Intelence Adverse Reactions

The following adverse reactions are described in greater detail in Precautions: Severe skin and hypersensitivity reactions.
Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction 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.
The safety assessment is based on all data from 1203 subjects in the Phase 3 placebo-controlled trials, TMC125-C206 and TMC125-C216, conducted in antiretroviral treatment-experienced HIV-1-infected adult subjects, 599 of whom received INTELENCE (200 mg twice daily). In these pooled trials, the median exposure for subjects in the INTELENCE arm and placebo arm was 52.3 and 51.0 weeks, respectively. Discontinuations due to adverse drug reactions (ADRs) were 5.2% in the INTELENCE arm and 2.6% in the placebo arm.
The most frequently reported ADR at least Grade 2 in severity was rash (10.0%). Stevens-Johnson syndrome, drug hypersensitivity reaction and erythema multiforme were reported in less than 0.1% of subjects during clinical development with INTELENCE [see Severe Skin and Hypersensitivity Reactions under Precautions]. A total of 2.2% of HIV-1-infected subjects in Phase 3 trials receiving INTELENCE discontinued due to rash. In general, in clinical trials, rash was mild to moderate, occurred primarily in the second week of therapy, and was infrequent after Week 4. Rash generally resolved within 1 to 2 weeks on continued therapy. The incidence of rash was higher in women compared to men in the INTELENCE arm in the Phase 3 trials (rash ≥ Grade 2 was reported in 9/60 [15.0%] women versus 51/539 [9.5%] men; discontinuations due to rash were reported in 3/60 [5.0%] women versus 10/539 [1.9%] men). Patients with a history of NNRTI-related rash did not appear to be at increased risk for the development of INTELENCE-related rash compared to patients without a history of NNRTI-related rash.
Common Adverse Reactions: Clinical ADRs of moderate intensity or greater (greater than or equal to Grade 2) and reported in at least 2% of subjects treated with INTELENCE and occurring at a higher rate compared to placebo (excess of 1%) are presented in Table 9 (see Table 9). Laboratory abnormalities considered ADRs are included in Table 10.

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Less Common Adverse Reactions: Treatment-emergent ADRs occurring in less than 2% of subjects (599 subjects) receiving INTELENCE and of at least moderate intensity (greater than or equal to Grade 2) are listed as follows by body system: Cardiac Disorders: myocardial infarction, angina pectoris, atrial fibrillation.
Ear and Labyrinth Disorders: vertigo.
Eye Disorders: blurred vision.
Gastrointestinal Disorders: gastroesophageal reflux disease, flatulence, gastritis, abdominal distension, pancreatitis, constipation, dry mouth, hematemesis, retching, stomatitis.
General Disorders and Administration Site Conditions: sluggishness.
Hematologic Disorders: hemolytic anemia.
Hepatobiliary Disorders: hepatic failure, hepatomegaly, cytolytic hepatitis, hepatic steatosis, hepatitis.
Immune System Disorders: drug hypersensitivity, immune reconstitution syndrome.
Metabolism and Nutrition Disorders: diabetes mellitus, anorexia, dyslipidemia.
Nervous System Disorders: paraesthesia, somnolence, convulsion, hypoesthesia, amnesia, syncope, disturbance in attention, hypersomnia, tremor.
Psychiatric Disorders: anxiety, sleep disorders, abnormal dreams, confusional state, disorientation, nervousness, nightmares.
Renal and Urinary Disorders: acute renal failure.
Reproductive System and Breast Disorders: gynecomastia.
Respiratory, Thoracic and Mediastinal Disorders: exertional dyspnea, bronchospasm.
Skin and Subcutaneous Tissue Disorders: night sweats, lipohypertrophy, prurigo, hyperhidrosis, dry skin, swelling face.
Additional ADRs of at least moderate intensity observed in other trials were acquired lipodystrophy, angioneurotic edema, erythema multiforme and haemorrhagic stroke, each reported in no more than 0.5% of subjects.
Laboratory Abnormalities in Treatment-Experienced Patients: Selected Grade 2 to Grade 4 laboratory abnormalities that represent a worsening from baseline observed in adult subjects treated with INTELENCE are presented in Table 10. (See Table 10.)

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Patients co-infected with hepatitis B and/or hepatitis C virus: In Phase 3 trials TMC125-C206 and TMC125-C216, 139 subjects (12.3%) with chronic hepatitis B and/or hepatitis C virus co-infection out of 1129 subjects were permitted to enroll. AST and ALT abnormalities occurred more frequently in hepatitis B and/or hepatitis C virus co-infected subjects for both treatment groups. Grade 2 or higher laboratory abnormalities that represent a worsening from baseline of AST, ALT or total bilirubin occurred in 27.8%, 25.0% and 7.1% respectively, of INTELENCE-treated co-infected subjects as compared to 6.7%, 7.5% and 1.8% of non-co-infected INTELENCE-treated subjects. In general, adverse events reported by INTELENCE-treated subjects with hepatitis B and/or hepatitis C virus co-infection were similar to INTELENCE-treated subjects without hepatitis B and/or hepatitis C virus co-infection.
Postmarketing Experience: The following events have been identified during postmarketing use of INTELENCE. Because these events are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune System Disorders: Severe hypersensitivity reactions including DRESS and cases of hepatic failure have been reported [see Severe Skin and Hypersensitivity Reactions under Precautions].
Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis.
Skin and Subcutaneous Tissue Disorders: Fatal cases of toxic epidermal necrolysis have been reported [see Severe Skin and Hypersensitivity Reactions under Precautions].