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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Drug Interactions

Drug Interactions between Protease Inhibitors and Other Drugs

(Last updated:2/12/2013; last reviewed:2/12/2013)

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This table provides information relating to pharmacokinetic (PK) interactions between PIs and non-antiretroviral (ARV) drugs. When information is available, interactions with boosted and unboosted PIs are listed separately. For interactions between ARV agents and for dosing recommendations, refer to Table 16a.

 

*Nelfinavir (NFV) and indinavir (IDV) are not included in this table. Please refer to the NFV and IDV FDA package inserts for information regarding drug interactions with these PIs.

Table 15a. Drug Interactions between Protease Inhibitors (PI)* and Other Drugs
Concomitant Drug PI Effect on PI or Concomitant Drug Concentrations Dosing Recommendations and Clinical Comments
Acid Reducers
Antacids ATV, ATV/r When given simultaneously, ↓ ATV expected Give ATV at least 2 hours before or 1 hour after antacids or buffered medications.
FPV APV AUC ↓ 18%; no significant change in APV Cmin Give FPV simultaneously with (or at least 2 hours before or 1 hour after) antacids.
TPV/r TPV AUC ↓ 27% Give TPV at least 2 hours before or 1 hour after antacids.
H2 Receptor Antagonists RTV-boosted PIs
ATV/r ↓ ATV H2 receptor antagonist dose should not exceed a dose equivalent to famotidine 40 mg BID in ART-naive patients or 20 mg BID in ART-experienced patients. Give ATV 300 mg + RTV 100 mg simultaneously with and/or ≥10 hours after the H2 receptor antagonist. If using TDF and H2 receptor antagonist in ART-experienced patients, use ATV 400 mg + RTV 100 mg
DRV/r, LPV/r No significant effect No dosage adjustment necessary.
PIs without RTV
ATV ↓ ATV H2 receptor antagonist single dose should not exceed a dose equivalent of famotidine 20 mg or total daily dose equivalent of famotidine 20 mg BID in ART-naive patients. Give ATV at least 2 hours before and at least 10 hours after the H2 receptor antagonist
FPV APV AUC ↓ 30%; no significant change in APV Cmin If concomitant use is necessary, give FPV at least 2 hours before H2 receptor antagonist. Consider boosting FPV with RTV.
Proton Pump Inhibitors (PPIs) ATV ↓ ATV PPIs are not recommended in patients receiving unboosted ATV. In these patients, consider alternative acid-reducing agents, RTV boosting, or alternative PIs.
ATV/r ↓ ATV PPIs should not exceed a dose equivalent to omeprazole 20 mg daily in PI-naive patients. PPIs should be administered at least 12 hours before ATV/r. PPIs are not recommended in PI-experienced patients.

