Epidemiological studies on bone fracture risk during exposure to some antidepressants, including SSRIs, have reported an association between antidepressant treatment and fractures. There are multiple possible causes for this observation,and it is unknown to what
extent fracture risk is directly attributable to SSRI treatment.
Use of SSRIs, including paroxetine, may cause symptoms of sexual dysfunction [see Adverse Reactions ( 6.1)]. In male patients, SSRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SSRI use may result in decreased libido and delayed or absent orgasm. It is important for prescribers to inquire about sexual function prior to initiation of paroxetine and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported. When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment.
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) ]
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety data for paroxetine are from:
- 6-week clinical trials in MDD patients who received paroxetine 20 mg to 50 mg once daily
- 12-week clinical trials in OCD patients who received paroxetine 20 mg to 60 mg once daily
- 10- to 12-week clinical trials in PD patients who received paroxetine 10 mg to 60 mg once daily
- 12-week clinical trials in SAD patients who received paroxetine 20 mg to 50 mg once daily
- 8-week clinical trials in GAD patients who received paroxetine 10 mg to 50 mg once daily
- 12-week clinical trials in PTSD patients who received paroxetine 20 mg to 50 mg once daily
Adverse Reactions Leading to Discontinuation
Twenty percent (1,199/6,145) of patients treated with paroxetine in clinical trials in MDD and 16.1% (84/522), 11.8% (64/542), 9.4% (44/469), 10.7% (79/735), and 11.7% (79/676) of patients treated with paroxetine in clinical trials in SAD, OCD, PD, GAD, and PTSD, respectively, discontinued treatment due to an adverse reaction. The most common adverse reactions (≥1%) associated with discontinuation (i.e., those adverse reactions associated with dropout at a rate approximately twice or greater for paroxetine compared to placebo) are presented in Table 3:
Table 3: Adverse Reactions Reported as Leading to Discontinuation (≥1% of Paroxetine Treated Patients and Greater than Placebo) in MDD, OCD, PD, SAD, GAD, and PTSD Trials
|PAROXETINE %||Placebo %||PAROXETINE %||Placebo %||PAROXETINE %||Placebo %||PAROXETINE %||Placebo %||PAROXETINE %||Placebo %||PAROXETINE %||Placebo %|
Where numbers are not provided the incidence of the adverse reactions in patients treated with paroxetine was not >1% or was not greater than or equal to 2 times the incidence of placebo.
a. Incidence corrected for gender.
Most Common Adverse Reactions
The most commonly observed adverse reactions associated with the use of paroxetine (incidence of 5% or greater and at least twice that for placebo) were:
MDD: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders.
OCD: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence, and abnormal ejaculation.
PD: Asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation, female genital disorders, and impotence.
SAD: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, libido decreased, yawn, abnormal ejaculation, female genital disorders, and impotence.
GAD: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, libido decreased, somnolence, tremor, sweating, and abnormal ejaculation.
PTSD: Asthenia, sweating, nausea, dry mouth, diarrhea, decreased appetite, somnolence, libido decreased, abnormal ejaculation, female genital disorders, and impotence.
Adverse Reactions in Patients with MDD
Table 4 presents the adverse reactions that occurred at an incidence of 1% or more and greater than placebo in clinical trials of paroxetine -treated patients with MDD.
Table 4: Adverse Reactions (≥1% of Paroxetine-Treated Patients and Greater than Placebo) in 6-Week Clinical Trials for MDD
|Body System/ Adverse Reaction||Paroxetine(n = 421) %||Placebo (n = 421) %|
|Body as a Whole|
|Oropharynx Disorder a||2||0|
|Ejaculatory Disturbance b,c||13||0|
|Other Male Genital Disorders b,d||10||0|
|Urination Disorder e||3||0|
|Female Genital Disorders b,f||2||0|
a Includes mostly “lump in throat” and “tightness in throat.”
b Percentage corrected for gender.
c Mostly “ejaculatory delay.”
d Includes “anorgasmia,” “erectile difficulties,” “delayed ejaculation/orgasm,” and “sexual dysfunction,” and “impotence.”
e Includes mostly “difficulty with micturition” and “urinary hesitancy.”
f Includes mostly “anorgasmia” and “difficulty reaching climax/orgasm.”
Adverse Reactions in Patients with OCD, PD, and SAD
Table 5 presents adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with OCD, PD, and SAD.
Table 5. Adverse Reactions (≥2% of Paroxetine -Treated Patients and Greater than Placebo) in 10 to 12-Week Clinical Trials for OCD, PD, and SAD
|Body System/Preferred Term||Obsessive Compulsive Disorder||Panic Disorder||Social Anxiety Disorder|
|PAROXETINE (n = 542 %||Placebo (n = 265) %||PAROXETINE (n = 469) %||Placebo (n = 324) %||PAROXETINE (n = 425) %||Placebo (n = 339) %|
|Body as a Whole|
a Percentage corrected for gender.
Adverse Reactions in Patients with GAD and PTSD
Table 6 presents adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with GAD and PTSD
Table 6. Adverse Reactions (≥2% of Paroxetine -Treated Patients and Greater than Placebo) in 8- to 12-Week Clinical Trials for GAD and PTSD a
|Body System/Preferr ed Term||Generalized Anxiety Disorder||Posttraumatic Stress Disorder|
|Paroxetine (n = 735) %||Placebo (n = 529) %||Paroxetine (n = 676) %||Placebo (n = 504) %|
|Body as a Whole|
|Abnormal Ejaculation a||25||2||13||2|
|Female Genital Disorder a||4||1||5||1|
a. Percentage corrected for gender.
Dose Dependent Adverse Reactions
A comparison of adverse reaction rates in a fixed-dose study comparing paroxetine 10 mg, 20 mg, 30 mg, and 40 mg once daily with placebo in the treatment of MDD revealed dose dependent adverse reactions, as shown in Table 7:
Table 7. Adverse Reactions (≥5% of Paroxetine -Treated Patients and ≥ Twice the Rate of Placebo) (in a Dose-Comparison Trail in the Treatment of MDD
|Body System/Preferred Term||Placebo n = 51 %||PAROXETINE 10 mg 20 mg 30 mg 40 mg n = 102 n = 104 n = 101 n = 102 % % % %|
|Body as a Whole Asthenia||0||2.9||10.6||13.9||12.7|
|Special Senses Blurred Vision||2||2.9||2.9||2||7.8|
|Male Genital Disorders||0||3.8||8.7||6.4||3.7|
In a fixed-dose study comparing placebo and paroxetine 20 mg, 40 mg, and 60 mg in the treatment of OCD, there was no clear relationship between adverse reactions and the dose of paroxetine to which patients were assigned.
In a fixed-dose study comparing placebo and paroxetine 10 mg, 20 mg, and 40 mg in the treatment of PD, the following adverse reactions were shown to be dose-dependent: asthenia, dry mouth, anxiety, libido decreased, tremor, and abnormal ejaculation.
In a fixed-dose study comparing placebo and paroxetine 20 mg, 40 mg and 60 mg in the treatment of SAD, for most of the adverse reactions, there was no clear relationship between adverse reactions and the dose of paroxetine to which patients were assigned.
In a fixed-dose study comparing placebo and paroxetine 20 mg and 40 mg in the treatment of GAD, the following adverse reactions were shown to be dose-dependent: asthenia, constipation, and abnormal ejaculation.
In a fixed-dose study comparing placebo and paroxetine 20 mg and 40 mg in the treatment of PTSD, the following adverse reactions were shown to be dose-dependent: impotence and abnormal ejaculation.
Male and Female Sexual Dysfunction
Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of SSRI treatment. However, reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and healthcare providers may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in labeling may underestimate their actual incidence. The percentage of patients reporting symptoms of sexual dysfunction in males and females with MDD, OCD, PD, SAD, GAD, and PTSD are displayed in Table 8.
Table 8. Adverse Reactions Related to Sexual Dysfunction in Patients Treated with Paroxetine in Clinical Trials of MDD, OCD, PD, SAD, GAD, and PTSD
|n (males)||1446 %||1042 %|
|Decreased Libido||6 to15||0 to 5|
|Ejaculatory Disturbance||13 to 28||0 to 2|
|Impotence||2 to 9||0 to 3|
|n (females)||1822 %||1340 %|
|Decreased Libido||0 to 9||0 to 2|
|Orgasmic Disturbance||2 to 9||0 to 1|
Paroxetine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae.
In pooled clinical trials of paroxetine, hallucinations were observed in 0.2% of paroxetine-treated patients compared to 0.1% of patients receiving placebo.
Less Common Adverse Reactions
The following adverse reactions occurred during the clinical studies of paroxetine and are not included elsewhere in the labeling.
Adverse reactions are categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse reactions are those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1,000 patients; rare adverse reactions are those occurring in fewer than 1/1,000 patients.
Body as a Whole
Infrequent: Allergic reaction, chills, face edema, malaise, neck pain; rare: Adrenergic syndrome, cellulitis, moniliasis, neck rigidity, pelvic pain, peritonitis, sepsis, ulcer.
Frequent: Hypertension, tachycardia; infrequent: Bradycardia, hematoma, hypotension, migraine, postural hypotension, syncope; rare: Angina pectoris, arrhythmia nodal, atrial fibrillation, bundle branch block, cerebral ischemia, cerebrovascular accident, congestive heart failure, heart block, low cardiac output, myocardial infarct, myocardial ischemia, pallor, phlebitis, pulmonary embolus, supraventricular extrasystoles, thrombophlebitis, thrombosis, varicose vein, vascular headache, ventricular extrasystoles.
Infrequent: Bruxism, colitis, dysphagia, eructation, gastritis, gastroenteritis, gingivitis, glossitis, increased salivation, abnormal liver function tests, rectal hemorrhage, ulcerative stomatitis; rare: Aphthous stomatitis, bloody diarrhea, bulimia, cardiospasm, cholelithiasis, duodenitis, enteritis, esophagitis, fecal impactions, fecal incontinence, gum hemorrhage, hematemesis, hepatitis, ileitis, ileus, intestinal obstruction, jaundice, melena, mouth ulceration, peptic ulcer, salivary gland enlargement, sialadenitis, stomach ulcer, stomatitis, tongue discoloration, tongue edema, tooth caries.
Rare: Diabetes mellitus, goiter, hyperthyroidism, hypothyroidism, thyroiditis.
Hemic and Lymphatic Systems
Infrequent: Anemia, leukopenia, lymphadenopathy, purpura; rare: Abnormal erythrocytes, basophilia, bleeding time increased, eosinophilia, hypochromic anemia, iron deficiency anemia, leukocytosis, lymphedema, abnormal lymphocytes, lymphocytosis, microcytic anemia, monocytosis, normocytic anemia, thrombocythemia, thrombocytopenia.
Metabolic and Nutritional
Frequent: Weight gain; infrequent: Edema, peripheral edema, SGOT increased, SGPT increased, thirst, weight loss; rare: Alkaline phosphatase increased, bilirubinemia, BUN increased, creatinine phosphokinase increased, dehydration, gamma globulins increased, gout, hypercalcemia, hypercholesteremia, hyperglycemia, hyperkalemia, hyperphosphatemia, hypocalcemia, hypoglycemia, hypokalemia, hyponatremia, ketosis, lactic dehydrogenase increased, non-protein nitrogen (NPN) increased.
Frequent: Arthralgia; infrequent: Arthritis, arthrosis; rare: Bursitis, myositis, osteoporosis, generalized spasm, tenosynovitis, tetany.
Frequent: Emotional lability, vertigo; infrequent: Abnormal thinking, alcohol abuse, ataxia, dystonia, dyskinesia, euphoria, hostility, hypertonia, hypesthesia, hypokinesia, incoordination, lack of emotion, libido increased, manic reaction, neurosis, paralysis, paranoid reaction; rare: Abnormal gait, akinesia, antisocial reaction, aphasia, choreoathetosis, circumoral paresthesias, convulsion, delirium, delusions, diplopia, drug dependence, dysarthria, extrapyramidal syndrome, fasciculations, grand mal convulsion, hyperalgesia, hysteria, manic-depressive reaction, meningitis, myelitis, neuralgia, neuropathy, nystagmus, peripheral neuritis, psychotic depression, psychosis, reflexes decreased, reflexes increased, stupor, torticollis, trismus, withdrawal syndrome.
Infrequent: Asthma, bronchitis, dyspnea, epistaxis, hyperventilation, pneumonia, respiratory flu; rare: Emphysema, hemoptysis, hiccups, lung fibrosis, pulmonary edema, sputum increased, stridor, voice alteration.
Skin and Appendages
Frequent: Pruritus; infrequent: Acne, alopecia, contact dermatitis, dry skin, ecchymosis, eczema, herpes simplex, photosensitivity, urticaria; rare: Angioedema, erythema nodosum, erythema multiforme, exfoliative dermatitis, fungal dermatitis, furunculosis; herpes zoster, hirsutism, maculopapular rash, seborrhea, skin discoloration, skin hypertrophy, skin ulcer, sweating decreased, vesiculobullous rash.
Frequent: Tinnitus; infrequent: Abnormality of accommodation, conjunctivitis, ear pain, eye pain, keratoconjunctivitis, mydriasis, otitis media; rare: Amblyopia, anisocoria, blepharitis, cataract, conjunctival edema, corneal ulcer, deafness, exophthalmos, eye hemorrhage, glaucoma, hyperacusis, night blindness, otitis externa, parosmia, photophobia, ptosis, retinal hemorrhage, taste loss, visual field defect.
Infrequent: Amenorrhea, breast pain, cystitis, dysuria, hematuria, menorrhagia, nocturia, polyuria, pyuria, urinary incontinence, urinary retention, urinary urgency, vaginitis; rare: Abortion, breast atrophy, breast enlargement, endometrial disorder, epididymitis, female lactation, fibrocystic breast, kidney calculus, kidney pain, leukorrhea, mastitis, metrorrhagia, nephritis, oliguria, salpingitis, urethritis, urinary casts, uterine spasm, urolith, vaginal hemorrhage, vaginal moniliasis.
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