BRISDELLE® (paroxetine) capsules

BRISDELLE® (paroxetine) capsules

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BRISDELLE® (paroxetine) capsules

BRISDELLE (paroxetine) is an orally administered selective serotonin reuptake inhibitor (SSRI) for the treatment of moderate to severe VMS associated with menopause. It is identified chemically as (-)-trans -4R-(4’-fluorophenyl) – 3S – [(3’, 4’-methylenedioxyphenoxy) methyl] piperidine mesylate and has the empirical formula of C19H20FNO3•CH3SO3H. The molecular weight is 425.5 (329.4 as free base).

The mesylate salt of paroxetine is an odorless, off-white powder, having a melting point range of 147° to 150°C and a solubility of more than 1 g/mL in water.

Each pink capsule contains 9.69 mg paroxetine mesylate equivalent to 7.5 mg paroxetine base.

Inactive ingredients consist of: dibasic calcium phosphate, sodium starch glycolate, magnesium stearate, gelatin, titanium dioxide, FD&C Yellow #6, FD&C Red #3, FD&C Red #40, shellac, and black iron oxide.

Indications and usage

BRISDELLE is a selective serotonin reuptake inhibitor (SSRI) indicated for the treatment of moderate to severe vasomotor symptoms associated with menopause (VMS)

Limitation of Use: BRISDELLE is not indicated for the treatment of any psychiatric condition. BRISDELLE contains 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 BRISDELLE have not been established for any psychiatric condition. Patients who require paroxetine for treatment of a psychiatric condition should discontinue BRISDELLE and initiate a paroxetine-containing medication that is indicated for such use.

Mechanism of Action

Nonclinical studies have shown that paroxetine is an SSRI. BRISDELLE is not an estrogen, and its mechanism of action for the treatment of VMS is unknown.

Dosage and administration

The recommended dosage of BRISDELLE for the treatment of moderate to severe VMS is 7.5 mg once daily, at bedtime, with or without food.

Use of BRISDELLE Before or After a Monoamine Oxidase Inhibitor (MAOI)

Wait at least 14 days after discontinuation of an MAOI before initiating therapy with BRISDELLE. Conversely, allow at least 14 days after stopping BRISDELLE before starting an MAOI

Adverse reactions

The most common adverse reactions (≥ 2%) reported in clinical trials were: headache, fatigue, and nausea/vomiting

Contraindications

Monoamine Oxidase Inhibitors: Concomitant use of an MAOI with BRISDELLE or within 14 days of stopping treatment with BRISDELLE is contraindicated because of an increased risk of serotonin syndrome. The use of BRISDELLE within 14 days of stopping an MAOI is also contraindicated

Starting BRISDELLE in a patient who is being treated with linezolid or intravenous methylene blue, both of which inhibit monoamine oxidase, is also contraindicated because of an increased risk of serotonin syndrome.

Thioridazine: Concomitant use of BRISDELLE with thioridazine is contraindicated, because thioridazine prolongs the QT interval, and paroxetine can increase thioridazine levels

Pimozide: Concomitant use of BRISDELLE with pimozide is contraindicated because pimozide prolongs the QT interval, and paroxetine increases pimozide levels.

Hypersensitivity to any Ingredient in BRISDELLE: BRISDELLE is contraindicated in patients with a history of hypersensitivity to paroxetine or any of the other ingredients in BRISDELLE.

Pregnancy: Menopausal VMS does not occur during pregnancy and BRISDELLE may cause fetal harm

Warnings and precautions

Suicidal Thoughts and Behaviors: BRISDELLE is not approved for any psychiatric condition.

Antidepressants, including those that contain an SSRI, increase the risk of suicidal thinking and behavior (suicidality) in pediatric and young adult patients when used to treat major depressive disorder (MDD) and other psychiatric disorders. There is limited information regarding suicidality in women who use BRISDELLE for treatment of VMS. The BRISDELLE trials excluded women with a presence or history of previous psychiatric disorders.

Consider discontinuing BRISDELLE in patients with worsening depression or those who experience emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.

Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with SSRIs, including paroxetine, alone but particularly with concomitant use of serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort), and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat depression and others such as linezolid and intravenous methylene blue).

