PEXEVA SIDE EFFECTS

Last updated on MDtodate: 10/10/2022

SIDE EFFECTS

The following adverse reactions are included in more detail in other sections of the prescribing information:

• Hypersensitivity reactions to paroxetine
• Suicidal Thoughts and Behaviors
• Serotonin syndrome
• Embryofetal and Neonatal Toxicity
• Increased Risk of Bleeding
• Activation of Mania/Hypomania
• Discontinuation Syndrome
• Seizure
• Angle-closure Glaucoma
• Hyponatremia
• Bone Fracture

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 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
• 8-week clinical trials in GAD patients who received paroxetine 10 mg to 50 mg once daily

Adverse Reactions Leading To Discontinuation

Twenty percent (1199/6145) of patients treated with paroxetine in clinical trials in MDD and 11.8% (64/542), 9.4% (44/469), and 10.7% (79/735) of patients treated with paroxetine in clinical trials in OCD, PD, and GAD, respectively, discontinued treatment due to an adverse reaction. Table 1 shows the most common reactions (≥1%) associated with discontinuation and considered to be drug related (i.e., those reactions associated with dropout at a rate approximately twice or greater for paroxetine compared to placebo).

TABLE 1: Adverse Reactions Reported as Leading to Discontinuation (≥1% of Paroxetine-Treated Patients and (≥2% Placebo) in MDD, OCD, PD, and GAD Trials

	MDD		OCD		PD		GAD
	Paroxetine %	Placebo %	Paroxetine %	Placebo %	Paroxetine %	Placebo %	Paroxetine %	Placebo %
CNS
Somnolence	2.3	0.7	–	–	1.9	0.3	2.0	0.2
Insomnia	–	–	1.7	0	1.3	0.3	–	–
Agitation	1.1	0.5	–	–	–	–	–	–
Tremor	1.1	0.3	–
Dizziness	–	–	1.5	0	–	–	1.0	0.2
Gastrointestinal
Constipation	–	–	1.1	0	–	–	–	–
Nausea	3.2	1.1	1.9	0	3.2	1.2	2.0	0.2
Diarrhea	1.0	0.3	–	–	–	–	–	–
Dry mouth	1.0	0.3	–	–	–	–	–	–
Vomiting	1.0	0.3	–	–	–	–	–	–
Other
Asthenia	1.6	0.4	1.9	0.4	–	–	1.8	0.2
Abnormal	1.6	0	2.1	0	–	–	2.5	0.5
Ejaculation 1
Sweating	1.0	0.3	–	–	–	–	1.1	0.2
Impotence 1	–	–	1.5	0	–	–	–	–
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 two times the incidence of placebo. 1 Incidence corrected for gender.

 

Most Common Adverse Reactions In MDD, OCD, PD, And GAD

The most commonly observed adverse reactions associated with the use of PEXEVA (incidence of 5% or greater and at least twice that for placebo) were:

Major Depressive Disorder: asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders.

Obsessive Compulsive Disorder: nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence, and abnormal ejaculation.

Panic Disorder: asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation, female genital disorders, and impotence. Generalized Anxiety Disorder: asthenia, infection, constipation, decreased appetite, dry mouth, nausea, libido decreased, somnolence, tremor, sweating, and abnormal ejaculation.

Adverse Reactions Occurring At An Incidence Of 1% Or More In Paroxetine Treated Patients

Major Depressive Disorder

Table 1 enumerates 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 2: Adverse Reactions (≥1% of Paroxetine-treated Patients and Greater than Placebo) in 6-Week Clinical Trials for MDD

Body System	Preferred Term	Paroxetine (n=421)%	Placebo (n=421)%
Body as a Whole	Headache	18	17
	Asthenia	15	6
Cardiovascular	Palpitation	3	1
	Vasodilation	3	1
Dermatologic	Sweating	11	2
	Rash	2	1
Gastrointestinal	Nausea	26	9
	Dry Mouth	18	12
	Constipation	14	9
	Diarrhea	12	8
	Decreased Appetite	6	2
	Flatulence	4	2
	Oropharynx Disorder 1	2	0
	Dyspepsia	2	1
Musculoskeletal	Myopathy	2	1
	Myalgia	2	1
	Myasthenia	1	0
Nervous System	Somnolence	23	9
	Dizziness	13	6
	Insomnia	13	6
	Tremor	8	2
	Nervousness	5	3
	Anxiety	5	3
	Paresthesia	4	2
	Libido Decreased	3	0
	Drugged Feeling	2	1
	Confusion	1	0
Respiration	Yawn	4	0
Special Senses	Blurred Vision	4	1
	Taste Perversion	2	0
Urogenital System	Ejaculatory Disturbance 2,3	13	0
	Other Male Genital Disorders 2,4	10	0
	Urinary Frequency	3	1
	Urination Disorder 5	3	0
	Female Genital Disorders 2,6	2	0
1 Includes mostly “lump in throat” and “tightness in throat.” 2 Percentage corrected for gender. 3 Mostly “ejaculatory delay.” 4 Includes “anorgasmia,” “erectile difficulties,” “delayed ejaculation/orgasm,” and “sexual dysfunction” and “impotence.” 5 Includes mostly “difficulty with micturition” and “urinary hesitancy.” 6 Includes mostly “anorgasmia” and “difficulty reaching climax/orgasm.”

