Paroxetine
Generic: PAROXETINE
Basic Information
Manufacturer
Padagis US LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
1383d713-79b9-45bd-bd06-65707f28bc99
Indications & Usage
1 INDICATIONS AND USAGE Paroxetine Capsules are indicated for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause.
Limitation of Use: Paroxetine capsules are not indicated for the treatment of any psychiatric condition.
Paroxetine capsules contain a lower dose of paroxetine than that used to treat depression, obsessive compulsive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, and post-traumatic stress disorder.
The safety and efficacy of this lower dose of paroxetine in paroxetine capsules have not been established for any psychiatric condition.
Patients who require paroxetine for treatment of a psychiatric condition should discontinue paroxetine capsules and initiate a paroxetine-containing medication that is indicated for such use.
• Paroxetine capsules are a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of moderate to severe vasomotor symptoms associated with menopause (VMS) ( 1 ) Limitation of Use: Paroxetine capsules are not indicated for the treatment of any psychiatric condition ( 1 )
Limitation of Use: Paroxetine capsules are not indicated for the treatment of any psychiatric condition.
Paroxetine capsules contain a lower dose of paroxetine than that used to treat depression, obsessive compulsive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, and post-traumatic stress disorder.
The safety and efficacy of this lower dose of paroxetine in paroxetine capsules have not been established for any psychiatric condition.
Patients who require paroxetine for treatment of a psychiatric condition should discontinue paroxetine capsules and initiate a paroxetine-containing medication that is indicated for such use.
• Paroxetine capsules are a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of moderate to severe vasomotor symptoms associated with menopause (VMS) ( 1 ) Limitation of Use: Paroxetine capsules are not indicated for the treatment of any psychiatric condition ( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in labeling: • Suicidality [see Warnings and Precautions (5.1)] • Serotonin syndrome [see Warnings and Precautions (5.2)] • Abnormal bleeding [see Warnings and Precautions (5.4)] • Angle-Closure Glaucoma [see Warnings and Precautions (5.5)] • Hyponatremia [see Warnings and Precautions (5.6)] • Bone Fracture [see Warnings and Precautions (5.7)] • Mania/Hypomania [see Warnings and Precautions (5.8)] • Seizure [see Warnings and Precautions (5.9)] • Akathisia [see Warnings and Precautions (5.10)] • The most common adverse reactions (≥ 2%) reported in clinical trials were: headache, fatigue, and nausea/vomiting ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot directly be compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to paroxetine capsules in the one 8-week Phase 2 randomized, placebo-controlled trial and the two Phase 3 randomized, placebo-controlled, 12-week and 24-week trials for the treatment of moderate to severe VMS [see Clinical Studies (14)] .
In these trials, a total of 635 women were exposed to paroxetine capsules 7.5 mg administered orally once daily and 641 women received placebo.
The majority of paroxetine capsule-treated patients were Caucasian (68%) and African American (30%), with a mean age of 55 years (range 40 to 73 years).
Women with a history of suicidal ideation or suicidal behavior were excluded from these studies.
Adverse Reactions Leading to Study Discontinuation: A total of 4.7% of women taking paroxetine capsules discontinued from the clinical trials due to an adverse reaction, compared to 3.7% of women on placebo; the most frequent adverse reactions leading to discontinuation among paroxetine-treated women were: abdominal pain (0.3%), attention disturbances (0.3%), headache (0.3%), and suicidal ideation (0.3%).
Common Adverse Reactions: Overall, based on investigators’ determinations about what events were likely to be drug-related, about 20% of women treated with paroxetine capsules reported at least 1 adverse reaction in the three controlled studies.
The most common adverse reactions (≥ 2% and more common among paroxetine capsule-treated women) reported in these studies were headache, fatigue/malaise/lethargy, and nausea/vomiting.
Of these commonly reported adverse reactions, nausea occurred primarily within the first 4 weeks of treatment and fatigue occurred primarily within the first week of treatment, and decreased in frequency with continued therapy.
