Imipramine 25mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Imipramine 25mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each Tablet contains 25mg Imipramine Hydrochloride For full list of excipients, see 6.1.
3 PHARMACEUTICAL FORM
Coated Tablet
Red-brown, circular, sugar-coated tablets
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
i) Treatment of Symptoms of depressive illness.
ii) Relief of nocturnal enuresis in children.
4.2 Posology and method of administration
Adults: 25 mg up to three times daily, increasing stepwise to 150-200 mg. This should be reached by the end of the first week and maintained until definite improvement has occurred. The subsequent maintenance dose should be individually determined by gradually reducing the dosage, usually to about 50-100 mg daily.
In patients in hospital, i.e. severe cases, the dose may be increased to 100 mg three times daily until a distinct improvement is seen. Again the subsequent maintenance dose should be determined individually by reducing the dosage, usually to about 100 mg daily.
Elderly: Patients over 60 years of age may respond to lower doses of imipramine than the dose recommended. Treatment should be initiated with 10mg daily and gradually, increasing to 30-50 mg daily. The optimum dose should be reached after about 10 days and then continued until the end of treatment.
Children (for nocturnal enuresis only): Imipramine tablets are not for use in children under 6 years.
6-7 years (weight 20-25kg or 44-55 lbs): 25 mg daily.
8-11 years (weight 25-35kg or 55-77 lbs): 25-50 mg daily.
Over 11 years (weight 35-54kg or 77-119 lbs): 50-75 mg daily.
A daily dosage of 2.5 mg/kg should not be exceeded in children. The dose should be taken just before bedtime. The maximum period of treatment should not exceed three months and withdrawal should be gradual. Should a relapse occur, a further course of treatment should not be started until a full physical examination has been made.
Method of administration:
For oral administration.
4.3 Contraindications
Known hypersensitivity to imipramine, any of the excipients or cross-sensitivity to other tricyclic antidepressants of the dibenzazepine group. Recent myocardial infarction. Any degree of heart block or other cardiac arrhythmias, porphyria, mania, severe liver disease, narrow angle glaucoma. Infants and children under 6 years. Retention of urine. Concurrent use in patients receiving, or within 3 weeks of cessation of therapy with, monoamine oxidase inhibitors. Concomitant treatment with selective, reversible MAO-A inhibitors such as moclobemide, is also contra-indicated.
4.4 Special warnings and precautions for use
Warnings: As improvement in depression may not occur during the first two to four weeks of treatment, and hence 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.
Precautions: As Tricyclic antidepressants are known to lower the convulsion threshold and imipramine should therefore be used with extreme caution in patients with epilepsy and other predisposing factors, e.g. brain damage of varying aetiology, concomitant use of neuroleptics, and withdrawal from alcohol or drugs with anticonvulsive properties (e.g. benzodiazepines). It appears that the occurrence of seizures is dose dependent.
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 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.
Concomitant treatment of imipramine and electroconvulsive therapy should only be resorted to under careful supervision.
Caution is called for when giving tricyclic antidepressants to patients with severe renal disease.
Caution is called for when giving tricyclic antidepressants to patients with tumours of the adrenal medulla (e.g. phaeochromocytoma, neuroblastoma), in whom they may provoke hypertensive crises.
Many patients with panic disorders experience intensified anxiety symptoms at the start of the treatment with antidepressants. This paradoxical initial increase in anxiety is most pronounced during the first few days of treatment and generally subsides within two weeks.
Caution is indicated in patients with hyperthyroidism or during concomitant treatment with thyroid preparations, since aggravation of unwanted cardiac effects may occur.
Before initiating treatment it is advisable to check the patient's blood pressure, because individuals with hypotension or a labile circulation may react to the drug with a fall in blood pressure.
Although changes in the white blood cell count have been reported with imipramine only in isolated cases, periodic blood cell counts and monitoring for symptoms such as fever and sore throat are called for, particularly during the first few months of therapy (see section 4.8).
