Brisdelle

Paroxetine is also sometimes used to treat chronic headaches, tingling in the hands and feet caused by diabetes, and certain male sexual problems. Paroxetine is also used with other medications to treat bipolar disorder (mood that changes from depressed to abnormally excited). Talk to your doctor about the possible risks of using this drug for your condition.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

• Brisdelle is classified as FDA pregnancy risk category X and should not be used during pregnancy because menopausal vasomotor symptoms do not occur during pregnancy, and Brisdelle can cause harm to the unborn baby.
• Paroxetine is excreted in human milk. Due to the potential risk of causing harm to the nursing infant, Brisdelle should only be using by a nursing mother if clearly needed.

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Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• MAO inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Emsam, Eldepryl, Zelapar) and tranylcypromine (Parnate)
• Mellaril (thioridazine)
• Orap (pimozide)
• triptans used to treat migraine headache
• other antidepressants (SSRIs, SNRIs, tricyclics, or lithium) or antipsychotics
• drugs that affect serotonin, such as lithium, tramadol, tryptophan, St. John’s wort
• certain drugs used to treat irregular heart beats
• certain drugs used to treat schizophrenia
• certain drugs used to treat HIV infection
• certain drugs that affect the blood, such as warfarin, aspirin, and ibuprofen
• certain drugs used to treat epilepsy
• atomoxetine
• cimetidine
• fentanyl
• metoprolol
• certain medicines used to treat seizures (like phenobarbital and phenytoin)
• procyclidine
• tamoxifen

Ask your healthcare provider if you are not sure if you are taking any of these medications.

Take Brisdelle exactly as prescribed. Follow the directions on your prescription label carefully.

The recommended dosage of Brisdelle is 7.5 mg once daily, at bedtime.

      Dosage Information

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 [see Contraindications ( 4.1), Warnings and Precautions ( 5.2) and Drug Interactions ( 7.3)] .

      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.

      Pharmacodynamics

Studies at clinically relevant doses in humans have demonstrated that paroxetine blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that paroxetine is a selective inhibitor of neuronal serotonin reuptake and has weak effects on norepinephrine and dopamine neuronal reuptake. In vitro radioligand binding studies indicate that paroxetine has little affinity for muscarinic alpha 1-, alpha 2-, beta-adrenergic-, dopamine (D 2)-, 5-HT 1-, 5-HT 2-, and histamine (H 1)-receptors.

      Pharmacokinetics

Absorption, Distribution, Metabolism and Excretion

• Absorption
  
  
• Paroxetine is completely absorbed after oral dosing of the mesylate salt. In a study in which healthy postmenopausal women (n=24) received Brisdelle 7.5 mg capsules as a daily dose for 14 days, steady-state paroxetine concentrations were achieved by approximately 12 days of dosing for most subjects, although it may take substantially longer in an occasional patient. Peak concentrations were reached at a median of 6 hours (3 to 8 hours range). Steady-state mean values of C max, C min, and AUC 0-last were 13.10 ng/mL (CV 91%), 7.17 ng/mL (CV 99%), and 237 hr*ng/mL (CV 94%), respectively.
  
  
• Steady-state AUC 0-24 values were about 3 times those of AUC 0-inf following a single dose, indicating non-linear pharmacokinetics. Steady-state C max values were approximately 5 times greater than those attained after a single dose and steady-state exposure based on AUC 0-24 was about 10 times greater than AUC 0-24 after a single dose.
  
  
• The nonlinear kinetics and excess accumulation are due to the fact that CYP2D6, an enzyme that is in part responsible for paroxetine metabolism, is readily saturable.
  
  
• The effects of food on the bioavailability of paroxetine were studied with paroxetine tablets at higher strength. AUC was only slightly increased (6%) when drug was administered with food but the C max was 29% greater, while the time to reach peak plasma concentration decreased from 6.4 hours post-dosing to 4.9 hours. Brisdelle can be taken with or without food.
  
  
• Distribution
  
  
• Paroxetine distributes throughout the body, including the central nervous system, with only 1% remaining in the plasma.
  
  
• Approximately 95% and 93% of paroxetine is bound to plasma protein at 100 ng/mL and 400 ng/mL, respectively. Under clinical conditions, paroxetine concentrations would normally be less than 100 ng/mL. Paroxetine does not alter the in vitro protein binding of phenytoin or warfarin.
  
