CITALOPRAM TABLETS, 20 mg

/CITALOPRAM TABLETS, 20 mg
CITALOPRAM TABLETS, 20 mg2018-09-06T09:12:40+00:00

Prescription Drug Name:

CITALOPRAM TABLETS, 20 mg

ID:

30abc373-2373-449c-9bb1-b22238402357

Code:

34391-3

DESCRIPTION


id: dda2039b-556a-46b4-9d95-7dcaaf0bccd2
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Citalopram HBr is an orally administered selective serotonin reuptake inhibitor (SSRI) with a chemical structure unrelated to that of other SSRIs or of tricyclic, tetracyclic, or other available antidepressant agents. Citalopram HBr is a racemic bicyclic phthalane derivative designated (±)-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1, 3-dihydroisobenzofuran-5-carbonitrile, HBr with the following structural formula:

The molecular formula is C20H22BrFN2O and its molecular weight is 405.35. Citalopram HBr occurs as a fine, white to off-white powder. Citalopram HBr is sparingly soluble in water and soluble in ethanol. Citalopram Tablets, USP 10 mg are film coated, round tablets containing citalopram HBr in strength equivalent to 10 mg citalopram base. Citalopram Tablets, USP 20 mg and 40 mg tablets are film coated, round, scored tablets containing citalopram HBr in strengths equivalent to 20 mg or 40 mg citalopram base. The tablets also contain the following inactive ingredients: colloidal silicon dioxide, corn starch, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. Orange 40L13864 is used as a coloring agent in the beige (10 mg) tablets and contains: FD&C yellow #6, hypromellose 2910 3cP, 6cP, and 50cP, polydextrose, polyethylene glycol, titanium dioxide, and triacetin. Orange 40L13950 is used as a coloring agent in the pink (20 mg) tablets and contains: FD&C red #40, FD&C yellow #6, hypromellose 2910 3cP, 6cP, and 50cP, polydextrose, polyethylene glycol, titanium dioxide, and triacetin. White Y-22-7719 is used as a coloring agent in the white (40 mg) tablets and contains: hypromellose 2910 3cP, 6cP, and 50cP, polydextrose, polyethylene glycol, titanium dioxide, and triacetin.

INDICATIONS AND USAGE


id: a9b08d2f-3c55-42cb-be2f-028214fcc91d
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Citalopram HBr Tablets are indicated for the treatment of depression. The efficacy of Citalopram HBr Tablets 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-lV) 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 Citalopram HBr Tablets in hospitalized depressed patients has not been adequately studied. The efficacy of Citalopram HBr Tablets 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 Citalopram HBr Tablets for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

CONTRAINDICATIONS


id: 584afa51-6663-48d1-bdfa-845ddfc8a36d
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated (see WARNINGS ). Concomitant use in patients taking pimozide is contraindicated (see PRECAUTIONS ). Citalopram HBr Tablets are contraindicated in patients with a hypersensitivity to citalopram or any of the inactive ingredients in Citalopram HBr Tablets.

ADVERSE REACTIONS


id: 6d23f185-b079-41c4-aa84-98afc86d983a
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

The premarketing development program for Citalopram HBr Tablets included citalopram exposures in patients and/or normal subjects from 3 different groups of studies: 429 normal subjects in clinical pharmacology/pharmacokinetic studies; 4422 exposures from patients in controlled and uncontrolled clinical trials, corresponding to approximately 1370 patientexposure years. There were, in addition, over 19,000 exposures from mostly open-label, European postmarketing studies. The conditions and duration of treatment with Citalopram HBr Tablets varied greatly and included (in overlapping categories) open-label and double-blind studies, inpatient and outpatient studies, fixed-dose and dose-titration studies, and short-term and long-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, ECGs, and results of ophthalmologic examinations. Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, standard World Health Organization (WHO) terminology has been used to classify reported adverse events. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Adverse Findings Observed in Short-Term, Placebo-Controlled Trials Adverse Events Associated with Discontinuation of Treatment Among 1063 depressed patients who received Citalopram HBr Tablets at doses ranging from 10 to 80 mg/day in placebo-controlled trials of up to 6 weeks in duration, 16% discontinued treatment due to an adverse event, as compared to 8% of 446 patients receiving placebo. The adverse events associated with discontinuation and considered drug-related (i.e., associated with discontinuation in at least 1% of Citalopram HBr Tablet-treated patients at a rate at least twice that of placebo) are shown in TABLE 2 . It should be noted that one patient can report more than one reason for discontinuation and be counted more than once in this table. Adverse Events Associated with Discontinuation of Treatment in Short-Term, Placebo Controlled, Depression Trials

