Consumer medicine information

Noumed Citalopram

Citalopram

BRAND INFORMATION

Brand name

Noumed Citalopram

Active ingredient

Citalopram

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Noumed Citalopram.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Noumed Citalopram.

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

All medicines have risks and benefits. Your doctor has weighed the risks of you taking this medicine against the benefits they expect it will have for you.

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

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

WHAT NOUMED CITALOPRAM IS USED FOR

This medicine is used for the treatment of depression.

It contains the active ingredient citalopram hydrobromide. Citalopram hydrobromide belongs to a group of medicines called selective serotonin reuptake inhibitors (SSRIs).

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

Depression is longer lasting or more severe than the "low moods" everyone has from time to time due to the stress of everyday life. It is thought to be caused by a chemical imbalance in parts of the brain. This imbalance affects your whole body and can cause emotional and physical symptoms such as feeling low in spirit, loss of interest in activities, being unable to enjoy life, poor appetite or overeating, disturbed sleep, often waking up early, loss of sexual drive, lack of energy and feeling guilty over nothing.

Noumed Citalopram corrects this chemical imbalance and may help relieve the symptoms of depression.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

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

Noumed Citalopram is not addictive. However, if you suddenly stop taking it, you may get side effects.

Tell your doctor if you get any side effects after stopping Noumed Citalopram.

BEFORE YOU TAKE NOUMED CITALOPRAM

When you must not take it

Do not take Noumed Citalopram if you have a condition called 'congenital long QT syndrome'. At high doses, Noumed Citalopram can cause changes in the way that your heart beats.

See your doctor immediately if you experience an irregular heartbeat, shortness of breath, dizziness or fainting while taking Noumed Citalopram.

Do not take this medicine if you have an allergy to:

  • citalopram hydrobromide, the active ingredient, or to any of the other ingredients listed at the end of this leaflet under Product Description
  • any other similar medicines, such as medicines of the same class, SSRIs, e.g. sertraline.

Some of the symptoms of an allergic reaction may include:

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

Do not take Noumed Citalopram at the same time as the following other medicines:

  • pimozide, a medicine used to treat mental disorders
  • linezolid, a medicine used to treat bacterial infections
  • monoamine oxidase inhibitors (MAOIs), which are also used for the treatment of depression.

Do not take Noumed Citalopram when you are taking a MAOI or when you have been taking a MAOI within the last 14 days. Taking Noumed Citalopram with MAOIs may cause a serious reaction with a sudden increase in temperature, extremely high blood pressure and severe convulsions. Your doctor will know when it is safe to start Noumed Citalopram after the MAOI has been stopped.

Do not take this medicine after the expiry date printed on the pack 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 this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding. Your doctor can discuss with you the risks and benefits involved.

If you take this medicine during the last three months of your pregnancy, the general condition of your newborn baby might be affected.

It is not recommended that you breastfeed while taking Noumed Citalopram as it is excreted in breast milk.

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

  • congenital long QT syndrome or other heart conditions. Your doctor may occasionally need to check your heart beat and rhythm with an ECG test
  • illnesses which require you to have regular blood tests
  • a tendency to bleed or bruise easily
  • diabetes
  • kidney disease
  • liver disease
  • bipolar disorder (manic depression)
  • a history of seizures or fits
  • restlessness and/or a need to move often.

Tell your doctor if you are receiving electroconvulsive therapy.

If you are lactose intolerant, contact your doctor before taking this medicine. Noumed Citalopram tablets contain lactose.

Do not give this medicine to a child under the age of 18 years. Safety and effectiveness in children younger than 18 years have not been established.

Noumed Citalopram can be given to elderly patients over 65 years of age with a reduced dose. The effects of Noumed Citalopram in elderly patients are similar to that in other patients.

If you have not told your doctor about any of the above, tell him/her before you start taking Noumed Citalopram.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and Noumed Citalopram may interfere with each other. These include:

  • ketoconazole and itraconazole, medicines used to treat fungal infections
  • macrolide antibiotics, e.g. erythromycin and clarithromycin, medicines used to treat infections
  • medicines used to treat reflux and ulcers e.g. cimetidine and omeprazole
  • medicines known to prolong bleeding, e.g. aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, diclofenac
  • warfarin, a medicine used to prevent blood clots
  • sumatriptan, a medicine used to treat migraines
  • tramadol, a medicine used to relieve pain
  • carbamazepine, a medicine used to treat convulsions
  • some heart medications, such as beta-blockers (e.g. metoprolol) or antiarrhythmics
  • selegiline, a medicine used in Parkinson's disease
  • tryptophan, an amino-acid contained in some multivitamin and mineral preparations
  • lithium, a medicine used to treat mood swings and some types of depression
  • antipsychotics, a class of medicines used to treat certain mental and emotional conditions
  • tricyclic antidepressants, e.g. imipramine, desipramine
  • St John's Wort (Hypericum perforatum), a herbal remedy
  • any other medicines for depression, anxiety, obsessive-compulsive disorder or pre-menstrual dysphoric disorder.

These medicines may be affected by Noumed Citalopram or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Some combinations of medicines may increase the risk of serious side effects and are potentially life threatening. See ‘Before you take Noumed Citalopram’ section.

Drugs that are known to affect the way the heart beats (for example some heart medicines, antibiotics, asthma medicines, antihistamines) should be avoided while taking Noumed Citalopram. If it is necessary for you to be on these medicines at the same time as Noumed Citalopram, your doctor may perform an ECG test to check your heart rate and rhythm.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

HOW TO TAKE NOUMED CITALOPRAM

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

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

How much to take

The standard dose for adults for this medicine is between 20mg and 40mg (one to two tablets) per day.

The recommended dose in elderly patients is 10mg (half a tablet) per day but may be increased to a maximum of 20mg (one tablet) per day by your doctor if needed.

If you have liver problems, or are taking medicines such as cimetidine and omeprazole, the recommended starting dose is 10mg (half a tablet) per day. The dose can be increased to a maximum of 20mg (one tablet) per day.

Your doctor may have prescribed a different dose. If you have been prescribed or are currently taking doses of Noumed Citalopram greater than 40mg, talk to your doctor about reducing the dose.

Ask your doctor or pharmacist if you are unsure of the correct dose for you. They will tell you exactly how much to take.

Follow the instructions they give you. If you take the wrong dose, Noumed Citalopram may not work as well and your problem may not improve.

How to take it

Swallow the tablets whole with a full glass of water.

Do not chew them.

If you need to break Noumed Citalopram tablets into two halves, place on a flat surface and press down on the scored side with the thumb or forefinger.

When to take Noumed Citalopram

Take Noumed Citalopram as a single dose either in the morning or in the evening.

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.

Take Noumed Citalopram with or without food.

How long to take Noumed Citalopram

Continue taking your medicine even if it takes some time before you feel any improvement in your condition.