Periodic monitoring of hepatic enzyme levels is recommended in patients with liver disease.
In elderly patients monitoring of cardiac function is indicated.
Because of its anticholinergic properties, imipramine should be used with caution in patients with a history of increased intra-ocular pressure, narrow angle glaucoma, or urinary retention (e.g. diseases of the prostate).
Caution is called for in patients with chronic constipation. Tricyclic antidepressants may cause paralytic ileus, particularly in the elderly and bedridden patients.
Before general or local anaesthesia, the anaesthetist should be aware that the patient has been receiving imipramine. Anaesthetics given during tri/tetracyclic antidepressant therapy may increase the risk of arrhythmias and hypotension (see interactions section 4.5).
An increase in dental caries has been reported during long-term treatment with tricyclic antidepressants. Regular dental check-ups are therefore advisable during long-term treatment.
Decreased lacrimation and accumulation of mucoid secretions due to the anticholinergic properties of tricyclic antidepressants may cause damage to the corneal epithelium in patients with contact lenses.
Imipramine may cause anxiety, feelings of unrest, and hyperexcitation in agitated patients and patients with accompanying schizophrenic symptoms.
Activation of psychosis has occasionally been observed in schizophrenic patients receiving tricyclic antidepressants. Hypomanic or manic episodes have also been reported during a depressive phase in patients with cyclic affective disorders receiving treatment with a tricyclic antidepressant. In such cases it may be necessary to reduce the dosage of imipramine or to withdraw it and administer an antipsychotic agent. After such episodes have subsided, low dose therapy with imipramine may be resumed if required.
In predisposed and elderly patients, imipramine may, particularly at night, provoke pharmacogenic (delirious) psychoses, which disappear without treatment within a few days of withdrawing the drug. Agitation, confusion and postural hypotension may occur.
Abrupt withdrawal should be avoided because of possible adverse reactions (see side effects section 4.8).
Behavioural changes may occur in children receiving imipramine for treatment of nocturnal enuresis.
4.5 Interaction with other medicinal products and other forms of interaction
MAO inhibitors: Do not give imipramine for at least 3 weeks after discontinuation of treatment with MAO inhibitors (there is a risk of severe symptoms such as hypertensive crisis, hyperpyrexia, myoclonus, agitation, seizures, delirium and coma). The same applies when giving a MAO inhibitor after previous treatment with imipramine. In both instances imipramine or the MAO inhibitor should initially be given in small, gradually increasing doses and its effects monitored. There is evidence to suggest that tricyclic antidepressants may be given as little as 24 hours after a reversible MAO inhibitor such as moclobemide, but the 3 week wash-out period must be observed if the MAO inhibitor is given after a tricyclic antidepressant has been used.
Selective serotonin reuptake inhibitors (SSRI): Co-medication may lead to additive effects on the serotonergic system. Fluoxetine and fluvoxamine may also increase plasma concentrations of imipramine, with corresponding adverse effects, resulting in increased plasma levels of tricyclic antidepressants, a lowered convulsion threshold and seizures.
CNS depressants: Tricyclic antidepressants may also increase the CNS depressant effect of alcohol and central depressant drugs (e.g. barbiturates, benzodiazepines or general anaesthetics) (see section 4.4).
Alprazolam and disulfiram: It may be necessary to reduce the dosage of imipramine if it is administered concomitantly with alprazolam or disulfiram.
Neuroleptics: Co-medication may result in increased plasma levels of tricyclic antidepressants, a lowered convulsion threshold and seizures. Combination with thioridazine may produce severe cardiac arrhythmias.
Adrenergic neurone blockers: Imipramine may diminish or abolish the antihypertensive effects of guanethidine, debrisoquine, betanidine, reserpine, clonidine and alphamethyldopa. Patients requiring co-medication for hypertension should therefore be given antihypertensives of a different type (e.g. diuretics, vasodilators, or betablockers).
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 antidepressant and a diuretic may increase the risk of postural hypotension.
