Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
Nortriptyline contains the active ingredient nortriptyline hydrochloride, which is a tricyclic antidepressant. Nortriptyline is used to treat major depression in adults.
Do not take Nortriptyline if: • you are allergic (hypersensitive) to nortriptyline or any of the other ingredients of Nortriptyline (see list of ingredients in Section 6). An allergic reaction may include rash, itching, difficulty breathing or swelling of the face, lips, throat or tongue • you have had a recent heart attack or heartbeat disorder, heart block or coronary artery disease • you are taking, or have stopped taking within the last 14 days, a monoamine oxidase inhibitor (e.g. phenelzine, isocarboxazid or tranylcypromine). If you are taking moclobemide you must stop this at least 24 hours before starting nortriptyline • You have to stop treatment with Nortriptyline and wait for 14 days before you start treatment with a monoamine oxidase inhibitor
Warnings and precautions Talk to your doctor before taking these tablets if: • you feel suicidal or aggressive • you are agitated, overactive, or suffer from schizophrenia • you have heart disease • you have a cardiac condition called Brugada syndrome • you have a thyroid condition or receive thyroid medication • you have a history of epilepsy
Package leaflet: Information for the user
• you have high pressure in the eyes (glaucoma) • you have an enlarged prostate • you are going to have electroconvulsive therapy (electric shock) • you are diabetic as you might need and adjustment of your antidiabetic medicine • you are going to receive an anaesthetic, e.g. for an operation - tell your doctor as it might be necessary to stop the treatment with nortriptyline before you are given anaesthetics • you have had an allergic reaction to another tricyclic antidepressant in the past • you have difficulty in passing urine • you have bipolar disorder, as some patients may enter into a manic phase • you have pylorus stenosis (narrowing of the gastric outlet) and paralytic ileus (blocked intestine) • you have excessive fever (hyperpyrexia) • you are going to have electroconvulsive therapy • you are elderly as you are more likely to suffer from certain side effects, such as dizziness when you stand up due to low blood pressure (see also section 4 Possible side effects) • you have severe liver disease
Thoughts of suicide and worsening of your depression If you are depressed 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.
Children and adolescents Do not give this medicine to children and adolescents aged below 18 years for these treatments as safety and efficacy have not been established in this age group.
Other medicines and Nortriptyline Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. • monoamine oxidase inhibitors
Prolonged QT interval A heart problem called 'prolonged QT interval' (which is shown on your electrocardiogram, ECG) and heart rhythm disorders (rapid or irregular heart beat) have been reported with Nortriptyline. Tell your doctor if you: • have slow heart rate • have or had a problem where your heart cannot pump the blood round your body as well as it should (a condition called heart failure) • are taking any other medication that may cause heart problems, or • have a problem that gives you a low level of potassium or magnesium, or a high level of potassium in your blood
You may find it helpful to tell a relative or close friend that you are depressed and ask them to read this leaflet. You might ask them to tell you if they think your depression is getting worse, or if they are worried about changes in your behaviour.
• (MAOIs) e.g. moclobemide, phenelzine, iproniazid, isocarboxazid, nialamide or tranylcypromine (used to treat depression) or selegiline (used to treat Parkinson's disease). These should not be taken at the same time as Nortriptyline (see section 2 Do not take Nortriptyline) • buprenorphine. This medicine may interact with Nortriptyline and you may experience symptoms such as involuntary, rhythmic contractions of muscles, including the muscles that control movement of the eye, agitation, hallucinations, coma, excessive sweating, tremor, exaggeration of reflexes, increased muscle tension, body temperature above 38°C. Contact your doctor when experiencing such symptoms. • adrenaline, ephedrine, isoprenaline, noradrenaline, phenylephrine and phenyl - propanolamine (these may be present in cough or cold medicine, and in some anaesthetics) • medicine to treat high blood pressure for example calcium channel blockers (e.g. diltiazem and verapamil), guanethidine, debrisoquine, bethanidine, clonidine reserpine and methyldopa • Anticholinergic drugs such as certain medicines to treat Parkinson's disease and gastrointestinal disorders (e.g. atropine, hyoscyamine) • thioridazine (used to treat schizophrenia) • tramadol (painkiller) • medicines to treat fungal infections (e.g. fluconazole, terbinafine, ketoconazole, and itraconazole) • sedatives (e.g. barbiturates) • antidepressants (e.g. SSRIs (fluoxetine, paroxetine, fluvoxamine), and bupropion) • medicines for certain heart conditions (e.g. beta blockers and antiarrhythmics) • cimetidine (used to treat stomach ulcers) • methylphenidate (used to treat ADHD) • oral contraceptives • rifampicin (to treat infections) • phenytoin and carbamazepine (used to treat epilepsy) • St. John's Wort (Hypericum perforatum) a herbal remedy used for depression • thyroid medication. You should also tell your doctor if you take or have recently taken medicine that may affect the heart´s rhythm. e.g.: • medicines to treat irregular heartbeats (e.g. quinidine and sotalol) • astemizole and terfenadine (used to treat allergies and hay fever) • medicines used to treat some mental illnesses (e.g. pimozide and sertindole) • cisapride (used to treat certain types of indigestion) • halofantrine (used to treat malaria) • methadone (used to treat pain and for detoxification) • diuretics ('water tablets' e.g. furosemide) • valproic acid (medicine used for the treatment of epilepsy and bipolar disorder)
Taking Nortriptyline with alcohol You should not drink alcohol while you are being treated with Nortriptyline as alcohol might increase the sedative effect.
Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. Nortriptyline should not be used during pregnancy unless your doctor considers it clearly necessary and only after careful consideration of the benefit and risk. If you have taken this medicine during the last part
If you are going to have an operation and receive general or local anaesthetics, you should tell your doctor that you are taking this medicine. Likewise, you should tell your dentist that you take this medicine if you are to receive a local anaesthetic.
of the pregnancy, the newborn may have withdrawal symptoms such as irritability, increased muscle tension, tremor, irregular breathing, poor drinking, loud crying, urinary retention, and constipation. Your doctor will advise you whether to start/continue/ stop breast-feeding, or stop using this medicine taking into account the benefit of breastfeeding for your child and the benefit of therapy for you.
Driving and using machines Do not drive or use machinery when you are on Nortriptyline unless you are sure your judgement and coordination are not affected. Antidepressants may affect your ability to drive or to operate machinery safely.
Nortriptyline contains lactose If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.
Adults • The recommended adult dose is 25 mg three or four times daily or the dose may be given once a day, usually at night. The dose should begin at a low level, 10 mg, 3-4 times daily, for example and be increased gradually as required. The maximum dose is 150 mg per day. • If your doctor tells you to take more than four 25 mg tablets a day, he or she may arrange for you to have regular blood tests.
Elderly The usual dose is 30 to 50 mg/day in divided doses.
Treatment may start at a low level (10-20 mg daily) and may be increased as required to the maximum dose of 50 mg. If you require a dose of 50 mg or over, your doctor will arrange for you to have a recording of your heart (ECG) and blood tests.
The 50 mg tablets are not appropriate for use in elderly patients.
Renal impairment In case of renal impairment, your doctor will increase or decrease the dose carefully and gradually. In most cases, however, the usual dosage will be given.
Hepatic impairment Patients with liver diseases or people known as 'poor metabolisers' usually receive lower doses. Your doctor may take blood samples to determine the level of nortriptyline in the blood.
Use in children and adolescent Nortriptyline should not be used in children and adolescents aged less than 18 years, as safety and efficacy have not been established.
Lower dosages are recommended for outpatients than for patients in hospital who will be under close supervision.
Duration of treatment
It may take a few weeks before you feel any improvement. Following remission maintenance treatment may be needed longer term, usually up to 6 months. This should be at the lowest dose that stops the symptoms of depression coming back.
If you take more Nortriptyline than you should Do not take more tablets than your doctor tells you to. If you ever take too many, or if a child has taken any nortriptyline, go to the nearest hospital casualty department or tell your doctor at once. Symptoms of overdose include blurred vision, fast or irregular heartbeats, difficulties passing water, dry mouth and tongue, intestinal blockage, fits, fever, agitation, confusion, hallucinations, uncontrolled movements, low blood pressure, weak pulse, pallor, difficulty breathing, blue discolouration of the skin, decreased heart rate, drowsiness, loss of consciousness, coma, various cardiac symptoms such as heart block, heart failure, cardiogenic shock, metabolic acidosis, hypokalaemia. An overdose can be very dangerous.
If you forget to take Nortriptyline If you forget to take a dose, take it as soon as you remember. If it is almost time for your next dose do not take a double dose to make up for a forgotten dose, just carry on as before. If you have missed several doses, discuss this with your doctor.