DRV/r, TPV/r ↓ omeprazole
PI: no significant effect
May need to increase omeprazole dose when using TPV/r.
FPV, FPV/r, LPV/r No significant effect No dosage adjustment necessary.
SQV/r SQV AUC ↑ 82% Monitor for SQV toxicities.
Anticoagulants
Warfarin ATV, ATV/r, DRV/r,
FPV, FPV/r, LPV/r, SQV/r, TPV/r
↑ or ↓ warfarin possible
DRV/r ↓ S-warfarin AUC 21%
Monitor INR closely when stopping or starting PI and adjust warfarin dose accordingly.
Rivaroxaban Rivaroxaban ↑ rivaroxaban Avoid concomitant use. Co-administration is expected to result in increased exposure of rivaroxaban which may lead to risk of increased bleeding.
Anticonvulsants
Carbamazepine RTV-boosted PIs
ATV/r, FPV/r, LPV/r, SQV/r, TPV/r ↑ carbamazepine possible
TPV/r ↑ carbamazepine AUC 26%
May ↓ PI levels substantially
Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response. Do not co-administer with LPV/r once daily.
DRV/r carbamazepine AUC ↑ 45%
DRV: no significant change
Monitor anticonvulsant level and adjust dose accordingly.
PIs without RTV
ATV, FPV May ↓ PI levels substantially Monitor anticonvulsant level and virologic response. Consider alternative anticonvulsant, RTV boosting for ATV and FPV, and/or monitoring PI level.
Lamotrigine LPV/r lamotrigine AUC ↓ 50%
LPV: no significant change
A dose increase of lamotrigine may be needed and therapeutic concentration monitoring for lamotrigine may be indicated; particularly during dosage adjustment or consider alternative anticonvulsant.
A similar interaction is possible with other RTV-boosted PIs.
Phenobarbital All PIs May ↓ PI levels substantially Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Do not co-administer with LPV/r once daily.
Phenytoin RTV-boosted PIs
ATV/r, DRV/r, SQV/r, TPV/r ↓ phenytoin possible
↓ PI possible
Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
FPV/r phenytoin AUC ↓ 22%
APV AUC ↑ 20%
Monitor phenytoin level and adjust dose accordingly. No change in FPV/r dose recommended.
LPV/r phenytoin AUC ↓ 31%
LPV/r AUC ↓ 33%
Consider alternative anticonvulsant or monitor levels of both drugs and assess virologic response.
Do not co-administer with LPV/r once daily.
PIs without RTV
ATV, FPV May ↓ PI levels substantially Consider alternative anticonvulsant, RTV boosting for ATV and FPV, and/or monitoring PI level.
Monitor anticonvulsant level and virologic response.
Valproic Acid (VPA) LPV/r ↓ or ↔ VPA possible
LPV AUC ↑ 75%
Monitor VPA levels and virologic response. Monitor for LPV-related toxicities.
Antidepressants
Bupropion LPV/r bupropion AUC ↓ 57% Titrate bupropion dose based on clinical response.
TPV/r bupropion AUC ↓ 46%
Paroxetine DRV/r paroxetine AUC ↓ 39% Titrate paroxetine dose based on clinical response.
FPV/r paroxetine AUC ↓ 55%
Sertraline DRV/r sertraline AUC ↓ 49% Titrate sertraline dose based on clinical response.
Trazodone ATV/r, ATV, DRV/r, FPV/r,  FPV, LPV/r, TPV/r RTV 200 mg BID (for 2 days)
↑ trazodone AUC 240%
Use lowest dose of trazodone and monitor for CNS and cardiovascular adverse effects.
SQV/r ↑ trazodone expected Contraindicated. Do not co-administer.
Tricyclic Antidepressants (TCAs)
(Amitriptyline, Desipramine, Imipramine, Nortriptyline)
All RTV-boosted PIs ↑ TCA expected Use lowest possible TCA dose and titrate based on clinical assessment and/or drug levels.
Antifungals
Fluconazole Fluconazole RTV-boosted PIs
ATV/r No significant effect No dosage adjustment necessary.
SQV/r No data with RTV boosting
SQV (1200 mg TID) AUC ↑ 50%
No dosage adjustment necessary.
TPV/r TPV AUC ↑ 50% Fluconazole >200 mg daily is not recommended. If high-dose fluconazole is indicated, consider alternative PI or another class of ARV drug.
Itraconazole RTV-boosted PIs
ATV/r, DRV/r, FPV/r, TPV/r ↑ itraconazole possible
↑ PI possible
