Norvir (ritonavir) is a prescription medication used to treat human immunodeficiency virus (HIV) infections in adults and children. Norvir belongs to a group of medicines called HIV protease inhibitors, which reduce the amount of HIV in the blood. (Norvir is not a cure for HIV or AIDS). This medication comes in capsule, tablet, and oral solution forms and is adminstered twice a day, with meals. Norvir tablets are available for oral administration in strength of 100 mg ritonavir with the following inactive ingredients: anhydrous dibasic calcium phosphate, copovidone, colloidal silicon dioxide, sodium stearyl fumarate, and sorbitan monolaurate. The following are the ingredients in the film coating: titanium dioxide, hypromellose, polyethylene glycol 400, hydroxypropyl cellulose, polyethylene glycol 3350, talc, polysorbate 80and colloidal silicon dioxide. Norvir oral solution is available for oral administration as 80 mg/mL of ritonavir in a peppermint and caramel flavored vehicle. Each 8-ounce bottle carries 19.2 grams of ritonavir. Norvir oral solution also contains polyoxyl 35 castor oil, propylene glycol, ethanol, water, anhydrous citric acid to adjust pH, saccharin sodium, creamy caramel flavoring, peppermint oil, as well as FD&C Yellow No. 6. Norvir soft gelatin capsules are available for oral administration in a strength of 100 mg ritonavir with the following inactive ingredients: ethanol, Butylated hydroxytoluene, polyoxyl 35 castor oil, oleic acid, gelatin, titanium dioxide and iron oxide.
b). Possible side effects of Norvir
Many medications can cause side effects. A side effect is an unwanted compliance to a medication when it is taken in normal doses. Side effects can be moderate or severe, temporary or permanent. Also the side effects Norvir listed below are not experienced by everyone who takes this medication. If you seek to know about side effects of Norvir, discuss the risks and benefits of this medication with your doctor.
The following side effects Norvir have been reported by at least 1% of people taking Norvir. Many of these side effects of Norvir can be managed, and some may go away on their own over time. Call your doctor if you witness these side effects Norvir whether they are severe or bothersome. Your health care professional may be able to advise you on managing Norvir side effects.
• Abdominal pain
• Change in sense of taste
• Loss of appetite
• Body aches or pain
• Difficulty with moving
• Dryness or soreness of the throat
• Enough gas or air in the stomach or intestines
• Feeling sad or empty
• Full feeling
• Increased crave to urinate during the night
• Lack of appetite
• Loss of interest or pleasure
• Mood or mental changes
• Muscle pain or stiffness
• Pain in the joints or in an unspecified location
• Passing gas
• Runny nose
• Tender, swollen glands in the neck
• Throat irritation
• Trouble concentrating
• Trouble swallowing
• Voice changes
• Waking to urinate at night
• Feeling faint, dizzy, or lightheaded
• Feeling of warmth or heat
• Flushing or redness of the skin, particularly on the face and neck
• Dry or itchy skin
• Fruity mouth odor
• Increased hunger
• Increased thirst
• Increased urination
Even though most of the side effects Norvir listed below don't happen very frequently, they could result to serious problems if you do not seek medical attention. Discuss with your physician as soon as possible if any of the following side effects of Norvir occur:
• Increased fat on the upper back, neck, breasts, and around the trunk; and loss of fat from the legs, face as well as the arms
• Numbness or tingling sensation adjacent the mouth
• Numbness or tingling sensation in the hands or feet
• Gaining weight adjacent upper back, your neck, breast, waist or face
• Signs of bleeding (e.g., unusual bleeding or bruising, bleeding gums, unexplained nosebleeds)
• Signs of diabetes or increased blood sugar, e.g., cuts that don't heal, fruity mouth odour, increased thirst and increased urination
• Signs of infection (e.g., include fever or chills, sore throat, cough)
• Signs of liver problems, e.g, dark urine, diarrhea, loss of appetite, nausea, pale stools, vomiting, weight loss, yellowing of the skin or whites of the eyes, sweating
Stop taking Norvir and seek immediate medical attention if any of the following occur:
• Chest pain
• Signs of a serious allergic reaction, e.g, abdominal cramps, difficulty breathing, nausea and vomiting, swelling of the face and throat,
• Signs of a severe skin reaction, e.g, a rash combined with fever or discomfort, a rash occupying a vast area of the body, a rash that spreads rapidly, peeling as well as blistering
• Signs of pancreatitis, e.g, abdominal pain on the upper left side, back pain, chills, fever, nausea, rapid heartbeat, swollen abdomen all are indicators of Norvir side effects.
