Approval Date:2006NovemberMarch17Day
Revision Date: 2007November 23Day23
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Paroxetine Hydrochloride Tablets Instructions
Please read the instructions carefully and use under the guidance of your physician
Warning
Suicidal ideation and antidepressants
Results from a short-term clinical trial of depression (MDD) and other psychiatric disorders showed that antidepressants increased suicidality compared with placebo in children, adolescents, and young adults (≤ 24 years of age) patients at risk for suicidal thoughts and committing suicidal behaviors (suicidal ideation). Anyone considering the use of this or other antidepressants in children, adolescents, or young adults (≤ 24 years of age) must weigh their risk against their clinical need. Short-term clinical trials have not shown an increased risk of suicidal ideation with antidepressant use compared with placebo in adults aged >24 years; and in adults aged 65 years and older, the risk of suicidal ideation was reduced with antidepressant use. Depression and certain psychiatric disorders are themselves associated with an increased risk of suicide, and patients of all ages must be closely monitored for worsening clinical symptoms, suicidal ideation, and abnormal changes in behavior after initiation of treatment with antidepressants. Families and caregivers should be advised that they must closely observe and communicate with their physicians. This product is not approved for use in pediatric patients (see [PRECAUTIONS]-Warning, Worsening of Clinical Symptoms and Risk of Suicide, [PRECAUTIONS]-Patient Medication Information, and [Pediatric Dosage]).
[Drug Name]
Generic Name: Paroxetine Hydrochloride Tablets
Trade Name: Xarelto
English Name:Paroxetine Hydrochloride Tablets
Hanyu Pinyin:Yansuan Paluoxiting Pian
[Ingredients]
The active ingredient of this product is paroxetine hydrochloride, whose chemical name is (- )-(3S,4R)-4-(4- fluorophenyl)-3-[[3,4-(methylenedioxy)phenoxy]methyl]]Piperidine hydrochloride hemihydrate.
Chemical structure formula:
Molecular Formula:C19H20FNO3-HCl-1/2H2O
Molecular weight:374.84
[Properties]
This product is an oval, double-sided, raised film-coated tablet with “SEROXAT 20” inscription on one side and a horizontal inscription on the other side. It appears white or off-white after removal of the coating.
[Indications]
This product is used for the treatment of depression, obsessive-compulsive disorder, panic disorder with or without agoraphobia, social phobia/Social Anxiety Disorder.
Continued use of this product after satisfactory treatment may prevent relapse of depression, panic disorder, and obsessive-compulsive disorder.
[Specifications]20mg(withC19H20FNO3count)
[Dosage]
Oral, recommended to be taken daily in the morning in a single dose (with or without food), without chewing.
Adults:
Depression:
General dose is 20mg daily. Take2~3weeks later, depending on the patient’s response, some patients need to increase the dose to 10mg per week50mg and should be followed. medical advice. Dose adjustment interval should be at least one week.
OCD:
The typical dose is 40mg daily at an initial dose of 20mg daily and weekly at10mg in weekly increments. The maximum daily dose can be up to60mg. The interval between dose adjustments is at least one week.
Panic disorder:
General dose is 40 mg dailywith an initial dose of10mgdaily and, depending on the patient’s response, weekly at. span>10mg in weekly increments, depending on the patient’s response, up to a maximum daily dose of50mg per day. The interval between dose adjustments is at least one week.
Social phobia/Social Anxiety Disorder:
General dose is 20 mg daily, and for patients who do not respond to 20mg, the dose may be increased to 20mg per week, depending on the patient’s clinical response. 10mg per week up to a maximum daily dose of50mg per day. The interval between dose adjustments is at least one week.
Like all antidepressants, the dose should be adjusted according to the condition during treatment. Patients should be treated for long enough to consolidate the effects, with maintenance treatment for at least several months after recovery from depression and longer for OCD and panic disorder. Discontinuation is similar to that of other psychiatric medications and should be gradual and not abrupt.
Discontinuation of paroxetine
Like other psychotropic drugs, this product should generally not be discontinued abruptly(see [Precautions] and [Adverse Reactions] sections). The tapered discontinuation regimen used in the clinical trial was to taper at weekly intervals, reducing the daily dose each week by 10 mg and reduce the dose 1 time per week.
Reduced to daily 20mg of the same day dose , the patient continues at that dose for 1 week and then discontinues the drug. If intolerable symptoms occur after dose reduction or discontinuation, consider returning to treatment at the previous dose. The physician can then continue the dose reduction regimen, but at a more gradual pace.
Kidney/hepatic impairment:
Severe renal impairment(Creatinine clearance<30ml/min)or patients with hepatic impairment have higher blood levels after taking this product than healthy individuals. Therefore, the recommended dose is 20 mg daily, and if an increased dose is needed, it should be limited to the lower limit of the dosing range.
[Adverse Reactions]
Some of the adverse reactions listed below may diminish or decrease with longer treatment duration and generally do not lead to discontinuation of therapy. Adverse drug reactions are listed below by system organ classification and incidence. The incidence is defined as very common(≥1/10), common, common (≥1/100,<1/10), occasionally (≥1/ 1,000,<1/100), rare(≥1/10,000, <1/1,000), very rare(<1/10,000), very rare(<1/10,000), including individual reports. The incidence of common and incident events is generally based on the safety of the patient (>8000) population in the paroxetine treatment group in clinical trials Pooled information is used to determine this, which generally refers to an additional increased incidence compared to the placebo group. Rare and very rare events are generally judged on the basis of post-marketing data and refer to the reported rate rather than the true incidence.
Blood and lymphatic system
Even
See: abnormal bleeding, mainly in the skin and mucous membranes,
anemia, leukopenia, lymphadenopathy, purpura;
Ham
See: abnormal erythrocytes, basophilia, prolonged bleeding time, eosinophilia, hypochromic anemia, iron deficiency anemia, leukocytosis, lymphedema, abnormal lymphocytes, lymphocytosis, microcytic anemia, monocytosis, normocytosis anemia, thrombocytosis, and thrombocytopenia.
Immune system
Very rare: severe allergic reactions(() “font-family:Arial”>including tachyphylactic reactions and angioedema).
Endocrine System
Ham
See: diabetes mellitus, goiter, hyperthyroidism, hypothyroidism, thyroiditis;
Very rare: syndrome of abnormal secretion of antidiuretic hormone(SIADH).
Metabolism and Nutrition
Often
See: elevated cholesterol levels, loss of appetite, weight gain;
Even
See: edema, peripheral edema, elevated glutathione transaminase, elevated glutathione transaminase, thirst, weight loss;
Ham
See: elevated alkaline phosphatase, bilirubinemia,
elevated blood urea nitrogen, elevated creatine kinase, dehydration,γ-globulin elevation, gout, hypercalcemia, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperphosphate(ates)emia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, ketosis, elevated lactate dehydrogenase, nonprotein nitrogen(NPN)elevation.
Reported hyponatremia is seen mainly in elderly patients, sometimes due to the syndrome of abnormal secretion of antidiuretic hormone (SIADH)causes.
Psychiatric abnormalities:
Often
See: drowsiness, insomnia, excitement, unusual dreams (including nightmares).
Even
See: blurred consciousness, hallucinations.
Ham
See: Mania.
Nervous system
Often
See: vertigo, tremor, headache, emotional instability;
Even
See: extrapyramidal symptoms,
abnormal thinking, alcoholism, ataxia, dystonia, dyskinesia, euphoria, hostility, hallucinations, hypertonia, hyperalgesia, hypoesthesia, hypokinesia, inability to coordinate, apathy,
enhanced sexual desire, mania, neurosis, paralysis, paranoia;
Ham
See: convulsions, inability to sit still, restless legs syndrome, abnormal gait, motor inability, social aversion, aphasia, choreoathetosis, perioral sensory abnormalities, delirium, delusions, diplopia, drug dependence, dysphonia, fasciculus tremens, grand mal seizures, convulsions, nociceptive hypersensitivity, hysteria bipolar disorder, cerebrospinal meningitis, myelitis, neuralgia, neuropathy, nystagmus, peripheral neuritis, depression, psychotic symptoms, diminished reflexes, enhanced reflexes, xerostomia, squinting neck, dentition, withdrawal syndrome;
Very rare:5-hydroxytryptamine syndrome(symptoms may include euphoria, confusion, hyperhidrosis, hallucinations, hyperreflexia, myoclonus, tremulous tachycardia and tremor).
Some patients report extrapyramidal symptoms, including abnormal orofacial dystonia, and these patients sometimes have an underlying movement disorder or are on psychostimulants.
Eye
Often
See: blurred vision;
Even
see: dilated pupils (see [Precautions]);
Very rare: acute glaucoma.
Cardiovascular system
Often
See: hypertension, tachycardia;
Even
See: sinus tachycardia, postural hypotension, bradycardia, hematoma, hypotension, migraine, upright hypotension, syncope;
Ham
See: angina pectoris, junctional arrhythmia, atrial fibrillation, bundle branch block, cerebral ischemia, cerebrovascular accident, congestive heart failure, heart block, low cardiac output, myocardial infarction, myocardial ischemia, pallor, phlebitis, supraventricular precontraction, thrombophlebitis, thrombus , varicose veins, vascular headache, ventricular preterm contraction.
Respiratory, thoracic and mediastinal
Often
See: Yawning
Even
See: asthma, bronchitis, dyspnea, rhinorrhea, hyperventilation, pneumonia, respiratory influenza;
Ham
See: emphysema, hemoptysis, hiccups, pulmonary fibrosis, pulmonary edema, increased sputum, wheezing and voice changes, pulmonary embolism.
