INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo RAN-CITALOPRAM Tablets

SCHEDULING STATUS:
Schedule 5

PROPRIETARY NAME
(and dosage form):

RAN-CITALOPRAM Tablets

Ran-Citalopram 10 Tablets
Ran-Citalopram 20 Tablets
Ran-Citalopram 40 Tablets

COMPOSITION
Sugar free.

Ran-Citalopram 10 Tablets
Each tablet contains citalopram hydrobromide equivalent to
citalopram 10 mg.
Ran-Citalopram 20 Tablets
Each tablet contains citalopram hydrobromide equivalent to citalopram 20 mg.
Ran-Citalopram 40 Tablets
Each tablet contains citalopram hydrobromide equivalent to citalopram 40 mg.

PHARMACOLOGICAL CLASSIFICATION
A 1.2 Psychoanaleptics (antidepressants)

PHARMACOLOGICAL ACTION
Citalopram is a bicyclic phthallane 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 also has little or no antidopaminergic, antiadrenergic, antiserotonergic, anthistaminergic or anticholinergic properties.
Pharmacokinetics
Oral bioavailability is about 80% with maximum plasma levels being reached in 4 hours (range 1 to 6 hours). Volume of distribution is about 14 L/kg (range 9 to 17 L/kg). Time to reach steady state concentration is 1 to 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 excreted mainly 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
Ran-Citalopram Tablets
are indicated for the treatment of:
Depression and prevention of relapse
Panic disorders with or without agoraphobia
Obsessive-compulsive disorder (OCD)

CONTRA-INDICATIONS
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 Ran-Citalopram Tablets. MAOI’s should not be introduced for 7 days after discontinuation of Ran-Citalopram Tablets. (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
Ran-Citalopram Tablets
should be used with caution in:
Elderly patients –Longer half-life and decreased clearance due to a reduced rate of metabolism. A lower dose is recommended in the elderly.
Hepatic impairment –Clearance of Ran-Citalopram Tablets is reduced. Cautious dosage titration and a lower maximum dose are recommended.
Renal impairment –Elimination is decreased. If creatinine clearance is less than 20 mL/min Ran-Citalopram Tablets should not be used. (See Contra-indications)
Seizures or history thereof –There is an increased risk of seizures. Ran-Citalopram Tablets 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.
Mania or history of mania –Condition may be re-activated. Ran-Citalopram Tablets should be discontinued if the patient enters the manic phase.
Ran-Citalopram Tablets may cause a reduction in heart rate. Caution is advised in patients with a pre-existing slow heart rate.
Diabetes mellitus –Rare occurrences of hypoglycaemia have been reported.
Ran-Citalopram Tablets should not be used with monoamine oxidase inhibitors; imipramine; other serotonergic medicines; moclobemide; alcohol; warfarin; and cimetidine (See Interactions).
Patients with major depressive disorder, both adults and children, 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 Ran-Citalopram Tablets should, 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 disorders 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 disorders 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 Ran-Citalopram Tablets in 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, Ran-Citalopram Tablets should be tapered (See Precautions and Dosage and Directions for Use).
Safety and efficacy in children under 18 years of age have not been established. (See Contra-indications and Side-effects and Special Precautions).

INTERACTIONS
Monoamine oxidase inhibitors (MAOI) - Concurrent use is contra-indicated. 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 Contra-indications)
Imipramine - An increase in the concentration of desimipramine (the active metabolite of imipramine) may occur. It appears that Ran-Citalopram Tablets do 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 Ran-Citalopram Tablets.
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 Ran-Citalopram Tablets are increased when Ran-Citalopram Tablets are administered concurrently with cimetidine.

PREGNANCY AND LACTATION
Safety and efficacy in pregnancy and lactation has not been established. Ran-Citalopram Tablets are excreted into the breast milk.

