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
Gonal-F Side Effects, and Drug Interactions - Follitropin Alfa
Gonal-F Side Effects, and Drug Interactions - Follitropin Alfa
SIDE EFFECTS
The safety of Gonal-F® was examined in four clinical
studies that enrolled 691 patients into two studies for ovulation
induction (454 patients)
and two studies for ART
(237 patients).
Adverse events occurring in more than 10% of patients were headache,
ovarian cyst, nausea,
and upper respiratory
tract infection
in the US ovulation induction study and headache
in the US ART study. Adverse
events (without regard to causality assessment) occurring in at
least 2% of patients are listed in Table 10 and Table 11.
Table 10: US Controlled Trial in Ovulation Induction, Study
5727
|
Body System
Preferred Term
|
Gonal-F®
Patients (%) Experiencing
Events Treatment
Cycles = 288*
n = 118
|
urofollitropin
Patients (%) Experiencing
Events Treatment
Cycles = 277
n = 114
|
| Reproductive, Female
|
| Intermenstrual Bleeding
|
9.3%
|
4.4%
|
| Breast Pain Female
|
4.2%
|
6.1%
|
| Ovarian Hyperstimulation**
|
6.8%
|
3.5%
|
| Dysmenorrhea |
2.5%
|
6.1%
|
| Ovarian Disorder
|
1.7%
|
2.6%
|
| Cervix Lesion |
2.5%
|
0.9%
|
| Menstrual Disorder
|
2.5%
|
0.9%
|
| Gastro-intestinal
System |
| Abdominal Pain |
9.3%
|
12.3%
|
| Nausea |
13.6%
|
3.5%
|
| Flatulence |
6.8%
|
8.8%
|
| Diarrhea |
7.6%
|
3.5%
|
| Vomiting |
2.5%
|
2.6%
|
| Dyspepsia |
1.7%
|
3.5%
|
| Central and Peripheral
Nervous System |
| Headache |
22.0%
|
20.2%
|
| Dizziness |
2.5%
|
0.0%
|
| Neoplasm |
| Ovarian Cyst |
15.3%
|
28.9%
|
| Body as a Whole--General
|
| Pain |
5.9%
|
6.1%
|
| Back Pain |
5.1%
|
1.8%
|
| Influenza-like Symptoms
|
4.2%
|
2.6%
|
| Fever |
4.2%
|
1.8%
|
| Respiratory System
|
| Upper Respiratory
Tract Infection |
11.9%
|
7.9%
|
| Sinusitis |
5.1%
|
5.3%
|
| Pharyngitis |
2.5%
|
3.5%
|
| Coughing |
1.7%
|
2.6%
|
| Rhinitis |
0.8%
|
2.6%
|
| Skin and Appendages
|
| Acne |
4.2%
|
2.6%
|
| Psychiatric |
| Emotional Lability
|
5.1%
|
2.6%
|
| Urinary System |
| Urinary Tract Infection
|
1.7%
|
4.4%
|
| Resistance Mechanism
|
| Moniliasis Genital
|
2.5%
|
0.9%
|
| Application Site
|
| Injection Site Pain
|
2.5%
|
0.9%
|
- * up to 3 cycles of therapy
- ** Severe = 0.8% of 118 patients in Study 5727
Additional adverse events not listed in Table 10 that occurred
in 1 to 2% of Gonal-F® treated patients in the US ovulation
induction study included
the fol lowing: leukorrhea, vaginal
hemorrhage, migraine,
fatigue, asthma, nervousness, somnolence,
and hypotension.
Table 11: US Controlled Trial in ART, Study 5533
|
Body System
Preferred Term
|
Gonal-F®
Patients (%)
Experiencing Events
n = 59
|
urofollitropin
Patients (%)
Experiencing Events
n = 61
|
| Reproductive, Female
|
| Intermenstrual Bleeding
|
3.6%
|
5.2%
|
| Leukorrhea |
1.7%
|
3.4%
|
| Vaginal Hemorrhage
|
3.6%
|
3.4%
|
| Gastro-intestinal
System |
| Nausea |
5.4%
|
1.7%
|
| Flatulence |
3.6%
|
0.0%
|
| Central and Peripheral
Nervous System |
| Headache |
12.5%
|
3.4%
|
| Body as a Whole-General
|
| Abdominal Pain |
8.9%
|
3.4%
|
| Pelvic Pain Female
|
7.1%
|
1.7%
|
| Respiratory System
|
| Upper Respiratory
Tract Infection |
3.6%
|
1.7%
|
| Metabolic and Nutritional
|
| Weight Increase |
3.6%
|
0.0%
|
Additional adverse events not listed in Table 11 that occurred
in 1 to 2% of Gonal-F® treated patients in the US Assisted Reproductive
Technology (ART) study included the following: D&C following
delivery or abortion,
dysmenorrhea, vaginal
hemorrhage, diarrhea,
tooth disorder, vomiting,
dizziness, paraesthesia,
abdomen enlarged, chest
pain, fatigue, dyspnea,
anorexia, anxiety,
somnolence, injection
site inflammation,
injection site reaction,
pruritus, pruritus
genital, myalgia,
thirst, and palpitation.
Two additional clinical
studies (for ovulation
induction and ART,
respectively) were conducted in Europe. The safety profiles from
these two studies were comparable to that of the data presented
above.
The following medical
events have been reported subsequent to pregnancies resulting from
Gonal-F® therapy
in controlled clinical
studies:
- 1. Spontaneous Abortion
- 2. Ectopic Pregnancy
- 3. Premature Labor
- 4. Postpartum Fever
- 5. Congenital abnormalities
TWO incidents of congenital
cardiac malformations
have been reported in children born following pregnancies resulting
from treatment with
Gonal-F® and hCG in Gonal-F® clinical
studies 5642 and 5727. In
addition, pregnancy occurring in study 5533 following treatment
with Gonal-F® and hCG was complicated by apparent
failure of intrauterine
growth and terminated
for a suspected syndrome
of congenital abnormalities.
No specific
diagnosis was made. The incidence
does not exceed that found in the general population.
The following adverse reactions have been previously reported during
menotropin therapy:
- 1. Pulmonary and vascular
complications (see WARNINGS),
- 2. Adnexal torsion
(as a complication
of ovarian enlargement),
- 3. Mild to moderate ovarian
enlargement,
- 4. Hemoperitoneum
There have been infrequent reports of ovarian
neoplasms, both benign and malignant,
in women who have undergone multiple
drug regimens for ovulation
induction; however, a causal relationship has not been established.
DRUG INTERACTIONS
No drug/drug interaction studies have been performed.
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