--

No dose adjustment necessary

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Pravastatin216, 78
(Pravachol)(Pravachol)
20 mg QD x 4 days400 mg/100 mg BID x 14 daysPravastatin AUC: increased 33%; Cmax: increased 26%No significant change-Unknown

No dose adjustment necessary

Prednisone425
(others)(Deltasone)
20 mg x 1not statedPrednisolone AUC: increased 31%- Possibly increased prednisolone effects-

No dose adjustment necessary

Proguanil487
(Malarone)(Malarone)
100 mg with 250 mg atovaquone x 1400/100 mg BIDProguanil AUC: decreased 38%; Cmax: no significant change-Potentially compromised antimalarial activityIncreased atovaquone glucuronidation; induction of CYP450 3A4 by lopinavir/ritonavir

Dose adjustment not established

Propafenone78
(Rythmol)(Rythmol)
- - Not studied; may increase propafenone levels- Increased propafenone effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

Quinidine78
(Quindex, others)(Quindex)
- - Not studied; may increase quinidine levels- Increased quinidine effects (eg, cardiac arrhythmias)-

Monitor and adjust quinidine as indicated

Raltegravir413
(RAL)(Isentress)
400 mg BID400 mg/100 mg BIDRaltegravir Cmin: decreased 30%No significant change--

No dose adjustment necessary

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Ranitidine243
(Zantac)(Zantac)
150 mg QD on day 11800 mg/200 mg tabs QD on days 1-15Not studiedLopinavir Cmin: decreased 35%; Ritonavir AUC: decreased 16%; Cmax: decreased 21%; Cmin: decreased 16%--

No dose adjustment necessary

Ranitidine243
(Zantac)(Zantac)
150 mg QD on day 11400 mg/100 mg BID on days 1-15Not studiedNo significant change--

No dose adjustment necessary

Rapamycin78
(Sirolimus)
--Not studied; may increase rapamycin levels-Increased rapamycin effectsInhibition of CYP450 3A4 by lopinavir/ritonavir

Monitor and adjust rapamycin as indicated

Rifabutin78
(Mycobutin)(Mycobutin)
150 mg QD x 10 days400 mg/100 mg BID x 20 days-Lopinavir AUC: increased 17%; Cmax: no significant change; Cmin: increased 20%Increased lopinavir/ritonavir effects-

No dose adjustment necessary

Rifabutin78
(Mycobutin)(Mycobutin)
300 mg QD x 10 days, 150 mg QD x 10 days400 mg/100 mg BID x 10 daysRifabutin AUC: increased 203%; Cmax: increased 112%; Cmin: increased 390%; 25-O-desacetyl rifabutin AUC: increased 4650%; Cmax: increased 2260%; Cmin: increased 9390%-Increased rifabutin effects (eg, uveitis)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Decrease rifabutin to 150 mg QOD

Rifampin459
(Rifampicin)(Rifadin)
600 mg QD400/100 mg Q12h x 7 days, 600/150 mg Q12H x 7 days then 800/200 Q12H x 7 days-Lopinavir AUC: decreased 71% (on 400/100 mg Q12H); AUC: decreased 40% (on 600/150 mg Q12H); AUC: no significant change (on 800/200 mg Q12H)Decreased lopinavir effects at lower dosagesInduction of CYP450 3A4 by rifampin

Lopinavir/ritonavir dosage of 800/200 mg Q12H appears to compensate for rifampin induced 3A4 induction

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Rifampin350, 351, 352
(Rifampicin)(Rifadin)
600 mg QD on days 11-24400/100 mg BID on days 1-15, then 800/200 mg BID or 400/400 mg BID on days 16-24Not studiedLopinavir AUC: decreased 16% (in 800/200 mg BID group when compared to 400/100 mg BID); Cmin: decreased 57%; Cmax: no significant change. Ritonavir AUC: increased 42%; Cmax: increased 75%; Cmin: no significant change.Lopinavir pharmacokinetics: No significant change (in 400/400 mg BID group)Ritonavir AUC: increased 612%; Cmax: increased 738%; Cmin: increased 389% (in 400 mg/400 mg BID group)Decreased lopinavir effectsInhibition of CYP450 3A4 by ritonavir; Induction of CYP450 3A4 by rifampin

