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The Protease Inhibitors (PIs)

Detailed Prescribing Information

October 2005

 

 

Direct Links to PI Info
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

 

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

 

 

 

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.

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. Johnís wort (hypericum perforatum) or products containing St. Johnís 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 NaÔve patients only - single daily dosing (approved 4/29/2005): 6 caps (133/33) as a single dose with food

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

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

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

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

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.
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
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
NB B NB B NB B
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
NA 4 NA 1-2
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

 

NB = nonboosted regimen

B = ritonavir-boosted regimen
NA = not applicable

 

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)

 

 

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

 

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Links to Antiretroviral Sections (click on anything)
Nucleoside & Nucleotide Reverse Transcriptase Inhibitors (NRTI)
AZT  |  ddC  |  ddI  |  d4T  |  3TC  |  ABC  |  FTC  |  TDF  |  Combivir  |  Trizivir  |  Epzicom  |  Truvada
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI)
efavirenz  |  nevirapine  |  delavirdine
Protease Inhibitors (PI)  Boosted Protease Inhibitors
saquinavir  indinavir  |  ritonavir  |  nelfinavir  |  amprenavir  |  lopinavir + ritonavir  |  atazanavir  |  fosamprenavir  | tipranavir
Fusion Inhibitors
enfuvirtide

 

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Introduction Principles Management NRTI Info NNRTI Info
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Bibliography Links Palliative Therapy

 

Updated 10.25.2005