Side Effects of Lexapro (escitalopram)

Lexapro(escitalopram) is a selective serotonin reuptake inhibitor (SSRI)antidepressantused to treatdepressionandgeneralized anxiety disorder.

Drug interactionsof Lexapro includemonoamine oxidase inhibitors(MAOIs),tryptophan, St. John's wort,meperidine,lithium, triptans,tramadol,warfarin,aspirin, nonsteroidal anti-inflammatorydrugs(NSAIDs), and otherdrugsthat cause bleeding.

The safety of Lexapro duringpregnancyandbreastfeedinghas not been established. Lexapro should not be used duringpregnancyunless the expected benefits to a patient outweigh unknown hazards to the fetus. Lexapro is excreted in母乳. Lexapro should not be given tonursingmothers unless the expected benefits to the patient outweigh the possible hazards to the child.

WARNING: Some patients experience withdrawal reactions upon stopping SSRI therapy. Symptoms may include

• dizziness,
• tingling,
• tiredness,
• vivid dreams,
• irritability, or
• poor mood.

In order to avoid these symptoms, the dose of SSRI can be slowly reduced instead of abruptly stopped.

What are the common side effects of Lexapro?

常见的副作用与Lex有关apro include:

• agitationor restlessness,
• blurred vision,
• diarrhea,
• difficulty sleeping,
• drowsiness,
• dry mouth,
• fever,
• frequent urination,
• headache,
• indigestion,
• nausea,
• increased ordecreased appetite,
• increasedsweating,
• sexual difficulties (decreased sexual ability or desire, ejaculatory delay),
• taste alterations,tremor(shaking), and
• weight changes.

Antidepressantsincreased the risk ofsuicidalthinking and behavior (suicidality) in short-term studies in children and adolescents withdepressionand other psychiatric disorders. Anyone considering the use of Lexapro or any otherantidepressantin a child or adolescent must balance this risk with the clinical need.

Short-term studies did not show an increase in the risk of suicidality withantidepressants与安慰剂相比,成人超过24年的age. There was a reduction in the risk of suicidality with antidepressants compared with placebo in adults 65 years of age and older.Depressionand certain other psychiatric disorders are themselves associated with increases in the risk ofsuicide. Patients who are started on therapy with antidepressants should be closely observed for clinical worsening, suicidality, or unusual changes in behavior.

Other side effects includeinfluenza-like symptoms andpainin the neck or shoulders.

Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as a result ofdepressionitself, they also may be a consequence of the drugs used to treatdepression. In particular, about one in 11 men given Lexapro report difficulties ejaculating.

What are the serious side effects of Lexapro?

Possible serious side effects of Lexapro include:

• Serotonin syndrome
• Suicidalthinking and behavior
• Abnormal bleeding
• Seizures
• Manicepisodes
• Confusion
• Highfever
• Slurred speech
• Muscle rigidity
• Low sodium
• Angle-closure glaucoma.

No information provided

Monoamine Oxidase Inhibitors (MAOIs)

Serotonergic Drugs

曲坦类

There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of Lexapro with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.

CNS Drugs

Given the primary CNS effects of escitalopram, caution should be used when it is taken in combination with other centrally acting drugs.

Alcohol

Although Lexapro did not potentiate the cognitive and motor effects ofalcoholin a clinical trial, as with other psychotropic medications, the use of alcohol by patients taking Lexapro is not recommended.

Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.)

Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of anNSAIDoraspirin会增强风险of bleeding. Alteredanticoagulanteffects, including increased bleeding, have been reported when SSRIs and SNRIs are coadministered withwarfarin. Patients receiving warfarin therapy should be carefully monitored when Lexapro is initiated or discontinued.

Cimetidine

In subjects who had received 21 days of 40 mg/day racemiccitalopram, combined administration of 400 mg twice a daycimetidinefor 8 days resulted in an increase incitalopramAUC and Cmax of 43% and 39%, respectively. The clinical significance of these findings is unknown.

