Summary of Product Characteristics (SmPC) - Dosulepin 75 mg tablets
1 NAME OF THE MEDICINAL PRODUCT
Dosulepin 75mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains dosulepin hydrochloride 75 mg.
Excipient(s) with known effect
Each tablet contains 140 mg of lactose monohydrate and colourants Sunset Yellow (E110) and Ponceau 4R Red (E124). For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Red, biconvex, film-coated tablets imprinted with ‘MP76’ on side and plain on the other side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Dosulepin is indicated in the treatment of symptoms of depressive illness especially where an anti-anxiety effect is required.
Due to its toxicity in overdose, Dosulepin should only be used in patients intolerant of or unresponsive to alternative treatment options (see sections 4.4 and 4.9).
Initiation of treatment for patients who have not previously received Dosulepin should be restricted to specialist care prescribers
4.2 Posology and method of administration
Posology
Adults
Initially 75 mg/day in divided doses or as a single dose at night. The dose may be increased to 150mg/day. In certain circumstances, e.g. under hospital conditions, dosages up to 225 mg daily have been used.
Suggested regimens: 25 or 50 mg three times daily or, alternatively, 75 or 150 mg as a single dose at night. Should the regimen of 150 mg as a single nighttime dose be adopted, it is better to give a smaller dose for the first few days.
Elderly:
50-75 mg daily initially. As with any antidepressant, the initial dose should be increased with caution under close supervision. Half the normal adult dose may be sufficient to produce a satisfactory clinical response.
Paediatric population
The use of dosulepin hydrochloride is not recommended in children.
Method of
administration
For oral administration.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Dosulepin is contraindicated following recent myocardial infarction and in patients with any degree of heart block or other cardiac arrhythmias. It is also contraindicated in mania and in severe liver disease.
4.4 Special warnings and precautions for use
It may be two to four weeks from the start of treatment before there is an improvement in the patient's depression; the subject should be monitored closely during this period. The anxiolytic effect may be observed within a few days of commencing treatment.
Toxicity in overdose
Dosulepin is associated with high mortality in overdose. There is a low margin of safety between the (maximum) therapeutic dose and potentially fatal doses. Onset of toxicity occurs within 4-6 hours. A limited number of tablets should be prescribed to reduce the risk from overdose for all patients and especially for patients at risk of suicide.
A maximum prescription equivalent to two weeks supply of 75mg/day should be considered in patients with increased risk factors for suicide at initiation of treatment, during any dosage adjustment and until improvement occurs.
Avoid concomitant medications which may increase the risk of toxicity associated with dosulepin (See Section 4.5) Patients should be advised to store the tablets securely, out of sight and reach of children.
In cases of overdose, patients should seek IMMEDIATE MEDICAL ATTENTION (see section 4.9)
The elderly are particularly susceptible to experience adverse reactions to antidepressants. In particular they may suffer from agitation, confusion and postural hypotension.
Dosulepin should be avoided in patients with a history of epilepsy.
Administration should be avoided if possible in patients with narrow angle glaucoma and symptoms suggestive of prostatic hypertrophy.
Dosulepin may increase the risk of cardiovascular toxicity (cardiac arrhythmias, conduction disorders, cardiac failure and circulatory collapse), especially in the elderly. Caution should be exercised in using Dosulepin in the elderly and in patients with suspected cardiovascular disease (see Section 4.3).
Tricyclic antidepressants potentiate the central nervous depressant action of alcohol.
Anaesthetics given during tricyclic antidepressant therapy may increase the risk of arrhythmias and hypotension. If surgery is necessary, the anaesthetist should be informed that a patient is being so treated.
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.
Other psychiatric conditions for which Dosulepin is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.
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.
Care should be taken where there is a history of mania or psychoses. Dosulepin may aggravate psychotic symptoms. Patients posing a high suicidal risk require close supervision.
Conduction defects or cardiac arrhythmias may occur in hyperthyroid patients.
Toxic levels of dosulepin may develop in patients with severe renal disease.
On stopping treatment, it is recommended that antidepressants are withdrawn gradually, wherever possible as withdrawal reactions may occur (see section 4.8).
Patients posing a high suicidal risk require close supervision.
Dosulepin hydrochloride should be given with caution to patients with a history of mania, history of urinary retention, or in patients with hepatic impairment, phaeochromocytoma, porphyria, and used with caution in patients having concurrent electroconvulsive therapy.
Blood sugar concentrations may be altered and as such dosulepin should be used in caution in diabetic patients.
Hyponatraemia (usually in the elderly and possibly due to an inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants and should be considered in all patients who develop drowsiness, confusion or convulsions while taking an antidepressant.
Dosulepin Tablets contain lactose, E124 and E110 colourants and sodium
The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Patients should be informed that this medicine also contains the colourants ponceau red (E124) and sunset yellow (E110) which may cause allergic reactions.
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.
4.5 Interaction with other medicinal products and other forms of interaction
Dosulepin hydrochloride should not be given concurrently with monoamine oxidase inhibitors nor within 14 days of ceasation of such treatment.
