Consumer medicine information

Allegron

Nortriptyline

BRAND INFORMATION

Brand name

Allegron

Active ingredient

Nortriptyline

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Allegron.

What is in this leaflet

This leaflet is designed to provide you with answers to some common questions about this medicine. It does not contain all the available information and does not take the place of talking with your doctor.

All medicines have risks and benefits.

Your doctor has more information about this medicine than is contained in this leaflet. Also, your doctor has had the benefit of taking a full and detailed history from you and is in the best position to make an expert judgement to meet your individual needs.

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

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

What ALLEGRON is used for

ALLEGRON is used to treat depression.

There are many different types of medicines used to treat depression. ALLEGRON belongs to a group of medicines called tricyclic antidepressants (TCAs). TCAs are thought to work by their action on brain chemicals called amines which are involved in controlling mood.

Your doctor may have prescribed ALLEGRON for another reason.

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

Before taking ALLEGRON

Tell your doctor if you have any of the following conditions or if you have ever experienced any of these conditions.

When you must not take ALLEGRON

Do not take ALLEGRON

  • if you have had an allergic reaction to any medicines containing nortriptyline or to any of the ingredients listed at the end of this leaflet (see 'Product Description').
    Signs of an allergic reaction may include rash, itching of the skin, shortness of breath and swelling of the tongue or face.
  • if you are taking another medicine for depression called a monoamine oxidase inhibitor (MAOI), or have been taking a MAOI within the last 14 days. Check with your doctor or pharmacist if you are unsure as to whether or not you are taking a MAOI.
  • if you are taking another medicine for sedation or anxiety.
    If you take both medicines together, you may have an allergic reaction.
  • if you have an irregular heart beat or have had a heart attack within the previous eight weeks.
  • if the expiry date on the pack has passed.
    If you take this medicine after the expiry date has passed, it may not work as well.
  • if the packaging is torn or shows signs of tampering.

Before you start taking ALLEGRON

Tell your doctor if you have allergies to any other medicines, including other medicines used to treat your current condition, or other substances such as foods, preservatives or dyes.

Tell your doctor if you are pregnant or intend to become pregnant. ALLEGRON is not recommended to be used during pregnancy. Your doctor will discuss the risks and benefits of using ALLEGRON if you are pregnant.

Tell your doctor if you are breast-feeding or plan to breast-feed. It is not known whether ALLEGRON passes into breast milk.

Tell your doctor if you have or have had any medical conditions, especially the following:

  • heart or blood vessel problems
  • diabetes
  • glaucoma (increased pressure in the eye)
  • difficulty in urinating
  • thyroid problems
  • epilepsy or seizures
  • mental illnesses such as mania or schizophrenia
  • family history of suicide or mania
  • psychiatric disorder such as suicidal thoughts

Tell your doctor if you plan to have surgery.

Tell your doctor about these things before you take ALLEGRON.

There is no specific information available to recommend the use of ALLEGRON in children or adolescents under 18 years of age.

Taking other medicines

Tell your doctor if you are taking any other medicines including any that you have bought from a pharmacy, supermarket or health food shop.

Some medicines may affect the way ALLEGRON works. These include:

  • cimetidine, a medicine used to treat ulcers and gastric reflux.
  • fluoxetine, a medicine used to treat depression.
  • quinidine, a medicine used to treat heart disease.
  • chlorpropamide, a medicine used to treat diabetes.
  • carbamazepine, a medicine used to treat epilepsy.
  • medicines used to treat high blood pressure.
  • medicines used to treat thyroid problems
  • selective serotonin reuptake inhibitors (SSRIs), a group of medicines used to treat depression and other mental illnesses, such as fluoxetine, sertraline and paroxetine. This could result in "serotonin syndrome". This condition may include feeling agitated or restless, confused, loss of muscle coordination or twitching muscles and shivering
  • anticholinergics, found in some medicines used to relieve stomach cramps; travel sickness; hayfever and allergies; cough and colds. This could result in high fever, particularly during hot weather. If you take these medicines together, you may feel drowsier and experience dry mouth, constipation, and dizziness for a longer period of time. Also, you may be more at risk of developing seizures and neuroleptic malignant syndrome. Neuroleptic malignant syndrome may include sudden increase in body temperature, sweating, fast heartbeat, muscle stiffness, high blood pressure and convulsions

Your doctor or pharmacist will be able to tell you what to do when taking ALLEGRON with other medicines.

