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
Fareston Side Effects, and Drug Interactions - Toremifene
Fareston Side Effects, and Drug Interactions - Toremifene
SIDE EFFECTS
Adverse drug reactions are principally due to the antiestrogenic hormonal actions
of FARESTON and typically occur at the beginning of treatment.
The incidences of the following eight clinical toxicities were prospectively
assessed in the North American Study. The incidence reflects the toxicities
that were considered by the investigator to be drug related or possible drug
related.
|
|
North American Study |
|
|
FAR60
n = 221 |
TAM20
n = 215 |
|
Hot Flashes
|
35% |
30% |
|
Sweating
|
20% |
17% |
|
Nausea
|
14% |
15% |
|
Vaginal Discharge
|
13% |
16% |
|
Dizziness
|
9% |
7% |
|
Edema
|
5% |
5% |
|
Vomiting
|
4% |
2% |
|
Vaginal Bleeding
|
2% |
4% |
Approximately 1% of patients receiving FARESTON (n = 592) in the three controlled
studies discontinued treatment as a result of adverse events (nausea and vomiting,
fatigue, thrombophlebitis, depression, lethargy, anorexia, ischemic attack,
arthritis, pulmonary embolism, and myocardial infarction).
Serious adverse events occurring in patients receiving FARESTON in the three
major trials are listed in the table below.
|
Adverse Events
|
North American |
Eastern European |
Nordic |
|
|
FAR60
n=221(%) |
TAM20
n=215(%) |
FAR60
n=157(%) |
TAM40
n=149(%) |
FAR60
n=214(%) |
TAM40
n=201(%) |
|
Cardiac
|
|
Cardiac Failure
|
2 (1) |
1 (<1) |
- |
1 (<1) |
2 (1) |
3 (1.5) |
|
Myocardial Infarction
|
2 (1) |
3 (1.5) |
1 (<1) |
2 (1) |
- |
1 (<1) |
|
Arrhythmia
|
- |
- |
- |
- |
3 (1.5) |
1 (<1) |
|
Angina Pectoris
|
- |
- |
1 (<1) |
- |
1 (<1) |
2 (1) |
|
Ocular *
|
|
Cataracts
|
22 (10) |
16 (7.5) |
- |
- |
- |
5 (3) |
|
Dry Eyes
|
20 (9) |
16 (7.5) |
- |
- |
- |
- |
|
Abnorma Visual Fields
|
8 (4) |
10 (5) |
- |
- |
- |
1 (<1) |
|
Corneal Keratopathy
|
4 (2) |
2 (1) |
- |
- |
- |
- |
|
Glaucoma
|
3 (1.5) |
2 (1) |
1 (<1) |
- |
- |
1 (<1) |
|
Abnormal Vision/Diplopia
|
- |
- |
- |
- |
3 (1.5) |
- |
|
Thromboembolic
|
|
Pulmonary Embolism
|
4 (2) |
2 (1) |
1 (<1) |
- |
- |
1 (<1) |
|
Thrombophlebitis
|
- |
2 (1) |
1 (<1) |
1 (<1) |
4 (2) |
3 (1.5) |
|
Thrombosis
|
- |
1 (<1) |
1 (<1) |
- |
3 (1.5) |
4 (2) |
|
CVA/TIA
|
1 (<1) |
- |
- |
1 (<1) |
4 (2) |
4 (2) |
|
Elevated Liver Tests **
|
|
SGOT
|
11 (5) |
4 (2) |
30 (19) |
22 (15) |
32 (15) |
35 (17) |
|
Alkaline Phosphatase
|
41 (19) |
24 (11) |
16 (10) |
13 (9) |
18 (8) |
31 (15) |
|
Bilirubin
|
3 (1.5) |
4 (2) |
2 (1) |
1 (<1) |
2 (1) |
3 (1.5) |
|
Hypercalcemia
|
6 (3) |
6 (3) |
1 (<1) |
- |
- |
- |
|
* Most of the ocular
abnormalities were observed in the North American Study in which
on-study and biannual ophthalmic examinations were performed.
No cases of retinopathy
were observed in any arm.
|
|
** Elevated defined as follows: North American Study:
SGOT >100 IU/L; alkaline
phosphatase >200
IU/L; bilirubin >2 mg/dL. Eastern European and Nordic studies:
SGOT, alkaline phosphatase, and bilirubin
- WHO Grade 1 (1.25 times
the upper limit of normal).
|
Other adverse events of unclear causal relationship to FARESTON included leukopenia
and thrombocytopenia, skin discoloration or dermatitis, constipation, dyspnea,
paresis, tremor, vertigo, pruritis, anorexia, reversible corneal opacity (corneal
verticulata), asthenia, alopecia, depression, jaundice, and rigors.
In the 200 and 240 mg FARESTON dose arms, the incidence of SGOT elevation and
nausea was higher. Approximately 4% of patients were withdrawn for toxicity
from the high-dose FARESTON treatment arms. Reasons for withdrawal included
hypercalcemia, abnormal liver function tests, and one case of toxic hepatitis,
depression, dizziness, incoordination, ataxia, blurry vision, diffuse dermatitis,
and a constellation of symptoms consisting of nausea, sweating, and tremor.
DRUG INTERACTIONS
Drugs that decrease renal calcium excretion, eg, thiazide diuretics, may increase the risk of hypercalcemia in
patients receiving FARESTON. There is a known interaction between antiestrogenic
compounds of the triphenylethylene derivative class and coumarin-type anticoagulants
(eg, warfarin), leading to an increased prothrombin time. When concomitant use
of anticoagulants with FARESTON is necessary, careful monitoring of the prothrombin
time is recommended.
Cytochrome P450 3A4 enzyme inducers, such as phenobarbital, phenytoin, and
carbamazepine increase the rate of toremifene metabolism, lowering the steady-state
concentration in serum. Metabolism of toremifene may be inhibited by drugs known
to inhibit the CYP3A4-6 enzymes. Examples of such drugs are ketoconazole and
similar antimycotics as well as erythromycin and similar macrolides. This interaction
has not been studied and its clinical relevance is uncertain.
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