"The U.S. Food and Drug Administration today approved Osphena (ospemifene) to treat women experiencing moderate to severe dyspareunia (pain during sexual intercourse), a symptom of vulvar and vaginal atrophy due to menopause.
The following serious adverse reactions are discussed elsewhere in labeling:
- Suicidality [see WARNINGS AND PRECAUTIONS]
- Serotonin syndrome [see WARNINGS AND PRECAUTIONS]
- Abnormal bleeding [see WARNINGS AND PRECAUTIONS]
- Hyponatremia [see WARNINGS AND PRECAUTIONS]
- Bone Fracture [see WARNINGS AND PRECAUTIONS]
- Mania/Hypomania [see WARNINGS AND PRECAUTIONS]
- Seizure [see WARNINGS AND PRECAUTIONS]
- Akathisia [see WARNINGS AND PRECAUTIONS]
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 BRISDELLE 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]. In these trials, a total of 635 women were exposed to BRISDELLE 7.5 mg administered orally once daily and 641 women received placebo. The majority of BRISDELLE-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 BRISDELLE 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 BRISDELLE reported at least 1 adverse reaction in the three controlled studies. The most common adverse reactions ( ≥ 2% and more common among BRISDELLE-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 BRISDELLE 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 (%)|
(n = 635)
(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)|
|Nausea, vomiting||27 (4.3)||15 (2.3)|
Certain symptoms were seen more frequently in women at the time of discontinuation of BRISDELLE 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 BRISDELLE-treated patients reported a serious adverse reaction of suicidal ideation and one BRISDELLE-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.
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.
General Disorders and Administration Site Conditions: Death, Drug withdrawal syndrome, Malaise.
Investigations: Elevated liver tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction).
Psychiatric Disorders: Aggression, Agitation, Anxiety, Confusional state, Depression, Disorientation, Homicidal ideation, Insomnia, Restlessness. 9
Respiratory, Thoracic and Mediastinal Disorders: Pulmonary hypertension.
Read the Brisdelle (paroxetine capsules 7.5 mg) Side Effects Center for a complete guide to possible side effects
No drug-drug interaction studies have been conducted with BRISDELLE.
Potential for BRISDELLE to Affect Other Drugs
Paroxetine is a strong CYP2D6 inhibitor. Clinical drug interaction studies have been performed with substrates of CYP2D6 and show that paroxetine can inhibit the metabolism of drugs metabolized by CYP2D6 [see CLINICAL PHARMACOLOGY]. Table 2 contains examples of drugs with a metabolism that may be affected by co-administration with BRISDELLE. 10
Table 2 : Effects of Paroxetine on Other Drugs
|Concomitant Drug Name||Effect of Paroxetine on Other Drugs||Clinical Recommendations|
|Thioridazine||Increased plasma concentrations of thioridazine||Concomitant use of thioridazine and BRISDELLE is contraindicated.|
|Potential QTc prolongation|
|Pimozide||Increased plasma concentrations of pimozide. Potential QTc prolongation||Concomitant use of pimozide and BRISDELLE is contraindicated.|
|Tamoxifen||Reduced plasma concentrations of active tamoxifen metabolite||Consider avoiding concomitant use of tamoxifen and BRISDELLE.|
|Tricyclic Antidepressant (TCA) (e.g., Desipramine)||Increased plasma concentrations and elimination half-life||Plasma TCA concentrations may need to be monitored and the dose of TCA may need to be reduced if a TCA is co-administered with BRISDELLE. Monitor tolerability.|
|Risperidone||Increased plasma concentrations of risperidone||A lower dosage of risperidone may be necessary (see the Full Prescribing Information for risperidone). Monitor tolerability.|
|Atomoxetine||Increased exposure of atomoxetine||A lower dosage of atomoxetine may be necessary (see Full Prescribing Information for atomoxetine). Monitor tolerability.|
|Drugs Highly Bound to Plasma Protein (e.g., Warfarin)||Increased free plasma concentrations||The dosage of warfarin may need to be reduced. Monitor tolerability and the International Normalized Ratio.|
|Digoxin||Decreased plasma concentrations of digoxin||Dosage of digoxin may need to be increased. Monitor digoxin concentrations and clinical effect.|
|Theophylline||Increased plasma concentrations of theophylline||Dosage of theophylline may need to be decreased. Monitor theophylline concentrations and tolerability.|
Use caution if co-administering BRISDELLE with other drugs that are metabolized by CYP2D6, including nortriptyline, amitriptyline, imipramine, desipramine, fluoxetine, phenothiazines, risperidone, and Type 1C antiarrhythmics (e.g., propafenone, flecainide, and encainide).
Potential for Other Drugs to Affect BRISDELLE
The metabolism and pharmacokinetics of paroxetine may be affected by the induction and inhibition of drug metabolizing enzymes such as CYP2D6. Table 3 contains a list of drugs that may affect the pharmacokinetics of BRISDELLE when administered concomitantly [see CLINICAL PHARMACOLOGY].
Table 3 : Effects of Other Drugs on Paroxetine
|Concomitant Drug Name||Effect of Concomitant Drug on Paroxetine||Clinical Recommendations|
|Phenobarbital||Decreased paroxetine exposure||No dose adjustment for BRISDELLE.|
|Phenytoin||Decreased paroxetine exposure||Monitor clinical effect of BRISDELLE.|
|Fosamprenavir/ Ritonavir||Decreased plasma concentration of paroxetine|
|Cimetidine||Increased plasma concentration of paroxetine|
Use caution if co-administering BRISDELLE with other drugs that inhibit CYP2D6 (e.g., quinidine).
Other Potentially Significant Drug Interactions
Monoamine Oxidase Inhibitors (MAOIs)
Serious adverse reactions such as serotonin syndrome have been reported in patients receiving a concomitant SSRI and MAOI, in patients started on an SSRI who recently received an MAOI and in patients started on an MAOI who recently received an SSRI. Therefore, concomitant use of MAOIs with BRISDELLE or use of BRISDELLE and an MAOI within 14 days of each other is contraindicated [see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].
If concomitant use of BRISDELLE with other serotonergic drugs (e.g., triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort) is clinically warranted, consider the increased risk of serotonin syndrome and carefully observe the patient, particularly during treatment initiation [see WARNINGS AND PRECAUTIONS].
An interaction between paroxetine and tryptophan may occur when they are co-administered. Adverse experiences, consisting primarily of headache, nausea, sweating, and dizziness, have been reported when tryptophan was administered to patients taking paroxetine. Consequently, concomitant use of BRISDELLE with tryptophan is not recommended.
If concomitant use of BRISDELLE with a serotonergic drug is warranted, carefully observe the patient, particularly during treatment initiation. There have been postmarketing reports of serotonin syndrome with the use of an SSRI and a triptan.
BRISDELLE contains paroxetine, which is also the active ingredient in other drugs. The concomitant use of BRISDELLE with other paroxetine products is not recommended [see INDICATIONS AND USAGE].
Drugs that Interfere with Homeostasis (e.g., NSAIDs, Aspirin, and Warfarin)
Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs are co-administered with NSAIDs, aspirin, and warfarin or other drugs that affect coagulation. There may be a pharmacodynamic interaction between paroxetine and warfarin that causes an increased bleeding diathesis despite unaltered prothrombin time. Carefully monitor patients receiving warfarin therapy when BRISDELLE is initiated or discontinued [see WARNINGS AND PRECAUTIONS].
Last reviewed on RxList: 7/12/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Brisdelle Information
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