Antiretroviral Agents: Protease Inhibitors

Nelfinavir = Viracept
Dosing Forms	Coated 250 mg tablets; 625 mg tablets; oral powder 50 mg/g
Dosing	2 x 625 mg twice a day or 5 x 250 mg twice a day or 3 x 250 three times a day, All nelfinavir regimens should be taken with food, preferably a meal Boosting with ritonavir is not generally recommended.
	Hepatic insufficiency: No data
	Renal insufficiency: No adjustment needed
Food dependence	Nelfinavir should be taken with food at every dose. Food increases absorption.
Adverse Effects	Soft stools or diarrhea (50%), hepatitis, hyperlipidemia, diabetes, fat redistribution Diarrhea: consider Imodium, calcium supplement (Tums, Rolaids, Ca carbonate 500 twice a day) or psyllium fiber twice a day
Interactions	Efavirenz decreases nelfinavir levels (increase nelfinavir to 6x250 twice a day) Nevirapine decreases nelfinavir levels (increase nelfinavir to 6x250 twice a day) Levels of all erectile dysfunction drugs are increased: the lowest dose of these drugs must be used as a maximum and at intervals not be be decreased beyond every 48-72 hours.
	Effects of nelfinavir on other drug levels: Mild increase in indinavir AUC 200-400% increase in saquinavir AUC and Cmax Significant increase in rifabutin levels: decrease rifabutin to 150 mg daily 100% increase in single dose azithromycin AUC and Cmax 100% increase in atorvastatin AUC and Cmax 500% increase in simvastatin AUC 20-50% reductions in levels of OCPs, methadone, phenytoin
	Drugs that increase nelfinavir levels: Indinavir: 83% increase in AUC and 31% increase in Cmax Ritonavir 500 mg q12hours: 152% increase in AUC, 44% increase in Cmax Saquinavir: slight increase Efavirenz: slight increase Delavirdine: approx 100% increase in AUC, Cmax, Cmin Ketoconazole: 15-35% increase
	Drugs that decrease nelfinavir levels: Nevirapine: 32% decrease in Cmin Rifabutin 150 mg daily: approx 20% decrease Rifabutin 300 mg daily: approx 25-50% decrease Carbamazepine Rifampin 600 mg daily: 75-92% decrease St John's wort
	No data: atazanavir, fosamprenavir, amprenavir
Contraindications	Antiarrhythmics: amiodarone, quinidine Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine Neuroleptics: pimozide Sedatives/hypnotics: midazolam, triazolam Statins other than atorvastatin, pravastatin St John's wort
Suggested laboratory evaluations	Liver profile and glucose monthly x 3 months, then every 3-4 months; lipid profile q3-4 months
Warnings	Carbamazepine decreases nelfinavir levels Monitor levels of cyclosporine, tacrolimus, sirolimus, phenytoin Additional contraception should be employed in addition to oral contraceptives Use reduced doses of drugs for erectile dysfunction
Full Prescribing Information	http://www.viracept.com

Boosting protease inhibitors increases the risk of hepatitis, hyperlipidemia, fat redistribution

Lipo = fat redistribution, hyperlipidemia, risk of Type 2 diabetes mellitus in nonboosted regimen
UPAM = universal protease associated mutations (I84V, V82F/L/T, L90M)

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Key Points
Generic	Brand
Nelfinavir	Viracept
Indinavir	Crixivan
Ritonavir	Norvir
Saquinavir	Fortovase Invirase
Amprenavir	Agenerase
Lopinavir / Ritonavir	Kaletra
Atazanavir	Reyataz
Tipranavir	Aptivus
Fosamprenavir	Lexiva
Protease Inhibitor Summary Information
Boosted Protease Inhibitor Regimens
PI Combinations Which Should Avoided