Digestive system
Very common: nausea;
Often
See: constipation, diarrhea, vomiting, dry mouth;
Even
See: nocturnal teething disorder, colitis, dysphagia, belching, gastritis, gastroenteritis, gingivitis, tongue inflammation,
polysalivation, abnormal liver function, rectal bleeding, ulcerative stomatitis;
Ham
See: stomatitis with mouth sores, bloody diarrhea, hyperphagia, pancreatic spasm, gallstone disease, duodenitis, enteritis, esophagitis, fecal impaction, fecal incontinence, bleeding gums, vomiting blood, hepatitis, ileitis, intestinal obstruction, intestinal obstruction, jaundice, black stool syndrome, mouth ulcers, peptic ulcers enlarged salivary glands, salpingitis, gastric ulcer, stomatitis, tongue discoloration, tongue swelling, dental caries;
Very rare: gastrointestinal bleeding.
Hepatobiliary system
Ham
See: Elevated transaminases
Very rare: hepatic events(such as hepatitis, jaundice, liver failure).
Elevated hepatic transaminases have been reported. Post-marketing reports of hepatic events have also been received(e.g., hepatitis, sometimes with jaundice and/or liver failure), and these reports are rare. Discontinuation of paroxetine should be considered if liver function labs remain elevated.
Dermal and subcutaneous tissue
Often
See: sweating, itching;
Even
See: rash, acne, alopecia, contact dermatitis, dry skin, bleeding spots, eczema, herpes simplex, photosensitivity, urticaria;
Ham
See: angioedema, erythema nodosum, erythema multiforme, exfoliative dermatitis, mycosis fungoides, boils, herpes zoster, hirsutism, maculopapular rash, seborrheic dermatitis, skin discoloration, skin hypertrophy, skin ulcers, decreased sweating, and blistering maculopapular rash;
Very rare: severe cutaneous adverse reactions (including erythema multiforme,Stevens-Johnsonsyndrome and toxic epidermal necrolysis), urticaria.
Renal and genitourinary system
Very common: sexual dysfunction;
Even
See: urinary retention, urinary incontinence, amenorrhea, breast pain, cystitis, dysuria, hematuria, menorrhagia, nocturia, polydipsia, pyuria, urgency, vaginitis;
Ham
See: hyperprolactinemia/Overflow, miscarriage, breast atrophy, breast distention, endometriosis, epididymitis, fibrocystic breast disease, kidney stones, kidney pain, leukorrhea, mastitis, irregular uterine bleeding, nephritis, oliguria, tuberculosis, urethritis, tubular urine, uterine cramps, urinary stones, menstrual irregularities (including excessive menstruation, uterine bleeding, and amenorrhea), vaginal bleeding, and vaginal candidiasis.
Systemic and site of administration reactions
Often
See: weakness and weight gain;
Even
See: chills, facial swelling, general weakness, neck pain;
Ham
See: adrenergic drug syndrome, cellulitis, candidiasis, cervical dystonia, pelvic pain, peritonitis, sepsis, and ulcers;
Very rare: peripheral edema.
Myoskeletal system:
Often
See: arthralgia;
Even
See: arthritis, joint disease;
Ham
See: bursitis, myositis, osteoporosis, generalized twitching, tenosynovitis, hand and foot twitching.
Specific sensations:
Often
See: Tinnitus;
Even
See: adaptation abnormalities, conjunctivitis, otalgia, ophthalmoplegia, keratoconjunctivitis, dilated pupils, otitis media;
Ham
See: amblyopia, pupil size discrepancy, blepharitis, cataract, conjunctival edema, corneal ulcer, deafness, ocular proptosis, ocular hemorrhage, glaucoma, auditory hypersensitivity, night blindness, otitis externa, olfactory inversion, photophobia, ptosis, retinal hemorrhage, loss of taste and visual field defects.
Symptoms of paroxetine discontinuation:
Often
See: vertigo, sensory disturbances, sleep disturbances, anxiety, headache.
Even
See: excitement, nausea, tremors, confusion, sweating, diarrhea.
Like many other psychotropic drugs, discontinuation of paroxetine (especially when stopped abruptly) may result in dizziness, sensory disturbances (including abnormal sensation, electric shock sensation and tinnitus ), sleep disturbances (including intense dreams), excitement or anxiety, nausea, headache, tremor, confusion, diarrhea, and sweating. In most patients, these events were mild to moderate in severity and were self-limiting. No group of patients was found to be at higher risk for these symptoms, so it is recommended that paroxetine therapy should be tapered off if no longer needed(see [dosage] and [precautions]).
Adverse events in pediatric clinical studies:
In clinical studies in children, at least 2% of family:Arial”> patients reported the following adverse events at least twice the rate of placebo: emotional instability (including self-harm, suicidal thoughts, suicide attempts, crying and mood swings), hostility, loss of appetite, tremors, sweating, cramping and agitation. Suicidal ideation and suicide attempts were mainly seen in clinical trials of adolescents with major depressive disorder. Hostility is seen mostly in children with OCD, especially in children 12 years of age and younger.
The trial used a tapered dosing regimen (weekly at a daily dose of 10 mg decreasing to a daily dose 10mg and continued to take (discontinue after one week). During taper or at discontinuation, at least 2% of patients reported the following symptoms at least twice the incidence of placebo: mood disturbance, nervousness, vertigo, nausea, and abdominal pain (see [Precautions]).
Some of the content under this column is from [Adverse Reactions] in the U.S. insert for Paroxetine Hydrochloride Tablets. Paroxetine hydrochloride tablets are not approved in China for the treatment of generalized anxiety (GAD) and post-traumatic stress disorder (PTSD).
Adverse reactions associated with treatment discontinuation: in clinical trials worldwide,20%(1199/6145 ) in patients treated with paroxetine hydrochloride tablets for depression and in clinical trials worldwide16.1%(84/522), 11.8%(64/542), 9.4%(44/469), 10.7%(79/735) and =”font-family:Times New Roman”>11.7%(79/676)Patients treated with paroxetine for social anxiety disorder, obsessive-compulsive disorder, panic disorder, generalized anxiety, and posttraumatic stress disorder discontinued treatment due to adverse events. The most frequent (≥ 1%) events associated with treatment discontinuation and considered medication-related (ie, associated with treatment discontinuation and in the paroxetine group incidence is approximately2fold or higher relative to placebo) include events listed as follows: =”font-family:Times New Roman”>
Table1
depressionOCD Panic disorderSocial anxiety disorderGeneralized anxietyPosttraumatic Stress Disorder ParoxetineplaceboParoxetine placeboParoxetineplaceboParoxetinePlacebo ParoxetineplaceboParoxetineplaceboCentral Nervous System Drowsiness2.3% 0.7%- 1.9%0.3%3.4% 0.3%2.0%0.2%2.8%0.6% Insomnia–1.7%0% 1.3%0.3%3.1%3.1%
a. Gender-corrected incidence.
Common Adverse Events:
Depression: The most frequently observed adverse event associated with paroxetine use (incidence in patients treated with paroxetine hydrochloride tablets5%or higher and an incidence of at least 2of the placebo group) associated with paroxetine use. Roman”>2fold, see Table 2) including: fatigue, sweating, nausea, decreased appetite, drowsiness, dizziness, insomnia, tremor, nervousness, ejaculatory disorders, and other male reproductive disorders.
OCD: The most frequently observed adverse events associated with paroxetine use (incidence in patients treated with paroxetine hydrochloride tablets5%or higher and an incidence of at least 2 of the placebo group) associated with the use of paroxetine. span>fold, see Table3) include. Nausea, dry mouth, decreased appetite, constipation, dizziness, drowsiness, tremors, sweating, impotence, and abnormal ejaculation.
Panic disorder: The most frequently observed adverse event associated with paroxetine use (incidence in patients treated with paroxetine hydrochloride tablets5%or higher and an incidence of at least 2fold, see Table 3) include: weakness, sweating, decreased appetite, decreased libido, tremor, abnormal ejaculation, female reproductive disorders, and impotence.
Social anxiety disorder: The most frequently observed adverse event associated with paroxetine use (incidence in patients treated with paroxetine hydrochloride tablets5%or higher and an incidence of at least2 in the placebo group). fold, see Table 3) including : Sweating, nausea, dry mouth, constipation, loss of appetite, drowsiness, tremor, decreased libido, yawning, abnormal ejaculation, female genital disorders, and impotence.
Generalized anxiety: The most frequently observed adverse event associated with paroxetine use (incidence in patients treated with paroxetine hydrochloride tablets) 5% or higher and an incidence of at least 2fold, as shown in Table 4) include: malaise, infection, constipation, decreased appetite, dry mouth, nausea, decreased libido, drowsiness, tremor, sweating, and abnormal ejaculation.
Posttraumatic Stress Disorder: The most frequently observed adverse event associated with paroxetine use (incidence in patients treated with paroxetine hydrochloride tablets5% or higher and an incidence of at least 5% of the placebo group2fold, see Table 4) include: weakness, sweating, nausea, dry mouth, diarrhea, loss of appetite, drowsiness, decreased libido, abnormal ejaculation, female genital disorders, and impotence.
