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IMIPRAMINE HCL 25MG

Active substance(s): IMIPRAMINE HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
PRAMINIL/Imipramine HCl 25 mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Imipramine HCl BP 25 mg

3

PHARMACEUTICAL FORM
Sugar-coated tablet

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the treatment of the symptoms of depressive illness and for the relief in
children of nocturnal enuresis.

4.2

Posology and method of administration
Adults:

Initially up to 75 mg per day in divided doses increased gradually to 150-200
mg (up to 300 mg in hospital patients). Up to 150 mg may be given as a
single dose at bedtime.

Elderly: Initially 10 mg a day, increased gradually to 30-50 mg daily. The initial dose
should be increased with caution under close supervision. A satisfactory
clinical response may be produced with half the normal maintenance dose.
Childre
n:

For nocturnal enuresis only.
7 years (weight 20-25 kgs or 44-45 lbs)
25 mg 30 minutes before bedtime.

8-11 years (weight 25-35 kgs or 55-77 lbs)
25-50 mg 30 minutes before bedtime.
Over 11 years (weight 35-54 kgs or 77-119 lbs)
50-75 mg 30 minutes before bedtime.
The maximum period of treatment should not exceed three months. A further
course of treatment should not be started until a full physical examination,
including an ECG, has been made.
Method of administration: Oral

4.3

Contraindications
Cardiac arrhythmias. Any degree of heart block. Recent myocardial
infarction. Severe liver disease. Mania. Children (including infants) under 7
years. During breast feeding.

4.4

Special warnings and precautions for use
If surgery is necessary the anaesthetist should be informed that the patient is being
treated with imipramine, since anaesthesia may increase the risk of hypotension and
arrhythmias.
Imipramine should be used with caution in patients with phaeochromocytoma, a
history of epilepsy, and in those with impaired liver function. Due to its atropine-like
action, it should be used with caution in patients with a history of urinary retention,
prostatic hypertrophy, narrow-angle glaucoma, or increased intra-ocular pressure.
Even average doses may precipitate an attack of glaucoma in patients with narrowangle glaucoma.
Patients with cardiovascular disorders, hyperthyroid patients and those receiving
thyroid medication or anticholinergic drugs should be closely monitored and the
dosage of all medications carefully adjusted.
Suicide/suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts, self harm and
suicide (suicide related events).This risk persists until significant remission occurs.
As improvement may not occur during the first few weeks or more of treatment,
patients should be closely monitored until such improvement occurs. It is general
clinical experience that the risk of suicide may increase in the early stages of
recovery.
Patients with a history of suicide-related events, or those exhibiting a significant
degree of suicidal ideation prior to commencement of treatment are know to be at
greater risk of suicidal thoughts or suicide attempts and should receive careful
monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of
antidepressant drugs in adult patients with psychiatric disorders showed an increased

risk of suicidal behaviour with antidepressants compared to placebo in patients less
than 25 years old.
Close supervision of patients and in particular those at high risk should accompany
drug therapy, especially in early treatment and following dose changes. Patients (and
caregoivers of patients) should be alerted about the need to monitor for any clinical
worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to
seek medical advice immediately if these symptoms present.
When used for the depressive component of schizophrenia, imipramine may
aggravate psychotic symptoms. In manic-depressives, a shift towards the manic phase
may occur. Paranoid delusions, with or without associated hostility, may be
aggravated. A major tranquilliser should be given concurrently in such cases, or
dosage of imipramine reduced.
Concurrent administration with ECT may increase the hazards of treatment, and
should be limited to patients for whom it is deemed essential.
The elderly are particularly prone to experience adverse reaction, especially agitation,
confusion and postural hypotension.
Abrupt withdrawal should be avoided because of possible adverse reactions (see
Undesirable Effects section).
Behavioural changes may present in children receiving Imipramine for the treatment
of nocturnal enuresis.