If you stop using Nortriptyline Antidepressants may not make you feel better for the first two weeks or more of treatment, so keep taking Nortriptyline until your doctor tells you to stop. Do not stop these tablets without discussing it with your doctor first. If you stop using Nortriptyline abruptly after prolong therapy you may have withdrawal symptoms, including not being able to sleep, headache, nausea, irritability and sweating.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately if you experience any of the following:
Rare (may affect up to 1 in 1,000 people): • bad constipation, a swollen stomach, fever and vomiting. These symptoms may be due to parts of the intestine becoming paralysed • any yellowing of the skin and the white in the eyes (jaundice). Your liver may be affected • bruising, bleeding, pallor or persistent sore throat and fever. These symptoms can be the first signs that your blood or bone marrow may be affected. Effects on the blood could be a decrease in the number of red cells (which carry oxygen around the body), white cells (which help to fight infection) and platelets (which help with clotting) • suicidal thoughts or behaviour
Very rare (may affect up to 1 in 10,000 people): • attacks of intermittent blurring of vision, rainbow vision, and eye pain. You should immediately have an eye examination before the treatment with this medicine can be continued. This condition may be signs of acute glaucoma
Not known (frequency cannot be estimated from the available): • involuntary, rhythmic contractions of muscles, including the muscles that control movement of the eye, agitation, hallucinations, coma, excessive sweating, tremor, exaggeration of reflexes, increased muscle tension, body temperature above 38°C. (signs of serotonin syndrome, a potentially life threatening condition).
• Brugada Syndrome (unmasking) (symptoms may include very fast heartbeat, dizziness, fainting, seizures). Tell your doctor straight away if you get these symptoms.
The following side effects have also been reported:
Very common (may affect more than 1 in 10 people): • dry mouth • excessive sweating • constipation • nausea (feeling sick) • headache • tremor • dizziness • blocked nose • accommodation disorder of the eyes • irregular or heavy heart beats • weight gain • aggression
Common (may affect up to 1 in 10 people): • strange body movements • flushing • weakness • fatigue • dizziness when you stand up due to low blood pressure (orthostatic hypotension) • disturbed coordination • disturbed attention • confusion • heart block • a heart problem called 'prolonged QT interval' (which is shown on your electrocardiogram, ECG) • changes in taste • blurred vision (dilated pupils) • decreases in libido and erectile dysfunction • agitation • tingling in arms & legs • problems urinating (increased or decreased) • feeling thirsty • low sodium concentration in the blood
Uncommon (may affect up to 1 in 100 people): • changes in sleep patterns (including nightmares) • numbness • vomiting • high blood pressure • anxiety • loss of appetite • diarrhoea • liver problems including jaundice • changes in sexual performance • increased production or outflow of breast milk without breast feeding
• increased pressure in the eye ball • collapse conditions • worsening of cardiac failure • convulsions (body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body) • ringing sounds in ear • an enlarged or swollen tongue • skin rash • swelling of the face
Rare (may affect up to 1 in 1,000 people): • mouth or gum problems • confusional states (delirium), especially in the elderly perhaps with anxiety and restlessness • hallucinations (in patients with schizophrenia) • more serious heart problems along with ringing in the ears, stomach cramps and clumsiness can also occasionally occur • increases in libido have been reported. • a rash, which may be itchy or get worse in sunlight. • Withdrawal symptoms; if you suddenly stop taking the tablets, you may not be able to sleep and may feel irritable or sweaty • Decreased appetite • Hair loss • Enlargement of male breast tissue • Weight loss • abnormal results of liver function tests • fever
Very rare (may affect up to 1 in 10,000 people): • alterations in brain function (including perhaps seizures) • swelling of ankles and in severe cases of the face & tongue • blood disorders may also occur along with changes in blood sugar level. In severe cases men may suffer from swelling of breasts & testicles whilst women may also notice an increase in breast size and spontaneous lactation. In extreme cases there may be swelling & damage to liver cells. • Increased pressure within eye • abnormal heart rhythm that can lead to sudden cardiac death (so called torsades de pointes) • heart muscle disease • feeling of inner restlessness and a compelling need to be in constant motion • disorder of the peripheral nerves • allergic inflammation of the lung alveoli and of the lung tissue
Not known (frequency cannot be estimated from the available): • changes of blood sugar levels • low sodium concentration in the blood • paranoia • movement disorders (involuntary movements or decreased movements) • hypersensitivity inflammation of heart muscle • hepatitis • syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
Reporting of side effects If you get any side effects, talk to your doctor 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 or search for MHRA Yellow Card in the Google Play or Apple App. By reporting side effects you can help provide more information on the safety of this medicine.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister, carton or bottle after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
What Nortriptyline contains The active substance is nortriptyline. Each 10 mg film-coated tablet contains 11.4 mg of nortriptyline (as hydrochloride). Each 25 mg film-coated tablet contains 28.5 mg of nortriptyline (as hydrochloride).
