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Viread (Tenofovir Disoproxil Fumarate) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The following adverse reactions are discussed in other sections of the labeling:

  • Lactic Acidosis/Severe Hepatomegaly with Steatosis [See Boxed Warning, Warnings and Precautions].
  • Severe Acute Exacerbation of Hepatitis [See Boxed Warning, Warnings and Precautions].
  • New Onset or Worsening Renal Impairment [See Warnings and Precautions].
  • Decreases in Bone Mineral Density [See Warnings and Precautions].
  • Immune Reconstitution Syndrome [See Warnings and Precautions].

Adverse Reactions from 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.

Clinical Trials in Patients with HIV Infection

More than 12,000 patients have been treated with VIREAD alone or in combination with other antiretroviral medicinal products for periods of 28 days to 215 weeks in clinical trials and expanded access studies. A total of 1,544 patients have received VIREAD 300 mg once daily in clinical trials; over 11,000 patients have received VIREAD in expanded access studies.

The most common adverse reactions (incidence ≥10%, Grades 2—4) identified from any of the 3 large controlled clinical trials include rash, diarrhea, headache, pain, depression, asthenia, and nausea.

Treatment-NaŻve Patients

Study 903 - Treatment-Emergent Adverse Reactions: The most common adverse reactions seen in a double-blind comparative controlled study in which 600 treatment-naive patients received VIREAD (N=299) or stavudine (N=301) in combination with lamivudine and efavirenz for 144 weeks (Study 903) were mild to moderate gastrointestinal events and dizziness.

Mild adverse reactions (Grade 1) were common with a similar incidence in both arms, and included dizziness, diarrhea, and nausea. Selected treatment-emergent moderate to severe adverse reactions are summarized in Table 2.

Table 2 Selected Treatment-Emergent Adverse ReactionsFrequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug. (Grades 2—4) Reported in ≥5% in Any Treatment Group in Study 903 (0—144 Weeks)
VIREAD + 3TC + EFV d4T + 3TC + EFV
N=299 N=301
Body as a Whole
  Headache 14% 17%
  Pain 13% 12%
  Fever 8% 7%
  Abdominal pain 7% 12%
  Back pain 9% 8%
  Asthenia 6% 7%
Digestive System
  Diarrhea 11% 13%
  Nausea 8% 9%
  Dyspepsia 4% 5%
  Vomiting 5% 9%
Metabolic Disorders
  LipodystrophyLipodystrophy represents a variety of investigator-described adverse events not a protocol-defined syndrome. 1% 8%
Musculoskeletal
  Arthralgia 5% 7%
  Myalgia 3% 5%
Nervous System
  Depression 11% 10%
  Insomnia 5% 8%
  Dizziness 3% 6%
  Peripheral neuropathyPeripheral neuropathy includes peripheral neuritis and neuropathy. 1% 5%
  Anxiety 6% 6%
Respiratory
  Pneumonia 5% 5%
Skin and Appendages
  Rash eventRash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, and pustular rash. 18% 12%

Laboratory Abnormalities: With the exception of fasting cholesterol and fasting triglyceride elevations that were more common in the stavudine group (40% and 9%) compared with VIREAD (19% and 1%) respectively, laboratory abnormalities observed in this study occurred with similar frequency in the VIREAD and stavudine treatment arms. A summary of Grade 3 and 4 laboratory abnormalities is provided in Table 3.

Table 3 Grade 3/4 Laboratory Abnormalities Reported in ≥1% of VIREAD-Treated Patients in Study 903 (0—144 Weeks)
VIREAD + 3TC + EFV d4T + 3TC + EFV
N=299 N=301
Any ≥ Grade 3 Laboratory Abnormality 36% 42%
Fasting Cholesterol
(>240 mg/dL)
19% 40%
Creatine Kinase
(M: >990 U/L)
(F: >845 U/L)
12% 12%
Serum Amylase (>175 U/L) 9% 8%
AST
(M: >180 U/L)
(F: >170 U/L)
5% 7%
ALT
(M: >215 U/L)
(F: >170 U/L)
4% 5%
Hematuria (>100 RBC/HPF) 7% 7%
Neutrophils (<750/mm3) 3% 1%
Fasting Triglycerides (>750 mg/dL) 1% 9%

Study 934 - Treatment Emergent Adverse Reactions: In Study 934, 511 antiretroviral-naive patients received either VIREAD + EMTRIVA® administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254). Adverse reactions observed in this study were generally consistent with those seen in previous studies in treatment-experienced or treatment-naive patients (Table 4).