  
• Metabolism
  
  
• Paroxetine is extensively metabolized after oral administration. The principal metabolites are polar and conjugated products of oxidation and methylation, which are readily cleared. Conjugates with glucuronic acid and sulfate predominate, and major metabolites have been isolated and identified. Data indicate that the metabolites have no more than 1/50 the potency of the parent compound at inhibiting serotonin uptake. The metabolism of paroxetine is accomplished in part by cytochrome CYP2D6. Saturation of this enzyme at clinical doses appears to account for the nonlinearity of paroxetine kinetics with increasing dose and increasing duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug-drug interactions [see Drug Interactions ( 7)] . At steady state, when the CYP2D6 pathway is essentially saturated, paroxetine clearance is governed by alternative P450 isozymes, which, unlike CYP2D6, show no evidence of saturation.
  
  
• Excretion
  
  
• Approximately 64% of a 30 mg oral solution of paroxetine was excreted in the urine with 2% as the parent compound and 62% as metabolites over a 10-day post-dosing period. About 36% of the dose was excreted in the feces (probably via the bile), mostly as metabolites and less than 1% as the parent compound over the 10-day post-dosing period.
  
  

Specific Populations

• Renal and Liver Impairment
  
  
• Increased plasma concentrations of paroxetine occur in subjects with renal and hepatic impairment. The mean plasma concentration in patients with creatinine clearance below 30 mL/min was approximately 4 times greater than seen in normal volunteers. Patients with creatinine clearance of 30 to 60 mL/min and patients with hepatic impairment had about a 2-fold increase in plasma concentrations (AUC, C max). No Brisdelle dose adjustment is considered necessary in patients with renal or hepatic impairment.
  
  
• Elderly Patients
  
  
• In a multiple-dose study in the elderly at daily paroxetine doses of 20, 30, and 40 mg, C min concentrations were about 70% to 80% greater than the respective C min concentrations in nonelderly subjects. No Brisdelle dose adjustment is considered necessary in elderly patients.
  
  

Drug Interaction Studies

• Potential Effect of Brisdelle on Other Drugs
  • 
    Drugs Metabolized by CYP3A4
    
    
  • An in vivo drug interaction study involving the co-administration under steady-state conditions of paroxetine and terfenadine, a substrate for cytochrome CYP3A4, revealed no effect of paroxetine on terfenadine pharmacokinetics. In vitro studies have shown ketoconazole, a potent inhibitor of CYP3A4 activity, to be at least 100 times more potent than paroxetine as an inhibitor of the metabolism of several substrates for CYP3A4, including astemizole, triazolam, and cyclosporine. Based on the assumption that the relationship between paroxetine’s in vitro Ki and its lack of effect on terfenadine’s in vivo clearance predicts its effect on other CYP3A4 substrates, paroxetine’s extent of inhibition of CYP3A4 activity is not likely to be of clinical significance.
    
    
  • Drugs Metabolized by CYP2D6
    
    
  • Many drugs are metabolized by the cytochrome P450 isozyme CYP2D6. Like other agents that are metabolized by CYP2D6, paroxetine may significantly inhibit the activity of this isozyme. In most patients (> 90%), this CYP2D6 isozyme is saturated early during paroxetine dosing.
    
    
  • Specific studies investigating the effect of paroxetine on drugs metabolized by CYP2D6 are listed below:
    
    
  • Pimozide: Higher doses of paroxetine have been shown to elevate plasma levels of pimozide. In a controlled study of healthy volunteers, after paroxetine was titrated to 60 mg daily, co-administration of a single dose of 2 mg pimozide was associated with mean increases in pimozide AUC of 151% and C max of 62%, compared to pimozide administered alone [see Drug Interactions ( 7.1)] .
    
    
  • Tamoxifen: 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 [see Warnings and Precautions ( 5.3) and Drug Interactions ( 7.1)] .
    
    
  • Desipramine: In one study, daily dosing of paroxetine (20 mg once daily) under steady-state conditions increased single dose desipramine (100 mg) C max, AUC, and T 1/2 by an average of approximately 2-, 5-, and 3-fold, respectively [see Drug Interactions ( 7.1)] .
    