Digoxin

In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of citalopram anddigoxin(单剂量of 1 mg) did not significantly affect the pharmacokinetics of either citalopram ordigoxin.

Lithium

Coadministration of racemic citalopram (40 mg/day for 10 days) andlithium(30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of escitalopram, caution should be exercised when Lexapro and lithium are coadministered.

Pimozide And Celexa

In a controlled study, a single dose ofpimozide2 mg co-administered with racemic citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10 msec compared topimozidegiven alone. Racemic citalopram did not alter the mean AUC or Cmax of pimozide. The mechanism of this pharmacodynamic interaction is not known.

Sumatriptan

There have been rare postmarketing reports describing patients withweakness, hyperreflexia, and incoordination following the use of an SSRI andsumatriptan. If concomitant treatment withsumatriptanand an SSRI (e.g.,fluoxetine,fluvoxamine,paroxetine,sertraline, citalopram, escitalopram) is clinically warranted, appropriate observation of the patient is advised.

Theophylline

Combined administration of racemic citalopram (40 mg/day for 21 days) and the CYP1A2 substratetheophylline(单剂量of 300 mg) did not affect the pharmacokinetics oftheophylline. The effect of theophylline on the pharmacokinetics of citalopram was not evaluated.

Warfarin

Administration of 40 mg/day racemic citalopram for 21 days did not affect the pharmacokinetics of warfarin, a CYP3A4 substrate. Prothrombin time was increased by 5%, the clinical significance of which is unknown.

Carbamazepine

Combined administration of racemic citalopram (40 mg/day for 14 days) andcarbamazepine(titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics ofcarbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme-inducing properties of carbamazepine, the possibility that carbamazepine might increase the clearance of escitalopram should be considered if the two drugs are coadministered.

Triazolam

Combined administration of racemic citalopram (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate三唑仑(单剂量of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or三唑仑.

Ketoconazole

Combined administration of racemic citalopram (40 mg) andketoconazole(200 mg), a potent CYP3A4 inhibitor, decreased the Cmax and AUC ofketoconazoleby 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram.

Ritonavir

Combined administration of a single dose ofritonavir(600 mg), both a CYP3A4 substrate and a potent inhibitor of CYP3A4, and escitalopram (20 mg) did not affect the pharmacokinetics of eitherritonaviror escitalopram.

CYP3A4 And -2C19 Inhibitors

In vitro studies indicated that CYP3A4 and -2C19 are the primary enzymes involved in the metabolism of escitalopram. However, coadministration of escitalopram (20 mg) and ritonavir (600 mg), a potent inhibitor of CYP3A4, did not significantly affect the pharmacokinetics of escitalopram. Because escitalopram is metabolized by multiple enzyme systems, inhibition of a single enzyme may not appreciably decrease escitalopram clearance.

Drugs Metabolized By Cytochrome P4502D6

In vitro studies did not reveal an inhibitory effect of escitalopram on CYP2D6. In addition, steady state levels of racemic citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggesting that coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on escitalopram metabolism. However, there are limited in vivo data suggesting a modest CYP2D6 inhibitory effect for escitalopram, i.e., coadministration of escitalopram (20 mg/day for 21 days) with the tricyclic antidepressantdesipramine(单剂量of 50 mg), a substrate for CYP2D6, resulted in a 40% increase in Cmax and a 100% increase in AUC ofdesipramine. The clinical significance of this finding is unknown. Nevertheless, caution is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6.

Metoprolol

Administration of 20 mg/day Lexapro for 21 days in healthy volunteers resulted in a 50% increase in Cmax and 82% increase in AUC of the beta-adrenergic blockermetoprolol(given in a single dose of 100 mg). Increasedmetoprololplasma levels have been associated with decreased cardioselectivity. Coadministration of Lexapro and metoprolol had no clinically significant effects on官网地址bwinorheartrate.

