Paroxetine: uses, appearance and warnings

Paroxetine HCL CR is indicated in adults for the treatment of: Major depressive disorder (MDD) Panic disorder (PD) Social anxiety disorder (SAD) Premenstrual dysphoric disorder (PMDD) Paroxetine HCL CR is a selective serotonin reuptake inhibitor (SSRI) indicated in adults for the treatment of ( 1 ): Major Depressive Disorder (MDD) Panic Disorder (PD) Social Anxiety Disorder (SAD) Premenstrual Dysphoric Disorder (PMDD)

Paroxetine HCL CR extended‑release tablets, USP are available as: • 12.5 mg yellow, round tablets, one face is plain and the other face is engraved with “12.5”. • 25 mg pink, round tablets, one face is plain and the other face is engraved with “25”. • 37.5 mg blue, round tablets, one face is plain and the other face is engraved with “37.5”. Extended-release tablets:12.5 mg, 25 mg, and 37.5 mg tablets. ( 3 )

Paroxetine HCL CR extended‑release tablets, USP are available as: 12.5 mg yellow, round tablets, one face is plain and the other face is engraved with “12.5”. Bottles of 30 NDC 60505-1316-3 25 mg pink, round tablets, one face is plain and the other face is engraved with “25”. Bottles of 30 NDC 60505-1317-3 37.5 mg blue, round tablets, one face is plain and the other face is engraved with “37.5”. Bottles of 30 NDC 60505-1318-3 Store at or below 25°C (77°F); [see USP].

Paroxetine HCL CR is contraindicated in patients: Taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome [See Warnings and Precautions ( 5.2 ), Drug Interactions (7)]. Paroxetine HCL CR should not be used in patients receiving medications that can prolong QT interval and are also metabolized by CYP450 2D6,such as thioridazine or pimozide [see Drug Interactions (7),Warnings and Precautions (5.3)]. With known hypersensitivity (e.g., anaphylaxis, angioedema, Stevens-Johnson syndrome) to paroxetine or to any of the inactive ingredients in Paroxetine HCL CR [see Adverse Reactions ( 6.1 , 6.2 )]. Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing a MAOIs. ( 4 , 5.2 , 7 ) Concomitant use of pimozide or thioridazine. ( 4 , 5.3 , 7 ) Known hypersensitivity to paroxetine or to any of the inactive ingredients in Paroxetine HCL CR. ( 4 )

Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone. If occurs, discontinue Paroxetine HCL CR and serotonergic agents and initiate supportive measures. ( 5.2 ) Embryofetal Toxicity : May cause fetal harm. Meta-analysis of epidemiological studies have shown increased risk (less than 2-fold) of cardiovascular malformations with exposure during the first trimester.( 5.4 , 8. 1) Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, other antiplatelet drugs, warfarin, and other anticoagulant drugs may increase risk. ( 5.5 ) Activation of Mania/Hypomania : Screen patients for bipolar disorder. ( 5.6 ) Seizures : Use with caution in patients with seizure disorders. ( 5.8 ) Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles, treated with antidepressants (5.9 ) Sexual Dysfunction: Paroxetine HCL CR may cause symptoms of sexual dysfunction. ( 5.13 ) 5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 2. Table 2: Risk Differences of the Number of Patients of Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range Drug-Placebo Difference in Number of Patients of Suicidal Thoughts and Behaviors per 1,000 Patients Treated I ncreases Compared to Placebo <18 years old 14 additional patients 18 to 24 years old 5 additional patients Decreases Compared to Placebo 25 to 64 years old 1 fewer patient ≥65 years old 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing Paroxetine HCL CR, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including Paroxetine HCL CR, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St. John's Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications ( 4 ), Drug Interactions ( 7.1 )]. Serotonin syndrome can also occur when these drugs are used alone. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The concomitant use of Paroxetine HCL CR with MAOIs is contraindicated. In addition, do not initiate Paroxetine HCL CR in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking Paroxetine HCL CR, discontinue Paroxetine HCL CR before initiating treatment with the MAOI [see Contraindications ( 4 ), Drug Interactions (7.1) ]. Monitor all patients taking Paroxetine HCL CR for the emergence of serotonin syndrome. Discontinue treatment with Paroxetine HCL CR and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Paroxetine HCL CR with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Drug Interactions Leading to QT Prolongation Cases of QT interval prolongation have been reported, although causality with Paroxetine HCL CR has not been established. Paroxetine HCL CR should be used with caution in patients with a history of QT interval prolongation, patients taking anti-arrhythmic or other medications that may potentially prolong QT interval, or those with relevant pre-existing cardiac disease. The CYP2D6 inhibitory properties of paroxetine can elevate plasma levels of thioridazine and pimozide. …

The following adverse reactions are included in more detail in other sections of the prescribing information: Hypersensitivity reactions to paroxetine [see Contraindications ( 4 )] Suicidal Thoughts and Behaviors [see Warnings and Precautions ( 5.1 )] Serotonin Syndrome [see Warnings and Precautions ( 5.2 )] Embryofetal and Neonatal Toxicity [see Warnings and Precautions ( 5.4 )] Increased Risk of Bleeding [see Warnings and Precautions ( 5.5 )] Activation of Mania/Hypomania [see Warnings and Precautions ( 5.6 )] Discontinuation Syndrome [see Warnings and Precautions ( 5.7 )] Seizures [see Warnings and Precautions ( 5.8 )] Angle-closure Glaucoma [see Warnings and Precautions ( 5.9 )] Hyponatremia [see Warnings and Precautions ( 5.10 )] Bone Fracture [see Warnings and Precautions ( 5.12 )] Sexual Dysfunction [see Warnings and Precautions ( 5.13 )] Most common adverse reactions (≥5% and at …

Drugs Highly Bound to Plasma Protein: Monitor for adverse reactions and reduce dosage of Paroxetine HCL CR or other protein-bound drugs (e.g., warfarin) as warranted. ( 7 ) Drugs Metabolized by CYP2D6: Reduce dosage of drugs metabolized by CYP2D6 as warranted. ( 7 ) Concomitant use with Tamoxifen: Consider use of an alternative antidepressant with little or no CYP2D6 inhibition. ( 5.11 , 7 ) 7.1 Clinically Significant Drug Interactions with Paroxetine HCL CR Table 6 includes clinically significant drug interactions with Paroxetine HCL CR. Table 6: Clinically Significant Drug Interactions with Paroxetine HCL CR Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact The concomitant use of SSRIs, including Paroxetine HCL CR, and MAOIs increases the risk of serotonin syndrome. …