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
Tofranil Side Effects, and Drug Interactions - Imipramine
Tofranil Side Effects, and Drug Interactions - Imipramine
SIDE EFFECTS
Note: Although the listing which follows includes a few
adverse reactions which have not been reported with this specific
drug, the pharmacological
similarities among the tricyclic antidepressant
drugs require that each of the reactions be considered when imipramine
is administered.
Cardiovascular: Orthostatic hypotension,
hypertension, tachycardia, palpitation,
myocardial infarction,
arrhythmias, heart block,
ECG changes, precipitation
of congestive heart failure,
stroke.
Psychiatric: Confusional states (especially in 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.
Anticholinergic: Dr.
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, urticania,
itching, photosensitization (avoid excessive exposure
to sunlight); edema (general
or of face and tongue);
drug fever; cross-sensitivity with desipramine.
Hematologic: Bone marrow
depression including
agranulocytosis; eosinophilia; purpura; thrombocytopenia.
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; syndrome of inappropriate ADH
(antidiuretic hormone) secretion.
Other: Jaundice (simulating obstructive); altered
liver function; weight
gain or loss; perspiration;
flushing; urinary frequency;
drowsiness; dizziness,
weakness and fatigue;
headache; parotid swelling;
alopecia; proneness to falling.
Withdrawal Symptoms: Though not indicative of addiction,
abrupt cessation of treatment
after prolonged therapy
may produce nausea, headache and malaise.
Note: In enuretic
children treated with imipramine hydrochloride the most common adverse
reactions have been nervousness, sleep
disorders, tiredness and mild gastrointestinal
disturbances. These usually disappear during continued drug
administration
or when dosage is decreased.
Other reactions which have been reported include constipation,
convulsions, anxiety, emotional instability, syncope
and collapse. All of the adverse effects reported with adult
uses should be considered.
DRUG INTERACTIONS
In occasional susceptible
patients or in those receiving anticholinergic drugs (including
antiparkinsonism agents) in addition, the atropine-like effects
may become more pronounced (e.g., paralytic
ileus).
Close supervision and careful adjustment
of dosage is required
when this drug is administered
concomitantly with anticholinergic
drugs.
Avoid the use of preparations such
as decongestants and local
anesthetics which contain any sympathomimetic
amine (e.g., epinephrine,
norepinephrine), since it has been reported that tricyclic antidepressants
can potentiate the effects of catecholamines.
Caution should be exercised when imipramine hydrochloride
is used with agents that lower blood
pressure. Imipramine hydrochloride
may potentiate the effects of CNS
depressant drugs.
The plasma concentration
of imipramine may increase when the drug
is given concomitantly with hepatic
enzyme inhibitors (e.g.,
cimetidine, fluoxetine) and decrease by concomitant
administration
of hepatic enzyme
inducers (e.g., barbiturates, phenytoin), and adjustment
of the dosage of imipramine
may therefore be necessary.
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 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 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 TCA5 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 cotherapy, 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.
top
