Ritonavir

What is Ritonavir?

• Ritonavir (NORVIR) tablets and oral solution are HIV protease inhibitors used in combination with other protease inhibitors in the therapy and prevention of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS).

Ritonavir

Ritonavir ball-and-stick

HIV protesase with ritonavir

What are the uses of this medicine?

• NORVIR tablets and oral solution are prescription medicines that are used with other antiviral medicines to treat people with human immunodeficiency virus (HIV-1) infection.
• NORVIR oral powder is a prescription medicine that is used with other antiviral medicines to treat children with HIV-1 infection.

How does this medicine work?

Ritonavir (ri toe' na vir) is peptidomimetic HIV protease inhibitor that acts by binding to the catalytic site of the viral protease, thereby preventing the cleavage of viral polyprotein precursors into mature, functional proteins that are necessary for viral replication.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• are allergic to ritonavir or any of the ingredients in NORVIR. See the end of this leaflet for a complete list of ingredients in NORVIR.

• take any of the following medicines:
• alfuzosin
• apalutamide
• ranolazine
• dronedarone
• colchicine, if you have kidney or liver problems.
• lurasidone
• pimozide
• amiodarone

ergot-containing medicines including:

• dihydroergotamine mesylate
• ergotamine tartrate
• methylergonovine maleate
• cisapride
• flecainide
• lovastatin
• simvastatin
• lomitapide
• sildenafil (REVATIO®) only when used for treating the lung problem, pulmonary arterial hypertension (PAH)
• triazolam
• midazolam when taken by mouth
• propafenone
• quinidine
• St. John’s Wort (Hypericum perforatum) or a product that contains St. John’s wort
• voriconazole if your NORVIR dose is 400 mg every 12 hours or greater

What drug interactions can this medicine cause?

Co-administration of NORVIR can alter the concentrations of other drugs. The potential for drug-drug interactions must be considered prior to and during therapy.

NORVIR cannot be used with fallowing drugs:

• alfuzosin
• apalutamide
• ranolazine
• dronedarone
• colchicine, if you have kidney or liver problems.
• lurasidone
• pimozide
• amiodarone
• ergot-containing medicines including:
• dihydroergotamine mesylate
• ergotamine tartrate
• methylergonovine maleate
• cisapride
• flecainide
• lovastatin
• simvastatin
• lomitapide
• sildenafil (REVATIO®) only when used for treating the lung problem, pulmonary arterial hypertension (PAH)
• triazolam
• midazolam when taken by mouth
• propafenone
• quinidine
• St. John’s Wort (Hypericum perforatum) or a product that contains St. John’s wort
• voriconazole if your NORVIR dose is 400 mg every 12 hours or greater

Is this medicine FDA approved?

• Ritonavir was approved for use in the United States in 1996 and is still widely used in combination with other antiretroviral agents for the prevention and treatment of HIV infection.

How should this medicine be used?

Recommended dosage: Adult patients: 600 mg twice-day with meals. Pediatrics patients:

• The recommended twice daily dose for children greater than one month of age is based on body surface area and should not exceed 600 mg twice daily with meals.
• NORVIR oral solution should not be administered to neonates before a postmenstrual age (first day of the mother’s last menstrual period to birth plus the time elapsed after birth) of 44 weeks has been attained.
• NORVIR oral powder can only be used for dosing increments of 100 mg.
• Dose modification for NORVIR is necessary when used with other protease inhibitors.

Administration:

