Zambian HIV Guidelines:: Fosamprenavir

	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>

Fosamprenavir

Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
06-11-2008

Currently not available in Zambia.

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

INDICATIONS

FDA

Treatment of HIV-infected pts in combination with other ARVs

FORMS

brand name	generic	Mfg	brand forms	cost*
Lexiva (U.S.); Telzir (Europe)	Fosamprenavir calcium (FPV)	GlaxoSmithKline	oral tablet 700 mg	$12.75
			oral suspension 50 mg/ml (225 ml bottle)	$117.24

*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: 4 tabs/d (unboosted or boosted with RTV)

FPV 700 mg twice-daily + RTV 100 mg twice-daily with or w/o food (author's preference due to superior PK profile & lack of resistance with failure) OR FPV 1400 mg twice-daily with or w/o food OR FPV 1400 mg + RTV 100-200 mg once-daily with or w/o food (once-daily dosing and unboosted regimen for PI-naive pts only).
With EFV: FPV 700 mg twice-daily + RTV100 mg twice-daily + EFV 600 mg qhs OR FPV 1400 mg once-daily + RTV 300 mg once-daily + EFV 600 mg qhs
With LPV/r: Generally not recommended. Consider FPV 1400 mg twice-daily + LPV/r 600/150 mg twice-daily with TDM
With NFV, IDV: Inadequate data; avoid co-administration.
With DLV: Not recommended
With ATV: Inadequate data; avoid or consider ATV 300 mg once-daily + FPV/r 700/100 mg twice-daily .
With SQV: Inadequate data; avoid or consider SQV/r 1000/100-200 mg twice-daily + FPV 700 mg twice-daily.
With TPV: Not recommended.
With NVP: FPV/r 700/100 mg twice-daily + NVP 200 mg twice-daily
With RAL: No data. Consider FPV/r 700/100 mg twice-daily + standard dose raltegravir with close monitoring.
With ETR: avoid co-administration per manufacturer, but clinical significance unclear. Consider FPV/r 700/100 mg twice-daily + standard dose etravirine.
With MVC: no data. Consider FPV/r 700/100 mg twice-daily + MVC150 mg twice-daily.
With DRV/r: no data. Avoid co-administration.
FPV tablets and liquid formulations interchangeable, but liquid formulation should be administered on empty stomach in adults (but with food in children).

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose

DOSING FOR GLOMERULAR FILTRATION OF 10-50

No data. Usual dose likely.

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

No data. Usual dose likely.

DOSING IN HEMODIALYSIS

No data. Usual dose likely (on days of HD dose post HD).

DOSING IN PERITONEAL DIALYSIS

No data. Usual dose likely.

DOSING IN HEMOFILTRATION

No data.

ADVERSE DRUG REACTIONS

ADRs similar to comparator PIs (NFV and LPV/r). GI intolerance and triglyceride elevation slightly higher compared to ATV/r.

COMMON

Rash in 12-33% of pts (<1% require discontinuation).
GI intolerance in up to 40-53%% (severe in 5-10%). Diarrhea less common than with NFV, but higher compared to ATV/r. .

OCCASIONAL

Triglyceride and LDL elevation(lower incidence compared to NFV); with RTV (200 mg/d) co-administration, incidence of hypertriglyceridemia (>750 mg/dL) was 11%. With FPV/r 1400/100 mg once-daily, LDL elevation comparable to ATV/r; however, triglyceride elevation was slightly higher in the FPV/r treated group (34 vs 7 g/dL increase from baseline).
Insulin resistance
Elevated transaminases in 6-8%
Fat accumulation

RARE

Stevens-Johnson syndrome reported. FPV has a sulfa moiety; incidence of cross-reaction with other sulfa drugs unknown. Use with caution in pts with severe skin reaction secondary to sulfonamides.

DRUG INTERACTIONS

Substrate, inhibitor, and likely an inducer of CYP3A4. CYP3A4 inhibitors may increase APV levels. CYP3A4 inducers may decrease APV levels. FPV may increase or decrease levels of CYP3A4 substrates.

