Zambian HIV Guidelines:: Saquinavir

	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>

Saquinavir

Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
04-01-2008

Available formulation in Zambia: Capsule: 200 mg.
Not first-line protease inhibitor. Inferior to LPV/r in PI-experienced patients, but non-inferior in treatment-naive patients.
Inferior to to EFV in ARV-naïve patients (possibly due to higher rates of GI intolerance in SQV/r-treated patients).
High pill burden compared to LPV/r.
Less effect on triglycerides than LPV/r.

Zambia Information Author: Paul A. Pham, Pharm.D.

INDICATIONS

FDA

Treatment of HIV-infection in combination with other antiretroviral agents.

FORMS

brand name	generic	Mfg	brand forms	cost*
Invirase	Saquinavir (SQV). Previously referred to as SQVhgc (hard-gel cap) to distinguish from SQVsgc (Fortovase), which is no longer manufactured.	Roche	oral hard gel capsule (hgc) 200 mg	$2.82
			oral tablet 500 mg	$6.86

*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: minimum 6/d (based on 2 SQV 500 mg tabs bid + 1 RTV 100 mg cap bid). Storage: SQV cap and tab can be stored at room temperature.

FDA approved dose: SQV 1000 mg bid + RTV 100 mg bid with or without food (500 mg tab preferred: lower pill burden)
Not recommended without RTV boosting
SQV 2000 mg qd + RTV 100 mg qd. Unapproved dose. Clinic trials in progress (for PI-naive pts only)
SQV 400 mg bid + RTV 400 mg bid (rarely used due to poor tolerability)
With LPV/r: SQV1000 mg bid + LPV/r 400/100 mg (2 tabs) bid
With NFV: SQV 1200 mg bid + NFV 1250 mg bid (large pill burden; rarely used)
With ATV: Consider ATV 300 mg + RTV 100 mg +SQV 1500-2000 mg qd. SQV 1200 mg qd + ATV 400 mg qd (poor clinical outcome) OR SQV 2000 mg qd +ATV 400 mg qd (based on PK data)
With NVP: SQV 1000 mg bid + RTV 100 mg bid + NVP 200 mg bid OR SQV 400 mg bid + RTV 400 mg bid + NVP 200 mg bid.
With EFV: Consider SQV 1000 mg bid + RTV 100 mg bid + EFV 600 mg qhs .
With DLV: SQV 800 mg tid + DLV 600 mg tid (limited data; rarely used)
With TPV: SQV AUC decreased by 76%. Co-administration not recommended.
With IDV: insufficient data.
With FPV: Consider SQV1000 mg bid + RTV 100-200 mg bid + FPV 700 mg bid
With DRV: Avoid co-administration.
With maraviroc: SQV 1000 mg bid + RTV 100 mg bid + MVC 150 mg bid.
With etravirine (TMC-125): SQV 1000 mg bid + RTV 100 mg bid + ETV usual dose.
With raltegravir (MK0518): usual doses likely.

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose likely

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Usual dose likely

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

Usual dose likely

DOSING IN HEMODIALYSIS

Usual dose (not removed in HD)

DOSING IN PERITONEAL DIALYSIS

No data: Usual dose likely (Unlikely to be removed in dialysis due to high protein binding and large volume of distribution.)

DOSING IN HEMOFILTRATION

No data

ADVERSE DRUG REACTIONS

COMMON

GI intolerance: nausea, diarrhea, abdominal pain

OCCASIONAL

Insulin resistance +/- hyperglycemia +/- diabetes
Hyperlipidemia: increased triglycerides and/or cholesterol (may be less common or severe than with other PIs except ATV)
Transaminase elevation (comparable to other PIs)
Fat accumulation

DRUG INTERACTIONS

Substrate and weak inhibitor of CYP3A4. May modestly increase serum level of other CYP3A4 substrates. Drugs that are inducers of CYP3A4 may decrease SQV levels.

