Summary of Product Characteristics (SmPC) - Dosulepin Hydrochloride 25 mg capsules
1 NAME OF THE MEDICINAL PRODUCT
Dosulepin Hydrochloride 25mg Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains Dosulepin Hydrochloride 25 mg.
Excipients with known effect:
Lactose monohydrate 109.40 mg per capsule.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Capsule, hard
Hard gelatin capsule size “4” with brown opaque body and reddish-brown opaque cap containing white to off white powder.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Dosulepin is indicated in the treatment of symptoms of depressive illness in adults, 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 section 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
Adults: Initially 75 mg/day in divided doses or as a single night-time dose, increasing to 150mg/day if required. In certain circumstances, e.g. in hospital use, 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 night-time dose be adopted, it is better to give a smaller dose for the first few days.
Elderly: 50 to 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.
Children: Not recommended.
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 contra-indicated
in mania, severe liver disease, narrow angle glaucoma or other causes of increased
intraocular pressure.
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.
The elderly are particularly liable to adverse effects with tricyclic antidepressants, especially agitation, confusion and postural hypotension.
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 overdoses, patients should seek IMMEDIATE MEDICAL ATTENTION (see section 4.9).
Similarly to other tricyclic antidepressants, it has anticholinergic, antihistaminic and anti-α1 adrenergic effects which may cause common adverse effects. For a better control of these adverse effects, it is recommended to start with a low dose and increasing gradually until a therapeutic dose is achieved.
Dosulepin should be avoided in patients with a history of epilepsy, thyroid disease, mania or urinary retention and in those with narrow-angle glaucoma or symptoms suggestive of prostatic hypertrophy. Patients with hepatic impairment and those undergoing electroconvulsive therapy, phaeochromocytoma, porphyria should also avoid Dosulepin use. 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).
Conduction defects or cardiac arrhythmias may occur in hyperthyroid patients.
Toxic levels of dosulepin may develop in patients with severe renal disease. The elderly are especially liable to experience adverse reactions to antidepressants.
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 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.
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 (see section 4.5).
On stopping treatment, it is recommended that antidepressants should be withdrawn gradually, wherever possible as withdrawal reactions may occur.
This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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.
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.
Use in Children and adolescents under 18 years of age
Dosulepin should not be used in the treatment of depression in children and adolescents under the age of 18 years. Studies in depression in this age group did not show a beneficial effect for tricyclic antidepressants. Studies with other classes of antidepressants have shown risk of suicidality, self-harm and hostility to be related to these compounds. This risk cannot be excluded with dosulepin. In addition, dosulepin is associated with a risk of cardiovascular adverse events in all age groups.
Furthermore, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are not available (see also section 4.8 Undesirable effects and Section 4.9 Overdose).
4.5 Interaction with other medicinal products and other forms of interaction
Dosulepin should not be given concurrently with a monoamine oxidase inhibitor, nor
within fourteen days of ceasing such treatment. The concomitant administration of
dosulepin and SSRIs should be avoided since increases in plasma tricyclic antidepressant levels have been reported following the co-administration of some
SSRIs.
Dosulepin 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.
Dosulepin has quinidine-like actions on the heart. For this reason, the concomitant
use of drugs that may affect cardiac conduction or prolong the QT interval (e.g.
sotalol, terfenadine, astemizole, halofantrine) may increase the risk of arrhythmias
when taken with tricyclic antidepressants and 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.
Oral contraceptives may antagonise the antidepressant effect but side effects may be
increased due to increased plasma concentrations of tricyclics. There is an increased risk of postural hypotension on concurrent use with diuretics.
The hypotensive activity of certain antihypertensive agents (eg betanidine, debrisoquine, guanethidine) may be reduced by dosulepin hydrochloride. It would be
advisable to review all antihypertensive therapy during treatment with tricyclic antidepressants.
The use of tricyclics with thyroid hormones may precipitate cardiac arrhythmias.
In general, the hypotensive effect of antihypertensives is enhanced by tricyclic antidepressants, but there may be antagonism of the effect of adrenergic neurone
blockers and of clonidine. It is advisable to review all antihypertensive therapy during
treatment 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 may decrease and methylphenidate may increase the serum concentration of dosulepin and thus affect its antidepressant action. 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 Fertility, pregnancy and lactation
Fertility
No studies have been carried out to prove the effect of dosulepin on fertility. Pregnancy
Treatment with dosulepin should be avoided during pregnancy unless there are compelling reasons. There is inadequate evidence of the safety of the drug during
human pregnancy.
