A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Combivir Side Effects, and Drug Interactions - Lamivudine and zidovudine
Combivir Side Effects, and Drug Interactions - Lamivudine and zidovudine
SIDE EFFECTS
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 clinical and laboratory adverse events
were observed (see Tables 4 and 5).
|
Table 4. Selected Clinical Adverse Events (³5% Frequency)
in 4 Controlled Clinical Trials With EPIVIR 300 mg/day and RETROVIR 600
mg/day
|
| |
EPIVIR plus RETROVIR
|
|
Adverse Event
|
(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 3 of the 656 adult patients (<0.5%)
who received EPIVIR in controlled clinical trials.
Selected laboratory abnormalities observed during therapy are
listed in Table 5.
|
Table 5. Frequencies of Selected Laboratory Abnormalities
Among Adults in 4 Controlled Clinical Trials of EPIVIR 300 mg/day plus
RETROVIR 600 mg/day*
|
|
Test
|
EPIVIR plus RETROVIR
|
|
(Abnormal Level)
|
% (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)
|
|
ULN = Upper limit of normal.
|
|
ANC = Absolute neutrophil count.
|
|
n = Number of patients assessed.
|
|
* Frequencies of these laboratory abnormalities were
higher in patients with mild laboratory
|
|
abnormalities at baseline.
|
Observed During Clinical Practice: In addition to adverse
events reported from clinical trials, the following events have been identified
during post-approval use of EPIVIR, RETROVIR, and/or COMBIVIR. Because they
are reported voluntarily from a population of unknown size, estimates of frequency
cannot be made. These events have been chosen for inclusion due to a combination
of their seriousness, frequency of reporting, or potential causal connection
to EPIVIR, RETROVIR, and/or COMBIVIR.
Body as a Whole: Redistribution/accumulation
of body fat (see PRECAUTIONS: Fat Redistribution).
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 exacerbation of hepatitis B (see WARNINGS).
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.
DRUG INTERACTIONS
Lamivudine: Trimethoprim (TMP) 160 mg/sulfamethoxazole
(SMX) 800 mg once daily has been shown to increase lamivudine exposure (AUC).
The effect of higher doses of TMP/SMX on lamivudine pharmacokinetics has not
been investigated (see CLINICAL PHARMACOLOGY).
No data are available regarding the potential for interactions with other drugs
that have renal clearance mechanisms similar to that of lamivudine.
Lamivudine and zalcitabine may inhibit the intracellular phosphorylation
of one another. Therefore, use of COMBIVIR in combination with zalcitabine is
not recommended.
Zidovudine: Coadministration of ganciclovir,
interferon-alpha, and other bone marrow suppressive or cytotoxic agents may
increase the hematologic toxicity of zidovudine.
Concomitant use of COMBIVIR with stavudine should be avoided
since an antagonistic relationship with zidovudine has been demonstrated in
vitro. In addition, concomitant use of zidovudine with doxorubicin or ribavirin
should be avoided because an antagonistic relationship has been demonstrated
in vitro. See CLINICAL PHARMACOLOGY for
additional drug interactions.
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