The concomitant administration of dosulepin and selective serotonin re-uptake inhibitors (SSRIs) should be avoided. The plasma concentrations of tricyclic antidepressants are increased when taken with SSRIs and dosulepin.
Dosulepin hydrochloride may alter the pharmacological effect of some concurrently administered drugs including CNS depressants such as alcohol and narcotic analgesics, the effect of these will be potentiated as will be the effects of adrenaline and noradrenaline ( some local anaesthetics contain these sympathomimetics).
Anaesthetics given during tricyclic antidepressant therapy may increase the risk of arrhythmias and hypotension.If surgery is necessary, the anaesthetist should be informed that the patient is being so treated.
Drugs which prolong the QT interval including antiarrhythmics such as quinidine, the antihistamines astemizole and terfenadine, some antipsychotics (notably pimozide and sertindole), cisapride, halofantrine and sotalol may increase the likelihood of ventricular arrhythmias when taken with tricyclic antidepressants and concurrent use should be avoided. The problem may be exacerbated where the interacting drug (such as quinidine or some antipsychotics) also reduces tricyclic metabolism.
Antimuscarinic side effects may be enhanced by concurrent use with antimuscarinic drugs.
Antidepressants may antagonise the activity of antiepileptics by lowering the convulsive threshold.
Oral contraceptives may antagonise the antidepressant effect but side effects may be increased due to increased plasma concentrations of tricyclics.
The hypotensive effect some antihypertensive agents (e.g. betandine, debrisoquine, guanethidine) may be reduced by dosulepin hydrochloride. It is advisable to review all antihypertensive therapy if administered concurrently with tricyclic antidepressants.
There is an increased risk of postural hypotension when tricyclic antidepressants are given with diuretics.
Tricyclic antidepressants may also antagonise the anticonvulsant effect of antiepileptics (convulsive threshold decreased).
Barbiturates and other enzyme inducers such as rifampicin and some antiepileptics may increase the metabolism of tricyclic antidepressants and result in lowered plasma concentrations and reduced antidepressant response. Cimetidine, methylphenidate, antipsychotics and calcium channel blockers (eg diltiazem, verapamil) may reduce the metabolism and increase plasma levels of tricyclics.
There is no evidence that dosulepin interferes with standard laboratory tests.
4.6 Pregnancy and lactation
Pregnancy
There is inadequate evidence as to the safety of the drug in human pregnancy, therefore it should only be administered if considered essential.
Breast-feeding
There is evidence that dosulepin is secreted in breast milk but this is at levels which are unlikely to cause problems.
4.7 Effects on ability to drive and use machines
Dosulepin hydrochloride may cause drowsiness in some patients, if this occurs it is advisable not to drive or operate machinery.
4.8 Undesirable effects
The following adverse effects, although not necessarily with dosulepin, have occurred with other tricyclic antidepressants.
Atropine-like side effects are common early in treatment, but usually lessen
Class effects:
Epidemiological studies, mainly conducted in patients 50 year of age and older, show an increased risk of bone fractures in patients receiving SSRIs and tricyclic antidepressants. The mechanism leading to this risk is unknown. Blood and lymphatic system disorders:
Rare: Bone marrow depression, thrombocytopenia, leucopenia, agranulocytosis, eosinophilia
Immune system disorders:
Hypersensitivity reactions (see Skin and subcutaneous tissue disorders)
Metabolism and nutrition disorders:
Hyponatraemia (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants and should be considered in all patients who develop drowsiness, confusion or convulsions while taking an antidepressant.
Increased appetite, weight gain, changes in blood sugar levels.
Psychiatric disorders:
Confusion, hypomania, nervousness
Psychotic manifestations including mania and paranoid delusions may be exacerbated during treatment with tricyclic antidepressants
Nervous system disorders:
Drowsiness, tremor, dyskinesia, movement disorders, convulsions (rare), epileptiform seizures, occasional extrapyramidal symptoms including speech difficulties.
Eye disorders:
Disturbances of accommodation, increased intraocular pressure.
Cardiac disorders:
Tachycardia, ECG changes including conduction defects, dizziness Cardiac arrhythmias and severe hypotension are likely to occur with high dosages or in deliberate overdosage. They may also occur in patients with pre-existing heart disease taking normal dosage.
Vascular disorders:
Postural hypotension, orthostatic hypotension, occasional hypertension
Gastrointestinal disorders:
Dry mouth, constipation, gastric irritation with nausea and vomiting,
Hepatobiliary disorders:
Increased liver function test values, cholestatic jaundice, hepatitis (rare)
Skin and subcutaneous tissue disorders:
Rash, urticaria, photosensitivity, purpura, increased sweating, photosensitization
Renal and urinary disorders:
Urinary hesitation
Reproductive system and breast disorders:
Sexual dysfunction, testicular enlargement, gynaecomastia, galactorrhoea.
Respiratory disorders
Idiosyncratic alveolitis which may prove fatal
General disorders:
Weakness, fatigue, ataxia, Weight loss may occur as may weight gain and the latter is sometimes associated with inappropriate appetite (carbohydrate craving),
Endocrine disorders:
Inappropriate ADH secretion.