Consider using lopinavir/ritonavir 400 mg BID with ritonavir 400 mg BID when combined with rifampin

Rifampin78
(Rifampicin)(Rifadin)
600 mg QD x 10 days400 mg/100 mg BID x 20 days- Lopinavir AUC: decreased 75%; Cmax: decreased 55%; Cmin: decreased 99%Decreased lopinavir/ritonavir effectsInduction of CYP450 3A4 by rifampin

Do not coadminister

Alternative Agents:
Rifabutin

Rilpivirine567
(RPV)(Edurant)
150 mg QD400/100 mg BIDRilpivirine AUC: increased 52%; Cmin: increased 74%; Cmax: increased 29%No significant changeIncreased rilpivirine effects-

No dose adjustment necessary

Ritonavir78
(RTV)(Norvir)
100 mg BID x 3-4 weeks400 mg/100 mg BID x 3-4 weeks- Lopinavir AUC: increased 46%; Cmax: increased 28%; Cmin: increased 116%Increased lopinavir/ritonavir effectsInhibition of CYP450 3A4 by ritonavir

Dose adjustment not established

Rosuvastatin170
(Crestor)
20 mg QD on days 1-7, 18-24400/100 mg BID on days 8-24Rosuvastatin AUC: increased 108%; Cmax: increased 366%; Cmin: no significant changeNot studiedIncreased rosuvastatin effects-

Do not coadminister

Alternative Agents:
Pravastatin; atorvastatin

Saquinavir150
(SQV)(Fortovase, Invirase)
1000 mg (soft gel caps) BID400/100 mg BIDSaquinavir AUC: no significant change; Cmax: no significant change; Cmin: increased 27% (compared to saquinavir/ritonavir control)Ritonavir AUC: decreased 54%; Cmax: decreased 37%; Cmin: decreased 60%; Clearance total: increased 107%(compared to saquinavir/ritonavir control)Lopinavir AUC: no significant change; Cmax: no significant change; Cmin: no significant change; (compared to historical control)-Possibly increased clearance resulting in decreased ritonavir levels

No dose adjustment necessary

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Saquinavir108
(SQV)(Fortovase, Invirase)
1200 mg TID on days 1-5, 800 mg BID on days 6-15400/100 mg BID on days 6-20Saquinavir AUC: increased 836%; Cmax: increased 517%; Cmin: increased 1700%No significant changeIncreased saquinavir effectsInhibition of CYP450 3A4 by lopinavir/ritonavir

Dose adjustment not established

Saquinavir78
(SQV)(Fortovase, Invirase)
800 mg BID400 mg/100 mg BID x 10 daysSaquinavir AUC: no significant change; Cmin: increased-Increased saquinavir effectsInhibition of CYP450 3A4 by lopinavir/ritonavir

Dose adjustment not established

Sildenafil78
(Viagra)
--Not studied; may increase sildenafil levels-Increased sildenafil effects (eg, hypotension, priapism)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Initiate sildenafil at 25 mg QOD-QD; adjust dose as indicated; not recommended to exceed 25 mg in a 48 hour period

Simvastatin78
(Zocor)(Zocor)
--May increase simvastatin levels-Increased simvastatin effects (eg, myopathy, rhabdomyolysis)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

Alternative Agents:
Atorvastatin Pravastatin

St. John's Wort78
(Hypericum perforatum, hypericin, hyperforin)
- - - Not studied; may decrease lopinavir/ritonavir levelsDecreased lopinavir/ritonavir effectsInduction of CYP450 3A4 by St. John's Wort

Do not coadminister

Tacrolimus78
(Prograf)(Prograf)
- - Not studied; may increase tacrolimus levels- Increased tacrolimus effects (increased immunosuppression)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Monitor and adjust tacrolimus as indicated

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Tadalafil78
--Not studied; may increase tadalafil levels-Increased tadalafil effects (eg, hypotension, priapism)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

Alternative Agents:
Sildenafil, vardenafil

Telaprevir571
(Incivek)
750 mg Q8H x 10 days400 mg lopinavir BID with 100 mg ritonavir BID x 20 daysTelaprevir AUC: decreased 54%; Cmin: decreased 52%; Cmax: decreased 53%No significant changeDecreased telaprevir effects-

