Consumer medicine information

Pharmacor Citalo Tablets

Citalopram

BRAND INFORMATION

Brand name

Pharmacor Citalo Tablets

Active ingredient

Citalopram

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Pharmacor Citalo Tablets.

What is in this leaflet?

This leaflet answers some common questions about PHARMACOR CITALO.

It does not contain all the available information that is known about PHARMACOR CITALO.

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 using this medicine against the benefits he/she expects 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 PHARMACOR CITALO is used for

PHARMACOR CITALO is used to treat depression. It 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 sex drive, lack of energy and feeling guilty over nothing.

PHARMACOR CITALO corrects this chemical imbalance and may help relieve the symptoms of depression.

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

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

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

Before you take it

When you must not take it

Do not take PHARMACOR CITALO if you are allergic to it or any of the ingredients listed at the end of this leaflet.

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, or rash, itching or hives on the skin.

Do not take PHARMACOR CITALO at the same time as the following other medicines:

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

Do not take PHARMACOR CITALO when you are taking a MAOI or when you have been taking a MAOI within the last 14 days.

Taking PHARMACOR CITALO with MAOIs may cause a serious reaction with a sudden increase in body temperature, extremely high blood pressure and severe convulsions. Your doctor will know when it is safe to start PHARMACOR CITALO after the MAOI has been stopped.

Do not take PHARMACOR CITALO after the expiry date printed on the pack.

If you take PHARMACOR CITALO after the expiry date has passed, it may not work as well. The expiry date refers to the last day of the month.

Do not take PHARMACOR CITALO if the packaging is torn or shows signs of tampering.

Before you start to take PHARMACOR CITALO

Tell your doctor if:

  1. you have allergies to such as foods, preservatives or dyes.
  2. you are pregnant or intend to become pregnant.
    Do not take PHARMACOR CITALO if you are pregnant unless you and your doctor have discussed 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. If you take a medicine from this group of medicines (antidepressants) during the last three months of pregnancy and until your baby is born, the following effects may be seen in your newborn baby: trouble with breathing, bluish skin, fits, body temperature changes, feeding difficulties, vomiting, low blood sugar, stiff or floppy muscles, vivid reflexes, tremor, jitteriness, irritability, lethargy, constant crying, sleepiness and sleeping difficulties. If your newborn baby has any of these symptoms, please contact your doctor immediately.
  3. you are breastfeeding or planning to breastfeed.
    Do not take PHARMACOR CITALO if you are breastfeeding unless you and your doctor have discussed the risks and benefits involved. It is not recommended that you breastfeed while taking PHARMACOR CITALO as it is excreted in breast milk.
  4. you have, or have had, the following medical conditions:
  • a tendency to bleed or bruise easily
  • diabetes
  • heart disease
  • kidney disease
  • liver disease
  • bipolar disorder (manic depression)
  • a history of seizures or fits
  • low blood levels of sodium (hyponatraemia)
  • restlessness and/or a need to move often (akathisia).
  1. you are receiving electroconvulsive therapy.

If you are lactose intolerant, contact your doctor before taking PHARMACOR CITALO.

PHARMACOR CITALO tablets contain lactose.

Do not give PHARMACOR CITALO to a child or adolescent.

There is no experience with its use in children or adolescents under 18 years old.

PHARMACOR CITALO can be given to elderly patients over 65 years of age with a reduced dose.

The effects of PHARMACOR CITALO in elderly patients are similar to that in other patients.

If you have not told your doctor about any of the above, tell them before you use PHARMACOR CITALO.

Taking other medicines

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

Some medicines and PHARMACOR CITALO 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 reflux and ulcers, such as cimetidine and omeprazole
  • medicines known to prolong bleeding, e.g. aspirin or other nonsteroidal anti-inflammatory drugs (NSAlDs)
  • warfarin, a medicine used to prevent blood clots
  • sumatriptan, used to treat migraines
  • tramadol 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 to treat Parkinson's disease
  • tryptophan, an aminoacid
  • lithium, 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 PHARMACOR CITALO, or may affect how well it works. You may need to use different amounts of your medicines, or take different medicines.

Your doctor will advise you. Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking PHARMACOR CITALO.

How to take it

How much to take

Your doctor will decide what dose you will receive. The standard dose for adults for this medicine is between 20 mg and 60 mg (one to three tablets) per day.

The recommended dose in elderly patients is 20 mg to 40 mg (one to two tablets) per day.

Your doctor may have prescribed a different 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 PHARMACOR CITALO may not work as well and your condition may not improve.

How to take it

Swallow the tablets whole with a full glass of water.

Do not chew them.