Indinavir = Crixivan
Dosing Forms	100, 200, 333, 400 mg capsules
Dosing	2x400 mg every 8 hours on an empty stomach Boosted dose: 2x400 mg twice a day plus ritonavir 1-2x100 mg twice a day, both with or without food Increase to 1,000 mg every 8 hours, when taken with nevirapine, efavirenz, rifabutin [unboosted dosing] Stagger dosing of indinavir after wafer form dosing of didanosine by a minimum of 1 hour. Decrease indinavir to 600 mg every 8 hours with delavirdine
	Hepatic insufficiency: reduce dose to 600 mg every 8 hours for mild to moderate cirrhosis [no data for severe cirrhosis]
	Nephrolithiasis: temporary cessation or discontinuation may be necessary
Food Dependence	Indinavir should be taken on an empty stomach (either 1 hour before food or 2 hours after food) except when co-administered with ritonavir
Adverse Effects	5-10% incidence of kidney stones. This may be prevented effectively by drinking 48-64 oz water or other nonalcoholic fluid per day! Asymptomatic hyperbilirubinemia is extremely common. No intervention is required. Chapped lips, ingrown toenails, and hair loss are occasionally seen. Also hepatitis, hyperlipidemia, Type 2 diabetes, fat redistribution, GI upset
Interactions	Effects of indinavir on other drugs Increases trazodone levels: consider dose decrease of trazodone. Levels of all erectile dysfunction drugs are increased: the lowest dose of these drugs must be used as a maximum and at intervals not be be decreased beyond every 48-72 hours.
	Effects of other drugs on indinavir Nevirapine, efavirenz, rifabutin lowers indinavir levels (dose adjustment above.) Itraconazole, ketoconazole, delavirdine increase indinavir levels Rifampin lowers indinavir to subtherapeutic levels
	Unknown interactions: phenytoin, carbamazepine, dexamethasone
Suggested laboratory evaluations	Liver profile and glucose monthly x 3 months, then every 3-4 months Lipid profile every 3-4 months
Contraindications	Indinavir should not be used with atazanavir due to possible severe hyperbilirubinemia. Rifampin should not be administered with indinavir
Warnings	The incidence of nephrolithiasis may be increased by boosting indinavir with low doses of ritonavir. Past history of kidney stones = relative contraindication. Avoid concomitant use of phenytoin, carbamazepine, dexamethasone
Full Prescribing Information	http://www.crixivan.com

Ritonavir = Norvir
Dosing Forms	100 mg capsules (refrigerate) and suspension 125 mg/cc (nonrefrigerated)
Storage	Optimally store ritonavir soft gel caps in the refrigerator. If necessary ritonavir soft gel caps may be stored outside of a refrigerator for up to 30 days if the ambient temperature is < 77 deg Fahrenheit.
Dosing	In boosting strategy: 100-200 mg once or twice a day depending on the regimen (see PI Boosting chart for further info) Used as active protease inhibitor: over 1-2 weeks, gradually increase dose from 3x100 mg twice a day to 6x100 mg twice a day with food (see usage suggestions below)
Adverse Effects	High incidence of GI intolerance (abdominal pain and diarrhea) severely limits the ability to use this drug as an active PI especially in patients who are already ill with concomitant GI disease. Also perioral paresthesia, hyperlipidemia, fat redistribution, Type II diabetes
Interactions	Probably more interactions than any other drug. Favorable interaction with most other PIs makes this drug the ideal PI booster. It is usually not an active PI when used this way. Voriconazole levels are reduced to subtherapeutic levels. Increases trazodone levels: consider decreasing trazodone dosage. Levels of all erectile dysfunction drugs are increased: the lowest dose of these drugs must be used as a maximum and at intervals not be be decreased beyond every 48-72 hours.
Interactions	Drugs of abuse/addiction: MDMA levels are increased and severe reactions/deaths have been reported.
Suggested laboratory evaluations	Liver profile and glucose monthly x 3 months, then every 3-4 months Lipid profile q3-4 months
Contraindications	Antiarrhythmics: amiodarone, bepridil, flecainide, propafenone, quinidine Ergot Derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonivine GI Motility Agent: cisapride Herbal Products: St. John's wort (hypericum perforatum) HMG-CoA Reductase Inhibitors: lovastatin, simvastatin Neuroleptic: pimozide Sedative/hypnotics: midazolam, triazolam Antifungal: voriconazole
Warnings	Examine patient's concomitant medications carefully before prescribing. Ritonavir is generally regarded as too toxic to be used as an active single protease inhibitor.
Usage Suggestions	Ritonavir is used nearly exclusively as an inhibitor of the metabolism of other protease inhibitors i.e. as a "boosting" agent. High dose ritonavir is usually too toxic and other agents such as indinavir and lopinavir/ritonavir have comparable potency as well as the ability to overcome some degree of protease inhibitor resistance.
Full Prescribing Information	http://www.norvir.com