The other ingredients are: Tablet core: lactose monohydrate (see section 2 'Nortriptyline contains lactose'), maize starch, microcrystalline cellulose (E460), magnesium stearate (E470b) Tablet film-coating: hypromellose (E464), titanium dioxide (E171), macrogol
What Nortriptyline looks like and contents of the pack Nortriptyline 10 mg film-coated tablets are white, round, 5.5 mm in diameter and debossed with '10' on one side. Nortriptyline 25 mg film-coated tablets are white, round, 8 mm in diameter and debossed with '25' on one side.
Nortriptyline 10 mg film-coated tablets are available in blisters packs containing 30 or 100 tablets and in plastic bottles containing 100 or 500 tablets. Nortriptyline 25 mg film-coated tablets are available in blisters packs containing 30 or 100 tablets and in plastic bottles containing 100 or 500 tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder Mylan, Station Close, Potters Bar, Herts EN6 1TL United Kingdom
Manufacturers Mylan Hungary Kft., H-2900 Komárom, Mylan utca. 1, Hungary
This leaflet was last revised in November 2025
Other sources of information This leaflet is also available in other formats for partially-sighted patients. To request a copy of this leaflet in large print please call the Medical Information Direct Line: +44 (0)1707 853 000 (UK only)
Nortriptyline 25 mg film-coated tablets comes as tablet containing 25mg. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
The active substance in Nortriptyline 25 mg film-coated tablets is nortriptyline hydrochloride.
Medicines with the same active substance, strength and form include: Nortriptyline 25 mg Film-Coated Tablets, Nortriptyline 25 mg Film-coated Tablets, Nortriptyline 25 mg film-coated tablets. In total there are 6 equivalent products. They are interchangeable only if your prescriber or pharmacist says so.
This leaflet reproduces the patient information leaflet approved for Nortriptyline 25 mg film-coated tablets, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
Nortriptyline is indicated for the treatment of Major Depressive Episodes in adults.
Posology
Adults
The usual adult dose is 25 mg three or four times daily. Dosage should begin at a low level e.g. 10 mg three or four times daily, and be increased as required. Alternatively, the total daily dose may be given once a day, usually given at night. When doses above 100 mg daily are administered, plasma levels of nortriptyline should be monitored and maintained in the optimum range of 50 to 150 ng/ml. Doses above 150 mg per day are not recommended.
Lower than usual dosages are recommended for elderly patients. Lower dosages are also recommended for outpatients than 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 side-effects, the dosage should be reduced. The drug should be discontinued promptly if adverse effects of a serious nature or allergic manifestations occur.
Elderly
30 to 50 mg/day in divided doses. Dosage should begin at a low level (10 – 20 mg daily) and be increased as required to the maximum dose of 50 mg. If it is considered necessary to use higher dosing in an elderly patient an ECG should be checked and plasma levels of nortriptyline should be monitored.
Older patients have been reported to have higher plasma concentrations of the active nortriptyline metabolite 10-hydroxynortriptyline. In one case, this was associated with apparent cardiotoxicity, despite the fact that nortriptyline concentrations were within the 'therapeutic range'. Clinical findings should predominate over plasma concentrations as primary determinants of dosage changes.
Plasma levels
Optimal responses to nortriptyline have been associated with plasma concentrations of 50 to 150 ng/ml. Higher concentrations may be associated with more adverse experiences. Plasma concentrations are difficult to measure, and physicians should consult the laboratory professional staff.
Cytochrome P450 isoenzyme CYP2D6 and poor metabolisers
Many antidepressants (tricyclic antidepressants, including nortriptyline, selective serotonin re-uptake inhibitors and others) are metabolised by the hepatic cytochrome P450 isoenzyme CYP2D6. Three to ten per cent of the population have reduced isoenzyme activity ('poor metabolisers') and may have higher than expected plasma concentrations at usual doses. The percentage of 'poor metabolisers' in a population is also affected by its ethnic origin.
Reduced renal function
Renal failure does not affect kinetics of nortriptyline. This medicinal product can be given in usual doses to patients with renal failure.
Reduced hepatic function
In case of reduced liver function careful dosing and, if possible, a serum level determination is advisable.