When to take it

Take PHARMACOR CITALO as a single dose either in the morning or in the evening.

Take PHARMACOR CITALO with or without food.

How long to take it

Continue to take PHARMACOR CITALO 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 PHARMACOR CITALO.

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 PHARMACOR CITALO 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 beats

When you have completed your course of treatment, the dose of PHARMACOR CITALO is gradually reduced over a couple of weeks rather than stopped abruptly.

Your doctor will tell you how to reduce the dosage so that you do not get these 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 you have missed.

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

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

If you take too much (overdose)

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

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 it

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking PHARMACOR CITALO

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

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

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

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 becomes 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 PHARMACOR CITALO, contact a health care provider immediately, or even to go to the nearest hospital for treatment:

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

Do not stop taking this medicine or change the dose without consulting your doctor, even if you experience increased anxiety at the beginning of treatment.

At the beginning of 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 weeks 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 abovementioned 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.

Things you must not do

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

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

Do not stop taking PHARMACOR CITALO, or lower the dosage, without checking with your doctor.

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

Suddenly stopping PHARMACOR CITALO may cause unwanted discontinuation symptoms such as dizziness, headache and nausea. Your doctor will tell you when and how PHARMACOR CITALO 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.

Things to be careful of

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

It may cause nausea, fatigue and dizziness in some people, especially early in the treatment. If you have any of these symptoms, do not drive or 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

All medicines may have some unwanted side effects. Sometimes they are serious, but most of the time they are not. Your doctor has weighed the risks of using this medicine

against the benefits he/she expects it will have for you.

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

It helps most people with depression, but it may have unwanted side effects in a few people.

The side effects of PHARMACOR CITALO are in general mild and disappear after a short period of time. Tell your doctor if you notice any of the following and they worry you:

  • 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
  • sense of indifference to everything
  • sexual disturbances (decreased sexual drive, problems with orgasm; problems with ejaculation or erection)
  • problems with menstrual periods.

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

  • chest pain
  • fast heart rate or decrease in heart rate
  • 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 muscles or feeling confused) which may be caused by SSRI antidepressants, especially in elderly patients increased tendency to develop bruises unusual bleeding, including bleeding from the 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.

These may be serious side effects of PHARMACOR CITALO. You may need urgent medical attention.

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

  • 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).

These are very serious side effects. You may need urgent medical attention or hospitalization.

Tell your doctor if you notice anything else that is making you feel unwell.

Other side effects not listed above may occur in some people.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

After taking it

Storage

Keep PHARMACOR CITALO tablets in the blister and bottle until it is time to take them.

If you take the tablets out of the box, blister or bottle they may not keep well.

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

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

Do not leave it in the car.

Heat and damp 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 the tablets, or the tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Return any unused medicine to your pharmacist.

Product description

What it looks like

  • PHARMACOR CITALO 10 mg tablets are white to offwhite, round, plain, filmcoated tablets.
  • PHARMACOR CITALO 20mg tablets are white to off white, oval. biconvex, fIlm-coated tablets, with BL embossed on one side & '20' on the other.
  • PHARMACOR CITALO 40 mg tablets are white to off white, oval, biconvex, film coated tablets with '40' embossed on one and 'BL' embossed on the other side.

Blister:

  • PHARMACOR CITALO tablets (10mg) in blister pack sizes of 7, 14, 28, 56 and 84 tablets.
  • PHARMACOR CITALO tablet (20mg) in blister pack sizes of 7, 14, 28, S6 and 84 tablets.
  • PHARMACOR CITALO tablet (40mg) in blister pack sizes of 7, 14, 28, S6 and 84 tablets.
  • PHARMACOR CITALO tablets (l0mg) in bottle pack sizes of 7, 14, 28, 56, 84, 100, 250, 500 and 1000 tablets.
  • PHARMACOR CITALO tablets (20mg) in bottle pack sizes of 7, 14, 28, 56, 84, 100, 250, 500 and 1000 tablets.
  • PHARMACOR CITALO tablets (40mg) in bottle pack sizes of 7, 14, 28, 56, 84, 100, 250, 500 and 1000 tablets.

Ingredients

Active ingredient(s):

  • PHARMACOR CITALO 10, 20 and 40 mg tablets - contain 10, 20 and 40 mg citalopram (as hydrobromide) per tablet

Inactive ingredients:

  • cellulosemicrocrystalline
  • croscarmellose sodium
  • hypromellose
  • lactose monohydrate
  • macrogol400
  • magnesium stearate
  • starch - maize, (For paste)
  • titanium dioxide.
  • Purified water
  • Talc - purified

PHARMACOR CITALO does not contain gluten, sucrose, tartrazine or any other azo dyes

Sponsor

Pharmacor Limited
5/36 Campbell Avenue
CROMER
NSW 2099 Australia

ARTG number:
PHARMACOR CITALO tablets
10 mg AUST R 158875, 158876
20 mg AUST R 158873, 158874.
40 mg AUST R 158877, 158878

BRAND INFORMATION

Brand name

Pharmacor Citalo Tablets

Active ingredient

Citalopram

Schedule

S4

 

Name of the medicine

Citalopram hydrobromide.