Saquinavir = Fortovase and Invirase 500 mg hard gel cap (Invirase) FDA Approved 12.20.2004 & available 2.18.2005
Dosing Forms	200 mg soft gel caps (Fortovase) 200 mg or 500 mg hard gel caps (Invirase)
Dosing	Without boosting: 8x200 mg soft gel caps twice a day with food or 6x200 mg soft gel caps three times a day with food [strongly consider boosting if possible] With boosting twice a day: 2x500 mg or 5x200 mg hard gel caps + 100 mg ritonavir, both twice a day with food With boosting once a day: 8x200 mg hard gel caps + 1-2x100 mg ritonavir, both once-a-day with food
	Renal dosing: no adjustment is necessary for renal insufficiency
	Hepatic dosing: there is no data available
Food dependence	Both forms of saquinavir should be taken with food (high or moderate fat)
Adverse Effects	Mainly GI disturbance including abdominal pain, diarrhea especially with soft gel form Also rash, hepatitis, fat redistribution, hyperlipidemia, Type 2 diabetes
Interactions
	Saquinavir effect on other drugs: Saquinavir may increase terfenadine, cisapride, astemizole, pimozide, triazolam, midazolam, ergot derivatives, rifampin or antiarrhythmic medications, which include amiodarone, bepridil, flecainide, propafenone, and quinidine Saquinavir increases rifabutin levels by approximately 50% Levels of all erectile dysfunction drugs are increased: the lowest dose of these drugs must be used as a maximum and at intervals not be be decreased beyond every 48-72 hours.
	Effect of other drugs on saquinavir: Clarithromycin increases saquinavir levels by 150-200% Efavirenz decreases saquinavir levels by 50-60% Ritonavir increases saquinavir levels Atazanavir increases saquinavir levels
Contraindications	INVIRASE should not be administered concurrently with terfenadine, cisapride, astemizole, pimozide, triazolam, midazolam, ergot derivatives, rifampin or antiarrhythmic medications, which include amiodarone, bepridil, flecainide, propafenone, and quinidine
Suggested laboratory evaluations	Liver profile and glucose monthly x 3 months, then every 3-4 months Lipid profile q3-4 months
Warnings	Concomitant use of INVIRASE with lovastatin or simvastatin is not recommended. Concomitant use of INVIRASE and St. John’s wort (hypericum perforatum) or products containing St. John’s wort is not recommended. Garlic capsules should not be used while taking saquinavir as the sole protease inhibitor due to the risk of decreased saquinavir plasma concentrations. No data are available for the coadministration of INVIRASE/ritonavir and garlic capsules.
Usage Suggestion	Hard gel cap form of saquinavir (Invirase) should not be used outside of a boosting strategy (i.e. without ritonavir or another protease inhibitor). Hard gel cap form (Invirase) is preferred when using a boosting strategy to minimize gastrointestinal side effects from the carrier oil in the soft gel form (Fortovase).
Full Prescribing Information	Invirase prescribing information