Drug-to-Drug Interactions

Drug-to-Drug Interaction

Drug	Effect of Interaction	Recommendations/Comments
Darunavir	No data	Avoid co-administration.
EFV	FPV 700 mg twice-daily + RTV 100 mg twice-daily + EFV 600 mg qhs x 2 wks: APV Cmin decreased by 17% compared to twice-daily boosted FPV. FPV 1400 mg once-daily + RTV 200 mg once-daily + EFV 600 mg qhs x 2 wks: APV Cmin decreased by 36% with EFV co-administration compared to once-daily boosted FPV.	Recommended dose: FPV 700 mg twice-daily + RTV 100 mg twice-daily + EFV 600 mg once-daily OR FPV 1400 mg once-daily + RTV 300 mg once-daily + EFV 600 mg qhs.
LPV/r	FPV 1400mg twice-daily + LPV/r 533mg/133mg twice-daily: APV Cmin decreased by 42% (compared to FPV 700mg + RTV100mg twice-daily) but 3-fold higher Cmin (compared to FPV1400mg twice-daily historical control); no significant change in LPV serum levels (compared to LPV/r 400mg/100mg twice-daily).	Co-administration generally not recommended. Consider FPV 1400 mg twice-daily + LPV/r 600/150 mg twice-daily. Consider TDM with co-administration.
Rifampin	No data, but significant decrease in APV serum levels expected.	Co-administration not recommended.
RTV	When co-administered with RTV, APV AUC increased by over 2-fold, Cmin increased by 4-fold w/ once-daily administration and 6-fold w/ twice-daily administration (compared to FPV 1400mg twice-daily).	Dose for PI experienced pts: FPV 700 mg twice-daily + RTV 100 mg twice-daily. Daily administration (FPV 1400 mg once-daily + RTV 200 mg once-daily) can be used in PI-naive pts.
Fluconazole	Interaction unlikely	Use standard doses of both drugs.
Clarithromycin	May increase clarithromycin AUC with FPV/r	No data with FPV, but APV increased 18% with clarithromycin co-administration. Consider dose adjustment renal insufficiency. CrCl 30-60 ml/min: 50% of dose. <30ml/min: 25% of the dose.
Etravirine	Amprenavir AUC increased by 69%.	Manufacturer recommends avoiding co-administration, but clinical significance unclear. Consider FPV/r 700/100 mg twice-daily with standard dose etravirine.
Maraviroc	FPV/r may increase maraviroc's serum concentrations.	No data. Consider FPV/r 700/100 mg twice-daily + maraviroc 150 mg twice-daily.
Nevirapine	APV serum concentration increased by 29% (compared to historical control). NVP increased 13%. .	FPV/r 700/100 mg twice-daily + NVP 200 mg twice-daily
Indinavir	APV AUC increased 33%.	Dose regimens not established. Avoid.
Tipranavir	APV AUC decreased 44%	Avoid co-administration.
Nelfinavir	APV AUC increased 150%.	Inadequate data; avoid co-administration.
Delavirdine	DLV AUC decreased 61%. APV AUC increased 130%	Avoid co-administration.
Atazanavir (ATV)	ATV AUC decreased 22%. Fosamprenavir AUC increased 78%.	Clinical significance of a 22% decrease in ATV AUC unknown. Consider FPV/r 700/100 mg twice-daily + ATV 300 mg once-daily.
Saquinavir (SQV)	SQV AUC decreased 14% (NS).	Limited data. Avoid or consider SQV/r 1000/100-200 mg twice-daily + FPV 700 mg twice-daily.
Alfuzosin	May significantly increase alfuzosin serum concentrations.	Avoid co-administration.
Alprazolam	May increase serum levels of alprazolam	Applies to all PIs and DLV: Consider alternative benzodiazepine (lorazepam, temazepam, or oxazepam).
Amilodipine	May increase serum levels 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 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.
Amiodarone	May significantly increase amiodarone serum levels	Applies to all PIs and DLV: Data limited to case report of increased amiodarone levels with IDV co-administration. The manufacturer of RTV, APV, and ATV recommends against use of amiodarone, but all PIs and DLV have the same potential of significantly increasing amiodarone serum levels. If co-administration can not be avoided, monitor for amiodarone ADRs (PFTs and TSH). Consider monitoring serum levels of amiodarone, but its long half-life may make titration difficult.
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	Atorvastatin AUC increased by 130% (w/o RTV) and 150% (w/RTV). No change in APV AUC.	Start with low doses (10-20 mg/d) and avoid doses > 40 mg/d or consider alternative agents (pravastatin, fluvastatin, or possibly rosuvastatin).
Azathioprine	Interaction unlikely	Applies to all PIs and NNRTI: Use standard dose.
Bepridil	May significantly increase bepridil serum levels	Applies to all PIs and DLV: No data. The manufacturer of ATV, RTV, and APV does not recommend bepridil co-administration, this contraindication should extend to all PIs and DLV since a significant increase in bepridil serum levels can result in pro-arrhythmic events such as VT, PVC, and VFib.
Carbamazepine	May decrease levels of PIs and NNRTI. PIs and NNRTI may increase or decrease carbamazepine levels.	Applies to all PIs and NNRTIs: Consider alternative anticonvulsants (valproic acid, lamotrigine, levetiracetam, or topiramate). Monitor carbamazepine levels and consider TDM of PIs and NNRTIs.
Chlordiazepoxide	May increase serum levels of chlordiazepoxide	Applies to all PIs and DLV: Consider alternative benzodiazepines (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 alternative benzodiazepines (lorazepam, temazepam, or oxazepam).
Cyclophosphamide	May increase serum levels 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 levels. Since all PIs and DLV have the potential of increasing cyclophosphamide levels, close monitoring of cyclophosphamide-induced toxicity is recommended.
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.
Dexamethasone	May decrease APV serum levels	Use with caution. Consider boosting (FPV700mg+ RTV100mg twice-daily).
Digoxin	Digoxin serum concentration may be increased with FPV/r co-administration.	Monitor digoxin serum concentrations closely with co-administration.
Diltiazem	May increase serum levels of diltiazem	Applies to all PIs and DLV: 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 the 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: 2-7.5 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 serum levels 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.
Ergot Alkaloid	May significantly increase serum levels 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 interaction occurred with CYP3A4 inhibitor).
Estazolam	May increase serum levels of estazolam	Applies to all PIs and DLV: Consider alternative benzodiazepines (lorazepam, temazepam, or oxazepam).
Ethinyl estradiol/norethindrone	May increase ethinyl estradiol serum concentrations. APV serum concentrations may decrease.	Avoid co-administration. Ethinyl estradiol Cmin increased 32%. Norethindrone AUC increased 18%, and Cmin increased 45%. Amprenavir AUC decreased 22%, and Cmin decreased 20% (studied using old formulation of amprenavir)
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 to PR interval prolongation). All PIs and DLV have the potential of prolonging the PR interval with Ca channel blockers co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse.