Excipients.

Lactose, starch-maize, purified water, cellulose-microcrystalline, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide, talc-purified, macrogol 400.

Description

Chemical name: 1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-Scarbonitrile hydrobromide. The active is present as a racemate. CAS number: 59729-32-7. Molecular formula: C20H22BrFN2O. Molecular weight: 405.3.
Citalopram hydrobromide is a fine 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.
Pharmacor Citalo 10, are 10 mg, white to off-white, round, plain, film-coated tablets.
Pharmacor Citalo 20, are 20 mg, white to off-white, oval, biconvex, film-coated tablets, with BL embossed on one side and '20' on the other.
Pharmacor Citalo 40, are 40 mg, white to off white, oval, biconvex, film coated tablets with '40' embossed on one side and 'BL' embossed on the other side.
The tablets contain the following excipients: lactose, starch-maize, purified water, cellulose-microcrystalline, croscarmellose sodium, magnesium stearate, hypromellose, titanium dioxide, talc-purified, macrogol 400.

Pharmacology

Pharmacological actions.

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 inhibitors of serotonin reuptake yet developed, with no, or minimal effect on noradrenaline (NA), dopamine (DA) and gamma aminobutyric acid (GABA) uptake. In comparison with other Selective Serotonin Reuptake Inhibitors (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-HT,A, 5-HT2, DA D1 and DA D2 receptors, α 1 receptors, α 2 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 SSRls 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 antinociceptive 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 SSRls although their potency and selectivity ratios are lower than those of citalopram but higher than those of many of the newer SSRls. 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 growth hormone. Like other SSRls, citalopram increases plasma prolactin, an effect secondary to the prolactin stimulating role of serotonin.

Pharmacokinetics.

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.

Elimination.

The elimination half-life (t1/2β) is about 11/2 days and the systemic citalopram plasma clearance (CIS) is about 0.3-0.4 L/min, and total (oral) plasma clearance (CIoral) 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 AUG observed in the extensive metabolisers (see Dosage and Administration).

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 re-randomised 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 tetra cyclic antidepressants and other SSRls 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 SSRls, there were 439 citalopram treated patients and 451 treated with other SSRls. 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 10 fluvoxamine in flexible doses (citalopram 20-40 mg (N=108) fluvoxamine 100-200 mg (N=109) also demonstrated equal efficacy.

Indications

Treatment of major depression.

Contraindications

Hypersensitivity to citalopram and any excipients in Pharmacor-Citalopram (see Description).
Concurrent administration of citalopram and Monoamine Oxidase Inhibitors (see Precautions).
Concomitant use in patients taking pimozide is contraindicated (see Interactions with Other Medicines).

Precautions

Use with caution in the following circumstances:

Clinical worsening and suicide risk associated with psychiatric disorders.

The risk of suicide attempt is inherent in depression and may persist until significant remission occurs. This risk must be considered in all depressed patients.
Patients with depression may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviours (suicidality) whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. As improvements 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/behavior 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 analyses of 24 short-term (4 to 16 week), placebo-controlled trials of nine antidepressant medicines (SSRls and others) in 4400 children and adolescents with major depressive disorder (16 trials), obsessive compulsive disorder (4 trials), or other psychiatric disorders (4 trials) have revealed a greater risk of adverse events representing suicidal behaviour or thinking (suicidality) during the first few months of treatment in those receiving antidepressants, The average risk of such events in patients treated with an antidepressant was 4%, compared with 2% of patients given placebo. There was considerable variation in risk among the antidepressants, but there was a tendency towards an increase for almost all antidepressants studied. The risk of suicidality was most consistently observed in the major depressive disorder trials, but there were signals of risk arising from trials in other psychiatric indications (obsessive-compulsive disorder and social anxiety disorder) as well. No suicides occurred in these trials. It is unknown whether the suicidality risk in children and adolescent patients extends to use beyond several months. The nine antidepressant medicines in the pooled analyses included five SSRls (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and four non-SSRls (buproprion, mirtazapine, nefazodone, venlafaxine).
Pooled analyses of short-term studies of antidepressant medications have also shown an increased risk of suicidal thinking and behaviour, known as suicidality, in young adults aged 18 10 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 behavior, and other symptoms described above, as well as the emergence of suicidality, and to report such symptoms to health care providers immediately. 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 Pharmacor Citalo should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

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 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 MAOls and a minimum of one drug free day after discontinuation of moclobemide. Treatment with MAOls may be introduced 14 days after discontinuation of citalopram.

