Ciproxin Tablets 750mg

Due to regulatory changes, the content of the following Patient Information Leaflet may vary from the one found in your medicine pack. Please compare the 'Leaflet prepared/revised date' towards the end of the leaflet to establish if there have been any changes.

If you have any doubts or queries about your medication, please contact your doctor or pharmacist.

Ciproxin 750 mg film-coated tablets

Ciprofloxacin

Read all of this leaflet carefully before you start taking this medicine.

• Keep this leaflet. You may need to read it again.


• If you have any further questions, ask your doctor or pharmacist.


• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.


• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

• 1. What Ciproxin is and what it is used for


• 2. Before you take Ciproxin


• 3. How to take Ciproxin


• 4. Possible side effects


• 5. How to store Ciproxin


• 6. Further information

What Ciproxin Is And What It Is Used For

Ciproxin is an antibiotic belonging to the fluoroquinolone family. The active substance is ciprofloxacin. Ciprofloxacin works by killing bacteria that cause infections. It only works with specific strains of bacteria.

Adults

Ciproxin is used in adults to treat the following bacterial infections:

• respiratory tract infections


• long lasting or recurring ear or sinus infections


• urinary tract infections


• infections of the testicles


• genital organ infections in women


• gastro-intestinal tract infections and intra-abdominal infections


• skin and soft tissue infections


• bone and joint infections


• to treat infections in patients with a very low white blood cell count (neutropenia)


• to prevent infections in patients with a very low white blood cell count (neutropenia)


• to prevent infections due to the bacterium Neisseria meningitidis


• anthrax inhalation exposure

If you have a severe infection or one that is caused by more than one type of bacterium, you may be given additional antibiotic treatment in addition to Ciproxin.

Children and adolescents

Ciproxin is used in children and adolescents, under specialist medical supervision, to treat the following bacterial infections:

• lung and bronchial infections in children and adolescents suffering from cystic fibrosis


• complicated urinary tract infections, including infections that have reached the kidneys (pyelonephritis)


• anthrax inhalation exposure

Ciproxin may also be used to treat other specific severe infections in children and adolescents when your doctor considered this necessary.

Before You Take Ciproxin

Do not take Ciproxin if you are:

• allergic (hypersensitive) to the active substance, to other quinolone drugs or to any of the other ingredients of Ciproxin (see section 6)


• taking tizanidine (see Section 2: Taking other medicines)

Take special care with Ciproxin

Before taking Ciproxin

Tell your doctor if you:

• have ever had kidney problems because your treatment may need to be adjusted


• suffer from epilepsy or other neurological conditions


• have a history of tendon problems during previous treatment with antibiotics such as Ciproxin


• have myasthenia gravis (a type of muscle weakness)


• have a history of abnormal heart rhythms (arrythmias)

While taking Ciproxin

Tell your doctor immediately, if any of the following occurs while taking Ciproxin. Your doctor will decide whether treatment with Ciproxin needs to be stopped.

• 
  Severe, sudden allergic reaction (an anaphylactic reaction/shock, angio-oedema). Even with the first dose, there is a small chance that you may experience a severe allergic reaction with the following symptoms: tightness in the chest, feeling dizzy, sick or faint, or experiencing dizziness when standing up. If this happens, stop taking Ciproxin and contact your doctor immediately.


• 
  Pain and swelling in the joints and tendinitis may occur occasionally, particularly if you are elderly and are also being treated with corticosteroids. At the first sign of any pain or inflammation stop taking Ciproxin and rest the painful area. Avoid any unnecessary exercise, as this might increase the risk of a tendon rupture.


• If you suffer from epilepsy or other neurological conditions such as cerebral ischemia or stroke, you may experience side effects associated with the central nervous system. If this happens, stop taking Ciproxin and contact your doctor immediately.


• You may experience psychiatric reactions the first time you take Ciproxin. If you suffer from depression or psychosis, your symptoms may become worse under treatment with Ciproxin. If this happens, stop taking Ciproxin and contact your doctor immediately.


• You may experience symptoms of neuropathy such as pain, burning, tingling, numbness and/or weakness. If this happens, stop taking Ciproxin and contact your doctor immediately.


• 
  Diarrhoea may develop while you are taking antibiotics, including Ciproxin, or even several weeks after you have stopped taking them. If it becomes severe or persistent or you notice that your stool contains blood or mucus, stop taking Ciproxin immediately, as this can be life-threatening. Do not take medicines that stop or slow down bowel movements and contact your doctor.


• Tell the doctor or laboratory staff that you are taking Ciproxin if you have to provide a blood or urine sample.


• Ciproxin may cause liver damage. If you notice any symptoms such as loss of appetite, jaundice (yellowing of the skin), dark urine, itching, or tenderness of the stomach, stop taking Ciproxin and contact your doctor immediately.


• Ciproxin may cause a reduction in the number of white blood cells and your resistance to infection may be decreased. If you experience an infection with symptoms such as fever and serious deterioration of your general condition, or fever with local infection symptoms such as sore throat/pharynx/mouth or urinary problems you should see your doctor immediately. A blood test will be taken to check possible reduction of white blood cells (agranulocytosis). It is important to inform your doctor about your medicine.


• Tell your doctor if you or a member of your family is known to have a deficiency in glucose-6-phosphate dehydrogenase (G6PD), since you may experience a risk of anemia with ciprofloxacin.


• Your skin becomes more sensitive to sunlight or ultraviolet (UV) light when taking Ciproxin. Avoid exposure to strong sunlight, or artificial UV light such as sunbeds.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including any that you obtained without a prescription.

Do not take Ciproxin together with tizanidine, because this may cause side effects such as low blood pressure and sleepiness (see Section 2: "Do not take Ciproxin").

The following medicines are known to interact with Ciproxin in your body. Taking Ciproxin together with these medicines can influence the therapeutic effect of those medicines. It can also increase the probability of experiencing side effects.

Tell your doctor if you are taking:

• warfarin or other oral anti-coagulants (to thin the blood)


• probenecid (for gout)


• methotrexate (for certain types of cancer, psoriasis, rheumatoid arthritis)


• theophylline (for breathing problems)


• tizanidine (for muscle spasticity in multiple sclerosis)


• clozapine (an antipsychotic)


• ropinirole (for Parkinson’s disease)


• phenytoin (for epilepsy)

Ciproxin may increase the levels of the following medicines in your blood:

• pentoxifylline (for circulatory disorders)


• caffeine

Some medicines reduce the effect of Ciproxin. Tell your doctor if you take or wish to take:

• antacids


• mineral supplements


• sucralfate


• a polymeric phosphate binder (e.g. sevelamer)


• medicines or supplements containing calcium, magnesium, aluminium or iron

If these preparations are essential, take Ciproxin about two hours before or no sooner than four hours after them.

