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Paroxetine Tablets, USP


Suicidality and Antidepressant Drugs


DESCRIPTION


CLINICAL PHARMACOLOGY


Pharmacodynamics


Pharmacokinetics


Other Clinical Pharmacology Information


Clinical Trials

 Worse 14% 7% 7% 3%
 No Change 44% 35% 22% 19%
 Minimally Improved 24% 33% 29% 34%
 Much Improved 11% 18% 22% 24%
 Very Much Improved 7% 7% 20% 20%

INDICATIONS AND USAGE


CONTRAINDICATIONS


WARNINGS


Clinical Worsening and Suicide Risk

Age Range Drug-Placebo Difference inNumber of Cases of Suicidality per 1,000 Patients Treated
Increases Compared to Placebo
<18 14 additional cases
18-24 5 additional cases
Decreases Compared to Placebo
25-64 1 fewer case
≥65 6 fewer cases

Screening Patients for Bipolar Disorder


Potential for Interaction With Monoamine Oxidase Inhibitors


Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions


Potential Interaction With Thioridazine


Usage in Pregnancy


Teratogenic Effects

  • A study based on Swedish national registry data demonstrated that infants exposed to paroxetine during pregnancy (n = 815) had an increased risk of cardiovascular malformations (2% risk in paroxetine-exposed infants) compared to the entire registry population (1% risk), for an odds ratio (OR) of 1.8 (95% confidence interval 1.1 to 2.8). No increase in the risk of overall congenital malformations was seen in the paroxetine-exposed infants. The cardiac malformations in the paroxetine-exposed infants were primarily ventricular septal defects (VSDs) and atrial septal defects (ASDs). Septal defects range in severity from those that resolve spontaneously to those which require surgery.
  • A separate retrospective cohort study from the United States (United Healthcare data) evaluated 5,956 infants of mothers dispensed antidepressants during the first trimester (n = 815 for paroxetine). This study showed a trend towards an increased risk for cardiovascular malformations for paroxetine (risk of 1.5%) compared to other antidepressants (risk of 1%), for an OR of 1.5 (95% confidence interval 0.8 to 2.9). Of the 12 paroxetine-exposed infants with cardiovascular malformations, 9 had VSDs. This study also suggested an increased risk of overall major congenital malformations including cardiovascular defects for paroxetine (4% risk) compared to other (2% risk) antidepressants (OR 1.8; 95% confidence interval 1.2 to 2.8).
  • Two large case-control studies using separate databases, each with >9,000 birth defect cases and >4,000 controls, found that maternal use of paroxetine during the first trimester of pregnancy was associated with a 2- to 3-fold increased risk of right ventricular outflow tract obstructions. In one study the odds ratio was 2.5 (95% confidence interval, 1 to 6, 7 exposed infants) and in the other study the odds ratio was 3.3 (95% confidence interval, 1.3 to 8.8, 6 exposed infants).

Animal Findings


Nonteratogenic Effects


PRECAUTIONS


General


Discontinuation of Treatment With Paroxetine Tablets


Hyponatremia


Information for Patients


Drugs That Interfere With Hemostasis (e.g., NSAIDs, Aspirin, and Warfarin)


Laboratory Tests


Drug Interactions


Tryptophan


Drugs Metabolized by CYP2D6


Tricyclic Antidepressants (TCAs)