Haemorrhage.

Bleeding abnormalities of the skin and mucous membranes have been reported with the use of SSRls (including purpura, ecchymosis, haematoma, epistaxis, vaginal bleeding and gastrointestinal bleeding). 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 non-steroidal anti-inflammatory medicinal products (NSAIDs), ticlopidine 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 SSRls. Especially elderly patients seem to be a risk group.

Akathisia/psychomotor restlessness.

The use of SSRls/SNRls has been associated with the development of akathisia, characterised 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 SSRls/SNRls.

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 patient's glucose balance.

Mania.

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

ECT (electroconvulsive therapy).

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

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.

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, diarrhoea, 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 Dosage and 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 SSRls, 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 hereditary 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, has been associated with convulsions and EGG abnormalities in experimental animals.

Effects of 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.

Use in pregnancy.

(Category C)
Category C Definition - Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations, These effects may be reversible. Accompanying texts should be consulted for further details.
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 fetal weight and fetal developmental changes, A no effect oral dose of 56 mg/kg/day was established for fetal 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 an SSRI at the end of pregnancy. Neonates 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.
Neonates exposed to citalopram, other SSRls (Selective Serotonin Reuptake Inhibitors), or SNRls (Serotonin Norepinephrine Reuptake Inhibitors), late in the third trimester have developed complications requiring prolonged hospitalisation, 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 SSRls and SNRls or possibly, a drug discontinuation syndrome.

Use in lactation.

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.

Paediatric use (< 18 years).

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.

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.

Genotoxicity.

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

Interactions

MAOls.

Monoamine Oxidase Inhibitors (MAOls) should not be used in combination with SSRls (see Contraindications).

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 OTc 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 Contraindications).

Serotonergic drugs.

SSRls 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 SSRls, 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 SSRls).
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 CYP1A2, -2D6, and -2C19. Citalopram would be expected to have little inhibitory effect on in vivo metabolism mediated by these iso enzymes. However, in vivo data to address this question are very limited.
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, might decrease the clearance of citalopram. Citalopram steady state levels were not significantly different in poor metabolisers and extensive 2D6 metabolisers after multiple dose administration of citalopram, suggesting that coadministration, with citalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on citalopram metabolism.

Lithium and tryptophan.

There is no pharmacokinetic interaction between lithium and citalopram. However, there have been reports of enhanced serotonergic effects when SSRls 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 co-administration of citalopram and tricyclic antidepressants.

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 this risk. Thus, patients should be cautioned about using such medicines concurrently with 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 co-administered.

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.

Cimetidine caused a moderate increase in the average steady state levels of citalopram. It is therefore advised to exercise caution at the upper end of the dose range of citalopram when it is used concomitantly with high doses of cimetidine.

Alcohol.

The combination of SSRls and alcohol is not advisable.

Others.

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 Contraindications and Interactions with Other Medicines, Pimozide). However, as with other SSRls, the possibility of a pharmacodynamic interaction cannot be excluded.

Adverse 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 SSRls 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 SSRls.

While sexual dysfunction is often part of depression and other psychiatric disorders, there is increasing evidence that treatment with selective serotonin reuptake inhibitors (SSRls) 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 SSRls 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 SSRls, 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.

Laboratorv changes.

Citalopram and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, hematology, 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 (1) mean change from baseline in various ECG parameters and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. The only statistically significant drug-placebo difference observed was a decrease in heart rate for citalopram of 1.7 bpm compared to no change in heart rate for placebo. There were no observed differences in OT or other ECG intervals.

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 to the Adverse Effects section, 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 remarketing database of 4,422 patients. All reported events are included except those already listed in the table or elsewhere in the Adverse Effects section, 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 emphasize that, although the events reported occurred during treatment with citalopram, they were not necessarily caused by it.
Events are further categorized 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 1110 but at least 11100; uncommon adverse events are those occurring in less than 1/100 patients but at least 111,000 patients; rare events are those occurring in fewer than 111,000 patients; unknown cannot be estimated from available data.

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.

Musculoskeletal system disorders.

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

Central and peripheral nervous system disorders.

Common: migraine.
Uncommon: vertigo, leg cramps, involuntary muscle contractions, speech disorder, abnormal gait, hypoaesihesia, psychomotor restlessness, akathisia (see Precautions) neuralgia, ataxia, convulsions.
Rare: abnormal coordination, hyperesthesia, ptosis, stupor.