The adverse reactions that occurred in at least 2% of patients in the paroxetine capsule group and at a higher incidence than placebo are shown in Table 1 for the pooled Phase 2 and Phase 3 trials.
Table 1 Frequency of Adverse Reactions in the Phase 2 and Phase 3 Trials (≥ 2% and at a higher incidence than placebo) Frequency n (%) Paroxetine Capsules (n = 635) Placebo (n = 641) Nervous system disorders Headache 40 (6.3) 31 (4.8) General disorders and administration site conditions Fatigue, malaise, lethargy 31 (4.9) 18 (2.8) Gastrointestinal disorders Nausea, vomiting 27 (4.3) 15 (2.3) Certain symptoms were seen more frequently in women at the time of discontinuation of paroxetine capsules compared to women discontinuing placebo, and have also been reported upon discontinuation of other formulations of paroxetine, particularly when abrupt.
These include increased dreaming/nightmares, muscle cramps/spasms/twitching, headache, nervousness/anxiety, fatigue/tiredness, restless feeling in legs, and trouble sleeping/insomnia.
While these events are generally self-limiting, there have been reports of serious discontinuation symptoms with other formulations of paroxetine.
Serious Adverse Reactions: In the pooled Phase 2 and Phase 3 trials, three paroxetine capsule-treated patients reported a serious adverse reaction of suicidal ideation and one paroxetine capsule-treated patient reported a serious adverse reaction of suicide attempt.
There were no serious adverse reactions of suicidal ideation or suicide attempt reported among the placebo-treated patients.
6.2 Postmarketing Experience The following adverse reactions have been identified from clinical studies of paroxetine and during post-approval use of other formulations of paroxetine.
Because some of these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders: Idiopathic thrombocytopenic purpura, Events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, agranulocytosis).
Cardiac Disorders: Atrial fibrillation, Pulmonary edema, Ventricular fibrillation, Ventricular tachycardia (including torsades de pointes).
Gastrointestinal Disorders: Pancreatitis, Pancreatitis hemorrhagic, Vomiting.
General Disorders and Administration Site Conditions: Death, Drug withdrawal syndrome, Malaise.
Hepatobiliary Disorders: Drug-induced liver injury, Hepatic failure, Jaundice.
Immune System Disorders: Anaphylactoid reaction, Angioedema, Toxic epidermal necrolysis.
Investigations: Elevated liver tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction).
Metabolism and Nutrition Disorders: Diabetes mellitus inadequate control, Type 2 diabetes mellitus.
Nervous System Disorders: Neuroleptic malignant syndrome, Paresthesia, Somnolence, Tremor, Anosmia, Hyposmia.
Psychiatric Disorders: Aggression, Agitation, Anxiety, Confusional state, Depression, Disorientation, Homicidal ideation, Insomnia, Restlessness.
Respiratory, Thoracic and Mediastinal Disorders: Pulmonary hypertension.
Skin and Subcutaneous Tissue Disorders: Hyperhidrosis, Stevens-Johnson syndrome, Drug reaction with eosinophilia and systemic symptoms (DRESS).
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot directly be compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to paroxetine capsules in the one 8-week Phase 2 randomized, placebo-controlled trial and the two Phase 3 randomized, placebo-controlled, 12-week and 24-week trials for the treatment of moderate to severe VMS [see Clinical Studies (14)] .
In these trials, a total of 635 women were exposed to paroxetine capsules 7.5 mg administered orally once daily and 641 women received placebo.
The majority of paroxetine capsule-treated patients were Caucasian (68%) and African American (30%), with a mean age of 55 years (range 40 to 73 years).
Women with a history of suicidal ideation or suicidal behavior were excluded from these studies.