Drug-to-Drug Interactions

Drug-to-Drug Interaction

Drug	Effect of Interaction	Recommendations/Comments
Clarithromycin	Clarithromycin increases SQV AUC 177% and SQV increases clarithromycin AUC 45%	Use standard doses.
Fluconazole	No significant interaction	Usual dose recommended.
Indinavir (IDV)	SQV AUC increased 4-7- fold; no effect on IDV	In vitro antagonism. Clinical significance unknown. Avoid co-administration.
Lopinavir/ritonavir (LPV/rtv)	Saquinavir AUC: increased 836%; Cmin: increased 1700%	Dose: SQV 800-1000 mg bid + LPV/r 400/100 mg bid.
Nelfinavir (NFV)	SQVsgc AUC increased by 3 to 5-fold. NFV AUC increased by 20%	Consider: SQV 1200 mg bid + NFV 1250 mg bid (limited clinical experience and rarely used)
Rifampin	Rifampin: SQV AUC: decreased by 84%	Coadministration of rifampin with SQV (as sole PI) is not recommended due to significant decrease in SQV PK parameters. Boosting SQV with RTV is not recommended due to high incidence (39.3%) of hepatotoxicity.
Ritonavir ( RTV )	SQV AUC increased by 20-fold.	Recommended doses: RTV 100 mg bid + SQV 1000 mg bid. RTV 400 mg bid + SQV 400 mg bid (higher rate of GI intolerance and hepatoxicity). RTV 100 mg + SQV 2000 mg qd (clinical studies in progress).
Darunavir (DRV)	DRV AUC decreased 26%.	Avoid co-administration.
Fosamprenavir (FPV)	SQV AUC decreased 14% (NS).	Consider SQV/r 1000/100-200 mg bid + FPV 700 mg bid
Etravirine (TMC-125)	Etravirine AUC decreased 33%.	Clinical significance unknown. SQV/r 1000/100 mg bid plus standard dose ETV likely.
Alprazolam	May increase serum level of alprazolam	Applies to all PIs and DLV: Consider an alternative benzodiazepine (i.e lorazepam, oxazepam, or temazepam)
Amiodarone	May significantly increase amiodarone serum level	Applies to all PIs and DLV: Data limited to case report of increased amiodarone levels with IDV co-administration. RTV, APV, and ATV manufacturer recommends against use of amiodarone, but all PIs and DLV have the same potential of significantly increasing amiodarone serum level. If coadministration can not be avoided, monitor for amiodarone ADRs (PFTs, TSH). Consider monitoring serum level of amiodarone, but its long half-life may make titration difficult.
Amlodipine	May increase serum level of amlodipine	Applies to all PIs and DLV: Data limited to an interaction study conducted with ATV and diltiazem which resulted in doubling of diltiazem serum level (this led to PR interval prolongation). All PIs and DLV have the potential of prolonging PR interval with calcium channel blocker coadministration. Ca channel blockers should be started with 50% of the recommended dose and slowly titrated with close monitoring of BP and pulse.
Amprenavir (APV)	SQV level decreased by 18%. APV intrinsic clearance was not affected.	Data based on PK modeling with many confounding variables (i.e EFV in the background regimen). Consider SQV 800 mg tid + APV 800 mg tid (but APV essentially replaced by FPV).
Artemether (artemisinin)	May increase serum level 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 level.	Contraindicated due to the potential for cardiac arrhythmias. Recommended alternative antihistamine: loratadine, fexofenadine, desloratidine, or cetirizine.
Atorvastatin	Atorvastatin increased by 450% (studied with RTV/SQV)	Use with caution. Use lowest possible dose of atrovastatin (10mg). Consider pravastatin or rosuvastatin.
Azathioprine	Interaction unlikely	Applies to all PIs and NNRTIs: Use standard dose
Bepridil	May significantly increase bepridil serum level	Applies to all PIs and DLV: No data. The manufacturer of ATV, RTV, and APV does not recommend bepridil coadministration. This contraindication should be extend to all PIs and DLV since a significant increase in bepridil serum level can result in pro-arrhythmic events such as VT, PVC, and VFib.
Carbamazepine	May decrease serum levels of SQV	Consider alternative anticonvulsants (i.e valproic acid, lamotrigine, levetiracetam, or topiramate). Monitor anticonvulsant levels and SQV Cmin with co-administration.
Chlordiazepoxide	May increase serum level of chlordiazepoxide	Applies to all PIs and DLV: Consider an alternative benzodiazepine (i.e lorazepam, temazepam, or oxazepam)
Cisapride	May significantly increase cisapride serum level.	Contraindicated due to potential for cardiac arrhythmias. Recommended alternative: metoclopramide.
Clorazepate	May increase serum level of clorazepate	Applies to all PIs and DLV: Consider an alternative benzodiazepine (i.e lorazepam, temazepam, or oxazepam)
