Zambian HIV Guidelines:: Indinavir

	Zambia HIV National Guidelines
	Introduction HIV Counseling and Testing Sexually Transmitted Infections (STIs) General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents Initial Regimen for ARV Therapy Adherence Baseline evaluation and Monitoring Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance ARV Therapy for Individuals with Tuberculosis Co-Infection Adverse Effects and Toxicity Immune Reconstitution Inflammatory Syndrome (IRIS) Changing or Stopping ART Treatment Failure Stopping ARV Therapy Post Exposure Prophylaxis Cotrimoxazole Prophylaxis WHO Staging in Adults and Adolescents Nutrition Care and Support 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>

Indinavir

Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
03-24-2008

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 antiretrovirals.

FORMS

brand name	generic	Mfg	brand forms	cost*
Crixivan	Indinavir sulfate (IDV)	Merck	oral capsule 100 mg	$0.76
			oral capsule 200 mg	$1.52
			oral capsule 333 mg	$2.53
			oral capsule 400 mg	$3.03

*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: 8 caps per day (based on IDV 1000 mg + RTV 100 mg bid using 333 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 bid + RTV 100mg bid with or w/o food (higher rate of nephrotoxicity) or IDV 400 mg bid + RTV 400 mg bid 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 bid + RTV 200 mg bid with or w/o food + EFV 600 mg qhs.
With NFV: IDV 1200 mg bid + NFV 1250 mg bid (rarely used; limited data).
With APV: IDV 800 mg q8h + APV 800 mg tid (rarely used; limited data).
With LPV/r: IDV 600 mg or 666 mg bid + LPV/r 400/100 mg bid.
With DLV: IDV 600 mg q8h + DLV 400 mg tid.
With NVP: IDV 1000 mg q8h + NVP 200 mg bid or IDV 800 mg bid + RTV 200 mg bid + NVP standard dose.
Not recommended with ATV (due to potential for additive hyperbilirubinemia and SQV (due to in vitro antagonism).
FPV: no data.
TPV: no data. Avoid co-administration.
DRV: Dose not established. May increase risk of nephrolithiasis.

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 bid + RTV 100-200 mg bid, lowest risk with IDV 400 mg bid + RTV 400 mg bid). 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, erythrocyturia, 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