    
  • Risperidone: Daily dosing of paroxetine 20 mg in patients stabilized on risperidone (4 to 8 mg/day), a CYP2D6 substrate, increased mean plasma concentrations of risperidone approximately 4-fold, decreased 9-hydroxyrisperidone concentrations approximately 10%, and increased concentrations of the active moiety (the sum of risperidone plus 9-hydroxyrisperidone) approximately 1.4-fold [see Drug Interactions ( 7.1)] .
    
    
  • Atomoxetine: The effect of paroxetine on the pharmacokinetics of atomoxetine has been evaluated when both drugs were at steady state. In healthy volunteers who were extensive metabolizers of CYP2D6, paroxetine 20 mg daily was given in combination with 20 mg atomoxetine every 12 hours. This resulted in increases in steady-state atomoxetine AUC values that were 6- to 8-fold greater and in atomoxetine C max values that were 3- to 4-fold greater than when atomoxetine was given alone [see Drug Interactions ( 7.1)] .
    
    
  • Digoxin: Mean digoxin AUC at steady state decreased by 15% in the presence of paroxetine [see Drug Interactions ( 7.1)] .
    
    
  • Beta Blockers: In a study in which propranolol (80 mg twice daily) was dosed orally for 18 days, the steady-state plasma concentrations of propranolol were unaltered during co-administration with paroxetine (30 mg once daily) for the final 10 days. The effects of propranolol on paroxetine have not been evaluated.
    
    
• Potential Effect of Other Drugs on Brisdelle
  • 
    Concomitant use of paroxetine with other drugs that alter CYP enzymes activities including CYP2D6 may affect the plasma concentrations of paroxetine. Specific studies investigating the effect of other drugs on paroxetine are listed below:
    
    
  • Cimetidine: Cimetidine inhibits many cytochrome P450 enzymes. In a study in which paroxetine (30 mg once daily) was dosed orally for 4 weeks, steady-state plasma concentrations of paroxetine were increased by approximately 50% during co-administration with oral cimetidine (300 mg three times daily) for the final week [see Drug Interactions ( 7.2)] .
    
    
  • Phenobarbital: Phenobarbital induces many cytochrome P450 enzymes. When a single oral 30 mg dose of paroxetine was administered at phenobarbital steady state (100 mg once daily for 14 days), paroxetine AUC and T 1/2 were reduced (by an average of 25% and 38%, respectively) compared to paroxetine administered alone. The effect of paroxetine on phenobarbital pharmacokinetics was not studied. Because paroxetine exhibits nonlinear pharmacokinetics, the results of this study may not address the case where the 2 drugs are both being chronically dosed [see Drug Interactions ( 7.2)] .
    
    
  • Phenytoin: When a single oral 30 mg dose of paroxetine was administered at phenytoin steady state (300 mg once daily for 14 days), paroxetine AUC and T 1/2 were reduced (by an average of 50% and 35%, respectively) compared to paroxetine administered alone. In a separate study, when a single oral 300 mg dose of phenytoin was administered at paroxetine steady state (30 mg once daily for 14 days), phenytoin AUC was slightly reduced (12% on average) compared to phenytoin administered alone. Because both drugs exhibit nonlinear pharmacokinetics, the above studies may not address the case where the 2 drugs are both being chronically dosed [see Drug Interactions ( 7.2)] .
    
    
  • Digoxin: A clinical drug interaction study showed that concurrent use of digoxin did not affect paroxetine exposure.
    
    
  • Diazepam: A clinical drug interaction study showed that concurrent use of diazepam did not affect paroxetine exposure.

      Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Two-year carcinogenicity studies were conducted in rodents given paroxetine in the diet at 1, 5, and 25 mg/kg/day (mice) and 1, 5, and 20 mg/kg/day (rats). The doses used in these carcinogenicity studies were approximately 16 (mouse) and 26 (rat) times the MHRD for VMS. There was a significantly greater number of male rats in the high-dose group with reticulum cell sarcomas (1/100, 0/50, 0/50, and 4/50 for control, low-, middle-, and high-dose groups, respectively) and a significantly increased linear trend across groups for the occurrence of lymphoreticular tumors in male rats. Female rats were not affected. Although there was a dose-related increase in the number of tumors in mice, there was no drug-related increase in the number of mice with tumors. The relevance of these findings to humans is unknown.