Incidence in Controlled Clinical Trials: Prescribers should be aware that the numbers in the table below cannot be used to predict the incidence of adverse reactions in routine medical practice, and that patient characteristics and other factors during routine medical practice differ from those in clinical trials. Similarly, the cited frequency of occurrence cannot be compared with data obtained in other clinical studies involving different treatments, uses, and investigators. However, the cited data do provide prescribers with some estimate of the relative role that drug and non-drug factors play in the incidence of adverse reactions in the studied population.
Depression: Table2is presented in Table 6weeks of participation in a short-term (6week) placebo-controlled trial span style=”font-family:Times New Roman”>≥1% of adverse events in patients treated with paroxetine in a placebo-controlled trial in which patients received doses ranging from to span>20to50 mg/day. Adverse events were reported using criteria based on the dictionary terminology classification of COSTART.
Table2. Incidence of adverse events in treatment in placebo-controlled clinical trials in depression a
Body SystemPreferred terminologyParoxetine
(n = 421)Placebo
(n = 421)full bodyHeadache18%17% weakness15%6%CardiovascularHeart palpitations3%1% vascular dilation3%1%skinSweating11%2% Rash2%1%GastrointestinalNauseous26%9% Dry mouth18%12% Constipation 14%9% Diarrhea12% 8% Loss of appetite6%2% Gas and bloating4% 2% Oropharyngeal Disordersb2%0%
Percentages after gender correction. Generalized Anxiety and Posttraumatic Stress Disorder:Table4 presents the results of the study after a period of participation. family:Times New Roman”>8week placebo-controlled trials in patients with generalized anxiety receiving paroxetine hydrochloride tablets with a frequency≥2% of adverse events in patients receiving a dose range of10 mg/day to50 mg/day. and frequency in patients with PTSD receiving paroxetine who participated in a placebo-controlled trial lasting 12weeks ≥2% of adverse events, patients received a dose range of20 mg/day to50 mg/day.
table4.incidence of adverse events in treatment in placebo-controlled clinical trials conducted in generalized anxiety and posttraumatic stress disordera
Body SystemsPreferred terminologyGeneralized anxietyPost-traumatic stress disorder Paroxetine
(n = 735)placebo
(n = 529)Paroxetine
(n = 676)placebo
(n = 504)full bodyFrail14%6%12%4%headache17%14%14%–Infection Infection6%3%5%4%Abdominal pain 4%3%Trauma 6%5%5%CardiovascularVascular Dilation 3%1%2%1%skinSweating6% 2%5%1% Gastrointestinal tractNauseous20%5%19% 8%Dry mouth11%5%10%5%Constipation10%2%5%
b4%1%5%1%impotence
b4%3%9%1%a. Table contains events other than those listed below in patients receiving paroxetine for generalized anxiety and posttraumatic stress disorder Events with an incidence of at least 2% (the incidence of the following events in patients receiving placebo ≥ when receiving paroxetine): [generalized anxiety] : abdominal pain, back pain, trauma, indigestion, myalgia and pharyngitis. [Post-traumatic stress disorder]: back pain, headache, anxiety, depression, nervousness, respiratory disorders, pharyngitis and sinusitis.
b. Incidence after gender correction. Dose dependence of adverse events: Comparing doses during depression treatment for10,20,30and40 mg/day, certain adverse events more commonly associated with paroxetine hydrochloride tablets showed showed significant dose dependence, as shown in Table 5:
Table5. Incidence of adverse events in treatment in dose-comparison trials for depressiona
Body System/Preferred TerminologyPlacebo Paroxetine n=5110 mg20 mg30 mg40 mgn=102n=104n=101n=102Body
Weakness0.0% 2.9%10.6%13.9%12.7%skin
Sweating2.0% 1.0%6.7%8.9%11.8%Gastrointestinal tract
Constipation 5.9%4.9%7.7%9.9%12.7%Loss of appetite 2.0%2.0%5.8%5.8%4.0%4.9%Diarrhea 7.8%9.8%19.2%7.9%14.7%Dry mouth2.0%10.8%18.3%15.8%15.8%15.8%20.6%Nauseous 13.7% 14.7%26.9%34.7% 36.3%Nervous System
Anxiety 0.0%2.0%5.8%5.9%5.9%Dizziness 3.9%6.9%6.7%6.7%8.9%12.7%Nervous and uncomfortable Nervous and uncomfortable0.0%5.9%5.8%4.0%2.9%Feeling abnormal0.0% 2.9%1.0%5.0%5.9%drowsiness7.8%12.7%18.3% 20.8%21.6% Tremor0.0% 0.0%7.7%7.9% 14.7%Special Feeling
Blurred vision2.0% 2.9%2.9%2.0%7.8%Genitourinary System
Ejaculatory abnormalities 0.0%5.8%6.5%10.6%13.0%impotence 0.0%1.9%4.3%4.3%6.4%1.9%Male Genital Diseases0.0% 3.8%8.7%6.4% 3.7%a. Include adverse events that meet the following rules included in the table above: an incidence of at least 5% in one of the paroxetine treatment groups and an incidence of ≥ in at least one of the paroxetine treatment groups 2 times in the placebo-treated group. In a study comparing paroxetine hydrochloride tablets in the treatment of obsessive-compulsive disorder20, 40and60 mg versus placebo in fixed-dose studies, there was no significant association. No new adverse events were observed in the paroxetine60 mgdose group relative to any other treatment group.
In a study comparing paroxetine during treatment of panic disorder10 “font-family:Arial”>,20and40 mg versus placebo in fixed-dose studies, there was no significant association between adverse events and the dose of paroxetine that patients were assigned, except for malaise, oral dryness, decreased libido, tremor, and abnormal ejaculation , however. In the flexible dose study, no new adverse events were observed in the paroxetine60 mg dose group relative to any other treatment group.
In a study comparing paroxetine hydrochloride tablets during the treatment of social anxiety disorder 20, 40and60 mg versus placebo in fixed-dose studies, there was no significant association between most adverse events and the dose of paroxetine to which patients were assigned.
In a study comparing paroxetine hydrochloride tablets during treatment of generalized anxiety 20and40 mg versus placebo in a fixed-dose study, except There was no significant association between most adverse events and the dose of paroxetine to which patients were assigned, except for malaise, constipation, and abnormal ejaculation.
In a study comparing paroxetine hydrochloride tablets during the treatment of posttraumatic stress disorder 20and40 mg versus placebo in a fixed-dose study, except for There was no significant association between most adverse events and the dose of paroxetine to which patients were assigned, except for impotence and abnormal ejaculation.
Adjustments for specific adverse events: 4to6weeks of treatment During this period, there was some evidence that continued treatment resulted in changes in some adverse events (e.g., nausea and dizziness), but others occurred to a lesser extent (e.g., dry mouth, drowsiness, and malaise).
Use selective5-hydroxytryptamine reuptake inhibitors: Although the changes in libido, sexual performance, and sexual satisfaction that typically occur are manifestations of psychiatric disorders, they may also be the result of pharmacotherapy. Of particular note is some evidence that selective5-hydroxytryptamine reuptake inhibitors can cause these adverse sexual experiences.
It is difficult to reliably estimate the incidence and severity of adverse events involving sexual desire, sexual performance, and sexual satisfaction, perhaps in part because patients and physicians are reluctant to discuss these aspects. Accordingly, the estimates of the incidence of adverse sexual experiences and sexual performance cited in product labeling likely underestimate the actual incidence of these events.
In cases involving more than3200patients in placebo-controlled clinical trials, the range of reported rates of sexual adverse reactions in male and female patients with depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety, and posttraumatic stress disorder are shown in Table6as listed in
Table6. 6. span>Incidence of neutral adverse events in controlled clinical trials
ParoxetinePlacebon(Male)14461042Sexual desire Decreased sex drive6-15%0-5%Ejaculatory disorders13-28%0-2%impotence2-9%0-3%n(Female)18221340Loss of libido0-9%0-2%Orgasmic Disorder2-9%0-1%There are no adequate and well-controlled studies testing the effects on sexual dysfunction in paroxetine treatment.
Paroxetine was associated with multiple cases of abnormal penile erection. In cases where the outcome was known, patients recovered with no sequelae.
Although it is difficult to know with selective5- family:Arial”>the exact risk of sexual dysfunction associated with the use of serotonin reuptake inhibitors, physicians should still routinely ask about these adverse effects whenever possible.
Weight and Vital Sign Changes: Adverse events of significant weight loss may occur in some patients receiving paroxetine. treatment. However, on average, patient weight loss was minimal (approximately 1pound) and the change between placebo and active control groups was smaller than in the control trial. No significant changes in vital signs (systolic and diastolic blood pressure, pulse, and temperature) were observed in patients treated with paroxetine in the control clinical trial.
Electrocardiographic changes: in paroxetine treated patients in controlled clinical trials span>682patients and those receiving placeboanalysis of the electrocardiograms of 415 patients showed that no clinically significant changes in the electrocardiogram were observed in any of the treatment groups.
Liver Function Tests: In placebo-controlled clinical trials, patients with abnormal liver function receiving paroxetine did not demonstrate a higher risk relative to the placebo group. Of particular note, there was no difference in the percentage of patients with significant abnormalities when comparing paroxetine to the placebo group for alkaline phosphatase, ghrelin, glutamic aminotransferase, and bilirubin.
Hallucinations: In the combined clinical trial of the immediate-release formulation of paroxetine hydrochloride, patients receiving the drug of 22 cases (total9089) patients and those receiving placebo4 family:Arial”> cases (total3187) hallucinations were observed in patients.