Amprenavir = Agenerase
Dosing Forms	50mg, 150 mg soft gel caps; also liquid form available 15 mg/cc
Dosing	Without boosting: 8x150 mg soft gel caps twice a day With boosting: 6x150 caps + 1x100 mg ritonavir, both twice a day, or 8x150 caps + 2x100 mg ritonavir both once a day Dose adjustment is required for hepatic insufficiency.
Food Dependence	Amprenavir may be taken with or without food, but it should not be taken with a high fat meal.
Adverse Effects	Mainly GI disturbance including nausea, abdominal pain, diarrhea Also perioral paresthesia, hepatitis, fat redistribution, hyperlipidemia, Type 2 diabetes Possible cross-hypersensitivity to sulfonamides 1% incidence of Stevens-Johnson: discontinue amprenavir for moderate rash, progression of rash, and/or systemic symptoms. Due to vitamin E contained in the formulation, vitamin E supplementation by patients should be avoided.
Interactions	Methadone levels are decreased and amprenavir levels are decreased: protease inhibitor alternatives should be considered. Rifampin decreases amprenavir levels significantly. St John's Wort decreases amprenavir levels. Amprenavir increases sildenafil levels Take amprenavir at least one hour before or one hour after antacids Anticonvulsants phenytoin, phenobarbital, carbamazepine all decrease amprenavir levels Use lowest possible dose of atorvastatin Dexamethasone should be used with caution due to lowering of amprenavir levels Amprenavir lowers lopinavir levels
Suggested laboratory evaluations	Liver profile and glucose monthly x 3 months, then every 3-4 months Lipid profile q3-4 months
Contraindications	Ergot derivatives, cisapride, pimozide, triazolam, midazolam Rifampin, oral contraceptives, delavirdine Lopinavir
Warnings	Use cautiously in patients with a history of sulfonamide hypersensitivity Liquid form should be used in children less than 4 years of age due to excess amounts of propylene glycol contained in the excipient. Concomitant use of amprenavir liquid and ritonavir is contraindicated due to interference with the metabolism of propylene glycol by ritonavir. This same issue is relevant to patients with hepatic failure: amprenavir liquid should not be used. Rifampin should not be used with amprenavir: rifabutin at reduced dosage may be substituted. St John's Wort should not be used. Lovastatin and simvastatin should not be used due to high levels of these drugs and possible toxicity.
Usage Suggestions	This drug may be largely supplanted by fosamprenavir which is a prodrug of amprenavir. Fosamprenavir has a lower pill burden and dosing frequency when boosted with ritonavir (see PI boosting below). Additionally fosamprenavir may be better tolerated and less likely to cause dyslipidemia. However, fosamprenavir may not be combined with lopinavir/ritonavir at least until further interaction data is known.
Full Prescribing Information	http://www.gsk.com/products/agenerase_us.htm

Lopinavir/ritonavir = Kaletra
Dosing Forms	133/33 mg lopinavir/ritonavir soft gel caps and liquid 400/100 mg per 5 cc
Dosing	Without boosting: 3-4 caps twice a day with food With boosting: 3 caps + 1x100 mg ritonavir, both twice a day with food Antiretroviral Naïve patients only - single daily dosing (approved 4/29/2005): 6 caps (133/33) as a single dose with food
Dosing	Mild to moderate hepatic impairment: increases lopinavir AUC 30% and CMax 20% with a decrease in protein binding - caution should be exercised Severe hepatic impairment: no data available
Food dependence	Kaletra should be taken with food (preferably a meal)
Adverse Effects	Mainly GI disturbance including nausea, abdominal pain, diarrhea (increased in single daily dosing) Also perioral paresthesia, hepatitis, fat redistribution, hyperlipidemia, Type 2 diabetes There appears to be a small chance (4%) of nephrolithiasis associated with lopinavir/ritonavir.
Contraindications	Concomitant use of any of the following: flecainide, propafenone, atemizole, terfenadine, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, midazolam, triazolam, rifampin, St. John’s wort (hypericum perforatum,) lovastatin, simvastatin, fosamprenavir, amprenavir
Interactions	Lopinavir/ritonavir produces the following interactions: Increases tenofovir levels significantly (~30%) in two studies with 1.8% of subjects developing renal insufficiency and 1 patient developed Fanconi syndrome Increases indinavir (consider use 600 twice a day of indinavir) Increases saquinavir (consider 800 mg twice a day of saquinavir) Increases antiarrhythmic levels (use drug level monitoring) Increases clarithromycin levels (decrease clarithromycin for Ccr < 60 cc/hr) Increases ketoconazole, itraconazole levels Increases rifabutin levels (decrease rifabutin to 150 mg every other day and monitor closely for toxicity and consider further dosing reduction) Increases dihydropyridine calcium channel blocker levels Increases intraconazole levels Increases tadalafil levels significantly: use tadalafil (Cialis) with caution at reduced doses of 10 mg every 72 hours with increased monitoring for adverse events Increases vardenafil levels significantly; Use vardenafil (Levitra) with caution at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring for adverse events Increases fluticasone levels such that adrenal suppression or Cushing's syndrome may develop Decreases atovaquone levels Decreases dexamethasone levels Increases sildenafil levels (decrease dose of sildenafil to 25 mg every other day maximum frequency) Decreases methadone levels - withdrawal may be precipitated Decreases oral contraceptive levels (use additional contraceptive method) Variably affects anticoagulation: monitor anticoagulation with warfarin closely
	Lopinavir/ritonavir is affected by the following: Lopinavir levels are decreased very significantly by amprenavir and fosamprenavir Lopinavir levels decreased by nevirapine and efavirenz (increase Kaletra to 4 caps twice a day with food) Delavirdine increases lopinavir levels Fosamprenavir decreases lopinavir levels by 60% and fosamprenavir levels are decreased by up to 70% by lopinavir Anticonvulsants decrease lopinavir levels (avoid use)
	No data: lopinavir + atazanavir
Suggested laboratory evaluations	Liver profile and glucose monthly x 3 months, then every 3-4 months; lipid profile q3-4 months
Warnings	Examine patient's concomitant medications carefully before prescribing. See interactions above. Concomitant fosamprenavir or amprenavir are not recommended (at least until much more data is available 6/2004) Due to markedly increased fluticasone levels avoid use of Flonase or other fluticasone containing medicatios if possible. Do not use single daily dosing in antiretroviral-experienced patients
Full Prescribing Information	http://www.kaletra.com

