Consumer medicine information

Deptran

Doxepin

BRAND INFORMATION

Brand name

Deptran

Active ingredient

Doxepin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Deptran.

What is in this leaflet

This leaflet answers some common questions about DEPTRAN.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking DEPTRAN against the benefits it is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What DEPTRAN is used for

DEPTRAN is used to treat depression.

DEPTRAN 10 mg and DEPTRAN25 mg capsules can be used at any stage in the treatment of depression. However, the higher strength, DEPTRAN50 mg tablets, is approved only for the maintenance treatment of depression (after your symptoms have improved).

DEPTRAN belongs to a group of medicines called tricyclic antidepressants (TCAs).

Antidepressants are thought to work by their action on brain chemicals called amines which are involved in controlling mood.

Your doctor, however, may prescribe DEPTRAN for another purpose.

Ask your doctor if you have any questions about why DEPTRAN has been prescribed for you.

This medicine is only available with a doctor's prescription.

DEPTRAN should not be used in children and adolescents under the age of 18 years.

The safety and effectiveness of DEPTRAN in this age group has not been satisfactorily established.

Before you take DEPTRAN

When you must not take it

Do not take DEPTRAN if you have an allergy to:

  • any medicine containing doxepin hydrochloride
  • any other tricyclic antidepressants such as amitriptyline and imipramine
  • any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction to DEPTRAN may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • skin rash, itching or hives on the skin
  • swelling of the face, lips, tongue or other parts of the body
  • increased sensitivity of the skin to the sun.

Do not take DEPTRAN if you are taking a medicine called a monoamine oxidase inhibitor (MAOI) or have been taking it within the last 14 days. Taking DEPTRAN with a MAOI may cause a serious reaction with a sudden increase in body temperature, extremely high blood pressure and convulsions.

Ask your doctor or pharmacist if you are not sure if you are taking, or have been taking a MAOI.

MAOIs are medicines used to treat depression and symptoms of Parkinson's Disease. Examples of MAOIs are phenelzine (Nardil), tranylcypromine (Parnate), moclobemide (e.g. Aurorix, Arima) and selegiline (Eldepryl, Selgene).

Do not take DEPTRAN if you are breastfeeding unless directed by your doctor. Like many other medicines, DEPTRAN can pass into breast milk and may affect your baby.

Do not take DEPTRAN if you have:

  • glaucoma, a condition where the pressure in the eye is increased, including a type of glaucoma called angle closure glaucoma
  • urinary retention (difficulty in passing urine)

Do not take DEPTRAN if the expiry date (EXP) printed on the pack has passed or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking DEPTRAN, talk to your doctor.

Before you start to take it

You must tell your doctor if you are allergic to:

  • any other medicines
  • any other substances such as foods, dyes or preservatives.

Tell your doctor if you are not well or have any other health problems or a history of, including:

  • any mental illness
  • heart disease
  • liver or kidney problems
  • diabetes

Tell your doctor if you are pregnant or intend becoming pregnant. Your doctor will discuss the risks and benefits of taking DEPTRAN during pregnancy.

If you have not told your doctor or pharmacist about these things, tell them before you start taking DEPTRAN.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including:

  • all prescription medicines
  • all medicines, vitamins, herbal supplements or natural therapies you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may be affected by DEPTRAN or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines. Your doctor will advise you.

Tell your doctor or pharmacist if you are taking any of the following:

  • monoamine oxidase inhibitors (MAOIs), medicines used for the treatment of depression
    Taking DEPTRAN with, or within 14 days of stopping a MAOI may cause a serious reaction with a sudden increase in body temperature, extremely high blood pressure and convulsions.
    Wait at least 14 days after stopping your MAOI before starting DEPTRAN.
  • other medicines for depression for example fluoxetine (e.g. Prozac, Lovan), sertraline (e.g. Zoloft) and paroxetine (e.g. Aropax, Paxtine)
  • cimetidine (e.g. Tagamet, Magicul), a medicine used to treat reflux and stomach ulcers
  • medicines for diabetes (e.g. Daonil, Minidiab)
  • anti-anxiety medicines (e.g. diazepam, Valium, Serepax)
  • medicines containing atropine (e.g. Atropt, Atropine eye drops, Atropine Sulphate injection) or medicines for irritable bowel syndrome (e.g. Pro-banthine, Buscopan)
  • tranquillisers such as Risperdal, or Largactil
  • medicines for controlling abnormal heart beats e.g. Durules, Tambocor
  • medicines for epilepsy e.g. Dilantin, Tegretol, Teril
  • medicines containing adrenaline (epinephrine) or noradrenaline (norepinephrine) (e.g. nasal drops, decongestants, some cough mixtures, some local anaesthetics)
  • stimulant medicines containing amphetamine (e.g. dexamphetamine)
  • guanethidine

Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking DEPTRAN.