Paediatric population
Nortriptyline should not be used in children and adolescents aged less than 18 years, as safety and efficacy have not been established (see section 4.4).
Duration of treatment
The antidepressant effect usually sets in after two to four weeks. Treatment with antidepressants is symptomatic and must therefore be continued for an appropriate length of time usually up to 6 months after recovery in order to prevent relapse.
Discontinuation of treatment
When stopping therapy nortriptyline should be gradually withdrawn over several weeks.
Method of administration
For oral administration.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Concomitant treatment with MAOIs (monoamine oxidase inhibitors) is contraindicated (see section 4.5).
Simultaneous administration of nortriptyline and MAOIs may cause serotonin syndrome (a combination of symptoms, possibly including agitation, confusion, tremor, myoclonus and hyperthermia).
Treatment with nortriptyline may be instituted 14 days after discontinuation of irreversible non-selective MAOIs and minimum one day after discontinuation of the reversible moclobemide. Treatment with MAOIs may be introduced 14 days after discontinuation of nortriptyline.
Recent myocardial infarction, any degree of heart block or disorders of cardiac rhythm and coronary artery insufficiency.
Suicide/suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts, Self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.
Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.
Close supervision of patients and in particular those at high risk should accompany drug therapy 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.
Withdrawal symptoms, including insomnia, irritability and excessive perspiration, may occur on abrupt cessation of therapy.
The use of nortriptyline in schizophrenic patients may result in an exacerbation of the psychosis or may activate latent schizophrenic symptoms. If administered to overactive or agitated patients, increased anxiety and agitation may occur. In manic depressive patients, nortriptyline may cause symptoms of the manic phase to emerge in which case the treatment with nortriptyline should be discontinued.
Cross sensitivity between nortriptyline and other tricyclic antidepressants is a possibility.
Caution should be exercised when treating patients with advance liver disease.
Patients with cardiovascular disease should be given nortriptyline 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. Great care is necessary if nortriptyline is administered to hyperthyroid patients or to those receiving thyroid medication, since cardiac arrhythmias may develop.
Cardiac arrhythmias are likely to occur with high dosage. They may also occur in patients with pre-existing heart disease taking normal dosage.
Unmasking of Brugada syndrome has been reported in patients treated with nortriptyline. Brugada syndrome is a rare hereditary disease of the cardiac sodium channel with characteristic ECG changes (ST segment elevation and T wave abnormalities in the right precordial leads), which may lead to cardiac arrest and/or sudden death. Nortriptyline should generally be avoided in patients with Brugada syndrome or those suspected of having Brugada syndrome. Caution is advised in patient with risk factors such as a family history of cardiac arrest or sudden death (see sections 4.8 and 4.9).
QT interval prolongation
Cases of QT interval prolongation and arrhythmia have been reported during the postmarketing period. Caution is advised in patients with significant bradycardia, in patients with uncompensated heart failure, or in patients concurrently taking QT-prolonging drugs. Electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia) are known to be conditions increasing the proarrhythmic risk.
The use of nortriptyline should be avoided, if possible, in patients with a history of epilepsy. If it is used, however, the patients should be observed carefully at the beginning of treatment, for nortriptyline is known to lower the convulsive threshold.
The elderly are particularly liable to experience adverse reactions, especially agitation, confusion and postural hypotension.
Troublesome hostility in a patient may be aroused by the use of nortriptyline.
If possible, the use of nortriptyline should be avoided in patients with narrow angle glaucoma or symptoms suggestive of prostatic hypertrophy.
When it is essential, nortriptyline may be administered with electroconvulsive therapy, although the hazards may be increased.
Both elevation and lowering of blood sugar levels have been reported. Significant hypoglycaemia was reported in a Type II diabetic patient maintained on chlorpropamide (250 mg/day), after the addition of nortriptyline (125 mg/day).
Anaesthetics given during tricyclic antidepressant therapy may increase the risk of arrhythmias and hypotension. If possible, discontinue this medicinal product several days before surgery; if emergency surgery is unavoidable, the anaesthetist should be informed that the patient is being so treated (see section 4.5).
Nortriptyline should be used with caution in patients with urinary retention, pylorus stenosis or paralytic ileus.
Hyperpyrexia has been reported with tricyclic antidepressants when administered with anticholinergic or with neuroleptic medications, especially in hot weather.