Serotonin syndrome 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), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Monitor patients for the emergence of serotonin syndrome

Potential Impact on Tamoxifen Efficacy: It is uncertain whether the co-administration of paroxetine and tamoxifen has a significant adverse effect on the efficacy of tamoxifen. Some studies have shown that the efficacy of tamoxifen, as measured by the risk of breast cancer relapse/mortality, may be reduced when co-prescribed with paroxetine as a result of paroxetine’s irreversible inhibition of CYP2D6. However, other studies have failed to demonstrate such a risk.

Abnormal Bleeding: SSRIs, including BRISDELLE, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to lifethreatening hemorrhages. Caution patients about the risk of bleeding associated with the concomitant use of BRISDELLE and NSAIDs, aspirin, or other drugs that affect coagulation.

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Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressants and BRISDELLE may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Hyponatremia: Hyponatremia may occur as a result of treatment with SSRIs, including BRISDELLE. Elderly patients may be at greater risk. In many cases, the hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Bone Fracture: Epidemiological studies on bone fracture risk following exposure to SSRIs have reported an association between SSRI treatment and fractures. It is unknown to what extent fracture risk is directly attributable to SSRI treatment. If a BRISDELLE-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising, consider the possibility of a fragility fracture.

Seizures: In premarketing testing of paroxetine, seizures occurred in 0.1% of paroxetine-treated patients. Use BRISDELLE cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold. Evaluate and consider discontinuing use in any patient who develops seizures.

Akathisia: The use of paroxetine or other SSRIs has been associated with the development of akathisia, which is characterized by an inner sense of restlessness and psychomotor agitation such as an inability to sit or stand still usually associated with subjective distress. This is most likely to occur within the first few weeks of treatment. Discontinue treatment with BRISDELLLE if akathisia occurs.

Potential for Cognitive and Motor Impairment: BRISDELLE has the potential to impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that the drug treatment does not affect them adversely.

Drug interactions

No drug-drug interaction studies have been conducted with BRISDELLE.

Use in specific populations

Pregnancy: Pregnancy Category X. BRISDELLE is contraindicated in pregnant women because menopausal VMS does not occur during pregnancy and paroxetine can cause fetal harm. Epidemiological studies have shown that infants exposed to paroxetine in the first trimester of pregnancy may have an increased risk of cardiovascular malformations. Cardiac malformations are a common congenital abnormality.

Nursing Mothers: Paroxetine is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from BRISDELLE, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established; BRISDELLE is not indicated in the pediatric population.

Geriatric Use: Clinical studies of BRISDELLE did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients may have elevated paroxetine plasma concentrations compared to younger patients. However, no BRISDELLE dose adjustment is considered necessary in elderly patients. SSRIs have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event.

Renal Impairment: No BRISDELLE dose adjustment is considered necessary in patients with renal impairment.

Hepatic Impairment: No BRISDELLE dose adjustment is considered necessary in patients with liver impairment.

Overdosage

There is limited clinical experience with BRISDELLE overdosage in humans, as there were no overdoses reported in the clinical studies.

Spontaneous cases of deliberate or accidental overdosage during paroxetine treatment have been reported; some of these cases were fatal and some of the fatalities appeared to involve paroxetine alone. Of nonfatal cases with known outcome, most recovered without sequelae. The largest known ingestion involved 2000 mg of paroxetine (267 times the maximum recommended daily dose) in a patient who recovered.

Commonly reported adverse reactions associated with paroxetine overdosage include somnolence, coma, nausea, tremor, tachycardia, confusion, vomiting, and dizziness. Other notable signs and symptoms observed with overdoses involving paroxetine (alone or with other substances) include mydriasis, convulsions (including status epilepticus), ventricular dysrhythmias (including torsades de pointes), hypertension, aggressive reactions, syncope, hypotension, stupor, bradycardia, dystonia, rhabdomyolysis, symptoms of hepatic dysfunction (including hepatic failure, hepatic necrosis, jaundice, hepatitis, and hepatic steatosis), serotonin syndrome, manic reactions, myoclonus, acute renal failure, and urinary retention.

Management of Overdosage

Treatment should consist of those general measures employed in the management of overdosage with any SSRI. Consult with a certified poison control center for up-to-date guidance and advice on treatment of overdosage.

Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. In managing overdosage, consider the possibility of multiple drug involvement.

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