Norvir Information
Norvir (Ritonavir) Warning
CO-ADMINISTRATION OF Norvir (Ritonavir) WITH SEDATIVE HYPNOTICS, ANTIARRHYTHMICS, OR ERGOT ALKALOID PREPARATIONS MAY RESULT IN POTENTIALLY SERIOUS AND/OR LIFE-THREATENING ADVERSE EVENTS DUE TO POSSIBLE EFFECTS OF Norvir (Ritonavir) ON THE HEPATIC METABOLISM OF CERTAIN DRUGS. SEE AND SECTIONS.
Norvir (Ritonavir) Description
Norvir (Ritonavir) is an inhibitor of HIV protease with activity against the Human Immunodeficiency Virus (HIV).
Ritonavir is chemically designated as 10-Hydroxy-2-methyl-5-(1-methylethyl)-1- [2-(1-methylethyl)-4-thiazolyl]-3,6-dioxo-8,11-bis(phenylmethyl)-2,4,7,12- tetraazatridecan-13-oic acid, 5-thiazolylmethyl ester, [5S-(5R*,8R*,10R*,11R*)]. Its molecular formula is CHNOS, and its molecular weight is 720.95. Ritonavir has the following structural formula:
Ritonavir is a white-to-light-tan powder. Ritonavir has a bitter metallic taste. It is freely soluble in methanol and ethanol, soluble in isopropanol and practically insoluble in water.
Norvir (Ritonavir) soft gelatin capsules are available for oral administration in a strength of 100 mg ritonavir with the following inactive ingredients: Butylated hydroxytoluene, ethanol, gelatin, iron oxide, oleic acid, polyoxyl 35 castor oil, and titanium dioxide.
Norvir (Ritonavir) oral solution is available for oral administration as 80 mg/mL of ritonavir in a peppermint and caramel flavored vehicle. Each 8-ounce bottle contains 19.2 grams of ritonavir. Norvir (Ritonavir) oral solution also contains 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 (Ritonavir) Indications And Usage
Norvir (Ritonavir) is indicated in combination with other antiretroviral agents for the treatment of HIV-infection. This indication is based on the results from a study in patients with advanced HIV disease that showed a reduction in both mortality and AIDS-defining clinical events for patients who received Norvir (Ritonavir) either alone or in combination with nucleoside analogues. Median duration of follow-up in this study was 13.5 months.
Norvir (Ritonavir) Warnings
When co-administering Norvir (Ritonavir) with other protease inhibitors, see the full prescribing information for that protease inhibitor including .
Norvir (Ritonavir) Precautions
When co-administering Norvir (Ritonavir) with other protease inhibitors, see the full prescribing information for that protease inhibitor including .
A statement to patients and health care providers is included on the product's bottle label: . A Patient Package Insert (PPI) for Norvir (Ritonavir) is available for patient information.
Patients should be informed that Norvir (Ritonavir) is not a cure for HIV infection and that they may continue to acquire illnesses associated with advanced HIV infection, including opportunistic infections.
Patients should be told that the long-term effects of Norvir (Ritonavir) are unknown at this time. They should be informed that Norvir (Ritonavir) therapy has not been shown to reduce the risk of transmitting HIV to others through sexual contact or blood contamination.
Patients should be advised to take Norvir (Ritonavir) with food, if possible.
Patients should be informed to take Norvir (Ritonavir) every day as prescribed. Patients should not alter the dose or discontinue Norvir (Ritonavir) without consulting their doctor. If a dose is missed, patients should take the next dose as soon as possible. However, if a dose is skipped, the patient should not double the next dose.
Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long term health effects of these conditions are not known at this time.
Norvir (Ritonavir) may interact with some drugs; therefore, patients should be advised to report to their doctor the use of any other prescription, non-prescription medication or herbal products, particularly St. John's wort.
Patients receiving PDE5 inhibitors for erectile dysfunction (eg, sildenafil, tadalafil, or vardenafil) should be advised that they may be at an increased risk of associated adverse events including hypotension, visual changes, and sustained erection, and should promptly report any symptoms to their doctor. Concomitant use of sildenafil with Norvir (Ritonavir) is contraindicated in patients with pulmonary arterial hypertension (PAH).
Patients receiving estrogen-based hormonal contraceptives should be instructed that additional or alternate contraceptive measures should be used during therapy with Norvir (Ritonavir) .
Patients should be informed that Norvir (Ritonavir) may produce changes in the electrocardiogram (e.g., PR prolongation). Patients should consult their physician if they experience symptoms such as dizziness, lightheadedness, abnormal heart rhythm, or loss of consciousness.
