In Section 4.4 (Special warnings and precautions for use) the following underlined text was added:
As improvement in depression may not occur for the first two to four weeks’ treatment, patients should be closely monitored during this period.
Hyponatraemia (usually in the elderly) has been associated with all types of antidepressants and should be considered in all patients who develop symptoms such as drowsiness, confusion or convulsions.
Suicide/suicidal thoughts or clinical worsening
Risk of suicide is inherent to severe depression and may persist until significant remission occurs. 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 posing a high suicide risk require close supervision. Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known 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 caregivers 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.
In section 4.5 (Interaction with other medicinal products and other forms of interaction) the following underlined text was added:
Beta-blockers: Blood concentrations of imipramine may be increased by drugs such as labetalol and propranolol. The clinical importance of these interactions is uncertain.
Diuretics: Concurrent use of a tricyclic and a diuretic may increase the risk of postural hypotension.
Alpha2-adrenoceptor stimulants: concomitant use of apraclonidine or brimonidine should be avoided.
Oestrogens: There is evidence that oestrogens can sometimes paradoxically reduce the effects of imipramine yet at the same time cause imipramine toxicity.
Antiviral agents: Drugs such as ritonavir have been reported to increase plasma concentrations of antidepressant drugs.
Calcium channel blockers: Blood levels of imipramine may be increased by calcium channel blockers such as diltiazem and verapamil.
Nitrates: Reduced salivary secretion may lessen the effectiveness of sub-lingual nitrate preparations.
Dopaminergic agents: CNS toxicity may be enhanced when tricyclic antidepressants are used in conjunction with dopaminergic drugs such as selegiline and entacapone.
Centrally acting appetite suppressants: Concomitant use is not recommended due to the increased risk of CNS toxicity.
Antineoplastic drugs: concomitant use of altretamine should be avoided due to the risk of severe postural hypotension.
Tricyclic antidepressants may also interact with the following drug classes:
Analgesics: Possible increase in risk of side effects (nefopam), convulsions (tramadol), sedation (opioid analgesics) or ventricular arrhythmias.
Anti-arrhythmics: Increased risk of ventricular arrhythmias with drugs, which prolong the QT interval.
Muscle relaxants: Enhanced muscle relaxant effect of baclofen
In Section 4.8 (Undesirable effects) the following underlined text was added:
Central Nervous System
Occasionally: fatigue, drowsiness, restlessness, delirium, confusion, disorientation and hallucination (particularly in geriatric patients and those suffering from Parkinson’s disease) increased anxiety, agitation, sleep disturbances, swings from depression to hypomania or mania.
Rarely: activation of psychotic symptoms
Isolated cases: aggressiveness
Paranoid delusion may be exacerbated during treatment with tricyclic
antidepressants. These are more frequently seen in elderly patients or
those on high doses.
Cases of suicidal ideation and suicidal behaviours
have been reported during Imipramine therapy or early after treatment
discontinuation (see section 4.4)
Frequently: sinus tachycardia and clinically irrelevant ECG changes (T and ST changes) in patients of normal cardiac status, postural hypotension are likely to occur with high dosage or in deliberate overdosage. They may also occur in patients with pre-existing heart disease taking normal dosage.
Occasionally: arrhythmias, conduction disorders (widening of QRS complex and PR interval, bundle-branch block), palpitations.
Isolated cases of increased blood pressure, cardiac decompensation, peripheral vasospastic reactions.
Occasionally: elevated transaminases
Rarely: impaired liver function
Isolated cases of hepatitis with or without jaundice
Endocrine System and Metabolism:
Frequently: weight gain
Occasionally: disturbances of libido, impotency or abnormal ejaculation.
Isolated cases of enlarged mammary glands, galactorrhoea, SIADH (syndrome of inappropriate antidiuretic hormone secretion), increase or decrease in blood sugar, weight loss.
Hyponatraemia, usually in the elderly, has been associated with all
types of antidepressants (see section 4.4).
Isolated cases of bone marrow depression including eosinophilia, leucopenia, agranulocytosis, thrombocytopenia and purpura have been reported. It is advisable to perform blood counts during treatment with
tritetracyclic antidepressants, especially if the patient develops fever,
sore throat or other signs of infection. (See section 4.4).
Occasional withdrawal symptoms following abrupt discontinuation of treatment: nausea, vomiting, abdominal pain, diarrhoea, insomnia, headache, nervousness, anxiety, irritability and excessive perspiration (see section 4.4). Contains 1.5g of sorbitol per 5ml spoonful so may cause stomach upset and diarrhoea, particularly at high doses.
Respiratory depression, agitation and withdrawal symptoms have been reported in neonates whose mothers received imipramine during the last trimester of pregnancy.
In section 10 (date of revision of the text) the date was changed to:
22nd March 2011