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
Ziagen Side Effects, and Drug Interactions - Abacavir
Ziagen Side Effects, and Drug Interactions - Abacavir
SIDE EFFECTS
WARNINGS
Hypersensitivity Reactions: Serious and sometimes fatal hypersensitivity reactions have
been associated with ZIAGEN (abacavir sulfate). Hypersensitivity to abacavir is a
multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of
the following groups: (1) fever, (2) rash, (3) gastrointestinal (including nausea, vomiting,
diarrhea, or abdominal pain), (4) constitutional (including generalized malaise, fatigue, or
achiness), and (5) respiratory (including dyspnea, cough, or pharyngitis). Discontinue
ZIAGEN as soon as a hypersensitivity reaction is suspected. Permanently discontinue
ZIAGEN if hypersensitivity cannot be ruled out, even when other diagnoses are possible.
Following a hypersensitivity reaction to abacavir, NEVER restart ZIAGEN or any other
abacavir-containing product because more severe symptoms can occur within hours and
may include life-threatening hypotension and death.
Reintroduction of ZIAGEN or any other abacavir-containing product, even in patients
who have no identified history or unrecognized symptoms of hypersensitivity to abacavir
therapy, can result in serious or fatal hypersensitivity reactions. Such reactions can occur
within hours (SEE WARNINGS, PRECAUTIONS:
Information for Patients).
Lactic Acidosis and Severe Hepatomegaly: Lactic acidosis and severe hepatomegaly
with steatosis, including fatal cases, have been reported with the use of nucleoside
analogues alone or in combination, including ZIAGEN and other antiretrovirals (SEE WARNINGS).
Hypersensitivity Reaction: Serious and sometimes fatal hypersensitivity reactions have
been associated with ZIAGEN (abacavir sulfate). In one study, once-daily dosing of
ZIAGEN was associated with more severe hypersensitivity reactions (see WARNINGS and
PRECAUTIONS: Information for Patients).
Therapy-Naive Adults: Treatment-emergent clinical adverse reactions (rated by the
investigator as moderate or severe) with a ≥5% frequency during therapy with ZIAGEN 300 mg
twice daily, lamivudine 150 mg twice daily, and efavirenz 600 mg daily compared with
zidovudine 300 mg twice daily, lamivudine 150 mg twice daily, and efavirenz 600 mg daily from
CNA30024 are listed in Table 4.
Table 4. Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate
Intensity (Grades 2-4, ≥5% Frequency) in Therapy-Naive Adults (CNA30024*) Through
48 Weeks of Treatment
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*This study used double-blind ascertainment of suspected hypersensitivity reactions. During the
blinded portion of the study, suspected hypersensitivity to abacavir was reported by
investigators in 9% of 324 patients in the abacavir group and 3% of 325 patients in the
zidovudine group.
† Ten (3%) cases of suspected drug hypersensitivity were reclassified as not being due to abacavir
following unblinding.
|
Treatment-emergent clinical adverse reactions (rated by the
investigator as moderate or severe) with a ≥ 5% frequency
during therapy with ZIAGEN 300 mg twice daily, lamivudine 150 mg twice daily,
and zidovudine 300 mg twice daily compared with indinavir 800 mg 3 times daily,
lamivudine 150 mg twice daily, and zidovudine 300 mg twice daily from CNA3005
are listed in Table 5.
Table 5. Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate
Intensity (Grades 2-4, ≥5% Frequency) in Therapy-Naive Adults (CNA3005) Through
48 Weeks of Treatment
Five patients receiving ZIAGEN in Study CNA3005 experienced
worsening of pre-existing depression compared to none in the indinavir arm.
The background rates of pre-existing depression were similar in the 2 treatment
arms.
ZIAGEN Once Daily versus ZIAGEN Twice Daily (Study CNA30021):
Treatment-emergent clinical adverse reactions (rated by the investigator as at least moderate)
with a ≥5% frequency during therapy with ZIAGEN 600 mg once daily or ZIAGEN 300 mg
twice daily both in combination with lamivudine 300 mg once daily and efavirenz 600 mg once
daily from Study CNA30021 were similar. (For hypersensitivity reactions, patients receiving
ZIAGEN once daily showed a rate of 9% in comparison to a rate of 7% for patients receiving
ZIAGEN twice daily.) However, patients receiving ZIAGEN 600 mg once daily, experienced a
significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea
compared to patients who received ZIAGEN 300 mg twice daily. Five percent (5%) of patients
receiving ZIAGEN 600 mg once daily had severe drug hypersensitivity reactions compared to
2% of patients receiving ZIAGEN 300 mg twice daily. Two percent (2%) of patients receiving
ZIAGEN 600 mg once daily had severe diarrhea while none of the patients receiving ZIAGEN
300 mg twice daily had this event.