How to take DEPTRAN

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

The dose of DEPTRAN varies from 30 mg to 300 mg daily.

Your doctor will decide the right dose for you. This depends on your condition, age, whether or not you are taking any other medicines, and how you respond to DEPTRAN.

It is usual to start with a low dose and then, if necessary, increase it gradually until the right dose is reached.

How to take it

Swallow the capsules or tablets whole with a glass of water or other liquid.

When to take it

DEPTRAN can be taken with or without food.

DEPTRAN can be taken as a single dose (e.g. at bedtime) or as divided doses (e.g. three times a day). Your doctor will advise you.

Take your medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How long to take it

Keep taking DEPTRAN until your doctor tells you to stop.

Most antidepressants take time to work so do not be discouraged if you do not feel better straight away. It may take 2 to 3 weeks to feel the full benefit of DEPTRAN.

Even when you feel well, you may need to take DEPTRAN for several months or longer, to make sure that the benefits last.

Do not stop taking DEPTRAN, or change the dose, without first checking with your doctor.

If you forget to take it

If it is almost time for your next dose (e.g. within 2 or 3 hours), skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, then go back to taking it as you would normally.

Do not try to make up for missed doses by taking more than one dose at a time. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at your nearest hospital if you think you or anyone else may have taken too much DEPTRAN.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include:

  • shortness of breath
  • feeling drowsy
  • fast or irregular heartbeats
  • feeling agitated
  • fever

While you are taking DEPTRAN

Things you must do

Tell all doctors, dentists and pharmacists who are treating you that you are taking DEPTRAN.

If you are about to start any new medicine, tell your doctor and pharmacist that you are taking DEPTRAN.

If you become pregnant while taking DEPTRAN, tell your doctor immediately.

If you are a woman of childbearing age, you should avoid becoming pregnant while taking DEPTRAN.

Tell your doctor immediately if you have any suicidal thoughts or other mental/mood changes.

If you or someone you know is demonstrating any of the following warning signs of suicide while taking DEPTRAN, contact your doctor or a mental health professional right away or go to the nearest hospital for treatment:

  • thoughts or talk of death or suicide
  • thoughts or talk of self-harm or harm to others
  • any recent attempts of self-harm
  • increase in aggressive behaviour, irritability or agitation
  • worsening of depression.

Occasionally, the symptoms of depression may include thoughts of suicide or self-harm. These symptoms may continue or get worse during the first one to two months of treatment until the full antidepressant effect of the medicine becomes apparent. This is more likely to occur in young adults under 24 years of age. All mentions of suicide or violence must be taken seriously.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. Your doctor may ask you to stop taking DEPTRAN a few days before surgery.

Things you must not do

Do not stop taking DEPTRAN, or change the dose, without first checking with your doctor.

Do not let yourself run out of DEPTRAN over the weekend or on holidays.

Suddenly stopping DEPTRAN may make you feel tired, sick in the stomach and give you a headache. To prevent this, your doctor may want to gradually reduce the amount you take each day before stopping the medicine completely.

Do not give DEPTRAN to anyone else, even if they have the same condition as you.

Do not take DEPTRAN to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving or operating machinery until you know how DEPTRAN affects you. DEPTRAN may cause drowsiness and affect coordination in some people.

If this occurs, do not drive, operate machinery or do things that may be dangerous if you are not alert.

Be careful when drinking alcohol while taking DEPTRAN. Combining DEPTRAN and alcohol can make you more sleepy, dizzy or light-headed.

Your doctor may suggest you avoid alcohol while you are being treated for depression.

All of the above precautions are important even after you have stopped taking DEPTRAN.

The effects of DEPTRAN may last for some days after you have stopped taking it.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking DEPTRAN.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

It can be difficult to tell whether side effects are the result of taking DEPTRAN, effects of your condition or side effects of other medicines you may be taking. For this reason, it is important to tell your doctor of any change in your condition.

Do not be alarmed by the list of side effects. You may not experience any of them.

Ask your doctor or pharmacist any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • drowsiness, dizziness, light-headedness
  • difficulty in sleeping, bad dreams
  • dry mouth
  • blurred vision
  • difficulty in passing urine
  • feeling sick, vomiting, indigestion
  • constipation, diarrhoea
  • changes in taste or taste sensitivity
  • loss of appetite or increase in appetite
  • mouth ulcers
  • numbness.

These side effects are usually mild.

