VIRTUAL MEDZONE
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Transcript of VIRTUAL MEDZONE
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VIRTUAL MEDZONEYour Resource for HIV Related Innovative Medical Communication
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HIV CASE PRESENTATIONSAlice Tseng Pharm.D., FCSHP, AAHIVPDavid Fletcher MD FRCPC
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CASE 1• 54 yo Caucasian woman, Dx HIV & HCV
in 2002 • ARV treatment (CD4 280, VL 40,526)
DATE ARV REGIMEN VL CD410/02 AZT/3TC/NFV <50 47710/07 AZT/3TC/LPVr <50 72709/09 TDF/FTC/LPVr <50 819
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CASE 1HCV 1a (gr 3-4 fibrosis, RNA 1.32E+6
IU/mL)DATE TREATMENT OUTCOME02/03 RBV+peg-IFN d/c after 2 doses
(↓Hgb, ANC)06/03 Amitriptyline,
RBV+peg-IFN, EPO, GCSF
d/c after 2 weeks
09/05 LFTs still pre-RBV, peg-IFN 2A
d/c after wk 12 (supoptimal response)
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CASE 1Considerations with HCV protease inhibitors:• Telaprevir:• LPVr: 54% AUC, 52% Cmin of TVR• DRVr: 35% AUC, 32% Cmin of TVR; also 40%
AUC, 42% Cmin of darunavir• ATVr: 20% AUC, 15% Cmin of TVR; least impact
of all current PIs ongoing evaluation in HIV/HCV• Tenofovir: AUC (relevance?). Monitor Scr.
• Boceprevir:• minimal effects of RTV 100 mg QD and BID on
BOC AUC
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CASE 1So how should we manage this patient on TDF /FTC/LPVr?...switch ARVs
Telaprevir• RTV/ATZ• EFV• RaltegravirBoceprevir…stay tuned
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CASE 2• 50 yo, Caucasian male, • HIV+ since 1992• VL suppressed since 1996, CD4 720• some NRTI mutations, no PI mutations,
R5+• on 3TC, SQV 600/RTV 300 mg BID, RAL
BID since 2008
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CASE 2Asthma: prev. on Symbicort (budesonide/formoterol) inhaler• interaction with RTV/SAQ adrenal
suppression/ insufficiency, Cushings Syndrome (2010)
• also has osteoporosis, hyperlipidemia, autoimmune retinopathy
How do you manage his asthma?
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CASE 3• 62 yo male, HIV+ 1992• extensive ARV history with AEs &
resistance• CAD, CHF, HTN, hyperlipidemia,
NIDDM, gout, chronic renal insufficiency
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CASE 3Meds:• ABC, 3TC, LPVr, T20• TMP/SMX DS, allopurinol, metoprolol,
furosemide, Aggrenox (dipyridamole 200 mg/ASA 25 mg), amlodipine, rosuvastatin
• Dx pulmonary arterial hypertension (PAH) 2003, respirologist Rx bosentan…
How do you manage this patient?
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PAH THERAPIES
Substrate P450
Substrate (other)
Inducer/ Inhibitor
Endothelin Receptor Antagonists:
Bosentan (Tracleer®) 3A4, 2C9 2C9, 3A4 (inducer)
Ambrisentan (Volibris®)
CYP3A4, 2C19
UGT1A9S, 2B7S, 1A3S, Pgp
Phosphodiesterase inhibitors:
Sildenafil (Revatio®) 3A4>>2C9
1A2, 2C9, 2C19, 2D6, 2E1, 3A4 (weak inhibitor)
Tadalafil (Adcirca®) 3A4
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POTENTIAL INTERACTION BETWEEN BOSENTAN & PIS
• Possibility of bosentan and/or lopinavir/r concentrations via CYP450 inhibition/induction
• Usual bosentan dose:• 62.5 mg BID x 4 weeks, then 125 mg BID
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POTENTIAL INTERACTION BETWEEN BOSENTAN & PIS
• May 2004: Rx bosentan 62.5 mg BID, LPV/r to 5 capsules BID
• 1 month later developed recurrent anemia requiring transfusions despite iron supplementation & EPO
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POTENTIAL INTERACTION BETWEEN BOSENTAN & PIS• anemia associated with bosentan is
dose-related• in controlled studies, Hgb of at least
10 g/L observed in 57% bosentan-tx subjects vs. 29% placebo group
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ADMINISTERING BOSENTAN WITH PROTEASE INHIBITORSManagement:• if already on stable PI tx: initiate bosentan
62.5 mg q1-2days• if on stable bosentan and require PI: d/c
bosentan for >36 h, start PI x 10 days, re-start bosentan at 62.5 mg q1-2days
[DHHS Guidelines, Oct 14/11; Tracleer monograph, June 2011; Reyataz monograph, May 2011.]
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ADMINISTERING BOSENTAN WITH PROTEASE INHIBITORSMonitoring parameters:• efficacy: improvement in exercise
tolerance, NYHA functional status severity and hemodynamic measures via right heart catheterization. Also suggest PI TDM & VL.
[DHHS Guidelines, Oct 14/11; Tracleer monograph, June 2011; Reyataz monograph, May 2011.]
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ADMINISTERING BOSENTAN WITH PROTEASE INHIBITORSMonitoring parameters:• toxicity: headache, flushing, GI effects,
anemia, liver injury, worsening CHF (wt gain, leg edema) and pulmonary edema (SOB, painful/difficult breathing)
• Atazanavir: do not use unboosted atazanavir with bosentan (may ATV)
[DHHS Guidelines, Oct 14/11; Tracleer monograph, June 2011; Reyataz monograph, May 2011.]
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CASE 4• 66 yo male, HIV+ 1992• NIDDM, hyperlipidemia, HTN,
renal dysfunction (multifactorial), peripheral neuropathy, depression, BPH, chronic pain
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CASE 4Medications• DRV/r BID, RAL BID, ETV BID• ASA, amlodipine, ramipril, coenzyme Q10,
fenofibrate, ezetimibe, atorvastatin, metformin, Prandase (acarbose), Januvia (sitagliptin), Cymbalta (duloxetine), ACV, Detrol (tolterodine), dulcolax, colace, metamucil, Flonase prn, testosterone cream
• Urologist wants to add daily tadalafil:Interaction with DRV/r?
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IMPACT OF PIS ON PDE5 INHIBITORS
Sildenafil
Tadalafil Vardenafil
Darunavir/r 300% Fosamprenavir/r
Priapism (case)
Lopinavir/r 100% Ritonavir 1000%
(500mg BID)
124% (200 mg BID)
49-fold (600 mg BID)
Saquinavir/r 210%
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DOSING OF PDE5 INHIBITORS WITH PIS
*if on stable tadalafil and starting PI therapy: d/c tadalafil for at least 24 h, start PI, restart tadalafil after 7 days at 20 mg QD with to 40 mg QD prn
For PAH Sildenafil Tadalafil VardenafilUsual Dose 20 mg TID 40 mg QDWith PI/r Contraindicate
d20mg QD, to 40 mg QD if tolerated
For ED Sildenafil Tadalafil VardenafilUsual Dose 50-100 mg QD 10-20 mg QD
prn2.5-5 mg OD (daily dosing)
With PI/r 25 mg q48h 10 mg q48h, max 3x/wk
No change
NB: Vardenafil is contraindicated with ritonavir, indinavir, ketoconazole and itraconazole