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Protease Inhibitors

HIV Medication Tables

Amprenavir (agenerase ® )

Discontinued product.

Atazanavir (reyataz ® )

DOSAGE AND ADMINISTRATION

General Dosing Recommendations:

•REYATAZ Capsules must be taken with food.
•Do not open the capsules.
•The recommended oral dosage of REYATAZ depends on the treatment history of the patient and the use of other coadministered drugs. When coadministered with H2-receptor antagonists or proton-pump inhibitors, dose separation may be required.
•When coadministered with didanosine buffered or enteric-coated formulations, REYATAZ should be given (with food) 2 hours before or 1 hour after didanosine.
•REYATAZ without ritonavir is not recommended for treatment-experienced adult or pediatric patients with prior virologic failure.
•Efficacy and safety of REYATAZ with ritonavir in doses greater than 100 mg once daily have not been established. The use of higher ritonavir doses might alter the safety profile of atazanavir (cardiac effects, hyperbilirubinemia) and, therefore, is not recommended. Prescribers should consult the complete prescribing information for NORVIR® (ritonavir) when using this agent.

Recommended Adult Dosage
Table 1 summarizes the recommended REYATAZ dosing regimen in adults. All REYATAZ dosing regimens are to be administered as a single dose with food.

Table 1: REYATAZ Dosing Regimens
Treatment-Naive Patients

REYATAZ 300 mg with ritonavir 100 mg once daily
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If unable to tolerate ritonavir:
REYATAZ 400 mg once daily
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When combined with any of the following:
Tenofovir
H2-receptor antagonist
Proton-pump inhibitor

REYATAZ 300 mg with ritonavir 100 mg once daily

•The H2-receptor antagonist dose should not exceed a dose comparable to famotidine 40 mg twice daily. Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H2-receptor antagonist.
•If unable to tolerate ritonavir, administer REYATAZ 400 mg once daily at least 2 hours before and at least 10 hours after the H2-receptor antagonist. No single dose of the H2-receptor antagonist should exceed a dose comparable to famotidine 20 mg and the total daily dose should not exceed a dose comparable to famotidine 40 mg.
•The proton-pump inhibitor dose should not exceed a dose comparable to omeprazole 20 mg daily and must be taken approximately 12 hours prior to REYATAZ and ritonavir.
-------------------------------------
When combined with efavirenz
REYATAZ 400 mg with ritonavir 100 mg once daily

•Efavirenz should be administered on an empty stomach, preferably at bedtime.

Treatment-Experienced Patients
REYATAZ 300 mg with ritonavir 100 mg once daily
Do not coadminister with proton-pump inhibitors or efavirenz in treatment-experienced patients.
-------------------------------------
When given with an H2-receptor antagonist
REYATAZ 300 mg with ritonavir 100 mg once daily

•The H2-receptor antagonist dose should not exceed a dose comparable to famotidine 20 mg twice daily. Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H2-receptor antagonist.
-------------------------------------
When given with both tenofovir and an H2-receptor antagonist
REYATAZ 400 mg with ritonavir 100 mg once daily

•The H2-receptor antagonist dose should not exceed a dose comparable to famotidine 20 mg twice daily. Administer REYATAZ and ritonavir simultaneously with, and/or at least 10 hours after the H2-receptor antagonist.

See package insert for pediatric patients and dosing in prenancy.

Renal Impairment
For patients with renal impairment, including those with severe renal impairment who are not managed with hemodialysis, no dose adjustment is required for REYATAZ. Treatment-naive patients with end stage renal disease managed with hemodialysis should receive REYATAZ 300 mg with ritonavir 100 mg. REYATAZ should not be administered to HIV-treatment-experienced patients with end stage renal disease managed with hemodialysis.

Hepatic Impairment
REYATAZ should be used with caution in patients with mild-to-moderate hepatic impairment. For patients with moderate hepatic impairment (Child-Pugh Class B) who have not experienced prior virologic failure, a dose reduction to 300 mg once daily should be considered. REYATAZ should not be used in patients with severe hepatic impairment (Child-Pugh Class C). REYATAZ/ritonavir has not been studied in subjects with hepatic impairment and is not recommended.