Some people may experience Norvir side effects other than those shortlisted. Discuss with your physician if you notice any symptom that worries you while you are taking this medication. You may report Norvir side effects to the FDA at 1-800-FDA-1088.
c). Patients Counseling information about Norvir
i). Liver disease
Some people taking Norvir in combination with other anti-HIV medicines have developed liver problems which may be life-threatening. Your doctor should do Constant blood tests during your combination therapy with Norvir. If you suffering from hepatitis B or C infection, your physician should examine your blood tests more often because you have an increased chance of developing liver problems. Discuss with your physician if you have any of the below signs and symptoms of liver problems:
- Loss of appetite
- Pain or tenderness on your right side beneath your ribs
- Yellowing of your body or whiteness of your eyes
- Itchy skin
ii). Swelling of your pancreas (Pancreatitis)
Norvir uses can cause serious pancreas problems, which may result to death. Tell your doctor right away if you have signs or symptoms of pancreatitis such as:
- stomach (abdominal) pain
iii). Allergic Reactions
Sometimes these allergic reactions can become severe and require treatment in a hospital. You should call your doctor straightaway if you develop a rash. Stop administering Norvir and get medical assistance right away if you have any of the following symptoms of a severe allergic reaction:
- Trouble breathing
- dizziness or fainting
- Throat tightness or hoarseness
- Fast heartbeat or pounding in your chest (tachycardia)
- Swelling of your face, lips or tongue
- Muscle or joint pain
- Blisters or skin lesions
- Mouth sores or ulcers
iv). Changes in the electrical activity of your heart called PR prolongation. PR prolongation can cause erratic heartbeats. Discuss your straightaway if you have symptoms such as:
- Feeling faint or passing out
- abnormal heart beat
v). Increase in some fats (cholesterol and triglyceride) levels in your blood
Treatment with Norvir uses may increase your blood levels of cholesterol and triglycerides. Your physician should carry out blood tests before you start your treatment with Norvir and regularly to check for an increase in your cholesterol and triglycerides levels.
vi). Diabetes and high blood sugar (hyperglycemia)
Some people who take protease inhibitors including Norvir can get high blood sugar, develop diabetes, or their diabetes can become aggravated. Discuss with your doctor if you experience an increase in thirst or urinate often while taking Norvir.
vii). Changes in your immune system (Immune reconstitution syndrome) can happen when you start taking HIV drugs. Your immune system may become stronger and begin to fight infections that have been hidden in your body for a long while. Discuss your doctor straightaway if you start having new symptoms after starting your HIV medicine.
viii). Change in body fat
These changes can happen in people who take antiretroviral therapy. The changes may include an accelerated amount of fat in the upper back and neck (“buffalo hump”), breast, and around the stomach area and back. Loss of fat from the arms, legs as well as face may also occur. The exact cause and long-term health effects of these conditions are not known.
ix). Increased bleeding for hemophiliacs
Some people with hemophilia have experienced accelerated bleeding with protease inhibitors including Norvir.
d). Warnings and Precautions of Norvir
i). Drug Interactions
Norvir is a CYP3A inhibitor. Initiating treatment with Norvir in patients receiving medications metabolized by CYP3A or initiating medications metabolized by CYP3A in patients already maintained on Norvir may result in increased plasma concentrations of concomitant medications. Increase plasma concentrations of concomitant medications can result in increased or prolonged therapeutic or adverse effects, potentially resulting to intense, life-threatening or fatal incidence. The potential for drug-drug fusions must be considered prior to and during treatment with Norvir. Assessment of other medications taken by patients and monitoring of patients for adverse effects is recommended during therapy with Norvir uses.
ii). Hepatic reactions
Hepatic transaminase elevations exceeding 5 times the upper limit of normal, clinical hepatitis, and jaundice have happened in patients receiving Norvir alone or in combination with other antiretroviral drug. There may be an increased danger for transaminase elevations in patients with underlying hepatitis B or C. Thus, caution should be taken when administering Norvir to patients with pre-existing hepatitis or liver enzyme abnormalities, and liver diseases. Elevated AST/ALT following up should be considered in these patients, particularly during the first three months of Norvir treatment. There have been post marketing reports of hepatic rupture, alongside some fatalities. These have widely occurred in patients taking multiple concomitant medications and/or with advanced AIDS.