Postmarketing reports: Spontaneous reports of adverse events have been received from patients taking paroxetine since the drug’s launch, and those not listed above,adverse events that may not be causally related to the drug include: acute pancreatitis, elevated liver function assays (the most serious cases were death due to hepatic necrosis and significant transaminases associated with severe liver dysfunction (the most severe cases were death due to hepatic necrosis and significant elevation of transaminases associated with severe liver dysfunction), Green-Barre syndrome,Stevens-Johnson syndrome, toxic epidermolysis bullosa, abnormal penile erection, abnormal antidiuretic hormone secretion syndrome, symptoms of prolactinemia, and overflow; extrapyramidal symptoms include inability to sit still, motor extrapyramidal symptoms include sedentary inability, bradykinesia, cogwheel ankylosis, dystonia, hypertonia, actinic nerve crisis associated with methylphenidate combination; tremors and clenching of teeth; persistent epilepsy, acute renal failure, pulmonary hypertension, allergic alveolitis, allergic reactions, eclampsia, laryngospasm, optic neuritis, porphyria, ventricular fibrillation, ventricular tachycardia (including tip-twist ventricular tachycardia), thrombocytopenia, hemolytic anemia, adverse events associated with hematopoietic impairment (including aplastic anemia, pancytopenia, bone marrow dysplasia, and granulocyte deficiency), and vasculitis syndromes (e.g., allergic purpura), and preterm birth. After 4 weeks of concomitant paroxetine and phenytoin, the receipt of family:Times New Roman”> 1 case of elevated phenytoin blood levels was reported. There were also 1 case of severe hypotension after the addition of paroxetine to long-term treatment with metoprolol reported.
[Contraindicated]
[Contraindicated in persons with known hypersensitivity to this product and its excipients.
This product should not be used in combination with monoamine oxidase inhibitors (including the antibiotics linezolid, a reversible, nonselective monoamine oxidase inhibitor, and methylene blue (hypomethylene blue)) or within two weeks of the end of monoamine oxidase inhibitor therapy. Similarly, monoamine oxidase inhibitors should not be used within two weeks of the end of treatment with this product(See [Drug Interactions] for details. ).
This product should not be used in combination with methiodiazine. Because of the combination with other inhibitors of hepatic cytochrome P450 isozymes CYP450 2D6 like the drug, this product can cause elevated blood levels of methiodiazine(see [Drug Interactions]). Methiodiazide can cause prolonged QT intervals with severe ventricular arrhythmias, which in severe cases can lead to tip-twisting ventricular tachycardia and Sudden death.
This product should not be used with pimozide (pimozide) in combination with pimozide.
(see [Drug Interactions]).
[Precautions]
Warning
Worsening of clinical symptoms and risk of suicide:
Adult and pediatric patients with depression, with or without antidepressants, are at risk for worsening of depression and for suicidal ideation and suicidal behavior and abnormal changes in behavior, which persist until the onset of until such time as significant remission occurs. Depression and certain psychiatric disorders are known to be associated with suicide risk, and these disorders themselves are the strongest predictors of suicide. However, there are long-standing concerns that antidepressants may play a role in inducing worsening of depressive symptoms and the development of suicidal ideation and behavior early in the treatment of some patients. A pooled analysis of short-term placebo-controlled studies of antidepressants (selective5-hydroxytryptamine reuptake inhibitors and others) showed that in children, adolescents, and adults with depression and other psychiatric disorders in children, adolescents, and young adults (18-24years) with depression and other psychiatric disorders, antidepressants compared with placebo increased the risk of suicidal ideation and behaviors at risk. However, short-term clinical trials did not show an increased risk of suicidal ideation and behavior with antidepressants compared with placebo in adults older than 24 years of age; in adults older than years of age, antidepressant use increased the risk of suicidal risk of suicidal ideation and behavior; in adults aged 65years and older, the risk of suicidal ideation and behavior was reduced with antidepressant use.
Placebo-controlled trials in children and adolescents with depression, obsessive-compulsive disorder, or other psychiatric disorders (total) 24 short-term clinical trials,9 antidepressants in more than 4400 patients) and in adult patients with depression or other psychiatric disorders (a total of placebo-controlled trials (a total of 295short-term clinical trials) and in adult patients with depression or other psychiatric disorders (a total of [median duration of2months], 11 antidepressants, more than 77,000 patients), the risk of suicidal ideation and behavior varies widely across medications, but most medication studies show a trend toward increased risk of suicidal ideation and behavior in younger patients. The absolute risk of suicidal ideation and behavior varied across indications, with the highest absolute risk in depression. Although the absolute risk varied across indications (drug versus placebo), the risk was relatively stable across age groups for different indications. Table 7provides the difference in risk (per1000 cases of difference in risk of suicidal ideation and behavior from drug and placebo treatment).
Table7
Age rangeper1000 Number of cases of difference in risk of suicidal ideation and behavior from drug and placebo treatment among patients Drug compared to placebo increased cases<18Added14Examples18-24increase5examples drug compared to placebo for reduction in cases25-64Reduction1Example≥65Reduce6ExamplesNo suicides in pediatric clinical trials. There were suicidal events in adult clinical trials, but they did not occur in sufficient numbers to draw conclusions about the effect of the drug in suicide.
It is unknown whether the risk of suicidal ideation and behavior continues over the course of long-term medication use (e.g., after several months). However, evidence from placebo-controlled maintenance treatment clinical trials in adults with depression strongly suggests that the use of antidepressants delays the relapse of depression.
Regardless of the indication for treatment, all patients treated with antidepressants should be closely observed and monitored for worsening clinical symptoms, suicidal ideation and behavior, and abnormal changes in behavior. This is especially true during the initial months of drug treatment and when increasing or decreasing the dose.
The following symptoms may occur when treating adult and pediatric patients with depression, other psychotic or non-psychotic disorders with antidepressants: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggression, impulsivity, sedentary inability (psychomotor agitation), and hypomania and mania. Although a causal relationship between the presence of these symptoms and the worsening of depression and/ or the development of suicidal ideation and behavior has not been established, it is noted that the presence of these symptoms may be a precursor to the development of suicidal ideation and behavior.
When a patient’s depressive symptoms continue to worsen, suicidal ideation and behaviors occur, or symptoms occur that may be precursors to worsening depressive symptoms or suicidal ideation and behaviors, treatment plan adjustments including discontinuation of medication should be carefully considered. This is especially true if these symptoms are severe, emergent, or inconsistent with the patient’s current symptoms.
If the decision is made to discontinue treatment, the dose should be tapered as soon as possible, but be aware that abrupt discontinuation may cause some symptoms (see [Precautions] and [Dosage]).
When treating pediatric patients with depression or other psychotic or non-psychotic disorders with antidepressants, families and caregivers should be reminded of the need to monitor the patient for agitation, irritability, abnormal changes in behavior, other symptoms mentioned above, and the development of suicidal thoughts and symptoms. and suicidal ideation and behavior, and to report these symptoms to a health care professional as soon as they occur. Family members and caregivers should monitor the patient daily for these symptoms. When using this product, the prescription should start with the smallest amount and be accompanied by good patient management to reduce the risk of overdose.
Screening of patients with bipolar disorder:
Depressive episodes may be the initial manifestation of bipolar disorder. It is generally believed (although not clarified by controlled trials) that treatment of such episodes with antidepressants alone may increase mixed/manic episode is possible. It is unclear whether the symptoms mentioned above imply that such a shift may occur. However, patients with depressive symptoms should be adequately screened for risk of bipolar disorder before initiating treatment with antidepressants; this screening should include a detailed psychiatric history including a family history of suicide and a family history of bipolar disorder and depression. This product is not approved for the treatment of bipolar disorder.
5-Serotonin syndrome
Similar to other5-hydroxytryptaminergic drugs, treatment with paroxetine may occurwith 5-hydroxytryptamine syndrome (a potentially life-threatening condition), especially when combined with other drugs that may act on the 5-serotonin transmitter system (e.g., tretinoin, Selective5-hydroxytryptamine reuptake inhibitors, norepinephrine reuptake inhibitors, lithium salts, sibutramine, amphetamines, St. John’s wort[Kineole extract[], fentanyl and its analogs, tramadol, methadone, tapentadol, pethidine, methadone, pentazocine, tricyclic antidepressants, tryptophan, and buspirone), with impairment5-hydroxytryptamine metabolism when combined with drugs that impairMAOIsof methylene blue), in combination with5-hydroxytryptamine precursor substances (e.g., tryptophan supplements), with antipsychotics or with other dopamine antagonists.
5-Serotonin syndrome may include altered mental status (e.g., agitation, hallucinations, delirium, coma), autonomic instability (e.g., tachycardia, blood pressure instability, hypothermia, sweating, flushing, and dizziness), neuromuscular disorders (e.g., tremor, tonicity, myoclonus, hyperreflexia, movement disorders), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The most severe5-hydroxytryptamine syndrome is similar to the manifestations of the nerve blocker malignant syndrome and includes hyperthermia, muscle tonicity, autonomic instability Stability may be accompanied by rapid fluctuations in vital signs, and altered mental status.
Prohibit the use of this product withMAOIs. family:Arial”>in combination. Patients being treated with linezolid or intravenous methylene blue, etc MAOIs should also not be treated with paroxetine. The route of administration of methylene blue in all reports was 1 mg/kg toto 8 mg/kg dose range for intravenous administration. No other routes (e.g., oral tablets or local tissue injections) or lower doses of methylene blue were reported to be given. In some cases, patients taking paroxetine may have to receive treatment with linezolid or intravenous methylene blue as MAOIs. Paroxetine should be discontinued before starting MAOIs therapy.