Vision disorders.

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

Special senses, other disorders.

Common: taste perversion.
Rare: taste loss.

Psychiatric disorders.

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.

Gastrointestinal system disorders.

Common: saliva increased. 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 haemorrhage.

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- arid pericardial and valve disorders.

Uncommon: angina pectoris, myocardial infarction, myocardial ischaemia.

Hearl rate and rhythm disorders.

Common: tachycardia.
Uncommon: bradycardia, extrasystoles, atrial fibrillation.
Rare: bundle branch block, cardiac arrest.

Vascular (extra cardiac) disorders.

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

Respiratory system disorders.

Uncommon: bronchitis, dyspnoea, pneumonia.
Rare: asthma, laryngitis, bronchospasm, pneumonitis, sputum increased.

Red blood cell disorders.

Uncommon: anaemia.
Rare: hypochromic anaemia.

White cell and reticuloendothelial system disorders.

Uncommon: leucopoenia, 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 oedema, haematuria, oliguria, pyelonephritis, renal calculus, renal pain.

Reproductive disorders/female.

Common: amenorrhoea.
Uncommon: lactation nonpuerperal, breast pain, breast enlargement, vaginal haemorrhage, menorrhagia.
Unknown: metrorrhagia (% based on female subjects only: 2955).

Reproductive system and breast disorders/male.

Unknown: priapism, galactorrhoea.

Body as a whole.

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

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 in the Adverse Effects section (total of 8 million patients estimated to have been treated with citalopram): angioedema, choreoathetosis, epidermal necrolysis (3 cases), erythema multiforme, hepatic necrosis (2 cases), hepatitis, cholestatic hepatitis, hyponatraemia, neuroleptic malignant syndrome, mania, pancreatitis, serotonin syndrome, spontaneous abortion, thrombocytopenia, ventricular arrhythmia, Torsades de pointes, 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.

Dosage and Administration

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 60 mg/day. As the treatment result in general can be evaluated only after 2-3 weeks of treatment, a possible dose increase should take place with intervals of 2-3 weeks.

Elderly patients.

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.

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.

Dosage should be restricted to the lower end of the dose range.

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.

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 20 mg daily depending on individual patient response (see Pharmacokinetics).

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 Precautions). 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.

Overdosage

In general, the main therapy for all overdoses is supportive and symptomatic care.
Citalopram is given to depressed patients who are at potential risk of suicide and 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, OT prolongation, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, dizziness, bundle branch block, QRS prolongation, hypertension, and mydriasis. As with other SSRls, fatalities have been reported.

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 have been ingested. Convulsions may be treated with diazepam.
Elimination half-life (T1/2β) and T are independent of the dose taken. Information on these pharmacokinetic parameters can be found under Pharmacology.
For further advice on management of overdose please contact the Poisons Information Centre (Tel: 131 126 for Australia).

Presentation

Pharmacor Citalo 10 are 10 mg white to off-white, round, plain, film-coated tablets.
Pharmacor Citalo 20 are 20 mg white to off-white, oval, biconvex, film-coated tablets, with BL embossed on one side and '20' on the other.
Pharmacor Citalo 40 are 40 mg white to off white, oval, biconvex, film coated tablets with '40' embossed on one side and 'BL' embossed on the other side.
Blister:
Pharmacor Citalo 10 -Citalopram tablets (10 mg) in blister pack sizes of 7*, 14*, 28, 56*# and 84*# tablets.
Pharmacor Citalo 20 -Citalopram tablets (20 mg) in blister pack sizes of 7*, 14*, 28, 56*# and 84*# tablets.
Pharmacor Citalo 40 -Citalopram tablets (40 mg) in blister pack sizes of 7*, 14*, 28, 56*# and 84*# tablets.
Bottle:
Pharmacor Citalo 10 - Citalopram tablets (10 mg) in bottle pack sizes of 7*, 14*, 28, 56*#, 84*#, 100*#, 250*#, 500*# and 1000*# tablets.
Pharmacor Citalo 20 - Citalopram tablets (20 mg) in bottle pack sizes of 7*, 14*, 28, 56*#, 84*#, 100*#, 250*#, 500*# and 1000*# tablets.
Pharmacor Citalo 40 - Citalopram tablets (40 mg) in bottle pack sizes of 7*, 14*, 28, 56*#, 84*#, 100*#, 250*#, 500*# and 1000*# tablets.
*These pack sizes are currently not marketed.
#Dispensing packs only.

Storage

Store below 25°C.

Poison Schedule

S4.