DOSAGE FORMS AND STRENGTHS

•150 mg capsule with blue cap and powder blue body, printed with white ink “BMS 150 mg” on the cap and with blue ink “3624” on the body.
•200 mg capsule with blue cap and blue body, printed with white ink “BMS 200 mg” on the cap and with white ink “3631” on the body.
•300 mg capsule with red cap and blue body, printed with white ink “BMS 300 mg” on the cap and with white ink “3622” on the body.

Darunavir (prezista™)

DOSAGE AND ADMINISTRATION

Adult Patients
PREZISTA must be co-administered with ritonavir to exert its therapeutic effect. Failure to correctly co-administer PREZISTA with ritonavir will result in plasma levels of darunavir that will be insufficient to achieve the desired antiviral effect and will alter some drug interactions.

Patients who have difficulty swallowing PREZISTA tablets can use the 100 mg/mL PREZISTA oral suspension.

Treatment-Naïve Adult Patients
The recommended oral dose of PREZISTA is 800 mg (one 800 mg tablet or 8 mL of the oral suspension) taken with ritonavir 100 mg (one 100 mg tablet/capsule or 1.25 mL of a 80 mg/mL ritonavir oral solution) once daily and with food. An 8 mL darunavir dose should be taken as two 4 mL administrations with the included oral dosing syringe.

Treatment-Experienced Adult Patients
Table 1: Treatment-Experienced Adult Patients

With no darunavir resistance associated substitutions* With at least one darunavir resistance associated substitution*
Formulations: PREZISTA tablets or oral suspension (100 mg/mL) and ritonavir tablets/capsules (100 mg) or solution (80 mg/mL)
PREZISTA 800 mg (one 800 mg tablet) or 8 mL†(oral suspension) once daily with ritonavir 100 mg (one 100 mg tablet/capsule or 1.25 mL (oral solution) once daily and with food PREZISTA 600 mg (e.g. one 600 mg tablet) or 6 mL (oral suspension) twice daily with ritonavir 100 mg (one 100 mg tablet/capsule or 1.25 mL (oral solution) twice daily and with food

*V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V
†An 8 mL darunavir dose should be taken as two 4 mL administrations with the included oral dosing syringe

For antiretroviral treatment-experienced patients genotypic testing is recommended. However, when genotypic testing is not feasible, PREZISTA/ritonavir 600/100 mg twice daily dosing is recommended.

See package insert for Pediatric  dosing.

Patients with Hepatic Impairment
No dose adjustment is required in patients with mild or moderate hepatic impairment. No data are available regarding the use of PREZISTA/ritonavir when co-administered to subjects with severe hepatic impairment; therefore, PREZISTA/ritonavir is not recommended for use in patients with severe hepatic impairment.

DOSAGE FORMS AND STRENGTHS
PREZISTA 100 mg/mL Oral Suspension
PREZISTA (darunavir) 100 mg/mL oral suspension is supplied as a white to off-white opaque suspension for oral use, containing darunavir ethanolate equivalent to 100 mg of darunavir per mL of suspension.

PREZISTA 75 mg Tablets
PREZISTA (darunavir) 75 mg tablets are supplied as white, caplet-shaped, film-coated tablets containing darunavir ethanolate equivalent to 75 mg of darunavir per tablet. Each tablet is debossed with "75" on one side and "TMC" on the other side.

PREZISTA 150 mg Tablets
PREZISTA (darunavir) 150 mg tablets are supplied as white, oval-shaped, film-coated tablets containing darunavir ethanolate equivalent to 150 mg of darunavir per tablet. Each tablet is debossed with "150" on one side and "TMC" on the other side.

PREZISTA 600 mg Tablets
PREZISTA (darunavir) 600 mg tablets are supplied as orange, oval-shaped, film-coated tablets containing darunavir ethanolate equivalent to 600 mg of darunavir per tablet. Each tablet is debossed with "600MG" on one side and "TMC" on the other side.