If clinically justified, combine paroxetine with some selective5-hydroxytryptamine reuptake inhibitor, norepinephrine reuptake inhibitor, or other5-5-hydroxytryptaminergic drugs (e.g., traptans, tricyclic antidepressants, mirtazapine, fentanyl, lithium salts, tramadol, buspirone, tryptophan, and St. John’s wort[[Kinense plant extract]), it is recommended to closely Observe the patient, especially at the beginning of treatment and at increasing doses.
The combination of paroxetine and5-is not recommended. family:Arial”>hydroxytryptamine precursor substances (e.g., tryptophan supplements).
When these events occur, paroxetine and any combination of5-hydroxytryptaminergic drugs and start symptomatic supportive therapy.
Angular glaucoma
In patients with narrowed atrial angles in the anatomy who have not undergone definitive iridectomy, pupil dilation that occurs with multiple antidepressants (including paroxetine) may cause glaucoma episodes due to atrial angle closure.
Possible interaction with methiodiazine: An in vivo trial showed that inhibition of CYP2D6 drugs (e.g., paroxetine) can elevate plasma levels of methiodiazide, and therefore the combination of paroxetine and methiodiazide is not recommended (see [Contraindications] and [Precautions]). Methiodiazide can cause prolongation of the QT interval with severe ventricular arrhythmias, which in severe cases can lead to tip-twisting ventricular tachycardia and Sudden death.
General information:
Bipolar/Mild mania: During the premarketing trial, mild mania or hypomania occurred in approximately1.0%1.0% of monophasic depressed patients treated with paroxetine hydrochloride tablets, while hypomania or mania occurred in approximately 1.1%of patients receiving active control therapy and0.3%among monophasic depressed patients treated with placebo. In a subgroup of patients classified as having bipolar disorder, the incidence of mania in the paroxetine hydrochloride tablet treatment group was 2.2%, whereas the combined active -control group had an incidence of 11.6%. As with all other medications that are effective in the treatment of depression, paroxetine hydrochloride tablets should be used with caution in patients with a history of mania.
Seizures: In pre-marketing trials, seizures occurred in0.1%of patients treated with paroxetine hydrochloride tablets, an incidence similar to that associated with other drugs that are effective in the treatment of depression. Paroxetine hydrochloride tablets should be used with caution in patients with a history of seizures. Paroxetine hydrochloride tablets should be discontinued in any patient who experiences seizures.
Discontinuation of Paroxetine Hydrochloride Tablets Treatment: Recent clinical studies supporting the use of Paroxetine Hydrochloride Tablets for multiple indications for which approval has been granted have used a gradual dose reduction regimen rather than immediate discontinuation of therapy. The dose reductions used in clinical trials for generalized anxiety and posttraumatic stress disorder used a weekly tapering of the daily dose by 10 mg/day regimen. When the daily dose reaches20 mg/day, the patient is treated before discontinuing1week before discontinuing treatment.
The incidence of the following adverse events in patients treated with paroxetine hydrochloride tablets after use of this regimen in the study was≥2% and were at least1 higher than the incidence in the placebo group style=”font-family:Arial”>fold: abnormal dreams, abnormal sensations, and dizziness. In most patients, these events are mild to moderate in severity and are self-limiting, requiring no medical intervention.
Paroxetine hydrochloride tablets and other selective5-hydroxytryptamine reuptake inhibitors and norepinephrine reuptake inhibitors during the marketing period, a number of adverse events have been reported spontaneously after discontinuation of these drugs (especially after abrupt discontinuation), including: agitation, irritability, agitation, dizziness, sensory disturbances (e.g., electric shock-like sensory disturbances and tinnitus), anxiety, confusion, headache, drowsiness , mood lability, insomnia, and mild mania. Although most of these events are self-limiting, severe discontinuation symptoms have been reported.
Patients should be monitored for these symptoms when discontinuing treatment with paroxetine hydrochloride tablets. Whenever possible, a gradual dose reduction is recommended rather than an abrupt cessation of dosing. If symptoms of intolerance occur after a dose reduction or cessation of treatment, it may be necessary to consider continuing to give the previously prescribed dose. Subsequently, the physician may continue to lower the dose at a more gradual rate (see [DOSAGE]).
See [Pediatric Dosage] for adverse events reported after discontinuation of paroxetine hydrochloride tablet therapy in pediatric patients.
Tamoxifen:
Several clinical studies have shown that in breast cancer recurrence/mortality risk due to paroxetine’s effect onCYP2D6is irreversibly inhibited (see [Drug Interactions]), so its efficacy is reduced in combination with paroxetine. This risk may increase with longer duration of combined use. However, this risk has not been confirmed in other studies. It has not been determined whether co-administration of paroxetine and tamoxifen has a significant negative effect on the efficacy of tamoxifen. One study suggests that the risk may increase with longer duration of combination therapy. When tamoxifen is used to combat breast cancer, prescribers should consider alternatives with little or no inhibition of CYP2D6 antidepressants.
Sedation cannot:
Use this product or other selective5-hydroxytryptamine reuptake inhibitors are associated with the development of an inability to sit still, characterized by restless internal feelings and psychomotor arousal, such as an inability to sit still or stand quietly, often due to self-conscious distress. This is most likely to occur within the first few weeks of treatment.
Hyponatremia: Selective including paroxetine Roman”>5-hydroxytryptamine reuptake inhibitor and norepinephrine reuptake inhibitor therapy may lead to hyponatremia. In many cases, hyponatremia is the result of the syndrome of abnormal secretion of antidiuretic hormone (SIADH). Cases of serum sodium levels below 110 mmol/L have been seen. Elderly patients treated with selective5-hydroxytryptamine reuptake inhibitors and norepinephrine reuptake inhibitors are at risk for hyponatremia may be higher. In addition, the risk of hyponatremia may be higher in patients taking diuretics or in patients who develop volume deficits (see [Geriatric Use]). Discontinuation of this product should be considered in patients presenting with symptomatic hyponatremia and appropriate medical intervention should be given. Signs and symptoms of hyponatremia include headache, poor concentration, memory impairment, confusion, weakness, unsteadiness, and possible falls. In severe or acute cases, signs and symptoms also include hallucinations, syncope, seizures, coma, respiratory arrest, and death.
Abnormal bleeding: Selective5-hydroxytryptamine reuptake inhibitors and norepinephrine reuptake inhibitors may increase the risk of bleeding events. Combined use of aspirin, NSAIDs, warfarin, and other anticoagulants may increase this risk. Case reports and epidemiologic studies (case-control and cohort designs) have demonstrated that drugs that can interfere with 5-hydroxytryptamine reuptake are associated with gastrointestinal bleeding events are associated. The range of bleeding events associated with selective5-hydroxytryptamine reuptake inhibitors and norepinephrine reuptake inhibitors is broad and includes petechiae , hematomas, epistaxis and petechiae, and life-threatening bleeding events. Patients should be especially cautious about the bleeding risks associated with the combination of paroxetine and NSAIDs, aspirin, or other drugs that affect anticoagulation.
Fractures: regarding certain antidepressants, including selective5-Epidemiological studies of fracture risk following exposure to serotonin reuptake inhibitors have reported an association between antidepressant treatment and fracture. There are many reasons for this observation, but it is unclear to what extent fracture risk is directly related to selective5-hydroxytryptamine reuptake inhibitor Treatment is directly related. The presence of unexplained bone pain, punctate tenderness, swelling, or bruising in patients treated with paroxetine should be considered for the possibility of pathologic fracture, that is, a fracture caused by very minor trauma in patients with reduced bone density.
Use in Patients With Concomitant Disease: There is limited clinical experience regarding the use of paroxetine hydrochloride tablets in patients with specific concomitant systemic disease. Caution is advised in the use of paroxetine hydrochloride tablets in patients with diseases or conditions that may affect metabolic or hemodynamic responses.
with other selective5-As with serotonin reuptake inhibitors, paroxetine hydrochloride tablets have rarely been reported with pupillary dilation in pre-marketing studies. Several cases of acute angle-closure glaucoma associated with paroxetine treatment have been reported in the literature. Because pupil dilation can lead to acute atrial angle closure in patients with narrow-angle glaucoma, caution should be exercised when prescribing paroxetine hydrochloride tablets to patients with narrow-angle glaucoma.
Paroxetine hydrochloride tablets have not been evaluated or used with experience in patients with a recent history of myocardial infarction or unstable heart disease. These patients were not enrolled in clinical studies in pre-marketing trials of the product. However, in a double-blind, placebo-controlled trial, electrocardiographic evaluation of 682 patients treated with paroxetine hydrochloride tablets demonstrated that paroxetine hydrochloride Paroxetine tablets were not associated with significant electrocardiographic abnormalities. Similarly, this product did not cause any clinically important changes in heart rate or blood pressure.
Severely impaired renal function (creatinine clearance< 30 ml/min) or in patients with severely impaired hepatic function, blood levels of paroxetine are elevated. Therefore, in these patients, a lower starting dose should be used (see [DOSAGE]).
Patient Reference: Paroxetine hydrochloride tablets should not be chewed or crushed and should be swallowed whole.
Patients should be warned about concomitant use of paroxetine hydrochloride tablets with trimethoprim, tramadol, or other5-serotonergic drugs when5-serotonin syndrome Risk.