Mutagenesis

Paroxetine produced no genotoxic effect in a battery of 5 in vitro and 2 in vivo assays that included the following: bacterial mutation assay, mouse lymphoma mutation assay, unscheduled DNA synthesis assay, and tests for cytogenetic aberrations in vivo in mouse bone marrow and in vitro in human lymphocytes and in a dominant lethal test in rats.

Impairment of Fertility

A reduced pregnancy rate was found in reproduction studies in rats at a paroxetine dose of 15 mg/kg/day, which is 19 times the MRHD for VMS on an mg/m 2 basis. Irreversible lesions occurred in the reproductive tract of male rats after dosing in toxicity studies for 2 to 52 weeks. These lesions consisted of vacuolation of epididymal tubular epithelium at 50 mg/kg/day and atrophic changes in the seminiferous tubules of the testes with arrested spermatogenesis at 25 mg/kg/day (65 times and 32 times the MHRD for VMS on an mg/m 2 basis, respectively).

Brisdelle (paroxetine) is an antidepressant belonging to a group of drugs called selective serotonin reuptake inhibitors (SSRIs). Paroxetine affects chemicals in the brain that may become unbalanced.

Brisdelle is use for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause.

Brisdelle contains a low dose of paroxetine, a medicine also used to treat a number of psychiatric disorders. The lower dose of paroxetine has not been studied in any psychiatric conditions and is therefore not approved for any psychiatric uses.

Do not take Brisdelle if you:

• take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid.
  • Do not take an MAOI within 14 days of stopping Brisdelle unless directed to do so by your healthcare provider.
  • Do not start this medicine if you stopped taking an MAOI in the last 14 days unless directed to do so by your healthcare provider.
  • People who take Brisdelle close in time to an MAOI may have serious or life-threatening side effects. Get medical help right away if you have any of these symptoms:
    • high fever
    • uncontrolled muscle spasms
    • stiff muscles
    • rapid changes in heart rate or blood pressure
    • confusion
    • loss of consciousness (pass out)
• take thioridazine. Do not take thioridazine together with Brisdelle because this can cause serious heart rhythm problems or sudden death.
• take the antipsychotic medicine pimozide. Do not take pimozide together with this medicine because this can cause serious heart problems.
• are allergic to paroxetine or any of the ingredients in Brisdelle. See the end of this Medication Guide for a complete list of ingredients.
• are pregnant. Paroxetine is not for pregnant women. Paroxetine, the active ingredient, can harm your unborn baby. Risks to your unborn baby include an increased risk of birth defects, particularly heart defects. Your baby may also have certain other serious symptoms shortly after birth.

• Brisdelle can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how it affects you.

Applies to paroxetine: oral capsule, oral suspension, oral tablet, oral tablet extended release

General

Side effects are generally reported as mild. The most common side effects associated with treatment discontinuation in clinical trials included somnolence, insomnia, agitation, tremor, anxiety, dizziness, headache, constipation, nausea, diarrhea, dry mouth, vomiting, flatulence, asthenia, abnormal ejaculation, sweating, impotence, and decreased libido.

The most common dose-dependent side effects associated with treatment discontinuation in clinical trials for the treatment of premenstrual dysphoric disorder with controlled-release paroxetine (the active ingredient contained in Brisdelle) 25 mg compared with 12.5 mg included nausea, somnolence, impaired concentration, dry mouth, dizziness, decreased appetite, sweating, tremor, and yawn.

The most common side effects associated with treatment discontinuation in the treatment of vasomotor symptoms in clinical trials included abdominal pain, attention disturbances, headache, and suicidal ideation.

In a placebo-controlled study in elderly patients with major depressive disorder, the most common side effects associated with treatment discontinuation of controlled-release paroxetine included nausea, headache, depression, and abnormal LFTs.

