Citalopram Hydrobromide (citalopram hydrobromide 40 mg) Dailymed

• QT-Prolongation and Torsade de Pointes: Dose-dependent QTc prolongation, Torsade de pointes, ventricular tachycardia, and sudden death have occurred. Avoid use of citalopram tablets in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent acute myocardial infarction, or uncompensated heart failure and patients taking other drugs that prolong the QTc interval. Monitor electrolytes in patients at high risk for hypokalemia or hypomagnesemia. Discontinue citalopram tablets in patients with persistent QTc measurements > 500 ms (5.2, 7).• Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If occurs, discontinue citalopram tablets and serotonergic agents and initiate supportive measures ( 5.3 ).• Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti- inflammatory drugs, other antiplatelet drugs, warfarin and other anticoagulants may increase this risk ( 5.4 ).• Activation of Mania/Hypomania: Screen patients for bipolar disorder ( 5.5 ).• Seizures: Use with caution in patients with seizure disorder ( 5.7 ).• Angle-Closure Glaucoma: Avoid use of citalopram tablets in patients with untreated anatomically narrow angles ( 5.8 ).• Hyponatremia: Can occur in association with syndrome of inappropriate antidiuretic hormone secretion ( 5.9 ).• Sexual Dysfunction: Citalopram tablets may cause symptoms of sexual dysfunction. ( 5.10 ).

5.1 Suicidal Thoughts and Behavior in Adolescents and Young Adults

In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients, and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1.

Table 1: Risk Differences of the Number of Patients with Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients

Age Range*	Drug-Placebo Difference in Number of Patients with Suicidal                                     Thoughts or Behaviors per 1,000 Patients Treated
	Increases Compared to Placebo
<18 years old	14 additional patients
18 to 24 years old	5 additional patients
	Decreases Compared to Placebo
25 to 64 years old	1 fewer patient
≥65 years old	6 fewer patients

*Citalopram tablets are not approved for use in pediatric patients.

It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors.

Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing citalopram tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

5.2 QT-Prolongation and Torsade de Pointes

Citalopram tablets cause dose-dependent QTc prolongation an ECG abnormality that has been associated with Torsade de Pointes (TdP), ventricular tachycardia, and sudden death, all of which have been observed in postmarketing reports for citalopram [see Adverse Reactions (6.2)] .

Because of the risk of QTc prolongation at higher citalopram tablet doses, it is recommended that citalopram tablets not be given at doses above 40 mg once daily [see Dosage and Administration (2.1), Clinical Pharmacology (12.2)] .

Citalopram tablets should be avoided in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent acute myocardial infarction, or uncompensated heart failure unless the benefits outweigh the risks for a particular patient. Citalopram tablets should also be avoided in patients who are taking other drugs that prolong the QTc interval [see Drug Interactions (7)] . Such drugs include Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone).

The citalopram dose should be limited in certain populations. The maximum dose should be limited to 20 mg once daily in patients who are CYP2C19 poor metabolizers or those patients receiving concomitant cimetidine or another CYP2C19 inhibitor, since higher citalopram exposures would be expected. The maximum dose should also be limited to 20 mg once daily in patients with hepatic impairment and in patients who are greater than 60 years of age because of expected higher exposures [see Dosage and Administration (2.3, 2.4), Drug Interactions (7), Use in Specific Populations (8.5), Clinical Pharmacology (12.3)] .

Electrolyte and/or ECG monitoring is recommended in certain circumstances. Patients being considered for treatment with citalopram tablets who are at risk for significant electrolyte disturbances should have baseline serum potassium and magnesium measurements with periodic monitoring. Hypokalemia (and/or hypomagnesemia) may increase the risk of QTc prolongation and arrhythmia, and should be corrected prior to initiation of treatment and periodically monitored. ECG monitoring is recommended in patients for whom citalopram use is not recommended unless the benefits clearly outweigh the risks for a particular patient (see above). These include those patients with the cardiac conditions noted above, and those taking other drugs that may prolong the QTc interval.

Discontinue citalopram tablets in patients who are found to have persistent QTc measurements >500 ms. If patients taking citalopram tablets experience symptoms that could indicate the occurrence of cardiac arrhythmias, e.g., dizziness, palpitations, or syncope, the prescriber should initiate further evaluation, including cardiac monitoring.

5.3 Serotonin Syndrome

SSRIs, including citalopram tablets, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications (4), Drug Interactions (7)] . Serotonin syndrome can also occur when these drugs are used alone. Symptoms of serotonin syndrome were noted in 0.1% of MDD patients treated with citalopram tablets in premarketing clinical trials.

Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

The concomitant use of citalopram tablets with MAOIs is contraindicated. In addition, do not initiate citalopram tablets in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking citalopram tablets, discontinue citalopram tablets before initiating treatment with the MAOI [see Contraindications (4), Drug Interactions (7)] .

