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HIV Meds Quarterly, 2011 Summer, Entire Issue

for Health Care Providers

HIV Meds Quarterly, 2011 Summer, Entire Issue

Buprenorphine/Naloxone with Raltegravir

An open-label pharmacokinetic (PK) study was conducted to identify possible interactions between buprenorphine/naloxone and raltegravir. Twelve HIV-uninfected volunteers who had been on at least 3 weeks of stable treatment with buprenorphine/naloxone were given raltegravir 400 mg BID. They underwent intensive PK sampling at steady state before and after the addition of raltegravir. Compared with baseline values, there was no significant change in Cmax or AUC of buprenorphine, its primary metabolite norbuprenorphine, or naloxone, and subjects did not experience opioid withdrawal symptoms. Raltegravir Cmax and AUC levels were not significantly different from those of historic controls. Patients on buprenorphine/naloxone may safely receive raltegravir with no dosage adjustments.

References

  1. Bruce RD, Moody K, Chodkowski D, et al. Pharmacokinetic interactions between buprenorphine/naloxone and raltegravir. In: Program and abstracts of the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention; July 17-20, 2011; Rome. Abstract MOPE176.

Pitavastatin with Lopinavir/Ritonavir

Pitavastatin, a newer statin, is metabolized primarily by glucuronidation rather than via the hepatic cytochrome P450 enzyme system, so it is expected to have fewer significant interactions with PIs than do other statins. To assess possible interactions between pitavastatin and lopinavir/ritonavir, an open-label, 2-way pharmacokinetic (PK) study was conducted with 24 HIV-uninfected subjects. Pitavastatin 4 mg QD was given on days 1-5 and 20-24, whereas lopinavir/ritonavir 400/100 mg BID was given on days 9-24. PK sampling was performed on days 5, 19, and 24.

Concurrent administration with lopinavir/ritonavir lowered the pitavastatin AUC by 20%, but there was no other significant change in any measured PK parameter (AUC, Cmax, T1/2) of pitavastatin, lopinavir, or ritonavir. Based on these data, pitavastatin may be coadministered with lopinavir/ritonavir without dosage adjustment.

References

  1. Morgan R, Campbell S, Suehira K, et al. Effects of steady-state lopinavir/ritonavir on the pharmacokinetics of pitavastatin in healthy adult volunteers. In: Programs and abstracts of the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. July 17-20, 2011; Rome. Abstract MOPE170.

Sustained Effect of Efavirenz on Rilpivirine Serum Concentrations

Efavirenz is a strong inducer of the CYP340 system and, because of its long half-life, may have lasting effects on the metabolism of other drugs even after it is discontinued. A recent study examined the pharmacokinetic effects of recent efavirenz exposure on the metabolism of rilpivirine, the recently approved NNRTI.

This open-label trial involved 17 healthy volunteers who received rilpivirine 25 mg daily for 14 days (period 1) followed by a 14- to 21-day washout, then efavirenz 600 mg daily for 14 days, followed immediately by rilpivirine 25 mg daily for 28 days (period 2). Pharmacokinetic evaluations were conducted during the two rilpivirine dosing periods. During period 2, when rilpivirine was initiated immediately after efavirenz discontinuation, levels of rilpivirine were reduced in comparison with levels for period 1: rilpivirine Cmin was 28% lower on days 1 and 14, and remained 25% lower on day 28, compared with the Cmin during period 1 of rilpivirine treatment.

Clinical bottom line

It is not currently known whether this prolonged reduction in rilpivirine Cmin will have any significant effect on virologic suppression or resistance development, but because it is likely that patients may be switched from efavirenz to rilpivirine, it is important to develop strategies for managing this interaction. Pending further study, direct switches from efavirenz to rilpivirine should be done cautiously and with close monitoring.

References

  1. Crauwels H, Vingerhoets J, Ryan R, et al. Pharmacokinetic parameters of once-daily TMC278 following administration of EFV in healthy volunteers. In: Program and abstracts of the 18th Conference on Retroviruses and Opportunistic Infections; February 27-March 2, 2011; Boston. Abstract 630.

Hepatitis C NS3 Protease Inhibitors and Antiretroviral Drugs

Boceprevir and telaprevir, 2 NS3 protease inhibitors for the treatment of hepatitis C, were recently approved by the FDA. These agents are CYP 3A4 substrates and inhibitors (as well as P-glycoprotein substrates), so they may have significant pharmacokinetic interactions with ARVs. To date, few studies have examined these potential drug-drug interactions, but 2 presentations at CROI earlier this year did provide data on select interactions.

Boceprevir1

Compared with monotherapy levels:

  • Efavirenz
    Boceprevir: AUC decreased 19%, Cmin decreased 44%
    EFV: AUC increased 20%, Cmax increased 11%
  • Ritonavir (100 mg QD)
    Boceprevir: AUC decreased 19%
  • Tenofovir
    TDF: Cmax increased 32%

Telaprevir2

Compared with monotherapy levels:

  • Efavirenz
    Telaprevir (dosed at 750 mg Q8H): AUC decreased 26%, Cmin decreased 47%
    EFV: no significant change (previous data)
    • With telaprevir 1,125 mg Q8H: telaprevir AUC decreased 18%,
      Cmin decreased 25%; EFV AUC decreased 18%, Cmin decreased 10%
  • Atazanavir/r (300/100 mg QD)
    Telaprevir: AUC decreased 20%, Cmin decreased 15%
    ATV: AUC increased 17%, Cmin increased 85%
  • Darunavir/r (600/100 mg BID)
    Telaprevir: AUC decreased 35%, Cmin decreased 32%
    DRV: AUC decreased 40%, Cmin decreased 42%
  • Fosamprenavir/r (700/100 mg BID)
    Telaprevir: AUC decreased 32%, Cmin decreased 30%
    Amprenavir: AUC decreased 47%, Cmin decreased 56%
  • Lopinavir/r (400/100 mg BID)
    Telaprevir: AUC decreased 54%, Cmin decreased 52%
    LPV: no significant changes
  • Tenofovir
    Telaprevir: no significant changes
    TDF: AUC increased 30%, Cmin increased 41%

Clinical bottom line

Unfortunately, interactions between telaprevir and many PIs and NNRTIs are expected to be clinically significant. Dosage adjustments may be possible in some cases (eg, increasing telaprevir dosage to compensate for the 3A4 induction attributable to efavirenz), but in many cases, appropriate adjustments have not been established. Some combinations should be avoided (eg, most PIs with telaprevir). Studies of boceprevir in combination with ARVs are lacking.


References

  1. Kasserra C, Hughes E, Treitel M, et al. Clinical pharmacology of BOC: metabolism, excretion and drug-drug interactions. In: Program and abstracts of the 18th Conference on Retroviruses and Opportunistic Infections; February 27-March 2, 2011; Boston. Abstract 118.
  2. van Heeswijk R, Vandevoorde A, Boogaerts G, et al. Pharmacokinetic interactions between ARV agents and the investigational HCV protease inhibitor TVR in healthy volunteers. In: Program and abstracts of the 18th Conference on Retroviruses and Opportunistic Infections; February 27-March 2, 2011; Boston. Abstract 119.

Lersivirine: A New NNRTI

Lersivirine (UK-453,061) is an investigational second-generation NNRTI that (in in vitro studies) is active against many HIV strains with NNRTI resistance mutations. At the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Rome this summer, researchers presented data on a multicenter Phase 2b study of lersivirine in treatment-naive individuals. Subjects (n = 193) were randomized to 1 of 2 dosages of lersivirine (500 mg QD or 750 mg QD) or to efavirenz, each in combination with tenofovir/emtricitabine. Mean baseline HIV RNA was 4.7 log10 copies/mL (one third of subjects had RNA levels of >100,000 copies/mL), and the median CD4 count was 320 cells/µL.

At 48 weeks, 79% of subjects in each of the lersivirine groups had HIV RNA levels of <50 copies/mL, as did 86% of subjects receiving efavirenz. The study was not powered for noninferiority analyses. In subjects with baseline HIV RNA of >100,000 copies/mL, the lersivirine groups had numerically lower overall rates of virologic suppression than the efavirenz group: 75% and 62% of the lersivirine 500 mg and 750 mg groups, respectively, achieved HIV RNA levels of <50 copies/mL through week 48, versus 82% of the efavirenz group. This difference was driven primarily by subjects from South African sites, in whom virologic suppression rates were sharply lower among lersivirine recipients with pretreatment viral loads of >100,000 copies/mL (50% and 38% in the 500 mg and 750 mg groups, respectively, versus 78% among efavirenz recipients); the presenter attributed this to adherence differences involving a small number of subjects (rather than to differences in HIV clade or other factors), but did not provide supporting data. CD4 increases were approximately 190 cells/µL in each treatment group.

