All you need to know about Ritonavir

Ritonavir (Norvir): Norvir was the first representative of a new class called protease inhibitors for the treatment of HIV-infected patients.

Ritonavir is basically indicated in combination with another antiretroviral nucleoside analogue (s) for treating the HIV-1 infected patients with advanced or progressive immunodeficiency”.

Some clinical studies shows that, ritonavir mainly used as a pharmacokinetic enhancer (low doses) in order to boost the plasma concentrations of other PIs (protease inhibitors) in Human Immunodeficiency Virus (HIV)-infected patients has become available. According to the review of CHMP of data on quality, efficacy, and safety, the CHMP (Committee for Medicinal Products for Human Use) considered by consensus that the benefit or risk profile of Ritonavir (Norvir) was quite favourable when it combines with other antiretroviral agents for the treatment of such patients who are HIV-1 infected (adults and children of 2 year age and older).

Ritonavir with Lopinavir:

The class of Lopinavir/ritonavir is an HIV protease inhibitor. The combination of Lopinavir ritonavir has antiviral activity against HIV-1.

Mechanism of Action: Lopinavir/ritonavir inhibits the HIV protease enzyme by forming an inhibitor-enzyme complex thereby preventing cleavage of the gag-pol polyproteins. Non-infectious viral particles (Immature) are subsequently produced.

Mechanism of Resistance: Greater levels of PIs (protease inhibitor) resistance result from the accumulation of multiple protease inhibitor-resistance mutations. There are several mechanisms of resistance. These include

• Effects on dimer stability.
• Alterations in enzyme catalysis. 
• Alterations in inhibitor binding kinetics. 
• Re-shaping of the active site.
• Reduced binding affinity between the protease enzyme and inhibitors.

Adverse Effects: Some side effects of this combined medication are as follows:

• Diarrhea
• Nausea
• Asthenia
• Abdominal pain
• Vomiting
• Headache
• Rash
• Hyperglycemia
• Uremia
• Hyperbilirubinemia
• Elevated AST or ALT
• Hypercholesterolemia
• Hypertriglyceridemia
• Elevated amylase
• Hypophosphatemia and Neutropenia

Dosage:

For adult patients the recommended dose of lopinavir and ritonavir tablets is 400/100mg (3 capsules or 5.0mL) twice daily, should be administered with food.

Contraindications Or Warnings: Lopinavir/ritonavir is contraindicated with the following medications:
astemizole, terfenadine, dihydroergotamine, ergonovine, ergotamine, methylergonovine,
cisapride, pimozide, midazolam, and triazolam.

Drug Interactions: In vitro, Lopinavir/ritonavir has been shown to be a substrate for, and inhibitor of, CYP3A. In vivo, this combined drug has shown induction and autoinduction of other drugs mainly metabolized by the CYP450 enzymes. The drug is generally metabolized through the enzyme named CYP450 which may interact with lopinavir/ritonavir.

Ritonavir with Atazanavir:

Atazanavir/ritonavir is a combination medication used in the treatment of HIV/AIDS. It combines atazanavir ritonavir. This combination can be preferred instead of the lopinavir/ritonavir.
Where Atazanavir works as Protease inhibitor and Ritonavir works as Protease inhibitor (pharmacokinetic booster).

Side Effects: Side effects with these combined medications are generally minimal.
They may include as follows:

• Abdominal pain
• Diarrhea
• Yellowish skin
• Muscle pains
• Headache.

Greater care is recommended in people with underlying liver problems.

Dosage: The recommended dose of Atazanavir Ritonavir tablets should be based on the prescription of your healthcare provider.

Ritonavir with Darunavir:

Combination of Darunavir Ritonavir:
This combination is also quite effective.
The combination often combines Darunavir and Ritonavir.  This antiretroviral medication is generally used in the treatment and prevention of HIV/AIDS.

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How Darunavir Ritonavir combination is useful in the treatment of HIV

Darunavir: 

Darunavir (DRV), is an antiretroviral medication, which is sold under the brand name Prezista in order to treat as well as prevent HIV/AIDS.
DRV (Darunavir) is generally recommended for use with other antiretrovirals. It is often used with low doses of ritonavir or cobicistat with the motive of increasing the levels of darunavir. Darunavir, combines with the ritonavir 100 mg antiretroviral and with some other antiretroviral agents, for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment experienced adult patients, such as those with Human Immunodeficiency Virus-1 (HIV-1) strains resistant to more than one protease inhibitor.

Darunavir comes as the strengths which are as follows:

• Darunavir 75 mg tablets
• Darunavir 150 mg tablets
• Darunavir 400 mg tablets
• Darunavir 600 mg tablets
• Darunavir 800 mg tablets

Side Effects of Darunavir: 

This is a quite well-tolerated medication and sometimes it may leave some adverse reactions, which are as follows:

• Skin rash
• Hepatotoxicity
• Diarrhea
• Nausea
• Headache
• Hyperlipidemia
• Serum transaminase elevation
• Hyperglycemia
• Fat maldistribution

Ritonavir:

Ritonavir (RTV), an antiretroviral medication, which is sold under the trade name Norvir in order to treat HIV/AIDS.
Ritonavir is generally prescribed for use along with other medications. When Ritonavir is used with the other medications, then this combination treatment is called HAART, which stands for highly active antiretroviral therapy. Often a low dose this medication is used with other protease inhibitors. It may also be used in combination with other medications for hepatitis C.

How Does Ritonavir Works: 

Initially, ritonavir was developed as an inhibitor of Human Immunodeficiency Virus (HIV) protease, which is one of a family of pseudo-C2-symmetric small molecule inhibitors.
The role of Ritonavir is as a booster. It is rarely used for its own antiviral activity.  This medication is mostly as well as widely used as a booster of other protease inhibitors.
Most important aspect of ritonavir is that it is used in order to inhibit a particular enzyme, in the liver, intestines, and elsewhere, that normally metabolizes protease inhibitors, cytochrome P450-3A4 (CYP3A4).
The drug binds to and inhibits CYP3A4 so that a low dose can be used in order to enhance the other protease inhibitors.
This medication comes as the strength of Ritonavir 100mg.

Side Effects of Ritonavir: 

Ritonavir most widely used as a lower dose. Its activity is mainly based on a CYP3A4 inhibitor.
The most common side effects of ritonavir are as follows:

• Asthenia, malaise
• Diarrhea
• Nausea and Vomiting
• Abdominal Pain
• Dizziness
• Insomnia
• Sweating
• Taste Abnormality
• Metabolic Effects

How Combination Of Darunavir/Ritonavir is Effective:

The reason behind taking both the protease inhibitors (darunavir, ritonavir) is that ritonavir has the potential that it will boost the level of darunavir and also it increases the effect of darunavir.

The recommended oral dose of darunavir tablets should be taken according to the prescribed by your healthcare provider. This medication should be taken with food. The sort of meal/food may not affect the exposure to darunavir.

Interaction: Darunavir ritonavir are both inhibitors of the CYP3A4 isoform.
Darunavir/Ritonavir should not be used in combination with rifampicin, as this may cause significant decreases in darunavir plasma concentrations. This may result in loss of therapeutic effect to Darunavir.

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