Consider monitoring itraconazole level to guide dosage adjustments. High doses (>200 mg/day) are not recommended unless dose is guided by itraconazole levels.
LPV/r ↑ itraconazole Consider monitoring itraconazole level to guide dosage adjustments. High doses (>200 mg/day) are not recommended unless dose is guided by itraconazole levels
SQV/r Bidirectional interaction has been observed Dose not established, but decreased itraconazole dosage may be warranted. Consider monitoring itraconazole level.
PIs without RTV
ATV, FPV ↑ itraconazole possible
↑ PI possible
Consider monitoring itraconazole level to guide dosage adjustments.
Posaconazole ATV/r ATV AUC ↑ 146% Monitor for adverse effects of ATV.
ATV ATV AUC ↑ 268% Monitor for adverse effects of ATV.
FPV FPV (1400 mg BID) ↓ posaconazole AUC 23%; (compared with FPV/RTV 700 mg/100 mg) APV AUC ↓ 65% Do not co-administer.
Voriconazole RTV-boosted PIs
All RTV-boosted PIs RTV 400 mg BID ↓ voriconazole AUC 82%
RTV 100 mg BID ↓ voriconazole AUC 39%
Do not co-administer voriconazole and RTV unless benefit outweighs risk. If administered, consider monitoring voriconazole level and adjust dose accordingly.
PIs without RTV
ATV, FPV ↑ voriconazole possible
↑ PI possible
Monitor for toxicities.
Antimycobacterials
Clarithromycin ATV/r, ATV clarithromycin AUC ↑ 94% May cause QTc prolongation. Reduce clarithromycin dose by 50%. Consider alternative therapy (e.g., azithromycin).
DRV/r, FPV/r, LPV/r, SQV/r, TPV/r DRV/r ↑ clarithromycin AUC 57%
FPV/r ↑ clarithromycin possible
LPV/r ↑ clarithromycin expected
RTV 500 mg BID ↑ clarithromycin 77%
SQV unboosted ↑ clarithromycin 45%
TPV/r ↑ clarithromycin 19%
clarithromycin ↑ unboosted SQV 177%
clarithromycin ↑ TPV 66%
Monitor for clarithromycin-related toxicities or consider alternative macrolide (e.g., azithromycin). Reduce clarithromycin dose by 50% in patients with CrCl 30-60 mL/min. Reduce clarithromycin dose by 75% in patients with CrCl <30 mL/min.
FPV APV AUC ↑ 18% No dosage adjustment necessary.
Rifabutin RTV-boosted PIs
ATV/r rifabutin (150 mg once daily)
AUC ↑ 110% and metabolite
AUC ↑ 2,101% compared with rifabutin (300 mg daily) administered alone
Rifabutin 150 mg once daily or 300 mg three times a week. Monitor for antimycobacterial activity and consider therapeutic drug monitoring. PK data reported in this table are results from healthy volunteer studies. Lower rifabutin exposure has been reported in HIV-infected patients than in the healthy study participants.
DRV/r rifabutin (150 mg every other day) AUC not significantly changed and metabolite AUC ↑ 881% compared with rifabutin (300 mg once daily) administered alone
FPV/r rifabutin (150 mg every other day) and metabolite AUC ↑ 64% compared with rifabutin (300 mg once daily) administered alone
LPV/r rifabutin (150 mg once daily) and metabolite AUC ↑ 473% compared with rifabutin (300 mg daily) administered alone
SQV/r ↑ rifabutin with unboosted SQV
TPV/r rifabutin (150 mg x 1 dose) and metabolite AUC ↑ 333%
PIs without RTV
ATV, FPV ↑ rifabutin AUC expected Rifabutin 150 mg daily or 300 mg three times a week
Rifampin All PIs ↓ PI conc. by  >75% Do not co-administer rifampin and PIs. Additional RTV does not overcome this interaction and increases hepatotoxicity.
Rifapentine All PIs ↓ PI expected Do not co-administer rifapentine and PIs.
Benzodiazepines
Alprazolam
Diazepam
All PIs ↑ benzodiazepine possible
RTV (200 mg BID for 2 days)
↑ alprazolam half-life 222% and AUC 248%
Consider alternative benzodiazepines such as lorazepam, oxazepam, or temazepam.
Lorazepam
Oxazepam
Temazepam
All PIs No data These benzodiazepines are metabolized via non-CYP450 pathways; there is less interaction potential than with other benzodiazepines.
Midazolam All PIs ↑ midazolam expected
SQV/r ↑ midazolam (oral) AUC 1,144% and Cmax 327%