PREZISTA 800 mg Tablets
PREZISTA (darunavir) 800 mg tablets are supplied as dark red, oval-shaped, film-coated tablets containing darunavir ethanolate equivalent to 800 mg of darunavir per tablet. Each tablet is debossed with "800" on one side and "T" on the other side.

Indications: Treatment of HIV-1 infections in combination with ritonavir and other antiretroviral agents; limited to highly treatment-experienced or multiprotease inhibitor-resistant patients

Fosamprenavir (lexiva ® )

DOSAGE & ADMINISTRATION

LEXIVA Tablets may be taken with or without food.

Adults should take LEXIVA Oral Suspension without food. Pediatric patients should take LEXIVA Oral Suspension with food. If emesis occurs within 30 minutes after dosing, re-dosing of LEXIVA Oral Suspension should occur.

Higher-than-approved dose combinations of LEXIVA plus ritonavir are not recommended due to an increased risk of transaminase elevations.

When LEXIVA is used in combination with ritonavir, prescribers should consult the full prescribing information for ritonavir.

Therapy-Naive Adults:
•LEXIVA 1,400 mg twice daily (without ritonavir).•LEXIVA 1,400 mg once daily plus ritonavir 200 mg once daily.•LEXIVA 1,400 mg once daily plus ritonavir 100 mg once daily. Dosing of LEXIVA 1,400 mg once daily plus ritonavir 100 mg once daily is supported by pharmacokinetic data

.•LEXIVA 700 mg twice daily plus ritonavir 100 mg twice daily.  Dosing of LEXIVA 700 mg twice daily plus 100 mg ritonavir twice daily is supported by pharmacokinetic and safety data

Protease Inhibitor-Experienced Adults:

•LEXIVA 700 mg twice daily plus ritonavir 100 mg twice daily.

The recommended dosage of LEXIVA in patients aged at least 4 weeks to 18 years should be calculated based on body weight (kg) and should not exceed the recommended adult dose (Table 1).

Table 1. Twice-Daily Dosage Regimens by Weight for Protease Inhibitor-Naive Pediatric Patients (Greater Than or Equal to 4 Weeks of Age) and for Protease Inhibitor-Experienced Pediatric Patients (Greater Than or Equal to 6 Months of Age) Using LEXIVA Oral Suspension With Concurrent Ritonavir

Weight
Twice-Daily Dosage Regimen
==========================================
<11 kg
LEXIVA 45 mg/kg plus ritonavir 7 mg/kga
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11 kg - <15 kg
LEXIVA 30 mg/kg plus ritonavir 3 mg/kga
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15 kg - <20 kg
LEXIVA 23 mg/kg plus ritonavir 3 mg/kga
------------------------------------------------
>/=20 kg
LEXIVA 18 mg/kg plus ritonavir 3 mg/kga
==========================================
a. When dosing with ritonavir, do not exceed the adult dose of LEXIVA 700 mg/
ritonavir 100 mg twice-daily dose.

Alternatively, protease inhibitor-naive children aged 2 years and older can be administered LEXIVA (without ritonavir) 30 mg per kg twice daily.

LEXIVA should only be administered to infants born at 38 weeks gestation or greater and who have attained a post-natal age of 28 days.

For pediatric patients, pharmacokinetic and clinical data:

•do not support once-daily dosing of LEXIVA alone or in combination with ritonavir

.•do not support administration of LEXIVA alone or in combination with ritonavir for protease inhibitor-experienced children younger than 6 months

.•do not support twice-daily dosing of LEXIVA without ritonavir in pediatric patients younger than 2 years

Other Dosing Considerations:
•When administered without ritonavir, the adult regimen of LEXIVA Tablets 1,400 mg twice daily may be used for pediatric patients weighing at least 47 kg.
•When administered in combination with ritonavir, LEXIVA Tablets may be used for pediatric patients weighing at least 39 kg; ritonavir capsules may be used for pediatric patients weighing at least 33 kg.

