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Interactions Between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors

(Last updated:5/1/2015; last reviewed:30/7/2015)

#1547 Pharmacokinetic enhancers - COBI
August 2015 - Feedback

Cobicistat (COBI) is only available within Australia as the co-formulated Stribild (EVG/cobi/ TDF/FTC). It does not have TGA approval for use as a pharmacological booster with other antiretroviral agents.


Table 20b. Interactions between Integrase Strand Transfer Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors or Protease Inhibitors
ARV Drugs by Drug Class
INSTI
DTG EVG/cobi/TDF/FTC EVG (EVG must be given with a PI/r) RAL
NNRTIs
EFV
PK Data
With DTG 50 mg Once Daily:
DTG: AUC ↓ 57%, C
min ↓ 75%
↑ or ↓ EVG, cobi, EFV possible
↓ EVG expected RAL: AUC ↓ 36%
Dose

In patients without INSTI resistance:

• DTG 50 mg BID

In patients with certain INSTI-associated resistancea or clinically suspected INSTI resistance:

Consider alternative combination.

Do not co-administer.
Do not co-administer. Standard
ETR PK Data
With ETR 200 mg BID plus DTG 50 mg Once Daily:
DTG: AUC ↓ 71%, Cmin ↓ 88%

With ETR 200 mg BID plus DRV/r 600/100 mg BID plus DTG 50 mg Once Daily:
DTG: AUC ↓ 25%, Cmin ↓ 37%

With ETR 200 mg BID plus LPV/r 400 mg/100 mg BID plus DTG 50 mg Once Daily:
DTG: AUC ↑ 11%, Cmin ↑ 28%
↑ or ↓ EVG, COBI, ETR possible

No significant
interaction between
EVG/r and ETR

ETR: Cmin ↓ 17%

RAL: C
min ↓ 34%
 
Dose
Do not co-administer ETR and DTG without concurrently administering ATV/r, DRV/r, or LPV/r.

In Patients without INSTI Resistance
DTG 50 mg daily with ETR (concurrently with ATV/r, DRV/r, or LPV/r) 

In Patients with Certain INSTI-Associated Resistance or Clinically Suspected INSTI Resistance:
DTG 50mg BID with ETR (concurrently with ATV/r, DRV/r, or LPV/r)
Do not co-administer.

May coadminister EVG with ETR plus (ATV/r, DRV/r, or LPV/r) 

EVG:
• Standard dose depending on the concomitant PI (see below)

Standard doses
NVP
 
PK Data ↓ DTG possible 
↑ or ↓ EVG, COBI, NVP possible
↓ EVG possible No data
Dose Do not co-administer. Do not co-administer. Do not co-administer. Standard doses
RPV PK Data With DTG 50mg Daily:
DTG: AUC ↔, C
min ↑ 22%
RPV: AUC ↔, Cmin ↑ 21%
↑ or ↓ EVG, COBI, RPV possible
↑ RPV expected

RPV <->

RAL Cmin ↑ 27%

Dose
Standard doses Do not co-administer.

EVG:

• Standard dose depending on the concomitant PI (see below)

RPV:

• Standard dose

Standard doses
PIs
ATV/c PK Data No data ATV/c plus EVG/c: No data No data No data
Dose Standard doses Do not co-administer Do not co-administer Standard doses
ATV
+/-
RTV
 
PK Data With Unboosted ATV plus DTG 30 mg Once Daily
DTG: AUC↑ 91%, C
min ↑ 180%

With (ATV 300 mg plus RTV 100 mg) Once Daily plus DTG 30 mg Once Daily:
DTG: AUC ↑ 62%, Cmin ↑ 121%
↑ or ↓ EVG, COBI, ATV possible

EVG 85 mg with (ATV 300 mg plus RTV 100 mg) once daily:

• EVG AUC <-> and Cmin ↑ 38%

• ATV AUC and Cmin <->

With unboosted ATV:
RAL: AUC ↑ 72%

With ATV 300 mg plus RTV 100 mg Once Daily:
RAL: AUC ↑ 41%
Dose Standard Do not co-administer.

