Tradução:

Carolina Palma
Catarina Pinheiro
Daniela Lobão
Joana C. Silva
Helena Barroso
Inês Bártolo
Patrícia Carvalho
Paula Matoso
Sheila Rocha
Victor Bezerra

Aviso Legal

página de impressão

Interacções medicamentosas

Leonie Meemken e Laura Dickinson

No sentido de prever ou evitar as interacções entra fármacos é necessária uma história completa da medicação, inluíndo remédios de ervanária e drogas de uso recreativo. Em particular as combinações que envolvem inductores (p. ex. rifampicin) e inibidores (p. ex. ketoconazole) podem resultar em concentrações plasmáticas desfavoráveis dos anti-retrovirais. Por exemplo, os inibidores aumentam a concentração de alguns fármacos de tal modo que se desenvolve toxicidades e os indutores podem reduzir a tal ponto que provoquem resistências. Se não existirem dados claros sobre as interacções entre fármacos devem considerar-se hipóteses teóricas no sentido de excluir interacções farmacológicas graves. É importante olhar para os efeitos colaterais da HAART. A HAART pode influenciar a co-medicação e vice-versa. Os ajustamentos de dose da ARV e/ou da co-medicação pode ser considerada. Para mais informação veja o website www.hiv-druginteractions.org

As concentrações plasmáticas também podem ser influenciadas por vários factores tais como a idade, o sexo, doenças hepáticas e o polimorfismo genético. A dosagem individual com o uso de TDM é, muitas vezes, importante.

Fármacos particulares

Comentários: as concentrações plasmáticas de fármacos são afectados por vários factores: etnicidade, insuficiência renal ou hepática, idade, sexo. A previsão de possíveis interacções pode ser discutível e nalguns casos ser útil a monitorização terapêutica de fármacos (TDM).

Abreviaturas usadas na tabela: AUC = área sob curva, /dia, 2x/dia, 3x/dia, ¯­ = AUC redução ou aumento, TDM = monitorização terapêutica de fármacos

3TC (Lamivudina, Epivir™; em Combivir™, Trizivir™, Kivexa™)
Abacavir (ABC, Ziagen™; em Trizivir™, Kivexa™)
Atazanavir (ATV, Reyataz™)
AZT (Zidovudin, Retrovir™; também Trizivir™, Combivir™)
D4T (Estavudina, Zerit™)
Darunavir (DRV, TMC 114, PrezistaTM)
DDI (Didanosina, Videx™)
Efavirenze (EFV, Sustiva™, Stocrin™)
Emtricitabina (FTC, Emtriva™; also in of Truvada™)
Fosamprenavir (FPV, Lexiva™, Telzir™)
Indinavir (IDV, Crixivan™)
Lopinavir/r (LPV/r, Kaletra™)
Nelfinavir (NFV, Viracept™)
Nevirapina (NVP, Viramune™)
Saquinavir (SQV, Invirase 500™)
T-20 (Enfuvirtide, Fuzeon™)
Tenofovir (TDF, Viread™; component of Truvada™)
Tipranavir (TPV/r, Aptivus™)

3TC (Lamivudina, Epivir™; em Combivir™, Trizivir™, Kivexa™)

Dose aprovada: 150 mg 2x/dia ou 300 mg/dia. Eliminação: renal

Bibliografia

1. Tseng A. www.tthhivclinic.com, General Hospital, Toronto 2006 Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com
2. US Department of Health and Human Services (DHHS) and National Institutes of Health (NIH). The living document: Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Retrieved April 14, 2004. www.aidsinfo.nih.gov.

Abacavir (ABC, Ziagen™; em Trizivir™, Kivexa™)

Dose aprovada: 300 mg 2x/dia ou 600 mg/dia. Metabolizada pela via da álcool dehidrogenase e glucuronidação

* HSR = reacção de hipersensibilidade

Bibliografia

1. Tseng A. www.tthhivclinic.com, General Hospital, Toronto 2004.
2. Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com
3. McDowell JA, Chittick GE, Pilati-Stevens C, et al. Pharmacokinetic interaction of abacavir and ethanol in HIV-infected adults. Antimicrob Agents Chemother 2000 ; 44: 1686-90. http://www.amedeo.com/lit.php?id=10817729
4. Aptivus™, Boehringer Ingelheim.

Atazanavir (ATV, Reyataz™)

Dose aprovada: ATV/RTV: 300/100 mg. Metabolismo: o atazanavir (ATV) é metabolizado primariamente pelo CYP3A4 e inibe o CYP3A4, CYP2C9, CYP1A2 e a UDP-glucuronosiltransferase(UGT)-1A1 [1].

Bibliografia

1. Tseng A. www.tthhivclinic.com, General Hospital, Toronto; 2004.
2. Kaul S, Bassi K, Damle BD, et al. Pharmacokinetic evaluation of the combination of atazanavir, enteric coated didanosine, and tenofovir disoproxil fumarate for a once daily antiretroviral regimen. Abstract A-1616, 43rd ICAAC 2003, Chicago.
3. Atazanavir. Bristol Myers-Squibb.
4. Preston S, Piliero P, O´Mara E, et al. Evaluation of steady-state interaction between atazanavir and efavirenz. Abstract 443, 9th CROI 2002, Seattle. http://63.126.3.84/2002/Abstract/13543.htm
5. Tackett D, Child M, Agarwala S, et al. Atazanavir: A summary of two pharmacokinetic drug interaction studies in healthy volunteers. Abstract 543, 10th CROI 2003, Boston.
6. Robinson BS, Riccardi KA, Gong YF, et al. BMS- 232632, a highly potent HIV protease inhibitor that can be used in in combination with other available antirtroviral agents. Antimicrob Agents Chemother 2000; 44: 2093-9. http://www.amedeo.com/lit.php?id=10898681
7. King J, Paul Lundy S, Kakuda TN et al. Pharmacokinetics of saquinavir with low-dose ritonavir or atazanavir twice daily in seronegativ volunteers. ASPIRE II. Abstract 586. 13th CROI 2006, Denver.
8. DeJesus E, Grinsztejn B, Rodriguez C, et al. Efficacy and safety of atazanavir with ritonavir or saquinavir vs lopinavir/ritonavir in patients who have experienced virologic failure on multiple HAART regimens: 48-Week results from BMS A1424-045. Abstract 54, 11th CROI 2004, San Francisco. http://www.retroconference.org/2004/cd/Abstract/547.htm
9. Boffito M, Kurowski M, Kruse G, et al. Atazanavir enhances saquinavir hard gel concentration in a ritonavir boosted once daily regimen. AIDS 2004; 18: 1292-7. http://www.amedeo.com/lit.php?id=15362661
10. Agarwala S, Russo R, Mummanemi V, et al. Steady-state pharmacokinetic interaction study of atazanavir with ritonavir in healthy subjects. Abstract H1716, 42nd ICAAC 2002, San Diego.
11. Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com
12. Mummaneni V, Randall D, Chabuel D, et al. Steady–state pharnacokinetic interaction study of atazanavir with clarithromycin in healthy subjects. Abstract H1717, 42nd ICAAC 2002, San Diego.
13. Benedek ICH, Joshi A, Fiske WD, et al. Pharmacokinetic studies in healthy volunteers with efavirenz and the macrolide antibiotics, azithromycin and chlarithromycin. Abstract 347, 5th CROI 1998, Chicago.
14. Richelson E. Pharmacokinetic interactions of antidepressiva. J Clin Psychiatry 1998; 59: 22-6. http://www.amedeo.com/lit.php?id=9720479
15. Pratt CM, Mason J, Russell T. Cardiovascular safety of fexofenadine HCL. Am J Cardiol 1999; 84: 278-9. http://www.amedeo.com/lit.php?id=10444240
16. Abernethy DR, Barbey JT. Loratadine and terfenadine interaction with nefazodone: Both antihistamines are associated with QT-prolongation. Clin Pharmacol Ther 2001; 69: 96-103. http://www.amedeo.com/lit.php?id=11240972
17. Rossi DR, Rathbun C, Slater LD. Symptomatic ortostasis with extended-release nifedipine and protease inhibitors. Ann Pharmacother 2002; 22: 1312-6. http://www.amedeo.com/lit.php?id=12389881
18. O´Mara E, Randall D, Uderman H, et al. Steady-state pharmacokinetics interaction study between BMS-232632 and ketoconazole in healthy subjects. Abstract 1646, 40th ICAAC 2000, Toronto.
19. Fichtenbaum CJ, Gerber JG, Rosenkranz S. Pharmacokinetic interaction between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. AIDS 2002; 16: 569-77. http://www.amedeo.com/lit.php?id=11873000
20. Antoniou T, Lin-in Tseng. Interactions between recreational drugs and antiretroviral agents. Annals Pharmacother 2002; 36: 1598-613. http://www.amedeo.com/lit.php?id=12243611
21. CDC. Notice to Readers: Updated guidelines for the use of rifamycins for the treatment of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR 2004; 53:37. http://www.amedeo.com/lit.php?id=11795500
22. Lam M, Ignoffo R, Meibohm B. Ein Leitfaden für klinisch-relevante Arzneimittel-Interaktionen in der Onkologie.
23. Ghofrani HA, Olschewski H, Seeger W, et al. Sildenafil for treatment of severe pulmonary hypertension and commencing right-heart failure. Pneumologie 2002; 56: 665-72. http://amedeo.com/lit.php?id=12442206
24. Alexander CS, Montaner JG, Langridge S, et al. Interaction between atazanavir/Ritonavir (ATV/r) and nevirapine (NVP) is observed in a clinical setting. Abstract P275, 7th Int Congr Drug Ther HIV Inf 2004, Glasgow.
25. Roter Hand Brief,  Bristol Myers-Squibb, December 2004
26. Kurowski M, Breske A, Kruse G, et al. Atazanavir (ATV) enhances through concentrations of nelfinavir (NFV) and its M8 metabolite in a treatment regimen without ritonavir (RTV). Abstract 90, 6th Int Worksh Clin Pharmacol HIV Ther 2005, Quebec.
27. Guttanti M, Raffaella de Pascalis C, Seminari E, et al. Pharmacokinetics of amprenavir given once or twice a day when combined with atazanavir in heavily pre-treated patients. AIDS 2003, 17: 2669-70. http://www.amedeo.com/lit.php?id=14685066
28. Colombo S, Buclin T, Franc C. Ritonavir-boosted atazanavir-lopinavir combination: a pharmacokinetic interaction study of total, unbound plasma and cellular exposures. Antivir Ther. 2006;11:53-62.
29. Agarwala S, Child M, Wang Y et al. Pharmacokinetic effect of famotidine on atazanavir with and without ritonavir in healthy subjects. Abstract 11, 6th Int Worksh Clin Pharmacol HIV Ther 2005, Quebec.
30. Wire MB et al. The pharmacokientic interaction between fosamprenavir/ritonavir and atazanavir in healthy adult subjects (APC 10018). Abstract 4.3/9. 10th EACS Conference 2005, Dublin.
31. Agarwala S, Eley T, Villegas C, et al. Pharmacokinetic interaction between tenofovir and atazanavir co-administered with ritonavir in healthy subjects. Abstract 16, 6th Int Worksh Clin Pharmacol HIV Ther 2005, Quebec.
32. Friedland G, Andrews L, Schreibman T et al. Lack of an effect of atazanavir on steady-state pharmcokinetics of methadone in patients chronically treated for opiate addiction. AIDS 2005; 19:1635-41. http://amedeo.com/lit.php?id=16184033
33. Sekar V, De Marez T, Spinosa-Guzman S et al. Pharmacokinetic Interaction between TMC114/RTV and Atazanavir in healthy volunteers. Abstract PE4/3.4, 10th EACS Conference 2005, Dublin.
34. Pham P, Parson T, Flexner C et al. Beneficial Pharmacokinetic Interaction between Atazanavir and Lopinavir/r. 13th CROI Denver 2006, abstract 585.
35. Vezina HE, Tschampa JM, Jennings C et al. Steady-state pharmacokinetic of lopinavir/ritonavir coadministered with atazanavir in HIV-infected subjects. Abstract 48. 7th Int Worksh Clin Pharmacol HIV Ther 2005, Lissabon.
36. Sabo JP, Elgadi M, Wruck J et al. The pharmacokinetic interaction between atazanavir/ritonavir and steady-state tipranavir/ritonavir in healthy volunteers. Abstract 41, 7th Int Worksh Clin Pharmacol HIV Ther 2005, Lissabon.