As with other medicines for the treatment of these conditions, it may take a few weeks before you feel any improvement.

Individuals will vary greatly in their response to Noumed Citalopram. Your doctor will check your progress at regular intervals.

The duration of treatment may vary for each individual, but is usually at least 6 months.

In some cases the doctor may decide that longer treatment is necessary.

Continue taking your medicine for as long as your doctor tells you, even if you begin to feel better.

The underlying illness may persist for a long time and if you stop your treatment too soon, your symptoms may return.

Do not stop taking this medicine suddenly. If Noumed Citalopram is stopped suddenly you may experience mild, but usually temporary, symptoms such as dizziness, pins and needles, sleep disturbances (vivid dreams, inability to sleep), feeling anxious or agitated, headaches, feeling sick (nausea), vomiting, sweating, tremor (shaking), feeling confused, feeling emotional or irritable, diarrhoea, visual disturbances, or fast or irregular heart beat.

Your doctor will tell you how to reduce the dosage so that you do not get unwanted effects.

If you forget to take it

If you miss a dose and remember in less than 12 hours, take it straight away, and then go back to taking it as you would normally. Otherwise, if it is almost time for your next dose, skip the dose you missed and take the next dose when you are meant to.

Do not take a double dose to make up for the dose that you missed. 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 Australia 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much Noumed Citalopram. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include nausea (feeling sick), vomiting, dizziness, fast or slow heart beat or change in heart rhythm, decreased or increased blood pressure, tremor (shaking), agitation, dilated pupils of the eyes, drowsiness and sleepiness. Convulsions or coma may occur. A condition called serotonin syndrome may occur with high fever, agitation confusion, trembling and abrupt contractions of muscles.

WHILE YOU ARE TAKING NOUMED CITALOPRAM

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Noumed Citalopram.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

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

Tell your doctor immediately if you have thoughts about killing yourself or other mental or mood changes, or if you are close to or care for someone using Noumed Citalopram who talks about or shows signs of killing him or herself. Persons taking Noumed Citalopram may be more likely to think about killing themselves or actually trying to do so, especially when Noumed Citalopram is first started or the dose is changed. All mentions of suicide or violence must be taken seriously.

Occasionally, the symptoms of depression may include thoughts of suicide or self-harm. It is possible that these symptoms continue or get worse until the full antidepressant effect of the medicine become apparent. This is more likely to occur if you are a young adult, i.e. 18 to 24 years of age, and you have not used antidepressant medicines before.

If you or someone you know demonstrates any of the following warning signs of suicide-related behaviour while taking Noumed Citalopram, tell your doctor immediately, or go to the nearest hospital for treatment; patients and care givers should pay attention to these warning signs:

  • 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.

Do not stop taking this medicine or change the dose without consulting you doctor, even if you experience increased anxiety at the beginning of the treatment. At the beginning of the treatment, some patients may experience increased anxiety which will disappear during continued treatment.

Tell your doctor immediately if you experience symptoms such as restlessness or difficulty in sitting or standing still. These symptoms can occur during the first week of treatment.

Contact your doctor as soon as possible if you suddenly experience an episode of mania. Some patients with bipolar disorder (manic depression) may enter into a manic phase. This is characterised by profuse and rapidly changing ideas, exaggerated gaiety and excessive physical activity.

Sometimes you may be unaware of the above-mentioned symptoms and therefore you may find it helpful to ask a friend or relative to help you to observe the possible signs of change in your behaviour.

Keep all of your doctor's appointments so that your progress can be checked.

Things you must not do

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

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

Do not stop taking your medicine or lower the dosage without checking with your doctor. Your doctor will gradually reduce the amount you are using, usually over a period of one to two weeks, before stopping completely. Suddenly stopping Noumed Citalopram may cause unwanted discontinuation symptoms such as dizziness, headache and nausea. Your doctor will tell you when and how Noumed Citalopram should be discontinued. Your doctor will gradually reduce the amount you are using, usually over a period of one to two weeks, before stopping completely.

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

Things to be careful of

Be careful driving or operating machinery until you know how Noumed Citalopram affects you. This medicine may cause nausea, fatigue and dizziness in some people, especially early in the treatment. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Avoid alcohol while you are taking this medicine. It is not advisable to drink alcohol while you are being treated for depression.

SIDE EFFECTS

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

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.

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

Ask your doctor or pharmacist to answer any questions you may have.

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

  • rash, itching
  • ringing or other persistent noise in the ears
  • aching muscles or joint pain
  • flu-like symptoms, fever, runny or blocked nose, sneezing, facial pressure or pain, coughing or sore throat
  • increased sweating
  • increased saliva or dry mouth, taste disturbance
  • loss of appetite or increased appetite, weight decrease or weight increase
  • diarrhoea, constipation, flatulence, indigestion, stomach pain or discomfort
  • dizziness
  • nausea (feeling sick) or vomiting
  • migraine, headache
  • sleepiness or drowsiness, fatigue, yawning
  • insomnia
  • a sense of indifference to everything
  • disturbance in attention
  • lack of energy
  • sexual disturbances (decreased sexual drive, problems with orgasm; problems with ejaculation or erection)
  • for females, problems with menstrual periods
  • restlessness or difficulty keeping still.

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

  • chest pain
  • fast heart rate (palpitations) or decrease in heart rate
  • shortness of breath
  • fainting
  • dizziness when you stand up due to low blood pressure
  • blurred vision
  • low sodium levels in the blood (the symptoms are feeling sick and unwell with weak muscle or feeling confused) which may be caused by SSRI antidepressants, especially in elderly patients
  • increased tendency to develop bruises
  • unusual bleeding, including bleeding from stomach or bowel
  • passing more urine than normal or problems when urinating
  • tingling or numbness of the hands or feet
  • nervousness, confusion, problems with concentration, loss of memory
  • agitation, anxiety, worsening of depression.

The above list includes serious side effects of Noumed Citalopram that may require medical attention.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • thoughts of suicide
  • serious allergic reaction (symptoms of an allergic reaction may include swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing, or hives)
  • high fever, agitation, confusion, trembling and abrupt contractions of muscles (these symptoms may be signs of a rare condition called serotonin syndrome which has been reported with the combined use of antidepressants)
  • tremors, movement disorders (involuntary movements of the muscles)
  • fast, irregular heart beat with feelings of dizziness or difficulty breathing.

The above list includes serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some people.

Other side effects not listed above may occur in some people. An increased risk of bone fractures has been observed in patients taking medicines like Citalopram.

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

AFTER TAKING NOUMED CITALOPRAM

Storage

Keep your medicine in the original container.

If you take it out of its original container it may not keep well.

Keep your medicine in a cool dry place where the temperature stays below 25°C.

Do not store Noumed Citalopram or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car.

Heat and dampness can destroy some medicines.

