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
Asendin Side Effects, and Drug Interactions - Amoxapine
Asendin Side Effects, and Drug Interactions - Amoxapine
SIDE EFFECTS
Adverse reactions reported in controlled studies in the United States
are categorized with respect to incidence
below. Following this is a listing of reactions known to occur with other
antidepressant drugs
of this class but not reported to date with Amoxapine Tablets.
Incidence Greater Than 1%
The most frequent types of adverse reactions occurring with Amoxapine
Tablets in controlled clinical
trials were sedative and
anticholinergic. These included:
- drowsiness (14 %)
- dry mouth ( 14 %)
- constpation (12 %)
- blurred vision ( 7 % )
Less frequently reported reactions are:
- CNS and Neuromuscular, anxiety,
insomnia, restlessness,
nervousness, palpitations, tremors, confusion,
excitement, nightmares, ataxia,
alterations in EEG patterns.
- Allergic edema, skin
rash.
- Endocrine elevation
of prolactin levels.
- Gastrointestinal nausea.
- Other - dizziness, headache,
fatigue, weakness, excessive
appetite, increased perspiration.
Incidence Less Than 1%
- Anticholinergic - disturbances of accommodation, mydriasis,
delayed micturition. urinary
retention. nasal stuffiness.
- Cardiovascular - hypotension. hypertension,, syncope,
tachycardia.
- Allergic - drug fever,urticaria,
photosensitizatlon, pruritus,
rarely vasulitis, hepatitis.
- CNS and Neuromuscular - tingling, paresthesias of the extremities
tinnitus., disorientation seizures, hypomania,
numbness, incoordinatlon, disturbed concentration, hyperthermia,
extrapyramidal symptoms,
including rarely, tardive dykinesia. Neuroleptic malignant
syndrome has been reported
(See WARNINGS)
- Hematologic - leukopenia,
agranulocytosis.
- Gastrointestinal - epigastric distress, vomiting,
flatulence, abdominal
pain, peculiar taste, diarrhea.
- Endocrine - increase or decreased libido,
impotence, menstrual irregularity,
breast enlargement, and alactorrhea in the female, syndrome
of inapproriate antidiuretic hormone
secretion.
- Other - lacrimation,
weight gain
or loss, altered liver function,
painful ejaculation.
Drug Relationship Unknown
The following reactions have been reported very rarely and occurred under
uncontrolled circumstances where a drug
relationship was difficult to assess. These observations are listed to
serve as alerting information to physicians.
- Anticholinergic - paralitic ileus
- Cardiovascular - atrial
arrhythmias (including atrial
fibrillation), myocardial infarction. stroke, heart
block.
- CNS and Neuromuscular - hallucinations.
- Hematologic - thrombocytopenia
eosinophilia, purpura,
petechiae.
- Gastrointestinal - parotid
swelling.
- Endocrine - change in blood
glucose levels.
- Other - pancreatitis,
hepatitis, jaundice,
urinary frequency, testicular
swelling anorexia. alopecia.
Additional Adverse REACTIONS
The following reactions have been reported with other antidepressant
drugs but not with Amoxapine Tablets
- Anticholinergic - sublingual
adenitis, dilation of the
urinary tract.
- CNS and Neuromuscular - delusions.
- Gastrointestinal - stomatitis,
black tongue.
- Endocrine - gynecomastia.
DRUG INTERACTIONS
See CONTRAINDICATIONS about
concurrent usage of tricyclic antidepressants and monoamine
oxidase inhibitors. Paralytic
ileus may occur in patients
taking tricyclic antidepressants in combination with anticholinergic
drugs. Amoxapine may enhance the response to alcohol
and the effects of barbiturates
and other CNS depressants. Serum
levels of several tricyclic antidepressants have been reported to be significantly
increased when cimetidine
is administered concurrently Although such an interaction has not been
reported to date with amoxapine, specific
interaction studies have not been done, and the possibility should be
considered.
Drugs Metabolized b P450 2D6
The biochemical activity
of the drug metabolizing isozyme
cytochrome P450 2D6 (dehrisoquin
hydroxylase) is reduced in a subset of the caucasian population
(about 7 to 10% of caucasians are so called of reduced P450 2D6 isozyme
activity among p.o.
metabolizers); reliable estimates of the prevalence
Asian, African and other populatlons are not yet available when given
usual doses. Poor metabolizers have higher than expected plasma
concentrations tricyclic antidepressants (TCAs) when given usual doses.
Depending on the fraction
of drug metabolized by P450 2D6,
the increase in plasma concentration
may be small, or quite large (8 fold
increase in plasma AUC
of the TCA).
In addition. certain drugs inhibit the activity
of this isozyme and make normal
metabolizers resemble p.o. metabolizers.
An individual who is stable
on a given dose of TCA may become
abruptly toxic when given one
of these inhibiting drugs as concomitant
therapy. The drugs that inhibit cytochrome P450 2D6 include some that
are not metabolized by the enzymes quinidine, cimetidine, and many that
are substrates for P450 2D6 (many other antidepressants, phenothiazines,
and the Type 1C antiarrhythmics propafenone and flecainide). While all
the selective serotonin
reuptake inhibitors (SSRls), e.g. fluoxetine, sertraline, and paroxetine
inhibit P450 2D6, they may vary in the extent of inhibition. The extent
to which SSRI-TCA interactions may pose clinical
problems will depend on the degree
of inhibition and the pharmacokmetics
of the SSRI involved. Nevertheless, caution is indicated in the co-administration
of TCA's with any of the SSRI's and also in switching from one class
to the other of particular importance. Sufficient time
must elapse before initiating TCA treatment in a patient
being withdrawn from fluoxetine given. The long half-life of the parent
and active metabolite (at
least 5 weeks may be necessary).
Concomitant use
of tricyclic antidepressants with drugs that can inhibit cytochrome
P450 2D6 may require lower doses than usually prescribed for either the
tricyclic antidepressant or the other drug. Furthermore, whenever one
of these other drugs is withdrawn from co-therapy, an increased dose
of tricyclic antidepressant may be required. It is desirable to monitor
TCA plasma levels whenever
a TCA is going to be co-administered with another drug
known to be an inhibitor of P450 2D6.
Therapeutic Interactions
Concurrent administration
with electroshock therapy may increase the hazards associated with such
therapy.
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