Doxepin 25mg capsules

United Kingdom - English - eMC (Electronic Medicines Compendium)

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Active ingredient:
Doxepin hydrochloride
Available from:
DE Pharmaceuticals
ATC code:
N06AA12
INN (International Name):
Doxepin hydrochloride
Dosage:
25mg
Pharmaceutical form:
Capsule
Administration route:
Oral
Class:
No Controlled Drug Status
Prescription type:
Valid as a prescribable product
Product summary:
BNF: 04030100
Authorization number:
; PL 23138/0002

PACKAGE LEAFLET:

INFORMATION FOR THE USER

Sinepin (doxepin)

25mg and 50mg Capsules

Read all of this leaflet carefully before you

start taking your medicine.

Keep this leaflet. You may need to read

it again. If you have any further questions,

please ask your doctor or pharmacist.

This medicine has been prescribed for you.

Do not pass it on to others. It may harm them,

even if their symptoms are the same as yours.

If any of the side effects get serious, or if you

notice any side effects not listed in this leaflet,

please tell your doctor or pharmacist.

In this leaflet:

1. What Sinepin is and what it is used for

2. Before you take Sinepin

3. How to take Sinepin

4. Possible side effects

5. How to store Sinepin

6. Further information

1. WHAT SINEPIN IS AND WHAT

IT IS USED FOR

The name of this medicine is Sinepin. The active

ingredient is doxepin hydrochloride.

Sinepin is an antidepressant. It is one of a group called

tricyclic antidepressants.

Your doctor has decided that this medicine is suitable

for treating your depression.

Depression is a clinical illness. If you have been feeling

sad, tearful or unable to enjoy life as you used to, Sinepin

may help you to feel better. It may also help if you have

difficulty sleeping because of your depression. If you

are not sure why you are on these capsules, ask your

doctor.

2. BEFORE YOU TAKE SINEPIN

Do not take Sinepin Capsules if:

You have ever had an allergic reaction to tricyclic

antidepressants,doxepin, or any of the inactive

ingredients of Sinepin Capsules

(see ‘Further information’

section)

You have serious liver problems

You have glaucoma (increased eye pressure)

You suffer from difficulty in passing urine

You are breast-feeding

You are taking, or have taken in the last two weeks,

any medicines called monoamine oxidase inhibitors

(MAOIs for short)

You suffer from a type of mood disorder called mania,

where you experience an abnormally elevated mood

state.

The patient is under 12 years of age

If you suffer from any of the above, speak to your doctor

or pharmacist before taking Sinepin.

Take special care with Sinepin Capsules if:

You are pregnant or trying to become pregnant

You have any heart problems

You have had a heart attack recently

You have kidney problems

You suffer from epilepsy (fits)

You have suicidal thoughts or have attempted suicide

in the past

If you answer YES to any of the above questions talk to

your doctor before taking this medicine.

If you are taking other medicines

It is very important that you inform your doctor if you are

taking or have taken any other medicines, as some medicines

may affect the way Sinepin works.

If you are going to have a surgical operation or dental

surgery tell the doctor or dentist in charge that you are

taking this medicine.

Some medicines can interfere with the action of Sinepin,

and Sinepin can sometimes affect the action of other

medicines. Check with your doctor if you are taking any of

the medicines listed below:

Monoamine oxidase inhibitors. These must not be used

with Sinepin (see ‘Before you take Sinepin’section above)

Other antidepressants, barbiturates (used to treat

insomnia) or other sleeping medicines or medicines

for anxiety. Sinepin will add to their effects and may

cause you to feel sleepy or drowsy.

Medicines to lower blood pressure.

Sympathomimetics, such as nasal decongestants

(used for colds or hay fever) and bronchodilators

(used to treat asthma).

Cimetidine (used to treat ulcers and other stomach

complaints).

Thyroid hormones (used to treat thyroid disorders).

Chlorpromazine (used to treat mental illness).