There may be adaptation to some side effects (such as nausea and dizziness) but not to others (such as dry mouth, somnolence, and asthenia) with continued therapy. Paroxetine is less likely than tricyclic antidepressants to be associated with dry mouth, constipation, and somnolence.[Ref]

Psychiatric

Very common (10% or more): Insomnia
Common (1% to 10%): Abnormal dreams, agitation, anxiety, depersonalization, depression, drugged feeling, emotional lability, lack of emotion, nervousness
Uncommon (0.1% to 1%): Abnormal thinking, alcohol abuse, bruxism, euphoria, hallucinations, hostility, lack of emotion, manic reaction, neurosis, paranoid reaction
Rare (less than 0.1%): Abnormal electroencephalogram, antisocial reaction, bulimia, delirium, delusions, drug dependence, hysteria, irritability, manic-depressive reaction, panic attacks, psychosis, psychotic depression, stupor, withdrawal syndrome
Frequency not reported: Suicidal ideation and behavior
Postmarketing reports: Confusional state, disorientation, homicidal ideation, restlessness[Ref]

Antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. An increased risk of suicidal thinking and behavior in children, adolescents, and young adults (aged 18 to 24 years) with major depressive disorder (MDD) and other psychiatric disorders has been reported with short-term use of antidepressant drugs.

Adult and pediatric patients receiving antidepressants for MDD, as well as for psychiatric and nonpsychiatric indications, have reported symptoms that may be precursors to emerging suicidality, including anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania. Causality has not been established.

Pooled results from clinical trials report hallucinations in 22 of 9089 patients who received paroxetine and 4 of 3187 patients who received placebo.[Ref]

Nervous system

Extrapyramidal symptoms such as akathisia, bradykinesia, cogwheel rigidity, dystonia, hypertonia, and oculogyric crisis have been associated with concomitant pimozide therapy.

Potentially life-threatening serotonin syndrome has been reported with SSRIs and SNRIs as monotherapy, but particularly with concomitant use of other serotonergic drugs and drugs that impair the metabolism of serotonin. Signs and symptoms associated with serotonin syndrome or neuroleptic malignant syndrome included agitation, confusion, diaphoresis, diarrhea, fever, hypertension, rigidity, and tachycardia, and were in some cases associated with concomitant use of serotonergic drugs.[Ref]

Very common (10% or more): Dizziness, headache, somnolence, tremor
Common (1% to 10%): Amnesia, anxiety, CNS stimulation, confusion, hypertonia, impaired concentration, migraine, myoclonus, paresthesia, taste perversion
Uncommon (0.1% to 1%): Ataxia, convulsion, dyskinesia, dystonia, hyperesthesia, hyperkinesia, hypokinesia, incoordination, neuralgia, neuropathy, nystagmus, paralysis, syncope
Rare (less than 0.1%): Abnormal gait, adrenergic syndrome, akathisia, akinesia, anticholinergic syndrome, aphasia, cerebral ischemia, cerebrovascular accident, choreoathetosis, circumoral paresthesia, dysarthria, extrapyramidal syndrome, fasciculations, grand mal convulsions, hyperalgesia, meningitis, myelitis, peripheral neuritis, reflexes decreased, reflexes increased, taste loss, torticollis, trismus, vascular headache
Postmarketing reports: Eclampsia, Guillain-Barre syndrome, neuroleptic malignant syndrome, restless legs syndrome, serotonin syndrome, status epilepticus[Ref]

Metabolic

The results of one study appear to indicate that treatment with selective serotonin reuptake inhibitors (i.e., paroxetine (the active ingredient contained in Brisdelle) sertraline, citalopram) may cause an increase in serum total cholesterol, HDL cholesterol, and/or LDL cholesterol. However, additional studies are necessary to confirm these findings.

Numerous cases of hyponatremia have been reported following treatment with a selective serotonin reuptake inhibitor (SSRI). Risk factors for the development of SSRI- associated hyponatremia including advanced age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium levels have been identified. Hyponatremia tends to develop within the first few weeks of treatment (range 3 to 120 days) and typically resolves within 2 weeks (range 48 hours to 6 weeks) after therapy has been discontinued with some patients requiring treatment. The proposed mechanism for the development of hyponatremia involves the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) via release of antidiuretic hormone.[Ref]