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

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

PRODUCT DESCRIPTION

What it looks like

Noumed Citalopram comes in 2 strengths:

Noumed Citalopram 20mg - white, oval, biconvex film-coated tablets with a score notch on one side, and embossed C 20.

Available in bottles and blister packs of 28 tablets.

Noumed Citalopram 40mg - white, oval, biconvex film-coated tablets with a score notch on one side, and embossed C 40.

Available in blister packs of 28 tablets.

All strengths and presentations may not be marketed.

Ingredients

Active ingredients: 20 mg or 40 mg citalopram (as hydrobromide)

Inactive ingredient:

  • maize starch
  • lactose monohydrate
  • copovidone
  • glycerol
  • microcrystalline cellulose
  • magnesium stearate
  • sodium starch glycollate
  • hypromellose
  • macrogol 6000
  • titanium dioxide
  • purified talc.

This medicine does not contain sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Avallon Pharmaceuticals Pty Ltd
Level 5, 7 Eden Park Avenue,
Macquarie Park, NSW 2113

Distributed in Australia by:

API Consumer Brands

This leaflet was prepared in December 2019.

Australian Register Numbers

20mg tablets: AUST R 298195 (blisters)

20mg tablets: AUST R 298196 (bottle)

40mg tablets: AUST R 298197 (blisters)

Published by MIMS March 2020

BRAND INFORMATION

Brand name

Noumed Citalopram

Active ingredient

Citalopram

Schedule

S4

 

1 Name of Medicine

Citalopram hydrobromide.

2 Qualitative and Quantitative Composition

Each Noumed Citalopram tablet contain 20 mg or 40 mg citalopram (as hydrobromide).

Excipients with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Noumed Citalopram 20 mg tablets.

Oval, white, biconvex film-coated tablets with a score notch on one side, and embossed C 20.

Noumed Citalopram 40 mg tablets.

Oval, white, biconvex film-coated tablets with a one-sided notch and embossment C 40.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of major depression.

4.2 Dose and Method of Administration

Noumed Citalopram should be administered as a single daily dose. The dose may be taken in the morning or evening without regard for food.

Adults.

The starting dose is 20 mg/day. The dose can be increased in increments of 10 mg until satisfactory clinical response is achieved. The maximum dose is 40 mg/day. As the treatment result in general can be evaluated only after 2-3 weeks' treatment, a possible dose increase should take place with intervals of 2-3 weeks.

Elderly patients.

The starting dose is 10 mg/day. The dose can be increased by 10 mg to a maximum of 20 mg/day. As the treatment result in general can be evaluated only after 2-3 weeks' treatment, a possible dose increase should take place after an interval of 2-3 weeks.

Children and adolescents (< 18 years of age).

The safety and efficacy of citalopram for the treatment of major depressive disorder have not been established in this population. Citalopram should not be used in children and adolescents under the age of 18 years.

Reduced hepatic function.

The maximum recommended dose is 20 mg/day.

Reduced renal function.

Dosage adjustment is not necessary in patients with mild or moderate renal impairment. No information is available on treatment of patients with severely reduced renal function (creatinine clearance < 20 mL/min).

Poor metabolisers of CYP2C19 and patients taking CYP2C19 inhibitors.

An initial dose of 10 mg daily during the first two weeks of treatment is recommended for patients who are known to be poor metabolisers with respect to CYP2C19. The dose may be increased to a maximum of 20 mg daily depending on individual patient response (see Section 5.2 Pharmacokinetic Properties). Patients taking cimetidine or other CYP2C19 inhibitors should not exceed the maximum dose of 20 mg/day.

Duration of treatment.

In treating depression a treatment period of at least six months is usually necessary to provide adequate maintenance against the potential for relapse.

Withdrawal symptoms seen on discontinuation of SSRI.

Abrupt discontinuation should be avoided. When stopping treatment with citalopram the dose should be gradually reduced over a period of a least one to two weeks in order to reduce the risk of withdrawal reactions (see Section 4.4 Special Warnings and Precautions for Use). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.

4.3 Contraindications

Hypersensitivity to citalopram and any excipients in Noumed Citalopram (see Section 6.1 List of Excipients).
Congenital long QT syndrome (see Section 4.4 Special Warnings and Precautions for Use).

Monoamine oxidase inhibitors.

Simultaneous administration of citalopram and a Monoamine oxidase inhibitor (MAOI) may cause serotonin syndrome, a serious, sometimes fatal, reaction in patients receiving an SSRI in combination with a MAOI, including the irreversible MAOI selegiline and reversible MAOIs linezolid and moclobemide and in patients treated with an SSRI and a MAOI in close temporal proximity. Some cases presented with features resembling neuroleptic malignant syndrome. Symptoms and signs of serotonin syndrome include: rapid onset, clonus, myoclonus, tremor, shivering, hyperreflexia, hyperthermia, rigidity, autonomic instability with possible rapid fluctuations of vital signs and mental status changes that include extreme agitation progressing to delirium and coma.
Treatment with citalopram may be instituted 14 days after discontinuation of irreversible MAOIs and a minimum of one drug free day after discontinuation of moclobemide. Treatment with MAOIs may be introduced 14 days after discontinuation of citalopram.
Citalopram is contraindicated in the combination with linezolid.

Pimozide.

Concomitant administration of citalopram and pimozide is contraindicated due to the risk of QT interval prolongation (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Use with caution in the following circumstances:

QT prolongation and torsade de pointes.

Citalopram can cause a dose-dependent increase in the QT interval and should not be dosed above 40 mg/day. Torsade de Pointes has been reported postmarketing. Citalopram should not be used in patients with congenital long QT syndrome. Patients at higher risk of developing prolongation of the QT interval include those with congestive heart failure, bradyarrhythmias or a predisposition to hypokalaemia or hypomagnesaemia because of concomitant illness or drugs. Hypokalaemia and hypomagnesaemia should be corrected prior to initiation of treatment and periodically monitored. Consider more frequent ECG monitoring in these patients and those with other risk factors for QT prolongation. Dose escalations over 20 mg/day in elderly patients (> 65 years), patients with hepatic dysfunction, CYP2C19 poor metabolisers or patients taking concomitant cimetidine or another CYP2C19 inhibitor are not recommended.
The influence of citalopram on QT interval at doses of 20 mg and 60 mg per day was evaluated in a randomised, placebo and active (moxifloxacin 400 mg) controlled cross-over, escalating multiple-dose study in 119 healthy subjects. The change from baseline in QTc (Fridericia correction) was 7.5 msec at the 20 mg/day dose and 16.7 msec at the 60 mg/day dose.
Citalopram has not been systematically evaluated in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were generally excluded from clinical studies during the product's premarketing testing.

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. The 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 co-morbid 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 analysis 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 patient 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 the 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 antidepressants medications have also shown an increased risk of suicidal thinking and behaviour, known as suicidality, in young adults aged 18 to 24 years 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 non-psychiatric. 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 non-psychiatric) 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 Noumed Citalopram should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Haemorrhage.