Atazanavir = Reyataz Approved June 20,2003
Dosing Forms	100, 150, and 200 mg caps
Dosing	Without boosting: 2x200 mg once a day with a light meal With boosting: 2x150 mg + ritonavir 100 mg, both once a day
Dosing	Hepatic impairment: dose reduction to 300 mg once a day should be considered for moderate hepatic insufficiency (Child Pugh Class B)
Food Dependence	Food enhances absorption and reduces pharmacokinetic variability
Adverse Effects	Mainly GI disturbance including nausea, abdominal pain, diarrhea Also perioral paresthesia, hepatitis, fat redistribution, hyperlipidemia, Type 2 diabetes
Contraindications	Concomitant lovastatin, simvastatin Concomitant St John's Wort Ergot derivatives, cisapride, pimozide, midazolam, triazolam Proton pump inhibitors Irinotecan, bepridil Indinavir should not be used due to combined and possibly severe hyperbilirubinemia.
Interactions	Atazanavir levels are decreased by tenofovir (use boosted atazanavir dosing) Atazanavir levels are decreased by efavirenz (use boosted atazanavir dosing) Atazanavir increases inhibits CYP3A pathway: therefore, drugs metabolized via this pathway may accumulate - sildenafil, calcium channel blockers, statins, immunosuppressants Levels of all erectile dysfunction drugs are increased: the lowest dose of these drugs must be used as a maximum and at intervals not be be decreased beyond every 48-72 hours. H2-inhibitor: decreases atazanavir absorption - recommend to take minimum dose separated from atazanavir dosing by 12 hours
Interactions	No data: lopinavir, nevirapine
Suggested laboratory evaluations	Liver profile and glucose monthly x 3 months, then every 3-4 months; lipid profile q3-4 months
Warnings	Warfarin therapy should be monitored closely. Antiarrythmic therapy should be monitored closely. Stagger H2-blockers by at least an hour from atazanavir (consider co-administration of acidic drink such as cola beverage or acidic citrus drink?)
Full Prescribing Information	http://www.reyataz.com

Fosamprenavir = Lexiva
Dosing Forms	700 mg tablets
Dosing	Without boosting: 2x700 mg twice a day with or without food With boosting: 2x700 mg + ritonavir 2x100 mg, both once a day (antiretroviral naive patients only) or 1x700 mg + ritonavir 1x100 mg, both twice a day; use 3x100 mg ritonavir with concomitant efavirenz
Dosing	Hepatic impairment: reduce dose to 1x700 twice a day in hepatic impairment (Pugh score 5-8)
Food dependence	Fosamprenavir may be taken with or without food.
Adverse Effects	Diarrhea, nausea & vomiting, rash Also perioral paresthesia, hepatitis, fat redistribution, hyperlipidemia, Type 2 diabetes
Contraindications	Rifampin (decreases fosamprenavir levels by up to 80%) Fosamprenavir should not be used in severe hepatic impairment (Pugh score 9-12)
Interactions	Fosamprenavir levels are decreased by efavirenz (use boosted dosing above) Fosamprenavir levels are increased by delavirdine Fosamprenavir decreases lopinavir levels by 60% and fosamprenavir levels are decreased by up to 70% by lopinavir
Interactions	No data: nevirapine, atazanavir (June 2004)
Suggested laboratory evaluations	Liver profile and glucose monthly x 3 months, then every 3-4 months; lipid profile q3-4 months
Warnings	Concomitant lopinavir/ritonavir (Kaletra) is not recommended due to decreased and possibly subtherapeutic lopinavir levels that result. There appears to be a chance of cross-hypersensitivity with sulfonamides (16% vs 14% incidence of reaction in persons with a history of sulfonamide hypersensitivity fosamprenavir vs placebo, respectively)
Usage Suggestions	This drug may largely supplant amprenavir due to decreased pill burden and better tolerance.
Full Prescribing Information	http://www.lexiva.com