Tell your doctor as soon as possible if you notice any of the following:

  • anxiety, nervousness, aggressive behaviour
  • fast or irregular heart beat
  • chest pain
  • bruising or bleeding more easily than normal, reddish or purple blotches under the skin
  • signs of frequent or worrying infections such as fever, severe chills, sore throat or mouth ulcers
  • yellowing of the skin and eyes (also called jaundice)
  • agitation, confusion
  • symptoms of tiredness, abdominal pain, jaundice and history of gallstones
  • symptoms of sunburn (such as redness, itching, swelling, blistering) which may occur more quickly than normal
  • unsteadiness, stiffness, shakiness or unwanted movements.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • seizures or fits.
  • symptoms of high fever, drowsiness, sweating, fast heartbeat and muscle stiffness
  • symptoms of allergy such as a skin rash, increased sweating, swelling of the face or tongue
  • thoughts of suicide or attempting suicide or self-harm
  • sudden pain or ache in or around your eye
  • eyes becoming red, or feeling hard or tender
  • vision worsening, becoming blurred or starting to see circles (haloes) around lights

These symptoms are usually rare but may be serious and need urgent medical attention.

Tell your doctor if you notice anything else that is making you feel unwell, even if it is not on this list. Other side effects not listed above may occur in some people.

Some of these side effects (e.g. changes in blood pressure, liver function or glucose control) can only be found when your doctor does tests from time to time to check your progress.

After taking DEPTRAN

Storage

Keep DEPTRAN where children cannot reach them. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep DEPTRAN 10 (containing 10mg of doxepin) in a cool, dry place where the temperature stays below 25°C.

Keep DEPTRAN 25 (containing 25mg of doxepin) in a cool, dry place where the temperature stays below 25°C.

Keep DEPTRAN 50 (containing 50mg of doxepin) in a cool, dry place where the temperature stays below 30°C.

Do not store it or any other medicine, in the bathroom or near a sink.

Do not leave it in the car or on window sills. Heat and dampness can destroy some medicines.

Keep your capsules in their blister pack until it is time to take them. If you take the capsules out of their container they may not keep well.

Disposal

If your doctor tells you to stop taking DEPTRAN, or the capsules or tablets have passed their expiry date, ask your pharmacist what to do with any left over.

Product description

What it looks like

  • DEPTRAN 10 - white capsule with "DP 10" written in black ink. Each pack contains 50 capsules.
  • DEPTRAN 25 - blue and white capsule. Each pack contains 50 capsules.
  • DEPTRAN 50 - six-sided, violet coloured tablet, marked "DN" over "50" on one side and a Greek alpha symbol on the other. Each pack contains 50 tablets.

Ingredients

The active ingredient in DEPTRAN is doxepin (as doxepin hydrochloride).

Each DEPTRAN 10 capsule contains 10 mg of doxepin.

The 10 mg capsules also contain:

  • lactose monohydrate
  • sodium starch glycolate
  • purified talc
  • magnesium stearate
  • empty Hard Gelatin Capsule White Opaque/White Opaque 10000368 (PI: 111127)
  • tekPrint SW-9008 Black Ink (PI: 2328)
  • tekPrint SW-9009 Black Ink (PI: 2343)

Each DEPTRAN 25 capsule contains 25 mg of doxepin.

The 25 mg capsules also contain:

  • lactose monohydrate
  • sodium starch glycolate
  • purified talc
  • magnesium stearate
  • sodium lauryl sulfate
  • colloidal anhydrous silica
  • gelatin
  • titanium dioxide
  • brilliant blue FCF CI42090
  • erythrosine CI45430

Each DEPTRAN 50 tablet contains 50 mg of doxepin.

DEPTRAN 50 tablets also contain:

  • lactose monohydrate
  • microcrystalline cellulose
  • povidone
  • purified talc
  • sodium starch glycollate
  • magnesium stearate
  • carnauba wax
  • hypromellose
  • diethyl phthalate
  • erythrosine CI45430
  • indigo carmine CI73015

DEPTRAN capsules and tablets are gluten free.

Supplier

DEPTRAN is supplied in Australia by:

Alphapharm Pty Ltd
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian registration numbers:

DEPTRAN 10 - AUST R 60447; 308999

DEPTRAN 25 - AUST R 60448

DEPTRAN 50 - AUST R 17637

This leaflet was prepared in July 2020.

DEPTRAN_cmi\Jul20/00

Published by MIMS August 2020

BRAND INFORMATION

Brand name

Deptran

Active ingredient

Doxepin

Schedule

S4

 

1 Name of Medicine

Doxepin (as hydrochloride).

2 Qualitative and Quantitative Composition

Doxepin hydrochloride, a dibenzoxepin derivative, consists of a mixture of the cis and trans isomers in a constant ratio (13 to 18.5% cis; 87 to 81.5% trans).
Each capsule contains either 10 mg or 25 mg of doxepin (as hydrochloride) as the active ingredient.
Each tablet contains either 50 mg or 75 mg of doxepin (as hydrochloride) as the active ingredient.

Excipients with known effect.