Ritonavir has been found to be an inhibitor of cytochrome P450 3A (CYP3A) both and (Table 3). Agents that are extensively metabolized by CYP3A and have high first pass metabolism appear to be the most susceptible to large increases in AUC (> 3-fold) when co-administered with ritonavir. Ritonavir also inhibits CYP2D6 to a lesser extent. Co-administration of substrates of CYP2D6 with ritonavir could result in increases (up to 2-fold) in the AUC of the other agent, possibly requiring a proportional dosage reduction. Ritonavir also appears to induce CYP3A as well as other enzymes, including glucuronosyl transferase, CYP1A2, and possibly CYP2C9.
Drugs that are contraindicated specifically due to the expected magnitude of interaction and potential for serious adverse events are listed both in and under in .
Those drug interactions that have been established based on drug interaction studies are listed with the pharmacokinetic results in and . The clinical recommendations based on the results of these studies are listed in . A systematic review of over 200 medications prescribed to HIV-infected patients was performed to identify potential drug interactions with ritonavir. There are a number of agents in which CYP3A or CYP2D6 partially contribute to the metabolism of the agent. In these cases, the magnitude of the interaction and therapeutic consequences cannot be predicted with any certainty.
When co-administering ritonavir with calcium channel blockers, immunosuppressants, some HMG-CoA reductase inhibitors, some steroids, or other substrates of CYP3A; or most antidepressants, certain antiarrhythmics, and some narcotic analgesics which are partially mediated by CYP2D6 metabolism, it is possible that substantial increases in concentrations of these other agents may occur, possibly requiring a dosage reduction (> 50%); examples are listed in .
When co-administering ritonavir with any agent having a narrow therapeutic margin, such as anticoagulants, anticonvulsants, and antiarrhythmics, special attention is warranted. With some agents, the metabolism may be induced, resulting in decreased concentrations (see ).
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The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV.
not to breast-feed if they are receiving Norvir (Ritonavir)
Norvir (Ritonavir) Adverse Reactions
When co-administering Norvir (Ritonavir) with other protease inhibitors, see the full prescribing information for that protease inhibitor including .
The safety of Norvir (Ritonavir) alone and in combination with nucleoside reverse transcriptase inhibitors was studied in 1270 adult patients. Table 7 lists treatment-emergent adverse events (at least possibly related and of at least moderate intensity) that occurred in 2% or greater of adult patients receiving Norvir (Ritonavir) alone or in combination with nucleoside reverse transcriptase inhibitors in Study 245 or Study 247 and in combination with saquinavir in study 462. In that study, 141 protease inhibitor-naive, HIV-infected patients with mean baseline CD of 300 cells/µL were randomized to one of four regimens of Norvir (Ritonavir) + saquinavir, including Norvir (Ritonavir) 400 mg twice-daily + saquinavir 400 mg twice-daily. Overall the most frequently reported clinical adverse events, other than asthenia, among adult patients receiving Norvir (Ritonavir) were gastrointestinal and neurological disturbances including nausea, diarrhea, vomiting, anorexia, abdominal pain, taste perversion, and circumoral and peripheral paresthesias. Similar adverse event profiles were reported in adult patients receiving ritonavir in other trials.
Adverse events occurring in less than 2% of adult patients receiving Norvir (Ritonavir) in all phase II/phase III studies and considered at least possibly related or of unknown relationship to treatment and of at least moderate intensity are listed below by body system.
Norvir (Ritonavir) Overdosage
Norvir (Ritonavir) oral solution contains 43% alcohol by volume. Accidental ingestion of the product by a young child could result in significant alcohol-related toxicity and could approach the potential lethal dose of alcohol.
Treatment of overdose with Norvir (Ritonavir) 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 (Ritonavir) . If indicated, elimination of unabsorbed drug should be achieved by emesis or 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. A Certified Poison Control Center should be consulted for up-to-date information on the management of overdose with Norvir (Ritonavir) .
Norvir (Ritonavir) Dosage And Administration
Norvir (Ritonavir) is administered orally. It is recommended that Norvir (Ritonavir) be taken with meals if possible. Patients may improve the taste of Norvir (Ritonavir) oral solution by mixing with chocolate milk, Ensure, or Advera within one hour of dosing. The effects of antacids on the absorption of ritonavir have not been studied.
Ritonavir should be used in combination with other antiretroviral agents (see ). The recommended dosage of ritonavir in children > 1 month is 350 to 400 mg/m twice daily by mouth and should not exceed 600 mg twice daily. Ritonavir should be started at 250 mg/m and increased at 2 to 3 day intervals by 50 mg/m twice daily. If patients do not tolerate 400 mg/m twice daily due to adverse events, the highest tolerated dose may be used for maintenance therapy in combination with other antiretroviral agents, however, alternative therapy should be considered. When possible, dose should be administered using a calibrated dosing syringe.