Sublingual nitrates (used to treat angina and heart

failure).

Pregnancy and breast-feeding

Do not take this medicine if you are pregnant or trying

to become pregnant without consulting your doctor.

Do not take this medicine if you are breast-feeding without

consulting your doctor.

Driving and using machines

You may feel sleepy when you take these capsules, do

not drive or work with machinery until this effect has

worn off.

Alcohol and Sinepin

Be careful when drinking alcohol. Alcoholic drinks (wine,

beer, spirits) may affect you much more than usual.

3. HOW TO TAKE SINEPIN

The label on the pack will tell you what dose YOU should

take and how often each day to take it. If you are still not

sure, ask your doctor or pharmacist.

Your medicine should only be taken by mouth.

Swallow your capsules whole with a drink of water.

Take the capsules while standing or when sitting

upright.

Do not crush or chew the capsules.

Keep taking the capsules every day

The usual starting dose is 75mg daily.

This dose

may be increased if necessary .

The maximum recommended dose is 100mg three

times daily.

If you are elderly these doses may be reduced.

If you are elderly and require an increased dose of

the medicine your doctor may wish to see you

regularly.

If you suffer from liver problems you may also be

started on a low dose.

The capsules may be prescribed once, twice or three

times daily.

Up to 100mg can be given as a single dose.

If you take more Sinepin Capsules than

you should

Too many capsules at once can be dangerous. Signs

and symptoms of mild overdosage include drowsiness,

stupor, blurred vision and excessive dryness of the mouth.

Severe overdosage may cause loss of consciousness,

reduced breathing rate, convulsions, low blood pressure,

unusually fast heart beat or palpitations. If you

take too

many capsules immediately contact your doctor or nearest

hospital Accident and Emergency Department. Do not

attempt to drive or work with machinery.

If you forget to take Sinepin Capsules

Do not worry. Take your usual dose at the next

correct time

Do not take a double dose to make up for a

forgotten capsule.

If you stop taking Sinepin Capsules

You should always check with your doctor before you

stop treatment. Your doctor may want you to reduce

gradually the amount you are taking before stopping the

medicine completely. This may help to prevent a

recurrence of the original trouble and reduce the chance

of withdrawal effects such as insomnia, irritability and

excessive sweating.

How quickly will the treatment start to work?

You may take Sinepin for 2-3 weeks before you start

to feel better.

You must keep taking Sinepin to help you get better.

See your doctor before your capsules run out.

Even if you begin to feel better, keep taking your

capsules. You may need to keep taking them to

stay well.

What if you do not feel better?

Tell your doctor if:

You have taken all your medicine and you

still feel unwell:

You feel worse.

4. POSSIBLE SIDE EFFECTS

Thoughts of suicide and worsening of your

depression or anxiety disorder.

If you are depressed and/or have anxiety disorders you

can sometimes have thoughts of harming or killing

yourself. These may be increased when first starting

antidepressants, since these medicines all take time to

work, usually about two weeks but sometimes longer.

You may be more likely to think like this:

If you have previously had thoughts about killing or

harming yourself.

If you are a young adult. Information from clinical trials

has shown an increased risk of suicidal behaviour in

adults aged less than 25 years with psychiatric

conditions who were treated with an antidepressant.

If you have thoughts of harming or killing yourself

at any time, contact your doctor or go to a hospital

straight away.You may find it helpful to tell a relative

or close friend that you are depressed or have an anxiety

disorder, and ask them to read this leaflet. You might ask

them to tell you if they think your depression or anxiety

is getting worse, or if they are worried about changes in

your behaviour.

Bone fractures

An increased risk of bone fractures has been observed

in patients taking this type of medicine.

Sinepin is well tolerated. Most undesirable effects are

usually mild and tend to wear off after continued treatment.

However, if the side effects are troublesome, your doctor

may decide to reduce your dose.

The most common side effects are:

Drowsiness

Dry mouth

Constipation

These are usually mild. If they last for more than several

days, check with your doctor.