Sugars (as lactose), galactose and sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Doxepin is a white crystalline powder, with a slight and amine-like odour. It is soluble in 1.5 parts of water, in 1 part of ethanol (96%) and in 2 parts of chloroform, and has a melting point of 185°-191°C.
Deptran 10: size 3 capsule with a white opaque body and white opaque cap with "DP 10" printed in black ink.
Deptran 25: size 3 capsule with a white opaque body and blue cap.
Deptran 50: violet film coated, hexagonal tablet, marked "DN" over "50" on one side and "α" on reverse.
Deptran 75: white film coated, hexagonal tablet, marked "DN" break line "75" on one side and "α" on reverse.

4 Clinical Particulars

4.1 Therapeutic Indications

For the treatment of major depression.
The 50 mg and 75 mg tablets are indicated only for the maintenance treatment of major depression (see Section 4.4 Special Warnings and Precautions for Use).

4.2 Dose and Method of Administration

The optimum oral dose depends on the severity of the condition and the individual patient's response. The dose varies from 30 mg to 300 mg daily, and is usually administered in a three times daily regimen. When the optimum dose has been reached, it may be given as a single daily dose up to a maximum of 150 mg.
For patients where the presenting symptoms are mild, it is advisable to initiate treatment at a dose of 30 mg daily; a good clinical response is obtained in many of these patients at a daily dose of 30 to 50 mg. The dosage may be adjusted according to the individual response.
For the majority of patients with moderate or severe symptoms, it is recommended that treatment commences with an initial dose of not more than 75 mg daily in divided doses. Many of these patients will respond satisfactorily at this dose level. For patients who do not respond at this dose level, the dosage may be adjusted according to individual response. In more severely ill patients, particularly where depression is the predominant presenting symptom, it may be necessary to administer a dose of up to 300 mg a day in divided doses to obtain a clinical response. This dosage is not intended for initiation of treatment.
Where insomnia is a troublesome symptom, it is recommended that after initial titration as discussed above, the total daily dose be divided so that a higher proportion but not more than 150 mg is given for the evening dose. A single daily dose of up to 150 mg may be given in the evening once the optimum daily dose has been reached. Similarly, should daytime drowsiness be experienced as a side effect of treatment, the same routine should be adopted, or the dosage may be reduced (see Section 4.4 Special Warnings and Precautions for Use).
It is often possible, in the individual patient, to reduce the dose for maintenance therapy having already obtained a satisfactory therapeutic response.
Dosage reduction may be required in elderly patients and in patients with hepatic impairment.
Optimal antidepressant effect may not be evident for two to three weeks whereas the antianxiety effect should be evident sooner.

4.3 Contraindications

Hypersensitivity to tricyclic antidepressants (TCAs), doxepin, or any of the inactive ingredients.
Glaucoma or a tendency to urinary retention, particularly in older patients.

4.4 Special Warnings and Precautions for Use

Therapeutic doses of tricyclic antidepressants have the potential to cause cardiac arrhythmias, and effects on cardiac conduction are dose related. Caution should be exercised in the use of Deptran in patients with cardiac disease.
The dosage of Deptran in patients with intercurrent illness or those taking other medications should be carefully adjusted. This is especially important in patients receiving other medications with anticholinergic effects (see Section 4.8 Adverse Effects (Undesirable Effects)).

Impairment of motor coordination.

Patients should be warned of the possibility of drowsiness or motor incoordination occurring with the use of this drug and should therefore be cautioned against driving a car or operating dangerous machinery while taking this drug.
Combined use with other antidepressants, alcohol or antianxiety agents should be undertaken with due recognition of the possibility of potentiation (see Section 4.8 Adverse Effects (Undesirable Effects)). It is known, for example, that monoamine oxidase (MAO) inhibitors may potentiate other drug effects; therefore, patients who have been receiving MAO inhibitors should discontinue that therapy for two weeks prior to starting on Deptran.
Should increased symptoms of psychosis or shift to manic symptomatology occur, it may be necessary to reduce dosage or add a major tranquilliser to the dosage regimen.

Bipolar disorder and activation of mania/hypomania.

A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed that treating such an episode with an antidepressant alone can increase the likelihood of precipitation of a mixed/manic episode in patients at risk of bipolar disorder. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder and depression.

Clinical worsening and suicide risk associated with psychiatric disorders.