TABLE 2
Percentage of Patients Discontinuing Due to Adverse Event

Body System/Adverse Event

Citalopram

Placebo
(N=1063) (N=446)
General
Asthenia 1% <1%
Gastrointestinal Disorders
Nausea 4% 0%
Dry Mouth 1% <1%
Vomiting 1% 0%
Central and Peripheral Nervous System Disorders
Dizziness 2% <1%
Psychiatric Disorders
Insomnia 3% 1%
Somnolence 2% 1%
Agitation 1% <1%
  Adverse Events Occurring at an Incidence of 2% or More Among Citalopram HBr Tablet-Treated Patients Table 3 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred among 1063 depressed patients who received Citalopram HBr Tablets 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 HBr Tablets and for which the incidence in patients treated with Citalopram HBr Tablets was greater than the incidence in placebo-treated patients. 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. The only commonly observed adverse event that occurred in Citalopram HBr Tablet patients with an incidence of 5% or greater and at least twice the incidence in placebo patients was ejaculation disorder (primarily ejaculatory delay) in male patients (see TABLE 3 ). Treatment-Emergent Adverse Events: Incidence in Placebo-Controlled Clinical Trials* (Percentage of Patients Reporting Event)
TABLE 3
Body System/Adverse Event Citalopram Placebo
(N=1063) (N=446)
Autonomic Nervous System Disorders
Dry Mouth 20% 14%
Sweating Increased 11% 9%
Central & Peripheral Nervous System Disorders
Tremor 8% 6%
Gastrointestinal Disorders
Nausea 21% 14%
Diarrhea 8% 5%
Dyspepsia 5% 4%
Vomiting 4% 3%
Abdominal Pain 3% 2%
General
Fatigue 5% 3%
Fever 2% <1%
Musculoskeletal System Disorders
Arthralgia 2% 1%
Myalgia 2% 1%
Psychiatric Disorders
Somnolence 18% 10%
Insomnia 15% 14%
Anxiety 4% 3%
Anorexia 4% 2%
Agitation 3% 1%
Dysmenorrhea1 3% 2%
Libido Decreased 2% <1%
Yawning 2% <1%
Respiratory System Disorders
Upper Respiratory Tract Infection 5% 4%
Rhinitis 5% 3%
Sinusitis 3% <1%
Urogenital
Ejaculation Disorder2,3 6% 1%
Impotence3 3% <1%
  *Events reported by at least 2% of patients treated with Citalopram HBr Tablets are reported, except for the following events which had an incidence on placebo ≥ Citalopram HBr Tablets: headache, asthenia, dizziness, constipation, palpitation, vision abnormal, sleep disorder, nervousness, pharyngitis, micturition disorder, back pain. 1 Denominator used was for females only (N=638 Citalopram HBr Tablets; N=252 placebo). 2 Primarily ejaculatory delay. 3 Denominator used was for males only (N=425 Citalopram HBr Tablets; N=194 placebo). Dose Dependency of Adverse Events The potential relationship between the dose of Citalopram HBr Tablets administered and the incidence of adverse events was examined in a fixed-dose study in depressed patients receiving placebo or Citalopram HBr Tablets 10, 20, 40, and 60 mg. Jonckheere’s trend test revealed a positive dose response (p<0.05) for the following adverse events: fatigue, impotence, insomnia, sweating increased, somnolence, and yawning. Male and Female Sexual Dysfunction with SSRIs Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences. Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling, are likely to underestimate their actual incidence. The table below displays the incidence of sexual side effects reported by at least 2% of patients taking Citalopram HBr Tablets in a pool of placebo-controlled clinical trials in patients with depression.
Treatment Citalopram HBr Tablets Placebo
(425 males) (194 males)
Abnormal Ejaculation (mostly ejaculatory delay) 6.1% (males only) 1% (males only)
Libido Decreased 3.8% (males only) <1% (males only)
Impotence 2.8% (males only) <1% (males only)
In female depressed patients receiving Citalopram HBr Tablets, the reported incidence of decreased libido and anorgasmia was 1.3% (n=638 females) and 1.1% (n=252 females), respectively. There are no adequately designed studies examining sexual dysfunction with citalopram treatment. Priapism has been reported with all SSRIs. While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects. Vital Sign Changes Citalopram HBr Tablet and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic blood pressure, and diastolic blood pressure) and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses did not reveal any clinically important changes in vital signs associated with Citalopram HBr Tablet treatment. In addition, a comparison of supine and standing vital sign measures for Citalopram HBr Tablet and placebo treatments indicated that Citalopram HBr Tablet treatment is not associated with orthostatic changes. Weight Changes Patients treated with Citalopram HBr Tablets in controlled trials experienced a weight loss of about 0.5 kg compared to no change for placebo patients. Laboratory Changes Citalopram HBr Tablet and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, hematology, and urinalysis variables, and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in laboratory test parameters associated with Citalopram HBr Tablet treatment. ECG Changes Electrocardiograms from Citalopram HBr Tablet (N=802) and placebo (N=241) groups were compared with respect to (1) mean change from baseline in various ECG parameters, and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. The only statistically significant drug-placebo difference observed was a decrease in heart rate for Citalopram HBr Tablets of 1.7 bpm