Pancreatitis has been observed in patients receiving Norvir treatment, alongside those who developed hypertriglyceridemia. In some situations fatalities have been realized. Patients with advanced HIV-1 disease may be at increased risk of elevated pancreatitis and triglycerides. Pancreatitis should be taken into account if clinical symptoms (abdominal pain, vomiting, nausea,) or complexities in laboratory values (such as increased serum lipase or amylase values) suggestive of pancreatitis should happen. Patients who show these signs or symptoms should be evaluated and Norvir therapy should be discontinued if a diagnosis of pancreatitis is made.
iv). Allergic reactions/hypersensitivity
Allergic reactions including urticaria, moderate skin eruptions, angioedema as well as bronchospasm, have been reported. Situations of anaphylaxis, toxic epidermal necrolysis (TEN), as well as Stevens-Johnson syndrome have also been disclosed. Discontinue treatment if severe reactions develop.
v). PR Interval Prolongation
Ritonavir prolongs the PR interval in some patients. Post marketing incidence of second or third degree atrioventricular block have been reported in patients. The uses of Norvir should be done with caution in patients with underlying cardiomyopathies, ischemic heart disease, structural preexisting conduction system abnormalities, heart disease, as these patients may be at increased risk for developing cardiac conduction abnormalities. The outcome on the PR interval of co-administration of ritonavir with other drugs that prolong the PR interval (including beta-adrenergic blockers, calcium channel blockers, atazanavir and digoxin) has not been assessed. For this reason therefore the result, co-administration of ritonavir with these drugs should be undertaken with caution, especially with those medicines metabolized by CYP3A. Clinical monitoring is approved.
vi). Lipid disorders
Treatment with Norvir therapy alone or in combination with saquinavir has resulted in substantial increases in the concentration of total triglycerides and cholesterol. Triglyceride as well as cholesterol diagnosis should be performed prior to initiating Norvir therapy and at periodic intervals during treatment. Lipid complications should be managed as clinically appropriate, taking into consideration any potential drug-drug interactions with Norvir uses and HMG CoA reductase inhibitors.
vi). Diabetes Mellitus/hyperglycemia
New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, couple with hyperglycemia have been reported during post marketing surveillance in HIV-1 infected patients receiving protease inhibitor treatment. Some patients need either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of this incidence. In some situations, diabetic ketoacidosis has happened. In those patients who stopped protease inhibitor treatment, hyperglycemia persisted in some situations. And for the fact that this incidence has been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between protease inhibitor therapy and these events has not been established.
vii). Immune reconstitution syndrome
Immune reconstitution syndrome has been reported in HIV-1 infected patients treated with combination antiretroviral therapy, alongside Norvir. At the time of the initial phase of combination antiretroviral treatment, patients whose immune system complies may develop an inflammatory response to indolent or residual opportunistic infections. Autoimmune disorders (such as Graves’ disease, Guillain-Barré syndrome as well as polymyositis) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more unstable, and can happen several months after initiation of treatment.
viii). Fat Redistribution
Redistribution/accumulation of body fat including dorsocervical increase enlargement (buffalohump), peripheral wasting, facial wasting, central obesity, breast increment, have been realized in patients receiving antiretroviral treatment. The mechanism and long-term repercussions of these events are presently unknown. A causal relationship has not been set up.
ix). Patients with Hemophilia
There have been reports of spontaneous skin hematomas, including increased bleeding, as well as hemarthrosis, in patients with hemophilia type A as well as B treated with protease inhibitors. In a handful of patients further factor VIII was given. In more than half of the reported situations, treatment with protease inhibitors was continued or reexamined. A causal relationship among protease inhibitor therapy and these events has not been established.
Varying degrees of cross-resistance among protease inhibitors have been realized. Ongoing administration of ritonavir 600 mg twice daily following loss of viral suppression may increase the likelihood of cross resistance to other protease inhibitors.
e). Uses of Norvir
Norvir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. The uses of Norvir Tablet include the prevention, treatment control, and improvement of the following diseases, signs and conditions.
- Urinary tract infections
- Sexually transmitted disease
- Reproductive organ infection
- Prostrate infection
- Stomach infection
- Eye and ear infection
- Intestine infections
- Typhoid fever bacterial infections
f). Dosage of Norvir
Norvir is administered orally in combination with other antiretroviral agents. It is approved that Norvir be taken with meals if possible.