Alpha2-adrenoceptor stimulants: concomitant use of apraclonidine or brimonidine should be avoided.
Anticoagulants: Tricyclic antidepressants may potentiate the anti-coagulant effect of coumarin drugs by inhibiting hepatic metabolism of these anticoagulants. Careful monitoring of plasma prothrombin is therefore advised.
Anticholinergic agents: Tricyclic antidepressants may potentiate the effects of these drugs (e.g. phenothiazine, antiparkinsonian agents, antihistamines, atropine, biperiden) on the eye, central nervous system, bowel and bladder.
Sympathomimetic drugs: Imipramine may potentiate the cardiovascular effects of adrenaline (epinephrine), ephedrine, isoprenaline, noradrenaline (norepinephrine), phenylephrine and phenylpropanolamine (e.g. as contained in local anaesthetic preparations and nasal decongestants).
Quinidine: Tricyclic antidepressants should not be employed in combination with anti-arrhythmic agents of the quinidine type.
Liver enzyme inducers: Drugs which activate the hepatic mono-oxygenase enzyme system (e.g. barbiturates, carbamazepine, phenytoin, nicotine, and oral contraceptives) may accelerate the metabolism and lower plasma concentrations of imipramine, resulting in decreased efficacy. Plasma levels of phenytoin and carbamazepine may increase, with corresponding adverse effects. It may be necessary to adjust the dosage of these drugs.
Cimetidine, methylphenidate: These drugs may increase the plasma concentrations of imipramine (tricyclic antidepressants), whose dosage should therefore be reduced.
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.
4.6 Pregnancy and lactation
Do not use during pregnancy especially during the first and last trimesters unless there are compelling reasons. There is no, or inadequate evidence, of safety of the drug in human pregnancy; there is evidence of harmful effects in pregnancy in animals when given in exceptionally high doses. There have been isolated reports of a possible connection between the use of tricyclic antidepressants and adverse effects (developmental disorders) on the foetus. Treatment with imipramine should be avoided during pregnancy, unless the anticipated benefits justify the potential risk to the foetus.
Neonates whose mothers had taken imipramine up until delivery have developed dyspnoea, lethargy, colic, irritability, hypotension or hypertension, tremor or spasms, during the first few hours or days.
Imipramine should if possible be gradually withdrawn at least 7 weeks before the calculated date of confinement. Imipramine is excreted in breast milk. Do not use during lactation unless considered essential; in this case nursing mothers should be advised to cease breast feeding.
4.7 Effects on ability to drive and use machines
Patients receiving imipramine should be warned that blurred vision, drowsiness and other CNS symptoms (see side effects section 4.8) may occur, in which case they should not drive, operate machinery, or do anything which may require alertness or quick actions. Patients should also be warned that alcohol or other drugs may potentiate these effects (see interactions section 4.5).
4.8 Undesirable effects
The following side effects, although not necessarily observed with imipramine, have occurred with tricyclic antidepressants.
(The following frequency estimates are used: frequent > 10%, occasional >1-10%, rare >0.001-1%, isolated cases < 0.001%)
If severe neurological or psychiatric reactions occur, imipramine should be withdrawn.
Elderly patients are particularly sensitive to anticholinergic, neurological, psychiatric, or cardiovascular effects. Their ability to metabolise and eliminate drugs may be reduced, leading to a risk of elevated plasma concentrations at therapeutic doses.
Effect on the Central nervous system:
Psychiatric effects: Occasionally fatigue, drowsiness, restlessness, delirium, confusion, disorientation and hallucinations (particularly in geriatric patients and those suffering from Parkinson’s disease), increased anxiety, agitation, sleep disturbances, swings from depression to hypomania or mania have been reported occasionally.
Rare: activation of psychotic symptoms. In isolated cases aggressiveness has been reported.
Paranoid delusion may be exacerbated during treatment with tricyclic antidepressants. These are more frequently seen in elderly patients or those on high doses.
