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
Abelcet Side Effects, and Drug Interactions - Amphotericin B
Abelcet Side Effects, and Drug Interactions - Amphotericin B
SIDE EFFECTS
The total safety data base is
composed of 921 patients treated with ABELCET® (5 patients
were enrolled twice and counted as separate patients), of whom 775 were
treated with 5 mg/kg/day. Of these 775 patients, 194 patients were treated
in four comparative studies; 25 were treated in open-label, non-comparative
studies; and 556 patients were treated in an open-label, emergency-use
program. Most had underlying hematologic neoplasms, and many were receiving
multiple concomitant
medications. Of the 556 patients treated with ABELCET®,
9% discontinued treatment due to adverse events regardless of presumed
relationship to study drug.
In general, the adverse events most commonly reported with ABELCET®
were transient chills and/or
fever during infusion
of the drug.
| Adverse Eventsa with
an Incidence of ³3% (N=556) |
| Adverse Event |
Percentage (%) of Patients |
|
|
18 |
|
|
14 |
Increased Serum Creatinine
|
11 |
|
|
11 |
|
|
9 |
|
|
8 |
|
|
8 |
|
|
8 |
|
|
7 |
|
|
7 |
|
|
6 |
|
|
6 |
|
|
6 |
|
|
5 |
|
|
5 |
|
|
5 |
|
|
5 |
|
|
5 |
|
|
5 |
|
|
4 |
|
|
4 |
|
|
4 |
Gastrointestinal Hemorrhage
|
4 |
|
|
4 |
|
|
4 |
|
|
4 |
|
|
3 |
|
|
3
|
The following adverse events have also been reported in patients using
ABELCET® in open-label, uncontrolled clinical
studies. The causal association
between these adverse events and ABELCET® is uncertain.
Body as a whole: malaise, weight
loss, deafness, injection site reaction
including inflammation
Allergic: bronchospasm, wheezing, asthma, anaphylactoid
and other allergic reactions
Cardiopulmonary: cardiac
failure, pulmonary edema, shock, myocardial infarction, hemoptysis, tachypnea,
thrombophlebitis, pulmonary embolus, cardiomyopathy, pleural
effusion, arrhythmias including ventricular fibrillation.
Dermatological: maculopapular
rash, pruritus, exfoliative dermatitis, erythema
multiforme
Gastrointestinal: acute
liver failure, hepatitis, jaundice,
melena, anorexia, dyspepsia, cramping, epigastric pain, veno-occlusive
liver disease, diarrhea, hepatomegaly, cholangitis, cholecystitis
Hematologic: coagulation defects, leukocytosis, blood dyscrasias
including eosinophilia
Musculoskeletal: myasthenia, including bone, muscle, and
joint pains
Neurologic: convulsions, tinnitus, visual
impairment, hearing loss, peripheral
neuropathy, transient vertigo,
diplopia, encephalopathy, cerebral vascular
accident, extrapyramidal
syndrome and other neurologic
symptoms
Urogenital: oliguria, decreased renal
function, anuria, renal tubular
acidosis, impotence, dysuria
Serum electrolyte
abnormalities: hypomagnesemia, hyperkalemia, hypocalcemia, hypercalcemia
Liver function test
abnormalities: increased AST, ALT, alkaline phosphatase, LDH
Renal function test
abnormalities: increased BUN
Other test abnormalities:
acidosis, hyperamylasemia, hypoglycemia, hyperglycemia, hyperuricemia,
hypophosphatemia
DRUG INTERACTIONS
No formal clinical studies
of drug interactions have been
conducted with ABELCET®. However, when administered concomitantly,
the following drugs are known to interact with amphotericin B; therefore,
the following drugs may interact with ABELCET®:
Antineoplastic agents: Concurrent use of antineoplastic
agents and amphotericin B may enhance the potential
for renal toxicity, bronchospasm,
and hypotension. Antineoplastic agents should be given concomitantly with
ABELCET® with great caution.
Corticosteroids and corticotropin
(ACTH): Concurrent use of corticosteroids and corticotropin
(ACTH) with amphotericin B may potentiate hypokalemia which could predispose
the patient to cardiac
dysfunction. If used concomitantly with ABELCET®, serum
electrolytes and cardiac function
should be closely monitored.
Gyclosporin A: Data from a prospective study of prophylactic
ABELCET® in 22 patients undergoing bone
marrow transplantation suggested
that concurrent initiation of cyclosporin A and ABELCET®
within several days of bone marrow
ablation may be associated
with increased nephrotoxicity.
Digitalis glycosides: Concurrent use of amphotericin B
may induce hypokalemia
and may potentiate digitalis
toxicity. When administered concomitantly with ABELCET®,
serum potassium
levels should be closely monitored.
Flucytosine: Concurrent use of flucytosine
with amphotericin B-containing preparations may increase the toxicity
of flucytosine by possibly
increasing its cellular uptake
and/or impairing its renal excretion.
Flucytosine should be given concomitantly with ABELCET®
with caution.
Imidazoles (e.g., ketoconazole, miconazole, clotrimazole, fluconazole,
etc.): Antagonism between amphotericin B and imidazole
derivatives such as miconazole and ketoconazole, which inhibit ergosterol
synthesis, has been reported in both in vitro and in vivo
animal studies. The clinical
significance of these findings has not been determined.
Leukocyte transfusions: Acute pulmonary toxicity has been
reported in patients receiving intravenous
amphotericin B and leukocyte transfusions. Leukocyte transfusions and
ABELCET® should not be given concurrently.
Other nephrotoxic medications: Concurrent use of amphotericin
B and agents such as aminoglycosides and pentamidine
may enhance the potential for drug-induced renal
toxicity. Aminoglycosides and pentamidine
should be used concomitantly with ABELCET® only with great
caution. Intensive monitoring of renal
function is recommended in
patients requiring any combination of nephrotoxic medications.
Skeletal muscle relaxants:
Amphotericin B-induced hypokalemia may enhance the curariform effect
of skeletal muscle
relaxants (e.g., tubocurarine) due to hypokalemia. When administered concomitantly
with ABELCET®, serum potassium
levels should be closely monitored.
Zidovudine: Increased myelotoxicity and nephrotoxicity
were observed in dogs when either ABELCET® (at doses 0.16
or 0.5 times the recommended human
dose) or amphotericin B desoxycholate (at 0.5 times the recommended human
dose) were administered concomitantly with zidovudine
for 30 days. If zidovudine
is used concomitantly with ABELCET®, renal and hematologic
function should be closely
monitored.
top
