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
Norpramin Side Effects, and Drug Interactions - Desipramine
Norpramin Side Effects, and Drug Interactions - Desipramine
SIDE EFFECTS
Note: Included in the following listing are a few adverse
reactions that have not been reported with this specific
drug. However, the pharmacologic similarities among the tricyclic
antidepressant
drugs require that each of the reactions be considered when desipramine
hydrochloride
is given.
Cardiovascular: hypotension,
hypertension, palpitations,
heart block, myocardial
infarction, stroke, arrhythmias, premature
ventricular contractions, tachycardia,
ventricular tachycardia,
ventricular fibrillation,
sudden death.
There has been a report
of an “acute collapse” and “sudden death” In an eight-year old (18
kg) male, treated for two years for hyperactivity. There have been
additional reports of sudden death
in children (See WARNINGS:
Use in Children).
Psychiatric: confusional states (especially in the
elderly) with hallucinations, disorientation, delusions; anxiety,
restlessness, agitation; insomnia
and nightmares; hypomania; exacerbation
of psychosis.
Neurologic: numbness, tingling, paresthesias of extremities;
incoordination, ataxia,
tremors: peripheral
neuropathy; extrapyramidal symptoms; seizures; alteration in EEG
patterns; tinnitus.
Anticholinergic: dry mouth,
and rarely associated sublingual adenitis; blurred vision, disturbance
of accommodation, mydriasis,
increased intraocular pressure; constipation,
paralytic ileus; urinary
retention, delayed micturition,
dilatation of urinary
tract.
Allergic: skin
rash, petechiae,
urticaria, itching,
photosensitization (avoid excessive exposure
to sunlight), edema (of
face and tongue
or general), drug fever,
cross sensitivity
with other tricyclic drugs.
Hematologic: Bone marrow
depressions including agranulocytosis, eosinophilia, purpura,
thrombocytopenia.
Gastrointestinal: anorexia,
nausea and vomiting,
epigastric distress, peculiar taste, abdominal
cramps, diarrhea, stomatitis,
black tongue, hepatitis,
jaundice (simulating
obstructive), altered liver
function, elevated liver
function tests, increased
pancreatic enzymes.
Endocrine: gynecomastia
in the male, breast enlargement
and galactorrhea
in the female; increased or decreased libido,
impotence, painful ejaculation,
testicular swelling;
elevation or depression
of blood sugar levels; syndrome
of inappropriate antidiuretic
hormone secretion (SIADH).
Other: weight
gain or loss; perspiration,
flushing; urinary frequency, nocturia; parotid
swelling; drowsiness,
dizziness, weakness
and fatigue, headache;
fever; alopecia; elevated alkaline
phosphatase.
Withdrawal Symptoms
Though not indicative of addiction,
abrupt cessation of treatment
after prolonged therapy
may produce nausea, headache,
and malaise.
DRUG INTERACTIONS
1. 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 to 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 traction
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 enzyme (quinidine; cimetidine) and
many that are substrates for P450 2D6 (many other antidepressants,
phenothiazines, and the Type 1C antiarrhythrnics propatenone and
flecainide). While all the selective serotonin
reuptake inhibitors (SSRIs), e.g., fluoxetine, seriraline, 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 T.A.
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.
2. Close supervision and careful adjustment
of dosage are required
when this drug is given
concomitantly with anticholinergic
or sympathomimetic drugs.
3. Clinical experience
in the concurrent administration
of ECT and antidepressant
drugs is limited. Thus, if such
treatment is essential,
the possibility of increased risk
relative to benefits should be considered.
4. If desipramine hydrochloride
is to be combined with other psychotropic agents such
as tranquilizers or sedative/hypnotics, careful consideration should
be given to the pharmacology
of the agents employed since the sedative
effects of desipramine and benzodiazepines (e.g., chlordiazepoxide
or diazepam) are additive. Both the sedative
and anticholinergic
effects of the major tranquilizers are also additive
to those of desipramine.
5. Concurrent administration
of cimetidine and
tricyclic antidepressants can produce clinically significant
increases in the plasma
levels of the tricyclic antidepressants. (See CLINICAL
PHARMACOLOGY: Metabolism) Conversely, decreases in
plasma levels of the tricyclic antidepressants have been reported
upon discontinuation of cimetidine
which may result in the loss
of the therapeutic
efficacy of the tricyclic antidepressant
6. There have been greater than two-fold increases of previously
stable plasma levels
of tricyclic antidepressants when fluoxetine has been administered
in combination with these agents.
top