Serotonin syndrome
Concomitant administration of tricyclic antidepressants including nortriptyline and other serotonergic agents such as MAO inhibitors (see section 4.3) or buprenorphine may result in serotonin syndrome, a potentially life-threatening condition (see section 4.5).
If concomitant treatment with other serotonergic agents is clinically warranted, close monitoring of the patient is advised, especially at initiation of treatment and dose increases.
Symptoms of serotonin syndrome may include mental-status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms.
If serotonin syndrome is suspected, dose reduction or treatment discontinuation should be considered, depending on the severity of symptoms.
Paediatric population
Nortriptyline should not be used in the treatment of depression in children and adolescents under the age of 18 years. Studies in depression of this age group did not show a beneficial effect for class of tricyclic antidepressants. Studies with other classes of antidepressants (SSRI's and SNRI's) have shown risk of suicidality, self-harm and hostility to be related to these compounds. This risk cannot be excluded with nortriptyline. In addition, nortriptyline is associated with a risk of cardiovascular adverse events in all age groups.
Furthermore, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are not available (see also section 4.8 Undesirable effects and Section 4.9 Overdose.)
Warnings: as improvement may not occur during the initial weeks of therapy, patients, especially those posing a high suicidal risk, should be closely monitored during this period.
Excipients
The tablets contain lactose. Patients with rare hereditary problems such as galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Contraindicated combinations
MAOIs (non-selective as well as selective A (moclobemide) and B (selegiline)) - risk of 'serotonin syndrome' (see section 4.3).
Combinations that are not recommended
Sympathomimetic agents
Nortriptyline should not be given with sympathomimetic agents such as adrenaline, ephedrine, isoprenaline, noradrenaline, phenylephrine and phenylpropanolamine (e.g. as contained in local and general anaesthetics and nasal decongestants).
Adrenergic neurone blockers/antihypertensives
Nortriptyline may decrease the antihypertensive effect of guanethidine, debrisoquine, bethanidine, methyldopa and possibly clonidine. Concurrent administration of reserpine has been shown to produce a 'stimulating' effect in some depressed patients. It would be is advisable to review all antihypertensive therapy during treatment with tricyclic antidepressants.
Anticholinergic agents
Tricyclic antidepressants may potentiate the effects of these medicinal products on the eye, central nervous system, bowel and bladder; concomitant use of these should be avoided due to an increased risk of paralytic ileus, hyperpyrexia, etc.
Drugs which prolong the QT-interval, including antiarrhythmics such as quinidine, the antihistamines astemizole and terfenadine, some antipsychotics (notably pimozide and sertindole), cisapride, halofantrine, and sotalol, may increase the likelihood of ventricular arrhythmias when taken with tricyclic antidepressants.
Use caution when using nortriptyline and methadone concomitantly due to a potential for additive effects on the QT interval and increased risk of serious cardiovascular effects.
Caution is also advised for co-administration of nortriptyline and diuretics inducing hypokalaemia (e.g. furosemide).
Thioridazine
Co-administration of nortriptyline and thioridazine (CYP2D6 substrate) should be avoided due to inhibition of thioridazine metabolism and consequently increased risk of cardiac side effects
Tramadol
Concomitant use of tramadol (a CYP2D6 substrate) and tricyclic antidepressants (TCAs), such as nortriptyline increases the risk for seizures and serotonin syndrome. Additionally, this combination can inhibit the metabolism of tramadol to the active metabolite and thereby increasing tramadol concentrations potentially causing opioid toxicity.
Antifungals such as fluconazole and terbinafine increase serum concentrations of tricyclics and accompanying toxicity. Syncope and torsade de pointes have occurred.
Combinations requiring precautions for use
Serotonergic medicines, such as buprenorphine, which increase the risk of serotonin syndrome, a potentially life-threatening condition (see section 4.4).
CNS depressants
Nortriptyline may enhance the sedative effects of alcohol, barbiturates and other CNS depressants.
Tricyclic antidepressants (TCA) including nortriptyline are primarily metabolised by various hepatic cytochrome P450 isozymes (e.g., CYP1A2, CYP2C, CYP2D6, CYP3A4).
CYP2D6 inhibitors
The CYP2D6 isozyme can be inhibited by a variety of medicinal products, e.g. neuroleptics, serotonin reuptake inhibitors, beta blockers, and antiarrhythmics. Examples of strong CYP2D6 inhibitors include bupropion, fluoxetine, paroxetine and quinidine. These drugs may produce substantial decreases in TCA metabolism and marked increases in plasma concentrations. Consider monitoring TCA plasma levels, whenever a TCA is to be co-administered with another medicinal product known to be an inhibitor of CYP2D6. Dose adjustment of nortriptyline may be necessary (see section 4.2).