Table 4 Selected Treatment-Emergent Adverse ReactionsFrequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug. (Grades 2—4) Reported in ≥5% in Any Treatment Group in Study 934 (0—144 Weeks)
VIREADFrom Weeks 96 to 144 of the study, patients received TRUVADA with efavirenz in place of VIREAD + EMTRIVA with efavirenz. + FTC + EFV AZT/3TC + EFV
N=257 N=254
Gastrointestinal Disorder
  Diarrhea 9% 5%
  Nausea 9% 7%
  Vomiting 2% 5%
General Disorders and Administration Site Condition
  Fatigue 9% 8%
Infections and Infestations
  Sinusitis 8% 4%
  Upper respiratory tract infections 8% 5%
  Nasopharyngitis 5% 3%
Nervous System Disorders
  Headache 6% 5%
  Dizziness 8% 7%
Psychiatric Disorders
  Depression 9% 7%
  Insomnia 5% 7%
Skin and Subcutaneous Tissue Disorders
  Rash eventRash event includes rash, exfoliative rash, rash generalized, rash macular, rash maculo-papular, rash pruritic, and rash vesicular. 7% 9%

Laboratory Abnormalities: Laboratory abnormalities observed in this study were generally consistent with those seen in previous studies (Table 5).

Table 5 Significant Laboratory Abnormalities Reported in ≥1% of Patients in Any Treatment Group in Study 934 (0—144 Weeks)
VIREADFrom Weeks 96 to 144 of the study, patients received TRUVADA with efavirenz in place of VIREAD + EMTRIVA with efavirenz. + FTC + EFV AZT/3TC + EFV
N=257 N=254
Any ≥ Grade 3 Laboratory Abnormality 30% 26%
Fasting Cholesterol (>240 mg/dL) 22% 24%
Creatine Kinase
(M: >990 U/L)
(F: >845 U/L)
9% 7%
Serum Amylase (>175 U/L) 8% 4%
Alkaline Phosphatase (>550 U/L) 1% 0%
AST
(M: >180 U/L)
(F: >170 U/L)
3% 3%
ALT
(M: >215 U/L)
(F: >170 U/L)
2% 3%
Hemoglobin (<8.0 mg/dL) 0% 4%
Hyperglycemia (>250 mg/dL) 2% 1%
Hematuria (>75 RBC/HPF) 3% 2%
Glycosuria (≥3+) <1% 1%
Neutrophils (<750/mm3) 3% 5%
Fasting Triglycerides (>750 mg/dL) 4% 2%

Treatment-Experienced Patients

Treatment-Emergent Adverse Reactions: The adverse reactions seen in treatment experienced patients were generally consistent with those seen in treatment naive patients including mild to moderate gastrointestinal events, such as nausea, diarrhea, vomiting, and flatulence. Less than 1% of patients discontinued participation in the clinical studies due to gastrointestinal adverse reactions (Study 907).

A summary of moderate to severe, treatment-emergent adverse reactions that occurred during the first 48 weeks of Study 907 is provided in Table 6.

