Concomitant Drug
Class/Name
|
Integrase Inhibitor
|
Effect on Integrase Inhibitor or Concomitant Drug Concentrations
|
Dosing Recommendations and Clinical Comments
|
Acid Reducers |
Antacids |
EVG/COBI/TDF/FTC |
EVG AUC ↓ 15%−20% if given 2 hours before or after antacid;
←→with 4-hour interval |
Separate EVG/COBI/FTC/TDF and antacid administration by more than 2 hours |
H2-Receptor Antagonists |
EVG/COBI/TDF/FTC |
No significant effect |
No dosage adjustment necessary. |
Proton Pump Inhibitors |
EVG/COBI/TDF/FTC |
No significant effect |
No dosage adjustment necessary. |
RAL |
RAL AUC ↑ 212%, Cmax ↑ 315%, and Cmin ↑ 46% |
No dosage adjustment necessary. |
Anticoagulants |
Warfarin |
EVG/COBI/TDF/FTC |
No data: but warfarin levels may be affected |
Monitor INR and adjust warfarin dose accordingly. |
Anticonvulsants |
Carbamazepine
Oxcarbazepine
Phenobarbital
Phenytoin |
EVG/COBI/TDF/FTC |
↑ carbamazepine possible
↓ EVG possible
↓ COBI possible |
Consider alternative anticonvulsant. |
Ethosuximide |
EVG/COBI/TDF/FTC |
↑ ethosuximide possible |
Clinically monitor for ethosuxamide toxicities. |
Antidepressants |
Selective Serotonin Reuptake Inhibitors (SSRIs) |
EVG/COBI/TDF/FTC |
↑ SSRI possible |
Initiate with lowest dose of SSRI and titrate dose carefully based on antidepressant response. |
Tricyclic Antidepressants (TCAs)
Amitriptyline
Desipramine
Imipramine
Nortriptyline |
EVG/COBI/TDF/FTC |
Desipramine AUC ↑ 65% |
Initiate with lowest dose and titrate dose of TCA carefully. |
Trazodone |
EVG/COBI/TDF/FTC |
↑ trazodone possible |
Initiate with lowest dose and titrate dose of trazodone carefully. |
Antifungals |
Itraconazole |
EVG/COBI/TDF/FTC |
↑ itraconazole expected
↑ EVG and COBI possible |
Consider monitoring itraconazole level to guide dosage adjustments. High doses (>200 mg/day) are not recommended unless dose is guided by itraconazole levels. |
Posaconazole |
EVG/COBI/TDF/FTC |
↑ EVG and COBI possible
↑ posaconazole possible
|
Monitor posaconazole concentrations with co-administration. |
Voriconazole |
EVG/COBI/TDF/FTC |
↑ voriconazole expecte
↑ EVG and COBI possible
|
Risk/benefit ratio should be assessed to justify use of voriconazole. If administered, consider monitoring voriconazole level. Adjust dose accordingly. |
Antimycobacterials |
Clarithromycin |
EVG/COBI/TDF/FTC |
↑ clarithromycin possible
↑ COBI possible |
CrCl ≥60 mL/min: No dose adjustment necessary
CrCl 50−60 mL/min: Reduce clarithromycin dose by 50%
CrCl <50 mL/min: EVG/COBI/TDF/FTC is not recommended.
|
Rifabutin |
EVG/COBI/TDF/FTC |
Rifabutin (150 mg every other day):
No significant change in rifabutin AUC;
For 25-O-desacetyl-rifabutin, AUC ↑ 625% compared with rifabutin (300 mg daily) administered alone
EVG AUC ↓ 21%, Cmin ↓ 67%
|
Do not co-administer. |
RAL |
RAL AUC ↑ 19%, Cmax ↑ 39%, and Cmin ↓ 20% |
No dosage adjustment necessary. |
Rifampin |
EVG/COBI/TDF/FTC |
Significant ↓ EVG and COBI expected |
Do not co-administer. |
RAL |
RAL 400 mg: RAL AUC ↓ 40% and Cmin ↓ 61%
Rifampin with RAL 800 mg BID compared with RAL 400 mg BID alone: RAL AUC ↑ 27% and Cmin ↓ 53%
|
Dose: RAL 800 mg BID
Monitor closely for virologic response or consider using rifabutin as an alternative rifamycin
|
Rifapentine |
EVG/COBI/TDF/FTC |
Significant ↓ EVG and COBI expected |
Do not co-administer. |
Benzodiazepines |
Clonazepam
Clorazepate
Diazepam
Estazolam
Flurazepam |
EVG/COBI/TDF/FTC |
↑ benzodiazepines possible |
Dose reduction of benzodiazepine may be necessary. Initiate with low dose and clinically monitor.
