Citalopramside effects

The following adverse reactions are discussed in greater detail in other sections of the labeling: Hypersensitivity reactions Suicidal thoughts and behaviors in adolescents and young adults QT-prolongation and torsade de pointes Serotonin syndrome Increased risk of bleeding Activation of mania or hypomania Discontinuation syndrome Seizures Angle-closure glaucoma Hyponatremia Sexual Dysfunction Most common adverse reaction (incidence ≥ 5% and twice placebo) is ejaculation disorder (primarily ejaculation delay). To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. The safety for CELEXA included citalopram exposures in patients and/or healthy subjects from 3 different groups of studies: 429 healthy subjects in clinical pharmacology/pharmacokinetic studies; 4,422 exposures from patients in controlled and uncontrolled clinical trials, corresponding to approximately 1,370 patient-exposure years. There were, in addition, over 19,000 exposures from mostly open-label, European postmarketing studies. The conditions and duration of treatment with CELEXA 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 Associated with Discontinuation of Treatment Among 1,063 patients with MDD who received CELEXA at doses ranging from 10 mg to 80 mg once daily in placebo-controlled trials of up to 6 weeks duration, 16% discontinued treatment due to an adverse reaction, as compared to 8% of 446 patients receiving placebo. The adverse reactions associated with discontinuation (i.e., associated with discontinuation in at least 1% of CELEXA-treated patients at a rate at least twice that of placebo) are shown in Table 2.

Table 2: Adverse Reactions Associated with Discontinuation of CELEXA Treatment in Short-Term, Placebo-Controlled MDD Trials Body System/Adverse Reaction CELEXA Placebo (N=1,063) % (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 * A patient can report more than one reason for discontinuation and be counted more than once in this table. Table 3 enumerates the incidence of adverse reactions that occurred among 1,063 patients with MDD who received CELEXA at doses ranging from 10 mg to 80 mg once daily in placebo-controlled trials of up to 6 weeks duration. The most common adverse reaction that occurred in CELEXA-treated 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 ).

Table 3: Adverse Reactions (≥2% and Greater than Placebo) Among CELEXA-Treated Patients* CELEXA Placebo Body System/Adverse Reaction (N=1,063) % (N=446) % Gastrointestinal Disorders Nausea 21 14 Diarrhea 8 5 Dyspepsia 5 4 Vomiting 4 3 Abdominal Pain 3 2 Autonomic Nervous System Disorders Dry Mouth 20 14 Sweating Increased 11 9 Psychiatric Disorders Somnolence 18 10 Insomnia 15 14 Anxiety 4 3 Anorexia 4 2 Agitation 3 1 Dysmenorrhea 1 3 2 Libido Decreased 2 <1 Yawning 2 <1 Central & Peripheral Nervous System Disorders Tremor 8 6 Urogenital Ejaculation Disorder 2,3 6 1 Impotence 3 3 <1 Respiratory System Disorders Upper Respiratory Tract Infection 5 4 Rhinitis 5 3 Sinusitis 3 <1 General Fatigue 5 3 Fever 2 <1 Musculoskeletal System Disorders Arthralgia 2 1 Myalgia 2 1 *Adverse reactions reported by at least 2% of patients treated with CELEXA are reported, except for the following adverse reactions which had an incidence on placebo ≥ CELEXA: headache, asthenia, dizziness, constipation, palpitation, vision abnormal, sleep disorder, nervousness, pharyngitis, micturition disorder, back pain. 1 Denominator used was for females only (N=638 CELEXA; N=252 placebo). 2 Primarily ejaculatory delay. 3 Denominator used was for males only (N=425 CELEXA; N=194 placebo). Dose Dependen t Adverse Reactions The potential relationship between the dosage of CELEXA and the incidence of adverse reactions was examined in a fixed-dose study in patients with MDD receiving placebo or CELEXA 10 mg, 20 mg 40 mg, or 60 mg (1.5 times the maximum recommended dosage). A positive dose response (p<0.05) was revealed for the following adverse reactions: fatigue, impotence, insomnia, increased sweating, 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 SSRI treatment. However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, in part because patients and healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence. Table 4 displays the incidence of sexual adverse reactions reported by at least 2% of male patients taking CELEXA in a pool of placebo-controlled clinical trials in patients with depression.

Table 4: Adverse Reactions (≥2%) Related to Sexual Dysfunction in CELEXA-Treated Male Patients in Pooled Placebo-Controlled Clinical Trials of MDD CELEXA Placebo n (males) 425 ( % ) 194 ( % ) Abnormal ejaculation (mostly ejaculatory delay) 6.1 1 Decreased libido 3.8 <1 Impotence 2.8 <1 In female depressed patients receiving CELEXA, the reported incidence of decreased libido and anorgasmia was 1.3% (n=638 females) and 1.1% (n=252 females), respectively. Weight Changes Patients treated with CELEXA in controlled trials experienced a weight loss of about 0.5 kg compared to no change for placebo patients. ECG Changes In a thorough QT study, CELEXA was found to be associated with a dose-dependent increase in the QTc interval. Electrocardiograms from CELEXA (N=802) and placebo (N=241) groups were compared with respect to outliers defined as subjects with QTc changes over 60 msec from baseline or absolute values over 500 msec post-dose, and subjects with heart rate increases to over 100 bpm or decreases to less than 50 bpm with a 25% change from baseline (tachycardic or bradycardic outliers, respectively). In the CELEXA group 1.9% of the patients had a change from baseline in QTcF >60 msec compared to 1.2% of the patients in the placebo group. None of the patients in the placebo group had a post-dose QTcF >500 msec compared to 0.5% of the patients in the CELEXA group. The incidence of tachycardic outliers was 0.5% in the CELEXA group and 0.4% in the placebo group. The incidence of bradycardic outliers was 0.9% in the CELEXA group and 0.4% in the placebo group. Other Adverse Reactions Observed During the Premarketing Evaluation of CELEXA The following list of adverse reactions does not include reactions that are: 1) included in Table 3 or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be uninformative, and those occurring in only one patient. Adverse reactions are categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse reactions are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in less than 1/100 patients to 1/1000 patients; rare adverse reactions 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, hypoesthesia, 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: hay fever. 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: abnormal accommodation, 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. 6. 2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of citalopram, the racemate, or escitalopram, the S-enantiomer of citalopram. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and L ymphatic S ystem D isorders: hemolytic anemia, thrombocytopenia, prothrombin decreased Cardiac D isorders: torsade de pointes, ventricular arrhythmia, QT prolonged Endocrine D isorders: hyperprolactinemia Eye D isorders: angle-closure glaucoma Gastrointestinal D isorders: gastrointestinal hemorrhage, pancreatitis General Disorders and A dministrative Site C onditions: withdrawal syndrome Hepatobiliary D isorders: hepatic necrosis Immune S ystem D isorders: anaphylaxis, allergic reaction Musculoskeletal and Connective Tissue D isorders: rhabdomyolysis Nervous S ystem D isorders: grand mal convulsion(s), myoclonus, choreoathetosis, dyskinesia, akathisia, nystagmus Pregnancy, P uerperium and P erinatal C onditions: spontaneous abortion Psychiatric D isorders: delirium Renal and U rinary D isorders: acute renal failure Reproductive S ystem and B reast D isorders: priapism Respiratory, Thoracic and Mediastinal Disorders: anosmia, hyposmia Skin and S ubcutaneous T issue D isorders: Stevens Johnson Syndrome, epidermal necrolysis, angioedema, erythema multiforme, ecchymosis Vascular D isorders: thrombosis