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 Zambia HIV National Guidelines
 


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ARV Therapy for Individuals with Tuberculosis Co-Infection  

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WHO Staging in Adults and Adolescents  

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Palliative Care in HIV and AIDS  

 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Drugs>Antiretrovirals>
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Indinavir

Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
10-29-2010

Zambia Specific Information

  • Available formulation in Zambia: Capsule: 200 mg; 333 mg; 400 mg (as sulfate).
  • Inferior to EFV-based regimen due to higher drop out rate
  • Rates of IDV-induced nephrolithiasis may be higher in warm climate countries. Pts should be encouraged to take adequate oral hydration.
Zambia Information Author: Paul A. Pham, Pharm.D.

INDICATIONS

FDA

  • Treatment of HIV infection in combination with other ARVs.

FORMS

brand 
name
 
generic 
Mfg 
brand 
forms
 
cost* 
Crixivan Indinavir sulfate (IDV)Merck

      oral
capsule
200 mg
$1.52
      oral
capsule
333 mg
n/a
      oral
capsule
400 mg
$3.05

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

Pill burden: 6 caps per day (based on IDV 800 mg + RTV 100 mg twice-daily using 400 mg caps)

  • IDV 800 mg q8h on an empty stomach or with a light snack (>1 hac and >2 hrs pc). Food restrictions apply to all unboosted IDV regimens below.
  • With RTV (preferred): IDV 800 mg twice-daily + RTV 100 mg twice-daily with or w/o food (higher rate of nephrotoxicity) or IDV 400 mg twice daily + RTV 400 mg twice-daily with or w/o food (higher rate of GI side effects).
  • With EFV: IDV 1000 mg q8h + EFV 600 mg qhs or IDV 800 mg twice-daily + RTV 200 mg twice daily with or w/o food + EFV 600 mg qhs.
  • With NFV: IDV 1200 mg twice-daily + NFV 1250 mg twice-daily (rarely used; limited data).
  • With LPV/r: IDV 600 mg or 666 mg twice-daily + LPV/r 400/100 mg twice-daily.
  • With NVP: IDV 1000 mg q8h + NVP 200 mg twice-daily or IDV 800 mg twice-daily + RTV 200 mg twice-daily + NVP standard dose.
  • Not recommended with ATV (due to potential for additive hyperbilirubinemia) or SQV (due to in vitro antagonism).
  • FPV: no data.
  • TPV: no data. Avoid co-administration.
  • DRV: Dose not established. May increase risk of nephrolithiasis.
  • ETR: avoid co-administration.
  • RAL: no data. Usual dose likely.
  • MVC: IDV standard dose + MVC 150 mg twice-daily.

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose.

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Usual dose likely HD.

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

Usual dose likely (pharmacokinetics unchanged in renal failure).

DOSING IN HEMODIALYSIS

Usual dose. Very small amount removed in HD.

DOSING IN PERITONEAL DIALYSIS

No data: usual dose likely.

DOSING IN HEMOFILTRATION

No data.

ADVERSE DRUG REACTIONS

COMMON

  • GI intolerance: nausea, vomiting, and diarrhea.
  • >2 retinoid-like side-effects (alopecia, dry skin, mouth, and eyes) in up to 30%; paronychia in 4-9%.
OCCASIONAL

  • Nephrolithiasis +/- hematuria: 5-20% (highest risk with IDV 800 mg twice daily + RTV 100-200 mg twice daily, lowest risk with IDV 400 mg twice daily + RTV 400 mg twice daily). Encourage adequate oral hydration.
  • Indirect hyperbilirubinemia (>2.5 mg/dL in 10-15% of pts but clinically insignificant).
  • Lipodystrophy, especially fat accumulation or gynecomastia.
  • Insulin resistance +/- hyperglycemia +/- diabetes.
  • Hyperlipidemia: increased triglycerides and/or cholesterol.
  • Increased transaminases.
  • Nephropathy: sterile leukocyturia, hematuria, IDV crystalluria, and albumin loss (35% with increased serum creatinine).
  • Interstitial nephritis with pyuria and renal insufficiency reported in 2% (Clin Infect Dis 2002;34:1122).
RARE

  • Pruritis and rash.

DRUG INTERACTIONS

Substrate and inhibitor of CYP3A4 and weak inhibitor of CYP2D6. May increase levels of CYP3A4 (and possibly 2D6) substrates. CYP3A4 inhibitors and inducers may increase and decrease IDV levels, respectively.