Consider alternative benzodiazepines to diazepam, such as lorazepam, oxazepam, or temazepam.
|
Midazolam
Triazolam |
EVG/COBI/TDF/FTC |
↑ midazolam expected
↑ triazolam expected |
Do not co-administer triazolam or oral midazolam and EVG/COBI.
Parenteral midazolam can be used with caution in a closely monitored setting. Consider dose reduction, especially if >1 dose is administered.
|
Cardiac Medications |
Anti-Arrhythmics
(amiodarone, bepridil, digoxin, disopyramide, dronedarone, flecainide, systemic lidocaine, mexilitine, propafenone, quinidine) |
EVG/COBI/TDF/FTC |
↑ anti-arrhythmics possible
digoxin Cmax ↑ 41%, AUC no significant change
|
Use anti-arrhythmics with caution. Therapeutic drug monitoring, if available, is recommended for anti arrhythmics. |
Bosentan |
EVG/COBI/TDF/FTC |
↑ bosentan possible |
In patients on EVG/COBI/FTC/TDF ≥10 days: start bosentan at 62.5 mg once daily or every other day based on individual tolerability.
In patients on bosentan who require EVG/COBI/FTC/TDF: stop bosentan ≥36 hours before EVG/COBI/FTC/TDF initiation. After at least 10 days following initiation of EVG/COBI/FTC/TDF, resume bosentan at 62.5 mg once daily or every other day based on individual tolerability.
|
Beta-blockers |
EVG/COBI/TDF/FTC |
↑ beta-blockers possible |
Adjust beta-blockers according to clinical response. Beta-blocker dose may need to be decreased.
Some beta-blockers are metabolized via CYP450 pathway (e.g., metoprolol, timolol). Consider using other beta-blockers (e.g., atenolol, labetalol, nadolol, sotalol) as these agents are not metabolized by CYP450 enzymes.
|
Dihydropyridine and Non-Dihydropyridine Calcium Channel Blockers |
EVG/COBI/TDF/FTC |
↑ CCBs possible |
Co-administer with caution. Monitor for CCB efficacy and toxicities. |
Corticosteroids |
Dexamethasone |
EVG/COBI/TDF/FTC |
↓ EVG and COBI possible |
Co-administer with caution, monitor HIV virologic response |
Fluticasone (inhaled/intranasal) |
EVG/COBI/TDF/FTC |
↑ fluticasone possible |
Use alternative inhaled corticosteroid, particularly for long-term use |
Hepatitis C NS3/4A—Protease Inhibitors |
Boceprevir |
EVG/COBI/TDF/FTC |
No data |
Do not co-administer. |
RAL |
No significant effect |
No dosage adjustment necessary. |
Telaprevir |
EVG/COBI/TDF/FTC |
No data |
Do not co-administer. |
RAL |
RAL AUC ↑ 31%
Telaprevir ←→ |
No dosage adjustment necessary. |
Hormonal Contraceptives |
Hormonal contraceptives |
RAL |
No clinically significant effect |
Safe to use in combination |
Norgestimate/ethinyl estradiol |
EVG/COBI/TDF/FTC |
Norgestimate AUC, Cmax, Cmin ↑ >2-fold
Ethinyl estradiol AUC ↓ 25%, Cmin ↓ 44% |
The effects of increases in progestin (norgestimate) are not fully known and can include insulin resistance, dyslipidemia, acne, and venous thrombosis. Weigh the risks and benefits of the drug, and consider alternative contraceptive method. |
HMG-CoA Reductase Inhibitors |
Atorvastatin |
EVG/COBI/TDF/FTC |
↑ atorvastatin possible |
Titrate statin dose slowly and use the lowest dose possible. |
Lovastatin |
EVG/COBI/TDF/FTC |