AZT (Zidovudin, Retrovir™; também Trizivir™, Combivir™)

Dose aprovada: 250 ou 300 mg 2x/dia. Metabolismo: via da glucuronidação, eliminação: renal

Bibliografia

1.         Tseng A. www.tthhivclinic.com, General Hospital, Toronto, 2006.

2.         Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com

3.         Product information: Retrovir™. Glaxo Smithkline.

4.         Polis MA, Piscitelli SC, Vogel S, et al. Chlarithromycin lowers plasma zidovudine levels in persons with HIV-infection. Antimicrob Agents Chemother 1997; 41: 1709-14. http://www.amedeo.com/lit.php?id=9257746

5.         US Department of Health and Human Services (DHHS) and National Institutes of Health (NIH). The living document: Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Retrieved April 14, 2004. www.aidsinfo.nih.gov.

6.         Foscavir™. Astra Zeneca.

7.         Cooper DA, Pehrson PO, Pedersen C, et al. The efficacy and safety of zidovudine alone or as co-therapy with acyclovir for the treatment of AIDS and AIDS-related complex: a double-blind randomized trial. European-Australian Collaborative Group. AIDS 1993; 7: 197-207. http://www.amedeo.com/lit.php?id=8096703

8.         Bach MC. Possible drug interaction during therapy with azidothymidine and acyclovir for AIDS [letter]. N Engl J Med 1987; 317: 547. http://www.amedeo.com/lit.php?id=3468354

9.         Hochster H, Dieterich D, Bozzette S, et al. Toxicity of combined ganciclovir and zidovudine for cytomegalovirus disease associated with AIDS. Ann Intern Med 1990; 113: 111-7. http://www.amedeo.com/lit.php?id=2163228

10.     Cimoch PJ, Lavelle J, Pollard R, et al. Pharmacokinetics of oral ganciclovir alone and in combination with zidovudine, didanosine and probenecid in HIV-infected subjects. JAIDS 1998; 17: 227-34. http://www.amedeo.com/lit.php?id=9495222

11.     Ruedy J, Schlechter M, Montaner JS. Zidovudine for early HIV-infection: who, when, and how? Ann Intern Med 1990; 112: 721-3.

12.     Sim SM, Higgard PG, Sales SD, et al. Effect of ribavirin on zidovudine efficacy and toxicity in vitro: a concentration-dependent interaction. AIDS Res Hum Retr 1998; 14: 1661-7.

13.     Kornhauser DM, Petty BG, Hendrix CW, et al. Probenecid and zidovudine metabolism. Lancet 1989; 2: 473-5. http://www.amedeo.com/lit.php?id=2570186

14.     Antoniou T, Lin-in Tseng. Interactions between recreational drugs and antiretroviral agents. Ann Pharmacother 2002; 36: 1598-613. http://www.amedeo.com/lit.php?id=12243611

15.      Roszko PJ, Curry K, Brazina B, et al. Standard doses of efavirenz, zidovudine, tenofovir, and didanosine may be given with tipranavir/ritonavir. Abstract 865, 2nd IAS 2003, Paris. http://www.aegis.com/conferences/2ndIASHIVPT /865.html

D4T (Estavudina, Zerit™)

Dose aprovada: 30-40 mg 2x/dia (< 60 kg: 30 mg 2x/dia). Eliminação: 34-43 % renal

Bibliografia

1.      Tseng A. www.tthhivclinic.com, General Hospital, Toronto, 2004.

2.      Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com

3.      Foisy MM, Slayter KL, Hewitt RG, et al. Pancreatitis during intravenous pentamidine therapy in an AIDS patient with prior exposure to didanosine. Ann Pharmacother 1994; 28: 1025-8. http://www.amedeo.com/lit.php?id= 7803875

4.      Landau A, Batisse D, Piketty C, et al. Lack of interference between ribavirin and nucleoside analogues in HIV/HCV co-infected individuals undergoing concomitant antiretroviral and anti-HCV combination therapy. AIDS 2000; 14: 1857-8. http://www.amedeo.com/lit.php?id=10985327

5.      Hittinger G. Mitochondrial toxicity in HIV/HCV co-infected patients treated with ribavirin, interferon alpha and antiretroviral therapy. Abstract TuPeB4516, XIV Int AIDS Conference 2002, Barcelona.

6. Smith DM, Puoti M, Sulkowski, et al. Symptomatic hyperlactatemia during a large hepatitis C treatment trial in HIV/HCV co-infected participants on stable antiretroviral therapy. Abstract MoOrB1059, XIV Int AIDS Conference 2002, Barcelona.

Darunavir (DRV, TMC 114, Prezista^TM)

Dose (aprovada nos EUA): TMC 114/r: 600/100 mg 2x/dia com alimentos [5]. Metabolismo: TMC 114 é metabolizado pelo isoenzima CYP3A4 [5]. Quando potenciado pelo, TMC 114 passa a inibidor do CYP3A4.

Bibliografia

1. Hoetelmans R, Marien K, De Pauw M et al. Pharmacokinetic Interaction between TMC114/RTV and Tenofovir in healthy volunteers. XVth World AIDS Conference 2004, Bangkok.
2. Sekar V, De Marez T, Spinosa-Guzman S et al. Pharmacokinetic Interaction between TMC114/RTV and Atazanavir in healthy volunteers. Abstract PE4/3.4, 10th European AIDS Conference 2005, Dublin.
3. Sekar VJ , Hoetelmans R , De Marez T et al. Pharmakokinetics of TMC114: Effect of Omeprazole and Ranitidin. Poster 2.10, 6^th Inter Worksh on Clin Pharmacol of HIV-Ther 2005, Quebec
4. Hoetelmans R, Lasure A, Koester A et al. The effect of TMC114, a potent next generation HIV Protease Inhibitor with low-dose Ritonavir on Atorvastatin Pharmakokinetics. Abstract H-885, 44^th ICAAC 2004, Washington
5. US product information on Prezista®.