Drug-to-Drug Interactions

Drug-to-Drug Interaction

DrugEffect of InteractionRecommendations/Comments
Efavirenz (EFV) IDV AUC: decreased by 31-35%; EFV: no effect.Recommended dosing: IDV 1000 mg q8H + EFV 600 mg qhs or IDV 800 mg twice daily + RTV 200 mg twice daily + EFV 600 mg qhs.
Fluconazole No significant interactionUse standard dose of both drugs.
LPV/r IDV AUC increased by 20%, Cmin increased by 46%; IDV Cmin increased by 247%; LPV no change.Dose: IDV 600 mg or 666 mg twice daily + LPV/r 400/100 mg twice daily
Nevirapine No effect on NVP; Decrease IDV AUC by 28%. IDV 1000 mg q8h + NVP 200 mg twice daily or IDV 800 mg twice daily + RTV 200 mg twice daily + NVP standard dose.
Nelfinavir NFV AUC: increased by 83%.Dose: IDV 1200 mg twice daily + NFV 1250 twice daily (limited clinical data).
Rifampin IDV AUC decreased by 89%.Do not co-administer IDV (even with the addition of RTV).
Ritonavir IDV Cmin increased by 10-fold (dose: IDV 800 mg + RTV 100 mg bid compared to IDV 800 mg q8h).Dose: IDV800 mg twice-daily+ RTV 100 mg twice-daily (high rate of nephrotoxicity) or I, or IDV 400 mg twice daily RTV 400 mg twice-daily (high rate of GI toxicity).
Saquinavir Increase SQV AUC by 4-7 fold; No effect on IDV. No data. Possible in vitro antagonism.
Darunavir IDV AUC and Cmin increased 23% and 125%, respectively. DRV AUC and Cmin increased 24% and 44%, respectively. Dose not established. May increase risk of nephrolithiasis.
ETR IDV AUC decreased 46% (studied with unboosted IDV). No data with IDV/r. Avoid co-administration.
MVC MVC serum concentrations may be increased. Decrease MVC to 150 mg twice-daily.
Clarithromycin Clarithromycin AUC increased 53%, Reduce clarithromycin dose by 50% in pts with CrCL 30-60 ml/min. Reduce clarithromycin dose by 75% in pts with CrCL <30 ml/min.
Tipranavir 
No data Avoid co-administration.
ddI (buffered)IDV AUC decreased by 84%.Administer IDV 1hr before or after ddI (buffered). Consider using ddI EC since there are no interactions with IDV.
Alprazolam May increase serum levels of alprazolam.Consider an alternative benzodiazepine (lorazepam, temazepam, or oxazepam).
AmiodaroneIn a case report amiodarone levels increased by 44%.Contraindicated. Monitor for amiodarone toxicity. Consider alternative antiarrhythmic with cardiology consult.
AmlodipineAmlodipine serum concentrations increased 90%All PIs have the potential of prolonging the PR interval with Ca channel blocker co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse.
Amprenavir APV clearance decreased by 54% APV AUC: increased by 33%; Cmin: increased by 25%; IDV AUC decreased by 38%.Data based on PK modeling with many confounding variables (i.e. EFV in background regimen). Consider IDV 800 mg q8h + APV 800 mg 3 times a day (limited data).
Artemether (artemisinin)May increase serum levels of artemether.Applies to all PIs: Close monitoring for artemether toxicity (bone marrow suppression, bradycardia, and seizure).
AstemizoleMay significantly increase astemizole serum levels.Contraindicated due to the potential for cardiac arrhythmias. Recommended alternative antihistamine: loratadine, fexofenadine, desloratidine, or cetirizine.
Atorvastatin May increase atorvastatin levels.Avoid combination. Consider alternative agents: pravastatin, fluvastatin, or rosuvastatin. With co-administration, use low dose atorvastatin and monitor for ADRs due to limited clinical data.
Atovaquone No significant interaction.Use standard dose of both drugs.
AzathioprineInteraction unlikely.Use standard doses.
BepridilMay significantly increase bepridil serum levels.No data. Manufacturers of ATV, RTV, and APV do not recommend bepridil co-administration; this contraindication should extend to all PIs since significant increase in bepridil serum levels can result in pro-arrhythmic events such as VT, PVC, and VF.
Bosentan Bosentan serum concentrations may be significantly increased with IDV/r Co-administer bosentan only after RTV dosing has reached steady-state. In pts on RTV >10 days: start bosentan at 62.5 mg once daily or every other day. In pts already on bosentan: discontinue bosentan for >36 hrs prior to initiation of RTV-boosted PIs and restart bosentan at 62.5 mg once daily or every other day after RTV has reached steady-state (after 10 days).
