Viramune

Viramune Side Effects

nevirapine

Manufacturer:

Boehringer Ingelheim

Distributor:

DKSH
Full Prescribing Info
Side Effects
Adults: Apart from rash and abnormal LFTs, the most frequently reported adverse events related to VIRAMUNE therapy across all clinical trials were rash, fever, nausea, headache, fatigue, somnolence, vomiting, diarrhea, abdominal pain and myalgia. Cases of anaemia and neutropenia may be associated with VIRAMUNE therapy. Arthralgia has been reported as a stand-alone event in rare instances in patients receiving VIRAMUNE containing regimens.
The post-marketing experience has shown that the most serious adverse reactions are Stevens-Johnson syndrome, toxic epidermal necrolysis, serious hepatitis/hepatic failure and hypersensitivity syndrome, characterised by rash with constitutional symptoms such as fever, arthralgia, myalgia and lymphadenopathy, plus visceral involvement, such as hepatitis, eosinophilia, granulocytopenia, and renal dysfunction. The first 18 weeks of treatment is a critical period which requires close monitoring (see Precautions).
Viramune:
Skin and Subcutaneous Tissues: The most common clinical toxicity of VIRAMUNE is rash. Severe or life-threatening skin reactions occur with a frequency of approximately 2% (see table 11). These include Stevens-Johnson syndrome (SJS) and, rarely, toxic epidermal necrolysis (TEN) which occur almost exclusively within the first six weeks of therapy. Based on a denominator of 2861 clinical trial patients treated with VIRAMUNE immediate-release tablets, the overall incidence of SJS was 0.3% (9/2,861).
Rashes occur alone or in the context of a hypersensitivity syndrome characterised by rash with constitutional symptoms such as fever, arthralgia, myalgia and lymphadenopathy plus visceral involvement, such as hepatitis, eosinophilia, granulocytopenia and renal dysfunction. Fatal cases of SJS, TEN and hypersensitivity syndrome have been reported. (See Table 9.)