Mild Hepatic Impairment (Child-Pugh Score Ranging From 5 to 6):LEXIVA should be used with caution at a reduced dosage of 700 mg twice daily without ritonavir (therapy-naive) or 700 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced).

Moderate Hepatic Impairment (Child-Pugh Score Ranging From 7 to 9):LEXIVA should be used with caution at a reduced dosage of 700 mg twice daily without ritonavir (therapy-naive), or 450 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced).

Severe Hepatic Impairment (Child-Pugh Score Ranging From 10 to 15):LEXIVA should be used with caution at a reduced dosage of 350 mg twice daily without ritonavir (therapy-naive) or 300 mg twice daily plus ritonavir 100 mg once daily (therapy-naive or protease inhibitor-experienced).

There are no data to support dosing recommendations for pediatric patients with hepatic impairment.

DOSAGE FORMS & STRENGTHS
LEXIVA Tablets, 700 mg, are pink, film-coated, capsule-shaped, biconvex tablets with “GX LL7” debossed on one face.

LEXIVA Oral Suspension, 50 mg per mL, is a white to off-white suspension that has a characteristic grape-bubblegum-peppermint flavor.

Indinavir (crixivan ® )

Dosing (Adult): Oral: 800 mg every 8 hours

Note:
Dosage adjustments for indinavir when administered in combination therapy:
Delavirdine, itraconazole, or ketoconazole: Reduce indinavir dose to 600 mg every 8 hours.
Efavirenz: Increase indinavir dose to 1000 mg every 8 hours
Lopinavir and ritonavir (Kaletra™): Indinavir 600 mg twice daily
Nevirapine: Increase indinavir dose to 1000 mg every 8 hours
Rifabutin: Reduce rifabutin to 1/2 the standard dose plus increase indinavir to 1000 mg every 8 hours

Ritonavir: Adjustments necessary for both agents:
Ritonavir 100-200 mg twice daily plus indinavir 800 mg twice daily or
Ritonavir 400 mg twice daily plus indinavir 400 mg twice daily

Dosage adjustment in hepatic impairment: Mild-moderate impairment due to cirrhosis: 600 mg every 8 hours or with ketoconazole coadministration

Administration
Drink at least 48 oz of water daily. Administer with water, 1 hour before or 2 hours after a meal. Administer around-the-clock to avoid significant fluctuation in serum levels.

Supplied:
Capsule: 100 mg, 200 mg, 333 mg, 400 mg

Kaletra ® (lopinavir  + ritonavir) 

DOSAGE AND ADMINISTRATION
KALETRA tablets may be taken with or without food. The tablets should be swallowed whole and not chewed, broken, or crushed.

KALETRA oral solution must be taken with food.

Adult Patients
KALETRA tablets 400/100 mg (given as two 200/50 mg tablets) twice daily.
KALETRA oral solution 400/100 mg (5 mL) twice daily.
KALETRA tablets 800/200 mg (given as four 200/50 mg tablets) once daily in patients with less than three lopinavir resistance-associated substitutions.
KALETRA oral solution 800/200 mg (10 mL) once daily in patients with less than three lopinavir resistance-associated substitutions.

Once daily administration of KALETRA is not recommended for adult patients with three or more of the following lopinavir resistance-associated substitutions: L10F/I/R/V, K20M/N/R, L24I, L33F, M36I, I47V, G48V, I54L/T/V, V82A/C/F/S/T, and I84V.

KALETRA should not be administered once daily in combination with carbamazepine, phenobarbital, or phenytoin.

Concomitant Therapy: Efavirenz, Nevirapine, or Nelfinavir
[see package insert for Clinical Pharmacology (12.3) and [Drug Interactions (7.3)]

KALETRA tablets and oral solution should not be administered as a once daily regimen in combination with efavirenz, nevirapine, or nelfinavir.

A dose increase is recommended for all patients who use KALETRA tablets. The recommended dose of KALETRA tablets is 500/125 mg (such as two 200/50 tablets and one 100/25 mg tablet) twice daily in combination with efavirenz, nevirapine, or nelfinavir.