How to take ALLEGRON

How much to take

Your doctor will tell you how much ALLEGRON you need to take each day. The usual adult dose for ALLEGRON is 75 to 100mg daily, in 3 or 4 divided doses. For elderly patients 25 to 50mg daily in divided doses is recommended. Your doctor may increase or decrease your dose depending on your condition.

How to take it

Tablets should be swallowed whole with a glass of water.

When to take it

ALLEGRON can be taken with or without food.

How long do I take it

For depression, the length of treatment will depend on how quickly your symptoms improve. Most antidepressants take time to work so don't be discouraged if you do not feel better right away. While some symptoms will be relieved sooner than others, ALLEGRON commonly takes two to four weeks before improvement is really apparent.

Continue taking ALLEGRON for as long as your doctor recommends.

If you do not start to feel better in about four weeks, check with your doctor.

If you forget to take it

Take it as soon as you remember, and then go back to taking it as you would normally.

Do not take an extra dose.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not try to make up for missed doses by taking more than one dose at a time.

If you take too much

Taking too much ALLEGRON at once can be dangerous and may cause death.

If you think that you have used too much ALLEGRON, you may need urgent medical attention.

Immediately telephone your doctor or Poisons Information Centre (13 11 26) or go to casualty at your nearest hospital, if you think you or anyone else has taken too much ALLEGRON.

Do this even if there are no signs of discomfort or poisoning.

If you have taken too much ALLEGRON you may exhibit the following signs:- confusion, blurred vision, drowsiness, hallucinations, agitation, vomiting, dizziness, body temperature changes (low and high), difficulty in breathing and increased or irregular heartbeat.

While you are taking ALLEGRON

Things you must do

Tell all doctors and pharmacists who are treating you that you are taking ALLEGRON.

Before you start any new medicine, tell your doctor or pharmacist that you are taking ALLEGRON.

Watch carefully for signs that your depression or anxiety is getting worse, especially in the first few weeks of treatment.

Tell your doctor immediately if you experience any of the following symptoms, especially if they are severe, you have not had these symptoms before or they happen very suddenly:

  • anxiety or agitation
  • panic attacks
  • difficulty sleeping
  • hostility or impulsiveness
  • restlessness
  • overactivity or uninhibited behaviour
  • thoughts of suicide

Tell your doctor immediately if you have any thoughts about suicide or doing harm to yourself.

The symptoms of depression or other psychiatric conditions may include thoughts of harming yourself or committing suicide. 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 children, adolescents and young adults ages 18 to 24.

Warning signs of suicide:

  • All thoughts or talk about suicide or violence are serious. If you or someone you know is showing the following warning signs, either contact your doctor or a mental health advisor right away or go to the nearest hospital for treatment.
  • Thoughts or talk about death or suicide
  • Thoughts or talk about self-harm or doing harm to others
  • Any recent attempts of self-harm
  • An increase in aggressive behaviour, irritability or agitation.

Tell your doctor if you develop a skin rash or hives while taking ALLEGRON.

Tell your doctor if you become pregnant while taking ALLEGRON.

Visit your doctor regularly so your progress can be checked.

Tell your doctor if your mouth feels dry and this lasts for more than 2 weeks. ALLEGRON causes dry mouth.

Things you must not do

Do not stop taking ALLEGRON or lower the dose without first checking with your doctor. Suddenly stopping ALLEGRON may cause unwanted side effects.

Do not drive or operate machinery until you know how ALLEGRON affects you.

Do not give ALLEGRON to anyone else. Your doctor has prescribed it specifically for you and your condition.

Things to be careful of

Be careful driving or operating machinery until you know how ALLEGRON affects you.

ALLEGRON may cause drowsiness in some people.

Make sure you know how you react to ALLEGRON before you drive a car or operate any machinery.

Be careful when drinking alcohol while taking ALLEGRON. Combining ALLEGRON and alcohol can make you more sleepy, dizzy or light-headed. Your doctor may suggest that you avoid alcohol while you are being treated with ALLEGRON.