The risk of suicide attempt is inherent in depression and may persist until significant remission occurs. This risk must be considered in all depressed patients.
Patients with depression may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviour (suicidality) whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored for clinical worsening and suicidality, especially at the beginning of a course of treatment, or at the time of dose changes, either increases or decreases. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset or was not part of the patient's presenting symptoms.
Patients (and caregivers of patients) should be alerted about the need to monitor for any worsening of their condition and/or the emergence of suicidal ideation/behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present. Patients with comorbid depression associated with other psychiatric disorders being treated with antidepressants should be similarly observed for clinical worsening and suicidality.
Patients with a history of suicide related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment.
Pooled analyses of 24 short-term (4 to 16 weeks), placebo controlled trials of nine antidepressant medicines (SSRIs and others) in 4400 children and adolescents with major depressive disorder (16 trials), obsessive compulsive disorder (4 trials) or other psychiatric disorders (4 trials) have revealed a greater risk of adverse events representing suicidal behaviour or thinking (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients treated with an antidepressant was 4% compared with 2% of patients given placebo. There was considerable variation in risk among the antidepressants, but there was a tendency towards an increase for almost all antidepressants studied. The risk of suicidality was most consistently observed in the major depressive disorder trials, but there were signals of risk arising from trials in other psychiatric indications (obsessive compulsive disorder and social anxiety disorder) as well. No suicides occurred in these trials. It is unknown whether the suicidality risk in children and adolescent patients extends to use beyond several months. The nine antidepressant medicines in the pooled analyses included five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and four non-SSRIs (bupropion, mirtazapine, nefazodone, venlafaxine).
A further pooled analysis of short-term placebo controlled studies of antidepressant medications (SSRIs and others) showed the increased risk of suicidal thinking and behaviour, known as suicidality, in the initial treatment (generally the first one to two months) extends to young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond the age of 24 years; there was a reduction with antidepressants compared to placebo in adults aged 65 years and older.
Symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness), impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adults, adolescents and children being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either worsening of depression and/or emergence of suicidal impulses has not been established, there is concern that such symptoms may be precursors of emerging suicidality.
Families and caregivers of children and adolescents being treated with antidepressants for major depressive disorder or for any other condition (psychiatric or nonpsychiatric) should be informed about the need to monitor these patients for the emergence of agitation, irritability, unusual changes in behaviour, and other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. It is particularly important that monitoring be undertaken during the initial few months of antidepressant treatment or at times of dose increase or decrease.
Prescriptions for Deptran should be written for the smallest quantity of tablets or capsules consistent with good patient management, in order to reduce the risk of overdose.

Angle closure glaucoma.

The pupillary dilation that occurs following use of many antidepressant drugs including doxepin may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Severe morbidity following overdosage.

Major depression carries an inherent and predictable risk of suicide, frequently involving drug overdose. Overdosage with tricyclic antidepressants, including Deptran, may lead to severe morbidity, requiring aggressive supportive therapy, and carries a significant risk of fatal outcome (see Section 4.9 Overdose). In view of this risk, before prescribing any tricyclic antidepressant, including Deptran, doctors should give serious consideration to the use of an antidepressant of a class with less potential for serious morbidity or mortality in the event of overdose. If the decision is made to prescribe Deptran, prescriptions should be written for the smallest feasible amount and patients should be supervised closely during the early course of treatment.

Deptran 50 mg and 75 mg tablets.

The 50 mg and 75 mg tablets are indicated only for the maintenance treatment of major depression. The 50 mg and 75 mg tablets should not be used in acutely ill patients where there is a risk of suicide. There is an increased risk of completed suicide by overdose with the 50 mg and 75 mg tablets compared with the 10 mg and 25 mg capsules.
The possibility of development of withdrawal symptoms on abrupt cessation of treatment after prolonged doxepin treatment should be borne in mind.

Use in hepatic or renal impairment.

Deptran should be used with caution in patients with hepatic or renal impairment.

Use in the elderly.

The dose of Deptran in elderly patients should be adjusted carefully, based on the patient's condition (see Section 4.3 Contraindications).

Paediatric use.

The safety and efficacy of Deptran for the treatment of depression or other psychiatric disorders in children and adolescents aged less than 18 years has not been satisfactorily established. Deptran should not be used in this age group for the treatment of depression or other psychiatric disorders.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Monoamine oxidase inhibitors.

Serious side effects and even death have been reported following the concomitant use of certain drugs with MAO inhibitors. Therefore, MAO inhibitors should be discontinued at least 2 weeks prior to the cautious initiation of Deptran therapy. The exact length of time may vary and is dependent upon the particular MAO inhibitor being used, the length of time it has been administered and the dosage involved.

Drugs metabolised by cytochrome P450 2D6.

The biochemical activity of the cytochrome P450 metabolising isoenzyme 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7 to 10%). Such individuals are called poor metabolisers and may have higher than expected plasma concentrations of tricyclic antidepressants when given usual doses.

Cytochrome P450 2D6 inhibitors.

Normal metabolisers may resemble poor metabolisers when given compounds that inhibit cytochrome P450 2D6. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolised by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines and the type 1C antiarrhythmics propafenone and flecainide). Concomitant use of tricyclic antidepressants with drugs that inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant (TCA) or the other drug. Whenever one of these other drugs is withdrawn from cotherapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is coadministered with a known inhibitor of P450 2D6.