Bleeding abnormalities of the skin and mucous membranes have been reported with the use of SSRIs (including purpura, haematoma, epistaxis, vaginal bleeding and gastrointestinal bleeding). Noumed Citalopram should therefore be used with caution in patients concomitantly treated with oral anticoagulants, medicinal products known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and dipyridamole) as well as in patients with a past history of abnormal bleeding or those with predisposing conditions. Pharmacological gastroprotection should be considered for high risk patients.

Hyponatraemia.

Probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported as a rare adverse reaction with the use of SSRIs. Especially elderly patients seem to be a risk group.

Akathisia/psychomotor restlessness.

The use of SSRIs/SNRIs has been associated with the development of akathisia, characterized by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental and it may be necessary to review the use of SSRIs/SNRIs.

Seizures.

Although animal experiments have shown that citalopram has no epileptogenic potential it should, like other antidepressants, be used with caution in patients with a history of seizures.

Diabetes.

As described for other psychotropics citalopram may modify insulin and glucose responses calling for adjustment of the antidiabetic therapy in diabetic patients; in addition the depressive illness itself may affect patients' glucose balance.

Mania.

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.
In patients with manic-depressive illness, a change towards the manic phase may occur. As with most antidepressants, citalopram should be discontinued if the patient enters a maniac phase.

ECT (electroconvulsive therapy).

There is little clinical experience of concurrent use of citalopram and ECT, therefore caution is advised.

Angle-closure glaucoma.

Selective serotonin reuptake inhibitor (SSRIs) including citalopram may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure and angle-closure glaucoma, especially in patients pre-disposed. Citalopram should therefore be used with caution in patients with angle-closure glaucoma or history of glaucoma.

Discontinuation/withdrawal.

Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt.
The risk of withdrawal symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability and visual disturbances are the most commonly reported reactions. Generally these symptoms are mild to moderate, however, in some patients they may be severe in intensity.
They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose.
Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that citalopram should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs (see Section 4.2 Dose and Method of Administration).

Use in patients with cardiac disease.

Citalopram has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Like other SSRIs, citalopram causes a small decrease in heart rate. Consequently, caution should be observed when citalopram is initiated in patients with pre-existing slow heart rate.

Excipients.

The tablets contain lactose monohydrate. Patients with rare heredity problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not receive this medicine.

Preclinical safety.

High doses of citalopram, which resulted in high plasma concentrations of citalopram and metabolites, have been associated with convulsions and ECG abnormalities in experimental animals.

Use in hepatic impairment.

See Section 4.2 Dose and Method of Administration.

Use in renal impairment.

See Section 4.2 Dose and Method of Administration.

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

The efficacy and safety of citalopram for the treatment of major depressive disorder has not been established in children and adolescents less than 18 years of age. Consequently, citalopram should not be used in children and adolescents less than 18 years of age.

Effects on laboratory tests.

See Section 4.8 Adverse Effects (Undesirable Effects).

4.5 Interactions with Other Medicines and Other Forms of Interactions

Drugs that prolong the QT interval.

More frequent ECG monitoring is recommended in patients on concomitant medications that prolong the QT interval (see Section 4.4 Special Warnings and Precautions for Use, QT prolongation and torsade de pointes).

MAOIs.

Monoamine Oxidase Inhibitors (MAOIs) should not be used in combination with SSRIs (see Section 4.3 Contraindications).
Treatment with citalopram may be instituted 14 days after discontinuation of irreversible MAOIs and a minimum of one drug free day after discontinuation of moclobemide. Treatment with MAOIs may be introduced 14 days after discontinuation of citalopram.

Serotonin syndrome.

Development of serotonin syndrome may occur in association with treatment with SSRIs and SNRIs, particularly when given in combination with MAOIs or other serotonergic agents. The simultaneous use of citalopram and MAO-inhibitors can result in severe undesirable effects, including the serotonin syndrome. Cases of serious and sometimes fatal reactions have been reported in patients receiving an SSRI in combination with a monoamine oxidase inhibitor (MAOI), including the irreversible MAOI selegiline and the reversible MAOIs linezolid and moclobemide and in patients who have recently discontinued an SSRI and have been started on a MAOI.
Some cases presented with features resembling serotonin syndrome. Symptoms and signs of serotonin syndrome include rapid onset of neuromuscular excitation (hyperreflexia, incoordination, myoclonus, tremor), altered mental status (confusion, agitation, hypomania) and autonomic dysfunction (diaphoresis, diarrhoea, fever, shivering and rapidly fluctuating vital signs). Treatment with citalopram should be discontinued if such events occur and supportive symptomatic treatment initiated.

Selegiline (selective MAO-B inhibitor).

A pharmacokinetic/ pharmacodynamic interaction study with concomitantly administered citalopram (20 mg daily) and selegiline (10 mg daily) (a selective MAO-B inhibitor) demonstrated no clinically relevant interactions. The concomitant use of citalopram and selegiline (in doses above 10 mg daily) is not recommended.

Pimozide.

Co-administration of a single dose of pimozide 2 mg to subjects treated with racemic citalopram 40 mg/day for 11 days caused an increase in AUC and Cmax of pimozide, although not consistently throughout the study. The co-administration of pimozide and citalopram resulted in a mean increase in the QTc interval of approximately 10 msec. Due to the interaction noted at a low dose of pimozide, concomitant administration of citalopram and pimozide is contraindicated (see Section 4.3 Contraindications).

Serotonergic drugs.

SSRIs may theoretically interact with 5-HT agonists. Co-administration with serotonergic drugs (e.g. tramadol, sumatriptan) may lead to enhancement of 5-HT associated effects. Until further evidence is available it is advised not to use citalopram simultaneously with 5-HT agonists. Similarly, Hypericum perforatum (St John's Wort) should be avoided as adverse interactions have been reported with a range of drugs including antidepressants.

Hepatic enzymes.

The metabolism of citalopram is only partly dependent on the hepatic cytochrome P450 isozyme CYP2D6 and, unlike some other SSRIs, citalopram is only a weak inhibitor of this important enzyme system which is involved in the metabolism of many drugs (including antiarrhythmics, neuroleptics, beta-blockers, tricyclic antidepressants and some SSRIs).
In vitro enzyme inhibition data did not reveal an inhibitory effect of citalopram on CYP3A4, but did suggest that it is a weak inhibitor of CYP-1A2, -2D6, and -2C19. Citalopram would be expected to have little inhibitory effect on in vivo metabolism mediated by these isoenzymes. However, in vivo data to address this question are very limited.
Citalopram steady state levels were not significantly different in poor metabolisers and extensive -2D6 metabolisers after multiple dose administration of citalopram, suggesting that co-administration, with citalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on citalopram metabolism.
Since CYP3A4 and -2C19 are the primary enzymes involved in the metabolism of citalopram, it is expected that potent inhibitors of -3A4, (e.g. ketoconazole, itraconazole, and macrolide antibiotics) and potent inhibitors of CYP2C19, (e.g. omeprazole, cimetidine) might decrease the clearance of citalopram. Citalopram 20 mg/day is the maximum recommended dose for patients taking concomitant cimetidine or another CYP2C19 inhibitor because of the risk of QT prolongation (see Section 4.2 Dose and Method of Administration).