Tipranavir = Aptivus Approved by US FDA 6.22.2005
Dosing Forms	250 mg gel caps
Dosing	2x250 mg twice a day + 2x100 mg ritonavir twice a day, both with food The drug is always administered with ritonavir.
Dosing	Hepatic impairment: Tipranavir should not be taken with moderate or severe hepatic impairment.
Food dependence	Tipranavir should be taken with food.
Adverse Effects	Diarrhea, nausea & vomiting, rash (14% females, 8-10% males) Elevated liver enzymes/hepatitis Also perioral paresthesia, hepatitis, fat redistribution, hyperlipidemia, Type 2 diabetes
Contraindications	Rifampin Other protease inhibitors aside from ritonavir: levels of other PIs are reduced to subtherapeutic levels
Interactions	When used with ethinyl estradiol - 33% chance of rash
Interactions	statins, certain antiarrhythmics, ergot derivatives, antihistamines, neuroleptics, sedatives - similar to other protease inhibitors (inhibitors of CY3PA) Protease inhibitors: levels of other PIs are reduced to subtherapeutic levels NNRTIs: no dose adjustment is required for tipranavir/ritonavir when used with other NNRTIs
Suggested laboratory evaluations	Liver profile and glucose monthly x 3 months, then every 3-4 months; lipid profile q3-4 months
Warnings	Tipranavir contains a sulfonamide component. Use cautiously in persons with sulfonamide allergy.
Usage Suggestions	The drug has been studied primarily as salvage therapy and appears active in the setting of multiple protease inhibitor mutations.
Full Prescribing Information	http://www.aptivus.com Patient information sheet HERE.

Protease Inhibitor Summary Information
Generic (Nomenclature) Brand	Pill Burden Per Day		Dose Frequency Per Day		GI	Lipo	Meal Dependence		Other	High Level Resistance Mutations
Generic (Nomenclature) Brand	NB	B	NB	B	GI	Lipo	NB	B	Other	High Level Resistance Mutations
saquinavir (SQV) Fortovase or Invirase	16-18	9-12	2-3	1-2	Diarrhea, nausea	+++	Meal	Meal	Refrigerated & large soft gel caps Both forms almost always boosted with ritonavir Hard gel caps must be boosted with ritonavir	48, I84V, L90M
saquinavir (SQV) Fortovase or Invirase	NA	4	NA	1-2	Diarrhea, nausea	+++	Meal	Meal		48, I84V, L90M
indinavir (INDV) Crixivan	6	6-8	3	2	Abdominal pain	++++	Empty	None	Nephrolithiasis	V82F/L/T, I84V
nelfinavir (NFVR) Viracept	4-10	?	2-3	NA	Diarrhea	++	Meal	NA	Boosting generally not useful	D30N, I84V, L90M
ritonavir (RTV) Norvir	12	NA	2	NA	Abdominal pain, diarrhea, nausea	++++	Meal	NA	Nearly unusable as single PI	V82F/L/T, I84V
amprenavir (AMP) Agenerase	16	8/2	2	1-2	Nausea	++	Not high fat meal	Not high fat meal	Large soft gel caps, rash Largely replaced by fosamprenavir	I50V
lopinavir / ritonavir (LPV/RTV) Kaletra	6-8	6/2	2	2	Abdominal pain, diarrhea, nausea	++++	Meal	Meal	Refrigerated, large soft gel caps	V82F/L/T, I84V, L90M
atazanavir (ATV) Reyataz	2	2/1	1	1	jaundice	+	Meal	Meal	Use boosted regimen in antiretroviral-experienced pt	I50L, I84V
fosamprenavir (F-AMP) Lexiva	4	2/2	2	1-2		++	None	None	Avoid use of single daily dosing in ARV-experienced pt Contains a sulfonamide component	50, I84V
tipranavir / ritonavir (TPV/RTV) Aptivus	NA	8	NA	2	Abdominal pain, diarrhea, nausea	++++ ?	NA	Meal	This drug appears very similar to lopinavir / ritonavir. May retain activity in the presence of multiple UPAMs* Contains a sulfonamide component Relatively high incidence of hepatitis, rash	V82F/L/T, I84V, L90M