Cyclophosphamide	May increase serum level of cyclophosphamide	Applies to all PIs and DLV: Data limited to an interaction study conducted with IDV resulting in a 50% increase in cyclophosphamide serum level. Since all PIs and DLV have the potential of increasing cyclophosphamide levels, close monitoring of cyclophosphamide-induced toxicity is recommended.
Cyclosporine	Cyclosporine Cmin: increased 300%	Case report of significant increase of cyclosporine levels. Monitor serum level of cyclosporine closely with co-administration. Cyclosporine dose may need to be decreased.
Dexamethasone	May decrease SQV serum levels	Clinical significance unknown
Digoxin	Digoxin AUC and Cmax increased by 49% and 27%, respectively.	Reduce digoxin dose with SQV/r co-administration. Magnitude of interaction higher in females (AUC increased 74% in females vs. 33% in males). Use with close monitoring. Significant increased in PR prolongation observed.
Digoxin	Digoxin serum concentrations may be increased.	Monitor digoxin serum concentrations closely with saquinavir co-administration. The dose of digoxin may need to be reduced.
Diltiazem	May increase serum level of diltiazem	Applies to all PIs and DLV: Data limited to an interaction study conducted with ATV which resulted in doubling of diltiazem serum level (this led to PR interval prolongation). All PIs and DLV have the potential of prolonging PR interval with diltiazem coadministration. Diltiazem should be started with 50% of the recommended 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 level (target: 2-7.5 mcg/mL).
Docetaxel	May increase serum level of docetaxel	Applies to all PIs and DLV: No data. Close monitoring of chemotherapy-induced toxicity recommended.
Dofetilide	May significantly increase serum level of dofetilide	Applies to all PIs and DLV: 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.
Echinacea	May decrease SQV serum level. Echinacea decreased (400 mg 4x/d) CYP3A4 substrate (midazolam) by 23%.	Clinical significance unknown but should avoided with PIs and NNRTIs until the safety of this combination is further evaluated.
Ergot Alkaloid	May significantly increase serum level of ergotamine resulting in acute ergot toxicity	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 level of estazolam	Applies to all PIs and DLV: Consider an alternative benzodiazepine (i.e 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 level of etoposide	Applies to all PIs and DLV: No data. Close monitoring of chemotherapy induced toxicity recommended.
Fatty Food	SQV AUC increased 18-fold	SQV should be taken with food.
Felodipine	May increase serum level 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 level (this led PR interval prolongation). All PIs and DLV has the potential of prolonging PR interval with calcium channel blockers coadministration. Calcium channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse.
Fentanyl	May increase fentanyl serum level	Use with caution. Consider morphine.
Flecainide	May increase antiarrhythmic serum levels	Applies to all PIs and DLV: Avoid coadministration; if necessary, monitor flecainide trough level with coadministration. Target: 200-1000ng/ml. Toxicity is frequent with trough serum levels above 1000 ng/mL.
Flurazepam	May increase serum level of flurazepam	Applies to all PIs and DLV: Consider an alternative benzodiazepine (i.e lorazepam, oxazepam, or temazepam).
Fluticasone	Fluticasone AUC increased 350-fold (studied with RTV 100 mg q12h)	Avoid long-term co-administration. Consider beclomethasone.
Garlic supplement	SQV Cmin decreased by 49%; AUC: decreased 51%; after 10 d washout period, pharmacokinetic values returned to only 60-70% of baseline.	Avoid concurrent administration with unboosted SQV. Clinical significance of boosted (SQV/RTV) is not known, but unlikely to be significant.
Granisetron	May increase serum level of granisetron	Applies to all PIs and DLV: Due to the large therapeutic index of granisetron, potential interaction is unlikely to be clinically significant.
Grapefruit juice	SQV AUC: increased 50% (grapefruit juice 200 mL from concentrate)	May be a beneficial 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 level of ifosphamide	Applies to all PIs and DLV: No data. Close monitoring of chemotherapy-induced toxicity recommended.
Irinoteacan	May increase irinoteacan serum level	Not recommended. All PIs and DLV also have the potential for significant interaction with Irinotecan, therefore the coadministration should be done with extreme caution.
Itraconazole	SQV: no significant change. Itraconazole level:no significant change.	No significant change. Use standard dose of both drugs
Ketoconazole	SQV AUC increased 30%	Use standard dose. If SQV coadministered with RTV, do not exceed ketoconazole 200 mg/d.
