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
Surmontil Side Effects, and Drug Interactions - Trimipramine
Surmontil Side Effects, and Drug Interactions - Trimipramine
SIDE EFFECTS
Note: The pharmacological similarities among the tricyclic
antidepressants require that each of the reactions be considered when Surmontil
is administered. Some of the adverse reactions included in this listing have
not in fact been reported with Surmontil.
Cardiovascular
Hypotension, hypertension, tachycardia, palpitation, myocardial infarction,
arrhythmias, heart block, stroke.
Psychiatric
Confusional states (especially the elderly) with hallucinations, disorientation,
delusions; anxiety, restlessness, agitation; insomnia and nightmares; hypomania;
exacerbation of psychosis.
Neurological
Numbness, tingling, paresthesias of extremities; incoordination, ataxia, tremors;
peripheral neuropathy; extrapyramidal symptoms; seizures, alterations in EEG
patterns; tinnitus; syndrome of inappropriate ADH (antidiuretic hormone) secretion.
Anticholinergic
Dry mouth and, rarely, associated sublingual adenitis; blurred vision, disturbances
of accommodation, mydriasis, constipation, paralytic ileus; urinary retention,
delayed micturition, dilation of the urinary tract.
Allergic
Skin rash, petechiae, urticaria, itching, photosensitization, edema of face
and tongue.
Hematologic
Bone-marrow depression including agranulocytosis, eosinophilia; purpura; thrombocytopenia.
Leukocyte and differential counts should be performed in any patient who develops
fever and sore throat during therapy; the drug should be discontinued if there
is evidence of pathological neutrophil depression.
Gastrointestinal
Nausea and vomiting, anorexia, epigastric distress, diarrhea, peculiar taste,
stomatitis, abdominal cramps, black tongue.
Endocrine
Gynecomastia in the male; breast enlargement and galactorrhea in the female;
increased or decreased libido, impotence; testicular swelling; elevation or
depression of blood-sugar levels.
Other
Jaundice (simulating obstructive); altered liver function; weight gain or loss;
perspiration; flushing; urinary frequency; drowsiness, dizziness, weakness,
and fatigue; headache; parotid swelling; alopecia.
Withdrawal Symptoms
Though not indicative of addiction, abrupt cessation of treatment after prolonged
therapy may produce nausea, headache, and malaise.
DRUG INTERACTIONS
Cimetidine
There is evidence that cimetidine inhibits the elimination of tricyclic antidepressants.
Downward adjustment of Surmontil dosage may be required if cimetidine therapy
is initiated; upward adjustment if cimetidine therapy is discontinued.
Alcohol
Patients should be warned that the concomitant use of alcoholic beverages may
be associated with exaggerated effects.
Catecholamines/Anticholinergics
It has been reported that tricyclic antidepressants can potentiate the effects
of catecholamines. Similarly, atropinelike effects may be more pronounced in
patients receiving anticholinergic therapy. Therefore, particular care should
be exercised when it is necessary to administer tricyclic antidepressants with
sympathomimetic amines, local decongestants, local anesthetics containing epinephrine,
atropine or drugs with an anticholinergic effect. In resistant cases of depression
in adults, a dose of 2.5 mg/kg/day may have to be exceeded. If a higher dose
is needed, ECG monitoring should be maintained during the initiation of therapy
and at appropriate intervals during stabilization of dose.
Drugs Metabolized by P450 2D6
The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6
(debrisoquin hydroxylase) is reduced in a subset of the caucasian population
(about 7-10% of caucasians are so called "poor metabolizers"); reliable estimates
of the prevalence of reduced P450 2D6 isozyme activity among Asian, African,
and other populations are not yet available. Poor metabolizers have higher than
expected plasma concentrations of 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 poor 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 enzyme (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 (SSRIs), 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 pharmacokinetics of the SSRI involved. Nevertheless, caution
is indicated in the co-administration of TCAs with any of the SSRIs 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.
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