Click on icon to see table/diagram/image

Hepatobiliary: The most frequently observed laboratory test abnormalities are elevations in liver function tests (LFTs), including ALAT, ASAT, GGT, total bilirubin and alkaline phosphatase. Asymptomatic elevations of GGT levels are the most frequent. Cases of jaundice have been reported.
Cases of hepatitis, severe and life-threatening hepatotoxicity, and fatal fulminant hepatitis, have been reported in patients treated with nevirapine in clinical trials. In clinical trials of VIRAMUNE tablets, the risk of clinical hepatic events with VIRAMUNE at 1 year was approximately 2-fold that of placebo.
Increased ASAT or ALAT levels and/or seropositivity for hepatitis B and/or C were associated with a greater risk of hepatic adverse events for both VIRAMUNE immediate-release and control groups. The risk of hepatic events at 1 year of treatment with VIRAMUNE immediate-release was less than 2% among patients who were hepatitis B and/or C negative.
The first 18 weeks of treatment is a critical period which requires close monitoring. The risk of hepatic events is greatest in the first 6 weeks of therapy. However the risk continues past this period and monitoring should continue at frequent intervals throughout treatment (see section Precautions).
Clinical hepatitis may be isolated or associated with rash and/or additional constitutional symptoms.
For liver function test monitoring see Precautions.
Viramune XR: The following adverse events which may be causally related to the administration of VIRAMUNE immediate-release have been reported. The frequencies estimated are based on pooled clinical trial data for events considered related to VIRAMUNE immediate-release treatment.
Frequency classes: Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000).
Blood and Lymphatic System Disorders: Common: granulocytopenia.
Uncommon: Anaemia.
Immune System Disorders: Common: hypersensitivity (including anaphylactic reaction, angioedema, urticaria).
Uncommon: Drug reaction with eosinophilia and systemic symptoms, anaphylactic reaction.
Nervous System Disorders: Common: Headache.
Gastrointestinal Disorders: Common: Nausea, vomiting, abdominal pain, diarrhoea.
Hepatobiliary Disorders: Common: Hepatitis (1.2%) (including severe and life threatening hepatotoxicity), liver function tests abnormal uncommon: Jaundice.
Rare: Liver failure/fulminant hepatitis (which may be fatal).
Skin and Subcutaneous Tissue Disorders: Very common: Rash.
Uncommon: Stevens-Johnson Syndrome (0.3%), toxic epidermal necrolysis (which may be fatal), urticaria, angiooedema.
Musculoskeletal and Connective Tissue Disorders: Common: Myalgia.
Uncommon: Arthralgia.
Investigations: Common: Liver function test abnormal (alanine aminotransferase increased; transaminases increased; aspartate aminotransferase increased; gamma-glutamyltransferase increased; hepatic enzyme increased; hypertransaminasaemia).
Uncommon: Blood phosphorus decreased, blood pressure increased.
In Trial 1100.1486 (VERxVE) antiretroviral-naïve patients received a lead-in dose of VIRAMUNE immediate-release 200 mg once daily for 14 days (n=1068) and then were randomised to receive either VIRAMUNE immediate-release 200 mg twice daily or VIRAMUNE XR extended-release 400 mg once daily. All patients received tenofovir + emtricitabine as background therapy. Safety data included all the patient visits up to the point in time when the last patient completed 144 weeks in the trial. This also includes safety data for patient visits in the post-week 144 open label extension (which patients in either treatment group who completed the 144 week blinded phase could enter). Severe or life-threatening rash considered related to VIRAMUNE treatment occurred in 1.1% of patients during the lead-in phase with VIRAMUNE immediate-release. Severe rash occurred in 1.4% and 0.2% of the VIRAMUNE immediate-release and VIRAMUNE XR extended-release groups respectively during the randomised phase. No life-threatening (Grade 4) rash events considered related to Viramune were reported during the randomised phase of this study. Six cases of Stevens-Johnson Syndrome were reported in the trial; all but one occurred within the first 30 days of VIRAMUNE treatment.
In Study 1100.1526 (TRANxITION) patients on VIRAMUNE immediate-release 200 mg twice daily treatment for at least 18 weeks were randomised to either receive VIRAMUNE XR extended-release 400 mg once daily (n=295) or remain on their VIRAMUNE immediate-release treatment (n=148). In this study, no Grade 3 or 4 rash was observed in either treatment group.
The most frequently observed laboratory test abnormalities are elevations in liver function tests (LFTs), including ALAT, ASAT, GGT, total bilirubin and alkaline phosphatase. Asymptomatic elevations of GGT levels are the most frequent. Cases of jaundice have been reported.
Cases of hepatitis, severe and life-threatening hepatotoxicity, and fatal fulminant hepatitis, have been reported in patients treated with nevirapine in clinical trials. In clinical trials of VIRAMUNE tablets, the risk of clinical hepatic events with VIRAMUNE at 1 year was approximately 2-fold that of placebo.