Taking Ciproxin with food and drink

Unless you take Ciproxin during meals, do not eat or drink any dairy products (such as milk or yoghurt) or drinks with added calcium when you take the tablets, as they may affect the absorption of the active substance.

Pregnancy and breast-feeding

It is preferable to avoid the use of Ciproxin during pregnancy. Tell your doctor if you are planning to get pregnant.

Do not take Ciproxin during breast feeding because ciprofloxacin is excreted in breast milk and can be harmful for your child.

Driving and using machines

Ciproxin may make you feel less alert. Some neurological adverse events can occur. Therefore, make sure you know how you react to Ciproxin before driving a vehicle or operating machinery. If in doubt, talk to your doctor.

How To Take Ciproxin

Your doctor will explain to you exactly how much Ciproxin you will have to take as well as how often and for how long. This will depend on the type of infection you have and how bad it is.

Tell your doctor if you suffer from kidney problems because your dose may need to be adjusted.

The treatment usually lasts from 5 to 21 days, but may take longer for severe infections. Take the tablets exactly as your doctor has told you. Ask your doctor or pharmacist if you are not sure how many tablets to take and how to take Ciproxin.

• a. Swallow the tablets with plenty of fluid. Do not chew the tablets because they do not taste nice.


• b. Do try to take the tablets at around the same time every day.


• c. You can take the tablets at mealtimes or between meals. Any calcium you take as part of a meal will not seriously affect uptake. However, do not take Ciproxin tablets with dairy products such as milk or yoghurt or with fortified fruit juices (e.g. calcium-fortified orange juice).

Remember to drink plenty of fluids while you are taking Ciproxin.

If you take more Ciproxin than you should

• If you take more than the prescribed dose, get medical help immediately. If possible, take your tablets or the box with you to show the doctor.

If you forget to take Ciproxin

• Take the normal dose as soon as possible and then continue as prescribed. However, if it is almost time for your next dose, do not take the missed dose and continue as usual. Do not take a double dose to make up for a forgotten dose. Be sure to complete your course of treatment.

If you stop taking Ciproxin

• It is important that you finish the course of treatment even if you begin to feel better after a few days. If you stop taking this medicine too soon, your infection may not be completely cured and the symptoms of the infection may return or get worse. You might also develop resistance to the antibiotic.

If you have any more questions about the use of this product, ask your doctor or pharmacist.

Possible Side Effects

Like all medicines, Ciproxin can cause side effects, although not everybody gets them.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, tell your doctor or pharmacist.

Common side effects (between 1 and 10 in every 100 people are likely to get these):

• nausea, diarrhoea


• joint pains in children

Uncommon side effects (between 1 and 10 in every 1,000 people are likely to get these):

• fungal superinfections


• a high concentration of eosinophils, a type of white blood cell


• loss of appetite (anorexia)


• hyperactivity or agitation


• headache, dizziness, sleeping problems, or taste disorders


• vomiting, abdominal pain, digestive problems such as stomach upset (indigestion/heartburn), or wind


• increased amounts of certain substances in the blood (transaminases and/or bilirubin)


• rash, itching, or hives


• joint pain in adults


• poor kidney function


• pains in your muscles and bones, feeling unwell (asthenia), or fever


• increase in blood alkaline phosphatase (a certain substance in the blood)

Rare side effects (between 1 and 10 in every 10,000 people are likely to get these):

• inflammation of the bowel (colitis) linked to antibiotic use (can be fatal in very rare cases) (see Section 2: Take special care with Ciproxin)


• changes to the blood count (leukopenia, leukocytosis, neutropenia, anaemia), increased or decreased amounts of a blood clotting factor (thrombocytes)


• allergic reaction, swelling (oedema), or rapid swelling of the skin and mucous membranes (angio-oedema)


• increased blood sugar (hyperglycaemia)


• confusion, disorientation, anxiety reactions, strange dreams, depression, or hallucinations


• pins and needles, unusual sensitivity to stimuli of the senses, decreased skin sensitivity, tremors, seizures (see Section 2: Take special care with Ciproxin), or giddiness


• eyesight problems


• tinnitus, loss of hearing, impaired hearing


• rapid heartbeat (tachycardia)


• expansion of blood vessels (vasodilation), low blood pressure, or fainting


• shortness of breath, including asthmatic symptoms


• liver disorders, jaundice (cholestatic icterus), or hepatitis


• sensitivity to light (see Section 2: Take special care with Ciproxin)


• muscle pain, inflammation of the joints, increased muscle tone, or cramp


• kidney failure, blood or crystals in the urine (see Section 2: Take special care with Ciproxin), urinary tract inflammation


• fluid retention or excessive sweating


• abnormal levels of a clotting factor (prothrombin) or increased levels of the enzyme amylase

Very rare side effects (less than 1 in every 10,000 people are likely to get these):

• a special type of reduced red blood cell count (haemolytic anaemia); a dangerous drop in a type of white blood cells (agranulocytosis ); a drop in the number of red and white blood cells and platelets (pancytopenia), which may be fatal; and bone marrow depression, which may also be fatal (see Section 2: Take special care with Ciproxin)


• severe allergic reactions (anaphylactic reaction or anaphylactic shock, which can be fatal - serum sickness) (see Section 2: Take special care with Ciproxin)


• mental disturbances (psychotic reactions) (see Section 2: Take special care with Ciproxin)


• migraine, disturbed coordination, unsteady walk (gait disturbance), disorder of sense of smell (olfactory disorders), pressure on the brain (intracranial pressure)


• visual colour distortions


• inflammation of the wall of the blood vessels (vasculitis)


• pancreatitis


• death of liver cells (liver necrosis) very rarely leading to life-threatening liver failure


• small, pin-point bleeding under the skin (petechiae); various skin eruptions or rashes (for example, the potentially fatal Stevens-Johnson syndrome or toxic epidermal necrolysis)


• muscle weakness, tendon inflammation, tendon rupture – especially of the large tendon at the back of the ankle (Achilles tendon) (see Section 2: Take special care with Ciproxin); worsening of the symptoms of myasthenia gravis (see Section 2: Take special care with Ciproxin)

Frequency not known (cannot be estimated from the available data)

• troubles associated with the nervous system such as pain, burning, tingling, numbness and/or weakness in extremities


• severe cardiac rhythm abnormalities, irregular heart beat (Torsades de Pointes)

How To Store Ciproxin

Keep out of the reach and sight of children.

Do not use Ciproxin after the expiry date, which is stated on the blister and carton after "EXP": The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any medicines no longer required. These measures will help to protect the environment.

Further Information

What Ciproxin contains

The active substance is ciprofloxacin.

Each film-coated tablet contains 750 mg ciprofloxacin (as hydrochloride).

The other ingredients are:

Tablet core: cellulose microcrystalline, crospovidone, magnesium stearate, maize starch, silica colloidal anhydrous.