Less common or rare side effects listed below. If they

don’t wear off after a few days or trouble you, check with

your doctor.

Dizziness, (if you experience dizziness you should be

particularly careful to stand up slowly).

Sweating.

Blurred vision.

Headache.

Insomnia.

Difficulty in passing urine.

Tiredness.

Weakness.

Weight gain.

Upset stomach.

Loss of appetite.

Vomiting or diarrhoea.

Mouth ulcers.

Unpleasant taste.

Fast heart beat (palpitations).

Changes in sex drive.

Swelling of testicles

Chills.

Flushing.

Hair loss from the scalp.

Shakiness or trembling.

Numbness in the hands or feet.

Feeling of pins and needles.

Agitation or confusion.

Ringing or buzzing in the ears.

Rare side effects:

The undesirable effects below

are rare but they have occurred in patients taking one of

the tricyclic antidepressants, however, not all have

occurred with Sinepin. You should check with your doctor

immediately if any of the following occur:

Skin rash, itching, face swelling. Your skin may be

more sensitive to sunlight than it is normally.

At high doses particularly in the elderly, unwanted

effects on muscles which may cause slowed

movements or stiffness of arms and legs, slurred

speech or odd tongue or eye movements.

Staggering walk which may occur on a mixture of

centrally acting drugs.

Worsening of an existing mental disorder;

Breast enlargement in both men and women, breast

milk production when not pregnant or breast feeding;

Worsening of asthma.

Convulsions (fits) are unlikely unless you already

suffer from these.

Nightmares, hallucinations (seeing or hearing things

that are not there), jaundice (yellow eyes or skin).

Changes to the heart rhythm may occur very rarely.

Blood disorders; these

may cause fever or chills and

painful ulceration in the mouth or rectum; unusual

bruising or bleeding.

Abnormal blood tests results i.e.- change in blood

sugar levels, lower sodium content of blood and low

blood cell count.

Elderly patients:

If you are elderly, you may be more

likely to be troubled by agitation or confusion

It is important to tell your doctor or

pharmacist if you suffer any of these or any

other undesirable effects which are not listed

above.

5. HOW TO STORE SINEPIN

Do not take Sinepin after the date stamped on the pack.

The expiry date refers to the last day of the month.

Sinepin should be kept in a cool, dry place (below 25°C).

Keep this medicine out of the sight and reach

of children.

Medicines should not be disposed of via wastewater or

household waste. Ask your pharmacist how to dispose

of medicines no longer required. These measures will

help protect the environment.

6. FURTHER INFORMATION

What Sinepin Capsules contain

The capsules are free of gluten and sucrose.

Sinepin 25mg Capsule.

Each capsule contains

25mg doxepin. Other ingredients: lactose, maize starch,

magnesium stearate and sodium lauryl sulphate. The

gelatin capsules are coloured with amaranth (E123),

erythrosine, (E127), paten

t blue V (E131), sunset yellow

(E110) and titanium dioxide (E171).

Sinepin 50mg Capsule.

Each capsule contains

50mg doxepin. Other ingredients: lactose, maize starch,

magnesium stearate and sodium lauryl sulphate. The

gelatin capsules are coloured with erythrosine, (E127),

patent blue V (E131) and titanium dioxide (E171).

What Sinepin Capsules look like and the

contents of the pack

Sinepin 25mg Capsules (blue and red) come in

packs of 28.

Sinepin 50mg Capsules (blue) come in packs of 28.

Marketing Authorisation Holder and

Manufacturer

Marketing Authorisation Holder

Manufacturer

Allphamed PHARBIL GmbH

Hildebrandstrasse 12, D-37081 Gottingen, Germany

This leaflet does not contain all the information about

this medicine. If you have any questions or are not sure

about anything, ask your doctor or pharmacist.

For information in large print, tape, CD or

Braille, telephone 01279 406759.