Lithium and tryptophan.

There is no pharmacokinetic interaction between lithium and citalopram. However, there have been reports of enhanced serotonergic effects when SSRIs have been given with lithium or tryptophan and therefore the concomitant use of citalopram with these drugs should be undertaken with caution. Increased monitoring of lithium levels is not required.

Imipramine and other tricyclic antidepressants (TCAs).

In a pharmacokinetic study, no effect was demonstrated on either citalopram or imipramine levels, although the level of desipramine, the primary metabolite of imipramine, was increased. The clinical significance of the desipramine change is unknown. Nevertheless, caution is indicated in the coadministration of citalopram and tricyclic antidepressants.

Medicines affecting the central nervous system.

Given the primary CNS effects of citalopram, caution should be used when it is taken in combination with other centrally acting drugs.

Digoxin.

In subjects who had received 21 days of 40 mg/day citalopram, combined administration of citalopram and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram or digoxin.

Medicines that interfere with haemostasis (NSAIDs, aspirin, warfarin, etc.).

Serotonin release by platelets plays an important role in haemostasis. There is an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of abnormal bleeding. Concurrent use of an NSAID, aspirin or warfarin potentiates the risk. Thus, patients should be cautioned about using such medicines concurrently with Noumed Citalopram.

Carbamazepine.

Combined administration of citalopram (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme inducing properties of carbamazepine, the possibility that carbamazepine might increase the clearance of citalopram should be considered if the two drugs are coadministered.

Metoprolol.

A pharmacokinetic interaction between citalopram and metoprolol was observed, resulting in a twofold increase in metoprolol concentrations. The change in metabolism of metoprolol suggests an interaction between metoprolol and demethylcitalopram related to the CYP2D6 isoenzyme. There was no statistically significant increase in the effect of metoprolol on blood pressure and heart rate in healthy volunteers by adding citalopram.

Cimetidine and other CYP2C19 inhibitors.

Cimetidine caused a moderate increase in the average steady state levels of citalopram. Co-administration of escitalopram (the active enantiomer of citalopram) with omeprazole 30 mg once daily (a CYP2C19 inhibitor) resulted in moderate increase in the plasma concentrations of escitalopram. Thus, caution should be exercised when used concomitantly with CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. A reduction in the dose of citalopram may be necessary based on monitoring of undesirable effects during concomitant treatment. Citalopram 20 mg/day is the maximum recommended dose for patients taking concomitant cimetidine because of the risk of QT prolongation.

Medicinal products inducing QT prolongation or hypokalaemia/hypomagnesaemia.

Caution is warranted for concomitant use of other QT interval prolonging medicines or hypokalaemia/hypomagnesaemia inducing drugs as they, like citalopram, potentially prolong the QT interval.
The risk of malignant arrhythmias is increased with concomitant use with hypokalaemia/hypomagnesaemia inducing medicinal products.

Medicinal products lowering the seizure threshold.

SSRIs can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold (e.g. antidepressants [tricyclics, SSRIs], neuroleptics [phenothiazines, thioxanthenes, and butyrophenones]), mefloquine, bupropion and tramadol).

Alcohol.

The combination of SSRIs and alcohol is not advisable.

Others.

At the pharmacodynamic level cases of serotonin syndrome with citalopram and moclobemide and buspirone have been reported.
No pharmacodynamic interactions have been noted in clinical studies in which citalopram has been given concomitantly with benzodiazepines, neuroleptics, analgesics, lithium, alcohol, antihistamines, antihypertensive drugs, beta-blockers and other cardiovascular drugs.
Experience with citalopram has not revealed any clinically relevant interactions with neuroleptics with the exception of pimozide (see Section 4.3 Contraindications; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Pimozide). However, as with other SSRIs, the possibility of a pharmacodynamic interaction cannot be excluded.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In rats, female fertility was unaffected by oral treatment with citalopram doses which achieved plasma drug concentrations slightly in excess of those expected in humans, but effects on male rat fertility have not been tested with adequate oral doses.
Animal data have shown that citalopram induces a reduction of fertility index and pregnancy index, reduction in number in implantation and abnormal sperm.
Animal data have shown that citalopram may affect sperm quality.
(Category C)
Reproduction studies performed in rats and rabbits at oral doses of up to 112 and 32 mg/kg, respectively, have revealed no evidence of teratogenic effects. Studies in rats have shown increased post-implantation loss, reduced foetal weight and foetal developmental changes. A no effect oral dose of 56 mg/kg/day was established for foetal development. There are no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Cases of withdrawal symptoms in newborns have been described after the use of SSRI at the end of pregnancy.
Newborns should be observed if maternal use of citalopram has continued into the later stages of pregnancy, particularly into the third trimester. Abrupt discontinuation should be avoided during pregnancy.
Newborns exposed to citalopram, other SSRIs (Selective Serotonin Reuptake Inhibitors), or SNRIs (Serotonin Norepinephrine Reuptake Inhibitors), late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome.
Epidemiological studies have shown that the use of SSRI's (including citalopram) in pregnancy, particularly use in late pregnancy, was associated with an increased risk of persistent pulmonary hypertension of the newborn (PPHN). The risk of PPHN among infants born to women who used SSRIs late in pregnancy was estimated to be 4 to 5 times higher than the rate of 1 to 2 per 1000 pregnancies observed in the general population.
 Citalopram appears in human breast milk in very low concentrations. In nursing mothers, caution is recommended as it is not known whether citalopram excreted in milk may affect the infant.

4.7 Effects on Ability to Drive and Use Machines

Patients who are prescribed psychotropic medication may be expected to have some impairment of general attention and concentration and should be cautioned about their ability to drive a car and operate machinery.

4.8 Adverse Effects (Undesirable Effects)

Adverse effects observed with citalopram are in general mild and transient. They are most frequent during the first one or two weeks of treatment and usually attenuate subsequently.
The most commonly observed adverse events associated with the use of citalopram in double-blind, placebo-controlled trials and not seen at an equal incidence among placebo-treated patients were: nausea, somnolence, dry mouth, increased sweating, tremor, diarrhoea and ejaculation disorder. The incidence of each in excess over placebo is low.
In comparative double-blind clinical trials with tri- and tetracyclic antidepressants (TTCAs), the incidence of 10 adverse events was statistically significantly higher on TTCAs (dry mouth, increased sweating, constipation, tremor, dizziness, somnolence, abnormal accommodation, postural hypotension, palpitation, perverted taste) compared to citalopram. For two events (nausea, ejaculation disorder) the incidence was statistically higher on citalopram compared to TTCAs.
In the comparative trials versus other SSRIs no statistical significant differences between the groups were found.
Adverse events reported in clinical trials with citalopram treated patients include those listed in Table 1.