Lidocaine	May increase antiarrhythmic serum levels	Applies to all PIs and DLV: No data. Use with caution; monitor lidocaine serum level (target: 1.5-6 mcg/mL) with coadministration.
Lovastatin	May increase lovastatin serum level	Contraindicated. Recommended alternatives include pravastatin (but pravastatin AUC decreased by 50% with SQV/r), fluvastatin, and rosuvastatin (and possibly atorvastatin). Monitor for adverse effects due to limited clinical data with these agents.
Maraviroc	Maraviroc AUC increased 732%	Recommended dose: SQV 1000 mg bid + RTV 100 mg bid + MVC 150 mg bid.
Mefloquine	May increase serum levels of mefloquine	Applies to all PIs and DLV: If available consider mefloquine serum level monitoring. Monitor for mefloquine toxicity (i.e dizziness, LFTs, and periodic ophthalmic examination).
Methadone	S-methadone AUC: decreased 25%; R-methadone (active) AUC: decreased 20% (studied with SQV/RTV)	Monitor for withdrawal symptoms but unlikely to be significant. No dose adjustment needed.
Mexiletine	May increase antiarrhythmic serum levels	Applies to all PIs and DLV: No data. Use with caution. Monitor EKG and serum level. Serum levels exceeding 1.5-2 mcg/mL have been associated with an increased risk of toxicity.
Midazolam	May increase midazolam serum level.	Concurrent administration contraindicated due to potential for prolonged sedation. Use alternative: lorazepam, oxazepam, or temazepam. Single dose midazolam may be used (chronic use not recommended).
Milk thistle	Unknown	Data limited to an interaction study with milk thistle and IDV. IDV AUC unchanged and IDV Cmin decreased by 47%. Avoid co-administration. No data available for other PIs and NNRTIs.
Mirtazapine	May increase serum level 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 level 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 level 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 level (this led PR interval prolongation). All PIs and DLV have the potential of prolonging PR interval with calcium channel blocker co-administration. Calcium channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse.
Nisoldipine	May increase serum level 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 level (this led PR interval prolongation). All PIs and DLV have the potential of prolonging PR interval with calcium channel blocker coadministration. Calcium channel blockers should be started with 50% of the recommended dose and slowly titrated with close monitoring of BP and pulse.
Oral Contraceptives	No data for NFV. Ethinyl estradiol AUC decreased by 47%, Norethindrone decreased by 18%.	Recommend an alternative form of contraception.
Paclitaxel	May increase paclitaxel serum level	Applies to all PIs and DLV: Data limited to case reports of severe toxicity associated with DLV and LPV/r coadministration with paclitaxel. Since all PIs have the potential of significantly increasing paclitaxel serum level, close monitoring of paclitaxel-induced toxicity is recommended.
PCP	May significantly increase serum level of PCP	Applies to all PIs and DLV: Avoid all illicit drug use with PIs and DLV.
Phenobarbital	May decrease serum levels of SQV	Consider alternative anticonvulsants (i.e valproic acid, lamotrigine, levetiracetam, or topiramate). Monitor anticonvulsant levels and SQV Cmin with coadministration.
Phenytoin	May decrease serum levels of SQV	Consider alternative anticonvulsants (i.e valproic acid, lamotrigine, levetiracetam, or topiramate). Monitor anticonvulsant levels and SQV Cmin with coadministration.
Pimozide	May significantly increase pimozide serum level resulting in QTc prolongation.	Contraindicated. Consider alternative: olanzapine.
Pravastatin	Pravastatin AUC decreased by 50% (studied with SQV/RTV)	Clinical significance unknown. May need to increase dose of pravastatin.
Prednisone	Prednisolone serum concentration may be increased with SQV/r co-administration.	Dose adjustment may be needed with long-term co-administration.
Propafenone	May increase antiarrhythmic serum levels	Applies to all PIs and DLV: No data. Co-administration should be avoided. Serum levels are not routinely recommended due to the poor correlation with efficacy and toxicity.
Quinidine	May increase antiarrhythmic serum levels	Applies to all PIs and DLV: No data. Contraindicated with RTV. With all PIs and NNRTIs co-administration, monitor EKG (QTc) and serum level: Target: 2-5 mcg/mL.
Raltegravir (MK0518)	Interaction unlikely	Data with RTV (100 mg bid) did not affect RAL PK parameters. SQV/r 1000/100 mg bid plus standard dose RAL likely.
Ranitidine	No significant interaction	Use standard dose