Table 6 Selected Treatment-Emergent Adverse ReactionsFrequencies of adverse reactions are based on all treatment-emergent adverse events, regardless of relationship to study drug. (Grades 2—4) Reported in ≥3% in Any Treatment Group in Study 907 (0—48 Weeks)
VIREAD
(N=368)
(Week 0—24)
Placebo
(N=182)
(Week 0—24)
VIREAD
(N=368)
(Week 0—48)
Placebo Crossover to VIREAD
(N=170)
(Week 24—48)
Body as a Whole
  Asthenia 7% 6% 11% 1%
  Pain 7% 7% 12% 4%
  Headache 5% 5% 8% 2%
  Abdominal pain 4% 3% 7% 6%
  Back pain 3% 3% 4% 2%
  Chest pain 3% 1% 3% 2%
  Fever 2% 2% 4% 2%
Digestive System
  Diarrhea 11% 10% 16% 11%
  Nausea 8% 5% 11% 7%
  Vomiting 4% 1% 7% 5%
  Anorexia 3% 2% 4% 1%
  Dyspepsia 3% 2% 4% 2%
  Flatulence 3% 1% 4% 1%
  Respiratory
  Pneumonia 2% 0% 3% 2%
Nervous System
  Depression 4% 3% 8% 4%
  Insomnia 3% 2% 4% 4%
  Peripheral neuropathyPeripheral neuropathy includes peripheral neuritis and neuropathy. 3% 3% 5% 2%
  Dizziness 1% 3% 3% 1%
Skin and Appendage
  Rash eventRash event includes rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, and pustular rash. 5% 4% 7% 1%
  Sweating 3% 2% 3% 1%
Musculoskeletal
  Myalgia 3% 3% 4% 1%
Metabolic
  Weight loss 2% 1% 4% 2%

Laboratory Abnormalities: Laboratory abnormalities observed in this study occurred with similar frequency in the VIREAD and placebo-treated groups. A summary of Grade 3 and 4 laboratory abnormalities is provided in Table 7.

Table 7 Grade 3/4 Laboratory Abnormalities Reported in ≥1% of VIREAD-Treated Patients in Study 907 (0—48 Weeks)
VIREAD
(N=368)
(Week 0—24)
Placebo
(N=182)
(Week 0—24)
VIREAD
(N=368)
(Week 0—48)
Placebo Crossover to VIREAD
(N=170)
(Week 24—48)
Any ≥ Grade 3 Laboratory Abnormality 25% 38% 35% 34%
Triglycerides (>750 mg/dL) 8% 13% 11% 9%
Creatine Kinase
(M: >990U/L)
(F: >845 U/L)
7% 14% 12% 12%
Serum Amylase (>175 U/L) 6% 7% 7% 6%
Glycosuria (≥3+) 3% 3% 3% 2%
AST
(M: >180 U/L)
(F: >170 U/L)
3% 3% 4% 5%
ALT
(M: >215 U/L)
(F: >170 U/L)
2% 2% 4% 5%
Serum Glucose (>250 U/L) 2% 4% 3% 3%
Neutrophils (<750/mm3) 1% 1% 2% 1%

Clinical Trials in Patients with Chronic Hepatitis B

Treatment-Emergent Adverse Reactions: In controlled clinical trials in patients with chronic hepatitis B, more patients treated with VIREAD experienced nausea: 9% with VIREAD versus 2% with HEPSERA. Other treatment-emergent adverse reactions reported in >5% of patients treated with VIREAD included: abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis, back pain and skin rash.

Laboratory Abnormalities: A summary of Grade 3 and 4 laboratory abnormalities is provided in Table 8.

Table 8. Grade 3/4 Laboratory Abnormalities Reported in ≥1% of VIREAD-Treated Patients in Studies 0102 and 0103 (0-48 Weeks)
VIREAD
(N=426)
HEPSERA
(N=215)
Any ≥ Grade 3 Laboratory Abnormality 19% 13%
Creatine Kinase
(M: >990U/L)
(F: >845 U/L)
2% 3%
Serum Amylase (>175 U/L) 4% 1%
Glycosuria (≥3+) 3% <1%
AST
(M: >180 U/L)
(F: >170 U/L)
4% 4%
ALT
(M: >215 U/L)
(F: >170 U/L)
10% 6%

The overall incidence of on-treatment ALT elevations (defined as serum ALT >2 — baseline and >10 — ULN, with or without associated symptoms) was similar between VIREAD (2.6%) and HEPSERA (2%). ALT elevations generally occurred within the first 4—8 weeks of treatment and were accompanied by decreases in HBV DNA levels. No patient had evidence of decompensation. ALT flares typically resolved within 4 to 8 weeks without changes in study medication.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of VIREAD. Because postmarketing 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.