Electroconvulsive Therapy (ECT)

There are no clinical studies of the combined use ofECTand escitalopram.

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Clinical Trial Data Sources

Pediatrics (6 -17 Years)

Adverse events were collected in 576 pediatric patients (286 Lexapro, 290 placebo) with major depressive disorder in double-blind placebo-controlled studies. Safety and effectiveness of Lexapro in pediatric patients less than 12 years of age has not been established.

Adults

Adverse events information for Lexapro was collected from 715 patients with major depressive disorder who were exposed to escitalopram and from 592 patients who were exposed to placebo in double-blind, placebo-controlled trials. An additional 284 patients with major depressive disorder were newly exposed to escitalopram in open-label trials. The adverse event information for Lexapro in patients withGAD从429例患者暴露于escital收集opram and from 427 patients exposed to placebo in double-blind, placebo-controlled trials.

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 reactions 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 Events Associated With Discontinuation Of Treatment

Major Depressive Disorder

Pediatrics(6 -17 years)

Adverse events were associated with discontinuation of 3.5% of 286 patients receiving Lexapro and 1% of 290 patients receiving placebo. The most common adverse event (incidence at least 1% for Lexapro and greater than placebo) associated with discontinuation wasinsomnia(1% Lexapro, 0% placebo).

Adults

Among the 715depressedpatients who received Lexapro in placebo-controlled trials, 6% discontinued treatment due to an adverse event, as compared to 2% of 592 patients receiving placebo. In two fixed-dose studies, the rate of discontinuation for adverse events in patients receiving 10 mg/day Lexapro was not significantly different from the rate of discontinuation for adverse events in patients receiving placebo. The rate of discontinuation for adverse events in patients assigned to a fixed dose of 20 mg/day Lexapro was 10%, which was significantly different from the rate of discontinuation for adverse events in patients receiving 10 mg/day Lexapro (4%) and placebo (3%). Adverse events that were associated with the discontinuation of at least 1% of patients treated with Lexapro, and for which the rate was at least twice that of placebo, werenausea(2%) and ejaculation disorder (2% of male patients).

Generalized Anxiety Disorder

Adults

Among the 429GADpatients who received Lexapro 10-20 mg/day in placebo-controlled trials, 8% discontinued treatment due to an adverse event, as compared to 4% of 427 patients receiving placebo. Adverse events that were associated with the discontinuation of at least 1% of patients treated with Lexapro, and for which the rate was at least twice the placebo rate, werenausea(2%),insomnia(1%), andfatigue(1%).

Incidence Of Adverse Reactions In Placebo-ControlledClinical Trials

Major Depressive Disorder

Pediatrics (6 -17 years)

The overall profile of adverse reactions in pediatric patients was generally similar to that seen in adult studies, as shown in Table 2. However, the following adverse reactions (excluding those which appear in Table 2 and those for which the coded terms were uninformative or misleading) were reported at an incidence of at least 2% for Lexapro and greater than placebo:back pain,urinary tract infection,vomiting, andnasal congestion.

Adults

The most commonly observed adverse reactions in Lexapro patients (incidence of approximately 5% or greater and approximately twice the incidence in placebo patients) wereinsomnia, ejaculation disorder (primarily ejaculatory delay), nausea,sweatingincreased,fatigue, and somnolence.

Table 2 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred among 715depressedpatients who received Lexapro at doses ranging from 10 to 20 mg/day in placebo-controlled trials. Events included are those occurring in 2% or more of patients treated with Lexapro and for which the incidence in patients treated with Lexapro was greater than the incidence in placebo-treated patients.