Film-coat: hypromellose, macrogol 4000, titanium dioxide (E171).

What Ciproxin looks like and contents of the pack

Ciproxin 750 mg tablets: oblong, nearly white to slightly yellowish tablets marked with "CIP 750" on one side and "BAYER" on the reverse side.

Pack sizes of 6, 10, 12, 14, 16, 20, 28, 50, 100, 160 or 500 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing authorisation holder

Bayer plc

Bayer Schering Pharma

Bayer House

Strawberry Hill

Newbury

Berkshire

RG14 1JA

Manufacturer: Bayer Schering Pharma AG

This medicinal product is authorised in the Member States of the EEA under the following names:

Austria: Ciproxin

Belgium: Ciproxine

Denmark: Ciproxin

Finland: Ciproxin

France: Ciflox

Germany: Ciprobay

Greece: Ciproxin

Iceland: Ciproxin

Ireland: Ciproxin

Italy: Ciproxin

Luxembourg: Ciproxine

Netherlands: Ciproxin

Norway: Ciproxin

Portugal: Ciproxina

Slovenia: Ciprobay

Spain: Baycip

Sweden : Ciproxin

United Kingdom: Ciproxin

This leaflet was last approved in April 2010.

Advice/medical education

Antibiotics are used to cure bacterial infections. They are ineffective against viral infections. If your doctor has prescribed antibiotics, you need them precisely for your current illness. Despite antibiotics, some bacteria may survive or grow. This phenomenon is called resistance: some antibiotic treatments become ineffective.

Misuse of antibiotics increases resistance. You may even help bacteria become resistant and therefore delay your cure or decrease antibiotic efficacy if you do not respect appropriate:

• dosages


• schedules


• duration of treatment

Consequently, to preserve the efficacy of this drug:

• 1 - Use antibiotics only when prescribed.


• 2 - Strictly follow the prescription.


• 3 - Do not re-use an antibiotic without medical prescription, even if you want to treat a similar illness.


• 4 - Never give your antibiotic to another person; maybe it is not adapted to her/his illness.


• 5 - After completion of treatment, return all unused drugs to your chemist’s shop to ensure they will be disposed of correctly.

Citalopram Tablets 10mg, 20mg, 40mg

Citalopram 10mg, 20mg

and 40mg tablets

Read all of this leaflet carefully before you start taking this medicine.

• Keep this leaflet. You may need to read it again.


• If you have any further questions, ask your doctor or pharmacist.


• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

Index

1 What Citalopram tablets are and what they are used for

2 Before you take

3 How to take

4 Possible side effects

5 How to store

6 Further information

What Citalopram tablets are and what they are used for

Citalopram is one of a type of antidepressants known as Selective Serotonin Re-uptake Inhibitors (SSRIs). It increases the effects of the body’s
naturally occurring hormone, serotonin, by inhibiting its re-uptake in the nerve cells.

Citalopram is used to treat major episodes of depression.

Before you take

Do not take Citalopram tablets and tell your doctor if you:

• are allergic (hypersensitive) to citalopram or any of the other ingredients (see section 6).


• are taking, or have taken within the last two weeks, any monoamine oxidase inhibitors (MAO- inhibitors). These are medicines used depression or Parkinson’s disease (e.g. selegiline or moclobemide).


• are taking pimozide (an antipsychotic medicine).

Check with your doctor or pharmacist before taking Citalopram tablets if you:

• suffer from mania (great excitement, hallucinations, difficulty in concentrating or staying still).


• suffer from any mental illnesses such as depression.


• are diabetic.


• suffer from epilepsy. If you start having more fits than usual stop taking citalopram and see your doctor immediately.


• suffer from liver damage or liver disease.


• suffer from severe kidney disease.


• suffer from heart problems or an abnormal heart rhythm.


• are having electro-convulsive therapy (ECT).


• have a history of bleeding disorders.


• are taking herbal products containing St. John’s wort (hypericum perforatum) used to treat depression.


• are taking sumatriptan or other triptans (for migraines), oxitriptan or tryptophan (substances that may influence the level of serotonin in the brain) or tramadol (to treat moderate to severe pain).

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Especially:

• tricyclic antidepressants such as desipramine or clomipramine to treat depression.


• medicines to thin your blood (eg warfarin), or other medicines which can cause bleeding, such as non-steroidal anti-inflammatory medicines, NSAIDs, (eg ibuprofen), aspirin, dipyridamole or ticlopidine.


• medicines to treat mental illness (eg chlorpromazine, haloperidol, thioridazine).


• lithium to treat mania or other mental illnesses.


• cimetidine, omeprazole, esomeprazole, lansoprazole to treat stomach ulcers.


• metoprolol to treat heart conditions.


• neuroleptics to treat schizophrenia.


• mefloquin to treat malaria.


• flecainide or propofenone to treat heart disorders.

Use in children and adolescents under 18 years:

Citalopram tablets should normally not be used for children and adolescents under 18 years. Also, you should know that patients under 18 have an increased risk of side-effects such as suicide attempt, suicidal thoughts and hostility (predominantly aggression, oppositional behaviour and anger) when they take this class of medicines. Despite this, your doctor may prescribe Citalopram for patients under 18 because he/she decides that this is in their best interest. If your doctor has prescribed Citalopram for a patient under 18 and you want to discuss this, please go back to your doctor. You should inform your doctor if any of the symptoms listed above develop or worsen when patients under 18 are taking Citalopram. Also, the long-term safety effects concerning growth, maturation and cognitive and behavioural development of Citalopram in this age group have not yet been demonstrated.

Thoughts of suicide and worsening of your depression or anxiety disorder

If you are depressed and/or have anxiety disorders you can sometimes have thoughts of harming or killing yourself. These may be increased when first starting antidepressants, since these medicines all take time to work, usually about two weeks but sometimes longer. You may be more likely to think like this:

• If you have previously had thoughts about killing or harming yourself.


• If you are a young adult. Information from clinical trials has shown an increased risk of suicidal behaviour in young adults (less than 25 years old) with psychiatric conditions who were treated with an antidepressant.

If you have thoughts of harming or killing yourself at any time, contact your doctor or go to a hospital straight away.

You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You might ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about changes in your behaviour.

Pregnancy and breast-feeding

If you are pregnant, planning to become pregnant or are breast-feeding ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Citalopram tablets may affect your ability to make judgements and to react to emergencies. Make sure you are not affected before you drive or operate machinery. If you are affected in any way, you should NOT drive or operate machinery.

How to take

Always take Citalopram tablets exactly as your doctor has told you. If you are not sure, check with your doctor or pharmacist.

You are advised NOT to drink alcohol with this medicine.

Swallow these tablets with water. These tablets are taken as a single dose, with or without food, either in the morning or evening.