Do not co-administer oral midazolam and PIs. Parenteral midazolam can be used with caution when given as a single dose in a monitored situation for procedural sedation.
Triazolam All PIs ↑ triazolam expected
RTV (200 mg BID) ↑ triazolam half-life 1,200% and AUC 2,000%
Do not co-administer triazolam and PIs.
Cardiac Medications
Bosentan All PIs LPV/r ↑ bosentan 48-fold (day 4) and 5-fold (day 10)
↓ ATV expected
Do not co-administer bosentan and ATV without RTV. In patients on a PI (other than unboosted ATV) >10 days: Start bosentan at 62.5 mg once daily or every other day. In patients on bosentan who require a PI (other than unboosted ATV): Stop bosentan >36 hours before PI initiation and restart 10 days after PI initiation at 62.5 mg once daily or every other day
Digoxin RTV, SQV/r RTV (200 mg BID) ↑ digoxin AUC 29% and half-life 43%
SQV/r ↑ digoxin AUC 49%
Use with caution. Monitor digoxin levels. Digoxin dose may need to be decreased.
Dihydropyridine Calcium Channel Blockers (CCBs) All PIs ↑ dihydropyridine possible Use with caution. Titrate CCB dose and monitor closely. ECG monitoring is recommended when CCB used with ATV.
Diltiazem ATV/r, ATV diltiazem AUC ↑ 125% Decrease diltiazem dose by 50%. ECG monitoring is recommended.
DRV/r, FPV/r, FPV
LPV/r, SQV/r, TPV/r
↑ diltiazem possible Use with caution. Adjust diltiazem according to clinical response and toxicities.
Corticosteroids
Budesonide (systemic) All PIs ↓ PI levels possible
↑ glucocorticoids
Use with caution.  Co-administration can result in adrenal insufficiency, including Cushing’s syndrome. Do not co-administer unless potential benefits of systemic budesonide outweigh the risks of systemic corticosteroid adverse effects.
Budesonide (inhaled or intranasal) All RTV-boosted PIs ↑ glucocorticoids Use with caution. Co-administration can result in adrenal insufficiency, including Cushing’s syndrome. Do not co-administer unless potential benefits of inhaled or intranasal budesonide outweigh the risks of systemic corticosteroid adverse effects.
Dexamethasone All PIs ↓ PI levels possible Use systemic dexamethasone with caution or consider alternative corticosteroid for long-term use.
Fluticasone
(inhaled or intranasal)
All RTV-boosted PIs RTV 100 mg BID ↑ fluticasone AUC 350-fold and ↑ Cmax 25-fold Co-administration can result in adrenal insufficiency, including Cushing’s syndrome. Do not co-administer unless potential benefits of inhaled fluticasone outweigh the risks of systemic corticosteroid adverse effects.
Prednisone LPV/r ↑ prednisolone AUC 31%
↓ lopinavir
Use with caution. Co-administration can result in adrenal insufficiency, including Cushing’s syndrome. Do not co-administer unless potential benefits of prednisone outweigh the risks of systemic corticosteroid adverse effects.
Hepatitis C NS3/4A Protease Inhibitors
Boceprevir ATV/r ATV AUC ↓ 35%, Cmin ↓ 49%
RTV AUC ↓ 36%
boceprevir AUC ↔
Co-administration is not recommended.
DRV/r DRV AUC ↓ 44%, Cmin ↓ 59%
RTV AUC ↓ 26%
boceprevir AUC ↓ 32%, Cmin ↓ 35%
Co-administration is not recommended.
LPV/r LPV AUC ↓ 34%, Cmin ↓ 43%
RTV AUC ↓ 22%
boceprevir AUC ↓ 45%, Cmin ↓ 57%
Co-administration is not recommended.
Telaprevir ATV/r telaprevir AUC ↓ 20% No dose adjustment necessary.
DRV/r telaprevir AUC ↓ 35%
DRV AUC ↓ 40%
Co-administration is not recommended.
FPV/r telaprevir AUC ↓ 32%
APV AUC ↓ 47%
Co-administration is not recommended.
LPV/r telaprevir AUC ↓ 54%
LPV: no significant change
Co-administration is not recommended.
Herbal Products
St. John’s Wort All PIs ↓ PI expected Do not co-administer.
Hormonal Contraceptives
Hormonal Contraceptives RTV-boosted PIs
ATV/r ethinyl estradiol AUC ↓ 19% and Cmin ↓ 37%
norgestimate ↑ 85%
Oral contraceptive should contain at least 35 mcg of ethinyl estradiol. Oral contraceptives containing progestins other than norethindrone or norgestimate have not been studied.a