4.5

Interaction with other medicinal products and other forms of interaction
MAO Inhibitors: The concurrent use of antidepressants having various
mechanisms of action should be undertaken only with due recognition of their
possible potentiation and with a thorough knowledge of their pharmacology.
Monoamine oxidase inhibitors can potentiate the effects of tricyclic
antidepressants such as imipramine and hyperpyretic crises, severe
convulsions and fatalities have occurred. A minimum of 3 weeks should
elapse between discontinuing an MAOI and starting imipramine, which should
be introduced cautiously and dosage increased gradually. Fluoxetine
markedly inhibits Cyt P450 II D6, which is involved in the metabolism of a
number of tricyclic antidepressants. Patients should be monitored for
increased antidepressant plasma levels and toxicity when Fluoxetine is used
concurrently. Adjustment of the antidepressant dosage may be necessary.
Antipsychotics: There is an increased risk of ventricular arrhythmias – avoid
concomitant use with pimozide. Increased plasma concentration and increased
anti-muscarinic side-effects with phenothiazines.
Antihypertensives: Imipramine may block the antihypertensive action of
guanethidine, debrisoquine, bethanidine and possibly clonidine. All
antihypertensive therapy should be reviewed during treatment with tricyclic
antidepressants.

Anti-arrhythmics: There is an increased risk of ventricular arrhythmias with
drugs that prolong the QT interval including amiodarone, disopyramide,
procainamide, propafenone and quinidine. The plasma concentration of
tricyclics is increased by dilitiazem and verapamil. The risk of ventricular
arrhythmias associated increased with beta-blockers (sotolol).
Sympathomimetics: Imipramine should not be given with sympathomimetic
agents such as adrenaline, ephedrine, isoprenaline, noradrenaline,
phenylephrine and phenylpropanolamine, due to enhanced pressor response to
these agents.
CNS depressants: Imipramine may enhance the response to alcohol,
barbiturates and other CNS depressants.
Antimuscarinics: Excessive anticholinergic effects may occur when tricyclic
antidepressants are combined with anticholinergic drugs. Paralytic ileus,
urinary retention or acute glaucoma may be precipitated, especially in elderly
patients. Increased antimuscarinic and sedative effects with antihistamines.
Avoid concomitant use with terfenadine due to increased risk of ventricular
arrythmias.
Ulcer-healing drugs: Cimetidine is reported to reduce hepatic metabolism of
certain tricyclic antidepressants.
Oral contraceptives: Oral contraceptives antagonise the antidepressant
effects of imipramine and side-effects may be increased due to the increased
plasma concentration of imipramine.
Others: Disulfiram inhibits the metabolism of tricyclics. The plasma
concentration of some tricyclics is reduced by rifampicin and antiepileptics.
There is an increased risk of postural hypotension with diuretics and
altretamine. The muscle relaxant effects of baclofen are enhanced. Possible
increased side-effects with concomitant use of some analgesics such as
nefopam, tramadol and opioid analgesics. Barbiturates and carbamazepine
may decrease, and methylphenidate may increase, the antidepressant action of
imipramine.
Avoid concomitant use with the following: The dopaminergics entacapone and
possibly selegiline, levothyroxine and levacetylmethadol.

4.6

Pregnancy and lactation
Do not use during pregnancy, particularly during the first and last trimester
unless clinically imperative. Safety in pregnancy has not been proven.
Imipramine is detectable in breast milk. It should be avoided while breastfeeding due to the potential for serious adverse reactions in the infant.

4.7

Effects on ability to drive and use machines
Patients should be warned of the possible hazard of driving or operating
machinery because Imipramine may impair alertness.