DDI (Didanosina, Videx™)

Dose aprovada: < 60 kg: 250 mg /dia, > 60 kg: 400 mg /dia. Metabolismo: Hipoxantina-oxidase; eliminação: 30-50 % renal

Bibliografia

1.         Tseng A. www.tthhivclinic.com, General Hospital, Toronto, 2004.

2.         US Department of Health and Human Services (DHHS) and National Institutes of Health (NIH). The living document: Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Retrieved April 14, 2004.

3.         Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com

4.         Moyle G, Maitland D, Hand J, et al. Early virological failure in persons with viral loads > 100.000 cps/ml and CD4 counts < 200/mm3 receiving DDI/tenofovir/ efavirenz as initial therapy: Results from a randomised comparative trial. Abstract H-566, 44th ICCAC 2004, Washington.

5.         Kearney BP, Isaacson E, Sayre J, et al. Didanosine and tenofovir DF drug-drug interaction: assessment of didanosine dose reduction. Abstract 533, 10th CROI 2003, Boston.

6.         Liang D, Breaux K, Rodriguez-Barradas M, et al. Allopurinol increases didanosine adsorption in HIV-infected patients. Abstract A498, 41st ICAAC 2001, Chicago.

7.         Sahai J, Garber G, Gallicano K, et al. Effects of the antacids in didanosine tablets on dapsone pharmacokinetics. Ann Intern Med 1995; 123: 584-7. http://www.amedeo.com/lit.php?id=7677298

8.         Cimoch PJ, Lavelle J, Pollard R, et al. Pharmacokinetics of oral ganciclovir alone and in combination with zidovudine, didanosine and probenecid in HIV-infected subjects. JAIDS 1998; 17: 227-34. http://www.amedeo.com/lit.php?id=9495222

9.         Jung D, Griffy K, Dorr A, et al. Effect of high dose oral ganciclovir on didansosine disposition in HIV-positive patients. J Clin Pharmacol 1998; 38: 1057-62. http://www.amedeo.com/lit.php?id=9824788

10.     Frascino RJ, Gaines Griffy K, Jung D, et al. Multiple dose crossover study of IV ganciclovir induction dose (5 mg/kg IV q12h) and didanosine (200 mg po q12h) in HIV-infected persons. Abstract A-27, 3th CROI 1995, San Francisco.

11.     Rainey PM, Friedland G, McCance-Katz EF, et al. Interaction of Methadone with didanosine and stavudine. JAIDS 2000; 24: 241-8. http://www.amedeo.com/lit.php?id=10969348

12.     Foisy MM, Slayter KL, Hewitt RG, et al. Pancreatitis during intravenous pentamidine therapy in an AIDS patient with prior exposure to didanosine. Ann Pharmacother 1994; 28: 1025-8. http://www.amedeo.com/lit.php?id=7803875

13.     Product nformation: Videx™, Bristol Myers-Squibb.

14.     Roszko PJ, Curry K, Brazina B, et al. Standard doses of efavirenz, zidovudine, tenofovir, and didanosine may be given with tipranavir/ritonavir. Abstract 865, 2nd IAS 2003, Paris. http://www.aegis.com/conferences/2ndIASHIVPT /865.html

Efavirenze (EFV, Sustiva™, Stocrin™)

Dose aprovada: 600 mg /dia. Metabolismo: efavirenze é sobretudo metabolizado pelo CYP2B6 e menos pelo CYP3A4 e CYP1A2. In vitro o EFV é um indutor do CYP3A4 e fraco inibidor do CYP3A4, -2C9 e -2C19 [1]. Nota: Pode dar falsos testes urinários positivos para Canabis com método CEDIA DAU multinível THC [2].

Bibliografia

1.         Tseng A. www.tthhivclinic.com, General Hospital, Toronto, 2004.

2.         Sustiva™, Bristol-Myers Squibb.

3.         Veldkamp AI, Harris M, Montaner JSG, et al. The steady-state pharmacokinetics of efavirenz und nevirapine when used in HIV-1 infected patients. J Infect Dis 2001; 184: 37-42. http://www.amedeo.com/lit.php?id=11398107

4.         Wire MB, Ballow C, Preston SL, et al. Pharmacokinetics and safety of GW433908 and ritonavir, with and without efavirenz, in healthy volunteers. AIDS 2004, 18: 897-907. http://www.amedeo.com/lit.php?id=15060437

5.         Klein C, ZHU T, Chiu YL et al. Effect of efavirenz on lopinavir/ritonavir pharmacokinetics from a new tablet formulation. Abstract 4.3/2, 10^th EACS 2005, Dublin.

6.         Alvarez-Amao D, Pace W, Gold M. Switch from high to low dose amprenavir in combination with efavirenz and ritonavir. Abstract 2.7, 3rd Int Worksh Clin Pharmacol HIV Ther 2002, Washington.

7.         Preston S, Piliero P, O´Mara E, et al. Evaluation of steady-state interaction between atazanavir and efavirenz. Abstract 433, 9th CROI 2002, Seattle.

8.         Reyataz™, Bristol-Myers Squibb.

9.         Aarnoutse RE, Grintjes KJT, Telgt DS, et al. The influence of efavirenz on the pharmacokinetics of a twice daily combination of indinavir and low-dose ritonavir in healthy subjects. JAIDS 2003; 34: 134-9. http://www.amedeo.com/lit.php?id=11823758

10.     Boyd MA, Aarnoutse RE, Ruxrungtham K, et al. Pharmacokinetics of indinavir/ritonavir (800/100 mg) in combination with efavirenz (600 mg) in HIV-infected subjects. JAIDS 2003; 34: 134-9. http://www.amedeo.com/lit.php?id=14526202

11.     Bertz R, Lam W, Hsu A, et al. Assessment of the pharmacokinetic interaction between ABT – 378/r and efavirenz in healthy volunteers and in HIV+subjects. Abstract 424, 40th ICAAC 2000, Toronto.

12.     Jorga K, Buss NE. Pharmacokinetic drug interaction with saquinavir sgc. Abstract 339, 39th ICAAC 1999, San Francisco.

13.     Hendrix CW, Fiske WD, Fuchs EJ, et al. Pharmacokinetics of the triple combination of saquinavir, ritonavir and efavirenz in HIV+subjects. Abstact 424, 11th CROI 2000, San Francisco.

14.     van Heeswijk RP, Cooper C, Gallicano A, et al. The pharmacokinetics of SQV/RTV 400/400 mg BID before, and after short- and long term co-administration of efavirenz 600 mg QD. Abstract 7.4, 3rd Int Worksh Clin Pharmacol HIV-Ther 2002, Washington.

15.     Lopez-Cortes LF, Viciana P, Ruiz-Valderas R, et al. Pharmacokinetics, efficacy and safety of once-daily saquinavir-sgc plus low-dose ritonavir (1200/100 mg) in combination with efavirenz in HIV-pretreated patients. Abstract 441, 9th CROI 2002, Seattle.

16.     Fiske WD, Benedek IH, White SJ, et al. Pharmacokinetic interaction between efavirenz and nelfinavir mesylate in healthy volunteers. Abstract 349, 5th CROI 1998, Chicago.

17.     Benedek ICH, Joshi A, Fiske WD, et al. Pharmacokinetic studies in healthy volunteers with efavirenz and the macrolide antibiotics, azithromycin and clarithromycin. Abstract 347, 5th CROI 1998, Chicago.

18.     Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com

19.     Pratt CM, Mason J, Russell T. Cardiovascular safety of fexofenadine HCL. Am J Cardiol 1999; 84: 278-9. http://www.amedeo.com/lit.php?id=10335761

20.     Abernethy DR, Barbey JT. Loratadine and terfenadine interaction with nefazodone: Both antihistamines are associated with QT-prolongation. Clin Pharmacol Ther 2001; 69: 96-103. http://www.amedeo.com/lit.php?id=11240972

21.     Vfend™, Pfizer.

22.     Michalets E: Update: Clinically Significant Cytochrome P-450 Drug Interaction. Ann Pharmacother 1998; 18: 84-112. http://www.amedeo.com/lit.php?id=9469685

23.     Rossi DR, Rathbun C, Slater LD. Symptomatic ortostasis with extended-release nifedipine and protease inhibitors. Ann Pharmacother 2002; 22:1312-16. http://www.amedeo.com/lit.php?id=12389881

24.     Gerber JG, Fichtenbaum CJ, Rosenkranz S, et al. Efavirenz is a significant inducer of simvastatin and atorvastatin metabolism: results of ACTG A5108 study. Abstract 603, 11th CROI 2004, San Francisco.

25.     Fichtenbaum CJ, Gerber JG, Rosenkranz S. Pharmacokinetic interaction between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. AIDS 2002; 16: 569-77. http://www.amedeo.com/lit.php?id=11873000

26.     Doser N, Kubli S, Telenti A. Efficacy and safety of fluvastatin in hyperlipidemic protease inhibitor-treated HIV-infected patients. AIDS 2002; 16: 1982-3. http://www.amedeo.com/lit.php?id=12351967

27.     Antoniou T, Lin-in Tseng. Interactions between recreational drugs and antiretroviral agents. Ann Pharmacother 2002; 36: 1598-613. http://www.amedeo.com/lit.php?id=12243611

28.     Tseng AL, Foisy MM. Significant interactions with new antiretrovirals and psychotropic drugs. Ann Pharmacother 1999; 33: 461-73. http://www.amedeo.com/lit.php?id=10332538

29.     Centers for Disease Control and Prevention (CDC). Notice to Readers: Updated guidelines for the use of rifamycins for the treatment of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR; 2004; 53: 37. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4909a4.htm

30.     Lam M, Ignoffo R, Meibohm B. Ein Leitfaden für klinisch-relevante Arzneimittel-Interaktionen in der Onkologie, Institute for Applied Healthcare Science.