DRV/r ethinyl estradiol AUC ↓ 44%
norethindrone AUC ↓ 14%
Use alternative or additional contraceptive method.
FPV/r ethinyl estradiol AUC ↓ 37%
norethindrone AUC ↓ 34%
Use alternative or additional contraceptive method.
LPV/r ethinyl estradiol AUC ↓ 42%
norethindrone AUC ↓ 17%
Use alternative or additional contraceptive method.
SQV/r ↓ ethinyl estradiol Use alternative or additional contraceptive method.
TPV/r ethinyl estradiol AUC ↓ 48%
norethindrone: no significant change
Use alternative or additional contraceptive method.
PIs without RTV
ATV ethinyl estradiol AUC ↑ 48%
norethindrone AUC ↑ 110%
Use oral contraceptive that contains no more than 30 mcg of ethinyl estradiol or use alternative contraceptive method. Oral contraceptives containing less than 25 mcg of ethinyl estradiol or progestins other than norethindrone or norgestimate have not been studied.b
FPV With APV: ↑ ethinyl estradiol and ↑ norethindrone Cmin;
APV Cmin ↓ 20%
Use alternative contraceptive method.
HMG-CoA Reductase Inhibitors
Atorvastatin ATV/r, ATV ↑ atorvastatin possible Titrate atorvastatin dose carefully and use lowest dose necessary.
DRV/r
FPV/r, FPV,
SQV/r
DRV/r + atorvastatin 10 mg similar to atorvastatin 40 mg administered alone;
FPV +/– RTV ↑ atorvastatin AUC 130%–153%;
SQV/r ↑ atorvastatin AUC 79%
Titrate atorvastatin dose carefully and use the lowest necessary dose. Do not exceed 20 mg atorvastatin daily.
LPV/r LPV/r ↑ atorvastatin AUC 488% Use with caution and use the lowest atorvastatin dose necessary. 
TPV/r ↑ atorvastatin AUC 836% Do not co-administer.
Lovastatin All PIs Significant ↑ lovastatin expected Contraindicated. Do not co-administer.
Pitavastatin All PIs ATV ↑ pitavastatin AUC 31% and
Cmax ↑ 60%
ATV: no significant effect
LPV/r ↓ pitavastatin AUC 20%
LPV: no significant effect
No dose adjustment necessary.
Pravastatin DRV/r pravastatin AUC ↑ 81% Use lowest possible starting dose of pravastatin with careful monitoring.
LPV/r pravastatin AUC ↑ 33% No dose adjustment necessary.
SQV/r pravastatin AUC ↓ 47%–50% No dose adjustment necessary.
Rosuvastatin ATV/r, LPV/r ATV/r ↑ rosuvastatin AUC 3-fold and Cmax ↑ 7-fold
LPV/r ↑ rosuvastatin AUC 108% and Cmax ↑ 366%
Titrate rosuvastatin dose carefully and use the lowest necessary dose. Do not exceed 10 mg rosuvastatin daily.
DRV/r rosuvastatin AUC ↑ 48% and
Cmax ↑ 139%
Titrate rosuvastatin dose carefully and use the lowest necessary dose while monitoring for toxicities.
FPV +/- RTV No significant effect on rosuvastatin No dosage adjustment necessary
SQV/r No data available Titrate rosuvastatin dose carefully and use the lowest necessary dose while monitoring for toxicities.
TPV/r rosuvastatin AUC ↑ 26% and Cmax ↑ 123% No dosage adjustment necessary.
Simvastatin All PIs Significant ↑ simvastatin level;
SQV/r 400 mg/400 mg BID
↑ simvastatin AUC 3,059%
Contraindicated. Do not co-administer.
Immunosuppressants
Cyclosporine
Sirolimus