Body surface area (BSA) can be calculated as follows:
Norvir (Ritonavir) How Supplied
Norvir (Ritonavir) (ritonavir capsules) soft gelatin are white capsules imprinted with the corporate , 100 and the Abbo-Code DS, available in the following package size:
Bottles of 120 capsules each ( 0074-6633-22).
Bottles of 30 capsules each ( 0074-6633-30).
Norvir (Ritonavir) (ritonavir oral solution) is an orange-colored liquid, supplied in amber-colored, multi-dose bottles containing 600 mg ritonavir per 7.5 mL marked dosage cup (80 mg/mL) in the following size:
240 mL bottles ( 0074-1940-63).
Store Norvir (Ritonavir) oral solution at room temperature 20°-25°C (68°-77°F). Do not refrigerate. Shake well before each use. Use by product expiration date.
Product should be stored and dispensed in the original container.
Avoid exposure to excessive heat. Keep cap tightly closed.
Norvir (Ritonavir) References
Norvir (Ritonavir) 100 mg capsules are manufactured for: Abbott LaboratoriesNorth Chicago, IL 60064, U.S.A.
Norvir (Ritonavir) Oral Solution is manufactured by: Abbott Laboratories North Chicago, IL 60064, U.S.A.
Read this Patient Information before you start taking Norvir (Ritonavir) and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.
Norvir (Ritonavir) is a prescription anti-HIV medicine used with other anti-HIV medicines to treat people with human immunodeficiency virus (HIV) infection. Norvir (Ritonavir) is a type of anti-HIV medicine called a protease inhibitor. HIV is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).
When used with other HIV medicines, Norvir (Ritonavir) may reduce the amount of HIV in your blood (called “viral load”). Norvir (Ritonavir) may also help to increase the number of CD (T) cells in your blood which help fight off other infections. Reducing the amount of HIV and increasing the CD (T) cell count may improve your immune system. This may reduce your risk of death or infections that can happen when your immune system is weak (opportunistic infections). Patients who took Norvir (Ritonavir) in clinical studies had significant reductions in both death and AIDS defining diseases; however Norvir (Ritonavir) may not have these effects in all patients.
Patients must stay on continuous HIV treatment to control infection and decrease HIV-related illnesses. Always practice safer sex by using a latex or polyurethane condom to lower the chance of sexual contact with any body fluids such as semen, vaginal secretions, or blood. Never re-use or share needles.
Ask your doctor if you have any questions on how to prevent passing HIV to other people.
Do not take Norvir (Ritonavir) if you are allergic to ritonavir or any of the ingredients in Norvir (Ritonavir) . See the end of this leaflet for a complete list of ingredients in Norvir (Ritonavir) .
Serious problems can happen if you or your child takes any of these medicines with Norvir (Ritonavir) .
Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. Taking Norvir (Ritonavir) and certain other medicines may affect each other causing serious side effects. Norvir (Ritonavir) may affect the way other medicines work and other medicines may affect how Norvir (Ritonavir) works.
Especially tell your doctor if you take:
This is not a complete list of medicines that you should tell your doctor that you are taking. Ask your doctor, provider or pharmacist if you are not sure if your medicine is one that is listed above.
Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine. Do not start any new medicines while you are taking Norvir (Ritonavir) without first talking with your doctor.
Norvir (Ritonavir) can cause serious side effects including:
The most common side effects of Norvir (Ritonavir) include:
Norvir (Ritonavir) liquid contains a large amount of alcohol. If a toddler or young child accidentally drinks more than the recommended dose of Norvir (Ritonavir) , it could make him/her sick from too much alcohol. Contact your local poison control center or emergency room immediately if this happens.
Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of Norvir (Ritonavir) . For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Store Norvir (Ritonavir) soft gelatin capsules in the refrigerator between 36°F to 46°F (2°C to 8°C) Norvir (Ritonavir) soft gelatin capsules may be stored below 77°F (25°C) is used within 30 days.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use this medicine for a condition for which it was not prescribed. Do not share this medicine with other people.
This leaflet summarizes the most important information about Norvir (Ritonavir) . If you would like more information, talk to your doctor. You can ask your doctor or pharmacist for information about Norvir (Ritonavir) that is written for healthcare professionals.
For more information, call 1-800-633-9110.
Norvir (Ritonavir) 100 mg capsules are manufactured for:
Abbott LaboratoriesNorth Chicago, IL 60064, U.S.A.
Norvir (Ritonavir) Oral Solution is manufactured by: Abbott Laboratories North Chicago, IL 60064, U.S.A.
* The brands listed are trademarks of their respective owners and are not trademarks of Abbott Laboratories. The makers of these brands are not affiliated with and do not endorse Abbott Laboratories or its products.
Rev. 12/2011
Norvir (Ritonavir)