CarbamazepineIDV levels: decreased 4-25% of mean population values.Consider alternative anticonvulsants (i.e valproic acid, lamotrigine, levetiracetam, or topiramate). With co-administration, monitor anticonvulsants levels and consider TDM of IDV.
Chlordiazepoxide May increase serum levels of chlordiazepoxideApplies to all PIs: Consider an alternative benzodiazepine ( lorazepam, temazepam, or oxazepam).
CisaprideMay significantly increase cisapride serum levels.Contraindicated due to potential for cardiac arrhythmias. Recommended alternative: metoclopramide.
Clorazepate May increase serum levels of clorazepate.Applies to all PIs: Consider an alternative benzodiazepine (lorazepam, oxazepam, or temazepam).
CyclophosphamideCyclophosphamide: clearance decreased by 1.5 fold; IDV: no change.Clinical significance unknown. May require cyclophosphamide dose adjustment.
CyclosporineMay significantly increase serum levels of cyclosporine.Applies to all PIs: Monitor serum levels of cyclosporine closely with co- administration. Cyclosporine dose may need to be decreased.
Dexamethasone May decrease IDV serum concentrations at steady-state. Avoid unboosted IDV. Use IDV/r with dexamethasone with close monitoring for virologic efficacy.
Digoxin Digoxin serum concentration may be increased with IDV/r co-administration. Monitor digoxin serum concentration closely with co-administration.
DiltiazemMay increase serum levels of diltiazem.Data limited to an interaction study conducted with ATV which resulted in doubling of diltiazem serum levels (this led to PR interval prolongation). All PIs have the potential of prolonging PR interval with diltiazem co-administration. Diltiazem should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse.
DisopyramideMay increase disopyramide serum levels.Applies to all PIs: No data. Monitor disopyramide serum levels (target: 2 to 7.5 mcg/mL).
DocetaxelMay increase serum levels of docetaxel.Applies to all PIs: No data. Close monitoring of chemotherapy-induced toxicity recommended.
DofetilideMay significantly increase dofetilide levels.No data. Use with caution. Monitor QTc closely and adjust dofetilide dosing based on QTc prolongation and renal function. Consider an alternative class III antiarrhythmic such as bretylium or ibutilide.
DoxorubicinDoxorubicin: no change in clearance; IDV: no change.Use standard dose. Close monitoring recommended due to limited clinical data.
Dronabinol No significant interaction.Use standard doses of both drugs.
Echinacea May decrease IDV serum level. Echinacea (400 mg 4x/d) decreased CYP3A4 substrate (midazolam) by 23%.Applies to all PIs and NNRTIs. Clinical significance unknown but should avoided until the safety of this combination is further evaluated.
Ergot alkaloidsMay significantly increase ergotamine levels. Case report of ergotism has been reported.Contraindicated. Consider alternative agent for migraine such as sumatriptan (but not eletriptan since it is a CYP3A4 substrate and significant drug-drug interaction occurred with CYP3A4 inhibitor).
Estazolam May increase serum levels of estazolam.Applies to all PIs: Consider an alternative benzodiazepine (lorazepam, oxazepam, or temazepam).
EthosuximideMay increase serum levels of ethosuximide.Applies to all PIs: Consider switching to valproic acid for the treatment of absence seizure.
EtoposideMay increase serum levels of etoposide.Applies to all PIs: No data. Close monitoring of chemotherapy-induced toxicity recommended.
FelodipineMay increase serum levels of felodipine.Applies to all PIs: Data limited to an interaction study conducted with ATV and diltiazem which resulted in doubling of diltiazem serum levels (this led PR interval prolongation). All PIs have the potential of prolonging PR interval with Ca channel blocker co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse.
Fentanyl May significantly increase serum levels of fentanyl.Use with caution. Consider morphine.
FlecainideMay increase antiarrhythmic serum levels.Applies to all PIs: Avoid co-administration; if necessary, monitor flecainide trough levels with co-administration. Target: 200-1000 ng/mL. Toxicity is frequent with trough serum levels above 1000 ng/mL.
Flurazepam May increase serum levels of flurazepam.Applies to all PIs: Consider an alternative benzodiazepine (lorazepam, oxazepam, or temazepam).
Fluticasone Fluticasone serum concentration may be increased with IDV/r co-administration. Avoid long term co-administration. Consider beclomethasone.