Monitor all patients taking citalopram tablets for the emergence of serotonin syndrome. Discontinue treatment with citalopram tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of citalopram tablets with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

5.4 Increased Risk of Bleeding

Drugs that interfere with serotonin reuptake inhibition, including citalopram tablets, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDS), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Based on data from the published observational studies, exposure to SSRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Use in Specific Populations (8.1)] . Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages.

Inform patients about the increased risk of bleeding associated with the concomitant use of citalopram tablets and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Drug Interactions (7)] .

5.5 Activation of Mania or Hypomania

In patients with bipolar disorder, treating a depressive episode with citalopram tablets or another antidepressant may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were excluded; however, symptoms of mania or hypomania were reported in 0.1% of undiagnosed patients treated with citalopram tablets. Prior to initiating treatment with citalopram tablets, screen patients for any personal or family history of bipolar disorder, mania, or hypomania [see Dosage and Administration (2.2)] .

5.6 Discontinuation Syndrome

Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [see Dosage and Administration (2.6)] .

5.7 Seizures

Citalopram tablets have not been systematically evaluated in patients with seizure disorders. Patients with a history of seizures were excluded from clinical studies. In clinical trials of citalopram tablets, seizures occurred in 0.3% of patients treated with citalopram tablets (a rate of one patient per 98 years of exposure) and 0.5% of patients treated with placebo (a rate of one patient per 50 years of exposure). Citalopram tablets should be prescribed with caution in patients with a seizure disorder.

5.8 Angle-closure Glaucoma

The pupillary dilation that occurs following use of many antidepressant drugs, including citalopram tablets, may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including citalopram tablets, in patients with untreated anatomically narrow angles.

5.9 Hyponatremia

Hyponatremia may occur as a result of treatment with SSRIs, including citalopram tablets. Cases of serum sodium lower than 110 mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

In patients with symptomatic hyponatremia, discontinue citalopram tablets and institute appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs [see Use in Specific Populations (8.5)] .

5.10 Sexual Dysfunction

Use of SSRIs, including citalopram tablets, may cause symptoms of sexual dysfunction [see Adverse Reactions (6.1)] . In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of citalopram tablets and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment.

6 Adverse Reactions

The following adverse reactions are discussed in greater detail in other sections of the labeling: • Hypersensitivity reactions [see Contraindications (4)] • Suicidal thoughts and behaviors in adolescents and young adults [see Warnings and Precautions (5.1)] • QT-prolongation and torsade de pointes [see Warnings and Precautions (5.2)] • Serotonin syndrome [see Warnings and Precautions (5.3)] • Increased risk of bleeding [see Warnings and Precautions (5.4)] • Activation of mania or hypomania [see Warnings and Precautions (5.5)] • Discontinuation syndrome [see Warnings and Precautions (5.6)] • Seizures [see Warnings and Precautions (5.7)] • Angle-closure glaucoma [see Warnings and Precautions (5.8)] • Hyponatremia [see Warnings and Precautions (5.9)] • Sexual Dysfunction [see Warnings and Precautions (5.10)]


Most common adverse reaction (incidence ≥ 5% and twice placebo) is ejaculation disorder (primarily ejaculation delay) (6.1) .

To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc . at 1-800-912-9561 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 citalopram tablets 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 citalopram 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 Associated with Discontinuation of Treatment

Among 1,063 patients with MDD who received citalopram tablets 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 citalopram-treated patients at a rate at least twice that of placebo) are shown in Table 2.

Table 2: Adverse Reactions Associated with Discontinuation of citalopram Treatment in Short-Term, Placebo-Controlled MDD Trials

Body System/Adverse Reaction	Citalopram	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 citalopram tablets 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 citalopram-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 Citalopram-Treated Patients*

Body System/Adverse Reaction	Citalopram		Placebo
	(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 citalopram are reported, except for the following adverse reactions which had an incidence on placebo ≥ citalopram: headache, asthenia, dizziness, constipation, palpitation, vision abnormal, sleep disorder, nervousness, pharyngitis, micturition disorder, back pain.

¹Denominator used was for females only (N=638 citalopram; N=252 placebo).

²Primarily ejaculatory delay.

³Denominator used was for males only (N=425 citalopram; N=194 placebo).

Dose Dependent Adverse Reactions

The potential relationship between the dosage of citalopram 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.

Table 4: Adverse Reactions (≥2%) Related to Sexual Dysfunction in citalopram-Treated Male Patients in Pooled Placebo-Controlled Clinical Trials of MDD

	Citalopram	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 (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 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 group. The incidence of tachycardic outliers was 0.5% in the citalopram group and 0.4% in the placebo group. The incidence of bradycardic outliers was 0.9% in the citalopram group and 0.4% in the placebo group.

Other Adverse Reactions Observed During the Premarketing Evaluation of Citalopram Tablets

The following ul 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 uled 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 1/1,000 patients; rare adverse reactions are those occurring in fewer than 1/1,000 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

Respiratory, Thoracic and Mediastinal Disorders: anosmia, hyposmia

Skin and Subcutaneous Tissue Disorders: Stevens Johnson Syndrome, epidermal necrolysis, angioedema, erythema multiforme, ecchymosis

Vascular Disorders: thrombosis