Frequency not known: cases of suicidal ideation and suicidal behaviours have been reported during imipramine therapy or early after treatment discontinuation (see section 4.4).
Neurological effects: Frequently tremor has been reported. Occasionally: paraesthesiae, headache, dizziness has been reported. Rarely, epileptic seizures has been reported. In isolated cases of EEG changes, myoclonus, weakness, extrapyramidal symptoms, ataxia, speech disorders, drug fever has been reported.
Effects on the Cardiovascular system: Frequently sinus tachycardia and clinically irrelevant ECG changes (T and ST changes) in patients of normal cardiac status, postural hypotension have been reported. Cardiac arrhythmias and severe 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 have been reported. Isolated cases of increased blood pressure, cardiac decompensation, peripheral vasospastic reactions have been reported.
Anticholinergic effects: Frequently: dry mouth, sweating, constipation, disorders of visual accommodation, blurred vision, hot flushes have been reported. Occasionally: disturbances of micturition have been reported. Isolated cases of mydriasis, glaucoma, paralytic ileus have been reported.
Effects on the Gastro-intestinal tract: Occasionally nausea, vomiting, anorexia have been reported. Isolated cases of stomatitis, tongue lesions, abdominal disorders have been reported.
Hepatic effects: Occasionally: elevated transaminases have been reported. Isolated cases of hepatitis with or without jaundice has been reported.
Impaired liver function has been reported.
Effects on the Skin: Occasionally: allergic skin reactions ( such as skin rash, urticaria) have been reported. Isolated cases of oedema (local or generalised), photosensitivity, pruritus, petechiae, hair loss have been reported.
Effects on the Endocrine system and metabolism: Frequently weight gain has been reported. Occasionally disturbances of libido and potency have been reported. Isolated cases of enlarged mammary glands, galactorrhoea, SIADH (syndrome of inappropriate antidiuretic hormone secretion), increase or decrease in blood sugar, weight loss have been reported.
Hyponatraemia, usually in the elderly, has been associated with all types of antidepressants (see section 4.4).
Hypersensitivity: Isolated cases of allergic alveolitis (pneumonitis) with or without eosinophilia, systemic anaphylactic/anaphylactoid reactions including hypotension have been reported.
Effects on the Blood: Isolated cases of agranulocytosis, bone marrow depression including leucopenia, eosinophilia, 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)
Effects on the Sense organs: Tinnitus has been reported.
Miscellaneous effects: Although not indicative of addiction, Occasional withdrawal symptoms may occur on the following abrupt discontinuation of treatment and include: nausea, vomiting, abdominal pain, diarrhoea, insomnia, headache, nervousness and anxiety irritability and excessive perspiration (see section 4.4).
Respiratory depression, agitation and withdrawal symptoms have been reported in neonates whose mothers received imipramine during the last trimester of pregnancy.
Class effects
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.
4.9 Overdose
The signs and symptoms of overdose with imipramine are similar to those reported with other tricyclic antidepressants. Cardiac abnormalities and neurological disturbances are the main complications. In children accidental ingestion of any amount should be regarded as serious and potentially fatal.
Signs and symptoms: Symptoms generally appear within 4 hours of ingestion and reach a maximum severity after 24 hours. Owing to delayed absorption (increased anticholinergic effect due to overdose), long half-life and enterohepatic recycling of the drug, the patient may be at risk for up to 4-6 days.
The following major symptoms of overdose may be encountered:
Effects on the Central nervous system: drowsiness, stupor, coma, ataxia, restlessness, agitation, enhanced reflexes, muscular rigidity, athetoid and choreiform movements, convulsions.
Effects on the Cardiovascular system: Hypotension, tachycardia, arrhythmia, conduction disorders, heart failure; in very rare cases, cardiac arrest. In addition, respiratory depression, cyanosis, shock, vomiting, fever, hydriasis, sweating and oliguria or anuria may occur.
Treatment: There is no specific antidote and treatment is essentially symptomatic and supportive.