Hepatic enzyme inducers.

Substances that activate the hepatic monooxygenase enzyme system (e.g. barbiturates, phenytoin, carbamazepine) may lower the plasma concentration of tricyclic antidepressants and so reduce their effect. In addition, concomitant administration of a tricyclic antidepressant with phenytoin or carbamazepine may lead to elevated serum phenytoin or carbamazepine concentrations. If necessary, the doses of these drugs should be adjusted.

Selective serotonin reuptake inhibitors.

The selective serotonin reuptake inhibitors (SSRIs), e.g. fluoxetine, sertraline and paroxetine, inhibit P450 2D6 and can elevate tricyclic antidepressant blood levels. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Caution is indicated in the coadministration of tricyclic antidepressants with any of the SSRIs and in switching from one class to the other. Sufficient time must elapse before initiating tricyclic antidepressant treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least five weeks may be necessary).

Sympathomimetic agents.

The cardiovascular effect of sympathomimetic agents such as adrenaline (epinephrine), noradrenaline (norepinephrine) and amphetamine (as well as nasal drops and local anaesthetics containing sympathomimetics) may be potentiated by tricyclic antidepressants.

Anticholinergic agents.

Tricyclic antidepressants may have an additive anticholinergic effect when given in combination with anticholinergics or neuroleptics with an anticholinergic action (e.g. phenothiazines); hyperexcitation states or delirium may occur, as well as attacks of glaucoma, urinary retention or paralytic ileus.

Cimetidine.

Cimetidine has been reported to produce clinically significant fluctuations in steady-state serum concentrations of various tricyclic antidepressants. Serious anticholinergic symptoms (i.e. severe dry mouth, urinary retention and blurred vision) have been associated with elevations in the serum levels of tricyclic antidepressants when cimetidine therapy is initiated. Additionally, higher than expected tricyclic antidepressant levels have been observed when they are begun in patients already taking cimetidine. In patients who have been reported to be well controlled on tricyclic antidepressants while receiving concurrent cimetidine therapy, discontinuation of cimetidine has been reported to decrease established steady-state serum tricyclic antidepressant levels and compromise their therapeutic effects.

Alcohol.

It should be borne in mind that alcohol ingestion may increase the danger inherent in any intentional or unintentional doxepin overdosage. This is especially important in patients who may use alcohol excessively.

Antihypertensive agents.

The antihypertensive effects of guanethidine and related agents are reduced or negated by concurrent use with TCAs (see Section 5.1, Mechanism of action).

Tolazamide.

A case of severe hypoglycaemia has been reported in a type II diabetic patient maintained on tolazamide (1 g/day) eleven days after the addition of doxepin (75 mg/day).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Tricyclic antidepressants have not been shown to be associated with an increased incidence of birth defects. However there is evidence of interference with central monoamine neurotransmission in rats. Care should be taken to ensure that there are sound reasons for the use of these antidepressants in pregnancy.
Withdrawal symptoms in newborn infants have been reported with prolonged maternal use of this class of drugs.
Tricyclic antidepressants have been found in small amounts in breast milk in an approximate milk to plasma ratio of 0.4:1.5. Limited data indicate that doxepin and its active metabolite desmethyldoxepin are excreted in breast milk. There has been a report of apnoea and drowsiness in a nursing infant whose mother was taking doxepin. Because of the potential for adverse effects to the nursing infant, breastfeeding is not recommended during doxepin therapy.

4.7 Effects on Ability to Drive and Use Machines

Since drowsiness or motor incoordination may occur with the use of this drug, patients should be warned of the possibility and cautioned against driving a car or operating dangerous machinery while taking this drug.
Patients should also be cautioned that their response to alcohol may be potentiated.
The possibility of development of withdrawal symptoms on abrupt cessation of treatment after prolonged Deptran treatment should be borne in mind.

4.8 Adverse Effects (Undesirable Effects)

Note.

Some of the adverse effects noted below have not been specifically reported with doxepin use. However, due to the close pharmacological similarities among the tricyclics, the effects should be considered when prescribing doxepin.

Anticholinergic effects.

Dry mouth, blurred vision, constipation and urinary retention have been reported. If they do not subside with continued therapy, or if the symptoms become severe, it may be necessary to reduce the dose. There have been isolated cases of elevated intraocular pressure.

Central nervous system effects.

The most commonly noticed side effect is drowsiness. 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, tardive dyskinesias, tremor, hallucinations, paraesthesias, ataxia, extrapyramidal symptoms, seizures, anxiety, nervousness and aggressive reaction. An NMS-like syndrome has occurred in a patient with a history of depression with psychotic features treated with a lithium/doxepin combination.