Dose dependency of adverse events.

The potential relationship between the dose of citalopram administered and the incidence of adverse events was examined in a fixed dose study in depressed patients receiving placebo or citalopram 10, 20, 40, and 60 mg. Jonckheere's trend test revealed a positive dose response (p < 0.05) for the following adverse events: fatigue, impotence, insomnia, sweating increased, somnolence, and yawning.

Male and female sexual dysfunction with SSRIs.

While sexual dysfunction is often part of depression and other psychiatric disorders, there is increasing evidence that treatment with selective serotonin reuptake inhibitors (SSRIs) may induce sexual side effects. This is a difficult area to study because patients may not spontaneously report symptoms of this nature, and therefore, it is thought that sexual side effects with the SSRIs may be underestimated. In placebo-controlled clinical trials (Table 1), the reported incidence of decreased libido for the whole population was 2.5%; ejaculation disorder (primarily ejaculatory delay), and impotence in male depressed patients receiving citalopram (N = 423) was 5.9%, and 2.8%, respectively. In female depressed patients receiving citalopram (N = 660), the reported incidence of anorgasmia was 0.5%. The reported incidence of decreased libido was 0.4% among depressed patients receiving placebo, whilst sex specific adverse events were not reported among male and female depressed patients receiving placebo.
While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.

Vital sign changes.

Citalopram and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic blood pressure, and diastolic blood pressure) and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses did not reveal any clinically important changes in vital signs associated with citalopram treatment. In addition, a comparison of supine and standing vital sign measures for citalopram and placebo treatments indicated that citalopram treatment is not associated with orthostatic changes.

Weight changes.

Patients treated with citalopram in controlled trials experienced a weight loss of about 0.5 kg compared to no change for placebo patients.

Laboratory changes.

Citalopram and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, haematology, and urinalysis variables and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in laboratory test parameters associated with citalopram treatment.

ECG changes.

Electrocardiograms from citalopram (n = 802) and placebo (n = 241) groups were compared with respect to outliers defined as subjects with QTc changes over 60 msec from baseline or absolute values over 500 msec post-dose, and subjects with heart rate increases to over 100 bpm or decreases to less than 50 bpm with a 25% change from baseline (tachycardic or bradycardic outliers respectively). In the citalopram group 1.9% of the patients had a change from baseline in QTcF > 60 msec compared to 1.2% of the patients in the placebo group. None of the patients in the placebo group had a post-dose QTcF > 500 msec compared to 0.5% of the patients in the citalopram group. The incidence of tachycardic outliers was 0.5% in the citalopram group and 0.4% in the placebo group. The incidence of bradycardic outliers was 0.9% in the citalopram group and 0.4% in the placebo group.
In a thorough QT study, citalopram was found to be associated with a dose dependent increase in the QTc interval (see Section 4.4 Special Warnings and Precautions for Use, QT prolongation and torsade de pointes).

Class effects.

Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this risk is unknown.

Other events observed during the premarketing evaluation of citalopram.

Following is a list of WHO terms that reflect treatment-emergent adverse events, as defined in the introduction (see Section 4.8 Adverse Effects (Undesirable Effects)), reported by patients treated with citalopram at multiple doses in a range of 10 to 80 mg/day during any phase of a trial within the premarketing database of 4422 patients. All reported events are included except those already listed in the table or elsewhere (see Section 4.8 Adverse Effects (Undesirable Effects)), those events for which a drug cause was remote, those event terms which were so general as to be uninformative, and those occurring in only one patient. It is important to emphasise that, although the events reported occurred during treatment with citalopram, they were not necessarily caused by it.
Events are further categorised by body system and listed in order of decreasing frequency according to the following definitions: very common adverse events are those occurring on one or more occasions in at least 1/10 patients; common adverse events are those occurring in less than 1/10 but at least 1/100; uncommon adverse events are those occurring in less than 1/100 patients but at least 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.

Skin and appendages disorders.

Uncommon: photosensitivity reaction, urticaria, acne, eczema, skin discoloration, alopecia, dermatitis, skin dry, psoriasis, rash.
Rare: hypertrichosis, decreased sweating, melanosis, keratitis, pruritus ani.
Unknown: ecchymosis, angioedema.

Musculo-skeletal system disorders.

Uncommon: arthritis, muscle weakness, skeletal pain.
Rare: bursitis, osteoporosis.

Central and peripheral nervous system disorders.

Very common: somnolence, insomnia, headache.
Common: migraine, tremor, paraesthesia, dizziness, disturbance in attention.
Uncommon: vertigo, leg cramps, involuntary muscle contractions, speech disorder, abnormal gait, hypoaesthesia, neuralgia, ataxia, convulsions.
Rare: abnormal coordination, hyperesthesia, psychomotor restlessness/akathisia (see Section 4.4 Special Warnings and Precautions for Use), ptosis, stupor.

Vision disorders.

Common: abnormal accommodation.
Uncommon: conjunctivitis, eye pain, mydriasis.
Rare: photophobia, abnormal lacrimation, cataract, diplopia.
Unknown: visual disturbance.

Special senses other, disorders.

Common: taste perversion.
Rare: taste loss.

Psychiatric disorders.

Very common: sleep disorder.
Common: amnesia, apathy, depression, increased appetite, aggravated depression.
Uncommon: aggressive reaction, increased libido, paroniria, drug dependence, depersonalisation, hallucination, euphoria, psychotic depression, delusion, paranoid reaction, emotional lability, panic reaction, psychosis, mania.
Rare: catatonic reaction, melancholia, suicide-related events.
Unknown: bruxism, restlessness.

Gastro-intestinal system disorders.

Very common: dry mouth, nausea.
Common: saliva increased, diarrhoea, vomiting, constipation, abdominal pain, flatulence, dyspepsia.
Uncommon: gastritis, gastroenteritis, eructation, haemorrhoids, dysphagia, gingivitis, stomatitis, teeth grinding, oesophagitis.
Rare: colitis, gastric ulcer, duodenal ulcer, gastroesophageal reflux, diverticulitis, glossitis, hiccups, rectal haemorrhage.
Unknown: gastrointestinal haemorhage.

Immune system disorders.

Unknown: anaphylactic reaction, hypersensitivity NOS.

Liver and biliary system disorders.

Uncommon: ALT increased, gamma-GT increased, AST increased.
Rare: cholecystitis, cholelithiasis, bilirubinaemia, jaundice, hepatitis.
Unknown: liver function test abnormal.