Adverse Reactions Leading to Study Discontinuation: A total of 4.7% of women taking paroxetine capsules discontinued from the clinical trials due to an adverse reaction, compared to 3.7% of women on placebo; the most frequent adverse reactions leading to discontinuation among paroxetine-treated women were: abdominal pain (0.3%), attention disturbances (0.3%), headache (0.3%), and suicidal ideation (0.3%).
Common Adverse Reactions: Overall, based on investigators’ determinations about what events were likely to be drug-related, about 20% of women treated with paroxetine capsules reported at least 1 adverse reaction in the three controlled studies.
The most common adverse reactions (≥ 2% and more common among paroxetine capsule-treated women) reported in these studies were headache, fatigue/malaise/lethargy, and nausea/vomiting.
Of these commonly reported adverse reactions, nausea occurred primarily within the first 4 weeks of treatment and fatigue occurred primarily within the first week of treatment, and decreased in frequency with continued therapy.
The adverse reactions that occurred in at least 2% of patients in the paroxetine capsule group and at a higher incidence than placebo are shown in Table 1 for the pooled Phase 2 and Phase 3 trials.
Table 1 Frequency of Adverse Reactions in the Phase 2 and Phase 3 Trials (≥ 2% and at a higher incidence than placebo) Frequency n (%) Paroxetine Capsules (n = 635) Placebo (n = 641) Nervous system disorders Headache 40 (6.3) 31 (4.8) General disorders and administration site conditions Fatigue, malaise, lethargy 31 (4.9) 18 (2.8) Gastrointestinal disorders Nausea, vomiting 27 (4.3) 15 (2.3) Certain symptoms were seen more frequently in women at the time of discontinuation of paroxetine capsules compared to women discontinuing placebo, and have also been reported upon discontinuation of other formulations of paroxetine, particularly when abrupt.
These include increased dreaming/nightmares, muscle cramps/spasms/twitching, headache, nervousness/anxiety, fatigue/tiredness, restless feeling in legs, and trouble sleeping/insomnia.
While these events are generally self-limiting, there have been reports of serious discontinuation symptoms with other formulations of paroxetine.
Serious Adverse Reactions: In the pooled Phase 2 and Phase 3 trials, three paroxetine capsule-treated patients reported a serious adverse reaction of suicidal ideation and one paroxetine capsule-treated patient reported a serious adverse reaction of suicide attempt.
There were no serious adverse reactions of suicidal ideation or suicide attempt reported among the placebo-treated patients.
6.2 Postmarketing Experience The following adverse reactions have been identified from clinical studies of paroxetine and during post-approval use of other formulations of paroxetine.
Because some of these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders: Idiopathic thrombocytopenic purpura, Events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, agranulocytosis).
Cardiac Disorders: Atrial fibrillation, Pulmonary edema, Ventricular fibrillation, Ventricular tachycardia (including torsades de pointes).
Gastrointestinal Disorders: Pancreatitis, Pancreatitis hemorrhagic, Vomiting.
General Disorders and Administration Site Conditions: Death, Drug withdrawal syndrome, Malaise.
Hepatobiliary Disorders: Drug-induced liver injury, Hepatic failure, Jaundice.
Immune System Disorders: Anaphylactoid reaction, Angioedema, Toxic epidermal necrolysis.
Investigations: Elevated liver tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction).
Metabolism and Nutrition Disorders: Diabetes mellitus inadequate control, Type 2 diabetes mellitus.
Nervous System Disorders: Neuroleptic malignant syndrome, Paresthesia, Somnolence, Tremor, Anosmia, Hyposmia.
Psychiatric Disorders: Aggression, Agitation, Anxiety, Confusional state, Depression, Disorientation, Homicidal ideation, Insomnia, Restlessness.
Respiratory, Thoracic and Mediastinal Disorders: Pulmonary hypertension.
Skin and Subcutaneous Tissue Disorders: Hyperhidrosis, Stevens-Johnson syndrome, Drug reaction with eosinophilia and systemic symptoms (DRESS).