Rifabutin	SQV AUC decreased by 43%.	Do not co-administer SQV with rifabutin as a sole PI. Consider RTV 400 mg bid + SQV 400 mg bid with rifabutin 150 mg 3x/wk OR SQV1000 mg + RTV100 mg bid with rifabutin 150 mg qod (No data, but likely to attain good PK).
Rifapentine	SQV serum levels may be significantly decreased.	Avoid coadministration. Consider using rifabutin.
Rosuvastatin	Other CYP3A4 inhibitor (i.e erythromycin) did not affect rosuvastatin serum level.	Applies to PIs and NNRTIs: Interaction unlikely, but close monitoring recommended due to limited clinical data.
Sildenafil	Sildenafil AUC increased by 210% (with SQV1200mg tid).	Use with caution. Do not exceed 25 mg of sildenafil in 48-hr period.
Simvastatin	Simvastatin AUC: increased 3059% (studied with SQV/RTV)	Contraindicated. Recommended alternatives include atorvastatin, pravastatin (but pravastatin AUC decreased by 50% with SQV/r), fluvastatin, and rosuvastatin. Monitor for adverse effects due to limited clinical data with these agents.
Sirolimus	May significantly increase serum level of sirolimus	Applies to All PIs: Dose sirolimus based on serum level. A significantly reduction of sirolimus dose with all PIs coadministration is highly likely.
St. John's wort	May decrease SQV serum level	Contraindicated. Use an alternative (more effective) antidepressant.
Tacrolimus	May significantly increase serum level of tacrolimus	Applies to all PIs: Dose tacrolimus based on serum level. A significantly reduction of tacrolimus dose with all PIs co-administration is recommended.
Tadalafil	May increase serum level 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 level of tamoxifen	Applies to all PIs and DLV: No data. Close monitoring of tamoxifen-induced toxicity recommended.
Teniposide	May increase serum level of teniposide	Applies to all PIs and DLV: No data. Close monitoring of teniposide-induced toxicity recommended.
Terfenadine	Terfenadine AUC: increased by 368%; Cmax: increased by 253%	Contraindicated due to the potential for cardiac arrhythmias. 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.
Trazadone	May increase serum level of trazadone	Applies to All PIs and DLV: Use with caution. Consider an alternative antidepressant (i.e SSRI:escitalopram, citalopram, sertraline, or fluoxetine)
Triazolam	May significantly increase triazolam serum level	Contraindicated. Alternative benzodiazepine that may be used(temazepam, oxazepam, or lorazepam).
Vardenafil	May significantly increase serum level of vardenafil.	Applies to all PIs and DLV: Do not exceed vardenafil 2.5 mg in 72 hrs (with RTV) or 2.5 mg in 24 hrs (with other PIs and DLV). Consider sildenafil due to more clinical data and less pronounced interaction. Avoid coadministration with IDV.
Verapamil	May increase serum level 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 level (this led PR interval prolongation). All PIs and DLV have the potential of prolonging PR interval with calcium channel blocker coadministration. Calcium channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse.
Vinblastine	May increase serum level of vinblastine	Applies to all PIs and DLV: No data. Close monitoring of vinblastine- induced toxicity recommended.
Vincristine	May increase serum level of vincristine	Applies to all PIs and DLV: No data. Close monitoring of vincristine- induced toxicity recommended.
Voriconazole	May decrease voriconazole AUC with SQV/r. Voriconazole may increase co-administered SQV.	Significant interaction with EFV and RTV (400 mg bid); contraindicated. Voriconazole AUC decreased 39% with RTV 100 mg bid co-administration; avoid co-administration with boosted PI. Consider another antifungal for aspergillosis (i.e ambisome or caspofungin) or use with TDM. Higher dose of voriconazole may be needed.

RESISTANCE

L90M: Selected by SQV, resulting in intermediate SQV and NFV resistance, and partial cross-resistance to other PIs.
G48V: Selected by SQV, resulting in intermediate SQV resistance and low-level cross-resistance to other PIs.
54V/L, 71VT, 73S, 77I, 82A, 84V, others: Multiple mutations increase resistance.

PHARMACOLOGY

Pharmacology

COMMENTS

Pros: Less effect on lipids than other LPV/r (except ATV), improved pill burden with 500 mg tablet; reasonable choice in PI-naive pts (not inferior compared to LPV/r); clinical trials of SQV/r 2000/100 mg qd in PI-naive pts in progress
Cons: Inferior to LPV/r in PI-experienced pts; higher pill burden than with LPV/r, ATV/r or FPV/r. ATV 400 mg + SQV 1200 mg did not perform well in pts with moderate PI experience.

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Abbreviations