TABLE 2: Treatment-Emergent Adverse Reactions observed with a frequency of ≥ 2% and greater than placebo for Major Depressive Disorder

Adverse Reaction	Lexapro (N=715)%	Placebo (N=592) %
Autonomic Nervous System Disorders
Dry Mouth	6%	5%
Sweating Increased	5%	2%
Central & Peripheral Nervous System Disorders
Dizziness	5%	3%
Gastrointestinal Disorders
Nausea	15%	7%
Diarrhea	8%	5%
Constipation	3%	1%
Indigestion	3%	1%
Abdominal Pain	2%	1%
General
Influenza-like Symptoms	5%	4%
Fatigue	5%	2%
Psychiatric Disorders
Insomnia	9%	4%
Somnolence	6%	2%
Appetite Decreased	3%	1%
Libido Decreased	3%	1%
Respiratory System Disorders
Rhinitis	5%	4%
Sinusitis	3%	2%
Urogenital
Ejaculation Disorder1,2	9%	<1%
Impotence2	3%	<1%
Anorgasmia3	2%	<1%
1Primarily ejaculatory delay. 2Denominator used was for males only (N=225 Lexapro; N=188 placebo). 3Denominator used was for females only (N=490 Lexapro; N=404 placebo).

Generalized Anxiety Disorder

Adults

The most commonly observed adverse reactions in Lexapro patients (incidence of approximately 5% or greater and approximately twice the incidence in placebo patients) were nausea, ejaculation disorder (primarily ejaculatory delay),insomnia,fatigue,decreased libido, and anorgasmia.

Table 3 enumerates the incidence, rounded to the nearest percent of treatment-emergent adverse events that occurred among 429 GAD patients who received Lexapro 10 to 20 mg/day in placebo-controlled trials. Events included are those occurring in 2% or more of patients treated with Lexapro and for which the incidence in patients treated with Lexapro was greater than the incidence in placebo-treated patients.

TABLE 3 : Treatment-Emergent Adverse Reactions observed with a frequency of ≥ 2% and greater than placebo forGeneralized Anxiety Disorder

Adverse Reactions	Lexapro (N=429)%	Placebo (N=427)%
Autonomic Nervous System Disorders
Dry Mouth	9%	5%
Sweating Increased	4%	1%
Central & Peripheral Nervous System Disorders
Headache	24%	17%
Paresthesia	2%	1%
Gastrointestinal Disorders
Nausea	18%	8%
Diarrhea	8%	6%
Constipation	5%	4%
Indigestion	3%	2%
Vomiting	3%	1%
Abdominal Pain	2%	1%
Flatulence	2%	1%
Toothache	2%	0%
General
Fatigue	8%	2%
Influenza-like Symptoms	5%	4%
Musculoskeletal System Disorder
Neck/Shoulder Pain	3%	1%
Psychiatric Disorders
Somnolence	13%	7%
Insomnia	12%	6%
Libido Decreased	7%	2%
梦想不正常	3%	2%
Appetite Decreased	3%	1%
Lethargy	3%	1%
Respiratory System Disorders
Yawning	2%	1%
Urogenital
Ejaculation Disorder1,2	14%	2%
Anorgasmia3	6%	<1%
Menstrual Disorder	2%	1%
1Primarily ejaculatory delay. 2Denominator used was for males only (N=182 Lexapro; N=195 placebo). 3Denominator used was for females only (N=247 Lexapro; N=232 placebo).

Dose Dependency Of Adverse Reactions

The potential dose dependency of common adverse reactions (defined as an incidence rate of ≥5% in either the 10 mg or 20 mg Lexapro groups) was examined on the basis of the combined incidence of adverse reactions in two fixed-dose trials. The overall incidence rates of adverse events in 10 mg Lexapro-treated patients (66%) was similar to that of the placebo-treated patients (61%), while the incidence rate in 20 mg/day Lexapro-treated patients was greater (86%). Table 4 shows common adverse reactions that occurred in the 20 mg/day Lexapro group with an incidence that was approximately twice that of the 10 mg/day Lexapro group and approximately twice that of the placebo group.