Doses:

• 
  Adults:
  
  
  A low starting dose of 20mg is recommended and depending on the response to treatment the dose may be increased to 40mg daily. The maximum daily dose is 60mg.


• 
  Elderly:
  
  
  Elderly patients would normally take half of the dose recommended for adults that is 10-20mg daily.


• 
  Children and adolescents:
  
  
  Not recommended for use in children aged under 18 years.


• 
  Kidney disease:
  
  
  If you suffer from severe kidney impairment, citalopram is not recommended.


• 
  Liver disease:
  
  
  A starting dose of 10mg daily for the first two weeks is recommended in patients with mild to moderate liver disease, the dose may be increased to 30mg daily. If you suffer from severe liver disease, your doctor will be extra careful with increasing the dose.

After starting treatment, the tablets may not take effect for at least 2 weeks. This medicine should be taken for as long as your doctor tells you to, it may be dangerous to stop the tablets without medical advice. Your doctor should continue to treat you with Citalopram tablets until you have been free of symptoms for 4-6 months.

If you take more than you should

If you (or someone else) swallow a lot of tablets at the same time, or you think a child may have swallowed any, contact
your nearest hospital casualty department or tell your doctor immediately. Signs of an overdose include feeling sleepy, feeling or being sick, seizures, a blue discolouration around your lips, nails or cheeks, sweating, coma, accelerated pulse rate, hyperventilation (accelerated and increased breathing) and changes in the activity of the heart muscle (ECG alterations).

If you forget to take the tablets

Do not take a double dose to make up for a forgotten dose. If you forget to take a dose take it as soon as you remember it and then take the next dose at the right time.

If you stop taking the tablets

Talk to your doctor before you stop taking the tablets and follow their advice. Citalopram tablets should be withdrawn slowly, gradually reducing the dose over periods of 1-2 weeks. If stopped suddenly, withdrawal reactions may occur including dizziness, ‘pins and needles’, headache, feeling or being sick, sleep disturbances (including insomnia and intense dreams), feeling agitated or anxious, tremor, confusion, sweating, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances.

Possible side effects

Like all medicines, Citalopram tablets can cause side effects, although not everybody gets them.

Stop taking Citalopram tablets and contact your doctor at once if you

• experience serotonin syndrome (a serious condition that can cause fever, confusion, abnormal movements, shivering, muscle spasms, agitation and progress to coma or loss of consciousness) restlessness, sweating, hallucinations, exaggeration of reflexes, muscle cramps, rapid heart rate.


• severe hypersensitivity reactions which may result in a strong decrease in blood pressure, paleness, anxiety, a fast weak
  pulse rate, a clammy skin, decreased consciousness, tremor, breathing difficulties and sudden swelling of the lips, eyes or tongue.

Tell your doctor if you notice any of the following side effects or notice any other effects not listed:

• 
  Very common (occurs in more than 1 in 10 users): feeling sick, dry mouth, sleepiness, shakiness of the arms and legs, diarrhoea, headache, dizziness, visual disturbances, difficulty in sleeping, constipation, weakness, increased sweating, palpitations, agitation, nervousness.


• 
  Common (occurs in less than 1 in 10 users): tingling (pins and needles), anxiety, problems with concentration, confusion, problems sleeping, abnormal dreams, tiredness, yawning, abnormalities of vision, migraine, loss of memory, feeling faint after standing, fast heart rate, low or high blood pressure, loss of appetite, increase in appetite, loss of or increase in weight, indigestion, stomach pain, wind, vomiting, abnormalities of taste, increased salivation, runny nose, sinusitis, impotence and problems with ejaculation, reduced libido, problems in reaching orgasm (women), problems with passing water, passing water frequently, period pains, rash, itching.


• 
  Uncommon (occurs in less than 1 in 100 users): muscle pain, jerky movements, fits, ringing in the ears, false sense of wellbeing, increased desire for sex, coughing, malaise (generally feeling unwell), sensitivity to sunlight, changes in liver function, slow heart rate, fainting.


• 
  Rare (occurs in less than 1 in 1,000 users): bleeding (in the skin, bruising, stomach and from the vagina), changes in the salt balance in your body, psychomotor restlessness. The syndrome of inappropriate anti-diuretic hormone secretion (SIADH, symptoms are confusion, hallucinations, drowsinesss, fits, coma and breathing difficulties).


• 
  Very rare (occurs in less than 1 in 10,000 users): irregular heart beats/pulse rate, hallucinations (seeing things, hearing things or feelings that are not there), mania, feeling of unreality, panic attacks, production of breast milk, joint pain.


• 
  Not known: bile flow stoppage (cholestasis), thoughts of suicide and suicidal behaviour (see: ‘section 2’).

If you notice any side effects, they get worse, or if you notice any not listed, please tell your doctor or pharmacist.

How to store

Keep out of the reach and sight of children.

No special precautions for storage.

Do not use Citalopram tablets after the expiry date stated on the label/carton/ bottle. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further information

What Citalopram tablets contain

• The active substance (the ingredient that makes the tablet work) is citalopram (as hydrobromide). Each tablet contains either 10mg, 20mg or 40mg of the active ingredient.


• The other ingredients are mannitol (E421), microcrystalline cellulose (E460), colloidal silica anhydrous, magnesium stearate. The film-coat contains hypromellose (E464), macrogol, titanium dioxide (E171).

What Citalopram tablets look like and contents of the pack

Citalopram tablets are round, white film-coated tablets.

Pack size of 28.

Marketing Authorisation Holder and Manufacturer

Actavis

Barnstaple

EX32 8NS

UK

Date of revision: June 2010

Actavis

Barnstaple

EX32 8NS

UK

50416258

Compound Macrogol Oral Powder Sugar Free

1. Name Of The Medicinal Product

Compound Macrogol Oral Powder Sugar Free.

2. Qualitative And Quantitative Composition

Each sachet contains the following quantitative composition of active ingredients:

Macrogol 3350	13.125g
Sodium Chloride	350.7mg
Sodium Hydrogen Carbonate	178.5mg
Potassium Chloride	46.6mg

The content of electrolyte ions per sachet following reconstitution in 125ml of water is equivalent to:

Sodium	65mmol/l
Chloride	53mmol/l
Hydrogen Carbonate (Bicarbonate)	17mmol/l
Potassium	5.4mmol/l

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Powder for oral solution. Single-dose sachet containing a free flowing white powder.

4. Clinical Particulars

4.1 Therapeutic Indications

For the treatment of chronic constipation. Compound Macrogol Oral Powder Sugar Free is also effective in resolving faecal impaction, defined as refractory constipation with faecal loading of the rectum and/or colon.

4.2 Posology And Method Of Administration

Compound Macrogol Oral Powder Sugar Free is for oral use.