Patients should be informed that administration of paroxetine hydrochloride tablets may cause mild pupillary dilation, which may lead to angle-closure glaucoma in susceptible individuals. Most pre-existing glaucoma is open-angle glaucoma, as closed-angle glaucoma can be completely treated with iridotomy after diagnosis. Open-angle glaucoma is not a risk factor for closed-angle glaucoma. Patients who are diagnosed as susceptible to closed-angle glaucoma may undergo prophylactic surgery (e.g., iridotomy).
The prescriber or other healthcare professional should inform the patient, the patient’s family, and the patient’s caregiver about the benefits and risks associated with treatment with paroxetine hydrochloride tablets and should counsel the patient about the appropriate use of paroxetine hydrochloride tablets. The prescribing physician or healthcare professional should guide the patient, the patient’s family, and the patient’s caregiver through the medication guide and assist them in understanding its contents. Patients should have the opportunity to discuss the content of the medication guide and have access to the answers to their questions.
Patients should be informed of the problems listed below and should be asked to inform their prescriber if they develop these conditions while taking paroxetine hydrochloride tablets.
Clinical deterioration and risk of suicide: Patients, their families, and their caregivers should be encouraged to pay special attention to patients, especially early in antidepressant therapy and when doses are being adjusted up or down. Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggression, impulsivity, inability to sit still (psychomotor agitation), mild mania, hypomania, other abnormal behavioral changes, worsening depression, and suicidal ideation. Because changes in the patient may occur suddenly, the patient’s family as well as caregivers should watch for these symptoms on a daily basis. These symptoms should be especially noted and reported to the patient’s prescribing physician or healthcare professional if they are severe, appear suddenly, or are not part of the patient’s pre-existing symptoms. These symptoms may be associated with elevated risk for suicidal ideation and behavior, requiring very close monitoring and possibly a change in medication.
Medications that can interfere with hemostasis (eg, NSAIDs, aspirin, warfarin): Patients should be especially cautious with the combination of paroxetine and NSAIDs, aspirin, or other combination with paroxetine and NSAIDs, aspirin, or other drugs that affect anticoagulant effects, because the combination of psychoactive drugs that interfere with 5-hydroxytryptamine reuptake with these drugs is associated with an increased risk of bleeding elevated risk.
Interference with cognition and motor skills: Any active psychotropic drug may impair judgment, thinking, or motor skills. Although controlled clinical studies have shown that paroxetine hydrochloride tablets do not impair psychomotor performance, patients should exercise special caution when operating hazardous machinery, including driving, until they are reasonably certain that treatment with paroxetine hydrochloride tablets will not interfere with their ability to engage in these activities.
Completion of the treatment course: Although patients were treated with paroxetine hydrochloride tablets for 1to4week may feel improvement, but they should still be advised to continue treatment as directed.
Combined Medications: Patients should be advised to inform their physician if they are taking or plan to take any prescription or over-the-counter medications due to possible drug interactions.
Alcohol: Although studies have demonstrated that paroxetine hydrochloride tablets do not increase alcohol-induced impairment of mental and motor skills, patients should still be advised to avoid ingesting alcohol.
[For pregnant and lactating women]
Fertility: Some clinical trials have shown that SSRIs (including paroxetine) may affect sperm quality. Such effects appear to be reversible after treatment discontinuation. Changes in sperm quality may affect fertility in some men.
Pregnancy and lactation: Animal studies have shown that paroxetine is not teratogenic and has no selective embryotoxic effects. Recent epidemiological studies of pregnancy outcomes following first-trimester exposure to antidepressants have reported an increased risk of congenital malformations associated with paroxetine use, particularly in the cardiovascular setting (e.g., atrial septal defect). This data suggests that the risk of cardiovascular defects in infants whose mothers were exposed to paroxetine is approximately 1/50, whereas the expected risk in the general population is approximately 1/100, while the expected risk for the general population is about 1/100.
For women who are pregnant or planning to become pregnant, prescribers should only use paroxetine if the potential benefit outweighs the potential risk, otherwise alternative treatment options are needed. If a pregnant woman needs to discontinue paroxetine, the prescriber should see [Dosage] – Discontinuation of Paroxetine and [Precautions] – Symptoms of Discontinuation of Paroxetine Therapy in Adults.
Although a causal relationship between preterm birth and drug therapy has not been clearly established, there has been exposure to paroxetine or other selective5-preterm births have been reported in pregnant women exposed to paroxetine or other selectivehydroxytryptamine reuptake inhibitors.
If the mother continues to use paroxetine into late gestation, the newborn should be observed because late second trimester exposure to paroxetine or other complications have been reported in neonates exposed to SSRIs . However, a causal relationship with drug therapy has not been demonstrated. Reported clinical findings include: respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremor, hypersensitivity, irritability, lethargy, frequent crying, and lethargy. In some cases, the reported symptoms have been described as neonatal withdrawal symptoms. In most cases, these complications were reported to occur immediately or shortly after delivery (<24 hours).
Epidemiological studies have shown that the use of selective 5-HT during pregnancy and especially during the second trimester reuptake inhibitors, including paroxetine, increase the risk of persistent pulmonary hypertension in the newborn. The increased risk has been reported to be higher in the general population (rate per 5-HT reuptake inhibitors) in those who have used selectivereuptake inhibitors in late pregnancy (rate per). 1000 women with 1-2 2 person)4 toto family:Times New Roman”> 5 times more.
Small amounts of paroxetine are excreted via breast milk.
In published studies, serum concentrations were not detectable in breastfed infants (<2 ng/ml)or very low(<4 ng/ml). There were no signs of drug effects in these infants. Nonetheless, paroxetine should not be used during breastfeeding unless there is evidence that the expected benefit to the mother outweighs the possible risk to the infant.
[Pediatric Use]
The safety and efficacy of the drug in pediatric and adolescent patients under the age of 18has not been established.
[Geriatric Use]
Selective5-including paroxetine family:Arial”>hydroxytryptamine reuptake inhibitors and norepinephrine reuptake inhibitors, are associated with clinically significant hyponatremia in older patients, with a higher risk of this adverse event in older patients (see [caution] -hyponatremia).
In pre-market paroxetine clinical trials worldwide,17%patients treated with paroxetine (approximately700 cases) of age 65 or65 years of age or older. Pharmacokinetic studies have shown that paroxetine clearance is decreased in the elderly population. Therefore, a lower starting dose is recommended for elderly patients. However, there was no overall difference in adverse events between older and younger patients, and efficacy was comparable between younger and older patients (see [DOSAGE]).
[Drug Interactions]
Tryptophan: with other5-hydroxytryptamine reuptake inhibitors, interactions between paroxetine and tryptophan may occur when co-administered. When tryptophan was given to patients who were taking paroxetine hydrochloride tablets, the main adverse events reported included headache, nausea, sweating, and dizziness. Therefore, co-administration of paroxetine hydrochloride tablets with tryptophan is not recommended (see [Precautions]-5hydroxytryptophan syndrome).
Monoamine oxidase inhibitors: See [Contraindications] and [Precautions].
Perhexiline: In a controlled study in healthy subjects, paroxetine hydrochloride tablets were dosed up to a daily60 mg followed by coadministration of a single dose of2 mgafter permethrin, the AUCof permethrin relative to permethrin list drug therapy family:Arial”>was elevated on average151%,Cmaxaverage elevation62%. PerphenazineAUCandCmax elevation by paroxetine’sCYP2D6inhibitory effect. Because of the narrow therapeutic index of permethrin and its known prolongation of the QTinterval, the combination of permethrin with paroxetine hydrochloride tablets is prohibited (see [Contraindications]).
5-Serotonergic drugs: based on norepinephrine reuptake inhibitors including paroxetine hydrochloride and selective5-serotonin reuptake inhibitor mechanism of action and possible5-serotonin syndrome, it is recommended that the combination of Paroxetine tablets with other drugs that may affect the 5-serotonergic neurotransmitter system (e.g., tritans, lithium, fentanyl, tramadol, amphetamines or St. John’s Wort[Goldenrod extract]) should be used with particular caution (see [Precautions]5-serotonin syndrome).
Concomitant use of paroxetine hydrochloride tablets with MAOI(including linezolid and intravenous methylene blue) (see [Contraindications]). The combination of paroxetine hydrochloride tablets with other selective5-hydroxytryptamine reuptake inhibitors, norepinephrine reuptake inhibitors, or tryptophan is not recommended. Use.
Thioridazine: See [Contraindications] and [Precautions].
Warfarin: Preliminary data suggest a pharmacodynamic interaction between paroxetine and warfarin (increased bleeding in the presence of unchanged prothrombin time). Caution should be exercised when combining paroxetine hydrochloride tablets with warfarin due to little clinical experience. (See [Precautions]).
Triptans: Post-marketing reports rarely report selective “font-family:Times New Roman”>5-hydroxytryptamine reuptake inhibitors and tritans after treatment5-hydroxytryptophan syndrome. If combination therapy with paroxetine hydrochloride tablets and a tritonide is clinically necessary, close observation of the patient is recommended, especially during the initiation and dose escalation phases of therapy (see [Precautions]5-Serotonin syndrome).
Drugs that can affect hepatic metabolism: The metabolism and pharmacokinetics of paroxetine may be affected by induction or inhibition of drug metabolizing enzymes.
Cimetidine:Cimetidine inhibits a variety of cytochromesP450(oxidative) enzymes. In one study, paroxetine hydrochloride tablets (30 mg once daily) were given orally =”font-family:Times New Roman”>4weeks vs. oral cimetidine (300 mg) /span>three times daily) during the last week of coadministration, steady-state paroxetine steady-state blood levels increased by approximately 50%. Therefore, when co-administered with this drug, after the administration of paroxetine hydrochloride tablets20 mgstarting dose, the dose of paroxetine hydrochloride tablets should be adjusted based on clinical outcomes. Paroxetine hydrochloride tablets should be dose adjusted based on clinical outcomes. The effect of paroxetine on the pharmacokinetics of cimetidine has not been studied.