TABLE 4: Incidence of Common Adverse Reactions in Patients with Major

Adverse Reaction	Placebo (N=311)	10 mg/day Lexapro (N=310)	20 mg/day Lexapro (N=125)
Insomnia	4%	7%	14%
Diarrhea	5%	6%	14%
Dry Mouth	3%	4%	9%
Somnolence	1%	4%	9%
Dizziness	2%	4%	7%
Sweating Increased	<1%	3%	8%
Constipation	1%	3%	6%
Fatigue	2%	2%	6%
Indigestion	1%	2%	6%

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.

TABLE 5: Incidence of Sexual Side Effects in Placebo-Controlled Clinical Trials

Adverse Event	Lexapro	Placebo
	In Males Only	(N=407)	(N=383)
	Ejaculation Disorder (primarily ejaculatory delay)	12%	1%
Libido Decreased	6%	2%
Impotence	2%	<1%
In Females Only	(N=737)	(N=636)
Libido Decreased	3%	1%
Anorgasmia	3%	<1%

There are no adequately designed studies examining sexual dysfunction with escitalopram treatment.

Priapismhas 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

Lexapro and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic官网地址bwin, 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 Lexapro treatment. In addition, a comparison of supine and standing vital sign measures in subjects receiving Lexapro indicated that Lexapro treatment is not associated with orthostatic changes.

Weight Changes

Patients treated with Lexapro in controlled trials did not differ from placebo-treated patients with regard to clinically important change in body weight.

Laboratory Changes

Lexapro and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, hematology, andurinalysisvariables, 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 Lexapro treatment.

ECG Changes

Electrocardiograms from Lexapro (N=625) and placebo (N=527) 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). None of the patients in the Lexapro group had a QTcF interval >500 msec or a prolongation >60 msec compared to 0.2% of patients in the placebo group. The incidence of tachycardic outliers was 0.2% in the Lexapro and the placebo group. The incidence of bradycardic outliers was 0.5% in the Lexapro group and 0.2% in the placebo group.

QTcF interval was evaluated in a randomized, placebo and active (moxifloxacin400 mg) controlled cross-over, escalating multipledose study in 113 healthy subjects. The maximum mean (95% upper confidence bound) difference from placebo arm were 4.5 (6.4) and 10.7 (12.7) msec for 10 mg and supratherapeutic 30 mg escitalopram given once daily, respectively. Based on the established exposure-response relationship, the predicted QTcF change from placebo arm (95% confidence interval) under the Cmax for the dose of 20 mg is 6.6 (7.9) msec. Escitalopram 30 mg given once daily resulted in mean Cmax of 1.7-fold higher than the mean Cmax for the maximum recommended therapeutic dose at steady state (20 mg). The exposure under supratherapeutic 30 mg dose is similar to the steady state concentrations expected in CYP2C19 poor metabolizers following a therapeutic dose of 20 mg.

Other Reactions Observed During The Premarketing Evaluation Of Lexapro

Following is a list of treatment-emergent adverse events, as defined in the introduction to the ADVERSE REACTIONS section, reported by the 1428 patients treated with Lexapro for periods of up to one year in double-blind or open-label clinical trials during its premarketing evaluation. The listing does not include those events already listed in Tables 2 & 3, those events for which a drug cause was remote and at a rate less than 1% or lower than placebo, those events which were so general as to be uninformative, and those events reported only once which did not have a substantial probability of being acutely life threatening. Events are categorized by body system. Events of major clinical importance are described in the Warnings and Precautions section (5).

Cardiovascular -hypertension, palpitation.

Central and Peripheral Nervous System Disorders -light-headed feeling,migraine.

Gastrointestinal Disorders -abdominal cramp,heartburn,gastroenteritis.

General -allergy,chest pain、发热、潮热、painin limb.

Metabolic and Nutritional Disorders -increased weight.

Musculoskeletal System Disorders -arthralgia,myalgiajawstiffness.