Metabolic and nutritional disorders.

Common: increased weight, decreased weight.
Uncommon: thirst, dry eyes, increased alkaline phosphatase, abnormal glucose tolerance.
Rare: hypokalaemia, obesity, hypoglycaemia, dehydration.

Endocrine disorders.

Rare: hypothyroidism, goitre, gynaecomastia.

Cardiovascular disorders, general.

Common: postural hypotension, hypotension.
Uncommon: hypertension, oedema (extremities), cardiac failure, bradycardia, tachycardia.
Unknown: orthostatic hypotension.

Myo-, endo-, pericardial and valve disorders.

Uncommon: angina pectoris, myocardial infarction, myocardial ischaemia.

Heart rate and rhythm disorders.

Common: tachycardia, palpitations.
Uncommon: bradycardia, extrasystoles, atrial fibrillation.
Rare: bundle branch block, cardiac arrest, QT prolongation, Torsade de Pointes.

Vascular (extracardiac) disorders.

Uncommon: cerebrovascular accident, flushing, transient ischemic attack.
Rare: phlebitis.

Respiratory system disorders.

Common: yawning, rhinitis.
Uncommon: bronchitis, dyspnea, pneumonia.
Rare: asthma, laryngitis, bronchospasm, pneumonitis, sputum increased, coughing.

Red blood cell disorders.

Uncommon: anaemia.
Rare: hypochromic anaemia.

White cell and reticuloendothelial system disorders.

Uncommon: leucopenia, leukocytosis, lymphadenopathy.
Rare: granulocytopenia, lymphocytosis, lymphopenia.

Platelet, bleeding and clotting disorders.

Uncommon: abnormal bleeding, predominantly of the skin and mucous membranes, including purpura, epistaxis, haematomas, vaginal bleeding and gastrointestinal bleeding.
Rare: pulmonary embolism, coagulation disorder, gingival bleeding.
Unknown: thrombocytopaenia.

Urinary system disorders.

Common: polyuria.
Uncommon: micturition frequency, urinary incontinence, urinary retention, dysuria.
Rare: facial edema, haematuria, oliguria, pyelonephritis, renal calculus, renal pain.

Reproductive disorders/female.

Common: amenorrhoea.
Uncommon: lactation nonpuerperal, breast pain, breast enlargement, vaginal haemorrhage, menorrhagia.
Unknown: metrorrhagia.

Reproductive system and breast disorder/male.

Unknown: priapism, galactorrhoea.

Body as a whole.

Uncommon: hot flushes, rigors, alcohol intolerance, syncope.
Rare: hayfever.

General disorders.

Very common: asthenia.
Common: fatigue.
Rare: pyrexia, malaise.

Other events observed during the postmarketing evaluation of citalopram.

Although no causal relationship to citalopram treatment has been found, the following adverse events have been reported to be temporally associated with citalopram treatment in at least 3 patients (unless otherwise noted) and not described elsewhere (see Section 4.8 Adverse Effects (Undesirable Effects)): choreoathetosis, epidermal necrolysis (3 cases), erythema multiforme, hepatic necrosis (2 cases), cholestatic hepatitis, hyponatraemia, neuroleptic malignant syndrome, pancreatitis, serotonin syndrome, spontaneous abortion, thrombocytopenia, ventricular arrhythmia, priapism, and withdrawal syndrome.
Akathisia has been reported very rarely (< 1/10,000).
Cases of QT-prolongation have been reported during the post-marketing period, predominantly in patients with pre-existing cardiac disease.

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

For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).
In general, the main therapy for all overdoses is supportive and symptomatic care. Noumed Citalopram is given to depressed patients who are at potential risk of suicide. Some reports of attempted suicide with citalopram-treated patients have been received. Detail is often lacking regarding precise dose or combination with other drugs and/or alcohol.

Symptoms.

The following symptoms have been seen in reported overdose of citalopram: convulsion, tachycardia, somnolence, QT prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, dizziness, bundle branch block, QRS prolongation, hypertension, mydriasis, nodal rhythm, ventricular arrhythmia and very rare cases of Torsade de pointes.

Treatment.

There is no specific antidote. Treatment is symptomatic and supportive. The use of activated charcoal should be considered. Activated charcoal may reduce absorption of the drug if given within one or 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, once the airway is protected. Medical surveillance is advisable. ECG monitoring is recommended when more than 600 mg has been ingested. Convulsions may be treated with diazepam.
Elimination half life (T½β) and Tmax are independent of the dose taken. Information on these pharmacokinetic parameters can be found, see Section 5.2 Pharmacokinetic Properties.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Biochemical and behavioural studies have shown that citalopram is a potent inhibitor of serotonin (5-HT)-uptake. Tolerance to the inhibition of 5-HT-uptake is not induced by long-term treatment with citalopram.
On the basis of in vitro studies, citalopram is one of the most selective Serotonin Reuptake Inhibitor (SSRI) yet developed, with no, or minimal effect on noradrenaline (NA), dopamine (DA) and gamma aminobutyric acid (GABA) uptake. In comparison with other SSRls the decreasing order of selectivity is escitalopram, citalopram, sertraline, paroxetine, fluvoxamine and fluoxetine. The clinical relevance of this in vitro finding has not been established.
In contrast to many tricyclic antidepressants and some of the newer SSRIs, citalopram has no or very low affinity for a series of receptors including 5-HT1A, 5-HT2, DA D1, and DA D2 receptors, α1 receptors, α2 receptors, β-adrenoceptors, histamine H1, muscarine cholinergic, benzodiazepine, and opioid receptors. A series of functional in vitro tests in isolated organs as well as functional in vivo tests have confirmed the lack of receptor affinity.
Suppression of rapid eye movement (REM) sleep is considered a predictor of antidepressant activity. Like tricyclic antidepressants, other SSRIs and MAO inhibitors, citalopram suppresses REM-sleep and increases deep slow-wave sleep (based upon a five week single blind study in 16 depressed patients given doses up to 40 mg daily).
Although citalopram does not bind to opioid receptors it potentiates the anti-nociceptive effect of commonly used opioid analgesics in rats. The clinical significance of this finding has not been established.
The main metabolites of citalopram are all SSRIs although their potency and selectivity ratios are lower than those of citalopram but higher than those of many of the newer SSRIs. The metabolites do not contribute to the overall antidepressant effect.
In humans, citalopram does not impair cognitive function or psychomotor performance to the same extent as amitriptyline and it has slight sedative properties. There were results suggestive of impairment in some tests (critical flicker fusion, coding skills, body sway, immediate memory recall).
Citalopram did not reduce saliva flow in a single dose study in human volunteers and in none of the studies in healthy volunteers did citalopram have significant influence on cardiovascular parameters. Citalopram has no effect on the serum levels of prolactin and growth hormone. Like other SSRIs, citalopram increases plasma prolactin, an effect secondary to the prolactin stimulating role of serotonin.