Protease Inhibitor Boosting Optimizing Protease Inhibitor Therapy: Improved Drug Levels and Improved Adherence
GENERIC	DOSE	ADVERSE EFFECTS	COMMENTS
Saquinavir boosted with ritonavir	1. 8 x 200 mg saquinavir hard-gel capsule + 100 mg ritonavir both once a day with food 2. 2 x 500 mg saquinavir hard-gel capsule + 100 mg ritonavir, both twice a day with food 3. 5 x 200 mg saquinavir hard-gel capsule + 100 mg ritonavir, both twice a day with food 4. 2 x 200 mg saquinavir hard-gel capsule + 4x100 mg ritonavir both twice a day with food	Hyperlipidemia, hepatitis, fat redistribution, diarrhea, abdominal pain, diarrhea	Higher doses of ritonavir may be associated with increasing hyperlipidemia, GI intolerance, hepatitis, perioral paresthesia, and increased drug interactions Twice daily boosted saquinavir is FDA-approved
Indinavir boosted with ritonavir	2 x 400 mg indinavir twice a day + 1-2 x 100 mg ritonavir twice a day with or without food	Hyperlipidemia, hepatitis, fat redistribution, diarrhea, abdominal pain, chapped lips, nephrolithiasis	Hydration with at least 48-64 oz of fluid per day is necessary.
Saquinavir boosted with lopinavir/ritonavir	2 x 500 mg saquinavir hard-gel caps twice a day + 3 caps lopinavir/ritonavir twice a day both with food	Hyperlipidemia, hepatitis, fat redistribution, diarrhea, abdominal pain, diarrhea
Amprenavir boosted with ritonavir	8 x 150 mg amprenavir daily + 2 x 100 mg ritonavir daily With food or 4 x 150 mg amprenavir twice a day + 1 x 100 mg ritonavir twice a day both with food	Hyperlipidemia, hepatitis, nausea, fat redistribution
Lopinavir/ritonavir boosted with ritonavir	3 caps lopinavir/ritonavir twice a day + 1 x 100 mg ritonavir twice a day dose with food	Hyperlipidemia, hepatitis, fat redistribution, diarrhea, abdominal pain, diarrhea
Atazanavir boosted with ritonavir	2 x 150 mg atazanavir + 1 x 100 mg ritonavir both once a day	Hyperlipidemia	Atazanavir should always be boosted in antiretroviral-experienced patients
Fosamprenavir boosted with ritonavir	2 x 700 mg fosamprenavir + 2 x 100 mg ritonavir both once a day with food or 1 x 700 mg fosamprenavir + 1 x 100 mg ritonavir both twice a day	Nausea, headache, rash, diarrhea	Newest PI with least experience Boosted once-a-day dosing is not recommended for antiretroviral-experienced patients.

Protease Inhibitor Combination Therapy (Two Active Protease Inhibitors)
Generic	Dosing	Adverse Effects	Comment
Saquinavir combined with Lopinavir/ritonavir	5 x 200 mg saquinavir hard-gel caps twice a day + 3 caps lopinavir/ritonavir twice a day both with food	Hyperlipidemia, hepatitis, fat redistribution, diarrhea, abdominal pain, diarrhea
Lopinavir/ritonavir combined with Indinavir	3 caps lopinavir/ritonavir twice a day + 2 x 333 mg indinavir twice a day Both with food	Hyperlipidemia, hepatitis, fat redistribution, diarrhea, abdominal pain, diarrhea, nephrolithiasis	May be one of the most successful PI strategies against PI-resistant virus?

Protease Inhibitor Combination Therapy That Is NOT RECOMMENDED (Two Active Protease Inhibitors)
Generic	Rationale for AVOIDANCE
Saquinavir combined with Indinavir	Antagonistic in vitro
Indinavir combined with Nelfinavir	Antagonistic in vitro
Lopinavir/ritonavir combined with Fosamprenavir or Amprenavir	Subtherapeutic levels of lopinavir