Nausea, mostly Grade 1, occurred at higher rates in both lersivirine groups (23% and 42% in the 500 mg and 750 mg groups, respectively) than in the efavirenz group (13%), but neuropsychiatric symptoms and rash were noted more frequently in the efavirenz group. Lersivirine had quite neutral effects on serum lipids, whereas efavirenz increased all lipid parameters.

Clinical bottom line

Larger studies are needed to define more fully the efficacy and tolerability of lersivirine in initial therapy, and to characterize patient groups in which lersivirine would be best suited; Phase 3 studies are under way.

References

  1. Vernazza P, Wang C, Pozniak A, et al. Efficacy and safety of lersivirine (UK-453,061) vs. efavirenz in antiretroviral treatment-naive HIV-1-infected patients: week 48 primary analysis results from an ongoing, multicentre, randomised, double-blind, phase IIb trial (study A5271015). In: Program and abstracts of the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 17-20, 2011; Rome. Abstract TUAB0101.

Preexposure Prophylaxis with Oral Tenofovir or Tenofovir/Emtricitabine

Preexposure prophylaxis (PrEP) using oral tenofovir/emtricitabine was demonstrated last year, in the iPrEx study, to significantly reduce the risk of HIV infection in HIV-seronegative men who have sex with men (MSM). At the recent 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention, results from 2 large randomized, double-blind studies show that oral PrEP also is effective in preventing infection in heterosexual women and men.

The Partners PrEP study, conducted in Kenya and Uganda, enrolled nearly 5,000 serodiscordant heterosexual couples in which the HIV-infected partner was not eligible for ART. The seronegative partner was randomized to 1 of 3 study arms: tenofovir, tenofovir/emtricitabine, or placebo, to be taken once daily. With up to 36 months of follow-up, significantly fewer HIV infections were found in each of the 2 active ARV arms than in the placebo arm. Efficacy of tenofovir and of tenofovir/emtricitabine were 62% and 73%, respectively, with no statistical difference between the ARV arms, or between women and men.(1)

The TDF2 Study randomized 1,200 HIV-uninfected heterosexual women and men in Botswana to daily oral tenofovir/emtricitabine or to placebo. In this study, the protective efficacy of tenofovir/emtricitabine was 63% (p = .013), and although low numbers of seroconversions precluded definitive analyses by sex, PrEP appeared to be effective in both women and men.(2)

In general, PrEP was well tolerated. Adverse effects included mild nausea in the initial weeks of PrEP but no significant renal or other toxicity. Partners PrEP reported no difference in pregnancy rates in the study arms. Overall, study participants appeared to decrease their HIV risk behaviors over time.

Researchers from the iPrEx study also presented an update on their data at the conference. Particularly notable findings included additional evidence that PrEP efficacy is strongly related to adherence, and that PrEP did not appear to be effective in the subgroup of transgender women who have sex with men.(3)

Clinical bottom line

Partners PrEP and TDF2, as with the previously reported iPrEx study of oral tenofovir/emtricitabine in MSM and the Caprisa 004 study of tenofovir gel in heterosexual women, confirm that ARV-based preexposure prophylaxis can significantly lower the risk of sexual acquisition of HIV (though efficacy has not been demonstrated in transgender women and further study is needed). Importantly, Partners PrEP and TDF2 demonstrate that oral PrEP was effective in both women and men, in contrast to the FEM-PrEP study of high-risk, HIV-uninfected women, which was halted earlier this year because of lack of efficacy.

It should be noted that, in each of these studies, ARV PrEP was given in conjunction with comprehensive packages of risk-reduction interventions, including adherence support, risk-reduction counseling, condom provision, and HIV testing, and that these likely are important components in preventing HIV infection. Strategies for "real life" use of PrEP have yet to be explored.

There is no information at present on efficacy of oral PrEP in several important risk populations, such as injection drug users, and very limited information in some others (eg, transgender women). There also is no information on topical PrEP in MSM or transgender women. Further studies are under way. Although the role that PrEP will play in prevention strategies in the United States is not yet clear, it is likely to be a useful tool for appropriate individuals, and, importantly, one that will be in the control of the at-risk HIV-uninfected individual. The CDC is developing guidance on use of PrEP in the United States.