Be careful to avoid exposure to sunlight while you are taking ALLEGRON, as symptoms of sunburn may occur more quickly than normal.

Some people may suffer symptoms such as nausea, headache or malaise if ALLEGRON is stopped suddenly. Your doctor may decide to reduce your dose, or the interval of your dose over 1 or 2 weeks.

Side effects

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

Like other medicines, ALLEGRON may cause some unwanted side effects. These are likely to vary from patient to patient. Some side effects may be related to the dose of ALLEGRON so it is important that you never exceed the stated dose.

It is important that you tell your doctor as soon as possible about any unwanted effects. Your doctor may then decide to adjust the dose of ALLEGRON you are taking.

Tell your doctor if you notice any of the following side effects and they worry you.

These are common side effects of tricyclic antidepressants.

  • Drowsiness, weakness, headache
  • blurred vision
  • constipation
  • diarrhoea and stomach pain
  • vomiting
  • dizziness or light-headedness (especially on standing rapidly)
  • nausea
  • difficulty passing urine
  • dry mouth

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

  • body temperature changes (low and high)
  • difficulty in breathing
  • increased heartbeat (palpitations) or irregular heartbeats
  • hallucinations
  • feeling anxious, restless or confused
  • tingling or numbness of the hands or feet
  • larger breast than normal (in men and women)
  • yellowing of the eyes or skin (jaundice)

These side effects are uncommon but may be serious and need urgent medical attention.

There are other rare side effects.

Tell your doctor if you notice any unusual symptoms or if you are concerned about any aspect of your health, even if you think the problems are not connected with this medicine and are not referred to in this leaflet.

After taking ALLEGRON

Storage

Keep your tablets in the blister pack until it is time to take them. If you take your tablets out of the blister pack, they may not keep as well.

Keep your tablets in a cool dry place where the temperature stays below 25 degrees C.

All medicines should be kept where young children cannot reach them.

There will be an expiry date (month, year) on your ALLEGRON carton.

The medicine should not be taken after this date because it may have lost some of its strength.

Disposal

If your doctor tells you to stop taking ALLEGRON or you find that this medicine has passed its expiry date, ask your pharmacist what to do with any remaining tablets.

Product description

What it looks like

ALLEGRON tablets are available in 2 strengths, 10mg and 25mg.

ALLEGRON tablets are available in packs of 50.

The 10mg tablets are round and white. The 25mg tablets are round and orange with a scoreline on one side.

Ingredients

Active Ingredient - 10mg or 25mg nortriptyline.

Inactive Ingredients - maize starch, magnesium stearate, lactose, calcium phosphate, glycerol and hypromellose.

The 25mg tablet also contains Sunset Yellow FCF CI15985.

Both the 10mg and 25mg tablet contain sugars as lactose.

Supplier

ALLEGRON is distributed by:

Arrow Pharma Pty Ltd
15-17 Chapel Street
Cremorne VIC 3121

Australian Registration Numbers:
10 mg: AUST R 14619
25 mg: AUST R 53747

This leaflet was revised in September 2022.

Published by MIMS November 2022

BRAND INFORMATION

Brand name

Allegron

Active ingredient

Nortriptyline

Schedule

S4

 

1 Name of Medicine

Nortriptyline hydrochloride.

2 Qualitative and Quantitative Composition

Allegron 10 mg and 25 mg tablets contain 10 mg and 25 mg nortriptyline (present as the hydrochloride) as the active ingredient, respectively.
Excipients with known effect: lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Allegron 10 mg tablets are plain, round, white tablets.
Allegron 25 mg tablets are orange round tablets with a scoreline on one side.

4 Clinical Particulars

4.1 Therapeutic Indications

Allegron is indicated for the treatment of major depression.

4.2 Dose and Method of Administration

Allegron is not recommended for children.
Allegron is administered orally in the form of tablets. Lower than usual dosages are recommended for elderly patients and adolescents. The dosage for outpatients should also be lower than that for hospitalised patients who will be under close supervision. The physician should initiate dosage at a low level and increase it gradually, noting carefully the clinical response and any evidence of intolerance. Following remission, maintenance medication may be required for a longer period of time at the lowest dose that will maintain remission.
If a patient develops minor adverse reactions, the dosage should be reduced. The drug should be discontinued promptly if adverse effects of a serious nature or allergic manifestations occur.