31.     Ghofrani HA, Olschewski H, Seeger W, et al. Sildenafil for treatment of severe pulmonary hypertension and commencing right-heart failure. Pneumologie 2002; 56: 665-72. http://www.amedeo.com/lit.php?id=12442206

32.     Sekar V, DePauw M, Marien K et al. No clinically significant pharmacokinetic drug-drug interaction is observed between the HIV protease inhibitor TMC 114 and the NNRTI Efavirenz. Abstract 55. 7^th Int Worksh Clin Pharmacol HIV Ther 2005, Lissabon.

33.     van Leth F, Phanuphak P, Ruxrungtham K, et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet 2004, 363:1253-63. http://www.amedeo.com/lit.php?id=15094269

34.     Roszko PJ, Curry K, Brazina B, et al. Standard doses of efavirenz, zidovudine, tenofovir, and didanosine may be given with tipranavir/ritonavir. Abstract 865, 2nd IAS 2003, Paris.

35.     Tseng A, Nguyen ME, Cardella C, et al. Probable interaction between efavirenz and Cylosporine. AIDS 2002,16:505-6.

36.     Sheehan NL, Richter C, Koopmans P et al. Efavirenz is not associated with subtherapeutic EFV concentrations whem given concomitantly with rifampin. Abstract 28. 6th Int Worksh Clin Pharmacol HIV Ther 2005, Quebec.

37.     Almond L, Gibbons S, Davies G et al. A retrospective survey of the Liverpool TDM service: Factors influencing Efavirenz concentrations in patients taking Rifampicin. Abstract 19. 6th Int Worksh Clin Pharmacol HIV Ther 2005, Quebec.

Emtricitabina (FTC, Emtriva™; also in of Truvada™)

Dose aprovada: 200 mg /dia. Eliminação: renal

Fosamprenavir (FPV, Lexiva™, Telzir™)

Dose aprovada: FPV/r: 700/100 mg 2x/dia. Metabolismo: O FPV é uma pro-fármaco do amprenavir (APV) e é hidrolisado no epitélio intestinal pela fosfatases celulares durante a absorção no composto activo. O APV é metabolizado pelo  CYP3A4 é é um inibidor do CYP3A4 (tão potente como o indinavir e o nelfinavir). Além disso há referências que sugerem que o APV é também um indutor do CYP3A4 [35]. Salvo a interacção entre o APV e o LPV/r, o efeito indutor pode não se observar com a dose usada em geral para a potenciação.

Bibliografia

1.         Tseng A. http://www.tthhivclinic.com/, General Hospital, Toronto, 2006.

2.         Agenerase™, GlaxoSmithKline.

3.         Telzir™, GlaxoSmithKline.

4.         Piscitelli S, Bechtel C, Sadler B, et al. The addition of a second protease inhibitor eliminates amprenavir-efavirenz drug interaction and increases plasma amprenavir concentrations. Abstract 78, 7th CROI 2000, San Francisco. http://www.retroconference.org/2000/abstracts/78.htm

5.         Alvarez-Amao D, Pace W, Gold M. Switch from high to low dose amprenavir in combination with efavirenz and ritonavir. Abstract 2.7, 3rd Int Worksh Clin Pharmacol HIV Ther, 2002, Washington.

6.         Wire MB, Ballow C, Preston SL, et al. Pharmacokinetics and safety of GW433908 and ritonavir, with and without efavirenz, in healthy volunteers. AIDS 2004, 18: 897-907. http://www.amedeo.com/lit.php?id=15060437

7.         Goujard C, Meynard JL, Choudet N, et al. Steady-state pharmacokinetics of amprenavir 600 mg BID and ritonavir 100 mg BID with or without NNRTI in HIV-1 infected patients. Abstract S92, 5th Int Congr Drug Ther HIV Inf 2000, Glasgow. http://www.aegis.com/conferences/hiv5/P268.html

8.         DeJesus E, Piliero P, Summers K, et al. Evaluation of the pharmacokinetik drug interaction between fosamprenavir (FPV), FPV plus ritonavir (RTV) and nevirapine (NVP) in HIV-infected patients (APV10014). Abstract A447, 44th ICAAC 2004, Washington.

9.         Kashuba ADM, Tierey C, Downey GF, et al. Combining fosamprenavir, 908 with lopinavir/ritonavir in HIV-1 infected adults in substantial reduction in amprenavir and lopinavir concentrations: pharmacokinetic results from Adult ACTG Protocol A5143. Abstract 855, 43rd ICAAC 2003, Chicago.

10.     Wire MB, Naderer OJ, Masterman AL, et al. The pharmacokinetic interaction between GW433908 and lopinavir/ritonavir (APV10011 and APV 10012). Abstract 612, 11th CROI 2004, San Francisco. http://www.amedeo.com/lit.php?id=15060437

11.     Corbett AH, Davidson L, Park JJ, et al. Dose separation strategies to overcome the pharmacokinetic interaction of a triple protease inhibitor regimen containing fosamprenavir, lopinavir and ritonavir. Abstract 611, 11th CROI 2004, San Francisco.

12.     Khanlou H, Graham E, Brill M, et al. Drug interaction between amprenavir and lopinavir/ritonavir in salvage therapy. AIDS 2002; 16: 797-8. http://www.amedeo.com/lit.php?id=11964539

13.     Bertz RJ, Foit C, Ashbrenner E, et al. Effect of amprenavir on the steady-state pharmacokinetics of lopinavir/ritonavir in HIV+ and healthy subjects. Abstract A1823, 42nd ICAAC 2002, San Diego.

14.     Taburet AM, Raguin G, Le Tiec C, et al. Interaction between Amprenavir and lopinavir –ritonavir combination in heavily pretreated patients infected by HIV. Clin Pharmacol Ther 2004; 75: 310-23. http://www.amedeo.com/lit.php?id=15060509

15.     Mauss S, Scholten S, Wolf E, et al. A prospective, controlled study assessing the effect of lopinavir on amprenavir concentrations boosted by ritonavir. HIV Med 2004; 5: 15-7. http://www.amedeo.com/lit.php?id=14731164

16.     Wynn Vezina HE, Brundage RC, Bushman L, et al. Pharmacologic management of the drug-drug interaction between lopinavir/ritonavir and amprenavir. Abstract 609, 11th CROI 2004, San Francisco. http://www.retroconference.org/2004/cd/PDFs/609.pdf

17.     Wire MB et al. The pharmacokientic interaction between fosamprenavir/ritonavir and atazanavir in healthy adult subjects (APC 10018). Abstract 4.3/9. 10th EACS Conference 2005, Dublin

18.     Guttanti M, Raffaella de Pascalis C, Seminari E, et al. Pharmacokinetics of amprenavir given once or twice a day when combined with atazanavir in heavily pre-treated patients. AIDS 2003, 17: 2669-70. http://www.amedeo.com/lit.php?id=14685066

19.     Sadler BM, Gillotin C, Lou Y, et al. Pharmacokinetic study of human immunodeficiency virus protease inhibitors used in combination with amprenavir. Antimicrob Agents Chemother 2001, 45: 3663-8. http://www.amedeo.com/lit.php?id=11709366

20.     Boffito M, Dickinson L, Hill A, et al. Steady state pharmacokinetics of saquinavir hard gel/fosamprenavir 1000/700 plus 100 und 200 mg of Ritonavir twice daily in HIV+ Patients. Abstract 608, 11th CROI 2004, San Francisco.

21.     Wolfe PR, Anderson PG, Gunawan S. Simultaneous administration of amprenavir and saquinavir does not appear to lower plasma levels of either agent when coadministered with low dose ritonavir. Abstract 7.11, 3rd Int Worksh Clin Pharmacol HIV Ther 2002, Washington.

22.     Ford SL, Wire MB, Lou Y, et al. The effect of antacids and ranitidine on the pharmacokinetic of GW433908 (APV10007). Abstract A-1606, 43rd ICAAC 2003, Chicago.

23.     Wire MB, Baker KL, Moore KHP, et al. The pharmacokinetic interaction of GW 433908 with atorvastatin and 908/ritonavir with atorvastatin (APV 10013). Abstract A1622, 43rd ICAAC 2003, Chicago.

24.     Hendrix C, Wakeford J, Wire MB, et al. Pharmacokinetic and pharmacodynamic evaluation of methadone enantiomers following coadministration with amprenavir in opiod-dependent subjects. Abstract 1649, 40th ICAAC 2000, Toronto.