FoodIDV AUC decreased by 77% with a 784 kcal meal (48.6 g fat, 31.3 g protein). IDV not significantly affected by a light meal (toast and jelly, apple juice, coffee with skim milk and sugar or a meal of corn flakes).Take on an empty stomach or with light snack >1 hr ac and >2 hrs pc when IDV given as the sole PI. IDV co-administered with RTV (IDV 800 mg twice daily + RTV 100 mg twice daily) removes food effect and is preferred.
Garlic SupplementsStudies only done with SQV and revealed 49% and 51% reduction of SQV Cmin and AUC, respectively when co-administered with garlic supplement (3.5 grams twice daily). Unknown interaction with other PIs. Studies only done with SQV but garlic supplement may affect serum levels of other PIs and NNRTIs. Avoid co-administration with PIs and NNRTIs.
GranisetronMay increase serum levels of granisetron.Applies to all PIs: Due to the large therapeutic index of granisetron, potential interaction is unlikely to be clinically significant.
Grape fruit or Seville orange juiceNo significant interaction. IDV AUC decreased by 26%. Clinically significant interaction unlikely. Studies conducted with unboosted IDV. Clinical significance unknown but boosting IDV with RTV (IDV 800 mg + RTV 100 mg twice daily) will likely overcome any potential interaction.
Heroin (Diamorphine)Drug interactions unlikely.Applies to PIs and NNRTIs: Interaction unlikely but illicit drug use should be avoided for obvious reasons.
IfosphamideMay increase serum levels of ifosphamide.Applies to all PIs: No data. Close monitoring of chemotherapy-induced toxicity recommended.
Irinotecan May increase irinotecan serum levels.Applies to all PIs: Co-administration of ATV is contraindicated by manufacturer. All PIs also have the potential for significant interaction with Irinotecan, therefore the co-administration should be done with extreme caution.
Itraconazole IDV serum levels may be increased by itraconazole.Dose: IDV 600 mg q8h. When co-administered with itraconazole, IDV 600 mg q8h has equivalent PK compared to IDV 800 mg q8h. Do not exceed itraconazole 200 mg twice daily. No data with IDV/RTV co-administration. Consider IDV 800 mg twice daily + RTV 100mg twice daily with aggressive hydration due to the potential increased risk of nephrolithiasis.
Ketoconazole IDV AUC: increased by 68%.Dose: IDV to 600 mg q8h. Consider IDV 800 mg twice daily + RTV 100 mg twice daily (do not exceed ketoconazole 200 mg/d) with aggressive hydration due to potential increased risk of nephrolithiasis.
LidocaineMay increase antiarrhythmic serum levels.Applies to all PIs: No data. Use with caution, monitor lidocaine serum levels (target: 1.5 to 6 mcg/mL) with co-administration.
Lovastatin May significantly increase lovastatin levels.Contraindicated. Recommended alternatives include pravastatin, rosuvastatin, or fluvastatin. Monitor for ADRs due to limited clinical data.
MefloquineMay increase serum levels of mefloquine.Applies to all PIs: Monitor mefloquine serum levels and for mefloquine toxicity (i.e dizziness, LFTs, and periodic ophthalmic examination).
Methadone No change in methadone or IDV serum levels. No interaction. Use standard dose of both drugs.
MexiletineMay increase antiarrhythmic serum levels.Applies to all PIs: No data. Use with caution. Monitor EKG and serum levels. Serum levels exceeding 1.5 to 2 mcg/mL have been associated with an increased risk of toxicity.
Midazolam May significantly increase midazolam levels.Concurrent administration contraindicated due to potential for prolonged sedation. Consider alternative benzodiazepines (lorazepam, oxazepam, or temazepam). Single dose midazolam may be used (chronic use not recommended).
Milk thistle (silymarin)IDV AUC: unchanged IDV Cmin: decreased by 25%.Clinical significance unknown. Since milk thistle has not shown clinical benefit for the treatment of viral hepatitis, avoid co-administration with IDV until it can be further evaluated.
MirtazapineMay increase serum levels of mirtazapine.Applies to all PIs: Use with caution. Consider an alternative antidepressant (i.e SSRI: escitalopram, citalopram, sertraline, or fluoxetine).
MycophenolateInteraction unlikely. No significant interaction observed with NVP.Applies to all PIs and NNRTIs: No significant interaction observed with NVP. Use standard dose.