Usual adult dose.

25 mg 3 or 4 times daily; dosage should begin at a low level and be increased as required. Doses above 100 mg per day are not recommended.

Use in children and adolescents (< 18 years).

The safety and efficacy of Allegron for the treatment of depression or other psychiatric disorders in children and adolescents aged less than 18 years has not been satisfactorily established. Allegron should not be used in this age group for the treatment of depression or other psychiatric disorders (see Section 4.4 Special Warnings and Precautions for Use).

Elderly patients.

25 to 50 mg/day in divided doses.

Plasma levels.

Optimal responses to nortriptyline have been associated with plasma concentrations of 50 to 150 microgram/L. Higher concentrations may be associated with more adverse experiences. Plasma concentrations are difficult to measure, and physicians should consult with the laboratory professional staff.
Older patients have been reported to have larger plasma concentrations of the active nortriptyline metabolite 10-hydroxy-nortriptyline. In one case, this was associated with apparent cardiotoxicity despite nortriptyline concentrations within the "therapeutic range". Clinical findings should predominate over plasma concentrations as primary determinants of dosage changes.

4.3 Contraindications

The use of Allegron or other tricyclic antidepressants concurrently with a monoamine oxidase (MAO) inhibitor is contraindicated. Hyperpyretic crises, severe convulsions and fatalities have occurred when similar tricyclic antidepressants were used in such combinations. It is advisable to have discontinued the MAO inhibitor for at least two weeks before treatment with Allegron is started.
Patients hypersensitive to Allegron should not be given the drug.
Cross sensitivity between Allegron and other dibenzazepines is a possibility.
Allegron is contraindicated during the acute recovery period after myocardial infarction.

4.4 Special Warnings and Precautions for Use

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 behaviours (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 other) in 4,400 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).
Pooled analyses of short-term studies of antidepressant medications have also shown an increased risk of suicidal thinking and behaviour, known as suicidality, in young adults ages 18 to 24 during initial treatment (generally the first one to two months). 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 and 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.

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.
Prescriptions for Allegron should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
Patients with cardiovascular disease should be given Allegron only under close supervision because of the tendency of the drug to produce sinus tachycardia and to prolong the conduction time. Myocardial infarction, arrhythmia and strokes have occurred. The antihypertensive action of guanethidine and similar agents may be blocked. Because of its anticholinergic activity, Allegron should be used with great caution in patients with glaucoma or a history of urinary retention. Patients with a history of seizures should be followed closely when Allegron is administered, since this drug is known to lower the convulsive threshold.
Great care is required if Allegron is administered to hyperthyroid patients or to those receiving thyroid medication, since cardiac arrhythmias may develop.

Impairment of motor coordination.

Allegron may impair the mental and/or physical abilities required for the performance of hazardous tasks, such as operating machinery or driving a car; therefore, the patient should be warned accordingly.
Excessive consumption of alcohol in combination with nortriptyline therapy may have a potentiating effect, which may lead to the danger of increased suicide attempts or overdosage, especially in patients with histories of emotional disturbances or suicidal ideation. The patient should be informed that the response to alcohol may be exaggerated.

Other precautions.

The use of Allegron in schizophrenic patients may result in an exacerbation of the psychosis or may activate latent schizophrenic symptoms. If the drug is given to overactive or agitated patients, increased anxiety and agitation may occur. In manic depressive patients, Allegron may cause symptoms of the manic phase to emerge. Troublesome patient hostility may be aroused by the use of Allegron. Epileptiform seizures may accompany its administration, as is true of other drugs of its class.
When it is essential, the drug may be administered with electroconvulsive therapy, although the hazards may be increased. Discontinue the drug for several days, if possible, prior to elective surgery.
The possibility of a suicidal attempt by depressed patients remains after the initiation of treatment; in this regard, it is important that the least possible quantity of drug be dispensed at any given time.
Both elevation and lowering of blood sugar levels have been reported.

Use in the elderly.

No data available.

