Lamivudine and Zidovudine (Page 2 of 6)

5.8 Lipoatrophy

Treatment with zidovudine, a component of lamivudine and zidovudine tablets, has been associated with loss of subcutaneous fat. The incidence and severity of lipoatrophy are related to cumulative exposure. This fat loss, which is most evident in the face, limbs, and buttocks, may be only partially reversible and improvement may take months to years after switching to a non-zidovudine-containing regimen. Patients should be regularly assessed for signs of lipoatrophy during therapy with zidovudine-containing products, and if feasible, therapy should be switched to an alternative regimen if there is suspicion of lipoatrophy.

6 ADVERSE REACTIONS

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

  • Hematologic toxicity, including neutropenia and anemia [see Boxed Warning, Warnings and Precautions (5.1)].
  • Symptomatic myopathy [see Boxed Warning, Warnings and Precautions (5.2)].
  • Lactic acidosis and severe hepatomegaly with steatosis [see Boxed Warning, Warnings and Precautions (5.3)].
  • Exacerbations of hepatitis B [see Boxed Warning, Warnings and Precautions (5.4)].
  • Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C [see Warnings and Precautions (5.5)].
  • Exacerbation of anemia in HIV-1/HCV co-infected patients receiving ribavirin and zidovudine [see Warnings and Precautions (5.5)].
  • Pancreatitis [see Warnings and Precautions (5.6)]
  • Immune reconstitution syndrome [see Warnings and Precautions (5.7)]
  • Lipoatrophy [see Warnings and Precautions (5.8)]

6.1 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 clinical practice.

Lamivudine Plus Zidovudine Administered As Separate Formulations:

In 4 randomized, controlled trials of EPIVIR 300 mg per day plus RETROVIR 600 mg per day, the following selected adverse reactions and laboratory abnormalities were observed (see Tables 1 and 2).

Table 1. Selected Clinical Adverse Reactions (Greater than or Equal to 5% Frequency) in 4 Controlled Clinical Trials with EPIVIR 300 mg per day and RETROVIR 600 mg per day

Adverse Reaction EPIVIR plus RETROVIR ( n = 251 )
Body as a whole
Headache 35%
Malaise & fatigue 27%
Fever or chills 10%
Digestive
Nausea 33%
Diarrhea 18%
Nausea & vomiting 13%
Anorexia and/or decreased appetite 10%
Abdominal pain 9%
Abdominal cramps 6%
Dyspepsia 5%
Nervous system
Neuropathy 12%
Insomnia & other sleep disorders 11%
Dizziness 10%
Depressive disorders 9%
Respiratory
Nasal signs & symptoms 20%
Cough 18%
Skin
Skin rashes 9%
Musculoskeletal
Musculoskeletal pain 12%
Myalgia 8%
Arthralgia 5%

Pancreatitis was observed in 9 of the 2,613 adult patients (0.3%) who received EPIVIR in controlled clinical trials [see Warnings and Precautions (5.6)].

Selected laboratory abnormalities observed during therapy are listed in Table 2.

Table 2. Frequencies of Selected Laboratory Abnormalities among Adults in 4 Controlled Clinical Trials of EPIVIR 300 mg per day plus RETROVIR 600 mg per day*

ULN = Upper limit of normal.

ANC = Absolute neutrophil count.

n = Number of patients assessed.

* Frequencies of these laboratory abnormalities were higher in subjects with mild laboratory abnormalities at baseline.

Test (Abnormal Level) EPIVIR plus RETROVIR % (n)
Neutropenia (ANC<750/mm3) 7.2% (237)
Anemia (Hgb<8.0 g/dL) 2.9% (241)
Thrombocytopenia (platelets<50,000/mm3) 0.4% (240)
ALT (>5.0 x ULN) 3.7% (241)
AST (>5.0 x ULN) 1.7% (241)
Bilirubin (>2.5 x ULN) 0.8% (241)
Amylase (>2.0 x ULN) 4.2% (72)

6.2 Postmarketing Experience

The following adverse reactions have been identified during postmarketing use. Because these reactions 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.

Body as a Whole

Redistribution/accumulation of body fat [see Warnings and Precautions (5.8)].

Cardiovascular

Cardiomyopathy.

Endocrine and Metabolic

Gynecomastia, hyperglycemia.

Gastrointestinal

Oral mucosal pigmentation, stomatitis.

General

Vasculitis, weakness.

Hemic and Lymphatic

Anemia, (including pure red cell aplasia and anemias progressing on therapy), lymphadenopathy, splenomegaly.

Hepatic and Pancreatic

Lactic acidosis and hepatic steatosis, pancreatitis, posttreatment exacerbations of hepatitis B [see Boxed Warning, Warnings and Precautions (5.3), (5.4), (5.6)].

Hypersensitivity

Sensitization reactions (including anaphylaxis), urticaria.

Musculoskeletal

Muscle weakness, CPK elevation, rhabdomyolysis.

Nervous

Paresthesia, peripheral neuropathy, seizures.

Respiratory

Abnormal breath sounds/wheezing.

Skin

Alopecia, erythema multiforme, Stevens-Johnson syndrome.

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