NefazodoneMay increase serum levels of nefazodone.Applies to all PIs: Use with caution. Consider an alternative antidepressant (i.e SSRI: escitalopram, citalopram, sertraline, or fluoxetine).
NifedipineMay increase serum levels of nifedipine.Applies to all PIs: Data limited to an interaction study conducted with ATV and diltiazem which resulted in doubling of diltiazem serum levels (this led to PR interval prolongation). All PIs have the potential of prolonging the PR interval with Ca channel blocker co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse.
NisoldipineMay increase serum levels of nisoldipine.Applies to all PIs: Data limited to an interaction study conducted with ATV and diltiazem which resulted in doubling of diltiazem serum levels (this led to PR interval prolongation). All PIs have the potential of prolonging the PR interval with Ca channel blocker co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse.
Norethindrone and EthinylestradiolNorethindrone levels increased by 26% and Ethinylestradiol by 24%.Use of barrier method of contraception is recommended to prevent pregnancy.
Omeprazole No significant interaction Use standard dose.
Paclitaxel May increase paclitaxel serum levels.Applies to all PIs: Since all PIs have the potential of significantly increasing paclitaxel serum levels, close monitoring of paclitaxel-induced toxicity is recommended.
PCPMay significantly increase serum levels of PCP.Applies to all PIs. Avoid all illicit drug use with PIs and NNRTIs.
PhenobarbitalMay decrease IDV serum levels. PIs and NNRTIs may increase or decrease phenobarbital serum levels.Applies to All PIs and NNRTIs: Consider alternative anticonvulsants (i.e valproic acid, lamotrigine, levetiracetam, or topiramate). With co-administration, monitor anticonvulsants levels and consider TDM of PIs and NNRTIs.
PhenytoinMay significantly decrease IDV serum levels.Applies to all PIs and NNRTIs: Consider alternative anticonvulsants (i.e valproic acid, lamotrigine, levetiracetam, or topiramate). Monitor anticonvulsant levels and consider TDM of PIs and NNRTIs.
PimozideMay significantly increase pimozide serum levels resulting in QTc prolongation.Contraindicated. Consider alternative: olanzapine.
PPI (Omeprazole)No significant interaction.Use standard dose of both drugs.
Prednisone Prednisolone serum concentration may be increased with IDV/r co-administration. Dose adjustment may be needed with long-term co-administration.
PropafenoneMay significantly increase serum levels of propafenone.Do not co-administer.
Quinidine IDV AUC increased by 10%(NS) based on a single dose study. Quinidine serum levels not reported.Manufacturer does not recommend dose adjustment; however, use with caution since this was a single dose study. Monitoring of EKG (QTc) and serum levels: Target: 2 to 5 mcg/mL.
RAL IDV may increase RAL serum concentrations. Usual dose likely.
Ranolazine May significantly increase ranolazine serum concentrations. Contraindicated. May increase risk of QTc prolongation.
Rifabutin (RFB) Rifabutin AUC increased by 204%; IDV AUC decreased by 32%.Recommended dose: RFB 150 mg once-daily (or 300 mg 3x/wk) + IDV 1000 mg q8h or RFB 150 mg every other day (or 150 mg 3x/wk) + IDV 800 mg + RTV 100 mg twice-daily (recommended but no data).
Rifapentine IDV AUC decreased by 75%. Rifapentine AUC not affected.Avoid co-administration. Consider using RFB.
Rosuvastatin Other CYP3A4 inhibitor (i.e erythromycin) did not affect rosuvastatin serum levels.Applies to PIs and NNRTI: interaction unlikely, but close monitoring recommended due to limited clinical data.
Salmeterol May increase salmeterol serum concentrations. Avoid co-administration. Consider formoterol
SildenafilMay significantly increase sildenafil serum levels.Use with caution. Do not exceed 25 mg of sildenafil in 48 hrs.
Simvastatin May significantly increase simvastatin levels.Contraindicated. Recommended alternatives include atorvastatin, pravastatin, fluvastatin, and rosuvastatin. Monitor for adverse effects due to limited clinical data with these agents.
SirolimusMay significantly increase serum levels of sirolimus.Applies to all PIs: Dose sirolimus based on serum level. A significant reduction in sirolimus dose when combined with any PI is likely to be necessary.
St. John's wortIDV AUC decreased by 57%.Contraindicated with all PIs and NNRTIs. Use an alternative antidepressant.