Cardiovascular.

Cardiovascular effects including hypotension, hypertension and tachycardia have been reported occasionally. Changes in ECG parameters (widening of the QRS and PR interval) very rarely.

Allergic.

Skin rash, facial oedema, photosensitisation, urticaria and pruritus have occasionally occurred.

Haematologic.

Eosinophilia has been reported in a few patients. There have been occasional reports of bone marrow depression manifesting as agranulocytosis, leukopenia, thrombocytopenia and purpura. Haemolytic anaemia.

Gastrointestinal.

Nausea, vomiting, indigestion, taste disturbances, diarrhoea, anorexia and aphthous stomatitis have been reported (see Anticholinergic effects above).

Endocrine.

Raised or lowered libido, testicular swelling, gynaecomastia in males, enlargement of breasts and galactorrhoea in females, syndrome of inappropriate antidiuretic hormone secretion and raising or lowering of blood sugar levels have been reported with tricyclic administration.

Other.

Dizziness, tinnitus, headache, weight gain, sweating, chills, fatigue, weakness, flushing, jaundice, alopecia, headache, exacerbation of asthma and hyperpyrexia (in association with chlorpromazine) have been occasionally observed. Rare reports of hepatitis, hepatic abnormalities and increased appetite.

Postmarketing experience.

The following adverse events have been identified from the postmarketing experience.

Central nervous system effects.

Disorientation, hallucinations, tardive dyskinesia, hypoaesthesia, dysgeusia and convulsion.

Cardiovascular.

Hypertension, conduction disorders and arrhythmias.

Allergic.

Facial oedema, photosensitisation, urticaria and tongue oedema.

Haematologic.

Eosinophilia, bone marrow depression manifesting as agranulocytosis, leukopenia, thrombocytopenia and purpura.

Gastrointestinal.

Upper abdominal pain and aphthous stomatitis.

Endocrine.

Testicular swelling, gynaecomastia (in males), galactorrhoea (in females), syndrome of inappropriate ADH secretion and raised blood sugar level.

Withdrawal symptoms.

Abrupt cessation of treatment after prolonged administration may produce nausea, headache and malaise. These are not indicative of addiction and gradual withdrawal of Deptran should not cause these symptoms.

Other.

Jaundice, alopecia, mydriasis, angle closure glaucoma and hyperpyrexia (in association with chlorpromazine).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Deaths may occur from overdosage with tricyclic antidepressants including doxepin, with the ingestion of 15 to 20 mg/kg or more being potentially fatal. Because of its rapid absorption and the onset of cardiac and central nervous system toxicity, the patient should be brought to hospital as soon as possible for immediate monitoring and treatment.
Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. As the management is complex and changing, it is recommended that the physician contact the Poisons Information Centre on 131126 for current information and treatment.

Signs and symptoms.

Symptoms and signs at presentation depend upon the dose and the time since ingestion. The rapid absorption of TCAs can cause a patient with initially trivial symptoms to deteriorate and develop life-threatening toxicity rapidly. Patients who are asymptomatic at three hours postingestion do not normally develop major toxicity. Mild toxicity is commonly manifested by anticholinergic effects such as drowsiness, blurred vision and excessive dryness of mouth.
However, major toxicity can develop rapidly within 6 hours resulting in severe neurologic, anticholinergic and cardiovascular syndromes including respiratory depression, mental status changes, delirium, convulsions, seizures, CNS depression (including coma), cardiac dysrhythmias (tachycardia is a common anticholinergic and early sympathomimetic effect, supraventricular and ventricular tachycardias, A-V block, torsades de pointes and ventricular fibrillation), hypotension and ECG changes (such as QRS widening and QTc prolongation).
Other signs may also include confusion, disturbed concentration, transient visual or auditory hallucinations, agitation, stupor, urinary retention (bladder atony), decreased gastrointestinal motility (paralytic ileus), hyperthermia or hypothermia, hyperpyrexia, dilated pupils, hyper-reflexia, muscle rigidity and vomiting.

Management and treatment.

Where the dose taken is known to be low (< 5 mg/kg) and manifested only by mild symptoms, ECG monitoring, supportive therapy and observation for signs of CNS or respiratory depression and cardiovascular effects for at least 6 hours may be all that is necessary. If signs of toxicity occur at any time during this period, extended monitoring is recommended.
Severe toxicity must be suspected if overdosage is unknown, complicated by intake of alcohol or multiple drugs or when symptoms have deteriorated. A maximal limb lead QRS duration of ≥ 0.10 seconds may be the best indication.
Management should include cardiac monitoring to detect ECG abnormalities, establishing an intravenous line (normal saline) and securing the patient's airway. Activated charcoal may reduce absorption of the drug if given within one to two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube ensuring that the airway is protected. Emesis is not indicated since rapid neurologic and haemodynamic deterioration may occur.