A dose increase is recommended for all patients who use KALETRA oral solution. The recommended dose of KALETRA oral solution is 533/133 mg (6.5 mL) twice daily when used in combination with efavirenz, nevirapine, or nelfinavir.

See package insert for pediatric dosing.

DOSAGE FORMS AND STRENGTHS
KALETRA Tablets, 200 mg lopinavir/50 mg ritonavir
Yellow, film-coated, ovaloid tablets debossed with the “a” logo and the code KA providing 200 mg lopinavir/50 mg ritonavir.

KALETRA Tablets, 100 mg lopinavir/25 mg ritonavir
Pale yellow, film-coated, ovaloid tablets debossed with the “a” logo and the code KC providing 100 mg lopinavir/25 mg ritonavir.

KALETRA Oral Solution
Light yellow to orange colored liquid containing 400 mg lopinavir/100 mg ritonavir per 5 mL (80 mg lopinavir/20 mg ritonavir per mL).

Nelfinavir (viracept ®) 

DOSAGE AND ADMINISTRATION

Adults and Adolescents (13 years and older)
The recommended dose is 1250 mg (five 250 mg tablets or two 625 mg tablets) twice daily or 750 mg (three 250 mg tablets) three times daily. VIRACEPT should be taken with a meal. Patients unable to swallow the 250 or 625 mg tablets may dissolve the tablets in a small amount of water

See package insert for pediatric dosing.

Method of Administration
For Patients Unable to Swallow Viracept Tablets:
Place VIRACEPT tablet(s) in small amount of water.
Once dissolved, mix the cloudy liquid well, and consume it immediately.
The glass should be rinsed with water and the rinse swallowed to ensure the entire dose is consumed.

Viracept Oral Powder:
Mix VIRACEPT Oral Powder with a small amount of water, milk, formula, soy formula, soy milk, or dietary supplements
Once mixed, the entire contents must be consumed in order to obtain the full dose.
If the mixture is not consumed immediately, it must be stored under refrigeration, but storage must not exceed 6 hours.
Acidic food or juice (e.g., orange juice, apple juice, or apple sauce) are not recommended for mixing VIRACEPT Oral Powder because the combination may result in a bitter taste.
VIRACEPT Oral Powder should not be reconstituted with water in its original container.

Hepatic Impairment
VIRACEPT can be used in patients with mild hepatic impairment without any dose adjustment. VIRACEPT should not be used in patients with either moderate or severe hepatic impairment.

DOSAGE FORMS AND STRENGTHS
VIRACEPT 250 mg Tablet: Light-blue, capsule-shaped tablets with a clear film coating engraved with "VIRACEPT" on one side and "250 mg" on the other.

VIRACEPT 625 mg Tablet: White oval tablet with a clear film coating engraved with "V" on one side and "625" on the other.

VIRACEPT Oral Powder: Off-white powder containing 50 mg (as nelfinavir-free base) in each level scoopful (1 gram).

Ritonavir (norvir ®) 

DOSAGE AND ADMINISTRATION
NORVIR is administered orally. NORVIR tablets should be swallowed whole, and not chewed, broken or crushed. Take NORVIR with meals. Patients may improve the taste of NORVIR oral solution by mixing with chocolate milk, Ensure®, or Advera® within one hour of dosing.

General Dosing Guidelines
Patients who take the 600 mg twice daily soft gel capsule NORVIR dose may experience more gastrointestinal side effects such as nausea, vomiting, abdominal pain or diarrhea when switching from the soft gel capsule to the tablet formulation because of greater maximum plasma concentration (Cmax) achieved with the tablet formulation relative to the soft gel capsule. Patients should also be aware that these adverse events (gastrointestinal or paresthesias) may diminish as therapy is continued.

Dose Modification for NORVIR
Dose reduction of NORVIR is necessary when used with other protease inhibitors: atazanavir, darunavir, fosamprenavir, saquinavir, and tipranavir.

Prescribers should consult the full prescribing information and clinical study information of these protease inhibitors if they are co-administered with a reduced dose of ritonavir.