Phenobarbital: Phenobarbital is capable of inducing a variety of cytochromesP450(oxidative) enzymes. When given at phenobarbital steady state (100 mgonce daily -family:Times New Roman”>14days) give a single oral dose of paroxetine hydrochloride tablets30 mgwhen compared to paroxetine monotherapy, theAUC of paroxetine family:Arial”>andT1/2declined (respectively, on average) 25%and38%) ). The effect of paroxetine on the pharmacokinetics of phenobarbital was not studied. Because paroxetine hydrochloride tablets have nonlinear pharmacokinetics, the results of this study may not be representative of long-term coadministration. Because no initial dose adjustment of paroxetine hydrochloride tablets is required for coadministration with phenobarbital, any subsequent dose adjustment should be made based on clinical outcomes.
Phenytoin: when at phenytoin steady state ( 300 mg given once daily for14day) when given as a single oral dose of 30 mg of paroxetine hydrochloride tablets, relative to paroxetine hydrochloride tablets monotherapy. Paroxetine’sAUCandT1/2declined (by an average of50% respectively) span style=”font-family:Arial”>and35%). In another study, when given at paroxetine steady state (30 mgonce daily14days) to a single oral dose of phenytoin300 mg300 mg, relative to phenytoin monotherapy, the phenytoinAUCwas slightly lower (mean decrease of approximately12%). Because both drugs exhibit nonlinear pharmacokinetics, the above study is not representative of long-term coadministration of both drugs. Because no initial dose adjustment of paroxetine hydrochloride tablets is required for coadministration with phenytoin, any subsequent dose adjustment should be based on clinical outcomes (see [Adverse Reactions] postmarketing report).
ByCYP2D6metabolized drugs:
Multiple drugs, including those most effective in the treatment of depression (paroxetine, other selective5-hydroxytryptamine reuptake inhibitors, multiple tricyclic antidepressants), via cytochromeP450isoenzymesCYP2D6metabolism. Similar to other drugs metabolized via CYP2D6, paroxetine may significantly inhibit the activity of this isoenzyme. In most patients (> 90%), the family:Times New Roman”>CYP2D6 isoenzyme is saturated early in the administration of paroxetine hydrochloride tablets. In one study, steady-state daily administration of paroxetine hydrochloride tablets (20 mg once daily) resulted in an increase in dexipramine () with single dosing. span>100 mg) of a single dose of Cmax, AUCandT1/2 respectively, were elevated on average2, 5and3fold. In one study, stable receipt of risperidone (4toto family:Times New Roman”>8 mg/day) in patients given20 mg per dayparoxetine increased mean plasma risperidone concentrations by approximately4fold and mean plasma9-hydroxyl risperidone concentrations decreased by approximately10% and plasma active ingredient (total combination of risperidone plus hydroxy risperidone) concentrations increase approximately1.4fold. In healthy volunteers with CYP2D6rapid metabolism, paroxetine was administered at a daily20 mg versus atomoxetine at20 mg. span>every12hours Co-dosing. This resulted in higher atomoxetine steady-stateAUCvalues relative to atomoxetine monotherapy “font-family:Times New Roman”>6to8fold, atomoxetineCmaxvalue is higher3toto4fold. Therefore, adjustments to atomoxetine may be required, and downward adjustment of the initial dose of atomoxetine is recommended when atomoxetine is coadministered with paroxetine.
Paroxetine hydrochloride tablets have not been formally studied in combination with other drugs that are administered via cytochromeCYP2D6metabolism, but the dose of either paroxetine hydrochloride tablets or other drugs should be lower than the normal prescribed dose.
Therefore, paroxetine hydrochloride tablets are compatible with other drugs that are metabolized by this enzyme including specific drugs that are effective in the treatment of depression (e.g., nortriptyline, amitriptyline, promethazine, desipramine, and fluoxetine), phenothiazine, risperidone, 1C class of antiarrhythmic drugs (e.g., propafenone, flecainide, and enkephalin) or drugs that inhibit this enzyme (e.g., quinidine) should be given in combination with particularly cautious.
However, thioridazine should not be co-administered with paroxetine because the risk of severe ventricular arrhythmias and sudden death may be associated with elevated plasma thioridazine levels (see [Contraindications]).
Tamoxifen is a drug that requiresCYP2D6metabolic activation of precursor drugs. Paroxetine-inducedCYP2D6inhibition may lead to active metabolites4-hydroxy-N-Desmethyltamoxifen (Endoxifen) blood levels decrease, which in turn decreases the efficacy of tamoxifen (see [Precautions]).
At steady state, whenCYP2D6pathway is saturated, the clearance of paroxetine is mainly mediated by P450 isozyme-mediated, this enzyme is different from CYP2D6 and has not shown evidence of saturation (see [Caution]).
by cytochromeCYP3A4Metabolism of drugs: drugs involving steady-state paroxetine with terfenadine (a cytochromesubstrate of CYP3A4), in vivo interaction studies involving the coadministration of paroxetine with terfenadine (a cytochrome) showed that paroxetine did not affect the pharmacokinetics of terfenadine. In addition, in vitro studies have also shown that ketoconazole (a potentinhibitor of CYP3A4activity) acts as a substrate for multiple substrates of this enzyme (including terfenadine Nadine, astemizole, cisapride, triazolam, and cyclosporine) are at least 100fold more potent than paroxetine for inhibition of metabolism of multiple substrates of this enzyme (including terfenadine, astemizole, cisapride, triazolam, and cyclosporine). Based on the association between the in vitroKi and the lack of effect of paroxetine on terfenadine clearance in vivo was able to predict the effect of paroxetine on otherCYP3A4substrates, the effect of paroxetine oninhibition of CYP3A4activity is unlikely to be clinically meaningful.
Tricyclic antidepressants: Particular caution should be exercised when co-administering tricyclic antidepressants and paroxetine hydrochloride tablets because paroxetine may inhibit the metabolism of tricyclic antidepressants. When tricyclic antidepressants are given in combination with paroxetine hydrochloride tablets, plasma tricyclic antidepressant concentrations may need to be monitored and the dose of tricyclic antidepressants may need to be reduced (see [Drug Interactions] via cytochromeCYP2D6 metabolized by drugs).
Drugs Highly Bound to Plasma Proteins: Because of the high binding of paroxetine to plasma proteins, administration of paroxetine in patients who are receiving another drug with a high binding to plasma proteins paroxetine hydrochloride tablets may increase the free concentration of the other drug, which may lead to adverse events. Conversely, paroxetine may also cause adverse reactions when it is replaced by other drugs with high binding rates.
Drugs that interfere with hemostasis (eg, NSAIDs, aspirin, and warfarin): Serotonin released by platelets plays an important role in hemostasis. Epidemiological studies in case-control and cohort designs have demonstrated that the use of psychoactive drugs that may interfere with 5-hydroxytryptamine reuptake and An association between the occurrence of upper gastrointestinal bleeding has also been demonstrated, and the combination of NSAIDs or aspirin may increase the risk of bleeding. Studies have reported that when selective5-hydroxytryptamine reuptake inhibitors or norepinephrine reuptake inhibitors are used in combination with warfarin, anticoagulation effects are altered, including increased bleeding. Careful monitoring should be received when starting or stopping paroxetine therapy in patients being treated with warfarin.
Alcohol: Although studies have demonstrated that paroxetine hydrochloride tablets do not increase alcohol-induced impairment of mental and motor skills, patients should still be advised to Avoid drinking alcohol.
Lithium: Multiple dosing studies have shown no pharmacokinetic interaction between paroxetine hydrochloride tablets and lithium carbonate. However, due to the potential for 5-hydroxytryptamine syndrome, particular caution should be exercised when co-administering paroxetine hydrochloride tablets with lithium.
Digoxin: The steady-state pharmacokinetics of paroxetine are unchanged when digoxin is given at steady state. When paroxetine was administered, the steady-state mean digoxinAUCdecreased by approximately15%. Due to less clinical experience, co-administration of paroxetine with digoxin should be particularly cautious.
Diazepam: At steady state, diazepam may not affect the pharmacokinetics of paroxetine. The effect of paroxetine on diazepam has not been evaluated.
Procyclidine: Relative to procyclidine monotherapy at steady state, daily oral paroxetine hydrochloride tablets (30 mg once daily) made procyclidine (5 mg, orally once daily) to a steady-stateAUC 0-24 “font-family:Arial”>,CmaxandCminvalues increase by35%, 37%and67%. If anticholinergic effects are observed, the dose of procyclidine should be reduced.
β-blockers: In one study, propranolol was given orally (80 mgtwice daily)18day and co-administered with paroxetine hydrochloride tablets (30 mgonce daily) for the lastday span>10day period, the established blood concentrations of propranolol at steady state did not change. The effect of propranolol on paroxetine has not been evaluated (see [Adverse Reactions] postmarketing report).
Theophylline: Elevated theophylline levels associated with treatment with paroxetine hydrochloride tablets have been reported in studies. Although the interaction between the two has not been formally studied, it is still recommended that theophylline levels be monitored when these drugs are co-administered.