25.     Centers for Disease Control and Prevention (CDC). Notice to Readers: Updated guidelines for the use of rifamycins for the treatment of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors 2004. MMWR; 53: 37. http://www.amedeo.com/lit.php?id=11795500

26.     Nandwani R, Gourlay Y. Possible Interaction between sildenafil and HIV combination therapy. Lancet 1999; 353: 840. http://www.amedeo.com/lit.php?id=10459981

27.     Hugen PWH, Burger DM, Brinkman K, et al. Carbamazepine-indinavir interaction causes antiretroviral therapy failure. Ann Pharmacother 2000; 34: 465-70. http://www.amedeo.com/lit.php?id=10772431

28.     Pratt CM, Mason J, Russell T. Cardiovascular safety of fexofenadine HCL. Am J Cardiol 1999; 84: 278-9. http://www.amedeo.com/lit.php?id=10335761

29.     Abernethy DR, Barbey JT. Loratadine and terfenadine interaction with nefazodone: Both antihistamines are as sociated with QT-prolongation. Clin Pharmacol Ther 2001; 69: 96-103. http://www.amedeo.com/lit.php?id=11240972

30.     Kurowski M, Walli R, Breske  et al. Co-administration of tenofovir 300 mg QD with fosamprenavir/ritonavir 1400/100 mg QD or 1400/200 mg QD does not affect amprenavir pharmacokinetics. Abstract 10, 6th Int Worksh Clin Pharmacol HIV Ther  2005, Quebec.

31.     Peytavin G, Rouault A, Agher R, et al. Plasma concentrations of amprenavir, ritonavir and tenofovir in HIV-infected patients treated with fosamprenavir / ritonavir (700 / 100 mg BID) and tenofovir (300 mg QD) containing regimen. Abstract 32, 6th Int. Worksh Clin Pharmacol HIV Ther 2005, Quebec.

32.     Shelton MJ, Wire MB, Lou Y, et al. Co-administration of esomeprazole (ESO) with fosamprenavir (FPV) has no impact on steady-state plasma amprenavir (APV) pharmacokinetics (APV10031). Abstract 24, 6th Int Worksh Clin Pharmacol HIV Ther 2005, Quebec.

33.     Blenke A, van der Lee M, Verweij-van Wissen C, et al. Combined use of paroxetine and fosamprenavir / ritonavir: a pharmacokinetic interaction study in healthy volunteers. Abstract 13, 6th Int  Worksh Clin Pharmacol HIV Ther 2005, Quebec.

34.     Leith J, Walmsley S, Katlama C, et al. Pharmacokinetics and safety of tipranavir/ritonavir alone or in combination with saquinavir, amprenavir, or lopinavir: interim analysis of BI1182.51. Abstract 34, 5th Int Worksh Clin Pharmacol HIV-Ther 2004, Rome..

Indinavir (IDV, Crixivan™)

Dose aprovada: IDV: 800 mg 3x/dia, IDV/r: 800/100 mg 2x/dia. Metabolismo: IDV é metabolizado primariamente pelo CYP3A4 e é um inibidor do CYP3A4. Para uma absorção óptima é necessário um pH ácido. O IDV deve ser tomado com refeição ligeira [1].

Bibliografia

1.         Tseng A. http://www.tthhivclinic.com/, General Hospital, Toronto, 2004.

2.         Crixivan™, MSD.

3.         Shelton MJ, Mei JH, Hewitt RG, et al. If taken 1 hour before indinavir, didanosine does not affect indinavir exposure, despite persistent buffering effects. Antimicrob Agents Chemother 2001; 45: 298-300. http://www.amedeo.com/lit.php?id=11120981

4.         Damle BD, Mummaneni V, Kaul S, et al. Lack of effect of simultaneously administered didanosine encapsulated enteric coated formulation (Videx EC) on oral absorption of indinavir, ketoconazol or ciprofloxacin. Antimicrob Agents Chemother 2002; 46: 385-91. http://www.amedeo.com/lit.php?id=11796346

5.         Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com

6.         Aarnoutse RE, Burger DM, Hugen PWH, et al. A Pharmacokinetic Study to investigate the influence of efavirenz on a BID indinavir 800 mg/ritonavir 100 mg in healthy volunteers. Abstract 423, 40th ICAAC 2000,Toronto.

7.         Saah A, Winchell G, Rhodes R, et al. Multiple-dose pharmacokinetics and tolerability of indinavir with ritonavir and efavirenz combinations in a once daily regimen in healthy volunteers (Merck 093). Abstract 284, 5th Int Congr Drug Ther HIV Inf 2000, Glasgow. http://www.aegis.com/conferences/hiv5/P284.html

8.         Burger DM, Prins JM, van der Ende ME, et al. The effect of nevirapine on the pharmakokinetics of indinavir/ritonavir 800/100 mg BID. JAIDS 2004; 35: 97-8. http://www.amedeo.com/lit.php?id=14707800

9.         Crommentuyn KML, van Heeswijk RPG, Veldkamp AI, et al. Nevirapine once daily versus twice daily: implications for drug-drug interactions. Abstract 1.11, 2nd Int Worksh Clin Pharmacol HIV Ther 2001, Noordwijk.

10.     Reyataz™, Bristol Myers-Squibb.

11.     Sadler BM, Gillotin C, Lou Y, et al. Pharmacokinetic study of human immunodeficiency virus protease inhibitors used in combination with amprenavir. Antimicrob Agents Chemother 2001; 45: 3663-8. http://www.amedeo.com/lit.php?id=11709366

12.     Riddler S, Havlir D, Sqires KE, et al. Coadministration of indinavir and nelfinavir in human immunodeficiency virus type 1-infected adults: safety, pharmacokinetics and antiretroviral activity. Antimicrob Agent Chemother 2002; 46: 3877-82. http://www.amedeo.com/lit.php?id=12435691

13.     Mc Crea J, Buss N, Stone J, et al. Indinavir-saqinavir single dose pharmacokinetic study. 4th CROI 1997, Washington.

14.     Manion D, Merill DP, Hirsch MS. Combination drug regimens against multidrug resistant HIV-1 in vitro. 4th CROI 1997, Washington.

15.     Buss N. Saquinavir soft gel capsule (Fortovase): Pharmacokinetics and drug interactions. Abstract 354, 5th CROI 1998, Chicago.

16.     Tseng A, Phillips E, Antoniou A, et al. Steady-state pharmacokinetics and tolerability of indinavir when administered with lopinavir/r in antiretroviral-experienced subjects. Abstract 8.10, 4th Int Worksh Clin Pharmacol HIV Ther 2003, Cannes.

17.     Bertz R, Foit C, Ashbrenner E, et al. Assessment of the steady-state pharmacokinetic interaction of lopinavir/ritonavir with either indinavir or saquinavir in healthy subjects. Abstract A1822, 42nd ICAAC 2002, San Diego.

18.     Burger DM, Schmitz K, Schneider K, et al. Pharmacokinetics of lopinavir and reduced dose indinavir as a part of salvage therapy regimen. 4th Abstract 8.2, 4th Int Worksh Clin Pharmacol HIV Ther 2003, Cannes.

19.     Harris M, Alexander C, Ting L, et al. Rescue therapy with indinavir 600 mg twice daily and lopinavir/ritonavir: baseline resistance, virologic response and pharmacokinetics. Abstract P170, 6th Int Congr Drug Ther HIV Inf 2002, Glasgow.

20.     Isaac A, Taylor S, Rubin G, et al. Lopinavir /ritonavir combined with twice daily indinavir: pharmacokinetics in blood, CSF and semen (the Protect Study). Abstract 531, 10th CROI 2003, Boston.

21.     DHHS: Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Retrieved April 14, 2004. http://www.amedeo.com/lit.php?id=11364535

22.     Burger DM, Hugen PW, Kroon FP, et al. Pharmacokinetic interaction between the proton pump inhibitor omeprazole and the HIV protease inhibitor indinavir. AIDS 1998; 12: 2080-2. http://www.amedeo.com/lit.php?id=9814882

23.     Hugen PWH, Burger DM, Brinkmann K, et al. Carbamazepine-indinavir interaction causes antiretroviral failure. Ann Pharmacother 2000; 34: 465-70. http://www.amedeo.com/lit.php?id=10772431

24.     Pratt CM, Mason J, Russell T. Cardiovascular safety of fexofenadine HCL. Am J Cardiol 1999; 84: 278-9. http://www.amedeo.com/lit.php?id=10335761

25.     Abernethy DR, Barbey JT. Loratadine and terfenadine interaction with nefazodone: Both antihistamines are associated with QT-prolongation. Clin Pharmacol Ther 2001; 69: 96-103. http://www.amedeo.com/lit.php?id=11240972

26.     Michalets E: Update: Clinically Significant Cytochrome P-450 Drug Interaction. Ann Pharmacother 1998; 18: 84-112. http://www.amedeo.com/lit.php?id=9469685

27.     Brinkmann K, Huysmans F, Burger DM. Pharmacokinetic interaction between Saquinavir and Cyclosporine. Ann Intern Med 1998; 129: 914-5. http://www.amedeo.com/lit.php?id=9867740

28.     Piscitelli SC, Vogel S, Figg WD, et al. Alteration in indinavir clearance during interleukin-2 infusions in patients infected with the human immunodeficieny virus. Ann Pharmacother 1998; 18: 1212-6. http://www.amedeo.com/lit.php?id=9855318

29.     Lanzafame M, Trevenzoli M, Faggian F, et al. Interaction between levothyroxine and indinavir in a patient with HIV infection. Infection 2002; 30: 54-8. http://www.amedeo.com/lit.php?id=11876520

30.     Centers for Disease Control and Prevention (CDC). Notice to Readers: Updated guidelines for the use of rifamycins for the treatment of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR; 2004; 53: 37. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4909a4.htm

31.     Merry C, Barry MG, Ryan M, et al. Interaction of sildefanil and indinavir when coadministered to HIV-positive patients. AIDS 1999; 13: 101-7. http://www.amedeo.com/lit.php?id=10546851

32.  Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. Abstract A-1610, 43rd ICAAC 2003, Chicago.