4.8

Undesirable effects
The side effects stated below include those of the tricyclic group of antidepressants in
general. Not all of them have been reported with imipramine, but are included due to
similar pharmacology of the group members.
As the antidepressant effects of imipramine may not become apparent for the first 2-4
weeks of therapy, patients should be closely monitored during this period.
Cases of suicidal ideation and suicidal behaviours have been reported during tricyclic
antidepressant therapy or soon after treatment discontinuation (see section 4.4).
Cardiovascular: Postural hypotension, hypertension, palpitations, tachycardia,
myocardial infarction, heart block and stroke. Arrhythmias and severe hypotension
are likely to occur with high doses or overdosage.
CNS and Neuromuscular: Disturbed concentration, disorientation, confusional
states, insomnia, nightmares, delusions, hallucinations, hypomania, excitement,
anxiety, restlessness, peripheral neuropathy, numbness, tingling and paraesthesia of
the extremities, inco-ordination, ataxia, tremors, convulsions, altered ECG, extrapyramidal symptoms and tinnitus.
Anticholinergic: Blurred vision, accommodation disturbance, increased intra-ocular
pressure, mydriasis, constipation, paralytic ileus, urinary retention, urinary tract
dilatation, hyperpyrexia and dry mouth.
Allergic: Skin rash, urticaria, photosensitisation, oedema of face and tongue.
Haematological: Bone marrow depression including agranulocytosis, eosinophilia,
leucopenia, thrombocytopenia and purpura.
Gastro-intestinal: Nausea, vomiting, diarrhoea, epigastric distress, anorexia,
dysgeusia, stomatitis, parotid swelling, black tongue, rarely hepatitis (including
altered liver function and jaundice).

Endocrine: Gynaecomastia, breast enlargement, galactorrhoea, testicular swelling,
changes in libido, interference with sexual function, elevation or lowering of blood
sugar levels, syndrome of inappropriate ADH secretion.
Musculoskeletal and Connective Tissue Disorders: Epidemiological studies,
mainly conducted in patients 50 years of age and older, show an increased risk of
bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this
risk is unknown.
Other reactions: Weakness, fatigue, headache, increased perspiration, urinary
frequency, alopecia, and drowsiness. Increased appetite and weight gain may be a
drug reaction or due to relief of depression. Abrupt withdrawal after prolonged
administration has caused nausea, headache and malaise.
Gradual withdrawal of imipramine has been associated with transient symptoms such
as irritability, restlessness, and dream and sleep disturbances during the first two
weeks of dosage reduction. These are not thought to be signs associated with
addiction.
Mania or hypomania have been reported rarely within 2-7 days of stopping therapy
with tricyclic antidepressants.
Side-effects in enuresis: As dosages used in enuresis are low compared with those
used for depression, side-effects are less frequent. The most common are drowsiness
and anticholinergic effects. Infrequently, mild sweating and itching have been
reported. Behavioural changes have been observed in children receiving tricyclics for
treatment of enuresis.
The recommended dosage must not be exceeded.

4.9

Overdose
Emergency treatment includes gastric lavage; intubation and ventilation.
Intravenous diazepam should be given to control convulsion.
Serious overdose requires continuous cardiac monitoring for at least 2 days.
Dysrrhythmias should be treated on an individual basis.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Imipramine prevents the re-uptake of noradrenaline and serotonin at nerve
terminals. The antidepressant response of the drug may take up to a month
after ingestion.

5.2

Pharmacokinetic properties
Imipramine is absorbed from the gastro-intestinal tract and demethylated by
first-pass metabolism in the liver to its active metabolite desipramine.
Imipramine is excreted in the urine, mainly in the form of its metabolites
either free or in conjugated form.
Imipramine and desipramine are widely distributed in the body and
extensively bound to plasma and tissue protein. Imipramine has a half-life
from between 8-19 hours and this may be considerably extended in
overdosage.
Imipramine and desipramine cross the blood-brain barrier and placental barrier
and are excreted in breast milk.

5.3

Preclinical safety data
Not applicable

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Lactose, maize starch, pregelatinised maize starch, colloidal anhydrous silica,
magnesium stearate. Bleached shellac, talc, titanium dioxide (E171), PVP 25
cps, sucrose, Opalux AS-F-9232 (E124, E172), beeswax, carnauba wax.

6.2

Incompatibilities
None stated.

6.3

Shelf life
36 months.

6.4

Special precautions for storage
Store below 25°C in a dry place in well closed containers.

6.5

Nature and contents of container
High density polystyrene with polythene lids and/or polypropylene containers
with polypropylene or polythene lids and polyurethane/polythene inserts.
Pack sizes: 100 and 500.

6.6

Special precautions for disposal
Not applicable.

7

MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited
11 Boumpoulinas Street,
3rd floor, 1060 Nicosia
Cyprus

8

MARKETING AUTHORISATION NUMBER(S)
PL 33414/0053

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION

10

DATE OF REVISION OF THE TEXT
20/09/2010

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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