Anyone suspected of receiving an overdose of imipramine, particularly children, should be nursed in an intensive care unit admitted to hospital and kept under close surveillance for at least 72 hours where full support of vital functions is possible.
Perform gastric lavage or induce vomiting as soon as possible if the patient is fully conscious. If the patient has impaired consciousness to reduce absorption of the drug, secure the airway with a cuffed endotracheal tube before beginning lavage, and do not induce vomiting. These measures are recommended for up to 12 hours or even longer after the overdose, since the anticholinergic effect of the drug may delay gastric emptying. Administration of activated charcoal may help reduce drug absorption.
Treatment of symptoms is based on modern methods of intensive care, with continuous monitoring of cardiac function, blood gases and electrolytes, and if necessary emergency measures such as:
- anticonvulsive therapy,
- artificial respiration,
- insertion of a temporary cardiac pacemaker,
- plasma expander, dopamine or dobutamine administered by intravenous drip,
- resuscitation.
Any serious overdosage requires continuous cardiac monitoring for at least 48 hours and dysrhythmias must be treated on an individual basis. Respiratory insufficiency may necessitate intubation and ventilation, and convulsions may be controlled with intravenous diazepam.
Since it has been reported that physostigmine may cause severe bradycardia, asystole and seizures, its use is not recommended in cases of overdosage with imipramine. Haemodialysis or peritoneal dialyses are ineffective because of the low plasma concentrations of imipramine.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group
Tricyclic antidepressant. Noradrenaline (NA) and serotonin (5HT) re-uptake inhibitor.
Mechanism of action
Imipramine is a tricyclic antidepressants and has several pharmacological actions including alpha-adrenolytic, antihistamine, anticholinergic and 5HT-receptor blocking properties. However, the main therapeutic activity is believed to be inhibition of the neuronal re-uptake of noradrenaline and 5HT. Imipramine is a so-called “mixed” reuptake blocker, i.e. it inhibits the reuptake of NA and 5HT to about the same extent. If a dose of 100mg of imipramine is given to a normal subject, he feels sleepy and tends to be quieter, his blood pressure falls slightly, and he feels light-headed. Often unpleasant anticholinergic effects (dry mouth and blurred vision) appear. There is little, if any, change in pupillary size. Gait may become unsteady, and the subject feels tired and clumsy. These drug effects are usually perceived as unpleasant, and may cause a feeling of “unhappiness” and an increase in anxiety. There may be a deterioration in tests of performance. These acute drug effects thus resemble those seen with certain phenothiazines. Repeated administration for several days may lead to accentuation of these symptoms and, in addition, to difficulty in concentrating and thinking, comparable to that experienced during the course of similar treatment with chlorpromazine. Imipramine seems to produce greater impairment of cognitive and affective processes and lesser reduction in physical movements than does chlorpromazine. In contrast, if the drug is given over a period of time to depressed patients, an elevation of mood occurs. About two or three weeks must pass before the therapeutic effects of the drug are evident. For this reason, the tricyclic antidepressants are not prescribed on an “as-needed” basis. The manner in which imipramine relieves the signs and symptoms of depression is not clear.
Its effect has been described as a dulling of depressive ideation rather than as euphoric stimulation. However, reports of manic excitement as well as euphoria and insomnia indicate that imipramine (and indeed, virtually all effective antidepressant treatments) does have stimulant-like actions under certain circumstances.