- General Dosing Guidelines
Noticed adverse events, such as mild to moderate gastro intestinal disturbances and paraesthesias, may diminish as therapy is continued.
- Dose modification for Norvir
The dosage of Norvir reduction is necessary when used with other protease inhibitors: saquinavir, atazanavir, fosamprenavir, darunavir, as well as tipranavir. Prescribers should consult the full prescribing information and clinical study information of these protease inhibitors if they are co-administered with a reduced dosage of Norvir.
g). Dosage forms and strengths of Norvir
Norvir (ritonavir) capsules, with softening gelat in white soft gelatin capsules imprinted with the corporate Abbott “A” logo , 100 and the Abbo-Code DS, providing 100 mg of ritonavir.
h). Overdose of Norvir
i). Human experience of acute overdose with Norvir is minute. One patient in clinical tests took Norvir1500 mg per day for two days. The patients were found with paresthesias which resolved after the dosage of Norvir was reduced. A post-marketing case of renal problem with eosinophilia has been reported with ritonavir overdosage. The precise lethal dose was noted to be greater than 20 times the related human dosage of Norvin in rats and 10 times the related human dose in mice.
i). Management 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 unique antidote for overdose with Norvir. If used, eradication of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to preserve the airway. Administration of heated charcoal may also be used to aid in removal of unabsorbed medicine. Since ritonavir is greatly metabolized by the liver and is highlyprotein bound, dialysis is not possible to be needful in significant removal of the medicine. A Legal Poison Control Center have to be consulted for up-to-date information on the management of overdose with Norvir.
i). Storage conditions of Norvir
Store Norvir soft gelatin capsules in the refrigerator between 2°-8°C (36°-46°F) until preservation. Moreover, the refrigeration of the soft gelatin capsules of Norvir by the patient is approved, but not needed if used within 30 days and stored below 25°C (77°F). Protect from light. Avoid exposure to excessive heat. Product should be stored and dispensed in the original container. Keep the cap tightly closed.
j). Use in specific populations
i). Pregnancy Category B
There are no adequate and well-controlled studies in pregnant women. Because animal reproduction researches are not always predictive of human response, this medicine should be administered during pregnancy only if clearly needed. Antiretroviral Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant women disclosure to Norvir, an Antiretroviral Pregnancy Registry is been established. Doctors are motivated to register patients by calling 1-800-258-4263.
No treatment related malformations were observed when Norvir (ritonavir) was administered to pregnant rabbits or rats. Developmental toxicity noticed in rats (early resorptions, reduced fetal body weight and ossification delays and developmental variations) occurred at a maternally toxic dosage at an exposure equivalent to approximately 30% of that achieved with the proposed therapeutic dose. A slight acceleration in the situation of cryptorchidism was also noted in rats at an exposure approximately 22% of that achieved with the proposed therapeutic dose. Developmental toxicity observed in rabbits (resorptions, reduced litter size and reduced fetal weights) also occurred at a maternally toxic dosage corresponding to 1.8 times the proposed therapeutic dose based on a body surface area conversion factor.
ii). Nursing Mothers
The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. It is unknown if ritonavir is secreted in human milk. For the purpose of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be guided not to breastfeed if they are receiving Norvir.
iii). Pediatric use
In HIV-1 infected patients age more than 1 month to 21 years, the antiviral activity and adverse event profile seen during clinical trials and through post marketing experience were similar to that for adult patients.
iv). Geriatric use
Clinical studies of Norvir did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from infants subjects. In general, dose selection for an older patient should be careful, usually beginning at the low end of the dosing range, reflecting the greater frequency of reduced hepatic, renal or cardiac function, as well as of concomitant disease or other drug therapy.
v). Hepatic Impairment
No dose adjustment of ritonavir is necessary for patients with either mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. No pharmacokinetic or safety archives are available regarding the uses of Norvir in subjects with severe hepatic impairment (Child-Pugh Class C), therefore, ritonavir is not approved for use in patients with severe hepatic impairment.
vi). Laboratory Tests
Norvir (Ritonavir) has been shown to increase triglycerides, cholesterol, and uric acid. Appropriate laboratory testing should be performed prior to initiating Norvir therapy and at periodic intervals or if any clinical signs or symptoms occur during treatment. For comprehensive information prior to laboratory test alterations associated with reverse transcriptase inhibitors, physicians should refer to the full product information for each of these drugs.
Disclaimer: All the sources elucidated in this article are for informative purposes. Therefore, on no account should they be prioritized beyond your health care professional’s prescription.