Ritonavir, protease inhibitor antiretroviral for HIV

Ritonavir belongs to a group of antiretroviral drugs called protease inhibitors, often referred to as ‘PIs’. Ritonavir is used in combination with other antiretroviral for the treatment of the human immunodeficiency virus (HIV). Ritonavir is always taken with another protease inhibitor as it is used as a ‘pharmacokinetic enhancer’ to boost levels of protease inhibitors in your body. Without ritonavir, other protease inhibitors may not be effective at controlling the virus. 
Ritonavir belongs to a group of antiretroviral



Therapeutic indications
Ritonavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infected patients (adults and children of 2 years of age and older).


Contraindications




Hypersensitivity to the active substance or to any of the excipients
When ritonavir is used as a pharmacokinetic enhancer of other PIs, consult the Summary of Product Characteristics of the co-administered protease inhibitor for contraindications.
Ritonavir should not be given as a pharmacokinetic enhancer or as an antiretroviral agent to patients with decompensated liver disease.

How should I take ritonavir?

There are a number of different doses of ritonavir. The most common dose is one 100mg tablet taken once daily with food. Sometimes ritonavir is taken twice daily, or at higher doses. The dose depends on which protease inhibitor you are taking it with. When taking ritonavir to ‘boost’ the levels of another protease inhibitor, the two drugs must be taken at the same time each day.

The following HIV-1 protease inhibitors have been approved for use with ritonavir as a pharmacokinetic enhancer at the noted doses.

Adults

  • Amprenavir 600 mg twice daily with ritonavir 100 mg twice daily.
  • Atazanavir 300 mg once daily with ritonavir 100 mg once daily.
  • Fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily.
  • Lopinavir co-formulated with ritonavir (lopinavir/ritonavir) 400 mg/100 mg or 800 mg/200 mg.
  • Saquinavir 1,000 mg twice daily with ritonavir 100 mg twice daily in ART experienced patients.
  • Initiate treatment with saquinavir 500 mg twice daily with ritonavir 100 mg twice daily for the first 7 days, then saquinavir 1,000 mg twice daily with ritonavir 100 mg twice daily in ART-naïve patients.
  • Tipranavir 500 mg twice daily with ritonavir 200 mg twice daily. Tipranavir with ritonavir should not be used in treatment-naïve patients.
  • Darunavir 600 mg twice daily with ritonavir 100 mg twice daily in antiretroviral treatment.
  • (ART) experienced patients. Darunavir 800 mg once daily with ritonavir 100 mg once daily may be used in some ART experienced patients. 
  • Darunavir 800 mg once daily with ritonavir 100 mg once daily in ART-naïve patients.
Children and adolescents
Ritonavir is recommended for children 2 years of age and older. For further dosage recommendations, refer to the product information of other Protease Inhibitors approved for co-administration with ritonavir.


Ritonavir dosed as an antiretroviral agent

Adults
The recommended dose of ritonavir is 600 mg (6 tablets) twice daily (total of 1,200 mg per day) by mouth. Gradually increasing the dose of ritonavir when initiating therapy may help to improve tolerance.
Treatment should be initiated at 300 mg (3 tablets) twice daily for a period of three days and increased by 100 mg (1 tablet) twice daily increments up to 600 mg twice daily over a period of no longer than 14 days. Patients should not remain on 300 mg twice daily for more than 3 days.

Pediatric population (2 years of age and above)
The recommended dosage of ritonavir in children is 350 mg/m2 by mouth twice daily and should not exceed 600 mg twice daily. Ritonavir should be started at 250 mg/m2 and increased at 2 to 3 day intervals by 50 mg/m2 twice daily.

What are the common side effects with ritonavir?

Ritonavir, like all other medicines, has some side effects. Most of these are minor and will settle within a few days or weeks. Make sure you read the leaflet that came with ritonavir for a complete list. Bear in mind that most of the studies with ritonavir were using much higher doses than we do now so not all of these may be relevant. Some examples of the most common side effects are listed below.
• ‘Stomach’ side effects: Feeling sick (nausea), being sick (vomiting), diarrhoea, stomach pain or discomfort, indigestion.
• ‘Head’ side effects: Headache.
• Changes in blood test: Changes in some of your liver or kidney tests, or changes in cholesterol.
• Other side effects: Rash.

Pregnancy

A large amount (6100 live births) of pregnant women were exposed to ritonavir during pregnancy; of these, 2800 live births were exposed during the first trimester. These data largely refer to exposures where ritonavir was used in combination therapy and not at therapeutic ritonavir doses but at lower doses as a pharmacokinetic enhancer for other PIs. These data indicate no increase in the rate of birth defects compared to rates observed in population-based birth defect surveillance systems. Animal data have shown reproductive toxicity. Ritonavir can be used during pregnancy if clinically needed.
Ritonavir adversely interacts with oral contraceptives (OCs). Therefore, an alternative, effective and safe method of contraception should be used during treatment.

Breast-feeding

Limited published data reports that ritonavir is present in human milk.
There is no information on the effects of ritonavir on the breastfed infant or the effects of the drug on milk production. Because of the potential for (1) HIV transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants) and (3) serious adverse reactions in a breastfed infant, HIV infected women should not breast feed their infants under any circumstances if they are receiving ritonavir.

Fertility

No human data on the effect of ritonavir on fertility are available. Animal studies do not indicate harmful effects of ritonavir on fertility.

Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed. Dizziness is a known undesirable effect that should be taken into account when driving or using machinery.



Reference
https://aidsinfo.nih.gov/drugs/244/ritonavir/0/patient
https://www.webmd.com/drugs/2/drug-8436-1138/ritonavir-oral/ritonavir-oral/details
https://reference.medscape.com/drug/norvir-ritonavir-342627
http://www.antimicrobe.org/drugpopup/ritonavir.htm
https://www.nejm.org/doi/full/10.1056/NEJMoa2001282
https://www.drugbank.ca/drugs/DB00503
https://www.aidsmap.com/about-hiv/arv-factsheet/ritonavir
https://medlineplus.gov/druginfo/meds/a602015.html
Ritonavir, protease inhibitor antiretroviral for HIV Ritonavir, protease inhibitor antiretroviral for HIV Reviewed by gafacom on June 21, 2020 Rating: 5

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