Immune System Disorders
allergic reaction

Metabolism and Nutrition Disorders
lactic acidosis, hypokalemia, hypophosphatemia

Respiratory, Thoracic, and Mediastinal Disorders
dyspnea

Gastrointestinal Disorders
pancreatitis, increased amylase, abdominal pain

Hepatobiliary Disorders
hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT)

Skin and Subcutaneous Tissue Disorders
rash

Musculoskeletal and Connective Tissue Disorders
rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy

Renal and Urinary Disorders
acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria

General Disorders and Administration Site Conditions
asthenia

The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, hypophosphatemia.



REPORTS OF SUSPECTED VIREAD SIDE EFFECTS / ADVERSE REACTIONS

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

Possible Viread side effects / adverse reactions in 39 year old female

Reported by a physician from United States on 2011-10-05

Patient: 39 year old female

Reactions: Thrombosis, Premature Separation of Placenta, Inflammation

Suspect drug(s):
Kaletra
    Dosage: 4 tablets daily, taken at conception
    Administration route: Oral
    Indication: Antiviral Treatment
    Start date: 2010-07-15

Epivir
    Dosage: 300 mg daily, taken at conception
    Administration route: Oral
    Indication: Antiviral Treatment
    Start date: 2010-07-15

Viread
    Dosage: 300 mg daily, taken at conception
    Administration route: Oral
    Indication: Antiviral Treatment
    Start date: 2010-07-15



Possible Viread side effects / adverse reactions in 39 year old female

Reported by a physician from United States on 2011-10-10

Patient: 39 year old female

Reactions: Thrombosis, Premature Separation of Placenta, Maternal Exposure During Pregnancy, Stillbirth, Inflammation

Suspect drug(s):
Kaletra
    Dosage: 4 tablets daily, taken at conception
    Administration route: Oral
    Indication: Antiviral Treatment
    Start date: 2010-07-15

Viread
    Dosage: 300 mg daily, taken at conception
    Administration route: Oral
    Indication: Antiviral Treatment
    Start date: 2010-07-15

Epivir
    Dosage: 300 mg daily, taken at conception
    Administration route: Oral
    Indication: Antiviral Treatment
    Start date: 2010-07-15



Possible Viread side effects / adverse reactions in male

Reported by a health professional (non-physician/pharmacist) on 2011-10-12

Patient: male weighing 3.4 kg (7.4 pounds)

Reactions: Gastroschisis, Abdominal Hernia, Maternal Drugs Affecting Foetus, Cardiac Murmur, Cryptorchism, Congenital Anomaly, Abdominal Distension, Exomphalos, Umbilical Hernia

Suspect drug(s):
Lamivudine
    Dosage: 1200 mg (1200 mg, 1 in 1 d), transplacental
    Indication: HIV Infection
    Start date: 2004-01-30
    End date: 2004-06-01

Retrovir
    Dosage: 600 mg (600 mg, 1 in 1 d), transplacental
    Indication: HIV Infection
    Start date: 2004-06-01
    End date: 2004-07-20

Truvada
    Dosage: 300 mg, transplacental
    Indication: HIV Infection

Viracept
    Dosage: 2500 mg (2500 mg, 1 in 1 d), transplacental
    Indication: HIV Infection
    Start date: 2004-01-30
    End date: 2004-06-01

Viread
    Dosage: 300 mg (300 mg, 1 in 1 d), transplacental
    Indication: HIV Infection
    Start date: 2004-06-06
    End date: 2004-09-10

Zidovudine
    Dosage: 600 mg (600 mg, 1 in 1 d), transplacental
    Indication: HIV Infection
    Start date: 2004-06-01
    End date: 2004-07-20

Indinivir Sulfate
    Dosage: transplacental
    Indication: Product Used FOR Unknown Indication
    Start date: 2004-06-01
    End date: 2004-07-20

Kaletra
    Dosage: 600 mg (600 mg, 1 in 1 d), transplacental
    Indication: HIV Infection
    Start date: 2001-06-01

Other drugs received by patient: Folic Acid



See index of all Viread side effect reports >>

Drug label data at the top of this Page last updated: 2009-07-21

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