Therapy-Experienced Pediatric Patients
Treatment-emergent clinical adverse reactions (rated by the
investigator as moderate or severe) with a ≥5% frequency
during therapy with ZIAGEN 8 mg/kg twice daily, lamivudine 4 mg/kg twice daily,
and zidovudine 180 mg/m2 twice daily compared with lamivudine 4 mg/kg
twice daily and zidovudine 180 mg/m2 twice daily from CNA3006 are
listed in Table 6.
Table 6. Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate
Intensity (Grades 2-4, ≥5% Frequency) in Therapy-Experienced Pediatric Patients
(CNA3006) Through 16 Weeks of Treatment
Laboratory Abnormalities: Laboratory abnormalities (Grades
3-4) in therapy-naive adults during therapy with ZIAGEN 300 mg twice daily,
lamivudine 150 mg twice daily, and efavirenz 600 mg daily compared with zidovudine
300 mg twice daily, lamivudine 150 mg twice daily, and efavirenz 600 mg daily
from CNA30024 are listed in Table 7.
Table 7. Laboratory Abnormalities (Grades 3-4) in Therapy-Naive Adults (CNA30024) Through 48 Weeks of Treatment
In another study of therapy-naive adults (CNA3005), hyperglycemia
and disorders of lipid metabolism occurred with similar frequency in patients
treated with ZIAGEN and patients treated with indinavir.
In a study of therapy-experienced pediatric patients (CNA3006), laboratory abnormalities (anemia, neutropenia,
liver function test abnormalities, and CPK elevations) were observed with similar
frequencies as in a study of therapy-naive adults (CNA30024). Mild elevations
of blood glucose were more frequent in pediatric patients receiving ZIAGEN (CNA3006)
as compared to adult patients (CNA30024).
The frequencies of treatment-emergent laboratory abnormalities were comparable between
treatment groups in Study CNA30021.
Other Adverse Events
In addition to adverse reactions in Tables 4, 5, 6, and 7, other
adverse events observed in the expanded access program were pancreatitis and increased GGT.
Observed During Clinical Practice:
In addition to adverse reactions reported from clinical
trials, the following events have been identified during use of abacavir in clinical practice.
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 either their seriousness,
frequency of reporting, potential causal connection to abacavir, or a combination of these factors.
Body as a Whole: Redistribution/accumulation
of body fat (see PRECAUTIONS: Fat Redistribution).
Hepatic: Lactic acidosis and hepatic steatosis (see
PRECAUTIONS and WARNINGS).
Skin: Suspected Stevens-Johnson syndrome (SJS)
and toxic epidermal necrolysis (TEN) have been reported in patients receiving
abacavir primarily in combination with medications known to be associated with
SJS and TEN, respectively. Because of the overlap of clinical signs and symptoms
between hypersensitivity to abacavir and SJS and TEN, and the possibility of
multiple drug sensitivities in some patients, abacavir should be discontinued
and not restarted in such cases. There have also been reports of erythema multiforme
with abacavir use.
DRUG INTERACTIONS
Pharmacokinetic properties of abacavir were not altered by
the addition of either lamivudine or zidovudine or the combination of lamivudine
and zidovudine. No clinically significant changes to lamivudine or zidovudine
pharmacokinetics were observed following concomitant administration of abacavir.
Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol
decreases the elimination of abacavir causing an increase in overall exposure
(see CLINICAL PHARMACOLOGY: Drug Interactions).
The addition of methadone has no clinically significant effect on the pharmacokinetic
properties of abacavir. In a study of 11 HIV-infected patients receiving methadone-maintenance
therapy (40 mg and 90 mg daily) with 600 mg of ZIAGEN twice daily (twice the
currently recommended dose), oral methadone clearance increased 22% (90% CI
6% to 42%). This alteration will not result in a methadone dose modification
in the majority of patients; however, an increased methadone dose may be required
in a small number of patients.
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