Common (1% to 10%): Decreased appetite, increased appetite, increases in cholesterol levels, weight gain, weight loss
Uncommon (0.1% to 1%): Hypoglycemia, hypokalemia, thirst
Rare (less than 0.1%): Alkaline phosphatase increased, creatinine phosphokinase increased, dehydration, diabetes mellitus, gamma globulins increased, gout, hypercalcemia, hypercholesteremia, hyperglycemia, hyperkalemia, hyperphosphatemia, hypocalcemia, hyponatremia, ketosis, lactic dehydrogenase increased, non-protein nitrogen increased, obesity
Postmarketing reports: Porphyria[Ref]

Cardiovascular

Common (1% to 10%): Chest pain, edema, palpitation, peripheral edema, tachycardia, vasodilation (usually flushing)
Uncommon (0.1% to 1%): Abnormal electrocardiogram, angina pectoris, bradycardia, conduction abnormalities, hematoma, hypertension, hypotension, palpitation, postural hypotension, sinus tachycardia, supraventricular tachycardia
Rare (less than 0.1%): Arrhythmia, arrhythmia nodal, atrial arrhythmia, atrial fibrillation, bundle branch block, cellulitis, congestive heart failure, extrasystoles, heart block, low cardiac output, myocardial infarct, myocardial ischemia, pallor, phlebitis, substernal chest pain, supraventricular extrasystoles, thrombophlebitis, thrombosis, varicose vein, ventricular extrasystoles
Postmarketing reports: Atrial fibrillation, pulmonary edema, ventricular fibrillation, ventricular tachycardia (including torsades de pointes)[Ref]

Other

Fatigue, malaise, and lethargy were very commonly reported in Phase 2 and 3 clinical trials with paroxetine (the active ingredient contained in Brisdelle) for treatment of vasomotor symptoms in postmenopausal women.[Ref]

Very common (10% or more): Asthenia
Common (1% to 10%): Chills, pain, tinnitus, trauma, vertigo
Uncommon (0.1% to 1%): Ear pain, fever, malaise, otitis media, overdose
Rare (less than 0.1%): Abscess, deafness, hypothermia, otitis externa, sepsis, ulcer, abnormal laboratory value, cyst, hernia, intentional overdose
Postmarketing reports: Death[Ref]

Genitourinary

Very common (10% or more): Decreased libido, ejaculation disturbance, other male genital disorders (primarily ejaculatory delay)
Common (1% to 10%): Female genital disorders (primarily anorgasmia and difficulty reaching climax/orgasm), dysmenorrhea, impotence, menorrhagia, menstrual disorder, urinary disorder (primarily difficulty with micturition and urinary hesitancy), urinary frequency, urination impaired, urinary tract infection, vaginal moniliasis, vaginitis
Uncommon (0.1% to 1%): Albuminuria, amenorrhea, breast pain, cystitis, dysuria, hematuria, increased libido, nocturia, ovarian cyst, polyuria, pyuria, pregnancy and puerperal disorders, testes pain, urinary incontinence, urinary retention, urinary urgency,
Rare (0.01% to 0.1%): Abortion, breast atrophy, breast enlargement, endometrial disorder, epididymitis, female lactation, fibrocystic breast, kidney calculus, kidney pain, leukorrhea, mastitis, metrorrhagia, nephritis, oliguria, pelvic pain, salpingitis, urethritis, urinary abnormality, urinary casts, uterine spasm, urolith, vaginal hemorrhage
Very rare (less than 0.01%): Priapism
Postmarketing reports: Premature births in pregnant women, symptoms suggestive of galactorrhea[Ref]

There are several reports of priapism associated with paroxetine use. In cases in which outcome was reported, all patients fully recovered.

In placebo-controlled clinical trials, ejaculatory disturbance in men was reported in 13% to 28% of men taking paroxetine, compared to 0% to 2% in the placebo group. Decreased libido was reported in 6% to 15% in men treated with paroxetine, compared to 0% to 5% in the placebo group, and in 0% to 9% in women treated with paroxetine, compared with 0% to 2% in placebo patients. The estimates of the incidence of untoward sexual experience and performance may underestimate their actual incidence, partly because patients and physicians may be reluctant to discuss this issue.[Ref]

Dermatologic

Seven cases of alopecia have been reported. In all cases, hair loss was eventually reversible.

