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
Eligard Side Effects, and Drug Interactions - Leuprolide acetate
Eligard Side Effects, and Drug Interactions - Leuprolide acetate
SIDE EFFECTS
The safety of ELIGARDÔ 7.5
mg was evaluated in eight surgically castrated males and 120 patients with advanced
prostate cancer in two clinical trials. ELIGARDÔ
7.5 mg, like other LH-RH analogs, caused a transient increase in serum testosterone
concentrations during the first week of treatment. Therefore, potential exacerbations
of signs and symptoms of the disease during the first few weeks of treatment
are of concern in patients with vertebral metastases and/or urinary obstruction
or hematuria. If these conditions are aggravated, it may lead to neurological
problems such as weakness and/or paresthesia of the lower limbs or worsening
of urinary symptoms (see WARNINGS and
PRECAUTIONS).
In Study AGL9904, 120 patients were dosed with ELIGARD™
7.5 mg for up to six months and injection sites were closely monitored. In all,
716 injections of ELIGARD™ 7.5 mg were administered. Transient burning/stinging
was reported following 248 (34.6%) of injections, with the majority (84%) of
these events reported as mild. Pain was reported following 4.3% of study injections
(18.3% of patients) and was generally reported as brief in duration and mild
in intensity.
Erythema was reported following 2.6% of injections (12.5% of
patients). These events were all reported as mild and generally resolved within
a few days post-injection. Mild bruising was reported following 2.5% of injections
(11.7% of patients). Pruritis, induration, and ulceration was reported following
1.4% (11 patients), 0.4% (3 patients), and 0.1% (1 patient) of study injections,
respectively.
These localized adverse events were non-recurrent over time.
No patient discontinued therapy due to an injection site adverse event.
The following possibly or probably related systemic adverse
events occurred during clinical trials of up to six months of treatment with
ELIGARD™ 7.5 mg, and were reported in ³ 2%
of patients (Tables 1 and 2). Often, casuality is difficult to assess in patients
with metastatic prostate cancer. Reactions considered not drug-related are excluded.
|
Table 1: Incidence (%) of Possibly or Probably Related
Systemic Adverse Events Reported by ³ 2% of
Patients(n = 120) Treated with ELIGARD™ 7.5 mg for up to Six Months
in Study AGL9904
|
|
Body System
|
Adverse Event
|
Number
|
Percent
|
|
Body as a Whole
|
Malaise and Fatigue
|
21
|
17.5%
|
| |
Dizziness
|
4
|
3.3%
|
|
Cardiovascular
|
Hot flashes/sweats*
|
68
|
56.7%
|
|
Genitourinary
|
Atrophy of Testes*
|
6
|
5.0%
|
|
Digestive
|
Gastroenteritis/Colitis
|
3
|
2.5%
|
|
Table 2: Incidence (%) of Possibly or Probably-Related
Systemic Adverse Events Reported by ³ 2% of
Surgically Castrated Patients (n = 8) Treated with a Single-Dose of ELIGARD™
7.5 mg in Study AGL9802
|
|
Body System
|
Adverse Event
|
Number
|
Percent
|
|
Cardiovascular
|
Hot flashes/sweats*
|
2
|
25.0%
|
In addition, the following possibly or probably related systemic
adverse events were reported by < 2% of the patients using ELIGARD™
7.5 mg in clinical studies.
General: Sweating, insomnia, syncope Gastrointestinal: Flatulence,
constipation
Hematologic: Decreased red blood cell count, hematocrit and
hemoglobin Metabolic: Weight gain Musculoskeletal: Tremor, backache, joint pain
Nervous: Disturbance of smell and taste, depression, vertigo Skin: Alopecia
Urogenital: Testicular soreness, impotence*, decreased libido*,
gynecomastia, breast soreness
_____________________
* Expected pharmacological consequences of testosterone suppression.
In the patient populations studied, a total of 86 hot flash/ sweats adverse
events were reported in 70 patients. Of these, 71 events (83%) were mild; 14
(16%) were moderate; 1 (1%) was severe.
Changes in Bone Density: Decreased bone density has
been reported in the medical literature in men who have had orchiectomy or who
have been treated with an LH-RH agonist analog.3 It can be anticipated
that long periods of medical castration in men will have effects on bone density.
DRUG INTERACTIONS
:
See PHARMACOKINETICS
Drug/Laboratory Test Interactions: Therapy with leuprolide
results in suppression of the pituitary-gonadal system. Results of diagnostic
tests of pituitary gonadotropic and gonadal functions conducted during and after
leuprolide therapy may be affected.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Two-year
carcinogenicity studies were conducted with leuprolide acetate in rats and mice.
In rats, a dose-related increase of benign pituitary hyperplasia and benign
pituitary adenomas was noted at 24 months when the drug was administered subcutaneously
at high daily doses (0.6 to 4 mg/kg). There was a significant but not dose-related
increase of pancreatic islet-cell adenomas in females and of testicular interstitial
cell adenomas in males (highest incidence in the low dose group). In mice, no
leuprolide acetate-induced tumors or pituitary abnormalities were observed at
a dose as high as 60 mg/kg for two years. Patients have been treated with leuprolide
acetate for up to three years with doses as high a 10 mg/day and for two years
with doses as high as 20 mg/day without demonstrable pituitary abnormalities.
No carcinogenicity studies have been conducted with ELIGARD™ 7.5 mg.
Mutagenicity studies have been performed with leuprolide acetate
using bacterial and mammalian systems and with ELIGARD™ 7.5 mg in bacterial
systems. These studies provided no evidence of a mutagenic potential.
Pregnancy, Teratogenic Effects: Pregnancy category X. (See
CONTRAINDICATIONS).
Pediatric Use: ELIGARD™ 7.5 mg is contraindicated in
pediatric patients and was not studied in children (see CONTRAINDICATIONS).
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