Psychiatric Disorders -appetite increased, concentration impaired, irritability.

Reproductive Disorders/Female -menstrual cramps, menstrual disorder.

Respiratory System Disorders -bronchitis,咳嗽,nasal congestion, sinuscongestion,sinus headache.

Skin and Appendages Disorders -rash.

Special Senses -vision blurred,tinnitus.

Urinary System Disorders -urinary frequency,urinary tract infection.

Post-Marketing Experience

Adverse Reactions Reported Subsequent To The Marketing Of Escitalopram

The following additional adverse reactions have been identified from spontaneous reports of escitalopram received worldwide. These adverse reactions have been chosen for inclusion because of a combination of seriousness, frequency of reporting, or potential causal connection to escitalopram and have not been listed elsewhere in labeling. However, because these adverse reactions were 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. These events include:

Blood and Lymphatic System Disorders:anemia, agranulocytis, aplasticanemia, hemolyticanemia, idiopathicthrombocytopeniapurpura, leukopenia,thrombocytopenia.

Cardiac Disorders:atrial fibrillation, bradycardia, cardiac failure,myocardial infarction, tachycardia, torsade de pointes, ventriculararrhythmia, ventricular tachycardia.

Ear andlabyrinthdisorders:vertigo

Endocrine Disorders:糖尿病,hyperprolactinemia,SIADH.

Eye Disorders:angle closureglaucoma,diplopia, mydriasis, visual disturbance.

Gastrointestinal Disorder:dysphagia, gastrointestinal hemorrhage, gastroesophageal reflux,pancreatitis, rectal hemorrhage.

General Disorders and Administration Site Conditions:abnormal gait, asthenia,edema, fall, feeling abnormal, malaise.

Hepatobiliary Disorders:fulminanthepatitis, hepatic failure, hepatic necrosis,hepatitis.

Immune System Disorders:allergic reaction,速发型过敏反应.

Investigations:bilirubinincreased, decreased weight,electrocardiogramQT prolongation, hepatic enzymes increased, hypercholesterolemia, INR increased, prothrombin decreased.

Metabolism andNutrition障碍:hyperglycemia,hypoglycemia,hypokalemia,hyponatremia.

Musculoskeletal and Connective Tissue Disorders:muscle cramp, musclestiffness, muscleweakness,rhabdomyolysis.

Nervous System Disorders:akathisia,amnesia,ataxia, choreoathetosis,cerebrovascular accident,dysarthria,dyskinesia,dystonia, extrapyramidal disorders,grand malseizures(or convulsions), hypoaesthesia, myoclonus, nystagmus,Parkinsonism, restless legs,seizures,syncope,tardive dyskinesia,tremor.

Pregnancy, Puerperium and Perinatal Conditions:spontaneous abortion.

Psychiatric Disorders:acute psychosis,aggression, agitation, anger,anxiety,apathy, completedsuicide, confusion, depersonalization,depression加剧,delirium, delusion, disorientation, feeling unreal,hallucinations(visual and auditory),mood swings, nervousness,nightmare, panic reaction,paranoia, restlessness, self-harm or thoughts of self-harm,suicideattempt,suicidalideation, suicidal tendency.

Renal and Urinary Disorders:acute renal failure,dysuria,urinary retention.

Reproductive System and Breast Disorders:menorrhagia,priapism.

Respiratory, Thoracic and Mediastinal Disorders:dyspnea, epistaxis,pulmonary embolism,pulmonary hypertensionof thenewborn.

Skin and Subcutaneous Tissue Disorders:alopecia,angioedema,dermatitis瘀斑,erythema multiforme,photosensitivityreaction, Stevens Johnson Syndrome, toxic epidermal necrolysis,urticaria.

Vascular Disorders:deep vein thrombosis, flushing, hypertensive crisis,hypotension,orthostatic hypotension,phlebitis, thrombosis.