5.2 Pharmacokinetic properties
Imipramine and other tricyclic antidepressants are fairly well absorbed after oral administration. While they are usually initially used in divided doses, their relatively long half-lives and rather wide range of tolerated concentration permit a gradual transition toward a single daily dose given at bedtime. This is most safely done for doses up to the equivalent of 150mg of imipramine. High doses of these strongly anticholinergic agents can slow gastrointestinal activity and gastric emptying time, resulting in slower or erratic absorption of these and other drugs taken concomitantly; this can complicate the management of acute overdosage. Concentrations in plasma typically peak within two to eight hours, but this can be delayed for over twelve hours. Once absorbed, these lipophilic drugs are widely distributed; their pharmacokinetic properties are similar to those of the phenothiazines. They are strongly bound to plasma proteins and to constituents of tissues. The latter fact accounts for their large volumes of apparent distribution, which are typically 10 to 50 litres per kilogram. The concentrations of these drugs in plasma that have been suggested to correlate best with satisfactory antidepressant responses range between 50 and 300ng/ml or, most narrowly, between 100 and 200ng/ml. Toxic effects of these drugs can be expected when their concentrations in plasma rise above 1pg/ml and can occur at even half this value.
The tricyclic antidepressants are oxidised by hepatic microsomal enzymes, followed by conjugation with glucuronic acid. The major route of metabolism of imipramine is to the active drug desimipramine; inactivation of either compound occurs largely by oxidation to 2-hydroxy metabolites (which retain some ability to block the uptake of amines) and conjugation with glucuronic acid, in contrast, amitriptyline (while mainly demethylated to nortriptyline) and nortriptyline undergo preferential oxidation at the 10 position, followed by glucuronidation; the 10-hydroxy metabolites may have some biological activity. While the demethylated metabolites of imipramine and amitriptyline possess antidepressant activity, it is not known to what extent they account for the activity of the parent drugs. These demethylated products can accumulate in concentrations approaching, or even succeeding, those of their precursors. Doxepin also appears to be converted to an active metabolite nordoxepin, by N-demethylation (Ziegler et al 1978). There is relatively little published information on the metabolism of the newer antidepressants in man. Amoxapine is primarily converted to the active 8-hydroxy metabolite. In rats, trazodant is cleaved to form m-chlorophenylpiperazine, a substance with tryptaminergic agonist and antagonist properties similar to those of the parent compound. In man, neither the extent of formation nor the biological activity of this metabolite is known. There is marked variation among subjects (up to 50 fold) in the ratio of methylated to demethylated molecules following administration of imipramine or amitriptyline in man (Nagy and Johans 1975). This variation, as well as that of the concentrations of the drug in blood, appears to be characteristic of the individual and is presumably under genetic control (Alexanderson and Sjoqvist 1978). These characteristics can be assessed quite reliably by the administration of a small test dose and a single measurement of the concentration in plasma.
5.3 Preclinical safety data
Imipramine has no mutagenic or carcinogenic potential. Studies in four species (mouse, rat, rabbit and monkey) led to the conclusion that orally administered imipramine has no teratogenic potential. Experiments with high doses of parenterally administered imipramine resulted mainly in severe maternal and embryotoxic effects, they were thus inconclusive with regard to teratogenic effects.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate, maize starch, povidone, magnesium stearate, stearic acid.
Sugar-coat excipients: Polyvinylacetate phthalate, talc, calcium carbonate, acacia, titanium dioxide (E171), sucrose, tartrazine aluminium lake (E102), amaranth aluminium lake (E123), erythrosine aluminium lake (E127),indigo carmine aluminium lake (E132), sodium benzoate (E211), shellac, yellow carnauba wax, white beeswax.
6.2 Incompatibilities
None stated.
6.3 Shelf life
5 Years
6.4 Special precautions for storage
Do not store above 25°C. Store in the original container. Keep the container tightly closed.
6.5 Nature and contents of container
Polypropylene container with low density polyethylene cap.
Pack sizes: 84, 100, 500 and 1000 tablets.
6.6 Special precautions for disposal
Not applicable
7 MARKETING AUTHORISATION HOLDER
BRISTOL LABORATORIES,
UNIT 3, CANALSIDE,
NORTHBRIDGE ROAD,
BERKHAMSTED HP4 1EG, UNITED KINGDOM
8 MARKETING AUTHORISATION NUMBER(S)
PL 17907/0341
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
07/06/2011
10 DATE OF REVISION OF THE TEXT
15/10/2014