A case of cutaneous leukocytoclastic vasculitis has been reported following treatment with paroxetine (the active ingredient contained in Brisdelle) The patient originally developed the lesions after treatment with escitalopram. The lesions disappeared one week following discontinuation of escitalopram and reappeared upon rechallenge. When the patient was switched to paroxetine a similar reaction occurred.[Ref]

Very common (10% or more): Sweating
Common (1% to 10%): Eczema, hypertension, photosensitivity, pruritus, rash, sweat gland disorder
Uncommon (0.1% to 1%): Acne, alopecia, contact dermatitis, dry skin, ecchymosis, furunculosis, purpura, urticaria
Rare (0.01% to 0.1%): Angioedema, erythema multiforme, erythema nodosum, exfoliative dermatitis, fungal dermatitis, hirsutism, maculopapular rash, pustular rash, seborrhea, skin discoloration, skin hypertrophy, skin ulcer, sweating decreased, vesiculobullous rash
Very rare (less than 0.01%): Severe cutaneous reactions such as Stevens Johnson syndrome and toxic epidermal necrolysis)
Postmarketing reports: Vasculitic syndromes (such as Henoch-Schonlein purpura)[Ref]

Endocrine

Rare (less than 0.1%): Goiter, hyperthyroidism, hypothyroidism, thyroiditis
Postmarketing reports: Syndrome of inappropriate antidiuretic hormone secretion, symptoms suggestive of prolactinemia[Ref]

Gastrointestinal

A study of 26,005 antidepressant users has reported 3.6 times more upper GI bleeding episodes with the use of SSRIs relative to the population who did not receive antidepressant medications. Upper gastrointestinal tract bleeding was observed up to 3.2 times more frequently in patients receiving paroxetine (the active ingredient contained in Brisdelle) [Ref]

Very common (10% or more): Constipation, diarrhea, dry mouth, nausea
Common (1% to 10%): Abdominal pain, dyspepsia, flatulence, gastrointestinal disorder, gingivitis, stomatitis, tooth disorder, vomiting
Uncommon (0.1% to 1%): Buccal cavity disorders, colitis, dysphagia, eructation, gastritis, gastroenteritis, gastroesophageal reflux, gastrointestinal flu, gingivitis, glossitis, increased salivation, melena, pancreatitis, rectal hemorrhage, toothache, ulcerative stomatitis
Rare (less than 0.1%): Aphthous stomatitis, bloody diarrhea, cardiospasm, cholelithiasis, duodenitis, enteritis, esophagitis, fecal impaction, fecal incontinence, gum hemorrhage, gum hyperplasia, hematemesis, ileitis, ileus, intestinal obstruction, mouth ulceration, peptic ulcer, peritonitis, salivary gland enlargement, sialadenitis, stomach ulcer, tooth caries, tongue discoloration, tongue edema, tooth malformation
Postmarketing reports: Acute pancreatitis, pancreatitis hemorrhagic[Ref]

Hematologic

Uncommon (0.1% to 1%): Anemia, eosinophilia, hypochromic anemia, leukocytosis, leukopenia, lymphadenopathy, WBC abnormality
Rare (less than 0.1%): Abnormal erythrocytes, abnormal lymphocytes, anisocytosis, basophilia, bleeding time increased, iron deficiency anemia, lymphedema, lymphocytosis, lymphopenia, microcytic anemia, monocytosis, normocytic anemia, thrombocytopenia, thrombocythemia,
Postmarketing reports: Events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, agranulocytosis), hemolytic anemia, idiopathic thrombocytopenic purpura[Ref]

Hepatic

Uncommon (0.1% to 1%): Abnormal liver function tests, SGOT increased, SGPT increased
Rare (less than 0.1%): Bilirubinemia, hepatitis, hepatosplenomegaly, jaundice
Postmarketing reports: Drug-induced liver injury, elevated liver function tests, hepatic failure[Ref]

In placebo-controlled clinical trials patients receiving paroxetine experienced abnormal values on liver function tests at a rate equal to or less than that reported in patients receiving placebo. However, there have been postmarketing reports of patients developing elevated serum transaminases resulting in severe liver dysfunction, as well as, a few cases of elevated liver function tests resulting in death secondary to liver necrosis.[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Allergic reaction, face edema
Rare (less than 0.1%): Anaphylactoid reaction
Postmarketing reports: Anaphylaxis[Ref]