Breast-feeding
There is evidence that dosulepin is secreted in breast milk. Although, this is at levels
which are unlikely to cause problems, caution should be exercised when prescribing
to breast-feeding women.
4.7 Effects on ability to drive and use machines
Initially, dosulepin may impair alertness. Patients likely to drive or operate machinery should be warned of this possibility.
Dosulepin 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 all reported with dosulepin,
have occurred with other tricyclic antidepressants:
Potentially serious adverse effects:
Rare (≥1/10,000 to <1/1,000)
- Include depression of the bone marrow, agranulocytosis, hepatitis (including altered liver function), cholestatic jaundice, convulsions and inappropriate ADH
secretion.
- Psychotic manifestations, including mania and paranoid delusions, may be exacerbated during treatment with tricyclic antidepressants.
- Cardiac arrhythmias and severe hypotension are likely to occur with high dosage
or in deliberate over dosage. They may also occur in patients with pre-existing heart disease taking normal dosage.
Other side effects:
Common (≥1/100 to <1/10)
- Atropine-like side effects including dry mouth, disturbances of accommodation,
tachycardia, constipation and hesitancy of micturition are common early in treatment, but usually lessen.
- Dizziness is also a common side effect of tricyclic antidepressants.
Uncommon (≥1/1,000 to <1/100)
- Uncommon adverse effects include drowsiness, sweating, postural hypotension,
tremor skin rashes, tachycardia, confusion, hallucinations, increased intraocular
pressure, hyponatraemia, hypersensitivity reactions, changes in blood sugar levels, endocrine side-effects and movement disorders. Interference with sexual
function may occur.
- Cases of suicidal ideation and suicidal behaviour have been reported during dosulepin therapy or early after treatment discontinuation (see section 4.4).
- Withdrawal symptoms may occur on abrupt cessation of tricyclic therapy and include insomnia, irritability and excessive perspiration. Similar symptoms in neonates whose mothers received tricyclic antidepressants during the third trimester have also been reported.
Class effects
Epidemiological studies, mainly 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 the risk is unknown.
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. Website 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, cardiac arrhythmias, hypotension, hypothermia, depression of respiration, visual
hallucinations, delirium, urinary retention and paralytic ileus.
Patients ingesting >5 mg/kg should seek immediate medical attention.
All children ingesting dosulepin should be assessed by a physician.
Onset of toxicity occurs within 4-6 hours after tricyclic antidepressant overdose.
Management
- A clear airway and adequate ventilation should be ensured. Hypoxia and acidbase
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 patients with an impaired airway.
- Blood pressure, pulse and cardiac rhythm should be monitored for at least 6 hours
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 1hr).
- 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 is a tricyclic antidepressant which acts by inhibiting the re-uptake of monoamine neurotransmitters into presynaptic neurone at central nervous system, so producing a clinical antidepressant effect.
Dosulepin, in common with other tricyclics, inhibits the reuptake of noradrenaline and 5- hydroxytryptamine, with a significantly greater action on the uptake of noradrenaline. In addition, dosulepin inhibits the neuronal uptake of dopamine.
As a consequence of its effects on monoamine levels, dosulepin appears to produce adaptive changes in the brain by reducing or down-regulating both noradrenaline receptor numbers and noradrenaline-induced cyclic-AMP formation.
Similarly to other tricyclic antidepressants, it has anticholinergic, antihistaminic and anti-α1 adrenergic effects.
5.2 Pharmacokinetic properties
Dosulepin is readily absorbed from the gastrointestinal tract and extensively metabolized in the liver. Metabolites include northiaden, dosulepin-S-oxide and northiaden-S-oxide. Dosulepin is excreted in the urine, mainly in the form of metabolites; appreciable amounts are also excreted in the faeces. A half-life of about
50 hours has been reported for dosulepin and its metabolites.
5.3 Preclinical safety data
There are no additional non-clinical data of relevance to the prescriber that are not stated elsewhere in the SmPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Capsule Content:
Lactose monohydrate
Maize starch
Magnesium stearate
Capsule shell:
Gelatin
Titanium dioxide (E 171)
Red iron oxide (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Alu/PVC/PVDC blister packs of 28 capsules.
6.6 Special precautions for disposal
No special requirements for disposal.
7 MARKETING AUTHORISATION HOLDER
Crescent Pharma Limited
Key House, Sarum Hill,
Basingstoke, RG21 8SR
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 20416/1220
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
09/02/2026
10 DATE OF REVISION OF THE TEXT
06/07/2026