Lopinavir/r (LPV/r, Kaletra™)

Dose aprovada: LPV/r 400/100 mg 2x/dia. Metabolismo: O LPV tem uma formulação conjunta com ritonavir é é metabolizado primariamente pelo CYP3A4. O LPV/r é um potente inibidor do CYP3A4 e induz a glucuronidação quer do CYP2C9 quer do CYP2C19 [1].

Bibliografia

1.         Tseng A. www.tthhivclinic.com, General Hospital, Toronto, 2006

2.         Kaletra™, Abbott.

3.         Bertz R, Lam W, Hsu A, et al. Assessment of the pharmacokinetic interaction between ABT-378/ritonavir and efavirenz in healthy volunteers and in HIV + subjects. Abstract 424, 40th ICAAC 2000, Toronto.

4.         Bertz R, Foit C, Burt D, et al. Assessment of the Effect of Nevirapine on the Pharmacokinetics of Lopinavir/Ritonavir after Multiple Dosing in HIV-infected Adults. Abstract TUPEB4565, XIV Int AIDS Conf 2002, Barcelona.

5.         Telzir™, GlaxoSmithKline.

6.         Kashuba ADM, Tierey C, Downey GF, et al. Combining fosamprenavir, 908 with lopinavir/Ritonavir in HIV-1 infected adults in substantial reduction in Amprenavir and lopinavir concentrations: pharmakokinetic results from Adult ACTG Protocol A5143. Abstract H-855a , 43rd ICAAC 2003, Chicacgo.

7.         Wire MB, Naderer OJ, Masterman AL, et al. The pharmacokinetic interaction between GW433908 and lopinavir/ritonavir (APV10011 and APV 10012). Abstract 612, 11th CROI 2004, San Francisco. http://www.retroconference.org/2004/cd/PDFs/612.pdf

8.         Corbett AH, Davidson L, Park JJ, et al. Dose separation strategies to overcome the pharmacokinetic interaction of a triple protease inhibitor regimen containing fosamprenavir, lopinavir and ritonavir. Abstract 611, 11th´CROI 2004, San Francisco.

9.         Khanlou H, Graham E, Brill M, et al. Drug interaction between amprenavir and lopinavir/ritonavir in salvage therapy. AIDS 2002; 16: 797-8. http://www.amedeo.com/lit.php?id=11964539

10.     Bertz RJ, Foit C, Ashbrenner E, et al. Effect of amprenavir on the steady-state pharmacokinetics of lopinavir/ritonavir in HIV+ and healthy subjects. Abstract A1823, 42nd ICAAC 2002, San Diego.

11.     Taburet AM, Raguin G, Le Tiec C, et al. Interaction between Amprenavir and lopinavir – ritonavir combination in heavily pretreated patients infected by HIV. Clin Pharmacol Ther 2004; 75: 310-23. http://www.amedeo.com/lit.php?id=15060509

12.     Mauss S, Scholten S, Wolf E, et al. A prospective, controlled study assessing the effect of lopinavir on amprenavir concentrations boosted by ritonavir. HIV Med 2004; 5: 15-7. http://www.amedeo.com/lit.php?id=14731164

13.     Wynn Vezina HE, Brundage RC, Bushman L, et al. Pharmacologic management of the drug-drug interaction between lopinavir/ritonavir and amprenavir. Abstract 609, 11th CROI 2004, San Francicsco.

14.     Colombo S, Buclin T, Franc C. Ritonavir-boosted atazanavir-lopinavir combination: a pharmacokinetic interaction study of total, unbound plasma and cellular exposures. Antivir Ther. 2006;11:53-62.

15.     Tseng A, Phillips E, Antoniou A, et al. Steady-state pharmacokinetics and tolerability of indinavir when administered with lopinavir/r in antiretroviral-experienced subjects. Abstract 8.10, 4th Int Worksh Clin Pharmacol HIV Ther 2003, Cannes.

16.     Bertz R, Foit C, Ashbrenner E, et al. Assessment of the steady-state pharmacokinetic interaction of lopinavir/ritonavir with either indinavir or saquinavir in healthy subjects. Abstract A1822, 42nd ICAAC 2002, San Diego.

17.     Burger DM, Schmitz K, Schneider K, et al. Pharmacokinetics of lopinavir and reduced dose indinavir as a part of salvage therapy regimen.  Abstract 8.2, 4th Int Worksh Clin Pharmacol HIV Ther 2003, Cannes.

18.     Burger DM, Schmitz K, Schneider K, et al. Rescue therapy with indinavir 600 mg twice daily and lopinavir/ritonavir: baseline resistance, virologic response and pharmacokinetics. Abstract P170, 6th Int Congr Drug Ther HIV Inf 2002, Glasgow.

19.     Isaac A, Taylor S, Rubin G, et al. Lopinavir /ritonavir combined with twice daily indinavir: pharmacokinetics in blood, CSF and semen (the Protect Study). Abstract 531, 10th CROI 2003, Boston.

20.     La Porte CJ, Wasmuth JC, Schneider K, et al. Lopinavir/ritonavir plus saquinavir in salvage therapy; pharmacokinetics, tolerability and efficacy. AIDS 2003; 17: 1700-2. http://www.amedeo.com/lit.php?id=12853756

21.     Ribera E, Diaz M, Pou L, et al. Steady-state pharmacokinetics of double boosting regimen of lopinavir, plus minidose Ritonavir, plus Saquinavir soft-gel in HIV-infected adults. Abstract TUPE4545, XIV Int AIDS Conf 2002, Barcelona.

22.     Staszewski S, Dauer B, Von Hentig N, et al. The LopSaq study: 24 week analysis of the double protease inhibitor salvage regimen containing lopinavir plus saquinavir without any additional antiretroviral therapy. Abstract 583, 2nd IAS Conference on HIV Pathogenesis and Treatment 2003, Paris.

23.     Stefan C, Von Hentig N, Kourbeti I, et al. Saquinavir drug exposure is not impaired by the boosted double protease inhibitor combination of lopinavir/Saquinavir. AIDS 2004; 18: 503-8. http://www.amedeo.com/lit.php?id=15090803

24.     Klein C, Bertz R, Ashbrenner E, et al. Assessment of the multiple dose pharmacokinetic interaction of lopinavit/ritonavir with nelfinavir. Abstract 536, 10th CROI 2003, Boston.

25.     Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com

26.     Michalets E. Update: Clinically Significant Cytochrome P-450 Drug Interaction. Ann Pharmacother 1998; 18: 84-112. http://www.amedeo.com/lit.php?id=9469685

27.     Benedek ICH, Joshi A, Fiske WD, et al. Pharmacokinetic studies in healthy volunteers with efavirenz and the macrolide antibiotics, azithromycin and chlarithromycin. Abstract 347, 5th CROI 1998, Chicago.

28.     Tseng AL, Foisy MM. Significant Interactions with New Antiretrovirals and Psychotropic Drugs. Ann Pharmacother 1999; 33: 461-73. http://www.amedeo.com/lit.php?id=10332538

29.     Pratt CM, Mason J, Russell T. Cardiovascular safety of fexofenadine HCL. Am J Cardiol 1999; 84: 278-9. http://www.amedeo.com/lit.php?id=10335761

30.     Abernethy DR, Barbey JT. Loratadine and terfenadine interaction with nefazodone: Both antihistamines are associated with QT-prolongation. Clin Pharmacol Ther 2001; 69: 96-103. http://www.amedeo.com/lit.php?id=11240972

31.     Rossi DR, Rathbun C, Slater LD. Symptomatic ortostasis with extended-release nifedipine and protease inhibitors. Ann Pharmacother 2002; 22: 1312-6. http://www.amedeo.com/lit.php?id=12389881

32.     Fichtenbaum CJ, Gerber JG, Rosenkranz S. Pharmacokinetic interaction between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. AIDS 2002; 16: 569-77. http://www.amedeo.com/lit.php?id=11873000

33.     Carr RA, Andre AK, Bertz RJ, et al. Concomitant administration of ABT-378/ritonavir results in a clinically important pharmacokinetic interaction with atorvastatin but not pravastatin. Abstract 1644, 40th ICAAC 2000, Toronto.

34.     Doser N, Kubli S, Telenti A et al. Efficacy and safety of fluvastatin in hyperlipidemic protease inhibitor-treated HIV-infected patients. AIDS 2002; 16: 1982-3. http://www.amedeo.com/lit.php?id=12351967

35.     Dube MP, Sprecher D, Henry WK, et al. Preliminary guidelines for the evaluation and management of dyslipidemia in HIV-infected adults receiving antiretroviral therapy. Recommendations of the adult ACTG Cardiovascular Disease Focus Group. Clin Infec Dis 2000; 31: 1216-24. http://www.amedeo.com/lit.php?id=11073755

36.     Antoniou T, Lin-in Tseng. Interactions between recreational drugs and antiretroviral agents. Annals Pharmacother 2002; 36: 1598-613. http://www.amedeo.com/lit.php?id=12243611

37.     Centers for Disease Control and Prevention (CDC). Notice to Readers: Updated guidelines for the use of rifamycins for the treatment of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR; 2004; 53: 37. http://www.amedeo.com/lit.php?id=11795500

38.     Lam M, Ignoffo R, Meibohm B: Ein Leitfaden für klinisch-relevante Arzneimittel-Interaktionen in der Onkologie, Institute for Applied Healthcare Science.