compared to no change in heart rate for placebo. There were no observed differences in QT or other ECG intervals. Other Events Observed During the Premarketing Evaluation of Citalopram HBr Tablets Following is a list of WHO terms that reflect treatment-emergent adverse events, as defined in the introduction to the ADVERSE REACTIONS section, reported by patients treated with Citalopram HBr Tablets at multiple doses in a range of 10 to 80 mg/day during any phase of a trial within the premarketing database of 4422 patients. All reported events are included except those already listed in Table 3 or elsewhere in labeling, those events for which a drug cause was remote, those event terms which were so general as to be uninformative, and those occurring in only one patient. It is important to emphasize that, although the events reported occurred during treatment with Citalopram HBr Tablets, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in less than 1/100 patients but at least 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Cardiovascular Frequent: tachycardia, postural hypotension, hypotension. Infrequent: hypertension, bradycardia, edema (extremities), angina pectoris, extrasystoles, cardiac failure, flushing, myocardial infarction, cerebrovascular accident, myocardial ischemia. Rare: transient ischemic attack, phlebitis, atrial fibrillation, cardiac arrest, bundle branch block. Central and Peripheral Nervous System Disorders Frequent: paresthesia, migraine. Infrequent: hyperkinesia, vertigo, hypertonia, extrapyramidal disorder, leg cramps, involuntary muscle contractions, hypokinesia, neuralgia, dystonia, abnormal gait, hypesthesia, ataxia. Rare: abnormal coordination, hyperesthesia, ptosis, stupor. Endocrine Disorders Rare: hypothyroidism, goiter, gynecomastia. Gastrointestinal Disorders Frequent: saliva increased, flatulence. Infrequent: gastritis, gastroenteritis, stomatitis, eructation, hemorrhoids, dysphagia, teeth grinding, gingivitis, esophagitis. Rare: colitis, gastric ulcer, cholecystitis, cholelithiasis, duodenal ulcer, gastroesophageal reflux, glossitis, jaundice, diverticulitis, rectal hemorrhage, hiccups. General Infrequent: hot flushes, rigors, alcohol intolerance, syncope, influenza-like symptoms. Rare: hayfever. Hemic and Lymphatic Disorders Infrequent: purpura, anemia, epistaxis, leukocytosis, leucopenia, lymphadenopathy. Rare: pulmonary embolism, granulocytopenia, lymphocytosis, lymphopenia, hypochromic anemia, coagulation disorder, gingival bleeding. Metabolic and Nutritional Disorders Frequent: decreased weight, increased weight. Infrequent: increased hepatic enzymes, thirst, dry eyes, increased alkaline phosphatase, abnormal glucose tolerance. Rare: bilirubinemia, hypokalemia, obesity, hypoglycemia, hepatitis, dehydration. Musculoskeletal System Disorders Infrequent: arthritis, muscle weakness, skeletal pain. Rare: bursitis, osteoporosis. Psychiatric Disorders Frequent: impaired concentration, amnesia, apathy, depression, increased appetite, aggravated depression, suicide attempt, confusion. Infrequent: increased libido, aggressive reaction, paroniria, drug dependence, depersonalization, hallucination, euphoria, psychotic depression, delusion, paranoid reaction, emotional lability, panic reaction, psychosis. Rare: catatonic reaction, melancholia. Reproductive Disorders/Female* Frequent: amenorrhea. Infrequent: galactorrhea, breast pain, breast enlargement, vaginal hemorrhage. * % based on female subjects only: 2955 Respiratory System Disorders Frequent: coughing. Infrequent: bronchitis, dyspnea, pneumonia. Rare: asthma, laryngitis, bronchospasm, pneumonitis, sputum increased. Skin and Appendages Disorders Frequent: rash, pruritus. Infrequent: photosensitivity reaction, urticaria, acne, skin discoloration, eczema, alopecia, dermatitis, skin dry, psoriasis. Rare: hypertrichosis, decreased sweating, melanosis, keratitis, cellulitis, pruritus ani. Special Senses Frequent: accommodation abnormal, taste perversion. Infrequent: tinnitus, conjunctivitis, eye pain. Rare: mydriasis, photophobia, diplopia, abnormal lacrimation, cataract, taste loss. Urinary System Disorders Frequent: polyuria. Infrequent: micturition frequency, urinary incontinence, urinary retention, dysuria. Rare: facial edema, hematuria, oliguria, pyelonephritis, renal calculus, renal pain. Other Events Observed During the Postmarketing Evaluation of Citalopram HBr Tablets It is estimated that over 30 million patients have been treated with Citalopram HBr Tablets since market introduction. Although no causal relationship to Citalopram HBr Tablet treatment has been found, the following adverse events have been reported to be temporally associated with Citalopram HBr Tablet treatment, and have not been described elsewhere in labeling: acute renal failure, akathisia, allergic reaction, anaphylaxis, angioedema, choreoathetosis, chest pain, delirium, dyskinesia, ecchymosis, epidermal necrolysis, erythema mutiforme, gastrointestinal hemorrhage, glaucoma, grand mal convulsions, hemolytic anemia, hepatic necrosis, myoclonus, neuroleptic malignant syndrome, nystagmus, pancreatitis, priapism, prolactinemia, prothrombin decreased, QT prolonged, rhabdomyolysis, serotonin syndrome, spontaneous abortion, thrombocytopenia, thrombosis, ventricular arrhythmia, torsades de pointes, and withdrawal syndrome.