Clinical trials.

Citalopram in the dose range 20-80 mg/day is more effective than placebo in the treatment of depression in the majority of trials, including relapse prevention trials. In the double-blind, placebo-controlled trials a total of 1083 patients received citalopram and 486 received placebo. There were three fixed dose trials of 6 weeks duration. In one trial a total of 650 patients with major depression were randomly allocated in approximately equal groups (~ 130 per group) to receive placebo or 10 mg, 20 mg, 40 mg or 60 mg citalopram. In the other two fixed dose studies, placebo was compared with 20 mg or 40 mg citalopram. Between 88 and 97 patients were treated in each group in one trial and approximately 48 in each group in the other. The remaining 5 trials of 4 or 6 weeks duration used flexible doses in the range of 20-80 mg/day.
In two relapse prevention or maintenance studies of 24 weeks duration, 257 patients were treated with citalopram and 116 with placebo. In one study, 147 citalopram-treated patients who were responders (MADRS ≤ 12) in two 6 weeks fixed dose studies were rerandomised to receive placebo (N = 42) or continue their previous treatment with 20 mg (N = 48) or 40 mg citalopram (N = 57). In the other study MADRS-responders (score ≤ 12) continued from an open 8-week trial and were randomised to receive placebo (N = 74) or continue with their optimal dose of citalopram (range 20-60 mg daily, N = 152). In both studies citalopram independent of dose reduced relapse rates and prolonged time to relapse compared to placebo.
The majority of the patients in the placebo-controlled trials received 40 mg/day. The minimal effective dose was 20 mg/day. Analyses of subgroups of patients showed that patients experiencing their first episode of depression or with less severe depression responded well to the minimal effective dose of 20 mg while patients suffering from severe or recurrent depression achieved better results with 40 or 60 mg/day.
Citalopram demonstrates an equivalent therapeutic efficacy to tricyclic and tetracyclic antidepressants and other SSRIs in the treatment of major depression. The active comparator studies were chiefly randomised double-blind studies. In the trials versus tri- and tetracyclic antidepressants (TTCA), a total of 682 patients received citalopram and 389 TTCAs. In the comparative trials versus other SSRIs, there were 439 citalopram treated patients and 451 treated with other SSRIs. In the 6-week comparison to imipramine, 20-30 mg (N = 187) and 40-60 mg (N = 193) citalopram were equally effective as imipramine 100-150 mg (N = 92). In an 8-week comparison carried out in hospital settings with fixed doses, 40 mg citalopram (N = 158) was equally effective to 20 mg fluoxetine (N = 158). Likewise in a general practice study, 20 mg citalopram (N = 173) was equally effective to 20 mg fluoxetine (N = 184). A 6-week comparison to fluvoxamine in flexible doses (citalopram 20-40 mg (N = 108)/ fluvoxamine 100-200 mg (N = 109)) also demonstrated equal efficacy.

5.2 Pharmacokinetic Properties

Absorption.

Oral bioavailability is about 80% and independent of food intake (Tmax mean 3.8 hours). The bioavailability of each enantiomer has not been studied separately, but the pharmacokinetics of each enantiomer is different.

Distribution.

The apparent volume of distribution (Vd)β is about 12-17 L/kg. The plasma protein binding is below 80% for citalopram and its main metabolites. After six weeks on 40-60 mg/day in 10 patients, the mean serum concentration of S-(+)-citalopram was about 50% of the R-(-)-citalopram concentration and the mean serum concentration of R-(-)-DCIT was 1.5 times that of S-(+)-DCIT.

Metabolism.

Citalopram is metabolised to the active demethylcitalopram (DCIT), didemethylcitalopram, citalopram-N-oxide and an inactive deaminated propionic acid derivative. All the active metabolites are also SSRls, although weaker than the parent compound. Unchanged citalopram is the predominant compound in plasma.

Excretion.

The elimination half-life (T½β) is about 1½ days and the systemic citalopram plasma clearance (Cls) is about 0.3-0.4 L/min, and total (oral) plasma clearance (Cloral) is about 0.4 L/min.
About 12-23% of the daily dose is excreted unchanged in the urine. Hepatic (residual) clearance is about 0.3 L/min and renal clearance about 0.05-0.08 L/min.
The kinetics are linear. Steady state plasma levels are achieved in 1-2 weeks. Average concentrations of 250 nanomol/L (100-500 nanomol/L) are achieved at a daily dose of 40 mg. There is no clear relationship between citalopram plasma levels and therapeutic response or side effects in a study of 650 patients.

Reduced hepatic function.

Citalopram is eliminated more slowly in patients with reduced hepatic function. The half-life of citalopram is about twice as long and steady state citalopram concentrations at a given dose will be about twice as high as in patients with normal liver function.

Reduced renal function.

Citalopram is eliminated more slowly in patients with mild to moderate reduction of renal function, without major impact on the pharmacokinetics of citalopram.

Elderly patients (> 65 years).

Longer half-lives and decreased clearance values due to a reduced rate of metabolism have been demonstrated in elderly patients.

Polymorphism.

There was no clinically relevant difference in the AUC between poor and extensive metabolisers with respect to CYP2D6 following administration of citalopram. The AUC for poor metabolisers with respect to CYP2C19 was less than 2-fold higher than the AUC observed in the extensive metabolisers (see Section 4.2 Dose and Method of Administration).

5.3 Preclinical Safety Data

Genotoxicity.

In assays of genotoxic activity, citalopram showed no evidence of mutagenic or clastogenic activity.

Carcinogenicity.

Citalopram did not show any carcinogenic activity in long term oral studies using mice and rats at doses up to 240 and 80 mg/kg/day, respectively.

6 Pharmaceutical Particulars

6.1 List of Excipients

Maize starch, lactose monohydrate, copovidone, glycerol, microcrystalline cellulose, magnesium stearate, sodium starch glycollate, hypromellose, macrogol 6000, titanium dioxide and purified talc.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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.

6.5 Nature and Contents of Container

Noumed Citalopram 20 mg tablets.

Available in PVC/PVDC/Al blisters and HDPE bottles of 28 tablets.

Noumed Citalopram 40 mg tablets.

Available in PVC/PVDC/Al blisters of 28 tablets.
Not all presentations may be marketed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Citalopram hydrobromide is a white to off-white, crystalline material.
Citalopram hydrobromide is sparingly soluble in water, soluble in ethanol (96%), freely soluble in chloroform and very slightly soluble in diethylether. No polymorphic forms have been detected.
Chemical name: 1-(3-dimethylaminopropyl)- 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile hydrobromide.
The active is present as a racemate.
Empirical formula: C20H21FN2O, HBr. MW: 405.32.

Chemical structure.


CAS number.

59729-32-7.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes