ACT CITALOPRAM

1 Adverse Reaction Overview During the premarketing clinical development, 3652 patients received citalopram for the treatment of depression. Of these patients, 66% were females and 34% were males. The mean age of the patients was 50 years, with 70% being <60 years old (30% < 40 years old, 40% 40 to 59 years old) and 30% being ≥ 60 years old.

Adverse events observed with citalopram are in general mild and transient. They usually attenuate during the first one or two weeks of treatment. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.

The adverse reaction rates observed in the clinical trials, therefore, may not reflect the rates observed in practice and should not be PrACT CITALOPRAM (citalopram hydrobromide) Page 20 of 56 compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. 9% (163/1027) of the citalopram-treated patients discontinued treatment due to an adverse event.

7% (33/426). 1% vs. 4% vs. 4% vs. 3% vs. 3% vs. 2% vs. 1% vs. 1% vs. 2%). Incidence of Adverse Events in Placebo-Controlled Studies Table 2 enumerates the incidence of treatment emergent adverse events that occurred in 1027 depressed patients who received citalopram at doses ranging from 10 to 80 mg/day in placebo-controlled trials of up to 6 weeks in duration.

Events included are those occurring in 2% or more of patients treated with citalopram, and for which the incidence in patients treated with citalopram was greater than the incidence in placebo-treated patients. Reported adverse events were classified using the standard World Health Organization (WHO)-based dictionary terminology.

The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials.

Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.

, Psychiatric, Potential Association with Behavioral and Emotional Changes, Including Self-Harm). 4 Geriatrics). 2 CONTRAINDICATIONS • ACT CITALOPRAM is contraindicated in patients who are hypersensitive to citalopram hydrobromide or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. 2 Drug Interactions Overview, Monoamine Oxidase Inhibitors). With the co-administration of an SSRI with MAOI, there have been reports of serious, sometimes fatal reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible fluctuations of vital signs, and mental status changes, including extreme agitation progressing to delirium and coma.

Some cases presented with features resembling serotonin syndrome. Therefore, citalopram should not be used in combination with a MAOI or within 14 days of discontinuing treatment with a MAOI, (including linezolid, an antibiotic which is a PrACT CITALOPRAM (citalopram hydrobromide) Page 5 of 56 reversible non-selective MAO inhibitor and methylene blue, which is a MAOI).

Similarly, at least 14 days should elapse after discontinuing citalopram treatment before starting a MAOI. • Pimozide Citalopram should not be used in combination with the antipsychotic drug pimozide, as results from a controlled study indicate that concomitant use is associated with an increased risk of QTc prolongation compared to pimozide alone.

2 Drug Interactions Overview, Drugs That Prolong the QT Interval). 2 Drug Interactions Overview, Drugs That Prolong the QT Interval; 4 DOSAGE AND ADMINISTRATION; 5 OVERDOSAGE). 3 SERIOUS WARNINGS AND PRECAUTIONS Serious Warnings and Precautions Increased risk of self-harm, harm to others, suicidal thinking and behavior with antidepressants use.

Closely monitor all antidepressant-treated patients for clinical worsening and for emergence of agitation-type and/or suicidal thoughts and behaviors (see 7 WARNINGS AND PRECAUTIONS, Psychiatric, Potential association with behavioural and emotional changes, including self-harm).

• ACT CITALOPRAM is contraindicated in patients who are hypersensitive to citalopram hydrobromide or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

2 Drug Interactions Overview, Monoamine Oxidase Inhibitors). With the co-administration of an SSRI with MAOI, there have been reports of serious, sometimes fatal reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible fluctuations of vital signs, and mental status changes, including extreme agitation progressing to delirium and coma.

Some cases presented with features resembling serotonin syndrome. Therefore, citalopram should not be used in combination with a MAOI or within 14 days of discontinuing treatment with a MAOI, (including linezolid, an antibiotic which is a PrACT CITALOPRAM (citalopram hydrobromide) Page 5 of 56 reversible non-selective MAO inhibitor and methylene blue, which is a MAOI).

Similarly, at least 14 days should elapse after discontinuing citalopram treatment before starting a MAOI. • Pimozide Citalopram should not be used in combination with the antipsychotic drug pimozide, as results from a controlled study indicate that concomitant use is associated with an increased risk of QTc prolongation compared to pimozide alone.

2 Drug Interactions Overview, Drugs That Prolong the QT Interval). 2 Drug Interactions Overview, Drugs That Prolong the QT Interval;