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Norvir (ritonavir)


Articles on Norvir
Full US Prescribing Information

Patient Information
What is Norvir?
How Does it Work?
What Are the Side Effects?
Cautions and Warnings
Drug Interactions

Norvir is approved by the FDA for use in combination with the protease inhibitors Aptivus (tipranavir), Lexiva (fosamprenavir), Invirase (saquinavir) Kaletra (lopinavir), and Prezista (darunavir).

Norvir is also frequently combined with Crixivan (indinavir) and Reyataz (atazanavir).

Articles on Norvir

FDA Approves New Heat-stable Ritonavir (Norvir) Tablet

How Much Ritonavir (Norvir) Is Needed to Boost HIV Protease Inhibitors?


How Effective Are Boosted Dual Protease Inhibitor Regimens with No Additional Drugs in Treatment-naive HIV Patients?

Suboptimal Adherence May Have Less Detrimental Effect in Patients Taking Boosted Darunavir (Prezista)


Two New Pharmaco-enhancers -- GS-9305 and SPI-452 -- May Rival Ritonavir (Norvir) as a Boosting Agent

A Review of HIV Monotherapy with Ritonavir-boosted Protease Inhibitors

FDA Announces Changes to Ritonavir (Norvir) Label to Reflect New Data on Heart Rhythm Abnormalities

Switching from Other Ritonavir-boosted Protease Inhibitors to Boosted Atazanavir (Reyataz) Did Not Improve Body Fat Accumulation: REAL Study

A Comparison of the Single-dose Bioavailability of a Ritonavir Tablet Formulation Compared with the Current Soft Gel Capsule

Modern Ritonavir-boosted Protease Inhibitors Demonstrate Increased Resilience against the Emergence of Drug-resistant HIV

Is There a Potential Role for
Ritonavir-boosted Protease Inhibitor Monotherapy?

100 mg Once- and Twice-daily Ritonavir (Norvir) Decreases HDL and CD36 Expression, but Only Twice-daily Dosing Increases Triglycerides

What is Norvir?

Norvir is an anti-HIV medication. It is in a category of HIV medications called protease inhibitors (PIs). Norvir prevents T-cells that have been infected with HIV from producing new HIV.

Norvir is manufactured by Abbott Laboratories. The U.S. Food and Drug Administration (FDA) approved it for the treatment of HIV infection in 1996.

How Does it Work?

As with all the protease inhibitor drugs, its mechanism of action is by blocking HIV's key protease enzyme that HIV needs to reproduce. This results in defective HIV particles that are unable to infect new cells.

When taken regularly as prescribed, Norvir combination therapy usually leads to a profound decrease in HIV viral load (RNA) in the blood and substantial increases in the CD4 (T) cell count.

These benefits have led to decreased rates of AIDS opportunistic infections, improved quality of life and increased survival.

What Are the Side Effects?

The most common side effects of Norvir therapy—which are usually more severe if the standard dose (600mg twice-daily) is used—are related to the gut. Nausea, vomiting, diarrhea, and appetite loss are common.

Another possible side effect of Norvir is numbness/tingling around the mouth (oral paresthesias).

Anti-HIV drug regimens containing protease inhibitors, including Norvir, can cause increased fat levels (cholesterol and triglycerides) in the blood, abnormal body-shape changes (lipodystrophy; including increased fat around the abdomen, breasts, and back of the neck, as well as decreased fat in the face, arms, and legs), and diabetes. These side effects of anti-HIV drug therapy are reviewed in our lessons on Lipodystrophy, Facial Lipoatrophy, and Risks To Your Heart (Hyperlipidemia).

Cautions and Warnings

1. Both the capsule and liquid formulations contain alcohol. Those who are taking disulfiram (Antabuse) therapy as a deterrent to alcohol use should choose a different protease inhibitor or a disulfiram reaction could occur. Note that a similar problem can occur when taking Norvir with the antibiotic (and anti-parasitic) metronidazole (Flagyl, Metrogel); therefore, Norvir and metronidazole should not be taken together.

