NORVIR SIDE EFFECTS
- Generic Name: ritonavir capsules, oral solution
- Brand Name: Norvir
- Drug Class: HIV, Protease Inhibitors
SIDE EFFECTS
The following adverse reactions are discussed in greater detail in other sections of the labeling.
- Drug Interactions
- Hepatotoxicity
- Pancreatitis
- Allergic Reactions/Hypersensitivity
When co-administering NORVIR with other protease inhibitors, see the full prescribing information for that protease inhibitor including adverse reactions.
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions In Adults
The safety of NORVIR alone and in combination with other antiretroviral agents was studied in 1,755 adult patients. Table 1 lists treatment-emergent Adverse Reactions (with possible or probable relationship to study drug) occurring in greater than or equal to 1% of adult patients receiving NORVIR in combined Phase II/IV studies.
The most frequently reported adverse drug reactions among patients receiving NORVIR alone or in combination with other antiretroviral drugs were gastrointestinal (including diarrhea, nausea, vomiting, abdominal pain (upper and lower)), neurological disturbances (including paresthesia and oral paresthesia), rash, and fatigue/asthenia.
Table 1: Treatment-Emergent Adverse Reactions (With Possible or Probable Relationship to Study Drug) Occurring in greater than or equal to 1% of Adult Patients Receiving NORVIR in Combined Phase II/IV Studies (N = 1,755)
| Adverse Reactions | n | % |
| Eye disorders | ||
| Blurred vision | 113 | 6.4 |
| Gastrointestinal disorders | ||
| Abdominal Pain (upper and lower)* | 464 | 26.4 |
| Diarrhea including severe with electrolyte imbalance* | 1,192 | 67.9 |
| Dyspepsia | 201 | 11.5 |
| Flatulence | 142 | 8.1 |
| Gastrointestinal hemorrhage* | 41 | 2.3 |
| Gastroesophageal reflux disease (GERD) | 19 | 1.1 |
| Nausea | 1,007 | 57.4 |
| Vomiting* | 559 | 31.9 |
| General disorders and administration site conditions | ||
| Fatigue including asthenia* | 811 | 46.2 |
| Hepatobiliary disorders | ||
| Blood bilirubin increased (including jaundice)* | 25 | 1.4 |
| Hepatitis (including increased AST, ALT, GGT)* | 153 | 8.7 |
| Immune system disorders | ||
| Hypersensitivity including urticaria and face edema* | 114 | 8.2 |
| Metabolism and nutrition disorders | ||
| Edema and peripheral edema* | 110 | 6.3 |
| Gout* | 24 | 1.4 |
| Hypercholesterolemia* | 52 | 3.0 |
| Hypertriglyceridemia* | 158 | 9.0 |
| Lipodystrophy acquired* | 51 | 2.9 |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia and back pain* | 326 | 18.6 |
| Myopathy/creatine phosphokinase increased* | 66 | 3.8 |
| Myalgia | 156 | 8.9 |
| Nervous system disorders | ||
| Dizziness* | 274 | 15.6 |
| Dysgeusia* | 285 | 16.2 |
| Paresthesia (including oral paresthesia)* | 889 | 50.7 |
| Peripheral neuropathy | 178 | 10.1 |
| Syncope* | 58 | 3.3 |
| Psychiatric disorders | ||
| Confusion* | 52 | 3.0 |
| Disturbance in attention | 44 | 2.5 |
| Renal and urinary disorders | ||
| Increased urination* | 74 | 4.2 |
| Respiratory, thoracic and mediastinal disorders | ||
| Coughing* | 380 | 21.7 |
| Oropharyngeal Pain* | 279 | 15.9 |
| Skin and subcutaneous tissue disorders | ||
| Acne* | 67 | 3.8 |
| Pruritus* | 214 | 12.2 |
| Rash (includes erythematous and maculopapular)* | 475 | 27.1 |
| Vascular disorders | ||
| Flushing, feeling hot* | 232 | 13.2 |
| Hypertension* | 58 | 3.3 |
| Hypotension including orthostatic hypotension* | 30 | 1.7 |
| Peripheral coldness* | 21 | 1.2 |
| * Represents a medical concept including several similar MedDRA PTs | ||
Laboratory Abnormalities In Adults
Table 2 shows the percentage of adult patients who developed marked laboratory abnormalities.