• You should stay under a healthcare provider's care during treatment with NORVIR. Do not change your dose of NORVIR or stop your treatment without talking with your healthcare provider first.
• If your child is taking NORVIR, your child’s healthcare provider will decide the right dose based on your child's height and weight. Tell your healthcare provider if your child’s weight changes. If your child does not tolerate NORVIR oral solution or NORVIR oral powder, ask your child’s healthcare provider for advice.
• Swallow NORVIR tablets whole. Do not chew, break, or crush tablets before swallowing. If you cannot swallow NORVIR tablets whole, tell your healthcare provider. You may need a different medicine.
• Take NORVIR with meals.
• NORVIR oral solution is peppermint or caramel flavored.
• You can take it alone, or may improve the taste by mixing it with 8 ounces of chocolate milk, Ensure®, or Advera®.
• NORVIR oral solution should be taken within 1 hour after mixing with these fluids.
• Ask your healthcare provider, nurse or pharmacist about other ways to improve the taste of NORVIR oral solution.
• Do not run out of NORVIR. Get your NORVIR prescription refilled from your healthcare provider or pharmacy before you run out.
• If you miss a dose of NORVIR, take it as soon as possible and then take your next scheduled dose at its regular time. If it is almost time for your next dose, wait and take the next dose at the regular time. Do not double the next dose.
• If you take too much NORVIR, call your local poison control center or go to the nearest hospital emergency room right away.
• Contact your doctor if you are planning to take Norvir Oral Solution through a feeding tube because some feeding tubes are not recommended for use with ethanol and/or propylene glycol-containing products like NORVIR.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Tablet: 100 mg
• Oral Solution: 80 mg per milliliter
• Oral Powder: 100 mg per packet

This medicine is available in fallowing brand namesː

• NORVIR

What side effects can this medication cause?

The most common side effects of this medicine include:

• diarrhea
• nausea
• vomiting
• upper and lower stomach (abdominal) pain
• tingling feeling or numbness in hands or feet or around the lips
• rash
• feeling weak or tired

NORVIR can cause serious side effects including:

• Liver problems
• Inflammation of your pancreas (pancreatitis)
• Allergic reactions
• Increase in cholesterol and triglyceride levels
• Diabetes and high blood sugar (hyperglycemia)
• Diabetes and high blood sugar (hyperglycemia)
• Change in body fat
• Increased bleeding for hemophiliacs
• Kidney stones

What special precautions should I follow?

• The concomitant use of NORVIR and certain other drugs may result in known or potentially significant drug interactions. Consult the full prescribing information prior to and during treatment for potential drug interactions.
• NORVIR oral solution should not be used in preterm neonates in the immediate postnatal period because of possible toxicities. A safe and effective dose of NORVIR oral solution in this patient population has not been established
• Hepatic transaminase elevations exceeding 5 times the upper limit of normal, clinical hepatitis, and jaundice have occurred in patients receiving NORVIR alone or in combination with other antiretroviral drugs. Fatalities have occurred. Monitor liver function before and during therapy, especially in patients with underlying hepatic disease, including hepatitis B and hepatitis C, or marked transaminase elevations.
• Pancreatitis has been observed in patients receiving NORVIR therapy. Fatalities have occurred; suspend therapy as clinically appropriate.
• Allergic reactions have been reported and include anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson syndrome, bronchospasm and angioedema. Discontinue treatment if severe reactions develop.
• Ritonavir prolongs the PR interval in some patients. Cases of second and third degree heart block have been reported. Use with caution with patients with preexisting conduction system disease, ischemic heart disease, cardiomyopathy, underlying structural heart disease or when administering with other drugs that may prolong the PR interval.
• Treatment with NORVIR therapy alone or in combination with saquinavir has resulted in substantial increases in the concentration of total cholesterol and triglycerides. Monitor prior to therapy and periodically thereafter
• Patients may develop new onset or exacerbations of diabetes mellitus, hyperglycemia. Consider monitoring for hyperglycemia, new onset diabetes mellitus, or an exacerbation of diabetes mellitus in patients treated with NORVIR.
• Patients may develop immune reconstitution syndrome.
• Patients may develop redistribution/accumulation of body fat.
• There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, in patients with hemophilia type A and B treated with protease inhibitors.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• renal failure with eosinophilia

Treatment of overdosage:

• Treatment of overdose with NORVIR consists of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.
• There is no specific antidote for overdose with NORVIR.
• If indicated, elimination of unabsorbed drug should be achieved by gastric lavage; usual precautions should be observed to maintain the airway. Administration of activated charcoal may also be used to aid in removal of unabsorbed drug. Since ritonavir is extensively metabolized by the liver and is highly protein bound, dialysis is unlikely to be beneficial in significant removal of the drug.