Increased ASAT or ALAT levels and/or seropositivity for hepatitis B and/or C were associated with a greater risk of hepatic adverse events for both VIRAMUNE immediate-release and control groups. The risk of hepatic events at 1 year of treatment with VIRAMUNE immediate-release was less than 2% among patients who were hepatitis B and/or C negative.
The first 18 weeks of treatment is a critical period which requires close monitoring. The risk of hepatic events is greatest in the first 6 weeks of therapy. However the risk continues past this period and monitoring should continue at frequent intervals throughout treatment (see Precautions).
Clinical hepatitis may be isolated or associated with rash and/or additional constitutional symptoms.
For liver function test monitoring see Precautions.
Viramune XR: In Trial 1100.1486 (VERxVE) treatment-naïve patients received a lead-in dose of VIRAMUNE 200 mg immediate-release once daily for 14 days and then were randomised to receive either VIRAMUNE immediate-release 200 mg twice daily or VIRAMUNE XR extended-release 400 mg once daily. All patients received tenofovir+emtricitabine as background therapy. Patients were enrolled with CD4+ counts <250 cells/mm3 for women and <400 cells/mm3 for men. Data on potential symptoms of hepatic events were prospectively collected in this trial. The safety data include all patient visits up to the time of the last patient’s completion of study week 144. The incidence of symptomatic hepatic events during the VIRAMUNE immediate-release lead-in phase was 0.5%. After the lead-in period the incidence of symptomatic hepatic events was 2.4% in the VIRAMUNE immediate-release group and 1.6% in the VIRAMUNE XR extended-release group. Overall, there was a comparable incidence of symptomatic hepatic events among men and women enrolled in VERxVE.
In Study 1100.1526 (TRANxITION) no Grade 3 or 4 clinical hepatic events were observed in either treatment group.
Post-Marketing Surveillance: Viramune XR:  The post-marketing experience has shown that the most serious adverse reactions are Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatitis/hepatic failure and hypersensitivity reactions, (characterised by rash with constitutional symptoms such as fever, arthralgia, myalgia and lymphadenopathy, plus visceral involvement, such as hepatitis, eosinophilia, granulocytopenia, and renal dysfunction).
The following events have been reported with the use of VIRAMUNE in clinical practice: Body as a Whole: Fever, somnolence, drug withdrawal, redistribution/accumulation of body fat.
Gastrointestinal: Vomiting.
Liver and Biliary: Jaundice, fulminant and cholestatic hepatitis, hepatic necrosis, hepatic failure.
Haematology: Anaemia, eosinophilia, neutropenia.
Musculoskeletal: Arthralgia.
Neurologic: Paraesthesia.
Skin and Appendages: Allergic reactions including anaphylaxis, angioedema, bullous eruptions, ulcerative stomatitis and urticaria have all been reported. In addition, hypersensitivity syndrome and hypersensitivity reactions with rash associated with constitutional findings such as fever, blistering, oral lesions, conjunctivitis, facial oedema, muscle or joint aches, general malaise, fatigue or significant hepatic abnormalities plus one or more of the following: hepatitis, eosinophilia, granulocytopenia, lymphadenopathy and/or renal dysfunction have been reported with the use of VIRAMUNE.
Paediatric Patients: Safety has been assessed in 361 HIV-1-infected paediatric patients between the ages of 3 days to 19 years. The majority of these patients received VIRAMUNE in combination with ZDV or ddI, or ZDV + ddI in two studies. In an open-label trial BI 882 (ACTG 180) 37 patients were followed for a mean duration of 33.9 months (range: 6.8 months to 5.3 years, including long-term follow-up trial BI 892).
In ACTG 245, a double-blind placebo controlled study, 305 patients with a mean age 7 years (range: 10 months to 19 years) received combination treatment with VIRAMUNE for at least 48 weeks at a dose of 120 mg/m2 once daily for two weeks followed by 120 mg/m2 twice daily thereafter. The most frequently reported adverse events related to VIRAMUNE were similar to those observed in adults, with the exception of granulocytopenia, which was more commonly observed in children. Two VIRAMUNE-treated patients in these studies experienced SJS or Stevens-Johnson/toxic epidermal necrolysis transition syndrome. Both patients recovered after VIRAMUNE treatment was discontinued.
In post-marketing surveillance anaemia has been more commonly observed in children.
Viramune: In summary the list of side effects, which can be expected with VIRAMUNE treatment, includes: Blood and Lymphatic System Disorders: Granulocytopenia, anaemia.
Immune System Disorders: Drug reaction with eosinophilia and systemic symptoms, anaphylactic reaction, hypersensitivity (including anaphylactic reaction, angioedema, urticaria).
Nervous System Disorders: Headache.
Gastrointestinal Disorders: Diarrhoea, abdominal pain, nausea, vomiting.
Hepatobiliary Disorders: Hepatitis (including severe and life threatening hepatotoxicity), hepatitis fulminant (which may be fatal), jaundice.
Skin and Subcutaneous Tissue Disorders: Rash, Stevens-Johnson Syndrome/toxic epidermal necrolysis (which may be fatal), angioedema, urticaria.
Musculoskeletal and Connective Tissue Disorders: Arthralgia, myalgia.
General Disorders and Administration Site Conditions: Pyrexia, fatigue.
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