Note that the HPTN 052 study, also presented at the conference and recently published, demonstrated that ARV therapy, given to the HIV-infected partner in a serodiscordant relationship, reduced HIV transmission to the uninfected partner by 96%.(4)

References

  1. Baeten J. Antiretroviral pre-exposure prophylaxis for HIV-1 prevention among heterosexual African men and women: the Partners PrEP study. In: Program and abstracts of the 6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 17-20, 2011; Rome. Abstract MOAX0106.
  2. Thigpen MC, Kebaabetswe PM, Smith DK, et al; TDF2 Study Group. Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 study. In: Program and abstracts of the 6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 17-20, 2011; Rome. Abstract WELBC01.
  3. Grant R, McMahan V, Liu A, et al; iPrEx Study Team. Completed observation of the randomized placebo-controlled phase of iPrEx: daily oral FTC/TDF pre-exposure HIV prophylaxis among men and trans women who have sex with men. In: Program and abstracts of the 6th IAS Conference on HIV Pathogenesis, Treatment, and Prevention; July 17-20, 2011; Rome. Abstract WELBC04.
  4. Cohen MS, Chen YQ, McCauley M, et al; HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493-505.

Dolutegravir in Treatment-Naive Patients

The 48-week results of the SPRING-1 study of dolutegravir (S/GSK 572), an investigational integrase inhibitor, were presented at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. This Phase 2b partially blinded dose-ranging study randomized 205 treatment-naive subjects to 1 of 3 dosages of dolutegravir (10, 25, or 50 mg QD) or to efavirenz, coadministered with either tenofovir/emtricitabine (67%) or abacavir/lamivudine (33%). The mean baseline HIV RNA level was 4.46 log10 copies/mL (roughly 20% had HIV RNA levels of >100,000 copies/mL) and the mean baseline CD4 count was 324 cells/µL.

At week 48, 88-91% of subjects in the dolutegravir groups had HIV RNA levels of <50 copies/mL, compared with 82% of the efavirenz group. The rate of virologic nonresponse or rebound was the same in the 3 dolutegravir groups and the efavirenz group. Virologic failure (HIV RNA levels of >400 copies/mL) was seen in 3 subjects who received dolutegravir; no integrase inhibitor resistance mutations or phenotypic changes were detected in the 2 subjects that have been evaluated to date. Dolutegravir in general was associated with fewer adverse effects than efavirenz, and fewer ART discontinuations. Rash and neuropsychiatric adverse effects were not seen in dolutegravir recipients, and adverse lipid changes were minimal. However, small increases in serum creatinine (0.1-0.15 mg/dL) were observed in dolutegravir recipients; these declined toward baseline over time and were not associated with decreases in glomerular filtration rate (GFR) as measured by iohexol clearance (the purported mechanism is inhibition of tubular secretion of creatinine by dolutegravir). Increases in CD4 counts were not statistically different in the 4 treatment groups.

Clinical bottom line

These and earlier efficacy and safety data are very encouraging, and they offer the possibility of another once-daily option for initial treatment of HIV. Phase 3 study of dolutegravir is under way, using the dolutegravir 50 mg QD dosage. In addition, a pharmacokinetic study of fixed-dose combination tablets comprising dolutegravir/abacavir/lamivudine is in progress.

References

  1. Min S, Carrod A, Curtis L, et al. Safety profile of dolutegravir (DTG, S/GSK1349572), in combination with other antiretrovirals in antiretroviral (ART)-na´ve and ART-experienced adults from two phase IIb studies. In: Program and abstracts of the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 17-20, 2011; Rome. Abstract TUPE238.
  2. Van Lunzen J, Maggiolo F, Phung B, et al. Rapid, robust and sustained antiviral response with once-daily (QD) dolutegravir (DTG, S/GSK1349572), a next generation integrase inhibitor (INI) in combination therapy in antiretroviral-na´ve adults: 48 week results from SPRING-1 (ING112276). In: Program and abstracts of the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 17-20, 2011; Rome. Abstract TUAB0102.

Updates to the Database of ARV Drug Interactions

The following table summarizes recent additions to the HIV InSite Database of Antiretroviral Drug InteractionsLink will take you outside the VA website. VA is not responsible for the content of the linked site.. For a full description of the updates, including references to the studies from which the data were derived, go to the database, click on a specific drug name, and search for the interacting agent.