Other Cytochrome P450 inhibitors
Cimetidine, methylphenidate and calcium-channel blockers (e.g. diltiazem and verapamil) may increase plasma levels of tricyclic antidepressants and accompanying toxicity.
Tricyclic antidepressants and neuroleptics mutually inhibit the metabolism of each other; this may lead to a lowered convulsion threshold, and seizures. It may be necessary to adjust the dosage of these drugs.
Cytochrome P450 inducers
Oral contraceptives, rifampicin, phenytoin, barbiturates, carbamazepine and St. John's Wort (Hypericum perforatum) may increase the metabolism of tricyclic antidepressants and result in lowered plasma levels of tricyclic antidepressants and reduced antidepressant response.
In the presence of ethanol nortriptyline plasma concentrations were increased.
The CYP3A4 and CYP1A2 isozymes metabolise nortriptyline to a lesser extent. However, fluvoxamine (strong CYP1A2 inhibitor) was shown to increase nortriptyline plasma concentrations and this combination should be avoided. Clinically relevant interactions may be expected with concomitant use of nortriptyline and strong CYP3A4 inhibitors such as ketoconazole, itraconazole and ritonavir.
Valproic Acid
Nortriptyline plasma concentration can be increased by valproic acid. Clinical monitoring is therefore recommended.
Buprenorphine
Nortriptyline should be used cautiously when co-administered with buprenorphine as the risk of serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4).
Pregnancy
There is a moderate amount of data from the use of nortriptyline in pregnant women.
Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Therefore, the drug should not be administered to pregnant patients or women of childbearing age unless the potential benefits clearly outweigh any potential risk.
Following administration in the final weeks of pregnancy, neonatal withdrawal symptoms may occur including irritability, hypertonia, tremors, irregular breathing, weak suckling and possibly anticholinergic symptoms (urine retention, obstipation).
Breast-feeding
Nortriptyline is excreted in limited amounts in breastmilk (corresponding to 0.6 % - 1 % of the maternal dose). Adverse effects for infants have not been reported thus far. Breastfeeding can be continued during nortriptyline therapy if the benefit of the mother outweighs the potential risk for the infant. Observation of the infant is advised, especially during the first four weeks after birth.
Fertility
The reproductive toxicity of nortriptyline has not been investigated in animals. For its parent substance amitriptyline, association with an effect on fertility in rats, namely a lower pregnancy rate was observed. (see section 5.3).
Nortriptyline has moderate influence on the ability to drive and use machines.
Nortriptyline 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.
In the listing below the MedDRA system organ system and frequency convention is used.
The frequencies are represented as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
System Organ Class
Frequency
Undesirable effects
Blood and lymphatic system disorders
Rare
Bone marrow depression, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia
Endocrine disorders
Not known
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Metabolism and nutrition disorders
Rare
Decreased appetite
Not known
Changes of blood sugar levels, hyponatraemia
Psychiatric disorders
Very common
Aggression
Common
Confusional state, libido decreased, agitation
Uncommon
Hypomania, mania, anxiety, insomnia, nightmares
Rare
Delirium (in elderly patients), hallucinations (in schizophrenic patients)
Not known
Suicidal ideation and suicidal behaviour*, paranoia
Nervous system disorders
Very common
Tremor, dizziness, headache
Common
Disturbance in attention, dysgeusia, paraesthesia, ataxia
Uncommon
Convulsion
Rare
Akathisia, dyskinesia
Not known
Extrapyramidal disorder, serotonin syndrome**
Eye disorders
Very common
Accommodation disorder
Common
Mydriasis
Very rare
Acute glaucoma
Ear and labyrinth disorders
Uncommon
Tinnitus
Cardiac disorders
Very common
Palpitations, tachycardia
Common
Atrioventricular block, bundle branch block
Uncommon
Collapse conditions, worsening of cardiac failure
Rare
Arrhythmia
Very rare
Cardiomyopathies, torsades de pointes
Not known
Hypersensitivity myocarditis, brugada syndrome (unmasking)
Vascular disorders
Common
Orthostatic hypotension
Uncommon
Hypertension
Not known
Hyperthermia
Respiratory, thoracic and mediastinal disorders
Very common
Congested nose
Very rare
Allergic inflammation of the pulmonary alveoli and of the lung tissue, respectively (alveolitis, Löffler's syndrome)
Gastrointestinal disorders
Very common
Dry mouth, constipation, nausea
Uncommon
Diarrhoea, vomiting, tongue oedema