Significant ↑ lovastatin expected |
Contraindicated. Do not co-administer. |
Pitavastatin
Pravastatin |
EVG/COBI/TDF/FTC |
No data |
No dosage recommendation |
Rosuvastatin |
EVG/COBI/TDF/FTC |
Rosuvastatin AUC ↑ 38% and Cmax ↑ 89% |
Titrate statin dose slowly and use the lowest dose possible. |
Simvastatin |
EVG/COBI/TDF/FTC |
Significant ↑ simvastatin expected |
Contraindicated. Do not co-administer. |
Immunosuppressants |
Cyclosporine
Sirolimus
Tacrolimus |
EVG/COBI/TDF/FTC |
↑ immunosuppressant possible |
Initiate with an adjusted immunosuppressant dose to account for potential increased concentrations and monitor for toxicities. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with specialist as necessary. |
Narcotics/Treatment for Opioid Dependence |
Buprenorphine |
EVG/COBI/TDF/FTC |
Buprenorphine: AUC ↑ 35%, Cmax ↑ 12%, Cmin ↑ 66%
Norbuprenorphine: AUC ↑ 42%,
Cmax ↑ 24%, Cmin ↑ 57%
|
No dosage adjustment necessary. Clinical monitoring is recommended. |
RAL |
No significant effect |
No dosage adjustment necessary. |
Methadone |
EVG/COBI/TDF/FTC |
No significant effect |
No dosage adjustment necessary. |
RAL |
No significant effect |
No dosage adjustment necessary. |
Neuroleptics |
Perphenazine
Risperidone
Thioridazine |
EVG/COBI/TDF/FTC |
↑ neuroleptic possible |
Initiate neuroleptic at low dose. Decrease in neuroleptic dose may be necessary. |
Phosphodiesterase Type 5 (PDE5) Inhibitors |
Avanafil |
EVG/COBI/TDF/FTC |
No data |
Co-administration is not recommended. |
Sildenafil |
EVG/COBI/TDF/FTC |
↑ sildenafil expected |
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 |
EVG/COBI/TDF/FTC |
↑ tadalafil expected |
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 EVG/COBI >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 EVG/COBI:
Stop tadalafil ≥24 hours before EVG/COBI initiation. Seven days after EVG/COBI initiation restart tadalafil at 20 mg once daily, and increase to 40 mg once daily based on tolerability.
|
Vardenafil |
EVG/COBI/TDF/FTC |
↑ vardenafil expected |
Start with vardenafil 2.5 mg every 72 hours and monitor for adverse effects of vardenafil. |
Sedatives/Hypnotics |
Buspirone |
EVG/COBI/TDF/FTC |
↑ buspirone possible |
Initiate buspirone at a low dose. Dose reduction may be necessary. |
Zolpidem |
EVG/COBI/TDF/FTC |
↑ zolpidem possible |
Initiate zolpidem at a low dose. Dose reduction may be necessary. |
Miscellaneous Interactions |
Colchicine |
EVG/COBI/TDF/FTC |
↑ colchicine expected |
Do not co-administer in patients with hepatic or renal impairment.
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.
For prophylaxis of gout flares:
If original regimen was colchicine 0.6 mg BID, the regimen should be decreased to 0.3 mg once daily. If regimen was 0.6 mg once daily, the regimen should be decreased to 0.3 mg every other day.
For treatment of familial Mediterranean fever:
Do not exceed colchicine 0.6 mg once daily or 0.3 mg BID.
|
Salmeterol |
EVG/COBI/TDF/FTC |
↑ salmeterol possible |
Do not co-administer because of potential increased risk of salmeterol-associated cardiovascular events. |