Withdrawal symptoms may occur abruptly ceassation of tricyclic therapy and include insomnia, irritability, headache, giddiness, panic-anxiety, extreme motor restlessness and excessive perspiration (see 4.4). Similar symptoms have been reported in neonates whose mothers received tricyclic antidepressants during the third trimester.
Cases of suicidal ideation and suicidal behaviours have been reported during dosulepin therapy or early after treatment discontinuation (see section 4.4).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
Symptoms of overdosage may include dryness of the mouth, excitement, ataxia, drowsiness, loss of consciousness, respiratory or metabolic alkalosis, muscle twitching, convulsions, widely dilated pupils, hyperreflexia, sinus tachycardia, hypothermia, cardiac arrhythmias, hypotension, depression of respiration, visual hallucinations, delirium, urinary retention, paralytic ileus,.
- Patients ingesting >5mg/kg should seek immediate medical attention.
- All children ingesting dosulepin should be assessed by a physician.
- Onset of toxicity occurs within 4-6 hours
Management
- A clear airway and adequate ventilation should be ensured. Hypoxia and acid-base imbalances should be corrected by assisted ventilation and IV sodium bicarbonate as appropriate.
- Do not give flumazenil to reverse benzodiazepine toxicity in mixed overdoses.
- The use of activated charcoal should be considered as a preferred initial means of reducing absorption in patients presenting within 2 hours of ingestion. The benefit of gastric lavage is uncertain and the technique should be avoided in any patient with an impaired airway.
Blood pressure, pulse and cardiac rhythm should be monitored for at least
6hrs after ingestion.
- Arrhythmias are best treated by correcting hypoxia and acid-base disturbances. Specialist poisons advice should be sought before using any antiarrhythmic agents as these may exacerbate the arrhythmia.
- In cases of cardiac arrest, persist with prolonged CPR (for at least 1 hr).
- Convulsions should be controlled with IV diazepam or lorazepam.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Non-selective monoamine reuptake inhibitors, ATC Code: N06AA16.
Dosulepin hydrochloride is a thio derivative of amitriptyline and is an antidepressant of the tricyclic family.
Dosulepin potentiates the effects of biogenic amines in the brain by inhibition of their reuptake at nerve terminals. Dosulepin is active in inhibiting the reuptake of noradrenaline, 5-hydroxytryptamine (5HT) and dopamine.
Dosulepin also reduces and/or down regulates central noradrenaline receptor numbers and reduces noradrenaline-induced cyclic AMP formation in the brain.
It inhibits the uptake of 5HT into the platelets.
Dosulepin also has some central and peripheral anticholinergic and antihistaminic activity at standard dose levels.
5.2 Pharmacokinetic properties
Dosulepin is readily absorbed from the gastro-intestinal tract and extensively metabolised in the liver. Metabolites include northiaden, dosulepin-S-oxide and northiaden-S-oxide. Dosulepin is excreted in the urine 50%-60%, mainly in the form of metabolites; appreciable amounts are also excreted in the faeces 15%-40%, most of which is first excreted in the bile. A half-life of about 50 hours has been reported for dosulepin and its metabolites.
Dosulepin has been found excreted in breast milk
5.3 Preclinical safety data
Pre-clinical information has not been included because the safety profile of dosulepin has been established after many years of clinical use. Please refer to Section 4.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Core:
Lactose monohydrate
Maize starch Povidone
Sodium starch glycollate
Magnesium stearate
Coating:
Red colorant containing:
Lactose
Hypromellose
Ponceau 4R Aluminium Lake
(E124) Polyethylene glycol
4000 Titanium Dioxide (E171)
Yellow Iron Oxide (E172)
Sunset Yellow FCF Aluminium Lake FD & C Yellow No. 6 (E110)
6.2 Incompatibilities
No other major incompatibilities are known.
6.3 Shelf life
250µm opaque UPVC/Al: 2 years
PVdC coated PVC/Al: 5 years
6.4 Special precautions for storage
Do not store above 25ºC. Store in the original package.
6.5 Nature and contents of container
Blister packs: UPVC /Child resistant push through foil blisters (250µm opaque UPVC
/20µm Al with 15µm PVC film) in pack sizes of 14 or 28 tablets, or
UPVC/Child resistant push through foil blister (60g/m2 PVdC on 250µm PVC film/16 µm Al/20 µm PVC) in pack size 14 or 28 tablets or
PVdC coated PVC /Child resistant push through foil blisters (60g/m2 PVdC on 250µm PVC/20µm Al with 15µm PVC film) in pack sizes of 14 or 28 tablets.
6.6 Special precautions for disposal
No special instructions.
7 MARKETING AUTHORISATION HOLDER
Genesis Pharmaceuticals Limited
1st Floor, 16/17 College Green
Dublin, D02 V078
Ireland
8 MARKETING AUTHORISATION NUMBER
PL 62354/0086
9 DATE OF FIRST AUTHORISATION/RENEWAL OF
THE
AUTHORISATION
02/06/2003 / 26/01/2009
10 DATE OF REVISION OF THE TEXT
01/10/2026