Paediatric use.

The safety and efficacy of Allegron for the treatment of depression or other psychiatric disorders in children and adolescents aged less than 18 years has not been satisfactorily established. Allegron 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

Steady-state serum concentrations of the tricyclic antidepressants are reported to fluctuate significantly as cimetidine is either added or deleted from the drug regimen. Serious anticholinergic symptoms (severe dry mouth, urinary retention, blurred vision) have been associated with elevations in the serum levels of the tricyclic antidepressant when cimetidine is added to the drug regimen. In addition, higher than expected steady-state serum concentrations of the tricyclic antidepressant have been observed when therapy is initiated in patients already taking cimetidine. Alternatively, decreases in the steady-state serum concentration of the tricyclic antidepressant have been reported in well controlled patients on concurrent therapy, on discontinuance of cimetidine. The therapeutic efficacy of the tricyclic antidepressant may be compromised in these patients as cimetidine is discontinued. Several of the tricyclic antidepressants have been cited in these reports.
There have been greater than twofold increases in previously stable plasma levels of other antidepressants, including nortriptyline, when Prozac 20 (fluoxetine hydrochloride) has been administered in combination with these agents. Fluoxetine and its active metabolite, norfluoxetine, have a long half-life (4 to 16 days for norfluoxetine) which might affect strategies during conversion from one drug to the other.
Administration of reserpine during therapy with a tricyclic antidepressant has been shown to produce a "stimulating" effect in some depressed patients. Close supervision and careful adjustment of the dosage are required when Allegron is used with other anticholinergic drugs and sympathomimetic drugs.
A case of significant hypoglycaemia has been reported in a type 2 diabetic patient maintained on chlorpropamide (250 mg/day) after the addition of nortriptyline (125 mg/day).
The concomitant administration of quinidine and nortriptyline may result in a significantly longer plasma half-life, higher AUC and lower clearance of nortriptyline.
Guanethidine and similar agents, thyroid medication, alcohol. (See Section 4.4 Special Warnings and Precautions for Use.)

Drugs metabolised by P450IID6.

A subset (3% to 10%) of the population has reduced activity of certain drug metabolising enzymes, such as cytochrome P450 isoenzyme P450IID6. Such individuals are referred to as 'poor metabolisers' of drugs, such as debrisoquine, dextromethorphan and the tricyclic antidepressants. These individuals may have higher than expected plasma concentrations of tricyclic antidepressants when given usual doses. In addition, certain drugs that are metabolised by this isoenzyme, including many antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors and others), may inhibit the activity of this isoenzyme, and thus may make normal metabolisers resemble poor metabolisers with regard to concomitant therapy with other drugs metabolised by this enzyme system, leading to drug interactions.
Concomitant use of tricyclic antidepressants with other drugs metabolised by cytochrome P450IID6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Therefore, coadministration of tricyclic antidepressants with other drugs that are metabolised by this isoenzyme, including other antidepressants, phenothiazines, carbamazepine and type IC antiarrhythmics (e.g. propafenone, flecainide and encainide), or that inhibit this enzyme (e.g. quinidine), should be approached with caution.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Animal reproduction studies have yielded inconclusive results.
(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 that there are sound indications for the use of these antidepressants in pregnancy.
Safe use of Allegron during pregnancy and lactation has not been established; therefore, when the drug is administered to pregnant patients, nursing mothers, or women of childbearing age, the potential benefits must be weighed against the possible hazards.
Daily feeding of nortriptyline at a diet level of 0.05% from day 5 to day 20 of the gestation period had no deleterious effects on foetal development of rabbits. Rats fed diets containing the equivalent of 30 mg/kg daily from the time of weaning until maturity and during breeding studies showed no indications of teratogenesis in the foetuses of two litters.
 See section Use in pregnancy.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Included in the following list are a few adverse reactions that have not been reported with this specific drug. However, the pharmacologic similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when nortriptyline is administered.

Cardiovascular.

Hypotension, hypertension, tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, stroke.

Psychiatric.

Confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia, panic, nightmares; hypomania; exacerbation of psychosis.

Neurological.

Numbness, tingling, paraesthesia of extremities; incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures; alteration in EEG patterns; tinnitus.