Leaflet prepared: May 2018

Reporting of side effects

If you get any side effects, talk to your doctor, nurse or

pharmacist. This includes any possible side effects not

listed in this leaflet. You can also report side effects

directly via the Yellow Card Scheme at

www.mhra.gov.uk/yellowcard.

By reporting the side effects you can help provide more

information on the safety of this medicine.

Marlborough Pharmaceuticals Ltd.

Sovereign House,

Miles Gray Road, Basildon,

Essex SS14 3FR, United Kingdom

TRADE NAME OF MEDICINAL PRODUCT

SINEPIN Capsules 25mg

Doxepin 25mg Capsules

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Active Ingredient: Doxepin Hydrochloride BP

The capsules contain Doxepin Hydrochloride BP equivalent to 25mg doxepin.

3

PHARMACEUTICAL FORM

Capsules for oral administration.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications

Symptoms of depressive illness, especially where sedation is required.

Posology and method of administration

The optimum oral dose depends on the severity of the condition and the

individual patient’s response. The dose required may vary from 25-300mg

daily. Doses up to 100mg daily may be given on a divided or once daily

schedule. Should doses over 100mg daily be required, they should be

administered in three divided doses daily. 100mg is the maximum dose

recommended at any one time. This dose may be given at bedtime.

For the majority of patients with moderate or severe symptoms, it is

recommended that treatment commences with an initial dose of 75mg daily.

Many of these patients will respond satisfactorily at this dose level. For

patients who do not, the dosage may be adjusted according to individual

response. In more severely ill patients, it may be necessary to administer a

dose of up to 300mg in divided doses daily, to obtain a clinical response.

In patients where insomnia is a troublesome symptom, it is recommended that

the total daily dose be divided so that a higher proportion is given for the

evening dose; similarly, if drowsiness is experienced as a side effect of

treatment, Doxepin 25mg Capsules may be administered by this regimen or

the dosage may be reduced. It is often possible, having once obtained a

satisfactory therapeutic response, to reduce the dose for maintenance therapy.

The optimal anti-depressant effect may not be evident for two to three weeks.

Use in children The use of Doxepin 25mg Capsules in children under 12

years is not recommended because safe conditions for its use have not been

established.

Use in the elderly In general, dose selection for an elderly patient should be

cautious, starting at the low end of the dosing range, reflecting the greater

susceptibility of elderly people to typical side effects of the drug.

Use in hepatic impairment Dosage reduction may be required in patients with

hepatic impairment (see ‘Special warnings and special precautions for use’).

Use in renal impairment Dosage reduction may be required in patients with

renal impairment (see ‘Special warnings and special precautions for use’).

4.3

Contra-indications

Doxepin is contra-indicated in individuals who have shown hypersensitivity to

tricyclic antidepressants (TCAs), doxepin, or any of the inactive ingredients.

Doxepin is also contra-indicated in patients with mania, severe liver disease,

lactation, glaucoma, tendency to urinary retention.

4.4

Special warnings and special precautions for use

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an associated with an increased risk of suicidal

thoughts, self harm and suicide (suicide related events). This risk persists until

significant remission occurs. As improvement many 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 with 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.

The once-a-day dosage regimen of Doxepin 25mg Capsules in patients with

intercurrent illness or patients taking other medications should be carefully

adjusted. This is especially important in patients receiving other medications

with anti-cholinergic effects.

The use of Doxepin 25mg Capsules on a once-a-day dosage regimen in

geriatric patients should be adjusted carefully on the basis of the patient’s

condition. The elderly are particularly liable to experience toxic effects,

especially agitation, confusion and postural hypotension. The initial dose

should be increased with caution under close supervision. Half the normal

maintenance dose may be sufficient to produce a satisfactory clinical response.

Patients should be warned that drowsiness may occur with the use of Doxepin

25mg Capsules. Patients should also be cautioned that their response to

alcohol may be potentiated.

Although Doxepin 25mg Capsules carry less risk than other tricyclic anti-

depressants, caution should be observed in the treatment of patients with

severe cardiovascular disease, including patients with heart block, cardiac

arrhythmia and those who have experienced a recent myocardial infarction.

Use in hepatic/renal impairment Use with caution in patients with hepatic

and/or renal impairment.

Use in patients with epilepsy Use with caution in patients with a history of

epilepsy.

Since suicide is an inherent risk in any depressed patient until significant

improvement has occurred, patients should be closely supervised during early

therapy.

Patients with benign prostatic hyperplasia may experience an increase in

associated urinary retention (see ‘Undesirable effects’).

4.5

Interactions with other medicinal products and other forms of interaction

Doxepin, like other tricyclic antidepressants (TCAs), is metabolised by

cytochrome P450 (CYP) 2D6. Inhibitors or substrates of CYP2D6 (e.g.

quinidine, selective serotonin reuptake inhibitors [SSRIs]) may increase the

plasma concentration of TCAs when administered concomitantly. The extent

of interaction depends on the variability of effect on CYP2D6 and the

therapeutic index of the TCA. The clinical significance of this interaction with

doxepin has not been systematically evaluated.

Combined use with other anti-depressants, alcohol or anti-anxiety agents

should be undertaken with due recognition of the possibility of potentiation. It

is known, for example, that monoamine oxidase inhibitors may potentiate

other drug effects, therefore Doxepin 25mg Capsules should not be given

concurrently, or within two weeks of cessation of therapy, with monoamine

oxidase inhibitors.

Cimetidine has been reported to produce clinically significant fluctuations in

steady-state serum concentrations of doxepin.

Doxepin should not be given with sympathomimetic agents such as ephedrine,

isoprenaline, noradrenaline, phenylephrine and phenylpropanolamine.

General anaesthetics and local anaesthetics (containing sympathomimetics)

given during tricyclic or tetracyclic anti-depressant therapy may increase the

risk of arrhythmias and hypotension, or hypertension. If surgery is necessary,

the anaesthetist should be informed that a patient is being so treated.

Doxepin may decrease the anti-hypertensive effect of agents such as

debrisoquine, bethanidine, guanethidine and possibly clonidine. It usually

requires daily doses of doxepin in excess of 150mg before any effect on the

action of guanethidine is seen. It would be advisable to review all anti-

hypertensive therapy during treatment with tricyclic anti-depressants.

Barbiturates may increase the rate of metabolism of doxepin.

Doxepin 25mg Capsules may reduce the effect of sublingual nitrates owing to

dry mouth.

The dose of thyroid hormone medication may need reducing if Doxepin 25mg

Capsules are being given concurrently.

4.6

Pregnancy and lactation

Doxepin crosses the placenta. Reproduction studies have been performed in

rats, rabbits and monkeys and there was no evidence of harm to the animal

foetus. The relevance to humans is not known. Since there is insufficient

experience in pregnant women who have received this drug, its safety in

pregnancy has not been established.

Doxepin and its active metabolite desmethyldoxepin are excreted in breast

milk. There has been a report of apnoea and drowsiness occurring in a nursing

infant whose mother was taking doxepin. The use of Doxepin 25mg Capsules

is contraindicated during lactation.

4.7

Effects on ability to drive and use machines

Since drowsiness may occur with the use of Doxepin 25mg Capsules, patients

should be warned of the possibility and cautioned against driving a car or

operating machinery while taking this drug.

4.8

Undesirable effects

Doxepin 25mg Capsules are well tolerated. Most side-effects are mild and

generally disappear with continued treatment, or if necessary a reduction in

dose.

Note Some of the side-effects noted below have not been specifically reported

with Doxepin 25mg Capsules. However, due to the close pharmacological

similarities amongst the tricyclics, the reactions should be considered when

prescribing Doxepin 25mg Capsules.

The most common side-effects to Doxepin 25mg Capsules are drowsiness, dry

mouth and constipation. For further details see below under central nervous

system and anti-cholinergic effects.