Can this medicine be used in pregnancy?

• Prospective pregnancy data from the Antiretroviral Pregnancy Registry (APR) are not sufficient to adequately assess the risk of birth defects or miscarriage.
• NORVIR oral solution is not recommended during pregnancy because there is no known safe level of ethanol exposure during pregnancy.

Can this medicine be used in children?

• In HIV-infected patients age greater than 1 month to 21 years have been established.

What are the active and inactive ingredients in this medicine?

Active ingredient: ritonavir

Inactive ingredients:

• NORVIR tablet: copovidone, anhydrous dibasic calcium phosphate, sorbitan monolaurate, colloidal silicon dioxide, and sodium stearyl fumarate. The film coating contains: hypromellose, titanium dioxide, polyethylene glycol 400, hydroxypropyl cellulose, talc, polyethylene glycol 3350, colloidal silicon dioxide, and polysorbate 80.

• NORVIR oral solution: ethanol, water, polyoxyl 35 castor oil, propylene glycol, anhydrous citric acid to adjust pH, saccharin sodium, peppermint oil, creamy caramel flavoring, and FD&C Yellow No. 6.

• NORVIR oral powder: copovidone, sorbitan monolaurate, and colloidal silicon dioxide.

Who manufactures and distributes this medicine?

• Manufactured and distributed by: Gilead Sciences, Inc. Foster City, CA

What should I know about storage and disposal of this medication?

Store NORVIR tablets:

• Store below 30°C (86°F). Exposure to temperatures up to 50°C (122°F) for seven days permitted.
• Exposure to high humidity outside the original container for longer than 2 weeks is not recommended.

Store NORVIR oral solution:

• At room temperature between 20°C to 25°C (68°F to 77°F).
• Do not refrigerate.
• Shake well before each use.
• Keep away from heat.
• Keep bottle cap tightly closed.

Store NORVIR oral powder:

• At or below 30°C (86°F).

Antiviral agents

Drugs for HIV Infection, in the Subclass Antiretroviral Agents

• Fusion Inhibitors (HIV)
  • Enfuvirtide, Maraviroc

• Integrase Inhibitors (HIV)
  • Dolutegravir, Elvitegravir, Raltegravir

• Monoclonal Antibodies
  • Ibalizumab

• Nonnucleoside Reverse Transcriptase Inhibitors (HIV)
  • Delavirdine, Efavirenz, Etravirine, Nevirapine, Rilpivirine

• Nucleoside Analogues (HIV)
  • Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Tenofovir, Zidovudine

• Protease Inhibitors (HIV)
  • Amprenavir, Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir,Ritonavir, Saquinavir, Tipranavir

Drugs for Hepatitis B

• • Alpha Interferon, Adefovir, Emtricitabine, Entecavir, Lamivudine, Telbivudine, Tenofovir

Drugs for Hepatitis C

• Interferon Based Therapies
  • Alpha Interferon and Peginterferon, Ribavirin

HCV NS5A Inhibitors

• Daclatasvir, Elbasvir, Ledipasvir, Ombitasvir, Pibrentasvir, Velpatasvir

HCV NS5B (Polymerase) Inhibitors

• Dasabuvir, Sofosbuvir

HCV Protease Inhibitors

• Asunaprevir, Boceprevir, Glecaprevir, Grazoprevir, Paritaprevir, Simeprevir, Telaprevir, Voxilaprevir

Combination Therapies

• Epclusa, Harvoni, Mavyret, Technive, Viekira Pak, Vosevi, Zepatier

Drugs for Herpes Virus Infections (HSV, CMV, others)

• Acyclovir, Cidofovir, Famciclovir, Foscarnet, Ganciclovir, Valacyclovir, Valganciclovir

Drugs for Influenza

• Amantadine, Oseltamivir, Peramivir, Rimantadine, Zanamivir

• Dailymed label info on Ritonavir
• FDA Ritonavir

Ritonavir Resources
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