New ARV Interactions (April 2011-August 2011)
Drug OneDrug TwoClinical EffectsMechanismsManagement
Source: McNicholl I. HIV InSite Database of Antiretroviral Drug InteractionsLink will take you outside the VA website. VA is not responsible for the content of the linked site.. University of California San Francisco: Center for HIV Information; 2011
AtazanavirColchicineIncreased colchicine effectsInhibition of CYP450 3A4 by atazanavir/ritonavirFor treatment of gout, reduce colchicine dosage to 0.6 mg x 1 then 0.3 mg 1 hour later; do not repeat dosing earlier than 3 days thereafter

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 dosage to 0.3 mg QOD if on 0.6 mg QD prior to PI therapy
AtazanavirTelaprevir No dosage adjustment necessary
DarunavirColchicineIncreased colchicine effectsInhibition of CYP450 3A4 by darunavir/ritonavirFor treatment of gout, reduce colchicine dosage to 0.6 mg x 1 then 0.3 mg 1 hour later; do not repeat dosing earlier than 3 days thereafter

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 dosage to 0.3 mg QOD if on 0.6 mg QD prior to PI therapy
DarunavirMaraviroc Inhibition of CYP450 3A4 by darunavir/ritonavirNo dosage adjustment necessary
DarunavirRilpivirineIncreased rilpivirine effects No dosage adjustment necessary
Darunavir
600 mg BID with ritonavir 100 mg BID x 20 days
Telaprevir
750 mg Q8H x 10 days
Decreased telaprevir effects; decreased darunavir effects Do not coadminister

Alternative agents:

Atazanavir/ritonavir
Darunavir
600 mg BID with ritonavir 100 mg BID x 24 days
Telaprevir
1,125 mg Q12H x 4 days
Possible telaprevir effects; decreased darunavir effects Do not coadminister

Alternative agents:
Atazanavir/ritonavir
DidanosineRilpivirine No dosage adjustment necessary; administer didanosine on an empty stomach and at least 2 hours before or at least 4 hours after rilpivirine (which must be administered with a meal)
Efavirenz
600 mg QD x 16 days
Boceprevir
800 mg TID x 6 days
Possible decreased boceprevir effects Do not coadminister

Alternative agents:

Telaprevir
EfavirenzCisaprideIncreased cisapride effects (eg, cardiac arrhythmias) Do not coadminister

Alternative agents:

Metoclopramide
EfavirenzClarithromycin Induction of CYP450 3A4 by efavirenzDosage adjustment not established
Efavirenz
600 mg QD x 7 days, administered with tenofovir 300 mg QD x 7 days
Telaprevir
1,125 mg Q8H x 7 days
No dosage adjustment necessary
Efavirenz
600 mg QD x 20 days
Telaprevir
750 mg Q8H x 10 days
Decreased telaprevir effectsInduction of CYP450 3A4 by efavirenzIncrease telaprevir dosage to 1,125 mg Q8H
FosamprenavirColchicineIncreased colchicine effectsInhibition of CYP450 3A4 by fosamprenavir/ritonavirFor treatment of gout, reduce colchicine dosage to 0.6 mg x 1 then 0.3 mg 1 hour later; do not repeat dosing earlier than 3 days thereafter

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 dosage to 0.3 mg QOD if on 0.6 mg QD prior to PI therapy
Fosamprenavir
700 mg with ritonavir
100 mg BID x 20 days
Telaprevir
750 mg Q8H x 10 days
Decreased telaprevir effects; decreased amprenavir effects Do not coadminister

Alternative agents:
Atazanavir/ritonavir
Fosamprenavir
700 mg with ritonavir
100 mg BID x 24 days
Telaprevir
1,125 mg Q12H x 4 days
Do not coadminister

Alternative agents:
Atazanavir/ritonavir
IndinavirColchicineIncreased colchicine effectsInhibition of CYP450 3A4 by indinavirFor treatment of gout, reduce colchicine dosage to 0.6 mg x 1 then 0.3 mg 1 hour later; do not repeat dosing earlier than 3 days thereafter

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 dosage to 0.3 mg QOD if on 0.6 mg QD prior to PI therapy
Lopinavir/ritonavirColchicineIncreased colchicine effectsInhibition of CYP450 3A4 by lopinavir/ritonavirFor treatment of gout, reduce colchicine dosage to 0.6 mg x 1 then 0.3 mg 1 hour later; do not repeat dosing earlier than 3 days thereafter

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 dosage to 0.3 mg QOD if on 0.6 mg QD prior to PI therapy
Lopinavir/ritonavirRilpivirineIncreased rilpivirine effectsNo dosage adjustment necessary
Lopinavir/ritonavirTelaprevirDecreased telaprevir effects Do not coadminister