Cardiovascular effects.

CV effects may be reversed by the use of intravenous hypertonic sodium bicarbonate to maintain the serum pH at 7.45 to 7.55. If the pH response is inadequate, hyperventilation may also be used, but extreme caution must be taken if conducted concomitantly so that pH > 7.60 or a pCO2 < 20 mmHg is avoided.
All class Ia and Ic antiarrhythmic drugs are contraindicated, whilst class Ib drugs may also exacerbate arrhythmias and the sodium channel blockade.
In rare instances, haemoperfusion may be beneficial in acute refractory cardiovascular instability in patients with acute toxicity. However, haemodialysis, peritoneal dialysis, exchange transfusions and forced diuresis are of little benefit due to high tissue and protein binding to doxepin.
Cardiovascular effects may persist beyond 48 hours.

CNS depression.

In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines or, if ineffective, by anticonvulsants (e.g. phenobarbital (phenobarbitone), phenytoin). Because of its potentially fatal adverse effects, physostigmine is not recommended except to treat life threatening symptoms that have been unresponsive to other therapies. Physostigmine should only be used in consultation with the Poisons Information Centre.
Neurologic effects may persist for 24 to 48 hours.

Follow-up.

Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase, therefore, psychiatric referral may be appropriate.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Deptran is a dibenzoxepin psychotherapeutic agent. The mechanism of action of doxepin is not definitely known. It is not a CNS stimulant nor a monoamine oxidase (MAO) inhibitor. The current theory 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 (norepinephrine) by reuptake into the nerve terminals is prevented.
Animal studies suggest that doxepin hydrochloride does not appreciably antagonise the antihypertensive action of guanethidine. In animal studies, anticholinergic, antiserotonin and antihistamine effects on smooth muscle have been demonstrated. At higher than usual clinical doses, noradrenaline (norepinephrine) response was potentiated in animals. This effect was not demonstrated in humans.
At clinical dosages up to 150 mg/day, Deptran can be given to man concomitantly with guanethidine and related compounds without blocking the antihypertensive effect. At dosages above 150 mg/day, blocking of the antihypertensive effect of these compounds has been reported.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Doxepin is readily absorbed from the gastrointestinal tract, and extensively demethylated by first-pass metabolism in the liver, to its primary active metabolite, desmethyldoxepin. Since doxepin slows gastrointestinal transit time, absorption can be delayed, particularly in overdosage.

Distribution.

Doxepin and desmethyldoxepin are widely distributed throughout the body and are extensively bound to plasma and tissue protein.
The estimated plasma half-life of doxepin ranges from 8 to 24 hours, and may be considerably extended in overdosage. The half-life of desmethyldoxepin is longer.
Doxepin crosses the blood brain barrier and the placental barrier.

Metabolism.

Paths of metabolism of both doxepin and desmethyldoxepin include hydroxylation, N-oxidation, and conjugation with glucuronic acid.

Excretion.

Doxepin is excreted in the urine, mainly in the form of its metabolites, either free or in conjugated form.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Deptran 10 mg capsules contain the following inactive ingredients: lactose monohydrate, sodium starch glycollate, purified talc, magnesium stearate, Empty Hard Gelatin Capsule White Opaque/White Opaque 10000368 (PI number: 111127), TekPrint SW-9008 Black Ink (PI number: 2328) and TekPrint SW-9009 (PI number: 2343).
Deptran 25 mg capsules contain the following inactive ingredients: lactose monohydrate, sodium starch glycollate, purified talc, magnesium stearate, sodium lauryl sulfate, colloidal anhydrous silica, gelatin, titanium dioxide, brilliant blue FCF CI42090 and erythrosine CI45430.
Deptran 50 mg tablets contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, povidone, purified talc, sodium starch glycollate, magnesium stearate, carnauba wax, hypromellose, titanium dioxide, diethyl phthalate, erythrosine CI45430 and indigo carmine CI73015.
Deptran 75 mg tablets contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, povidone, purified talc, sodium starch glycollate, magnesium stearate, carnauba wax, hypromellose, titanium dioxide and macrogol 400.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

10 mg and 25 mg capsules: store below 25°C.
50 mg and 75 mg tablets: store below 30°C.

6.5 Nature and Contents of Container

Container type.

PVC/PVDC/Al blister pack.

Pack sizes.

10 mg: 50; 25 mg: 10, 50, 90, 100; 50 mg: 10, 50, 1000; 75 mg: 30.
Some strengths, pack sizes and/or pack types may not be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


Chemical name: 11-[3-dimethylaminopropylidene]-6H-dibenz[b,e]oxepin hydrochloride.
Molecular formula: C19H21NO.HCl.
Molecular weight: 315.8.

CAS number.

1229-29-4.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes