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Isentress (Raltegravir) - Side Effects and Adverse Reactions

 
 



ADVERSE 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.

Treatment-Experienced Studies

The safety assessment of ISENTRESS in treatment-experienced subjects is based on the pooled safety data from the randomized, double-blind, placebo-controlled trials, BENCHMRK 1 and BENCHMRK 2 (Protocols 018 and 019) in antiretroviral treatment-experienced HIV-1 infected adult subjects. A total of 462 subjects received the recommended dose of ISENTRESS 400 mg twice daily in combination with optimized background therapy (OBT) compared to 237 subjects taking placebo in combination with OBT. The median duration of therapy in these trials was 48 weeks for subjects receiving ISENTRESS and 38 weeks for subjects receiving placebo. The total exposure to ISENTRESS was 387 patient-years versus 156 patient-years on placebo. The rates of discontinuation due to adverse events were 2% in subjects receiving ISENTRESS and 3% in subjects receiving placebo.

Clinical adverse drug reactions (ADRs) were considered by investigators to be causally related to ISENTRESS + OBT or placebo + OBT. Clinical ADRs of moderate to severe intensity occurring in ≥2% of subjects treated with ISENTRESS and occurring at a higher exposure adjusted rate compared to placebo are presented in Table 1.

Table 1: Adverse Drug Reactions 1 of Moderate to Severe Intensity 2 Occurring in ≥2% of Treatment-Experienced Adult Subjects Receiving ISENTRESS and at a Higher Exposure Adjusted Rate Compared to Placebo (48 Week Analysis, Exposure Adjusted Incidence Rates)
System Organ Class,
Adverse Reactions
Randomized Studies Protocol 018 and 019
ISENTRESS 400 mg Twice Daily
+ OBT
(n = 462) 3
Placebo + OBT
(n = 237)  

Rate per 100 Patient-Years

Rate per 100 Patient-Years

Nervous System Disorders
Headache31
Gastrointestinal Disorders
Nausea21
General Disorders and Administration Site Conditions
Asthenia21
Fatigue21

1 Includes adverse reactions at least possibly, probably, or definitely related to the drug.
2 Intensities are defined as follows: Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating with inability to work or do usual activity).
3 n=total number of subjects per treatment group.

Less Common Adverse Reactions

The following ADRs occurred in <2% of subjects receiving ISENTRESS + OBT. These events have been included because of either their seriousness, increased frequency on ISENTRESS compared with placebo or investigator's assessment of potential causal relationship.

Gastrointestinal Disorders: abdominal pain, gastritis

Hepatobiliary Disorders: hepatitis

Immune System Disorders: hypersensitivity

Infections and Infestations: genital herpes, herpes zoster

Nervous System Disorders: dizziness

Renal and Urinary Disorders: renal failure

Adverse Events

Regardless of Drug Relationship

Cancers were reported in treatment-experienced subjects who initiated ISENTRESS with OBT; several were recurrent. The types and rates of specific cancers were those expected in a highly immunodeficient population (many had CD4+ cell counts below 50 cells/mm3 and most had prior AIDS diagnoses). The cancers included Kaposi’s sarcoma, lymphoma, squamous cell carcinoma, hepatocellular carcinoma and anal cancer. Most subjects had other risk factors for cancer including tobacco use, papillomavirus and active hepatitis B virus infection. It is unknown if these cancer diagnoses were related to ISENTRESS use.

Grade 2-4 creatine kinase laboratory abnormalities were observed in subjects treated with ISENTRESS (see Table 2). Myopathy and rhabdomyolysis have been reported; however, the relationship of ISENTRESS to these events is not known. Use with caution in patients at increased risk of myopathy or rhabdomyolysis, such as patients receiving concomitant medications known to cause these conditions.

Laboratory Abnormalities

The percentages of adult subjects treated with ISENTRESS 400 mg twice daily or placebo in Protocols 018 and 019 with selected Grade 2 to 4 laboratory abnormalities representing a worsening from baseline are presented in Table 2.

Table 2: Selected Grade 2 to 4 Laboratory Abnormalities Reported in Treatment-Experienced Subjects (48 Week Analysis)
Randomized Studies Protocol 018
and 019
Laboratory
Parameter
Preferred Term
(Unit)
Limit ISENTRESS
400 mg Twice Daily +
OBT

