Zambian HIV Guidelines:: Nelfinavir

	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>

Nelfinavir

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

Available formulation in Zambia: Oral powder: 50 mg/g. Tablet: 250 mg (as mesilate).
Not first-line PI due to lower potency vs. EFV and LPV/r.
Since absorption dependent on fatty food intake, suboptimal serum concentrations may be more common in resource-limited countries.
Extensive experience in pregnancy, but no longer recommended due to presence of ethyl methanesulfonate (a carcinogenic impurity found in nelfinavir).

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*
Viracept	Nelfinavir (NFV)	Agouron (U.S. Canada) and Roche (outside the US and Canada)	oral tablet 250 mg; 625 mg	$2.52 per 250 mg tablet; $6.30 per 625 mg tablet.
			oral powder 50 mg/g (144 gm container)	$66.48

*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 (625 tab)

With EFV or NVP: standard doses
With IDV: NFV 1250 mg bid + IDV 1200 mg bid (limited data, not recommended).
With RTV: NFV 500-750 mg bid + RTV 400 mg bid (limited data, high rate of GI intolerance with marginal PK benefit, not recommended).
With SQV:NFV 1250 mg bid + SQV 1200 mg bid or NFV 750 mg tid + SQV 800 mg tid (not recommended)
With LPV/r: NFV 1250 mg bid + LPV/r 600/150 mg (3 tabs) bid (no data; not recommended)
ATV , FPV, TPV, and DRV: no data, avoid co-administration.
Not recommended with DLV.

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose.

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Usual dose likely.

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

Usual dose likely (PK unchanged in renal failure).

DOSING IN HEMODIALYSIS

Usual dose. Removed with HD, must be given post-HD on days of dialysis.

DOSING IN PERITONEAL DIALYSIS

No data: Usual dose likely.

DOSING IN HEMOFILTRATION

No data.

ADVERSE DRUG REACTIONS

COMMON

Self-limited secretory diarrhea in 10-30%. Typically responds to regular use of fiber and calcium supplements, or loperamide.

OCCASIONAL

Fat accumulation
Hyperlipidemia
Insulin resistance, +/- hyperglycemia or diabetes
Transaminase elevation

RARE

Urticaria (rare)
Severe hepatitis

DRUG INTERACTIONS

Substrate of 2C19 (major) and CYP3A4 (minor), inducer and inhibitor at CYP 3A4, and inducer of glucuronosyl transferase. NFV active M8 metabolite is a substrate of CYP3A4 (major). Drugs that are inhibitors of CYP3A4 may increase levels of main NFV metabolite (N8). Drugs that are inducers of CYP2C19 may decrease NFV serum levels.