Drug	Effect of Interaction	Recommendations/Comments
Delavirdine	IDV AUC: increased by 44% (compared to 800 mg q8h).	Recommended dose: decrease IDV to 600 mg q8h + DLV 400 mg tid.
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 bid + RTV 200 mg bid + EFV 600 mg qhs.
Fluconazole	No significant interaction	Use 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 bid + LPV/r 400/100 mg bid.
Nevirapine	No effect on NVP; Decrease IDV AUC by 28%.	IDV 1000 mg q8h + NVP 200 mg bid or IDV 800 mg bid + RTV 200 mg bid + NVP standard dose.
Nelfinavir	NFV AUC: increased by 83%.	Dose: IDV 1200 mg bid + NFV 1250 bid (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 bid + RTV 100 mg bid (high rate of nephrotoxicity) or I, or IDV 400 mg bid + RTV 400 mg bid (high rate of GI toxicity).
Saquinavir	Increase SQV AUC by 4-7 fold; No effect on IDV.	No data. Possible in vitro antagonism.
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).
Amiodarone	In a case report amiodarone levels increased by 44%.	Contraindicated. Monitor for amiodarone toxicity. Consider alternative antiarrhythmic with cardiology consult.
Amlodipine	May increase serum levels of amlodipine.	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 and DLV 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 the background regimen). Consider IDV 800 mg q8h + APV 800 mg tid (limited data).
Artemether (artemisinin)	May increase serum levels of artemether.	Applies to all PIs and DLV: Close monitoring for artemether toxicity (bone marrow suppression, bradycardia, and seizure).
Astemizole	May 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.
Azathioprine	Interaction unlikely.	Use standard doses.
Bepridil	May 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 and DLV since significant increase in bepridil serum levels can result in pro-arrhythmic events such as VT, PVC, and VF.
Carbamazepine	IDV 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 chlordiazepoxide	Applies to all PIs and DLV: Consider an alternative benzodiazepine ( lorazepam, temazepam, or oxazepam).
Cisapride	May 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 and DLV: Consider an alternative benzodiazepine (lorazepam, oxazepam, or temazepam).
Cyclophosphamide	Cyclophosphamide: clearance decreased by 1.5 fold; IDV: no change.	Clinical significance unknown. May require cyclophosphamide dose adjustment.
Cyclosporine	May 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.
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.
Digoxin	Digoxin serum concentration may be increased with IDV/r co-administration.	Monitor digoxin serum concentration closely with co-administration.
Diltiazem	May 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 and DLV 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.
Disopyramide	May increase disopyramide serum levels.	Applies to all PIs and DLV: No data. Monitor disopyramide serum levels (target: 2 to 7.5 mcg/mL).
Docetaxel	May increase serum levels of docetaxel.	Applies to all PIs and DLV: No data. Close monitoring of chemotherapy-induced toxicity recommended.
Dofetilide	May 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.
Doxorubicin	Doxorubicin: 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 alkaloids	May 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 and DLV: Consider an alternative benzodiazepine (lorazepam, oxazepam, or temazepam).
Ethosuximide	May increase serum levels of ethosuximide.	Applies to all PIs and DLV: Consider switching to valproic acid for the treatment of absence seizure.
Etoposide	May increase serum levels of etoposide.	Applies to all PIs and DLV: No data. Close monitoring of chemotherapy-induced toxicity recommended.
Felodipine	May increase serum levels of felodipine.	Applies to all PIs and DLV: 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 and DLV 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.
Flecainide	May increase antiarrhythmic serum levels.	Applies to all PIs and DLV: 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 and DLV: 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.
Food	IDV 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 bid + RTV 100 mg bid) removes food effect and is preferred.
Garlic Supplements	Studies 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 bid).	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.
Granisetron	May increase serum levels of granisetron.	Applies to all PIs and DLV: Due to the large therapeutic index of granisetron, potential interaction is unlikely to be clinically significant.
Grape fruit or Seville orange juice	No 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 bid) 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.
Ifosphamide	May increase serum levels of ifosphamide.	Applies to all PIs and DLV: No data. Close monitoring of chemotherapy-induced toxicity recommended.
Irinoteacan	May increase irinotecan serum levels.	Applies to all PIs and DLV: Co-administration of ATV is contraindicated by manufacturer. All PIs and DLV 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 bid. No data with IDV/RTV co-administration. Consider IDV 800 mg bid + RTV 100mg bid 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 bid + RTV 100 mg bid (do not exceed ketoconazole 200 mg/d) with aggressive hydration due to potential increased risk of nephrolithiasis.
Lidocaine	May increase antiarrhythmic serum levels.	Applies to all PIs and DLV: 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.
Mefloquine	May increase serum levels of mefloquine.	Applies to all PIs and DLV: 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.
Mexiletine	May increase antiarrhythmic serum levels.	Applies to all PIs and DLV: 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.
Mirtazapine	May increase serum levels of mirtazapine.	Applies to all PIs and DLV: Use with caution. Consider an alternative antidepressant (i.e SSRI: escitalopram, citalopram, sertraline, or fluoxetine).
Mycophenolate	Interaction unlikely. No significant interaction observed with NVP.	Applies to all PIs and NNRTIs: No significant interaction observed with NVP. Use standard dose.
Nefazodone	May increase serum levels of nefazodone.	Applies to all PIs and DLV: Use with caution. Consider an alternative antidepressant (i.e SSRI: escitalopram, citalopram, sertraline, or fluoxetine).
Nifedipine	May increase serum levels of nifedipine.	Applies to all PIs and DLV: 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 and DLV 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.
Nisoldipine	May increase serum levels of nisoldipine.	Applies to all PIs and DLV: 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 and DLV 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 Ethinylestradiol	Norethindrone levels increased by 26% and Ethinylestradiol by 24%.	Use of barrier method of contraception is recommended to prevent pregnancy.
Paclitaxel	May increase paclitaxel serum levels.	Applies to all PIs and DLV: Data limited to case reports of severe toxicity associated with DLV and LPV/r co-administration with paclitaxel. Since all PIs have the potential of significantly increasing paclitaxel serum levels, close monitoring of paclitaxel-induced toxicity is recommended.
PCP	May significantly increase serum levels of PCP.	Applies to all PIs and DLV. Avoid all illicit drug use with PIs and NNRTIs.
Phenobarbital	May 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.
Phenytoin	May 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.
Pimozide	May 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.
Propafenone	May 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.
Rifabutin(RFB)	Rifabutin AUC increased by 204%; IDV AUC decreased by 32%.	Recommended dose: RFB 150 mg qd (or 300 mg 3x/wk) + IDV 1000 mg q8h or RFB 150 mg qod (or 150 mg 3x/wk) + IDV 800 mg + RTV 100 mg bid (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.
Sildenafil	May 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.
Sirolimus	May 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 wort	IDV AUC decreased by 57%.	Contraindicated with all PIs and NNRTIs. Use an alternative antidepressant.
Tacrolimus	May 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.
Tadalafil	May increase serum levels of tadalafil.	Applies to all PIs and DLV: 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.
Tamoxifen	May increase serum levels of tamoxifen.	Applies to all PIs and DLV: No data. Close monitoring of tamoxifen-induced toxicity recommended.
Teniposide	May increase serum levels of teniposide.	Applies to all PIs and DLV: No data. Close monitoring of teniposide-induced toxicity recommended.
Terfenadine	May 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.
THC	Based 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.
Tipranavir	No data	Avoid co-administration.
Trazadone	May increase serum levels of trazadone.	Applies to all PIs and DLV: 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).
Vardenafil	Vardenafil 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.
Venlafaxine	IDV 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).
Verapamil	May increase serum levels of verapamil.	Applies to all PIs and DLV: 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 and DLV 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.
Vinblastine	May increase serum levels of vinblastine.	Applies to all PIs and DLV: No data. Close monitoring of vinblastine-induced toxicity recommended.
Vincristine	May increase serum levels of vincristine.	Applies to all PIs and DLV: 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 bid + RTV 100 mg bid) 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.
Warfarin	Case 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/A/C, 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, L33F, 36I, 46I/L, 54V, 71V/T, 73S/A, 77I, 84V/A/C, 90M): >3 results in >4-fold decrease in susceptibility.
RTV boosting can increase 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).

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Abbreviations