Adult Patients
Recommended Dosage for Treatment of HIV-1:

The recommended dosage of ritonavir is 600 mg twice daily by mouth to be taken with meals. Use of a dose titration schedule may help to reduce treatment-emergent adverse events while maintaining appropriate ritonavir plasma levels. Ritonavir should be started at no less than 300 mg twice daily and increased at 2 to 3 day intervals by 100 mg twice daily. The maximum dose of 600 mg twice daily should not be exceeded upon completion of the titration.

See package insert for pediatric dosing.

DOSAGE FORMS AND STRENGTHS
NORVIR Tablets
White film-coated ovaloid tablets debossed with the "a" logo and the code NK providing 100 mg ritonavir.

NORVIR Oral Solution
Orange-colored liquid containing 600 mg ritonavir per 7.5 mL marked dosage cup (80 mg per mL).

Saquinavir  (fortovase ® ,invirase ®)

Dosing (Adult):
Note: Fortovase® and Invirase® are not bioequivalent and should not be used interchangeably; only Fortovase® should be used to initiate therapy:

Fortovase®: 1200 mg (six 200 mg capsules) 3 times/day within 2 hours after a meal in combination with a nucleoside analog or 1000 mg (five 200 mg capsules) twice daily in combination with ritonavir 100 mg twice daily

Invirase®: 1000 mg (five 200 mg capsules or two 500 mg tablets) twice daily given in combination with ritonavir 100 mg twice daily; this combination should be given together and within 2 hours after a full meal in combination with a nucleoside analog

Note: Dosage adjustments of Fortovase® when administered in combination therapy:
Delavirdine: Fortovase® 800 mg 3 times/day

Lopinavir and ritonavir (Kaletra™): Fortovase® 800 mg twice daily

Nelfinavir: Fortovase® 1200 mg twice daily

Elderly: Clinical studies did not include sufficient numbers of patients >/= 65 years of age; use caution due to increased frequency of organ dysfunction

Supplied:
Capsule, as mesylate (Invirase®): 200 mg
Capsule, soft gelatin, as base (Fortovase®): 200 mg
Tablet, as base (Invirase®): 500 mg

Tipranavir (aptivus ® )

Protease Inhibitor.
Dosing (Adult)
: 500 mg twice daily with a high-fat meal. Note: Coadministration with ritonavir (200 mg twice daily) is required.

Supplied: 250 mg capsule.

Evotaz™ (atazanavir and cobicistat) 

Drug UPDATES:  EVOTAZ™ (atazanavir and cobicistat) tablet
[Drug information  /  PDF]  led Click link for the latest monograph
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2015

Mechanism of Action: EVOTAZ is a fixed-dose combination of the HIV-1 antiretroviral drug, atazanavir and the CYP3A inhibitor, cobicistat.

INDICATIONS AND USAGE:  EVOTAZ™ (atazanavir and cobicistat) is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in adults.

Limitation of Use:
Use of EVOTAZ in treatment-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions.

HOW SUPPLIED: EVOTAZ Tablets contain 342 mg atazanavir sulfate, equivalent to 300 mg of atazanavir, and 150 mg of cobicistat and are oval, biconvex, pink, film-coated, and debossed with '3641' on one side and plain on the other side.

Prezcobix ™(darunavir and cobicistat) tablets 

Drug UPDATES:  PREZCOBIX ™(darunavir and cobicistat) tablets
[Drug information  /  PDFled   Click link for the latest monograph
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2015

Mechanism of Action: PREZCOBIX is a fixed-dose combination of an HIV-1 antiviral drug, darunavir and a CYP3A inhibitor, cobicistat

INDICATIONS AND USAGE:  PREZCOBIX is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in treatment-naïve and treatment-experienced adults with no darunavir resistance-associated substitutions (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V).

HOW SUPPLIED:  Tablets: 800 mg of darunavir and 150 mg of cobicistat.

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates.  A local search option of this data can be found here.

Protease Inhibitors

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