Drug-to-Drug Interactions

Drug-to-Drug Interaction

Drug	Effect of Interaction	Recommendations/Comments
Azithromycin	NFV not significantly affected. Azithromcycin AUC increased by 100%.	Monitor for azithromcyin adverse drug reaction (reversible ototoxicity and elevated LFTs).
DLV	DLV AUC decreased by 42% and Cmin decreased by 52%. NFV AUC increased by 72%.	Avoid co-administration
EFV	NFV AUC increased by 20%. EFV levels unchanged.	No significant drug interaction. Use standard doses of both drugs.
Fluconazole	NFV AUC increased by 30%.	Use standard dose.
IDV	IDV AUC increased by 51%; NFV AUC increased by 83%.	Limited data for dosing IDV 1200 mg bid + NFV 1250 mg bid.
LPV/r	LPV AUC decreased by 27%; NFV Cmin increased by 113%.	Avoid co-administration or Consider increasing LPV/r dose to 3 tabs bid with NFV co-administration (no data).
NVP	No significant drug interaction	Use standard dose of both drugs.
Rifampin	NFV AUC decreased by 82%.	Co-administration not recommended.
RTV	NFV AUC increased by 150%, Cmax by 95%.	Limited data: RTV 400 mg bid and NFV 500 mg or 750 mg bid. Generally not combined since boosting with RTV will yield only minimal PK enhancement of NFV serum concentrations at the expense of GI intolerance.
SQV	SQVsgc AUC increased by 3-5 fold; NFV AUC increased by 18% and Cmax not altered	Dose NFV 1250 mg bid + SQV 1200 mg bid or NFV 750 mg tid + SQV 800 mg tid.
FPV	APV increased 1.5-fold.	Insufficient data for dose recommendation.
Alprazolam	May increase serum levels of alprazolam	Applies to all PIs and DLV: Consider alternative benzodiazepine (i.e lorazepam, oxazepam, or temazepam).
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. RTV, APV, and ATV manufactors recommend 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 ADR (PFTs and TSH). Consider monitoring serum levels of amiodarone, but its long half-life may make titration difficult.
Amlodipine	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 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.
APV	APV clearance was decreased by 41%. NFV AUC increased by 15%.	Data based on PK modeling with many confounding variables (i.e EFV in background regimen). Consider NFV 1250 mg bid + APV 1200 mg bid or APV 800 mg tid + NFV 750 mg tid with TDM.
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 74%	Use with caution. Monitor for adverse effects (LFTs and CPK). Consider alternative agents: pravastatin, fluvastatin, or 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 FPV does not recommend bepridil co-administration. This contraindication should 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.
Bupropion	May increase bupropion serum levels slightly	Not likely to be clinically significant. Start with the lowest possible dose of bupropion. In a small case series no seizures reported with co-administration.
Carbamazepine	May significantly decrease serum levels of NFV	Consider alternative anticonvulsants (i.e valproic acid, lamotrigine, levetiracetam, or topiramate). Monitor carbamazepine levels and consider TDM of NFV.
Caspofungin	Caspofungin serum levels were not affected. NFV not measured.	Use standard dose.
Chlordiazepoxide	May increase serum levels of chlordiazepoxide	Applies to all PIs and DLV: Consider alternative benzodiazepine (lorazepam, oxazepam, or temazepam).
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	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.
Depo-medroxyprogesterone acetate (DMPA)	NFV and M8 metabolite were not affected.DMPA levels were not reported.	No evidence of ovulation occurring based on progesterone levels through week 12. Use standard dose 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 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 serum levels of dofetilide	No data. 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.
Dronabinol	No significant interaction.	Use standard dose.
Echinacea	May decrease NFV serum levels. Echinacea decreased CYP3A4 substrate (midazolam) by 23%	Clinical significance unknown but should be avoided with all PIs and NNRTIs until its safety is further evaluated.
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-drug interaction occurred with CYP3A4 inhibitor).
Estazolam	May increase serum levels of estazolam	Applies to all PIs and DLV: Consider alternative benzodiazepines (lorazepam, oxazepam, or temazepam).
Ethinyl estradiol and northindrone	Ethinyl estradiol AUC decreased by 47%, Northindrone decreased by 18%.	Advise pts to use additional or alternative method of contraception.
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.
Etravirine	NFV serum concentrations may be increased.	Consider usual dose, but no PK data.
Felodipine	May increase serum levels of felodipine	Applies to all PIs and DLV: Data limited to 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.
Fentanyl	May increase fentanyl serum levels	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 alternative benzodiazepines (lorazepam, oxazepam, or temazepam).
Fluticasone	Fluticasone may be significantly increased.	Avoid long term co-administration. Consider beclomethasone.
Food	NFV AUC increased by 2-fold with 125 kcal with 20% fat meal. NFV AUC increased 5-fold 1000 kcal with 50% fatty meal.	NFV must be taken with a fatty meal (a minimum of 500 kcal with 20% fat).
Garlic supplement	49% and 51% reduction of SQV Cmin and AUC, respectively.	Studies only done with SQV. Effect of garlic on the PK parameters of NFV is not known. Avoid co-administration with PIs and NNRTIs until it can be further studied.
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.
Irinoteacan	May increase irinoteacan 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	CYP3A4 inhibitor and substrate -bidirectional inhibition with the potential to increase levels of itraconazole and co-administered PI.	No data with NFV. Standard dose NFV likely. Consider monitoring itraconazole with co-administration.
Ketoconazole	NFV AUC increased by 35%.	Use standard dose.
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, and fluvastatin (and possibly atorvastatin - start with 10 mg/d and monitor for myopathy).
Mefloquine	May increase serum levels of mefloquine	Applies to all PIs and DLV: Consider monitoring mefloquine levels and mefloquine-induced toxicity (i.e dizziness, LFTs, and periodic ophthalmic examination).
Methadone	Decreased serum levels of inactive methadone (S)-isomer. No change in active methadone R-isomer.	Use standard dose. No withdrawal symptoms observed.