Alternative agents:
Atazanavir/ritonavir
NelfinavirColchicineIncreased colchicine effectsInhibition of CYP450 3A4 by nelfinavirFor treatment of gout, reduce colchicine dosage to 0.6 mg x 1 then 0.3 mg 1 hour later; do not repeat dosing earlier than 3 days thereafter

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 dosage to 0.3 mg QOD if on 0.6 mg QD prior to PI therapy
RilpivirineAcetaminophen No dosage adjustment necessary
RilpivirineAntacidsPossible decreased rilpivirine effectsDecreased gastric acidity, leading to impaired drug solubility and absorptionAdminister antacids at least 2 hours before or at least 4 hours after rilpivirine
RilpivirineAtorvastatin No dosage adjustment necessary
RilpivirineChlorzoxazone No dosage adjustment necessary
RilpivirineEthinyl estradiol/norethindrone acetate No dosage adjustment necessary
Rilpivirine
150 mg x 1
Famotidine
40 mg x 1 taken 2 hours before rilpivirine
Decreased rilpivirine effectsDecreased gastric acidity, leading to impaired drug solubility and absorptionAdminister H2 antagonist at least 12 hours before or at least 4 hours after rilpivirine
Rilpivirine
150 mg x 1
Famotidine
40 mg x 1 taken 4 hours after rilpivirine
No dosage adjustment necessary
Rilpivirine
150 mg x 1
Famotidine
40 mg x 1 taken 12 hours before rilpivirine
No dosage adjustment necessary
RilpivirineKetoconazoleDecreased ketoconazole effects No dosage adjustment necessary, but monitor for failure of antifungal therapy
RilpivirineMethadonePossible decreased methadone effects (eg, withdrawal) Monitor for signs and symptoms of methadone withdrawal; some patients may need an increase in the methadone dosage
RilpivirineOmeprazoleDecreased rilpivirine effectsDecreased gastric acidity, leading to impaired drug solubility and absorptionDo not coadminister

Alternative agents:

H2 antagonists, if administered at least 12 hours before or at least 4 hours after rilpivirine
RilpivirineRifabutinDecreased rilpivirine effects Do not coadminister
RilpivirineRifampinDecreased rilpivirine effectsInduction of CYP450 3A4 by rifampinDo not coadminister
RilpivirineSildenafil No dosage adjustment necessary
RilpivirineTenofovirPossible increased tenofovir effects No dosage adjustment necessary
RitonavirBoceprevirPossible decreased boceprevir effects; effect on ritonavir concentrations unknown Clinical significance unknown, especially when combined with other PIs
RitonavirQuinineIncreased quinine effectsPossible competitive displacement from CYP450 3A4 and inhibition of 2D6Avoid combination if possible; if combination must be used a potential 4-fold reduction in quinine dosage may be needed
Ritonavir
100 mg x 1
Telaprevir
750 mg x 1
Dosage adjustment not established
Ritonavir
100 mg Q12H x 14 days
Telaprevir
750 mg Q12H x 14 days
Dosage adjustment not established
SaquinavirColchicineIncreased colchicine effectsInhibition of CYP450 3A4 by saquinavirFor treatment of gout, reduce colchicine dosage to 0.6 mg x 1 then 0.3 mg 1 hour later; do not repeat dosing earlier than 3 days thereafter

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 dosage to 0.3 mg QOD if on 0.6 mg QD prior to PI therapy
Telaprevir
750 mg Q8H x 7 days
Tenofovir
300 mg QD x 7 days
Possible increased tenofovir effects Dosage adjustment not established
Telaprevir
1,125 mg Q8H x 7 days
Tenofovir
300 mg QD administered with efavirenz 600 mg QD x 7 days
Possible increased tenofovir effects No dosage adjustment necessary
Telaprevir
1,500 mg Q12H x 7 days
Tenofovir
300 mg QD administered with efavirenz 600 mg QD x 7 days
Possible decreased telaprevir effects Adjust telaprevir dosage to 1,125 mg Q8H when used with efavirenz
TenofovirBoceprevir No dosage adjustment necessary
TipranavirColchicineIncreased colchicine effectsInhibition of CYP450 3A4 by tipranavir/ritonavirFor treatment of gout, reduce colchicine dosage to 0.6 mg x 1 then 0.3 mg 1 hour later; do not repeat dosing earlier than 3 days thereafter

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 dosage to 0.3 mg QOD if on 0.6 mg QD prior to PI therapy

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