DOSAGE AND DIRECTIONS FOR USE
Depression
20 mg a day as a single dose. Dosage may be increased by 20 mg a day at intervals of at least one week to a maximum of 60 mg depending on the patient’s response.
Panic Disorder
10 mg a day as a single dose for the first week then increasing to 20 mg a day. The dose may be increased thereafter as required to a maximum of 60 mg a day depending on the patient’s response.
Obsessive-Compulsive Disorder
20 mg a day as a single dose. This dose can be increased by 20 mg increments to a maximum of 60 mg a day depending on the patient’s response.
Special populations
Elderly: 20 mg a day as a single dose. Depending on the patient’s response, the dose can be increased to a maximum of 30 mg a day.
Reduced hepatic function: Dose should be halved.
Reduced renal function: Dose adjustment is not necessary in cases of mild or moderate renal impairment.
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).
Ran-Citalopram Tablets may be taken with or without food in the morning or evening.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-effects
Endocrine/Metabolic
Frequent: Weight changes.
Central nervous system
Frequent:Sleep disturbances, parasthesia, restlessness, somnolence, headache, dizziness, fatigue.
Less frequent: Agitation, confusion, impaired concentration, malaise, mania, convulsions, serotonin syndrome, neuroleptic malignant syndrome
Ocular
Frequent:Accommodation disturbances.
Less frequent:Mydriasis.
Cardiovascular system
Frequent:Palpitations, tremor.
Less frequent:Bradycardia.
Respiratory
Less frequent: Nasal congestion.
Gastro-intestinal
Frequent: Nausea, constipation, diarrhoea, dyspepsia, dry mouth.
Less frequent:Salivation.
Liver
Less frequent: Hepatitis.
Skin
Frequent: Sweating.
Less frequent:Rash.
Musculoskeletal
Frequent:Asthenia.
Kidney/Genitourinary
Frequent: Micturition disorders.
Less frequent: Sexual dysfunction including ejaculation disorder, decreased libido, anorgasmia
Other
Less frequent: Yawning.
Hostility, suicidal ideation and self harm have been reported in children.
Discontinuation symptoms which require medical attention if they occur
Incidence unknown: Agitation, anxiety, confusion, dysphoric mood, dizziness, emotional lability, headache, hypomania, insomnia, irritability, lethargy, nervousness, parasthesiae and tremor.
Note: Discontinuation symptoms have been reported very rarely following citalopram use. This rarity is believed to be due to the intermediate half-life of citalopram which provides self-tapering and to the selectivity of citalopram for serotonin reuptake inhibition. Tapering citalopram at discontinuation generally is not required, but is advised.
Special Precautions
Patients should be monitored during early therapy until improvement in depression is observed because suicide is an inherent risk in depressed patients.
Ran-Citalopram Tablets 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.
If therapy with Ran-Citalopram Tablets is to be discontinued, it is recommended that the dose is decreased gradually in order to prevent the possibility of a withdrawal syndrome.
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.
Treatment of overdose
Treatment is symptomatic and supportive.
There is no specific antidote to Ran-Citalopram Tablets.
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
Ran-Citalopram 10 Tablets
White to off-white, circular, biconvex film coated tablets debossed with ‘10’ on one side and plain on the other side with intact coating.
Ran-Citalopram 20 Tablets
White to off-white, circular, biconvex film coated tablets debossed with ‘20’ on one side and a lip shaped break line on the other side with intact coating.
Ran-Citalopram 40 Tablets
White to off-white, circular, biconvex film coated tablets debossed with ‘40’ on one side and a lip shaped break line on the other side with intact coating.

PRESENTATION
Tablets are packaged in strips comprising clear transparent PVC film coated uniformly with PVdC on the inner side with a backing of aluminium foil (coated with heat seal lacquer).
Blister pack is of 10’s, 14’s or 28’s.

STORAGE INSTRUCTIONS
Store below 25°C, protected from moisture.
KEEP OUT OF REACH OF CHILDREN

REGISTRATION NUMBERS
Ran-Citalopram 10 Tablets:         38/1.2/0034
Ran-Citalopram 20 Tablets:         38/1.2/0039
Ran-Citalopram 40 Tablets:         38/1.2/0036

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
RANBAXY (SA) (PTY) LTD
Third Floor
Outspan House
1006 Lenchen Avenue North
Centurion

DATE OF PUBLICATION OF THE PACKAGE INSERT
July 2005

New addition to this site: September 2005
Source: Pharmaceutical Industry

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