Chronic Constipation:

A course of treatment for chronic constipation with Compound Macrogol Oral Powder Sugar Free does not normally exceed 2 weeks, although this can be repeated if required. As for all laxatives, prolonged use is not usually recommended. Extended use may be necessary in the care of patients with severe chronic or resistant constipation, secondary to multiple sclerosis or Parkinson's Disease, or induced by regular constipating medication in particular opioids and antimuscarinics.

Adults, adolescents and the elderly: 1-3 sachets daily in divided doses, according to individual response. For extended use, the dose can be adjusted down to 1 or 2 sachets daily.

Children below 12 years old: Not recommended.

Faecal Impaction:

A course of treatment for faecal impaction with Compound Macrogol Oral Powder Sugar Free does not normally exceed 3 days.

Adults, adolescents and the elderly: 8 sachets daily, all of which should be consumed within a 6 hour period.

Children below 12 years old: Not recommended.

Patients with impaired cardiovascular function: For the treatment of faecal impaction the dose should be divided so that no more than 2 sachets are taken in any one hour.

Patients with renal insufficiency: No dosage change is necessary for the treatment of constipation or faecal impaction.

Administration:

Each sachet should be dissolved in 125 ml water. For use in faecal impaction, 8 sachets may be dissolved in 1 litre of water.

4.3 Contraindications

Compound Macrogol Oral Powder Sugar Free is contraindicated in intestinal obstruction or perforation caused by functional or structural disorder of the gut wall, ileus and in patients with severe inflammatory conditions of the intestinal tract (e.g. ulcerative colitis, Crohn's disease and toxic megacolon).

Hypersensitivity to the active substances or any of the excipients.

4.4 Special Warnings And Precautions For Use

The faecal impaction diagnosis should be confirmed by appropriate physical or radiological examination of the rectum and abdomen.

Mild adverse drug reactions are possible as indicated in Section 4.8. If patients develop any symptoms indicating shifts of fluids/electrolytes (e.g. oedema, shortness of breath, increasing fatigue, dehydration, cardiac failure) Compound Macrogol Oral Powder Sugar Free should be stopped immediately and electrolytes measured and any abnormality should be treated appropriately.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

There are no known interactions of Compound Macrogol Oral Powder Sugar Free with other medicinal products. However, macrogol 3350 raises the solubility of medicinal products that are soluble in alcohol and mainly insoluble in water. It is a theoretical possibility that absorption of these drugs could be reduced transiently. Therefore, other medicines should not be taken orally for one hour before and for one hour after taking Compound Macrogol Oral Powder Sugar Free.

4.6 Pregnancy And Lactation

There is no experience with the use of Compound Macrogol Oral Powder Sugar Free during pregnancy and lactation and it should not be used during pregnancy and lactation unless clearly necessary.

4.7 Effects On Ability To Drive And Use Machines

Compound Macrogol Oral Powder Sugar Free has no influence on the ability to drive and use machines.

4.8 Undesirable Effects

Immune System Disorders:

Allergic reactions are possible.

Gastro-intestinal Disorders:

Potential gastro-intestinal effects that may occur include abdominal distension and pain, borborygmi and nausea. Mild diarrhoea may also occur, but normally resolves after dose reduction.

4.9 Overdose

Severe distension or pain can be treated using nasogastric aspiration. Vomiting or diarrhoea may induce extensive fluid loss, possibly leading to electrolyte disturbances that should be treated appropriately.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Osmotically acting laxatives.

ATC code: A06A D65

Macrogol 3350 induces a laxative effect through its osmotic action in the gut. This product also contains electrolytes to ensure that there is no overall gain or loss of water, potassium or sodium.

Clinical studies using the listed active substances for the treatment of chronic constipation have shown that the dose required to produce normally formed stools tends to decrease over time. For most patients, the maintenance dose will be one to two sachets per day (adjusted according to individual response).

Comparative studies in faecal impaction using active controls (e.g. enemas) have not been performed. However, results from a non-comparative study have shown that, from a population of 27 adult patients, the listed combination of active substances cleared faecal impaction in 12/27 (44%) patients after one day's treatment, increasing to 23/27 (85%) following two days' treatment and 24/27 (89%) recovered at the end of three days.

5.2 Pharmacokinetic Properties

Macrogol 3350 is virtually unabsorbed from the gastro-intestinal tract and is excreted, unaltered, in faeces. Any macrogol 3350 that enters the systemic circulation is excreted in urine.

5.3 Preclinical Safety Data

Preclinical studies provide evidence that macrogol 3350 has no significant systemic toxicity potential, although no tests of its effects on reproduction or genotoxicity have been conducted.

There are no long-term animal toxicity or carcinogenicity studies involving macrogol 3350, although there are toxicity studies using high levels of orally administered high-molecular weight macrogols that provide evidence of safety at the recommended therapeutic dose.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Acesulfame Potassium (E950)

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

Sachet: Two years.

Reconstituted solution: Six hours.

6.4 Special Precautions For Storage

Sachet: Store below 25°C.

Reconstituted solution: Store covered in a refrigerator (2°C to 8°C).

6.5 Nature And Contents Of Container

The sachet is composed of paper, low density polyethylene and aluminium.

Sachets are packed in cartons of 2, 8, 10, 20, 30, 50 and 100.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Galen Limited

Seagoe Industrial Estate

Craigavon

BT63 5UA

UK

8. Marketing Authorisation Number(S)

PL 21590/0088.

9. Date Of First Authorisation/Renewal Of The Authorisation

01 May 2008

10. Date Of Revision Of The Text

09 January 2009

Citalopram 20 mg Tablets

1. Name Of The Medicinal Product

Citalopram 20 mg Tablets

2. Qualitative And Quantitative Composition

Each coated tablet contains citalopram hydrobromide equivalent to 20 mg citalopram.

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Film-Coated Tablet

White to off white, round, biconvex, film coated tablets debossed with 'DU' on one side and lip shaped breakline on the other side.

4. Clinical Particulars

4.1 Therapeutic Indications

Citalopram Tablets are indicated for the treatment of depressive illness in the initial phase and as maintenance against potential relapse/recurrence.

Citalopram Tablets are also indicated in the treatment of panic disorder with or without agoraphobia.

4.2 Posology And Method Of Administration

Posology

MAJOR DEPRESSIVE EPISODES

The recommended dose is 20 mg daily. In general, improvement in patients starts after one week, but may only become evident from the second week of therapy.

As with all antidepressant medicinal products, dosage should be reviewed and adjusted, if necessary, within 3 to 4 weeks of initiation of therapy and thereafter as judged clinically appropriate. Although there may be an increased potential for undesirable effects at higher doses, if after some weeks on the recommended dose insufficient response is seen, some patients may benefit from having their dose increased up to a maximum of 60 mg a day in 20 mg steps according to the patient's response (see section 5.1). Dosage adjustments should be made carefully on an individual patient basis, to maintain the patient at the lowest effective dose.

Patients with depression should be treated for a sufficient period of at least 6 months to ensure that they are free from symptoms.

PANIC DISORDER

Patients should be started on 10 mg/day and the dose gradually increased in 10 mg steps according to the patient's response up to the recommended dose. The recommended dose is 20-30 mg daily. A low initial starting dose is recommended to minimise the potential worsening of panic symptoms, which is generally recognised to occur early in the treatment of this disorder. Although there may be an increased potential for undesirable effects at higher doses, if after some weeks on the recommended dose insufficient response is seen some patients may benefit from having their dose increased gradually up to a maximum of 60 mg/day (see section 5.1). Dosage adjustments should be made carefully on an individual patient basis, to maintain the patients at the lowest effective dose.

Patients with panic disorder should be treated for a sufficient period to ensure that they are free from symptoms. This period may be several months or even longer.

Elderly patients (> 65 years of age)

The recommended daily dose is 20 mg. Dependent on individual patient response this may be increased to a maximum of 40 mg daily.

Children and adolescents (< 18 years of age)

Citalopram should not be used in the treatment of children and adolescents under the age of 18 years (see section 4.4).

Reduced hepatic function

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

Reduced renal function

Dosage adjustment is not necessary in cases of mild or moderate renal impairment. No information is available in cases of severe renal impairment (creatinine clearance <20 mL / min).

Withdrawal symptoms seen on discontinuation of citalopram

Abrupt discontinuation should be avoided. When stopping treatment with citalopram the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions (see section 4.4 Special Warnings and Precautions for Use and section 4.8 Undesirable Effects). 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.

Method of administration

Citalopram tablets are administered as a single daily dose. Citalopram tablets can be taken at any time of the day without regard to food intake.

4.3 Contraindications

Hypersensitivity to active substance or to any of the excipients (see section 6.1).

Monoamine Oxidase Inhibitors: Some cases presented with features resembling serotonin syndrome.

Citalopram should not be given to patients receiving Monoamine Oxidase Inhibitors (MAOIs) including selegiline in daily doses exceeding 10 mg/day. .

Citalopram should not be given for fourteen days after discontinuation of an irreversible MAOI or for the time specified after discontinuation of a reversible MAOI (RIMA) as stated in the prescribing text of the RIMA.MAOIs should not be introduced for seven days after discontinuation of citalopram (see section 4.5). Citalopram is contraindicated in the combination with linezolid unless there are facilities for close observation and monitoring of blood pressure (see section 4.5).

Citalopram should not be used concomitantly with pimozide (see also section 4.5).

4.4 Special Warnings And Precautions For Use

Use in children and adolescents under 18 years of age

Citalopram should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken; the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.

Elderly patients

Caution should be used in the treatment of elderly patients (see section 4.2).

Reduced kidney and liver function

Caution should be used in the treatment of patients with reduced kidney and liver function (see section 4.2).

Paradoxical anxiety

Some patients with panic disorder may experience intensified anxiety symptoms at the start of treatment with antidepressants. This paradoxical reaction usually subsides within the first two weeks of starting treatment. A low starting dose is advised to reduce the likelihood of a paradoxical anxiogenic effect (see section 4.2).

Hyponatraemia

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

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which Citalopram is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Akathisia/psychomotor restlessness

The use of SSRIs/SNRIs 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.

Mania

In patients with manic-depressive illness a change towards the manic phase may occur. Should the patient enter a manic phase citalopram should be discontinued.

Seizures

Seizures are a potential risk with antidepressant drugs. The drug should be discontinued in any patient who develops seizures. Citalopram should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Citalopram should be discontinued if there is an increase in seizure frequency.

Diabetes

In patients with diabetes, treatment with an SSRI may alter glycaemic control. Insulin and or oral hypoglycaemic dosage may need to be adjusted.

Serotonin syndrome

In rare cases, serotonin syndrome has been reported in patients using SSRIs. A combination of symptoms, possibly including agitation, confusion, tremor, myoclonus and hyperthermia, may indicate the development of this condition (see section 4.5). Treatment with citalopram should be discontinued immediately and symptomatic treatment initiated.

Serotonergic medicines

Citalopram should not be used concomitantly with medicinal products with serotonergic effects such as sumatriptan or other triptans, tramadol, oxitriptan, and tryptophan.

ECT

There is little clinical experience of concurrent administration of citalopram and ECT, therefore caution is advisable.

Haemorrhage

There have been reports of prolonged bleeding time and/or bleeding abnormalities such as ecchymoses, gynaecological haemorrhages, gastrointestinal bleedings, and other cutaneous or mucous bleedings with SSRIs (see section 4.8). Caution is advised in patients taking SSRIs, particularly with concomitant use of active substances known to affect platelet function or other active substances that can increase the risk of haemorrhage, as well as in patients with a history of bleeding disorders (see section 4.5).

Reversible, selective MAO-A inhibitors

The combination of citalopram with MAO-A inhibitors is generally not recommended due to the risk of onset of a serotonin syndrome (see section 4.5).

For information on concomitant treatment with non-selective, irreversible MAO-inhibitors see section 4.5.

St. John's Wort

Undesirable effects may be more common during concomitant use of citalopram and herbal preparations containing St John's wort (Hypericum perforatum). Therefore citalopram and St John's wort preparations should not be taken concomitantly (see section 4.5).

Glaucoma

As with other SSRIs, citalopram can cause mydriasis and should be used with caution in patients with narrow angle glaucoma or history of glaucoma.

Withdrawal symptoms seen on discontinuation of SSRI treatment

Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt (see section 4.8 Undesirable effects). In a recurrence prevention clinical trial with citalopram, adverse events after discontinuation of active treatment were seen in 40% patients versus 20% in patients continuing citalopram.

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 and headache 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 "Withdrawal symptoms seen on discontinuation of citalopram", Section 4.2 Posology and Method of Administration)

Psychosis

Treatment of psychotic patients with depressive episodes may increase psychotic symptoms.

QT prolongation

Elevated levels of a side metabolite (didemethylcitalopram) can theoretically prolong the QT interval in patients predisposed, patients with congenitally prolonged QT syndrome or in patients with hypokalaemia/hypomagnesiaemia. ECG monitoring may be advisable in case of overdose or conditions of altered metabolism with increased peak levels, e.g. liver impairment.

Excipients

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

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Pharmacodynamic Interactions

At the pharmacodynamic level cases of serotonin syndrome with citalopram and moclobemide and buspirone have been reported.

Contraindicated combinations

Monoamine Oxidase Inhibitors (MAOIs):

The simultaneous use of citalopram and MAO-inhibitors can result in severe undesirable effects, including the serotonin syndrome (see section 4.3).

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 and SSRI and have been started on a MAOI.

Some cases presented with features resembling serotonin syndrome. Symptoms of an active substance interaction with a MAOI include: agitation, tremor, myoclonus, and hyperthermia.

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.

Combinations requiring precaution for use

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.

Serotonergic medicinal products

Lithium and tryptophan

No pharmacodynamic interactions have been found in clinical studies in which citalopram has been given concomitantly with lithium. However there are have been reports of enhanced 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. Routine monitoring of lithium levels need not be adjusted.

Co-administration with serotonergic drugs (e.g. tramadol, sumatriptan) may lead to enhancement of 5-HT associated effects.

Until further information is available, the simultaneous use of citalopram and 5-HT agonists, such as sumatriptan and other triptans, is not recommended (see section 4.4).

St John's wort

Dynamic interactions between citalopram and herbal remedy St John's wort (Hypericum perforatum) can occur, resulting in an increase in undesirable effects. occur, resulting in an increase in undesirable effects (see section 4.4). Pharmacokinetic interactions have not been investigated.

Haemorrhage

Caution is warranted for patients who are being treated simultaneously with anticoagulants, medicinal products that affect the platelet function, such as non steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, dipyridamol, and ticlopidine or other medicines (e.g. atypical antipsychotics, phenothiazines, tricyclic depressants) that can increase the risk of haermorrhage (see section 4.4).

ECT (electroconvusive therapy)

There are no clinical studies establishing the risks or benefits of the combined use of electroconvulsive therapy (ECT) and citalopram (see section 4.4).

Alcohol

No pharmacodynamic or pharmacokinetic interactions have been demonstrated between citalopram and alcohol. However, the combination of citalopram and alcohol is not advisable.

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.

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]), mefloquin, bupropion and tramadol).

Desipramine, imipramine

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. When desipramine is combined with citalopram, an increase of the desipramine plasma concentration has been observed. A reduction of the desipramine dose may be needed.

Neuroleptics

Experience with citalopram has not revealed any clinically relevant interactions with neuroleptics. However, as with other SSRIs, the possibility of a pharmacodynamic interaction cannot be excluded.

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.

Pharmacokinetic interactions

Biotransformation of citalopram to demethylcitalopram is mediated by CYP2C19 (approx. 38%), CYP3A4(approx. 31%) and CYP2D6 (approx. 31%) isozymes of the cytochrome P450 system. The fact that citalopram is metabolised by more than one CYP means that inhibition of its biotransformation is less likely as inhibition of one enzyme may be compensated by another. Therefore co-administration of citalopram with other medicinal products in clinical practice has very low likelihood of producing pharmacokinetic medicinal product interactions.

Food

The absorption and other pharmacokinetic properties of citalopram have not been reported to be affected by food.

Influence of other medicinal products on the pharmacokinetics of citalopram

Co-administration with ketoconazole (potent CYP3A4 inhibitor) did not change the pharmacokinetics of citalopram.

A pharmacokinetic interaction study of lithium and citalopram did not reveal any pharmacokinetic interactions (see also above).

Cimetidine

Cimetidine, a known enzyme-inhibitor, caused a slight rise in the average steady-state citalopram levels. Caution is therefore recommended when administering high doses of citalopram in combination with high doses of cimetidine. Co-administration of escitalopram (the active enantiomer of citalopram) with omeprazole 30 mg once daily (a CYP2C19 inhibitor) resulted in moderate (approximately 50%) increase in the plasma concentrations of escitalopram. Thus, caution should be exercised when used concomitantly with CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, luvoxamine, lansoprazole, ticlopidine) or cimetidine. A reduction in the dose of citalopram may be necessary based on monitoring of undesirable effects during concomitant treatment.

Metoprolol

Escitalopram (the active enantiomer of citalopram) is an inhibitor of the enzyme CYP2D6. Caution is recommended when citalopram is co-administered with medicinal products that are mainly metabolised by this enzyme, and that have a narrow therapeutic index, e.g. flecainide, propafenone and metoprolol (when used in cardiac failure), or some CNS acting medicinal products that are mainly metabolised by CYP2D6, e.g. antidepressants such as desipramine, clomipramine and nortriptyline or antipsychotics like risperidone, thioridazine and haloperidol. Dosage adjustment may be warranted. Co-administration with metoprolol resulted in a twofold increase in the plasma levels of metoprolol, but did not statistically significant increase the effect of metoprolol on the blood pressure and cardiac rhythm.

Effects of citalopram on other medicinal products

A pharmacokinetic / pharmacodynamic interaction study with concomitant administration of citalopram and metoprolol (a CYP2D6 substrate) showed a twofold increase in metoprolol concentrations, but no statistically significant increase in the effect of metoprolol on blood pressure and heart rate in healthy volunteers.

Citalopram and demethylcitalopram are negligible inhibitors of CYP2C9, CYP2E1 and CYP3A4, and only weak inhibitors of CYP1A2, CYP2C19 and CYP2D6 as compared to other SSRIs established as significant inhibitors.

Levomepromazine, digoxin, carbamazepine

Thus no change or only very small changes of no clinical importance were observed when citalopram was given with CYP1A2 substrates (clozapine and theophylline), CYP2C9 (warfarin), CYP2C19 (imipramine and mephenytoin), CYP2D6 (sparteine, imipramine, amitriptyline, risperidone) and CYP3A4 (warfarin, carbamazepine (and its metabolite carbamazepine epoxid) and triazolam). No pharmacokinetic interaction was observed between citalopram and levomepromazine, or digoxin, (indicating that citalopram neither induce nor inhibit P-glycoprotein).

4.6 Pregnancy And Lactation

Pregnancy:

A large amount of data on pregnant women (more than 2500 exposed outcomes) indicate no malformative feto/ neonatal toxicity. Citalopram can be used during pregnancy if clinically needed, taking into account the aspects mentioned below.

Neonates should be observed if maternal use of citalopram continues into the later stages of pregnancy, particularly in the third trimester. Abrupt discontinuation should be avoided during pregnancy.

The following symptoms may occur in the neonates after maternal SSRI/SNRI use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These symptoms could be due to either serotonergic effects or discontinuation symptoms. In a majority of instances the complications begin immediately or soon (<24 hours) after delivery.

Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases per 1000 pregnancies. In the general population 1 to 2 cases of PPHN per 1000 pregnancies occur.

Lactation:

Citalopram is excreted into breast milk. It is estimated that the suckling infant will receive about 5% of the weight related maternal daily dose (in mg/kg). No or only minor events have been observed in the infants. However, the existing information is insufficient for assessment of the risk to the child.

Caution is recommended. If treatment with citalopram is considered necessary, discontinuation of breast feeding should be considered

4.7 Effects On Ability To Drive And Use Machines

Citalopram has minor or moderate influence on the ability to drive and use machines.

Patients who are prescribed psychotropic medication may be expected to have some impairment of general attention and concentration due to the illness itself and psychoactive medicinal products can reduce the ability to make judgements and to react to emergencies. Patients should be informed of these effects and be warned that their ability to drive a car or operate machinery could be affected.

4.8 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 adverse reactions are presented at the MedDRA Preferred Term Level.

For the following reactions a dose-response was discovered: Sweating increased, dry mouth, insomnia, somnolence, diarrhoea, nausea and fatigue. The table shows the percentage of adverse drug reactions associated with SSRIs and/or citalopram seen in either

	Very Common	Common	Uncommon	Rare	Not Known
Blood and lymphatic disorders					Thrombocytopenia
Immune system disorders					Hypersensitivity, Anaphylactic reaction
Endocrine disorders					Inappropriate ADH secretion
Metabolism and nutrition disorders		Appetite decreased, weight decreased	Increased appetite, weight increased	Hyponatraemia,	Hypokalaemia
Psychiatric disorders		Agitation, libido decreased, anxiety, nervousness, confusional state, abnormal orgasm (female), abnormal dreams	Aggression, depersonalization, hallucination, mania		Panic attack, bruxism, restlessness, suicide ideation and suicidal behaviour2
Nervous system disorders	Somnolence, insomnia	Tremor , paraesthesia, dizziness, disturbance in attention	Syncope	Convulsion grand mal, dyskinesia , taste disturbance	Convulsions, serotonin syndrome, extrapyramidal disorder , akathisia, movement disorder
Eye disorders			Mydriasis (which may lead to acute narrow angle glaucoma), see section 4.4 Special warnings and precautions for use)		Visual disturbance
Ear and labyrinth disorders		Tinnitus
Cardiac disorders			Bradycardia, tachycardia		QT-prolongation1
Vascular disorders				Haemorrhage	Orthostatic hypotension
Respiratory thoracic and mediastinal disorders		Yawning			Epistaxis
Gastrointestinal disorders	Dry mouth, Nausea	Diarrhoea, vomiting , Constipation			Gastrointestinal haemorrhage (including rectal haemorrhage)
Hepatobiliary disorders				Hepatitis	Liver function test abnormal
Skin and subcutaneous tissue disorders	Sweating increased	Pruritus	Urticaria, alopecia, rash , purpura, photosensitivity reaction		Ecchymosis, angioedemas
Musculoskeletal, connective tissue and bone disorders		Myalgia, arthralgia
Renal and urinary disorders			Urinary retention
Reproductive system and breast disorders		Impotence, ejaculation disorder, ejaculation failure	Female: Menorrhagia		Female: Metrorrhagia Male: Priapism, galactorrhoea
General disorders and administration site conditions		Fatigue,	Oedema	pyrexia

Number of patients: Citalopram / placebo = 1346 / 545

¹ Cases of QT-prolongation have been reported during the post-marketing period, predominantly in patients with pre-existing cardiac disease

² Cases of suicidal ideation and suicidal behaviours have been reported during citalopram therapy or early after treatment discontinuation (see section 4.4).

The following adverse events have also been reported in clinical trials:

Very common: Headache, asthenia, sleep disorder.

Common: Migraine, palpitation, taste perversion, impaired concentration, amnesia, anorexia, apathy, dyspepsia, abdominal pain, flatulence, increased salivations, rhinitis.

Rare: Increased libido, coughing, and malaise.

Class Effects

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

Withdrawal symptoms seen on discontinuation of SSRI treatment.

Discontinuation of citalopram (particularly when abrupt) commonly leads to withdrawal symptoms. 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 events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when citalopram treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see section 4.2 Posology and Method of Administration and section 4.4 Special Warnings and Precaution for use).

4.9 Overdose

Toxicity

Comprehensive clinical data on citalopram overdose are limited and many cases involve concomitant overdoses of other drugs/alcohol. Fatal cases of citalopram overdose have been reported with citalopram alone; however, the majority of fatal cases have involved overdose with concomitant medications.

Fatal dose is not known. Patients have survived ingestion of more than 2 g citalopram.

The effects may be potentiated by alcohol taken at the same time.

Potential interaction with TCAs, MAOIs and other SSRIs.

Symptoms of overdose

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, torsade de pointes, stupor, sweating, cyanosis, hyperventilation, and atrial and ventricular arrythmia.

ECG changes including nodal rhythm, prolonged QT intervals and wide QRS complexes may occur. Fatalities have been reported.

Prolonged bradycardia with severe hypotension and syncope has also been reported.

Rarely, features of the "serotonin syndrome" may occur in severe poisoning. This includes alteration of mental status, neuromuscular hyperactivity and autonomic instability. There may be hyperpyrexia and elevation of serum creatine kinase. Rhabdomyolysis is rare.

Treatment

There is no known specific antidote to citalopram.

Treatment should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of ECG and vital signs until stable.

Consider oral activated charcoal in adults and children who have ingested more than 5 mg/kg body weight within 1 hour. Activated charcoal given ½ hour after ingestion of citalopram has been shown to reduce absorption by 50%.

Osmotically working laxative (such as sodium sulphate) and stomach evacuation should be considered.

If consciousness is impaired the patient should be intubated.

Control convulsions with intravenous diazepam if they are frequent or prolonged.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group : Selective Serotonergic Reuptake Inhibitors

ATC Code: N 06A B 04

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.

Citalopram is the most Selective Serotonin Reuptake Inhibitor (SSRI) yet described, with no, or minimal, effect on noradrenaline (NA), dopamine (DA) and gamma aminobutyric acid (GABA) uptake.

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 _1A, 5-HT₂, DA D₁ and D₂ receptors, α₁-, α₂-, 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. This absence of effects on receptors could explain why citalopram produces fewer of the traditional side effects such as dry mouth, bladder and gut disturbance, blurred vision, sedation, cardiotoxicity and orthostatic hypotension.

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.

Although citalopram does not bind to opioid receptors it potentiates the anti-nociceptive effect of commonly used opioid analgesics. There was potentiation of d-amphetamine-induced hyperactivity following administration of citalopram.

The main metabolites of citalopram are all SSRIs although their potency and selectivity ratios are lower than those of citalopram. However, the selectivity ratios of the metabolites are 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 (intellectual function) and psychomotor performance and has no or minimal sedative properties, either alone or in combination with alcohol.

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.

Dose response

In the fixed dose studies there is a flat dose response curve, providing no suggestion of advantage in terms of efficacy for using higher than the recommended doses. However, it is clinical experience that up-titrating the dose might be beneficial for some patients.

5.2 Pharmacokinetic Properties

Absorption

Absorption of citalopram is almost complete and independent of food intake (T_max average/mean 3.8 hours). Oral bioavailability is about 80%.