Citalopram: Package Insert and Label Information (Page 3 of 7)
Dose Dependent Adverse Reactions
The potential relationship between the dosage of citalopram tablets and the incidence of adverse reactions was examined in a fixed-dose study in patients with MDD receiving placebo or citalopram tablets 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 citalopram tablets in a pool of placebo-controlled clinical trials in patients with depression.
| Citalopram Tablets | 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 citalopram tablets, 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 citalopram tablets 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, citalopram tablets were found to be associated with a dose-dependent increase in the QTc interval.
Electrocardiograms from citalopram tablets (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 citalopram tablets 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 citalopram tablets group. The incidence of tachycardic outliers was 0.5% in the citalopram tablets group and 0.4% in the placebo group. The incidence of bradycardic outliers was 0.9% in the citalopram tablets group and 0.4% in the placebo group.
Other Adverse Reactions Observed During the Premarketing Evaluation of Citalopram Tablets
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 Lymphatic System Disorders: hemolytic anemia, thrombocytopenia, prothrombin decreased
Cardiac Disorders: torsade de pointes, ventricular arrhythmia, QT prolonged
Endocrine Disorders: hyperprolactinemia
Eye Disorders: angle-closure glaucoma
Gastrointestinal Disorders: gastrointestinal hemorrhage, pancreatitis
General Disorders and Administrative Site Conditions: withdrawal syndrome
Hepatobiliary Disorders: hepatic necrosis
Immune System Disorders: anaphylaxis, allergic reaction
Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis
Nervous System Disorders: grand mal convulsion(s), myoclonus, choreoathetosis, dyskinesia, akathisia, nystagmus
Pregnancy, Puerperium and Perinatal Conditions: spontaneous abortion
Psychiatric Disorders: delirium
Renal and Urinary Disorders: acute renal failure
Reproductive System and Breast Disorders: priapism
Skin and Subcutaneous Tissue Disorders: Stevens Johnson Syndrome, epidermal necrolysis, angioedema, erythema multiforme, ecchymosis
Vascular Disorders: thrombosis
7 DRUG INTERACTIONS
Table 5 presents clinically important drug interactions with citalopram tablets.
| Monoamine Oxidase Inhibitors (MAOIs) | |
| Clinical Impact: | Concomitant use of SSRIs, including citalopram tablets, and MAOIs increases the risk of serotonin syndrome. |
| Intervention: | Citalopram tablets are contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration (2.5), Contraindications (4), Warnings and Precautions (5.3)]. |
| Pimozide | |
| Clinical Impact: | Concomitant use of citalopram tablets with pimozide increases plasma concentrations of pimozide, a drug with a narrow therapeutic index, and may increase the risk of QT prolongation and/or ventricular arrhythmias compared to use of citalopram tablets alone [see Clinical Pharmacology (12.2)]. |
| Intervention: | Citalopram tablets are contraindicated in patients taking pimozide [see Contraindications (4), Warnings and Precautions (5.2)]. |
| Drugs that Prolong the QTc Interval | |
| Clinical Impact: | Concomitant use of citalopram tablets with drugs that prolong QT can cause additional QT prolongation compared to the use of citalopram tablets alone [see Clinical Pharmacology (12.2)]. |
| Intervention: | Avoid concomitant use of citalopram tablets with drugs that prolong the QT interval (citalopram tablets are contraindicated in patients taking pimozide) [see Contraindications (4), Warnings and Precautions (5.2)]. |
| CYP2C19 Inhibitors | |
| Clinical Impact: | Concomitant use of citalopram tablets with CYP2C19 inhibitors increases the risk of QT prolongation and/or ventricular arrhythmias compared to the use of citalopram tablets alone [see Clinical Pharmacology (12.2)]. |
| Intervention: | The maximum recommended dosage of citalopram tablets is 20 mg daily when used concomitantly with a CYP2C19 inhibitor [see Dosage and Administration (2.4), Warnings and Precautions (5.2)]. |
| Serotonergic Drugs | |
| Clinical Impact: | Concomitant use of citalopram tablets and other serotonergic drugs increases the risk of serotonin syndrome. |
| Intervention: | Monitor patients for signs and symptoms of serotonin syndrome, particularly during citalopram tablets initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of citalopram tablets and/or concomitant serotonergic drugs [see Warnings and Precautions (5.3)]. |
| Drugs That Interfere With Hemostasis (antiplatelet agents and anticoagulants) | |
| Clinical Impact: | Concomitant use of citalopram tablets and an antiplatelet or anticoagulant may potentiate the risk of bleeding. |
| Intervention: | Inform patients of the increased risk of bleeding associated with the concomitant use of citalopram tablets and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Warnings and Precautions (5.4)]. |
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/antidepressants.
DrugInserts.com provides trustworthy package insert and label information about marketed drugs as submitted by manufacturers to the US Food and Drug Administration. Package information is not reviewed or updated separately by DrugInserts.com. Every individual package label entry contains a unique identifier which can be used to secure further details directly from the US National Institutes of Health and/or the FDA.