Fosamprenavir/Ritonavir:Fosamprenavir// “font-family:Arial”>Coadministration of ritonavir with paroxetine results in a significant decrease in plasma levels of paroxetine. Any dose adjustment should be made based on clinical outcomes (tolerability and efficacy).
Electroconvulsive therapy (ECT): There is noECTclinical studies in combination with paroxetine hydrochloride tablets.
[Drug overdose]
Human experience:
Since its launch in the United States, during paroxetine treatment, a total of 342 were reported worldwide. 342spontaneous cases of intentional or unintentional overdose (circa 1999 =”font-family:Arial”>). These cases included paroxetine overdose alone, and overdose when combined with other drugs. Of these,17 cases (total48 cases) fatal cases may be associated with paroxetine only. 8fatal cases with documented paroxetine intake were confounded by other drugs, alcohol, or significant comorbid conditions. Of the 145 nonfatal cases with unknown outcomes, most recovered with no sequelae. The maximum known intake was 2000 mgof paroxetine in one patient (the maximum recommended daily dose of33fold), the patient recovered.
Common adverse events associated with paroxetine overdose include: drowsiness, coma, nausea, tremor, tachycardia, confusion, vomiting, and dizziness. Other significant signs and symptoms associated with paroxetine overdose (alone or in combination with other drugs) include dilated pupils, convulsions (including seizures), ventricular arrhythmias (including tip-twisting ventricular tachycardia), hypertension, attack reactions, syncope, hypotension, coma, bradycardia, dystonia, rhabdomyolysis, signs of impaired liver function (including liver failure, hepatic necrosis, jaundice, hepatitis, and fatty liver),5-hydroxytryptamine syndrome, manic reaction, myoclonus, acute renal failure, and urinary retention.
Overdose management:
At present, there is no specific antidote for paroxetine. Therapeutic measures for overdose should be the general measures used in the management of any effective drug overdose in the treatment of depression.
Adequate airway clearance, adequate oxygen supply, and ventilation should be ensured, and cardiac rhythm and vital signs should be monitored. General supportive and symptomatic treatment measures are also recommended. The use of emetics is not recommended. Due to the large volume of distribution of paroxetine, patients are unlikely to benefit from forced diuresis, dialysis, hemoperfusion, or blood exchange.
Particular attention should be paid to patients who may have previously overdosed on tricyclic antidepressants and are taking or have recently taken paroxetine. In such cases, accumulation of tricyclic antidepressant parent drugs and/ or active metabolites may increase the likelihood of significant clinical sequelae and prolong potential for the time required for close medical observation (see [Drug Interactions] By CytochromeCYP2D6metabolized drugs).
In the process of overdose management, physicians should consider the possibility of multiple drug associations.
[Pharmacologic Toxicology]
Pharmacological effects
Paroxetine hydrochloride is a potent, highly selective 5-HT reuptake inhibitor, the mechanism of action of paroxetine hydrochloride is to cause a decrease in the synaptic gap 5-HT concentrations are elevated, enhancing central 5-hydroxytryptaminergic nerve function. Only weakly inhibits reuptake of norepinephrine and dopamine with muscarinic receptors, adrenergic α1, α2, beta receptors, dopamine 2receptors (D2),5-hydroxytryptamine 1,2 receptor(5-HT1, 5-HT2) and histamine H1
receptors with little affinity. No inhibitory effect on monoamine oxidase.
Toxicological studies
Genotoxicity:
Paroxetine Ames assay, mouse lymphoma assay, extra-procedural DNA synthesis assay, human lymphocyte chromosome aberration test, mouse bone marrow micronucleus test and rat dominant lethality test were all negative.
Reproductive toxicity:
Rats were given paroxetine 15 mg/kg/ in a reproductive toxicity test >day (in mg/m2)
is approximately equivalent to the recommended maximum human dose (MRHD). family:Arial”>) of 2fold), conception rates decreased. At 2 to 2 to 52 week toxicity test found irreversible damage to the reproductive tract in male rats (50 mg/kg/days,25mg/kg/day accompanied by testicular vas deferens atrophy with spermatogenesis inhibition). Paroxetine was administered to rats and rabbits at the organogenesis stage for 50 mg/kg/day and 6mg/kg/day (in mg /m2
are calculated to be equivalent to MRHDof 8 and 2 times), no teratogenic effect was observed. However, in rats given continuously during late gestation and throughout lactation, there was an increase in pup mortality during the first 4 days of lactation, and this effect occurred during 1 mg/kg/ day (in mg/m2, which is approximately equivalent toMRHDof1/6), the cause of death is unknown, and a no-effect dose for pup mortality could not be determined.
Carcinogenicity:
In a two-year rodent adulteration carcinogenicity test, mice and rats were given paroxetine at doses up to25 mg/kg/day and 20 mg/kg/day (in mg/m2)
calculated to be equivalent to MRHD of 2 and 3 times). The incidence of reticulocytoma was significantly increased in male rats in the high-dose group ( 1/100, 0/50,0/50and 4/50), there was a dose-dependent increase in the incidence of lymphoreticular endothelial cell tumors. No effect was seen in female rats. A dose-related increase in the number of tumors was seen in mice, but no drug-related increase was seen in the number of mice that developed tumors. The relevance of these findings to humans is unclear.
[Pharmacokinetics]
Paroxetine hydrochloride solution is completely absorbed after oral administration. Paroxetine30mg per day orally, continuously. family:Times New Roman”>30days, with a mean clearance half-life of approximately21hours (CV 32%). Paroxetine is primarily degraded by metabolism and its metabolites are not pharmacologically active. It exhibits a nonlinear pharmacokinetic process at increasing doses. Paroxetine is partially metabolized by CYP2D6, with metabolites excreted primarily in the urine and to a lesser extent in the feces. There are no data evaluating the pharmacokinetics of paroxetine in CYP2D6deficient patients (lacking the metabolic phenotype). 4 multiple doses of paroxetine in healthy volunteers20 mg/day to40 mg/day in a meta-analysis of studies of male subjects with Cmaxor span>AUCvalues were not significantly lower than in female subjects.
Uptake and distribution
The product is completely absorbed after oral administration and is metabolized by first-pass metabolism after absorption. In normal men taking paroxetine30mg orally daily, most family:Times New Roman”>10days to reach steady state, with a very small number of patients requiring a slightly longer time to reach steady stateCmaxis61.7ng/mlandTmaxwas5.2hr,,Cminis 30.7ng/ml. T½for21hours (CV 32%). Steady-stateCmaxandandCminvalues are the predicted values for single-dose clinical trials6-14 fold. Based onAUC0-24
The calculated steady-state drug exposure was then 8 of the predicted value from the single-dose clinical trial. font-family:Arial”> times. The excessive accumulation is the result of rapid saturation of the metabolizing enzymes of paroxetine.
Using a single dose administered with a meal/or without food, the effect of food on the bioavailability of paroxetine was studied. When taken with food, the AUC increased slightly ( 6%), butCmaxincreased more (29%), and the blood concentration peaked The time to peak blood level was shortened from 6.4 hours to 4.9 hours.
Paroxetine95%binds to plasma proteins and is distributed throughout the body, including the central nervous system, with only 1% remaining in the body circulation.
Metabolism and excretion
Paroxetine hydrochloride tablets30 mgper day orally style=”font-family:Arial”>for 30days with a mean clearance half-life of approximately 1.5 years. span>21hours (CV 32%). In the steady-state dose ratio study involving elderly and non-elderly patients, the dose in the elderly was 20 mg dailyto40 mg and for non-elderly people the dose is20 mg daily Roman”>20 mgto50 mg. The nonlinearity observed in both populations again reflects the saturable metabolic pathways of paroxetine. With a daily20 mgdose after theCmin values compared to daily40 mg values =”font-family:Arial”> at a dose of only about2 to3fold. The major metabolites of paroxetine after oral absorption are oxidized and methylated polar covalent complexes that are readily cleared. Covalent conjugates with glucuronide and sulfate predominate, and the major metabolites have been isolated and identified. The data show that the metabolites of the drug inhibit the activity of 5-hydroxytryptamine reuptake less than that of the parent drug1/50. CYP2D6is partially involved in the metabolism of paroxetine. At clinical doses, saturation of this enzyme causes the pharmacokinetic process to be nonlinear at increasing doses of paroxetine and at increasing courses of therapy. The effect of this enzyme on paroxetine metabolism suggests some potential drug-drug interactions (see [Precautions]).
Oral paroxetine solution30 mgdose after10days, nearly64%is excreted by urine, of which2%is the parent drug and 62%is the metabolite; about 36%are excreted in the feces (possibly via bile), most of which are metabolites, with insufficient parent drug1%.
[Storage]Store away from light, tightly sealed, in a dry place.
[Package]
Aluminum-plastic blister, per plate7tablets, each box1plate.
Aluminum-plastic blister, per plate10tablets, per box1plate.
[Expiration date]24months
[Executive Standard]
[Approval number]国药准字 H10950043
[Manufacturer]
[Principal Company]
Enterprise name: Sino-US Tianjin Shih-Ke Pharmaceutical Co.
Address: Chenglinzhuang Road Chengzhou Intersection, Dongli District, Tianjin
Postal Code:300163
Tel:022-24700556,022-24700592
Fax Number:022-24700532
[Trustee Company]
Enterprise name: GlaxoSmithKline (Tianjin) Ltd
Address: Fifth Street, Tianjin Economic and Technological Development Area65No.
Postal Code:300457
Phone Number:022-62012222
GSKService Hotline:800-820-3383/400-183-3383
Fax Number:022-62017150
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