TacrolimusMay significantly increase tacrolimus levels.Dose tacrolimus based on serum levels. A significant reduction of tacrolimus dose with IDV co-administration is likely to be necessary.
TadalafilMay increase serum levels of tadalafil.Applies to all PIs: Start with 5 mg. Do not exceed 10 mg in 72 hrs. Consider sildenafil due to more clinical data and shorter half-life allowing for easier titration.
TamoxifenMay increase serum levels of tamoxifen.Applies to all PIs: No data. Close monitoring of tamoxifen-induced toxicity recommended.
TeniposideMay increase serum levels of teniposide.Applies to all PIs: No data. Close monitoring of teniposide-induced toxicity recommended.
TerfenadineMay significantly increase terfenadine serum levels.Removed from IDV contraindicated list since it is no longer available in the U.S. However, the potential of an old terfenadine bottle still poses a risk for cardiac arrhythmias with co-administration. Recommended alternative antihistamine: loratadine, fexofenadine, desloratidine, or cetirizine.
THCBased on data with NFV and IDV interactions are unlikely.Applies to PIs and NNRTIs: interactions are unlikely but illicit drug use should be avoided for obvious reasons.
TrazadoneMay increase serum levels of trazadone.Applies to all PIs: Use with caution. Consider alternative antidepressants (i.e SSRI: escitalopram, citalopram, sertraline, or fluoxetine).
Triazolam May significantly increase triazolam serum levels.Concurrent administration contraindicated due to potential for prolonged sedation. Consider alternative benzodiazepines (lorazepam, oxazepamor temazepam).
VardenafilVardenafil AUC increased by 16-fold. IDV AUC decreased by 30%.Do not exceed vardenafil 2.5 mg in 24 hrs. Consider sildenafil due to more clinical data and less pronounced interaction.
VenlafaxineIDV AUC decreased by 28%. Venlafaxine: no effect.Clinical significance unknown. Small study PK that used unboosted IDV; the observed change may be within the PK variability of IDV. Consider alternative SSRI (i.e escitalopram).
VerapamilMay increase serum levels of verapamil.Applies to all PIs: Data limited to an interaction study conducted with ATV and diltiazem which resulted in doubling of diltiazem serum levels (this led to PR interval prolongation). All PIs have the potential of prolonging the PR interval with Ca channel blocker co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse.
VinblastineMay increase serum levels of vinblastine.Applies to all PIs: No data. Close monitoring of vinblastine-induced toxicity recommended.
VincristineMay increase serum levels of vincristine.Applies to all PIs: No data. Close monitoring of vincristine-induced toxicity recommended.
Vitamin C IDV AUC decreased by 14% and Cmin by 32% when co-administered with vitamin C (1 mg/d).Clinical significance unknown due to small sample size (n=7). Boosting IDV with RTV (IDV 800 mg twice daily + RTV 100 mg twice daily) will likely overcome this potential interaction. Unknown effect on the serum levels of other PIs and NNRTIs.
Voriconazole No significant change voriconazole and IDV AUC. Voriconazole serum concentration may be decreased with IDV/r.No significant interaction with unboosted IDV. Use standard dose of both drugs. WIth IDV/r, monitor voriconazole serum concentration.
WarfarinCase report of increased INR.Other PIs and NNRTIs may also affect warfarin requirements. Monitor INR closely with co-administration.

RESISTANCE

  • V82A/T/F/S: Most common mutations with IDV monotherapy, results in intermediate IDV resistance and cross-resistance to other PIs. 82I does not cause PI resistance. Primary mutation (82A/F/T/S, 84V, 46I/L): Low to intermediate resistance with individual mutations, but significant IDV resistance with multiple mutations.
  • Other PI mutations: (10I/R/V, 20M/R, 24I, 32I,, 36I, , 54V, 71V/T, 73S/A, 76V, 77I,, 90M): >3 results in >4-fold decrease in susceptibility.
  • RTV boosting increases activity against PI-resistant virus.

PHARMACOLOGY

Pharmacology

COMMENTS

  • Pros: Long-term clinical data supporting durability and potency; multiple mutations required for resistance.
  • Cons: Variable PK and inconvenient dosing without RTV boosting; nephrolithiasis (unique to IDV); GI side effects; retinoid effects (unique to IDV); insulin resistance (more common than with other PIs). No longer recommended or widely used because of better alternatives.

REFERENCES

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