Tacrolimus
All PIs ↑ immunosuppressant possible Initiate with an adjusted dose of immunosuppressant to account for potential increased concentrations of the immunosuppressant and monitor for toxicities. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with specialist as necessary.
Narcotics/Treatment for Opioid Dependence
Buprenorphine ATV buprenorphine AUC ↑ 93% norbuprenorphinec AUC ↑ 76%
↓ ATV possible
Do not co-administer buprenorphine with unboosted ATV.
ATV/r buprenorphine AUC ↑ 66% norbuprenorphinec AUC ↑ 105% Monitor for sedation. Buprenorphine dose reduction may be necessary.
DRV/r buprenorphine: no significant effect
norbuprenorphinec AUC ↑ 46% and Cmin ↑ 71%
No dosage adjustment necessary. Clinical monitoring is recommended.
FPV/r buprenorphine: no significant effect
norbuprenorphinec AUC ↓ 15%
No dosage adjustment necessary. Clinical monitoring is recommended.
LPV/r No significant effect No dosage adjustment necessary
TPV/r buprenorphine: no significant effect
norbuprenorphinec AUC, Cmax, and Cmin ↓ 80%
TPV Cmin ↓ 19%–40%
Consider monitoring TPV level.
Oxycodone LPV/r oxycodone AUC ↑ 2.6 fold Monitor for opioid-related adverse effects. Oxycodone dose reduction may be necessary.
Methadone RTV-boosted PIs
ATV/r, DRV/r,
FPV/r, LPV/r,
SQV/r, TPV/r
ATV/r, DRV/r, FPV/r
↓ R-methadoned AUC 16%-18%;
LPV/r ↓ methadone AUC 26%–53%;
SQV/r 1000/100 mg BID
↓ R-methadoned AUC 19%;
TPV/r ↓ R-methadoned AUC 48%
Opioid withdrawal unlikely but may occur. Dosage adjustment of methadone is not usually required, but monitor for opioid withdrawal and increase methadone dose as clinically indicated.
PIs without RTV
ATV No significant effect No dosage adjustment necessary.
FPV No data with unboosted FPV
APV ↓ R-methadoned Cmin 21%, AUC no significant change
Monitor and titrate methadone as clinically indicated. The interaction with FPV is presumed to be similar.
Phosphodiesterase Type 5 (PDE5) Inhibitors
Avanafil ATV, ATV/r,
DRV/r, FPV/r,
SQV/r, LPV/r
RTV (600 mg BID x 5 days)
↑ avanafil AUC 13-fold, Cmax 2.4-fold
Co-administration is not recommended.
FPV No data Avanafil dose should not exceed 50 mg once every 24 hours.
Sildenafil All PIs DRV/r + sildenafil 25 mg similar to sildenafil 100 mg alone;
RTV 500 mg BID ↑ sildenafil AUC 1,000%;
SQV unboosted ↑ sildenafil AUC 210%
For treatment of erectile dysfunction
Start with sildenafil 25 mg every 48 hours and monitor for adverse effects of sildenafil.
For treatment of PAH
Contraindicated
Tadalafil All PIs RTV 200 mg BID ↑ tadalafil AUC 124%;
TPV/r (1st dose) ↑ tadalafil AUC 133%;
TPV/r steady state: no significant effect 
For treatment of erectile dysfunction
Start with tadalafil 5-mg dose and do not exceed a single dose of 10 mg every 72 hours. Monitor for adverse effects of tadalafil.
For treatment of PAH
In patients on a PI >7 days:
Start with tadalafil 20 mg once daily and increase to 40 mg once daily based on tolerability.