DRUG ABUSE AND DEPENDENCE


id: 2653706e-9d4b-4993-ae68-7b15e803fd3c
displayName: DRUG ABUSE AND DEPENDENCE SECTION
FDA Article Code: 42227-9

Controlled Substance Class Citalopram HBr Tablet is not a controlled substance. Physical and Psychological Dependence Animal studies suggest that the abuse liability of Citalopram HBr Tablets is low. Citalopram HBr Tablets have not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. The premarketing clinical experience with Citalopram HBr Tablets did not reveal any drug seeking behavior. However, these observations were not systematic and it is not possible to predict, on the basis of this limited experience, the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate Citalopram HBr Tablet patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).

OVERDOSAGE


id: 91c658e5-8256-4005-a729-c26a4985c031
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Human Experience In clinical trials of citalopram, there were reports of citalopram overdose, including overdoses of up to 2000 mg, with no associated fatalities. During the postmarketing evaluation of citalopram, Citalopram HBr Tablet overdoses, including overdoses of up to 6000 mg, have been reported. As with other SSRIs, a fatal outcome in a patient who has taken an overdose of citalopram has been rarely reported. Symptoms most often accompanying citalopram overdose, alone or in combination with other drugs and/or alcohol, included dizziness, sweating, nausea, vomiting, tremor, somnolence, and sinus tachycardia. In more rare cases, observed symptoms included amnesia, confusion, coma, convulsions, hyperventilation, cyanosis, rhabdomyolysis, and ECG changes (including QTc prolongation, nodal rhythm, ventricular arrhythmia, and very rare cases of torsades de pointes). Acute renal failure has been very rarely reported accompanying overdose. Management of Overdose Establish and maintain an airway to ensure adequate ventilation and oxygenation. Gastric evacuation by lavage and use of activated charcoal should be considered. Careful observation and cardiac and vital sign monitoring are recommended, along with general symptomatic and supportive care. Due to the large volume of distribution of citalopram, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. There are no specific antidotes for Citalopram HBr Tablets. In managing overdosage, consider the possibility of multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose.

HOW SUPPLIED


id: f15f8e3a-ed86-4169-b141-26fa1a2e5387
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Citalopram Tablets, USP 20 mg Blister of 30 NDC # 67046-111-30 Pink, round, bi-convex, scored, film coated tablets debossed “KALI” on one side and “281” on the scored side.

ANIMAL TOXICOLOGY


id: 9595f92a-33bd-4976-8e82-a8a79daaf15f
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

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.

Principal Display Panel – 30 Tablet Label


id: 690a794a-8e2f-453e-9d74-9548057dd1af
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

Citalopram Tablets, USP 20 mg* Rx Only