Do not coadminister

Alternative Agents:
Atazanavir/ritonavir

Tenofovir96, 98
(TDF)(Viread)
300 mg QD400 mg/100 mg BID x 14 daysTenofovir AUC: increased 34%; Cmax: increased 31%; Cmin: increased 29%Lopinavir AUC: decreased 15%; Cmax: decreased 15%; Cmin: no significant change; Ritonavir AUC: decreased 24%; Cmax: decreased 28%; Cmin: no significant changeIncreased tenofovir effects-

No dose adjustment necessary

Tenofovir104
(TDF)(Viread)
300 mg QD400/100 mg BIDNot studiedLopinavir: no significant change. Ritonavir: no significant change--

No dose adjustment necessary

Tenofovir78, 96
(TDF)(Viread)
300 mg QD400/100 mg BIDTenofovir AUC: increased 32%; Cmin: increased 51%; half-life: no significant changeNo significant changePossibly increased tenofovir effects-

No dose adjustment necessary

Terfenadine78
(Seldane)(Seldane)
- - Not studied; may increase terfenadine levels- Increased terfenadine effects (eg, cardiac arrhythmias)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Do not coadminister

Alternative Agents:
Cetirizine Fexofenadine Loratadine

Coadministered DrugDose of DrugDose of Lopinavir/ritonavirEffect on Drug LevelsEffect on Lopinavir/ritonavir LevelsPotential Clinical EffectsMechanism of InteractionManagement
Tinidazole329
(Tindamax)
- Oral solution (contains alcohol)- - Disulfiram like reaction (eg, nausea, vomiting, headache, hypotension)Inhibition of alcohol and aldehyde dehydrogenase by tinidazole

Do not coadminister; may consider lopinavir/ritonavir capsules

Tipranavir154
(TPV)(Aptivus)
500 mg BID with 200 mg ritonavir BID400 mg/100 mg BID- Lopinavir AUC: decreased 55%; Cmax: decreased 47%; Cmin: decreased 70%Decreased lopinavir effectsInduction of CYP450 3A4 by tipranavir/ritonavir

Do not coadminister

Trazodone78
(Desyrel)(Desyrel)
--Increased trazodone concentrations-Increased trazodone effects (eg, nausea, dizziness, hypotension, syncope)Possible inhibition of trazodone metabolism

Use with caution; if benefit outweighs risk, initiate trazodone at lower dose

Triazolam78
(Halcion)(Halcion)
--Not studied; may increase triazolam levels-Increased triazolam effects (eg, increased sedation, confusion, respiratory depression)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Avoid combination; consider alternative agents

Alternative Agents:
Lorazepam Oxazepam Temazepam Trazodone

Valproic acid220
(Depakote, Depakene, Depacon)(Depakene, Depakote)
250 mg BID x 7 days400/100 mg BIDNo significant changeLopinavir Cmax: increased 33%; Cmin: increased 57%; AUC: increased 75%; half-life: no significant changeIncreased lopinavir effectsPossible inhibition of UGT-mediated metabolism of lopinavir

Dose adjustment not established

Vardenafil78
--Not studied; may increase vardenafil levels-Increased vardenafil effects (eg, hypotension, priapism)Inhibition of CYP450 3A4 by lopinavir/ritonavir

Initiate vardenafil at 5 mg QD; adjust dose as indicated; not recommended to exceed 20 mg in a 48 hour period

Voriconazole78
(VFend)(VFend)
--Decreased voriconazole levels-Decreased voriconazole effectsPossible induction of CYP450 by ritonavir

Do not coadminister

Warfarin78
(Coumadin)
--Not studied; may increase or decrease warfarin levels-Increased or decreased warfarin effects (eg, altered INR, increased risk of bleeding or clotting)Possible inhibition of CYP450 by lopinavir/ritonavir

Monitor INR and adjust warfarin as indicated

Zidovudine78
(AZT, ZDV)(Retrovir)
--Not studied; may decrease zidovudine levelsNot studiedDecreased zidovudine effectsInduction of glucuronidation by lopinavir/ritonavir

No dose adjustment necessary

"-" indicates that there are no data available
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