In patients on tadalafil who require a PI:
Stop tadalafil >24 hours prior to PI initiation, restart 7 days after PI initiation at 20 mg once daily, and increase to 40 mg once daily based on tolerability.
For treatment of benign prostatic hyperplasia
Maximum recommended daily dose is 2.5 mg per day
Vardenafil All PIs RTV 600 mg BID ↑ vardenafil AUC 49-fold Start with vardenafil 2.5 mg every 72 hours and monitor for adverse effects of vardenafil.
Miscellaneous Interactions
Colchicine All PIs RTV 100 mg BID ↑ colchicine AUC 296%, Cmax 184% With all PIs: significant  ↑ in colchicine AUC expected For treatment of gout flares
Colchicine 0.6 mg x 1 dose, followed by 0.3 mg 1 hour later. Do not repeat dose for at least 3 days.

With FPV without RTV: 1.2 mg x 1 dose and no repeat dose for at least 3 days For prophylaxis of gout flares
Colchicine 0.3 mg once daily or every other day

With FPV without RTV: colchicine 0.3 mg BID or 0.6 mg once daily or 0.3 mg once daily For treatment of familial Mediterranean fever
Do not exceed colchicine 0.6 mg once daily or 0.3 mg BID.

With FPV without RTV: Do not exceed 1.2 mg once daily or 0.6 mg BID. Do not co-administer in patients with hepatic or renal impairment.
Salmeterol All PIs ↑ salmeterol possible Do not co-administer because of potential increased risk of salmeterol-associated cardiovascular events.
Atovaquone/proguanil ATV/r, LPV/r ATV/r ↓ atovaquone AUC 46% and ↓ proguanil AUC 41%
LPV/r ↓ atovaquone AUC 74% and ↓ proguanil AUC 38%
No dosage recommendation. Consider alternative drug for malaria prophylaxis, if possible.
a The following products contain at least 35 mcg of ethinyl estradiol combined with norethindrone or norgestimate (generic formulation may also be available): Ovcon 35, 50; Femcon Fe; Brevicon; Modicon; Ortho-Novum 1/35, 10/11, 7/7/7; Norinyl 1/35; Tri-Norinyl; Ortho-Cyclen; Ortho Tri-Cyclen.
b The following products contain no more than 30 mcg of ethinyl estradiol combined with norethindrone or norgestimate (generic formulation may also be available): Loestrin 1/20, 1.5/30; Loestrin Fe 1/20, 1.5/30; Loestrin 24 Fe; Ortho Tri-Cyclen Lo.
c Norbuprenorphine is an active metabolite of buprenorphine.
d R-methadone is the active form of methadone.


Acronyms
: APV = amprenavir, ART = antiretroviral therapy, ARV = antiretroviral, ATV = atazanavir, ATV/r = atazanavir + ritonavir, AUC = area under the curve, BID = twice daily, CCB = calcium channel blocker, Cmax = maximum plasma concentration, Cmin = minimum plasma concentration, CNS = central nervous system, CrCl = creatinine clearance, CYP = cytochrome P, DRV = darunavir, DRV/r = darunavir + ritonavir, ECG = electrocardiogram, FDA = Food and Drug Administration, FPV = fosamprenavir (FPV is a pro-drug of APV), FPV/r = fosamprenavir + ritonavir, IDV = indinavir, INR = international normalized ratio, LPV = lopinavir, LPV/r = lopinavir + ritonavir, NFV = nelfinavir, PAH = pulmonary arterial hypertension, PDE5 = phosphodiesterase type 5, PI = protease inhibitor, PK = pharmacokinetic, PPI = proton pump inhibitor, RTV = ritonavir, SQV = saquinavir, SQV/r = saquinavir + ritonavir, TCA = tricyclic antidepressant, TDF = tenofovir disoproxil fumarate, TID = three times a day, TPV = tipranavir, TPV/r = tipranavir + ritonavir, VPA = valproic acid