39.     Ghofrani HA, Olschewski H, Seeger W et al. Sildenafil for treatment of severe pulmonary hypertension and commencing right-heart failure. Pneumologie. 2002; 56: 665-72. http://www.amedeo.com/lit.php?id=12442206

40.     DICenzo R, Petersen D, Cruttenden K, et al. Effect of Valproic Acid Coadministration on Plasma Efavirenz and Lopinavir Concentrations in Human Immunodeficiency Virus-Infected Adults. Antimicrobial Agents and Chemotherapy 2004; 48: 4328-31. http://www.amedeo.com/lit.php?id=15504860

41.     Breilh D, Rouzes A, Djabarouti S et al. Pharmacokinetic drug interaction of lopinavir/ritonavir in combination with tenofovir in experienced HIV+patients. Abstract A-445, 44th ICAAC 2004, Washington.

42.     Kearney BP, Mittan A, Sayre J, et al. Pharmacokinetic drug interaction and long term safety profile of tenofovir DF and lopinaivr/ritonavir. Abstract A-1617, 43rd ICAAC 2003, Chicago. http://www.natap.org/2003/ICAAC/day5_2.htm

43.     Jain AB, Venkataramanan R, Eghtesad B, et al. Effect of coadministered lopinavir and ritonavir (Kaletra) on tacrolimus blood concentration in liver transplantation patients. Liver Transpl 2003, 9:954-60.  http://amedeo.com/lit.php?id=12942457

44.     Bertz RJ, Chiu YL, Naylor C et al. Lack of Effect of gastric acid reducing agents on lopinavir/ritonavir plasma concentrations in HIV-infected patients. Abstract 201, 7th Int Congr Drug Ther HIV Inf 2004, Glasgow.

45.     Negredo E, Moltó J, Burger D et al. Lopinavir/ritonavir plus nevirapine as a nucleoside-sparing approach in antiretroviral-experienced patients (NEKA study). JAIDS 2005; 38: 47-52. http://www.amedeo.com/lit.php?id=15608524

46.     Vezina HE, Tschampa JM, Jennings C et al. Steady-state pharmacokinetic of lopinavir/ritonavir coadministered with atazanavir in HIV-infected subjects. Abstract 48. 7th Int Worksh Clin Pharmacol HIV Ther 2005, Lissabon.

47.     Van der Lee MJ, Dawood L, ter Hofstede H, et al. The effect of lopinavir / ritonavir on the pharmacokinetic of lamotrigine in healthy subjects. Abstract 12, 6th Int Worksh Clin Pharmacol HIV Ther 2005, Quebec.

48.     Faivre L, T. H., Vincent I, Abbara C, et al (2005). Potent drug interactions between tacrolismus and lopinavir / ritonavir therapy in HIV-infected liver transplant recipients. Abstract 26, 6th Int  Worksh Clin Pharmacol HIV Ther 2005, Quebec.

49.     Leith J, Walmsley S, Katlama C, et al. Pharmacokinetics and safety of tipranavir/ritonavir alone or in combination with saquinavir, amprenavir, or lopinavir: interim analysis of BI1182.51. Abstract 34 , 5th Int Worksh Clin Pharmacol HIV-Ther 2004, Rome.

50.     Klein C, ZHU T, Chiu YL et al. Effect of efavirenz on lopinavir/ritonavir pharmacokinetics from a new tablet formulation. Abstract 4.3/2, 10th EACS 2005, Dublin.

51.     Pham P, Parson T, Flexner C et al. Beneficial Pharmacokinetic Interaction between Atazanavir and Lopinavir/r. Abstract 585.13th CROI 2006, Denver.

52.  US product information on Prezista®.

Nelfinavir (NFV, Viracept™)

Dose aprovada: 1.250 mg 2x/dia. Metabolismo: O nelfinavir (NFV) é primariamente metabolizado pelo CYP2C19mais do que pelo CYP3A4 e CYP2D6. O NFV é um inibidor do CYP3A4. É metabolizado num metabolito activo M8 (aprox. 30 % do composto principal), com potência igual ao NLF. O M8 é metabolizado pelo CYP3A4 [1,2].

Bibliografia

1.         Tseng A. www.tthhivclinic.com, General Hospital, Toronto, 2004.

2.         Viracept™, Hoffmann-La Roche.

3.         Kruse G, Esser S, Stocker H, et al.Tenofovir does not impair the pharmacokinetic of Nelfinavir in HIV-infected patients. Abstract A446, 44th ICCAC 2004, Washington.

4.         Lee CA, Liang BH, Wu EY, et al. Prediction of nelfinavir mesylate (Viracept) clinical drug interactions based on in vitro human P450 metabolism studies. 4th CROI 1997, Washington.

5.         Smith PF, Robbins G, Shafer R, et al. Effect of efavirenz on the pharmacokinetics of nelfinavir and M8 in naïve, HIV-infected subjects receiving long-term HAART therapy. Abstract 148, 10th CROI 2003, Boston.

6.         Vilaro J, Mascaro J, Colomer J, et al. The pharmacokinetics of combination therapy with nelfinavir plus nevirapine in HIV-positive patients. Abstract A497, 41st ICAAC 2001, Chicago.

7.         Klein C, Bertz R, Ashbrenner E, et al. Assessment of the multiple dose pharmacokinetic interaction of lopinavit/ritonavir with nelfinavir. Abstract 536, 10th CROI 2003, Boston.

8.         Robinson BS, Riccardi KA, Gong YF, et al. BMS- 232632, a highly potent human immunodeficieny virus protease inhibitor that can be used in in combination with other available antirtroviral agents. Antimicrob Agents Chemother 2000; 44: 2093-9. http://www.amedeo.com/lit.php?id=10898681.

9.         Sadler BM, Gillotin C, Lou Y, et al. Pharmacokinetic study of human immunodeficiency virus protease inhibitors used in combination with amprenavir. Antimicrob Agents Chemother 2001; 45: 3663-8. http://www.amedeo.com/lit.php?id=11709366

10.     Riddler S, Havlir D, Sqires KE, et al. Coadministration of indinavir and nelfinavir in human immunodeficiency virus type 1-infected adults: safety, pharmacokinetics and antiretroviral activity. Antimicrob Agent Chemother 2002; 46: 3877-82. http://www.amedeo.com/lit.php?id=12435691

11.     Buss N. Saquinavir soft gel capsule (Fortovase): Pharmacokinetics and drug interactions. Abstract 354, 5th CROI 1998, Chicago.

12.     Merry C, Barry MG, Mulcahy FM, et al. Saquinavir pharmacokinetics alone and in combination with nelfinavir in HIV infected patients. Abstract 352, 5th CROI 1998, Chicago.

13.     Gallicano K, Sanai J, Kravcik S, et al. Nelfinavir increases plasma exposure of saquinavir in hard gel capsule in HIV+ patients. Abstract 353, 5th CROI 1998, Chicago.

14.     Stocker H, Kruse G, Arasteh K, et al. Pharmacokinetic interaction between saquinavir/r und nelfinavir in HIV-Infected patients. Abstract A-454, 44th ICAAC 2004, Washington.

15.     Amsden GW, Foulds G. The pharmacokinetics of azithromycin and nelfinavir when coadministered in healthy volunteers. Abstract 1651, 40th ICAAC 2000, Toronto.

16.     Pratt CM, Mason J, Russell T. Cardiovascular safety of fexofenadine HCL. Am J Cardiol 1999; 84: 278-9. http://www.amedeo.com/lit.php?id=10335761

17.     Abernethy DR, Barbey JT. Loratadine and terfenadine interaction with nefazodone: Both antihistamines are associated with QT-prolongation. Clin Pharmacol Ther 2001; 69: 96-103. http://www.amedeo.com/lit.php?id=11240972

18.     Schippers EF, Eugen PW, den Hartigh J, et al. No drug drug interaction between nelfinavir and indinavir mefloquine in HIV-1 infected patients. AIDS 2000; 14: 2794-5. http://www.amedeo.com/lit.php?id=11125902

19.     Kerr B, Yuen G, Daniels R, et al. Strategic approach to nelfinavir mesylate (NFV) drug interactions involving CYP3A metabolism. 4th National CROI 1997, Washington.

20.     Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com

21.     Hsyu PH,Smith MD, Lillibridge JH, et al. Pharmacokinetic interactions between nelfinavir and 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors atorvastatin and simvastatin. Antimicrob Agents Chemother 2001; 45: 3445-50. http://www.amedeo.com/lit.php?id=11709322

22.     Smith PF, Booker BM, Difrancesco R, et al. Effect of methadone or LAAM on the Pharmacokinetics of nelfinavir & M8. Abstract A-491, 41st ICAAC 2001, Chicago.

