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What are protease inhibitors (PIs), and how
do they work?
Protease inhibitors (PIs) are antiviral drugs used for treating human immunodeficiency virus (HIV) infections and
hepatitis C virus (HCV) infections.
During infection with HIV or
hepatitis C, the HIV or
HCV multiply within the body’s cells. Viruses are released from the cells and spread throughout the body where they infect other cells. In this manner, HIV and
hepatitis C infection is perpetuated among new cells that the body produces continually. During the production of the viruses, new proteins are made. Some of the proteins are structural proteins that form the body of the virus. Other proteins are enzymes that manufacture DNA and other components for the new viruses. Protease is an enzyme that is used in the formation of new structural proteins and enzymes. Protease inhibitors block the activity of protease (cleavage of protein precursors needed for viral structure synthesis) and this results in the formation of defective viruses that are unable to infect the body’s cells. As a result, the number of HIV or
hepatitis C viruses in the body (the viral load) decreases.
List of 16 examples of brand and generic names available for protease inhibitors (PIs) in the US
HIV protease inhibitors
- Aptivus (tipranavir)
- Reyataz (atazanavir)
- Crixivan, IDV (indinavir)
- Prezista (darunavir)
- Lexiva (fosamprenavir)
- Invirase (saquinavir)
- Kaletra (lopinavir/ritonavir)
- Viracept (nelfinavir)
- Norvir (ritonavir)
Hepatitis C virus (HCV) protease inhibitors
- Victrelis (boceprevir
– discontinued) - Incivek (telaprevir
– discontinued) - Olysio (simeprevir)
- Technivie (ombitasvir/paritaprevir and ritonavir, a combination of these
three
drugs) - Viekira Pak (ombitasvir/paritaprevir/ritonavir and dasabuvir, a combination of
these four drugs)
QUESTION
Hepatitis C virus causes an infection of the ______________.
See Answer
What are the uses for protease inhibitors (PIs)?
- Protease inhibitors are used to treat HIV or hepatitis C virus infections. HIV protease inhibitors do not prevent the transmission of HIV among individuals, and they do not cure HIV infection or AIDS. However, HIV protease inhibitors can reduce the viral load to very low levels and reduce the risk of opportunistic infections. The discovery of HIV protease inhibitors revolutionized the management of HIV infection and the course of the disease.
- Hepatitis C virus protease inhibitors can cure hepatitis C infection, and are more effective than other
hepatitis C treatments. - The FDA approved the first hepatitis C virus protease inhibitor in 2011.
What are the side effects of HIV protease inhibitors (PIs)?
Common side effects of HIV protease inhibitors:
Serious side effects of HIV protease inhibitors include:
- Skin reactions
- Liver failure
- Seizures
- Failure of the
pancreas (pancreatitis) - Redistribution or
accumulation of body fat - Increased cholesterol
- Worsening of diabetes
- Heart block
- Immune reconstitution
syndrome
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What are the side effects of hepatitis C virus (HCV) protease inhibitors?
Common side effects of hepatitis C virus protease inhibitors:
- Rash
- Itching
- Muscle pain
- Headache
- Shortness of breath (dyspnea)
- Nausea
- Fatigue
- Diarrhea
- Dizziness
- Hyperbilirubinemia
- Elevated alkaline phosphatase
- Elevated amylase
- Elevated lipase
Serious side effects of hepatitis C virus protease inhibitors include:
- Liver failure
- Sun sensitivity
- Severe skin reactions
- Reactivation of HBV infection (hepatitis B virus)
What drug interactions occur with protease inhibitors (PIs)?
Protease inhibitors have many drug interactions because they affect the
action of liver enzymes that alter many drugs and because several other drugs
affect the breakdown of protease inhibitors in the liver. Here are some examples
of protease inhibitor drug interactions.
Protease inhibitor drugs may increase blood levels of the following drugs:
- alfuzosin (Uroxatral)
- doxazosin (Cardura)
- silodosin (Rapaflo)
- tamsulosin (Flomax)
- sildenafil (Viagra, Revatio)
- tadalafil (Cialis)
- warfarin (Coumadin, Jantoven)
- simvastatin (Zocor)
- lovastatin (Mevacor)
- amiodarone (Cordarone)
These drugs may increase blood levels of protease inhibitors:
- ketoconazole (Nizoral)
- itraconazole (Sporanox)
- fluconazole (Diflucan)
- voriconazole (Vfend)
- clarithromycin (Biaxin)
- erythromycin (Erythrocin)
- fluoxetine (Prozac)
The following drugs reduce blood levels of protease inhibitors:
- carbamazepine (Tegretol)
- phenobarbital
- phenytoin (Dilantin)
- rifampin
- St. John’s
Wort
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Are protease inhibitors (PIs) safe to use during pregnancy or while breastfeeding?
- Lopinavir/ritonavir and indinavir/ritonavir combinations are used for the treatment of HIV-infected
pregnant women. Other HIV protease inhibitor regimens have not been adequately studied in pregnant women, may not be effective, or may have unacceptable toxicity. - Hepatitis C virus protease inhibitors have not been adequately evaluated in pregnant women or
nursing mothers. - The patient's OB/GYN doctor should be consulted before protease inhibitors are used in a pregnant or nursing woman. Guidelines are available for the use of protease inhibitors in pregnant women, neonates, and children
(see references).
What forms and preparations of protease inhibitors (PIs)
are available?
- Protease inhibitors are supplied as capsules, tablets, oral suspension or solution, and powder for suspension.