Flecainide	May increase serum levels of flecainide	Applies to all PIs and DLV: Avoid co-administration; if necessary, monitor flecainide trough levels with co-administration. Target: 200-1000ng/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 alternative benzodiazepines (lorazepam, temazepam, or oxazepam).
Fluticasone	Fluticasone AUC increased 350-fold (studied with RTV 100 mg q12h).	Avoid long-term co-administration. Consider beclomethasone.
Garlic Supplement	49% and 51% reduction in SQV AUC and Cmin, respectively	Studies only done with SQV, but garlic may affect the serum levels of other PIs and NNRTIs. Avoid co-administration of garlic with other 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.
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.
Irinotecan	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 co-administration should be done with extreme caution.
Itraconazole	May increase itraconazole serum concentrations	Monitor for itraconazole serum concentrations.
Ketoconazole	May increase ketoconazole serum concentrations	Do not exceed ketoconazole 200 mg/day.
Ketoconazole	May increase APV and ketoconazole serum concentrations.	With old APV formulation, APV AUC increased 32% and ketoconazole AUC increased 44%.Use standard dose of both drugs, but 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 levels (target:1.5-6 mcg/mL) with co-administration.
Lovastatin	Serum levels of lovastatin may be significantly increased	Contraindicated. Recommended alternatives include pravastatin, rosuvastatin, or fluvastatin (and atorvastatin - start with 10mg/d). Monitor for ADRs due to limited clinical data.
Maalox	APV AUC decreased by 18%	No significant interaction.
Mefloquine	May increase serum levels of mefloquine	Applies to all PIs and DLV: Monitor mefloquine serum levels and mefloquine-induced toxicity (i.e dizziness, LFTs, and periodic ophthalmic examination).
Methadone	May decrease methadone-R AUC by 13% (studied with APV)	Monitor for withdrawal symptoms.
Methadone	S-methadone serum concentrations may be decreased.	Studied with APV. S-methadone (active) was decreased 13% and APV AUC was decreased 25%; no withdrawal symptom observed. Co-administer with close monitoring.
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 1.5-2 mcg/mL have been associated with an increased risk of toxicity.
Midazolam	May significantly increase midazolam levels	Chronic use of midazolam should be avoided; single use IV midazolam may be used. Consider alternative benzodiazepines(temazepam, oxazepam, or lorazepam).
Milk thistle	Data limited to a drug interaction study with milk thistle and IDV. IDV AUC unchanged but Cmin decreased by 47%.	Clinical significance unknown. May affect the serum levels of other PIs and NNRTIs.
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 NNRTI: 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 blockers 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 blockers co-administration. Ca channel blockers should be started with 50% of the dose and slowly titrated with close monitoring of BP and pulse.
Paclitaxel	May significantly increase serum levels of paclitaxel	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 and DLV 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: Illicit drug use should be avoided for obvious reasons.
Phenobarbital	May decrease serum levels of PIs and NNRTIs. PIs and NNRTIs may increase or decrease phenobarbital serum levels	Applies to all PIs and NNRTI: Consider alternative anticonvulsants (valproic acid, lamotrigine, levetiracetam, or topiramate). With co-administration, monitor anticonvulsants levels and consider TDM of PIs and NNRTIs.
Phenytoin	May decrease serum levels of PIs and NNRTIs. PIs and NNRTIs may increase or decrease phenytoin serum levels.	Applies to all PIs and NNRTIs: Consider alternative anticonvulsants (valproic acid, lamotrigine, levetiracetam, or topiramate). With co-administration, monitor anticonvulsants levels and consider TDM of PIs and NNRTIs.
Pimozide	May significantly increase pimozide serum levels resulting in QTc prolongation.	Contraindicated. Consider alternative: Olanzapine.
PPI	No significant interaction	FPV may be co-administered with PPI.
Propafenone	May significantly increase serum levels of propafenone	Contraindicated.
Propafenone	May significantly increase serum levels of propafenone	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 Ps and NNRTIs co-administration, monitor EKG (QTc) and serum levels: target: 2-5 mcg/mL.
Raltegravir	Interaction unlikely	No data, but RTV (100 mg twice-daily) did not affect raltegravir PK parameters. Consider standard dose with close monitoring.
Ranitidine	APV AUC decreased by 30%	With boosted FPV (FPV700mg + RTV100mg twice-daily); interaction not significant.
Ranolazine	May significantly increase ranolazine serum concentrations.	Contraindicated. May increase risk of QTc prolongation.
Rifabutin	Based on APV data, an increase in rifabutin levels is expected.	CDC recommendation: FPV 1400mg twice-daily + rifabutin 150mg once-daily OR 300g 3x/wk OR FPV 700mg + RTV100mg twice-daily + 150mg every other day OR 150mg 3x/wk.
Rifapentine	FPV serum levels may be significantly decreased	Avoid co-administration. Consider using rifabutin.
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 increase sildenafil serum levels.	Applies to all PIs and DLV: .Start with 25 mg, and avoid dosing on consecutive days.
Simvastatin	May significantly increase simvastatin levels	Contraindicated. Alternatives include atorvastatin (start with 10-20 mg/d), pravastatin, rosuvastatin, or fluvastatin. Monitor for adverse effect due to limited clinical data.
Sirolimus	May significantly increase serum levels of sirolimus	Applies to all PIs: Dose sirolimus based on serum levels. A significantly reduction of sirolimus dose with all PIs co-administration is highly likely.
St. John's wort	May significantly decrease FPV levels	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	May significantly increase terfenadine serum level	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. Consider alternative benzodiazepines (temazepam, oxazepam, and lorazepam).
Vardenafil	May significantly increase serum level of vardenafil.	Applies to all PIs and DLV: Do not exceed vardenafil 2.5 mg in 72hrs (with RTV) OR 2.5mg in 24 hrs (with other PIs and DLV). Consider sildenafil due to more clinical data and less pronounced interaction. Avoid co-administration 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 Ca channel blocker coadministration. 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 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 FPV/r. Voriconazole may increase co-administered ART.	Significant interaction with RTV (400mg twice-daily); contraindicated. Voriconazole AUC decreased 39% with RTV 200 mg/d co-administration; avoid co-administration with boosted PI. Consider another antifungal for aspergillosis (i.e ambisome or caspofungin) or use with TDM.
Warfarin	Case report of increased warfarin requirements after RTV initiation	Other PIs and NNRTIs may also affect warfarin requirements. Monitor INR closely with co-administration.