(N = 462)
Placebo
+
OBT

(N = 237)
ULN = Upper limit of normal range
Hematology
Absolute neutrophil count (103/μL)
Grade 20.75 - 0.9993%5%
Grade 30.50 - 0.7493%3%
Grade 4<0.501%<1%
Hemoglobin (gm/dL)
Grade 27.5 - 8.41%3%
Grade 36.5 - 7.41%<1%
Grade 4<6.5<1%0%
Platelet count (103/μL)
Grade 250 - 99.9993%5%
Grade 325 - 49.9991%<1%
Grade 4<251%<1%
Blood chemistry
Fasting (non-random) serum glucose test (mg/dL)
Grade 2126 – 250 8%5%
Grade 3251 – 500 2%1%
Grade 4>500 0%0%
Total serum bilirubin
Grade 21.6 - 2.5 x ULN5%3%
Grade 32.6 - 5.0 x ULN 2%2%
Grade 4>5.0 x ULN 1%0%
Serum aspartate aminotransferase
Grade 22.6 - 5.0 x ULN 8%6%
Grade 35.1 - 10.0 x ULN 3%3%
Grade 4>10.0 x ULN<1%1%
Serum alanine aminotransferase
Grade 22.6 - 5.0 x ULN 7%8%
Grade 35.1 - 10.0 x ULN3%2%
Grade 4>10.0 x ULN1%2%
Serum alkaline phosphatase
Grade 22.6 - 5.0 x ULN 2%<1%
Grade 35.1 - 10.0 x ULN<1%1%
Grade 4>10.0 x ULN1%<1%
Serum pancreatic amylase test
Grade 21.6 - 2.0 x ULN2%1%
Grade 32.1 - 5.0 x ULN3%3%
Grade 4>5.0 x ULN<1%0%
Serum lipase test
Grade 21.6 - 3.0 x ULN4%3%
Grade 33.1 - 5.0 x ULN1%<1%
Grade 4>5.0 x ULN0%0%
Serum creatine kinase
Grade 26.0 - 9.9 x ULN2%2%
Grade 310.0 - 19.9 x ULN3%3%
Grade 4>10.0 x ULN2%1%

Patients with Co-existing Conditions

Patients Co-infected with Hepatitis B and/or Hepatitis C Virus

In the clinical studies, P018 and P019, subjects with chronic (but not acute) active hepatitis B and/or hepatitis C virus co-infection (N = 114/699 or 16%) were permitted to enroll provided that baseline liver function tests did not exceed 5 times the upper limit of normal (ULN). The rates of AST and ALT abnormalities were higher in the subgroup of subjects with hepatitis B and/or hepatitis C virus co-infection for both treatment groups. In general the safety profile of ISENTRESS in subjects with hepatitis B and/or hepatitis C virus co-infection was similar to subjects without hepatitis B and/or hepatitis C virus co-infection. Grade 2 or higher laboratory abnormalities that represent a worsening Grade from baseline of AST, ALT or total bilirubin occurred in 25%, 31% and 12%, respectively, of co-infected subjects treated with ISENTRESS as compared to 8%, 7% and 8% of all other subjects treated with ISENTRESS.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of ISENTRESS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Psychiatric Disorders: depression (particularly in patients with a pre-existing history of psychiatric illness), including suicidal ideation and behaviors

Skin and Subcutaneous Tissue Disorders: rash, Stevens-Johnson syndrome



REPORTS OF SUSPECTED ISENTRESS SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Isentress. The information is not vetted and should not be considered as verified clinical evidence.

Possible Isentress side effects / adverse reactions in 82 year old female

Reported by a physician from France on 2011-10-03

Patient: 82 year old female

Reactions: Fungal Test Positive, Candida Sepsis, non-Hodgkin's Lymphoma, Septic Shock, Fall

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Isentress

Other drugs received by patient: Emtricitabine and Tenofovir Disoproxil Fumarate; Cyclophosphamide; Prednisone; Olanzapine; Rituximab; Vincristine Sulfate



Possible Isentress side effects / adverse reactions in 57 year old male

Reported by a health professional (non-physician/pharmacist) from France on 2011-10-03

Patient: 57 year old male weighing 54.0 kg (118.8 pounds)

Reactions: Jaundice, Hepatitis Cholestatic, Hepatic Failure

Adverse event resulted in: death, life threatening event, hospitalization

Suspect drug(s):
Ritonavir
    Administration route: Oral
    Indication: HIV Infection
    End date: 2010-02-22

Darunavir
    Administration route: Oral
    Indication: HIV Infection
    Start date: 2010-02-09
    End date: 2010-02-22

Esomeprazole Magnesium
    Administration route: Oral
    Indication: Gastroduodenal Ulcer
    Start date: 2010-01-27

Isentress
    Administration route: Oral
    Indication: HIV Infection
    End date: 2010-02-22

Other drugs received by patient: Atazanavir Sulfate



Possible Isentress side effects / adverse reactions in male

Reported by a physician from France on 2011-10-03

Patient: male weighing 3.0 kg (6.6 pounds)

Reactions: Premature Baby, Maternal Exposure During Pregnancy

Adverse event resulted in: hospitalization

Suspect drug(s):
Isentress

Other drugs received by patient: Enoxaparin Sodium; Lamivudine and Zidovudine



See index of all Isentress side effect reports >>

Drug label data at the top of this Page last updated: 2009-02-12

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