23.     Centers for Disease Control and Prevention. Updated guidelines for the use of rifamycins for the treatment of tubercolosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR Morbid Mortal Wkly Rep 2004; 53:37. http://www.amedeo.com/lit.php?id=11795500

24.     Nandwani R, Gourlay Y. Possible Interaction between sildenafil and HIV combination therapy. Lancet 1999; 353: 840. http://www.amedeo.com/lit.php?id=10459981

25.     Bratt G, Stahle L. Sildenafil does not alter nelfinavir pharmacokinetics. Therapeutic Drug Monitoring 2003; 25: 240-2. http://www.amedeo.com/lit.php?id=12657921

26.     Ghofrani HA, Olschewski H, Seeger W, et al. Sildenafil for treatment of severe pulmonary hypertension and commencing right-heart failure. Pneumologie. 2002; 56: 665-72. http://www.amedeo.com/lit.php?id=12442206

27.     Jain AK, Venkataramanan R, Shapiro R, et al. The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients. Liver Transpl. 2002, 8:841-5. http://amedeo.com/lit.php?id=12200788

28.     Kurowski M, Breske A, Kruse G, et al. Atazanavir (ATV) enhances through concentrations of nelfinavir (NFV) and its M8 metabolite in a treatment regimen without ritonavir (RTV). Abstract 90, 6th Int Worksh Clin Pharmacol HIV Ther 2005, Quebec.

Nevirapina (NVP, Viramune™)

Dose aprovada: NVP 200 mg 2x/dia (período inicial: 200 mg/dia nos primeiros 14 dias) Metabolismo: nevirapina (NVP) é primariamente metabolizada pelo CYP3A4 e é indutor do CYP3A4 e 2B6 [1,2].

Bibliografia

1.         Tseng A. www.tthhivclinic.com, General Hospital, Toronto, 2006

2.         Viramune, Boehringer Ingelheim.

3.         Clinical Pharmacology, Gold Standard Multimedia, 2004. http://www.gsm.com

4.         Veldkamp AI, Harris M, Montaner JSG, et al. The steady-state pharmacokinetics of efavirenz and nevirapine when used in combination in HIV type 1 infected persons. J Infect Dis 2001; 184: 37-42. http://www.amedeo.com/lit.php?id=11398107

5.         Kaletra™, Abbott.

6.         Goujard C, Meynard JL, Choudet N, et al. Steady-state pharmacokinetics of amprenavir 600 mg BID and ritonavir 100 mg BID with or without NNRTI in HIV-1 infected patients. Abstract P268, 5th Int Congr Drug Ther HIV Inf 2000, Glasgow. http://www.aegis.com/conferences/hiv5/P268.html

7.         Degen O, Kurowski M, van Lunzen J, et al. Amprenavir and ritonavir: intraindividual comparison of different doses and influence of concomitant NNRTI on steady-state pharmacokinetics in HIV-infected patients. Abstract 739, 8th CROI 2001, Chicago. http://www.retroconference.org/2001/abstracts/abstracts/abstracts/739.htm

8.         Burger DM, Prins JM, van der Ende ME, et al. The effect of nevirapine on the pharmakokinetics of indinavir/ritonavir 800/100 mg BID. JAIDS 2004; 35: 97-8. http://www.amedeo.com/lit.php?id=14707800

9.         Murphy R, Gagnier P, Lamson M, et al. Effect of nevirapine on pharmacokinetics of indinavir and ritonavir in HIV-1 patients. Abstract 374, 4th CROI 1997, Washington.

10.     Crommentuyn KML, van Heeswijk RPG, Veldkamp AI, et al. Nevirapine once daily versus twice daily: implications for drug-drug interactions. Abstract 1.11, 2nd Int Worksh Clin Pharmacol HIV Ther 2001, Noordwijk.

11.     Skowron G, Leoung G, Kerr B, et al. Lack of pharmacokinetic interaction between nelfinavir and Nevirapine. AIDS 1998; 12: 1243-4. http://www.amedeo.com/lit.php?id=9677174

12.     Vilaro J, Mascaro J, Colomer J, et al. The pharmacokinetics of combination therapy with nelfinavir plus nevirapine in HIV-positive patients. Abstract A497, 41st ICAAC 2001, Chicago.

13.     Sahai J, Cameron W, Salgo M, et al. Drug interaction study between saquinavir (SQV) and nevirapine (NVP). Abstract 376, 4th National CROI 1997, Washington.

14.     Sabo J, MacGregor T, Lamson M, et al. Pharmacokinetics of tipranavir and nevirapine. Abstract 249, 10th Annual Canadian Conference on HIV/AIDS Research 2001, Toronto.

15.     Robinson P, Gigliotti M, Lamson M, et al. Effect of the reverse transcriptase inhibitor nevirapine, on the steady-state pharmacokinetics of clarithromycin in HIV positive patients. Abstract 374, 6th CROI 1999, Chicago.

16.     Lamson M, Robinson P, Gigliotti M, et al. The pharmacokinetic interactions of nevirapine and ketoconazol. Abstract 12218, 12th World AIDS Conference 1998, Geneva.

17.     Mildvan D, Yarrish R, Marshak A, et al. Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when admnistered concurrently to HIV-infected women. Journal of the Acquired Immune Deficiency Syndrome 2002; 29: 471-7. http://www.amedeo.com/lit.php?id=11981363

18.     Antoniou T, Lin-in Tseng. Interactions between Recreational Drugs and antiretroviral agents. Ann Pharmacother 2002; 36: 1598-613. http://www.amedeo.com/lit.php?id=12243611

19.     Altice FL, Friedland GH, Cooney E. Nevirapine induced opiate withdrawal among injection drug users with HIV infection receiving methadon. AIDS 1999; 13: 957-62. http://www.amedeo.com/lit.php?id=10371177

20.     Clarke S, Mulcahy F, Back D, et al. Managing methadone and non-nucleoside reverse transcriptase inhibitors: guidelines for clinical practise. Abstract 88, 7th CROI 2000, San Francisco.

21.     Maldonaldo S, Lamson M, Gigliotti M, et al. Pharmacokinetic interaction between nevirapine and rifabutin. Abstract 341, 39th ICAAC 1999, San Francisco.

22.     Centers for Disease Control and Prevention (CDC). Notice to Readers: Updated guidelines for the use of rifamycins for the treatment of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR; 2004; 53: 37. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4909a4.htm

23.     Robinson P, Lamson M, Gigliotti M, et al. Pharmacokinetic interaction between nevirapine and rifampin. Abstract 60623, 12th World AIDS Conference 1998, Geneva.

24.     Ribera E, Pou L, Lopez RM, et al. Pharmacokinetic interaction between nevirapine and rifampicin in HIV-infected patients with tuberculosis. JAIDS 2001; 28: 450-3. http://www.amedeo.com/lit.php?id=11744833

25.     Oliva J, Moreno S, Sanz J, et al. Co-administration of rifampin and nevirapine in HIV-infected patients with tuberculosis [letter]. AIDS 2003; 17: 637-8. http://www.amedeo.com/lit.php?id=12598789

26.     Ghofrani HA, Olschewski H, Seeger W, et al. Sildenafil for treatment of severe pulmonary hypertension and commencing right-heart failure. Pneumologie 2002; 56: 665-72. http://www.amedeo.com/lit.php?id=12442206

27.     Dioniso D, Mininni S, Bartolozzi D, et al. Need for increased dose of warfarin in HIV patients taking nevirapine. AIDS 2001; 15: 277-8. http//www.amedeo.com/lit.php?id=11216940 

28.     Tripranavir Investigators Broschüre, Boehringer Ingelheim, 2004.

29.     Barry M, Mulcahy F, Merry C, et al. Pharmacokinetics and potential interactions among antiretroviral agents used to treat patients with HIV infection. Clin Pharmacokinet. 1999; 36: 289-304. http://www.amedeo.com/lit.php?id=10320951

30.     Alexander CS, Montaner JG, Langridge S, et al. Interaction between atazanavir/Ritonavir (ATV/r) and nevirapine (NVP) is observed in a clinical setting. Abstract P275, 7th Int Congr Drug Ther HIV Inf 2004, Glasgow.

31.     DeJesus E, Piliero P, Summers K, et al. Evaluation of the pharmacokinetik drug interaction between fosamprenavir (FPV), FPV plus ritonavir (RTV) and nevirapine (NVP) in HIV-infected patients (APV10014). Abstract A-447, 44th ICAAC 2004, Washington.

32.     van Leth F., Hassink E., Phanuphak P. et al. Results of the 2NN Study: A randomized comparative trial of first-line antiretroviral therapy with regimens containing either NVP alone, EFV alone or both drugs combined, together with stavudine and lamivudine. Abstract 176, 10th CROI 2003.

33.     Bertz R, Foit C, Burt D, et al. Assessment of the effect of nevirapine on the pharmacokinetics of lopinavir/ritonavir after multiple dosing in HIV-infected adults. Abstract TUPEB4565, XIV Int AIDS Conf 2002, Barcelona.

34.     Negredo E, Moltó J, Burger D et al. Lopinavir/ritonavir plus nevirapine as a nucleoside-sparing approach in antiretroviral-experienced patients (NEKA study). JAIDS 2005; 38: 47-52. http://www.amedeo.com/lit.php?id=15608524

Saquinavir (SQV, Invirase 500™)

Dose aprovada SQV: SQV/r:1000/100 mg 2x/dia [3]. Metabolismo: 90 % de SQV émetabolizado pelo isoenzima CYP3A4. O SQV é um fraco inibidor do CYP3A4. Estudos in vitro mostraram que o SQV é também um substrato da P-glicoproteina (P-gp) [1,2].