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	Do not co-administer. Consider alternative benzodiazepines (temazepam, oxazepam,or lorazepam).
Milk thistle	Data limited to interaction study with milk thistle and IDV. IDV AUC: unchanged; IDV Cmin: decreased by 25%.	Clinical significance unknown. Unknown effect on the metabolism of other PIs or NNRTIs. Avoid co-administration with PIs and NNRTIs 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).
MVC	May increase maraviroc's serum concentrations.	No data, but dose reduction of MVC to 150 mg BID should be considered.
Mycophenolate (MMF)	NFV AUC decreased by 32%; NFV-M8 metabolite decreased by 32%.	Clinical significance unknown. Proper dosing has not been established. Consider an alternative boosted PI.
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 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 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.
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. Illicit drug use should be avoided for obvious reasons.
Phenobarbital	May significantly decrease serum levels of NFV	Consider alternative anticonvulsants (i.e valproic acid, lamotrigine, levetiracetam, or topiramate). Monitor phenobarbital levels and consider TDM of NFV.
Phenytoin	Phenytoin AUC decreased by 20-40%; No change in NFV AUC.	Monitor phenytoin levels, may need to increase phenytoin dose.
Pimozide	May significantly increase pimozide serum levels resulting in QTc prolongation	Contraindicated. Consider alternative: Olanzapine.
PPI	Nelfinavir and M8 metabolite AUC decreased by 36% and 92%, respectively.	Contraindicated.
Pravastatin	Pravastatin AUC decreased with co-administration.	Clinical significance unknown. May need to increase dose of pravastatin.
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 Ps and NNRTI co-administration, monitor EKG (QTc) and serum levels: Target: 2 to 5 mcg/mL.
Raltegravir	NFV may induce raltegravir's metabolism.	RAL 400 mg twice daily currently recommended, but no PK data.
Rifabutin	NFV AUC decreased by 32%; Rifabutin levels increased by 207%.	If co-administration required, dose NFV to 1000 mg PO tid with rifabutin to 150 mg PO qd or 300 mg 3x/wk.
Rifapentine	NFV serum levels may be significantly decreased.	Avoid co-administration. Consider using rifabutin.
Rosiglitazone	NFV AUC increased by 14% and Cmin increased by 18% (NS) (n="3).	No significant interaction. Use standard dose.
Rosuvastatin	Other CYP3A4 inhibitor (i.e erythromycin) did not affect rosuvastatin serum level.	Applies to PIs and NNRTI. In one study, rosuvastatin AUC and Cmax increased when co-administered with LPV. Clinical significance unknown and no data available with other PIs and NNRTIs. Close monitoring recommended due to limited clinical data.
Sildenafil	May increase sildenafil levels. No change in NFV serum levels.	Use with caution. Do not exceed 25 mg of sildenafil in 48hrs.
Simvastatin	Simvastatin AUC increased by 506%.	Contraindicated. Alternatives include pravastatin, fluvastatin, and atorvastatin (start with 10 mg/day). Monitor for ADRs due to limited clinical data.
Sirolimus	Case report of sirolimus Cmin increased by 5-fold with NFV co-administration	Dose sirolimus based on serum levels. A significantly reduction of sirolimus dose with NFV co-administration is recommended.
St. John's wort	May significantly decrease NFV serum levels	Contraindicated. Studies done with IDV and NVP but St John's wort may affect the metabolism of other PIs and NNRTIs. Use an alternative (more effective) antidepressant.
Tacrolimus	Case report of increased tacrolimus serum levels with NFV co-administration.	Dose tacrolimus based on serum levels. A significantly reduction of tacrolimus dose with NFV co-administration is recommended.
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	Contraindicated due to the potential for cardiac arrhythmias. Recommended alternative antihistamine: loratadine, fexofenadine, desloratidine, or cetirizine.
THC	No interactions.	No drug interactions but illicit drug use should be avoided for obvious reasons.
Trazodone	May increase serum levels of trazodone	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 levels	Contraindicated. Consider alternative benzodiazepines(temazepam, oxazepam, or lorazepam).
Vardenafil	May significantly increase serum levels of vardenafil	Applies to all PIs and DLV: Do not exceed vardenafil 2.5 mg in 72hrs (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 co-administration with IDV.
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 blockers 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	Data limited to interaction study with IDV and vitamin C (1 g/d): IDV AUC decreased by 14% and Cmin by 32%.	Clinical significance unknown. Data not available for other PIs or NNRTIs.
Voriconazole	May decrease voriconazole AUC. Voriconazole may increase NFV levels.	Significant interaction with EFV and RTV (400 mg bid) but not IDV, data with other PIs and NNRTIs are not available and should be used with caution. In severe cases of invasive aspergillosis where voriconazole is clearly the first line agent, the authors recommend close monitoring for therapeutic efficacy (+/- addition of another antifungal for aspergillosis i.e ambisome or caspofungin).
Warfarin	Case report of increased INR when co-administered with IDV.	Other PIs and NNRTIs may affect warfarin requirements. Monitor INR closely.

RESISTANCE

D30N: most common primary mutation selected by NFV, resulting in intermediate resistance to NFV, but no cross-resistance to other PIs.
L90M: can also be selected by NFV, resulting in intermediate resistance to NFV and SQV, and low-level cross-resistance to other PIs.
Other PI mutations (L33F, 82A/F/T/S, 84V/A/C, 46I/L): multiple mutations will result in high-level resistance.

PHARMACOLOGY

Pharmacology

COMMENTS

Pros: Extensive experience in pregnancy, but no longer recommended due to presence of ethyl methanesulfonate (a carcinogenic impurity found in nelfinavir); lack of PI cross-resistance with most failure (D30N mutation).
Cons: Unboostable PI; less potent than NNRTIs and boosted PIs; high variability in absorption with dependence on fatty foods; more diarrhea compared to the other PIs; failure with L90M can occur (compared to little or no resistance with boosted PIs), leading to greater PI cross-resistance; bid dosing; recent finding of EMS in NFV, leading to FDA letter warning against used in pediatrics and pregnant women.

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Abbreviations