Immunologic

Common (1% to 10%): Infection
Uncommon (0.1% to 1%): Flu syndrome, herpes simplex
Rare (less than 0.1%): Herpes zoster, moniliasis[Ref]

Musculoskeletal

Epidemiological studies, primarily in patients aged 50 years or older, have shown an increased risk of bone fractures in patients receiving SSRIs or TCAs.[Ref]

Common (1% to 10%): Arthralgia, back pain, migraine, myalgia, myasthenia, myopathy
Uncommon (0.1% to 1%): Arthritis, arthrosis, bursitis, myositis, neck pain, tendonitis, traumatic fracture
Rare (less than 0.1%): Cartilage disorder, generalized spasm, myositis, neck rigidity, osteoporosis, tenosynovitis, tetany[Ref]

Ocular

Common (1% to 10%): Abnormality of accommodation, abnormal vision, blurred vision
Uncommon (0.1% to 1%): Conjunctivitis, eye pain, keratoconjunctivitis, mydriasis, photophobia, retinal hemorrhage
Rare (less than 0.1%): Anisocoria, blepharitis, cataract, conjunctival edema, corneal lesion, corneal ulcer, diplopia, exophthalmos, eye hemorrhage, glaucoma, hyperacusis, night blindness, ptosis, visual field defect
Frequency not reported: Angle-closure glaucoma, eye pain
Postmarketing reports: Acute glaucoma, optic neuritis[Ref]

Renal

Rare (less than 0.1%): Abnormal kidney function, BUN increased
Postmarketing reports: Acute renal failure[Ref]

Respiratory

Common (1% to 10%): Bronchitis, cough increased, oropharynx disorder, pharyngitis, respiratory disorder, rhinitis, sinusitis, yawn
Uncommon (0.1% to 1%): Asthma, dyspnea, epistaxis, hyperventilation, laryngitis, pneumonia, respiratory flu
Rare (less than 0.1%): Dysphonia, emphysema, hemoptysis, hiccups, lung fibrosis, parosmia, pulmonary edema, pulmonary embolus, sputum increased, stridor, throat tightness, voice alteration
Postmarketing reports: Allergic alveolitis, laryngismus, pulmonary hypertension[Ref]

Some side effects of Brisdelle may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Benefit should outweigh risk; use with caution. Excreted into human milk: Yes Comments: -This drug has been considered one of the preferred antidepressants during breastfeeding. -Mild side effects have been occasionally reported, particularly in infants whose mothers took paroxetine during the third trimester of pregnancy. -Mothers taking an SSRI during pregnancy and postpartum may have difficulty breastfeeding and may require additional breastfeeding support.

Low-dose paroxetine marketed under the name Brisdelle (R) is only indicated for the treatment of menopause and would not be expected to be used in breastfeeding women. The manufacturer of this product recommends discontinuing nursing or discontinuing the drug, taking into the account the importance of the drug to the mother. Data from a pooled analysis of serum levels from published studies and 3 unpublished cases involving 50 mothers taking an average paroxetine daily dose of 21 mg estimated that an exclusively breastfed infant would receive approximately 1.2% of the maternal weight-adjusted dosage of paroxetine. Authors of a pooled analysis of 40 mother-infant pairs from published and unpublished cases found no measurable paroxetine plasma levels in the infants. Sixteen breastfed infants (2 were about 50% breastfed and the others 95% or more breastfed) aged 6 to 13 weeks had undetectable levels of paroxetine (less than 1 mcg/L) during maternal therapy with an average daily paroxetine dose of 18.75 mg. In a controlled cohort study of mothers who took paroxetine during pregnancy there were 36 mothers who took paroxetine during the third trimester and breastfed their infants. Of the 36 mothers, 8 reported side effects in their infants, including alertness, constipation, sleepiness, and irritability. There were no reports of side effects in the control group. No data are available on the contribution of transplacental and breast milk acquisition of the drug. Another study comparing the infants of mothers who took an SSRI during pregnancy for major depression with those of mothers who did not take an SSRI showed mental development and most motor development as being normal at follow-up after about 12.9 months in both groups. Four of the treated mothers took paroxetine at an average daily dose of 28.6 mg for an average of 7.8 months while breastfeeding their infants. Psychomotor development was slightly delayed compared to controls; however, the extent to which breastfeeding contributed to abnormal development could not be determined.