RESISTANCE

As with other boosted PIs, PI mutations uncommon with failure of FPV/r in previously PI-naive pts
I50V: primary mutation selected by APV and FPV that confers intermediate resistance to APV and low-level resistance to LPV.
I54M/L: selected by APV and FPV, causes low-to-intermediate level APV resistance.
I84V: primary PI mutations that causes intermediate APV resistance.
Other PI mutations (10F/I/R/V, 32I, 46I/L, 47V, 54V, 73S, 76V, , 82A/F/S/T , 90M): increasing APV resistance with multiple mutations.
Predominant mutation observed in clinical trials: 32I, 33F, 46I, 47V, and 54L/V/M.
Use of FPV (without RTV) may lead to cross-resistance with DRV due to selection of DRV mutations (I50V, I54M/L, I84V, 32I, 33F, 47V).

PHARMACOLOGY

Pharmacology

COMMENTS

Pros: Equivalent to LPV/r in treatment-naive pts; option for once-daily administration (with RTV in PI-naive pts); can be taken with or without food; no significant PPI or H2 blocker drug-interactions; no PI resistance and reduced NRTI resistance with failure of FPV/r compared to FPV; FPV/r with lower dose RTV (1400/100 mg once-daily) effective in treatment naive pts with similar tolerability and lipid effects as ATV/r.
Cons: Higher pill burden than ATV or ATV/r; FPV/r has comparable ADRs to LPV/r when used with 200 mg/d of RTV; may not be as effective as LPV/r in PI experienced pts.

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Abbreviations