Suicidal Ideation and Behaviours Cases of suicidal ideation and suicidal

behaviours have been reported during doxepin therapy or early after treatment

discontinuation (see section 4.4)

Bone fractures 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.

Anti-cholinergic effects Anti-cholinergic effects are relatively common and

may occur immediately following the first dose of a tricyclic anti-depressant.

Dry mouth and constipation are the most common anti-cholinergic effects.

Blurred vision and sweating occur occasionally. Urinary retention is rare

except in predisposed males who have an enlarged prostate gland. Tolerance

is often achieved if treatment is continued. If these undesirable effects do not

subside with continued therapy, or if they become severe, it may be necessary

to reduce the dosage.

Central nervous system effects Drowsiness is the most commonly noticed

side effect. This tends to disappear as therapy is continued. Insomnia and

nightmares have also been reported. Other infrequently reported CNS side

effects are confusion, disorientation, agitation, numbness or paraesthesiae,

tremor (which is usually mild). But at high doses, in susceptible individuals

(particularly the elderly) other extrapyramidal symptoms may occur including

tardive dyskinesia. Rarely reported are hallucinations, ataxia (generally where

mixtures of CNS drugs have been given), and convulsions. Convulsions are

unlikely except in people predisposed to seizure activity by brain damage or

alcohol and drug abuse.

Psychotic manifestations, including mania and paranoid delusions may be

exacerbated during treatment with tricyclic anti-depressants.

Cardiovascular Cardiovascular effects including postural hypotension, and

tachycardia have been reported occasionally and changes in ECG parameters

(widening of the QRS and PR interval) very rarely (see ‘Special warnings and

special precautions for use’).

Allergic Allergic reactions to tricyclic anti-depressants are uncommon. They

include skin rash, facial oedema, photosensitisation, pruritus and urticaria.

Haematological Rare cases of eosinophilia and bone marrow depression

manifesting as agranulocytosis, leucopenia, thrombocytopenia and

purpura. Haemolytic anaemia.

Gastro-intestinal Nausea, vomiting, indigestion, taste disturbances, diarrhoea,

anorexia and aphthous stomatitis have been reported (see ‘Anti-cholinergic

effects’).

Endocrine Occasional reports of raised or lowered libido, testicular swelling,

raised or lowered blood sugar levels. Rarely the syndrome of inappropriate

anti-diuretic hormone secretion, gynaecomastia, enlargement of breasts and

galactorrhoea in the female.

Other Dizziness, weight gain, chills, fatigue, weakness, flushing, alopecia,

headache, exacerbation of asthma and hyperpyrexia (in association with

chlorpromazine) have been occasionally observed. Rare reports of jaundice

and of tinnitus.

Withdrawal Withdrawal symptoms may occur on abrupt cessation of tricyclic

anti-depressant therapy and include insomnia, irritability and excessive

perspiration. Withdrawal symptoms in neonates whose mothers received

tricyclic anti-depressants during the third trimester have also been reported

and include respiratory depression, convulsions and “jitteriness” (hyper-

reflexia).

4.9

Overdose

Signs and symptoms

Mild: drowsiness, stupor, blurred vision, excessive dryness of mouth.

Severe: respiratory depression, hypotension, coma, convulsions, cardiac

arrhythmias and tachycardias.

Also urinary retention (bladder atony), decreased gastrointestinal motility

(paralytic ileus), hyperthermia (or hypothermia), hypertension, dilated pupils,

hyperactive reflexes.

Deaths have been reported involving overdoses of doxepin. The reported

cases involved doxepin alone and in combination with other drugs and/or

alcohol.

Management and treatment

Mild: observation and supportive therapy is all that is usually necessary.

Severe: medical management of severe doxepin overdosage consists of

aggressive supportive therapy. If the patient is conscious, gastric lavage with

appropriate precautions to prevent pulmonary aspiration should be performed

even though doxepin is rapidly absorbed. The use of activated charcoal has

been recommended, as has been continuous gastric lavage with saline for 24

hours or more. An adequate airway should be established in comatose patients

and assisted ventilation used if necessary. ECG monitoring may be required

for several days, since relapse after apparent recovery has been reported.