Carcinogenesis, Mutagenesis, Impairment of Fertility


Pregnancy


Labor and Delivery


Nursing Mothers


Pediatric Use


Geriatric Use


ADVERSE REACTIONS

   CNS
      Somnolence 2.3% 0.7% 1.9% 0.3% 2% 0.2%
      Insomnia 1.7% 0% 1.3% 0.3%
      Agitation 1.1% 0.5%
      Tremor 1.1% 0.3%
      Anxiety
      Dizziness 1.5% 0% 1% 0.2%
   Gastrointestinal
      Constipation 1.1% 0%
      Nausea 3.2% 1.1% 1.9% 0% 3.2% 1.2% 2% 0.2%
      Diarrhea 1% 0.3%
      Dry mouth 1% 0.3%
      Vomiting 1% 0.3%
      Flatulence
   Other
      Asthenia 1.6% 0.4% 1.9% 0.4% 1.8% 0.2%
      Abnormal Ejaculation11.6% 0% 2.1% 0% 2.5% 0.5%
      Sweating 1% 0.3% 1.1% 0.2%
      Impotence11.5% 0%
      Libido Decreased
   Body as a Whole   Headache 18%17%
   Asthenia 15%6%
   Cardiovascular   Palpitation 3%1%
   Vasodilation 3%1%
   Dermatologic   Sweating 11%2%
   Rash 2%1%
   Gastrointestinal   Nausea 26%9%
   Dry Mouth 18%12%
   Constipation 14%9%
   Diarrhea 12%8%
   Decreased Appetite 6%2%
   Flatulence 4%2%
   Oropharynx Disorder22%0%
   Dyspepsia 2%1%
   Musculoskeletal   Myopathy 2%1%
   Myalgia 2%1%
   Myasthenia 1%0%
   Nervous System   Somnolence 23%9%
   Dizziness 13%6%
   Insomnia 13%6%
   Tremor 8%2%
   Nervousness 5%3%
   Anxiety 5%3%
   Paresthesia 4%2%
   Libido Decreased 3%0%
   Drugged Feeling 2%1%
   Confusion 1%0%
   Respiration   Yawn 4%0%
   Special Senses   Blurred Vision 4%1%
   Taste Perversion 2%0%
   Urogenital System   Ejaculatory Disturbance3,413%0%
   Other Male Genital Disorders3,510%0%
   Urinary Frequency 3%1%
   Urination Disorder63%0%
   Female Genital Disorders3,72%0%
   Body as a Whole   Asthenia 22%14%14%5%
   Abdominal Pain 4%3%
   Chest Pain 3%2%
   Back Pain 3%2%
   Chills 2%1%2%1%
   Trauma
   Cardiovascular   Vasodilation 4%1%
   Palpitation 2%0%
   Dermatologic   Sweating 9%3%14%6%
   Rash 3%2%
   Gastrointestinal   Nausea 23%10%23%17%
   Dry Mouth 18%9%18%11%
   Constipation 16%6%8%5%
   Diarrhea 10%10%12%7%
   Decreased Appetite 9%3%7%3%
   Dyspepsia
   Flatulence
   Increased Appetite 4% 3% 2% 1%
   Vomiting
   Musculoskeletal Myalgia
   Nervous System   Insomnia 24% 13% 18% 10%
   Somnolence 24% 7% 19% 11%
   Dizziness 12% 6% 14% 10%
   Tremor 11% 1% 9% 1%
   Nervousness 9% 8%
   Libido Decreased 7% 4% 9% 1%
   Agitation 5% 4%
   Anxiety 5% 4%
   Abnormal Dreams 4% 1%
   Concentration Impaired 3% 2%
   Depersonalization 3% 0%
   Myoclonus 3% 0% 3% 2%
   Amnesia 2% 1%
   Respiratory System   Rhinitis 3% 0%
   Pharyngitis
   Yawn
   Special Senses   Abnormal Vision 4% 2%
   Taste Perversion 2% 0%
   Urogenital System   Abnormal Ejaculation223% 1% 21% 1%
   Dysmenorrhea
   Female Genital Disorder23% 0% 9% 1%
   Impotence28% 1% 5% 0%
   Urinary Frequency 3% 1% 2% 0%
   Urination Impaired 3% 0%
   Urinary Tract Infection 2% 1% 2% 1%
   Body as a Whole   Asthenia14%6%
   Headache 17%14%
   Infection 6%3%
   Abdominal Pain
   Trauma
   Cardiovascular   Vasodilation 3%1%
   Dermatologic    Sweating 6%2%
   Gastrointestinal   Nausea 20%5%
   Dry Mouth 11%5%
   Constipation 10%2%
   Diarrhea 9%7%
   Decreased Appetite 5%1%
   Vomiting 3%2%
   Dyspepsia
   Nervous System   Insomnia11%8%
   Somnolence 15%5%
   Dizziness 6%5%
   Tremor 5%1%
   Nervousness 4%3%
   Libido Decreased 9%2%
   Abnormal Dreams
   Respiratory System   Respiratory Disorder 7%5%
   Sinusitis 4%3%
   Yawn 4%
   Special Senses   Abnormal Vision 2%1%
   Urogenital System   Abnormal Ejaculation225%2%
   Female Genital Disorder24%1%
   Impotence24%3%
   Body as a Whole
      Asthenia 0%2.9%10.6%13.9%12.7%
   Dermatology
      Sweating 2%1%6.7%8.9%11.8%
   Gastrointestinal
      Constipation5.9%4.9%7.7%9.9%12.7%
      Decreased Appetite2%2%5.8%4%4.9%
      Diarrhea7.8%9.8%19.2%7.9%14.7%
      Dry Mouth2%10.8%18.3%15.8%20.6%
      Nausea13.7%14.7%26.9%34.7%36.3%
   Nervous System
      Anxiety0%2%5.8%5.9%5.9%
      Dizziness3.9%6.9%6.7%8.9%12.7%
      Nervousness0%5.9%5.8%4%2.9%
      Paresthesia0%2.9%1%5%5.9%
      Somnolence7.8%12.7%18.3%20.8%21.6%
      Tremor0%0%7.7%7.9%14.7%
   Special Senses
      Blurred Vision2%2.9%2.9%2%7.8%
   Urogenital System
      Abnormal Ejaculation0%5.8%6.5%10.6%13%
      Impotence0%1.9%4.3%6.4%1.9%
      Male Genital Disorders0%3.8%8.7%6.4%3.7%
   Decreased Libido6-15%0-5%
   Ejaculatory Disturbance13-28%0-2%
   Impotence2-9%0-3%
n (females)18221340
   Decreased Libido0-9%0-2%
   Orgasmic Disturbance2-9%0-1%

Postmarketing Reports


DRUG ABUSE AND DEPENDENCE


Controlled Substance Class


OVERDOSAGE


DOSAGE AND ADMINISTRATION


Discontinuation of Treatment With Paroxetine Tablets


HOW SUPPLIED


Medication Guide

If you take paroxetine tablets, you should not take any other medicines that contain paroxetine, including PAXIL CR and PEXEVA® (paroxetine mesylate).
  • Paroxetine tablets and other antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, or young adults within the first few months of treatment or when the dose is changed.
  • Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions.
  • Watch for these changes and call your healthcare provider right away if you notice: New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe. Pay particular attention to such changes when paroxetine tablets are started or when the dose is changed.

Relabeling and Repackaging by:

STAT Rx USA LLC

Gainesville, GA 30501


PACKAGE LABEL - PAROXETINE 10 MG TABLETS