Rare
Salivary gland enlargement, ileus paralytic
Hepatobiliary disorders
Uncommon
Hepatic impairment (e.g. cholestatic liver disease)
Rare
Jaundice
Not known
Hepatitis
Skin and subcutaneous tissue disorders
Very common
Hyperhidrosis
Uncommon
Rash, urticaria, face oedema
Rare
Alopecia, photosensitivity reaction
Renal and urinary disorders
Uncommon
Urinary retention
Common
Micturition disorders
Reproductive system and breast disorders
Common
Erectile dysfunction
Uncommon
Galactorrhoea
Rare
Gynaecomastia
General disorders and administration site conditions
Common
Fatigue, feeling thirst
Rare
Pyrexia
Investigations
Common
Electrocardiogram abnormal, electrocardiogram QT prolonged, electrocardiogram QRS complex prolonged, hyponatremia
Uncommon
Intraocular pressure increased
Rare
Weight decreased, liver function test abnormal, blood alkaline phosphatase increased, transaminases increased
* Cases of suicidal ideation and suicidal behaviours have been reported during nortriptyline therapy or early after treatment discontinuation (see section 4.4)
** This event has been reported for serotonergic medicines such as the therapeutic class of tricyclic antidepressants (see sections 4.4 and 4.5).
Withdrawal symptoms
Abrupt cessation of treatment after prolonged therapy may produce nausea, headache and malaise.
Class Effects
Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRs and TCAs. The mechanism leading to this risk is unknown.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at:www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Signs and symptoms
50 mg of a tricyclic antidepressant can be an overdose in a child.
Of patients who are alive at presentation, mortality of 0-15% has been reported. Symptoms may begin within several hours and may include blurred vision, confusion, restlessness, dizziness, hypothermia, hyperthermia, agitation, vomiting, hyperactive reflexes, dilated pupils, fever, rapid heart rate, decreased bowel sounds, dry mouth, inability to void, myoclonic jerks, seizures, respiratory depression, myoglobinuric renal failure, nystagmus, ataxia, dysarthria, choreoathetosis, coma, hypotension and cardiac arrhythmias. Cardiac conduction may be slowed, with prolongation of QRS complex and QT intervals, right bundle branch and AV block, ventricular tachyarrhythmias (including Torsade de pointes and fibrillation) and death. Prolongation of QRS duration to more than 100msec is predictive of more severe toxicity. The absence of sinus tachycardia does not ensure a benign course. Hypotension may be caused by vasodilatation, central and peripheral alpha adrenergic blockade and cardiac depression. In a healthy young person, prolonged resuscitation may be effective; one patient survived 5 hours of cardiac massage.
Brugada syndrome (unmasking) and Brugada ECG pattern (BEP) have been reported in post-marketing surveillance in association with nortriptyline overdose.
Treatment
The treatment is symptomatic and supportive. Patients must be continuously monitored and closely followed up, even in apparently uncomplicated situations.
The airways, breathing and circulation (ABC) must be evaluated and treated, if necessary. Patency of the airway is maintained by intubation, where required. Treatment with artificial respiration is recommended in order to prevent a possible respiratory arrest. Continuous ECG-monitoring of cardiac function should continue, at least until the QRS duration is normal. Ventricular arrhythmias, especially when accompanied by lengthened QRS intervals, may respond to alkalinisation by hyperventilation or administration of sodium bicarbonate. Quinidine and procainamide usually should not be used because they may exacerbate arrhythmias and conduction already slowed by the overdose. Urea and electrolyte levels must be monitored, especially for low potassium. Urinary output must be monitored. Arterial blood gases must be monitored, especially for acidosis. Consider gastric lavage only if it can be performed within one hour of a potentially fatal overdose. Give 50 g of activated charcoal (1 g/ kg body weight if given to a child) if within one hour of ingestion. Activated charcoal may be more effective than emesis or lavage to reduce absorption. Diuresis and dialysis have little effect. Haemoperfusion is unproven.
Treatment of the following should be decided on a case-by-case basis:
– Wide QRS-intervals, cardiac failure and ventricular arrhythmias
– Circulatory failure
– Hypotension
– Hyperthermia
– Convulsions
– Metabolic acidosis
Agitation and convulsions may be treated with diazepam.
Ask anything about Nortriptyline 25 mg film-coated tablets. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.
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