Arrhythmias should be treated with the appropriate anti-arrhythmic agent. It

has been reported that many of the cardiovascular and CNS symptoms of

tricyclic anti-depressant poisoning in adults may be reversed by the slow

intravenous administration of 1mg to 3mg of physostigmine salicylate.

Because physostigmine is rapidly metabolised, the dosage should be repeated

as required. Convulsions may respond to standard anti-convulsant therapy.

However, barbiturates may potentiate any respiratory depression. Dialysis and

forced diuresis generally are not of value in the management of overdosage

due to high tissue and protein binding of doxepin.

5.1

Pharmacodynamic properties

The mechanism of action of doxepin is not definitely known. It is not a central

nervous system stimulant nor a monoamine oxidase inhibitor. The current

hypothesis is that the clinical effects are due, at least in part, to influences on

the adrenergic activity at the synapses so that deactivation of noradrenaline by

reuptake into the nerve terminals is prevented. In animal studies anti-

cholinergic, anti-serotonergic and anti-histaminergic effects on smooth muscle

have been demonstrated. At higher than usual clinical doses, adrenaline

response was potentiated in animals. This effect was not demonstrated in

humans.

5.2.

Pharmacokinetic Properties

Doxepin is well absorbed from the gastro-intestinal tract. Approximately

55%-87% of orally administered doxepin undergoes first pass metabolism in

the liver, forming the primary active metabolite desmethyldoxepin.

In healthy volunteers, a single oral dose of 75mg resulted in peak plasma

concentrations for doxepin ranging from 8.8-45.8 ng/ml (mean 26.1 ng/ml).

Peak levels were reached between 2 and 4 hours (mean 2.9 hours) after

administration. Peak levels for the primary metabolite desmethyldoxepin

ranged from 4.8-14.5 ng/ml (mean 9.7 ng/ml) and were achieved between 2

and 10 hours after administration. The mean apparent volume of distribution

for doxepin is approximately 20 l/kg. The protein binding for doxepin is

approximately 76%. In healthy volunteers the plasma elimination half-life of

doxepin ranged from 8 to 24 hours (mean 17 hours). The half-life of

desmethyldoxepin ranged from 33-80 hours (mean 51 hours). Mean plasma

clearance for doxepin is approximately 0.84 l/kg.hr. Paths of metabolism of

doxepin include demethylation, N-oxidation, hydroxylation and glucuronide

formation. Doxepin is excreted primarily in the urine, mainly as its

metabolites, either free or in conjugate form.

5.3.

Pre-clinical Safety Data

Not applicable

6.1

List of excipients

Doxepin 25mg Capsule: lactose, magnesium stearate, maize starch dried,

sodium lauryl sulphate; capsule shell constituents: amaranth (E123),

erythrosine (E127), gelatin, patent blue V(E131), sunset yellow (E110) and

titanium dioxide (E171).

Doxepin 25mg Capsules are free of gluten and sucrose.

6.2.

Incompatibilities

None known.

6.3

Shelf-life

3 years.

6.4.

Special Precautions for Storage

Store below 25ºC.

6.5

Nature and contents of container

Doxepin 25mg Capsules are available as:

Packs of 28 capsules. Aluminium/PVC blister strips; 2 rows of 7 capsules per

strip, 2 strips in a carton box.

6.6

Instructions for Use and Handling

No special requirements.

7

MARKETING AUTHORISATION HOLDER

Marlborough Pharmaceuticals Ltd

Sovereign House, Miles Gray Road,

Basildon, Essex SS14 3FR, UK

8

MARKETING AUTHORISATION NUMBER(S)

PL 23138/0002

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

06/09/2006

10

DATE OF REVISION OF THE TEXT

04/06/2018

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