2. Norvir capsules should preferentially be stored in the refrigerator, but it is not essential as long as the drug is used within 60 days and is kept at temperatures of approximately 70° F and is not exposed to extreme cold or heat. Avoid exposure to light. It is recommended to store the capsules in the original container with the cap on tightly in between usage.

3. The liquid formulation should be stored at room temperature (68-77° F or 20-25° C) and not refrigerated. The solution should be shaken well before pouring. Solution should be used by the expiration date. Discard any unused Norvir solution after 30 days. After using the dosing cup, it should be washed with soap and warm water as soon as possible. The dosing cup is not dishwasher safe.

4. Liver toxicity associated with Norvir occurs more frequently among those with pre-existing liver disease, including hepatitis B or C viral infection.

5. The safety and dosing in infants and toddlers under age 2 has not been determined.

6. Tobacco use (smoking or chewing) leads to an 18% decreased blood level of Norvir. However, a dose increase of Norvir is not specifically recommended for users of tobacco.

7. If you miss a dose of Norvir, take that dose as soon as possible and the next dose at the scheduled time. However, if a dose is accidentally skipped altogether, do not double the next dose. Take that next dose at the regularly scheduled time. Better yet, try not to miss any doses; HIV only sleeps when you take your medications regularly.

8. Norvir combination therapy does not completely eliminate HIV DNA (genes) in semen and vaginal-cervical fluids. To help prevent HIV transmission to sex partners, barrier protection (safer sex) is warranted. This includes using either a male (external, penis) or female (internal) condom. Potential benefits of using an internal condom in the rectum during anal intercourse have not been established.

9. If Videx is a part of your Norvir combination therapy, dosing of the 2 should be separated by at least 2 1/2 hours.

10. Severe allergic reactions to Norvir can be life threatening if untreated. Life threatening heart attack or chest pain due to clogged heart arteries can result from abnormal increases in blood fats (cholesterol) due to Norvir. A rare vein blood clot due to Norvir could break off and lodge in the lung (pulmonary embolus), which can be life threatening. Symptoms include shortness-of-breath, palpitations and chest pain with breathing.

11. Some persons develop immune system flare illnesses within a few months after starting potent combination therapy for HIV infection. These occur due to inflammation associated with an improved immune system. The risk of these illnesses decreases significantly after the first 3-6 months of combination therapy.

12. The long-term effects (many years to decades) from Norvir are unknown.

13. Do not take Norvir as monotherapy (only one anti-HIV drug) as this will quickly lead to drug resistance. Always take anti-HIV therapy as a combination of several anti-retroviral drugs.


When Norvir is being used as the primary protease inhibitor, not as a booster of the other protease inhibitor in the regimen, the standard dose of Norvir is six 100 mg capsules (600 mg) every 12 hours, although there are some data that indicate that four 100 mg capsules (400 mg) every 12 hours is also effective. When given as a protease inhibitor booster, the dosing may range from 100-400mg twice daily or, if used as a part of a once-daily regimen, 100-200mg once-daily. While Norvir is rarely used as the only protease inhibitor, and is generally used for protease inhibitor boosting, the decision regarding which dose of Norvir to use should be made by a clinician with experience in treating HIV infection.

It is recommended that Norvir capsules be taken with food, since this increases the absorption. However, it is not mandatory to do so. When first starting Norvir, a gradual lead-in dosing over 2 weeks is recommended to help minimize side effects. The lead-in dosing still allows for therapeutic drug levels in blood, since the drug slowly induces its own metabolism. Start with 300 mg every 12 hours for up to 2 days. Then increase to 400 mg every 12 hours for up to 4 days. Then increase to 500 mg every 12 hours for up to 8 days. Then increase to the full dose of 600 mg every 12 hours no later than 15 days after starting.

The standard pediatric dose is 400 mg per square meter twice daily and should not exceed 600 mg twice daily. Body surface area in square meters can be calculated by: square root of [(height in centimeters X weight in kilograms) ÷ 3,600]. (Note 2.54 centimeters = one inch) A lead-in dosing is also recommended for pediatric patients. On day 1, start with 250 mg per square meter, twice daily. Then increase the twice daily dose by 50 mg per square meter every 2-3 days until the recommended maximum dose is reached.