Anticholinergic.

Dry mouth and, rarely, associated sublingual adenitis or gingivitis; blurred vision, disturbance of accommodation, mydriasis; constipation, paralytic ileus; urinary retention, delayed micturition, dilation of the urinary tract.

Allergic.

Skin rash, petechiae, urticaria, itching, photosensitization (avoid excessive exposure to sunlight); oedema (general or of face and tongue), drug fever, cross sensitivity with other tricyclic drugs.

Haematologic.

Bone marrow depression, including agranulocytosis; aplastic anaemia; eosinophilia; purpura; thrombocytopenia.

Gastrointestinal.

Nausea and vomiting, anorexia, epigastric distress, diarrhoea; peculiar taste, stomatitis; abdominal cramps, black tongue, constipation, paralytic ileus.

Endocrine.

Gynaecomastia in the male; breast enlargement and galactorrhoea in the female; increased or decreased libido, impotence; testicular swelling; elevation or depression of blood sugar levels; syndrome of inappropriate ADH (antidiuretic hormone) secretion.

Other.

Jaundice (simulating obstructive); altered liver function, hepatitis and liver necrosis; weight gain or loss; perspiration; flushing; urinary frequency, nocturia; drowsiness, dizziness, weakness, fatigue; headache; parotid swelling; alopecia.

Withdrawal symptoms.

Though these are not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaise.

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 this class of drugs. 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 a poison control centre for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose; therefore, hospital monitoring is required as soon as possible.

Manifestations.

Critical manifestations of overdose include cardiac dysrhythmias, severe hypotension, convulsions and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Other signs of overdose may include confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia or many of the symptoms. See Section 4.8 Adverse Effects (Undesirable Effects).

Treatment.

In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs and unusual drug kinetics in your patient. Protect the patient's airway and support ventilation and perfusion. Meticulously monitor and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing charcoal.
Ventricular arrhythmias, especially when accompanied by lengthened QRS intervals, may respond to alkalinisation by hyperventilation or administration of sodium bicarbonate. It is important to monitor and manage serum electrolyte levels. Refractory arrhythmias may respond to propranolol, bretylium, or lignocaine. Quinidine and procainamide usually should not be used because they may exacerbate arrhythmias and conduction already slowed by the overdosage. Seizures may respond to diazepam. Phenytoin has pharmacologic properties that may be helpful in dealing with both the seizures and cardiac rhythm disturbances of tricyclic antidepressant overdose. Although the prophylactic use of phenytoin has been suggested, it is not yet of proven value.
Diuresis and dialysis remove little of the tricyclic antidepressant present in the body of a patient who has taken an overdose. Haemoperfusion is of unproven benefit. The patient who has taken a tricyclic overdose should be monitored closely, at least until the QRS duration is normal.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The mechanism of mood elevation by such tricyclic antidepressants is at present unknown. Allegron is not a monoamine oxidase inhibitor. It inhibits the activity of such diverse agents as histamine, 5-hydroxytryptamine and acetylcholine. It increases the pressor effect of noradrenaline but blocks the pressor effect of phenethylamine. Studies suggest that Allegron interferes with the transport, release and storage of catecholamines. Operant conditioning techniques in rats and pigeons suggest that Allegron has a combination of stimulant and depressant properties.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

No data available.

Distribution.

No data available.

Metabolism.

No data available.

Excretion.

No data available.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Allegron 10 mg and 25 mg tablets contain maize starch, magnesium stearate, lactose monohydrate, calcium phosphate, glycerol and hypromellose. Allegron 25 mg tablets also contain sunset yellow FCF aluminium lake as the colouring agent.

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

Store below 25°C, protect from light.

6.5 Nature and Contents of Container

Allegron 10 mg and 25 mg tablets are available in blister pack (PVC/Aluminium) of 50 tablets.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Nortriptyline hydrochloride is 5-(3-methylamino -propylidene)- 10,11-dihydro- 5H-dibenzo [a,d] cycloheptene hydrochloride. Its molecular weight is 299.8 and its empirical formula is C19H21N.HCl.

Chemical structure.

The structural formula is as follows:

CAS number.

894-71-3.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes