INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
DRL CITALOPRAM 20 (film-coated tablet)
DRL CITALOPRAM 40 (film-coated tablet)

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

DRL CITALOPRAM 20 (film-coated tablet)
DRL CITALOPRAM 40 (film-coated tablet)

COMPOSITION
DRL CITALOPRAM 20: Each film-coated tablet contains citalopram hydrobromide equivalent to citalopram 20 mg
DRL CITALOPRAM 40: Each film-coated tablet contains citalopram hydrobromide equivalent to citalopram 40 mg
Sugar free

PHARMACOLOGICAL CLASSIFICATION
A 1.2 Psychoanaleptics (antidepressants)

PHARMACOLOGICAL ACTION
Citalopram is a bicyclic phthalane derivative with antidepressant effect. Its effect is linked to the selective inhibition of specific serotonin (5-HT) reuptake.Citalopram, primarily through its (S)-enantiomer, blocks 5-HT reuptake, leading to potentiation of serotonergic activity in the central nervous system (CNS). Neither citalopram nor its metabolites have an effect on noradrenaline, dopamine and GABA reuptake. Citalopram has little or no antidopaminergic, antiadrenergic, antiserotonergic, antihistaminergic or anticholinergic properties.
Pharmacokinetics
Oral bioavailability is about 80%with maximum plasma levels being reached in 4 hours (range 1 - 6 hours). Volume of distribution is about 14 L/kg (range 9 - 17 L/kg). Time to reach steady state concentration is 1 - 2 weeks. Protein binding is about 80%. Elimination half-life is 36 hours (range 28 - 42 hours). Citalopram undergoes hepatic metabolism primarily involving the cytochrome P450 (CYP3A4) and 2C19 (CYP2C19) isoenzymes and to a small extent cytochrome P450 2D6 (CYP2D6) isoenzymes. The metabolites inhibit the reuptake of serotonin but are less potent than the parent molecule. Citalopram is mainly excreted via the liver with the remainder via the kidneys (approximately 20% of which 12% is unchanged medicine). Longer half-lives and decreased clearance due to a reduced rate of metabolism have been demonstrated in the elderly.

INDICATIONS
DRL CITALOPRAM is indicated for the treatment of:

•	Depression and prevention of relapse
•	Panic disorder with or without agoraphobia
•	Obsessive-compulsive disorder

CONTRAINDICATIONS
Hypersensitivity to citalopram or any of the ingredients in the formulation.
Concurrent use with a monoamine oxidase inhibitor (MAOI). At least 14 days should elapse between discontinuing the MAOI and initiating therapy with DRL CITALOPRAM. MAOIs should not be introduced for 7 days after discontinuation of DRL CITALOPRAM (see INTERACTIONS).
Severe renal impairment (creatinine clearance less than 20 mL/min).
Safety and efficacy in pregnancy and lactation has not been established.
Children under the age of 18 years (see WARNINGS and SIDE-EFFECTS AND SPECIAL PRECAUTIONS).

WARNINGS
Use in the elderly- The half-life is increased and clearance decreased due to a reduced rate of metabolism. A lower dose is recommended in the elderly.
Use in impaired hepatic function- Clearance of DRL CITALOPRAM is reduced. Cautious dosage titration and a lower maximum dose are recommended.
Use in renal impairment- Elimination is decreased. If creatinine clearance is less than 20 mL/min, DRL CITALOPRAM should not be used (see CONTRAINDICATIONS).
Other serotonergic medicines or medicines with serotonergic activity - Increased risk of developing serotonin syndrome, a rare but potentially fatal hyperserotonergic state (see INTERACTIONS).
Use in seizures or history thereof - There is an increased risk of seizures. DRL CITALOPRAM should be used with caution in patients with controlled epilepsy and avoided in patients who are poorly controlled epileptics.Care is advised in patients receiving electroconvulsive therapy.
Use in mania or history of mania- The condition may be re-activated.DRL CITALOPRAM should be discontinued if the patient enters the manic phase.
Use in pre-existing slow heart rates - DRL CITALOPRAMmay cause a reduction in heart rate. Caution is advised in patients with pre-existing slow heart rates.
Diabetes mellitus - Rare occurrences of hypoglycaemia have been reported.
Use with other medicines- DRL CITALOPRAM should not be used with monoamine oxidase inhibitors (MAOIs), imipramine, other serotonergic medicines, moclobemide, alcohol, warfarin, and cimetidine (see INTERACTIONS).
Patients with major depressive disorder may experience worsening of their depression and/or the emergence of suicidal ideation and behaviour, whether or not they are taking antidepressant medicines. This risk may persist until significant remission occurs. A causal role, however, for antidepressant medicines in inducing such behaviour has not been established. Patients being treated with DRL CITALOPRAMshould, nevertheless, be observed closely for clinical worsening and suicidality, especially at the beginning of a course of therapy or at any time of dose changes, either increases or decreases.
Because of the possibility of co-morbidity between major depressive disorder and other psychiatric and non-psychiatric disorders, the same precautions observed when treating patients with major depressive disorder should be observed when treating patients with other psychiatric and non-psychiatric disorders.
The following symptoms have been reported in patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and non-psychiatric: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, consideration should be given to changing the therapeutic regimen, including possibly discontinuing DRL CITALOPRAMin patients for whom such symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
If the decision is made to discontinue treatment, DRL CITALOPRAMshould be tapered (see PRECAUTIONSand DOSAGE AND DIRECTIONS FOR USE).
If therapy with DRL CITALOPRAM is to be discontinued it is recommended that the dose is decreased gradually in order to prevent the possibility of a withdrawal syndrome.
Safety and efficacy in children under 18 years of age have not been established (see CONTRAINDICATIONS and SIDE-EFFECTS AND SPECIAL PRECAUTIONS).

INTERACTIONS
Monoamine oxidase inhibitors (MAOIs) - Concurrent use is contraindicated. Serious and potentially fatal reactions have occurred such as hyperthermia, rigidity, myoclonus, autonomic instability with rapid fluctuation of vital signs and mental status changes including extreme agitation progressing to delirium and coma(see CONTRAINDICATIONS).
Imipramine - An increase in the concentration of desimipramine (the active metabolite of imipramine) may occur. It appears that DRL CITALOPRAM does not cause a marked increase in plasma levels of some tricyclic antidepressants.
Other serotonergic medicines or medicines with serotonergic activity - Increased risk of developing the serotonin syndrome, a rare but potentially fatal hyperserotonergic state.
Moclobemide - Serotonin syndrome has developed after taking overdoses of moclobemide and DRL CITALOPRAM.
Alcohol - The effects of alcohol may be increased.
Warfarin - The anticoagulant activity of warfarin may be increased.
Cimetidine - The AUC and the maximum plasma concentration of DRL CITALOPRAM are increased when DRL CITALOPRAM is administered concurrently with cimetidine.

PREGNANCY AND LACTATION
Safety and efficacy in pregnancy and lactation has not been established.DRL CITALOPRAM is excreted into breast milk. Pregnant and breastfeeding mothers should not be treated with DRL CITALOPRAM (see CONTRAINDICATIONS).

DOSAGE AND DIRECTIONS FOR USE
If therapy with DRL CITALOPRAM is to be discontinued, it is recommended that the dose is decreased gradually in order to prevent the possibility of a withdrawal syndrome.
Adults
Depression: 20 mg per day as a single dose. Dosage may be increased by 20 mg per day at intervals of at least one week to a maximum of 60 mg depending on the patient’s response.
PanicDisorder: 10 mg per day as a single dose for the first week then increasing to 20 mg per day. The dose may be increased thereafter as required to a maximum of 60 mg per day depending on the patient’s response.
Obsessive-Compulsive Disorder: Initially 20 mg per day as a single dose. This dose can be increased by 20 mg increments to a maximum of 60 mg per day depending on the patient’s response.
Special populations
Elderly: 20 mg per day as a single dose. Depending on the patient’s response the dose can be increased to a maximum of 30 mg per day.
Reduced hepatic function: Dose should be halved.
Reduced renal function: Dose adjustment is not necessary in cases of mild or moderate renal impairment.
Duration of treatment: The onset of action is seen within 2 to 4 weeks. Treatment should be continued for an appropriate length of time (up to six months) after recovery in order to prevent relapse. The medicine should be gradually withdrawn during a couple of weeks when stopping therapy (see SIDE-EFFECTS AND SPECIAL PRECAUTIONS).
DRL CITALOPRAMmay be taken with or without food in the morning or evening.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Very common (> 1/10), Common (> 1/100 and <1/10), Uncommon (>1/1 000 and <1/100), Rare (> 1/10 000 and <1/1 000), Very Rare (< 1/10 000)
Adverse events usually decrease in intensity and frequency as the depressive state improves.
Clinical evidence shows that citalopram is not associated with tachycardia or postural hypotension. A decrease in pulse rate has been reported.
General disorders
Common: Sweating, asthenia/fatigue, weight loss/weight gain
Uncommon: Malaise, yawning
Circulation disorders
Common: Palpitation
Uncommon: Decrease in pulse rate
Central nervous system disorders
Common: Headache, sleep disturbances, somnolence, paraesthesia, restlessness, tremor, dizziness, sweating
Uncommon: Agitation, confusion, impaired concentration, decreased libido, ejaculation disorder, mania
Very rare: Convulsions, serotonin syndrome, neuroleptic malignant syndrome
Gastrointestinal disorders
Common: Nausea, constipation, diarrhoea, dyspepsia, dry mouth
Uncommon: Salivation
Urogenital disorders
Common: Micturition disorder
Eye disorders
Common: Accommodation disturbances
Uncommon: Mydriasis
Skin disorders
Uncommon: Rash
Respiratory system disorders
Uncommon: Nose congestion
Hepatic disorders
Very rare: Hepatitis
Special precautions
Patients should be monitored during early therapy until improvement in depression is observed because suicide is an inherent risk in depressed patients.
DRL CITALOPRAM may impair performance of skilled tasks. If affected these patients should not operate machinery or drive.
Serotonin syndrome is more likely to occur after an increase in dose.
Serotonin syndrome is not a spontaneous drug reaction; it is a consequence of excess serotonergic activity at central nervous system (CNS) and peripheral serotonin receptors. This excess serotonin activity produces a specific spectrum of clinical findings which may range from barely perceptible to fatal.
Avoid alcohol (see INTERACTIONS).
Safety and efficacy in children under 18 years of age have not been established. In clinical trials in Major Depressive Disorder, there were increased reports of hostility and suicide –related adverse events such as suicidal ideation and self-harm.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
See SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Symptoms of overdose
Tiredness, weakness, sedation, dizziness, tremor, nausea, somnolence and sinus tachycardia.
Treatmentof overdose
Treatment is symptomatic and supportive.
There is no specific antidote to DRL CITALOPRAM.
The stomach should be emptied as soon as possible by emesis or gastric lavage. Monitoring of cardiac and vital signs is necessary and medical surveillance is advisable for about 24 hours.

IDENTIFICATION

DRL CITALOPRAM 20:	Pink, round biconvex film-coated tablets embossed ‘RDY’‘343’on one side and scored on the other side
DRL CITALOPRAM 40:	White, round biconvex film-coated tablets embossed ‘RDY’‘344’on one side and scored on the other side

PRESENTATION

DRL CITALOPRAM 20:	30 film-coated tablets in white HDPE containers
DRL CITALOPRAM 40:	30 film-coated tablets in white HDPE containers

STORAGE INSTRUCTIONS
Store below 25ºC.
Keep bottles well-closed. Keep tablets in the original container.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS

DRL CITALOPRAM 20:	41/1.2/0458
DRL CITALOPRAM 40:	41/1.2/0459

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
Dr Reddy’s Laboratories (Pty) Limited
381 Rossouw Street
Murrayfield
Pretoria
0184

DATE OF PUBLICATION OF PACKAGE INSERT
April 2009

New addition to this site: March 2010
Source: Pharmaceutical Industry
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