• EVG 85 mg once daily

• (ATV 300 mg plus RTV 100 mg) once daily

Standard doses
DRV/c PK Data No data

DRV/c plus EVG/c:

• ↓ EVG possible

No data No data
Dose Standard doses Do not co-administer Do not co-administer Standard doses
DRV/r
PK Data With (DRV 600 mg plus RTV 100 mg) BID plus DTG 30 mg Once Daily:
DTG: AUC ↓ 22%, C
min ↓ 38%
↑ or ↓ EVG, cobi, DRV possible

EVG 125 mg once
daily with (DRV 600 mg
plus RTV 100 mg) BID:

• EVG AUC and Cmin <->
• DRV AUC and Cmin <->

With DRV 600 mg plus RTV 100 mg BID:
RAL: AUC ↓ 29% and C
min ↑ 38%
Dose
Standard

Can use either once or twice daily dosing of DRV/r without dose adjustments.
Do not co-administer.

• EVG 150 mg once daily

• (DRV 600 mg plus RTV 100 mg) BID

Standard doses
FPV
+/-
RTV
PK Data With (FPV 700 mg plus RTV 100 mg) BID plus DTG 50 mg Once Daily:
DTG: AUC ↓ 35%, C
min ↓ 49%
↑ or ↓ EVG, cobi, FPV possible
No significant interaction with FPV and EVG FPV: No significant effect
Dose
DTG 50 mg BID in patients without INSTI resistance

Consider alternative combination in patients with certain INSTI-associated resistancea or clinically suspected INSTI resistance.
Do not co-administer.

• EVG 150 mg once daily

• (FPV 700 mg plus RTV 100 mg) BID

Standard
LPV/r PK Data With LPV/r 400 mg/100 mg BID plus DTG 30 mg Once Daily:
DTG: no significant effect
↑ or ↓ EVG, cobi, LPV possible

RTV and cobi have similar effects on CYP3A.

EVG 125 mg once daily with (LPV 400 mg plus RTV 100 mg) BID:

• EVG AUC ↑ 75% and Cmin ↑ 138%

• LPV AUC and Cmin <->

↓ RAL

↔ LPV/r
Dose
Standard

Can use either once or twice daily dosing of LPV/r without dose adjustments.
Do not co-administer.

• EVG 85 mg once daily

• (LPV 400 mg plus RTV 100 mg) BID

Standard doses
SQV/r
PK Data
No data ↑ or ↓ EVG, cobi, SQV possible

RTV and cobi have similar effects on CYP3A.
No data No data
Dose
Standard doses
Do not co-administer.
No dosage recommendation Standard
TPV/r PK Data With (TPV 500 mg plus 
RTV 200 mg) BID plus DTG 50 mg Once Daily:

DTG: AUC ↓ 59%, C
min ↓ 76%
↑ or ↓ EVG, cobi, TPV possible

RTV and cobi have similar effects on CYP3A.

EVG 200 mg once
daily with (TPV 500 mg
plus RTV 200 mg) BID:
• EVG AUC and Cmin <->
• TPV AUC and Cmin <->

With TPV 500 mg plus 
RTV 200 mg BID:

RAL: AUC ↓ 24%
Dose

In patients without INSTI resistance:

• DTG 50 mg BID

In patients with certain INSTIassociated resistancea or clinically suspected INSTI resistance:

Consider alternative combination.

Do not co-administer.

• EVG 150 mg once
daily
• (TPV 500 mg plus
RTV 200 mg) BID

Standard doses
a Refer to Tivicay product label for details.

Key to Acronyms: APV = amprenavir; ART = antiretroviral therapy; ATV/c = atazanavir/cobicistat, ATV = atazanavir; AUC = area under the curve; BID = twice daily; cobi= cobicistat; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; CYP = cytochrome P; DLV = delavirdine; DRV = darunavir; DRV/r = ritonavir-boosted darunavir; DTG = dolutegravir; EFV = efavirenz; EVG = elvitegravir; EVG = elvitegravir, ETR = etravirine; EVG/r = elvitegravir/ ritonavir, FDA = Food and Drug Administration; FPV = fosamprenavir; IDV = indinavir; INSTI = integrase strand transfer inhibitor; LPV = lopinavir; LPV/r = ritonavir-boosted lopinavir; MVC = maraviroc; NFV = nelfinavir; NVP = nevirapine; PI = protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQV = saquinavir; SQV/r = ritonavir-boosted saquinavir; TDF = tenofovir disoproxil fumarate; TID = three times a day; TPV = tipranavir



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