Celexa (Citalopram Hydrobromide) - Indications and Dosage

INDICATIONS AND USAGE

Celexa (citalopram HBr) is indicated for the treatment of depression.

The efficacy of Celexa in the treatment of depression was established in 4-6 week, controlled trials of outpatients whose diagnosis corresponded most closely to the DSM-III and DSM-III-R category of major depressive disorder (see CLINICAL PHARMACOLOGY).

A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least five of the following nine symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt or suicidal ideation.

The antidepressant action of Celexa in hospitalized depressed patients has not been adequately studied.

The efficacy of Celexa in maintaining an antidepressant response for up to 24 weeks following 6 to 8 weeks of acute treatment was demonstrated in two placebo-controlled trials (see CLINICAL PHARMACOLOGY). Nevertheless, the physician who elects to use Celexa for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

DOSAGE AND ADMINISTRATION

INITIAL TREATMENT

Celexa (citalopram HBr) should be administered at an initial dose of 20 mg once daily, generally with an increase to a dose of 40 mg/day. Dose increases should usually occur in increments of 20 mg at intervals of no less than one week. Although certain patients may require a dose of 60 mg/day, the only study pertinent to dose response for effectiveness did not demonstrate an advantage for the 60 mg/day dose over the 40 mg/day dose; doses above 40 mg are therefore not ordinarily recommended.

Celexa should be administered once daily, in the morning or evening, with or without food.

SPECIAL POPULATIONS

20 mg/day is the recommended dose for most elderly patients and patients with hepatic impairment, with titration to 40 mg/day only for nonresponding patients.

No dosage adjustment is necessary for patients with mild or moderate renal impairment. Celexa should be used with caution in patients with severe renal impairment.

TREATMENT OF PREGNANT WOMEN DURING THE THIRD TRIMESTER

Neonates exposed to Celexa and other SSRIs or SNRIs, late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding (see PRECAUTIONS). When treating pregnant women with Celexa during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. The physician may consider tapering Celexa in the third trimester.

MAINTENANCE TREATMENT

It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacologic therapy. Systematic evaluation of Celexa in two studies has shown that its antidepressant efficacy is maintained for periods of up to 24 weeks following 6 or 8 weeks of initial treatment (32 weeks total). In one study, patients were assigned randomly to placebo or to the same dose of Celexa (20-60 mg/day) during maintenance treatment as they had received during the acute stabilization phase, while in the other study, patients were assigned randomly to continuation of Celexa 20 or 40 mg/day, or placebo, for maintenance treatment. In the latter study, the rates of relapse to depression were similar for the two dose groups (see Clinical Trials under CLINICAL PHARMACOLOGY). Based on these limited data, it is not known whether the dose of citalopram needed to maintain euthymia is identical to the dose needed to induce remission. If adverse reactions are bothersome, a decrease in dose to 20 mg/day can be considered.

DISCONTINUATION OF TREATMENT WITH CELEXA

Symptoms associated with discontinuation of Celexa and other SSRIs and SNRIs have been reported (see PRECAUTIONS). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. 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.

SWITCHING PATIENTS TO OR FROM A MONOAMINE OXIDASE INHIBITOR

At least 14 days should elapse between discontinuation of an MAOI and initiation of Celexa therapy. Similarly, at least 14 days should be allowed after stopping Celexa before starting an MAOI (see CONTRAINDICATIONS and WARNINGS).

HOW SUPPLIED

Tablets:

10 mg        Bottle of 100         NDC # 0456-4010-01

Beige, oval, film-coated.

Imprint on one side with "FP". Imprint on the other side with "10 mg".

20 mg        Bottle of 100         NDC # 0456-4020-01

10 × 10 Unit Dose                NDC # 0456-4020-63

Pink, oval, scored, film-coated.

Imprint on scored side with "F" on the left side and "P" on the right side.

Imprint on the non-scored side with "20 mg".

40 mg        Bottle of 100         NDC # 0456-4040-01

10 × 10 Unit Dose                NDC # 0456-4040-63

White, oval, scored, film-coated.

Imprint on scored side with "F" on the left side and "P" on the right side.

Imprint on the non-scored side with "40 mg".

Oral Solution:

10 mg/5 mL, peppermint flavor (240 mL) NDC 0456-4130-08

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

ANIMAL TOXICOLOGY

RETINAL CHANGES IN RATS

Pathologic changes (degeneration/atrophy) were observed in the retinas of albino rats in the 2-year carcinogenicity study with citalopram. There was an increase in both incidence and severity of retinal pathology in both male and female rats receiving 80 mg/kg/day (13 times the maximum recommended daily human dose of 60 mg on a mg/m² basis). Similar findings were not present in rats receiving 24 mg/kg/day for two years, in mice treated for 18 months at doses up to 240 mg/kg/day, or in dogs treated for one year at doses up to 20 mg/kg/day (4, 20, and 10 times, respectively, the maximum recommended daily human dose on a mg/m² basis).

Additional studies to investigate the mechanism for this pathology have not been performed, and the potential significance of this effect in humans has not been established.

CARDIOVASCULAR CHANGES IN DOGS

In a one-year toxicology study, 5 of 10 beagle dogs receiving oral doses of 8 mg/kg/day (4 times the maximum recommended daily human dose of 60 mg on a mg/m² basis) died suddenly between weeks 17 and 31 following initiation of treatment. Although appropriate data from that study are not available to directly compare plasma levels of citalopram (CT) and its metabolites, demethylcitalopram (DCT) and didemethylcitalopram (DDCT), to levels that have been achieved in humans, pharmacokinetic data indicate that the relative dog-to-human exposure was greater for the metabolites than for citalopram. Sudden deaths were not observed in rats at doses up to 120 mg/kg/day, which produced plasma levels of CT, DCT, and DDCT similar to those observed in dogs at doses of 8 mg/kg/day. A subsequent intravenous dosing study demonstrated that in beagle dogs, DDCT caused QT prolongation, a known risk factor for the observed outcome in dogs. This effect occurred in dogs at doses producing peak DDCT plasma levels of 810 to 3250 nM (39-155 times the mean steady state DDCT plasma level measured at the maximum recommended human daily dose of 60 mg). In dogs, peak DDCT plasma concentrations are approximately equal to peak CT plasma concentrations, whereas in humans, steady state DDCT plasma concentrations are less than 10% of steady state CT plasma concentrations. Assays of DDCT plasma concentrations in 2020 citalopram-treated individuals demonstrated that DDCT levels rarely exceeded 70 nM; the highest measured level of DDCT in human overdose was 138 nM. While DDCT is ordinarily present in humans at lower levels than in dogs, it is unknown whether there are individuals who may achieve higher DDCT levels. The possibility that DCT, a principal metabolite in humans, may prolong the QT interval in dogs has not been directly examined because DCT is rapidly converted to DDCT in that species.

Forest Pharmaceuticals, Inc.

Subsidiary of Forest Laboratories, Inc.

St. Louis, MO 63045 USA

Licensed from H. Lundbeck A/S

Rev. 06/04

© 2004 Forest Laboratories, Inc.

MG #13940(17)