Drug Interactions

Due to extremely potent effects upon liver enzymes that metabolize many drugs, Norvir has the longest list of drugs (among the anti-HIV drugs) that cannot be taken with it.

Norvir should not be taken with any of the following drugs due to life-threatening complications:
Pain medications: meperidine (Demerol);
piroxicam (Feldene);
propoxyphene (Darvon).

Pain medication alternatives that may be taken with Norvir include:
oxycodone (Percodan);
aspirin; acetaminophen (Tylenol, others).

Heart rhythm drugs:
amiodarone (Cordarone);
encainide (Enkaid);
flecainide (Tambocor);
propafenone (Rythmol); and
quinidine (Quinaglute, Quinidex).

There is limited experience with alternative heart rhythm drugs.

Anti-mycobacterial antibiotics: rifabutin (Mycobutin). Anti-mycobacterial alternatives that may be taken with Norvir include clarithromycin (Biaxin) and ethambutol (Myambutol).

Heart-blood pressure calcium channel blocker drugs: bepridil (Vascor). There is limited experience with alternative calcium channel blockers.

Cold and allergy antihistamines: astemizole (Hismanal) and terfenadine (Seldane). Cold and allergy antihistamine alternatives that may be taken with Norvir include loratadine (Claritin).

Ergot-migraine headache (blood vessel constricting) drugs: dihydroergotamine (D.H.E. 45) and ergotamine (several). There is limited experience with alternative ergot drugs.

Stomach-intestinal pro-movement drugs: cisapride (Propulsid). There is limited experience with alternative pro-movement drugs.

Antidepressant-psychotropic drugs: bupropion (Wellbutrin, note also used as an aid in tobacco cessation as Zyban). Antidepressant-psychotropic alternatives that may be taken with Norvir include desipramine (Norpramin); however, a dose reduction of desipramine may be necessary.

Psychotropic-neuroleptic drugs: clozapine (Clozaril) and pimozide (Orap). There is limited experience with alternative psychotropic-neuroleptic drugs.

Psychotropic-sedative-hypnotic drugs: clorazepate (Tranxene); diazepam (Valium); estazolam (ProSom); flurazepam (Dalmane); midazolam (Versed); triazolam (Halcion); and zolpidem (Ambien). Alternative psychotropic-sedative-hypnotic drugs that may be taken with Norvir include: temazepam (Restoril); lorazepam (Ativan); and alprazolam (Xanax--note that a slightly lower dose of alprazolam may be necessary; reference Frye, 37th Interscience Conference on Antimicrobial Agents and Chemotherapy abstract A-59)

When taken with didanosine (ddI, Videx), dosing should be separated by 2 1/2 hours to prevent formulation incompatibility, according the package insert.

When taken with the oral contraceptive ethinyl estradiol, blood levels of the hormone decreased significantly. Since this would prevent adequate contraception, hormone dosage increase or alternate (non-hormone) contraceptive measures are necessary (condoms).

When taken with the thyroid supplement hormone thyroxine, hormone levels may decrease significantly, requiring a dose increase of thyroxine.

When taken with the asthma drug theophylline (Theodur, others), the blood levels of theophylline decreased significantly. Increased theophylline dosing may be necessary.

When using the nose-allergy steroid spray fluticasone (Flonase), Cushing's syndrome may result (adrenal gland hormone excess with weight gain and diabetes) due to Norvir's inhibition of fluticasone's normal metabolism. The 2 drugs should not be combined.

Due to the presence of alcohol in both the capsule and liquid formulations of Norvir, neither disulfiram (Antabuse) nor metronidazole (Flagyl, Metrogel) should be taken with Norvir. A serious disulfiram reaction could occur.

Norvir decreases the drug concentration of methadone (used to treat narcotic heroin addiction) by approximately one-third. The dose of methadone may need to be increased in patients taking both medications.

Note that there are 136 other medications listed in the Norvir package insert whose levels may be significantly affected by co-administration with Norvir. Make sure you and your physician know what they are before you take any other medication with Norvir.

Significant drug interactions occur when Norvir is combined with any other anti-HIV protease inhibitor. Only take 2 protease inhibitors as prescribed by your physician.