Table 2: Percentage of Adult Patients, by Study and Treatment Group, with Chemistry and Hematology Abnormalities Occurring in greater than 3% of Patients Receiving NORVIR
| Variable | Limit | Study 245 Naive Patients | Study 247 Advanced Patients | Study 462 PI-Naive Patients | |||
| NORVIR plus ZDV | NORVIR | ZDV | NORVIR | Placebo | NORVIR plus Saquinavir | ||
| Chemistry | High | ||||||
| Cholesterol | > 240 mg/dL | 30.7 | 44.8 | 9.3 | 36.5 | 8.0 | 65.2 |
| CPK | >1000IU/L | 9.6 | 12.1 | 11.0 | 9.1 | 6.3 | 9.9 |
| GGT | > 300 IU/L | 1.8 | 5.2 | 1.7 | 19.6 | 11.3 | 9.2 |
| SGOT (AST) | > 180 IU/L | 5.3 | 9.5 | 2.5 | 6.4 | 7.0 | 7.8 |
| SGPT (ALT) | > 215 IU/L | 5.3 | 7.8 | 3.4 | 8.5 | 4.4 | 9.2 |
| Triglycerides | > 800 mg/dL | 9.6 | 17.2 | 3.4 | 33.6 | 9.4 | 23.4 |
| Triglycerides | > 1500 mg/dL | 1.8 | 2.6 | – | 12.6 | 0.4 | 11.3 |
| Triglycerides Fasting | > 1500 mg/dL | 1.5 | 1.3 | – | 9.9 | 0.3 | – |
| Uric Acid | > 12 mg/dL | – | – | – | 3.8 | 0.2 | 1.4 |
| Hematology | Low | ||||||
| Hematocrit | < 30% | 2.6 | – | 0.8 | 17.3 | 22.0 | 0.7 |
| Hemoglobin | < 8.0 g/dL | 0.9 | – | – | 3.8 | 3.9 | – |
| Neutrophils | < 0.5 x 109/L | – | – | – | 6.0 | 8.3 | – |
| RBC | < 3.0 x 1012/L | 1.8 | – | 5.9 | 18.6 | 24.4 | – |
| WBC | < 2.5 x 109/L | – | 0.9 | 6.8 | 36.9 | 59.4 | 3.5 |
| -Indicates no events reported. | |||||||
Adverse Reactions In Pediatric Patients
NORVIR has been studied in 265 pediatric patients greater than 1 month to 21 years of age. The adverse event profile observed during pediatric clinical trials was similar to that for adult patients.
Vomiting, diarrhea, and skin rash/allergy were the only drug-related clinical adverse events of moderate to severe intensity observed in greater than or equal to 2% of pediatric patients enrolled in NORVIR clinical trials.
Laboratory Abnormalities In Pediatric Patients
The following Grade 3-4 laboratory abnormalities occurred in greater than 3% of pediatric patients who received treatment with NORVIR either alone or in combination with reverse transcriptase inhibitors: neutropenia (9%), hyperamylasemia (7%), thrombocytopenia (5%), anemia (4%), and elevated AST (3%).
Postmarketing Experience
The following adverse events (not previously mentioned in the labeling) have been reported during post-marketing use of NORVIR. Because these reactions are reported voluntarily from a population of unknown size, it is not possible to reliably estimate their frequency or establish a causal relationship to NORVIR exposure.
Body As A Whole
Dehydration, usually associated with gastrointestinal symptoms, and sometimes resulting in hypotension, syncope, or renal insufficiency has been reported. Syncope, orthostatic hypotension, and renal insufficiency have also been reported without known dehydration.
Co-administration of ritonavir with ergotamine or dihydroergotamine has been associated with acute ergot toxicity characterized by vasospasm and ischemia of the extremities and other tissues including the central nervous system.
Cardiovascular System
First-degree AV block, second-degree AV block, third-degree AV block, right bundle branch block have been reported.
Cardiac and neurologic events have been reported when ritonavir has been co-administered with disopyramide, mexiletine, nefazodone, fluoxetine, and beta blockers. The possibility of drug interaction cannot be excluded.
Endocrine System
Cushing’s syndrome and adrenal suppression have been reported when ritonavir has been co-administered with fluticasone propionate or budesonide.
Nervous System
There have been postmarketing reports of seizure.
Skin And Subcutaneous Tissue Disorders
Toxic epidermal necrolysis (TEN) has been reported.
SRC: NLM .