 

Obsessive Compulsive Disorder And Panic Disorder

Table 3 enumerates adverse reactions that occurred at a frequency of 2% or more in clinical trials in patients with OCD and PD.

TABLE 3: Adverse Reactions (≥2% of Paroxetine-Treated Patients and Greater than Placebo) in 10-to 12-Week Clinical Trials for OCD and PD

Body System	Preferred Term	Obsessive Compulsive Disorder		Panic Disorder
		Paroxetine (n=542)%	Placebo (n=265)%	Paroxetine (n=469)%	Placebo (n=324)%
Body as a Whole	Asthenia	22	14	14	5
	Abdominal Pain	–	–	4	3
	Chest Pain	3	2	–	–
	Back Pain	–	–	3	2
	Chills	2	1	2	1
Cardiovascular	Vasodilation	4	1	–	–
	Palpitation	2	0	–	–
Dermatologic	Sweating	9	3	14	6
	Rash	3	2	–	–
Gastrointestinal	Nausea	23	10	23	17
	Dry Mouth	18	9	18	11
	Constipation	16	6	8	5
	Diarrhea	10	10	12	7
	Decreased Appetite	9	3	7	3
	Increased Appetite	4	3	2	1
Nervous System	Insomnia	24	13	18	10
	Somnolence	24	7	19	11
	Dizziness	12	6	14	10
	Tremor	11	1	9	1
	Nervousness	9	8	–	–
	Libido Decreased	7	4	9	1
	Agitation	–	–	5	4
	Anxiety	–	–	5	4
	Abnormal Dreams	4	1	–	–
	Concentration Impaired	3	2	–	–
	Depersonalization	3	0	–	–
	Myoclonus	3	0	3	2
	Amnesia	2	1	–	–
Respiratory System	Rhinitis	–	–	3	0
Special Senses	Abnormal Vision	4	2	–	–
	Taste Perversion	2	0	–	–
Urogenital System	Abnormal Ejaculation 1	23	1	21	1
	Female Genital	3	0	9	1
	Disorder 1
	Impotence 1	8	1	5	0
	Urinary Frequency	3	1	2	0
	Urination Impaired	3	0	–	–
	Urinary Tract Infection	2	1	2	1
1 Percentage corrected for gender.

 

Generalized Anxiety Disorder

Table 4 enumerates adverse reactions that occurred at a frequency of 2% or more among GAD patients on paroxetine who participated in placebo-controlled trials of 8-weeks duration in which patients were dosed in a range of 10 mg/day to 50 mg/day.

TABLE 4: Adverse Reactions (≥2% of Paroxetine-Treated Patients and Greater than Placebo) in 8-Week Clinical Trials for GAD

Body System	Preferred Term	Paroxetine (n=735)%	Placebo (n=529)%
Body as a Whole	Asthenia	14	6
	Headache	17	14
	Infection	6	3
Cardiovascular	Vasodilation	3	1
Dermatologic	Sweating	6	2
Gastrointestinal	Nausea	20	5
	Dry Mouth	11	5
	Constipation	10	2
	Diarrhea	9	7
	Decreased Appetite	5	1
	Vomiting	3	2
Nervous System	Insomnia	11	8
	Somnolence	15	5
	Dizziness	6	5
	Tremor	5	1
	Nervousness	4	3
	Libido Decreased	9	2
Respiratory System	Respiratory Disorder	7	5
	Sinusitis	4	3
	Yawn	4	–
Special Senses	Abnormal Vision	2	1
Urogenital System	Abnormal Ejaculation 1	25	2
	Female Genital	4	1
	Disorder 1
	Impotence 1	4	3
1 Percentage corrected for gender.

 

Dose Dependency Of Adverse Reactions

A comparison of adverse reaction rates in a fixed-dose study comparing paroxetine 10, 20, 30, and 40 mg/day with placebo in the treatment of MDD revealed a clear dose dependency for some of the more common adverse reactions associated with paroxetine use, as shown in Table 5:

TABLE 5: Adverse Reactions (≥5% of Paroxetine-Treated Patients and Twice that of Placebo) in a Dose-Comparison Trial in the Treatment of MDD*

Body System/Preferred Term	Placebo n=51%	Paroxetine
		10 mg n=102%	20 mg n=104%	30 mg n=101%	40 mg n=102%
Body as a Whole
Asthenia	0	2.9	10.6	13.9	12.7
Dermatology
Sweating	2.0	1.0	6.7	8.9	11.8
Gastrointestinal
Constipation	5.9	4.9	7.7	9.9	12.7
Decreased Appetite	2.0	2.0	5.8	4.0	4.9
Diarrhea	7.8	9.8	19.2	7.9	14.7
Dry Mouth	2.0	10.8	18.3	15.8	20.6
Nausea	13.7	14.7	26.9	34.7	36.3
Nervous System
Anxiety	0	2.0	5.8	5.9	5.9
Dizziness	3.9	6.9	6.7	8.9	12.7
Nervousness	0	5.9	5.8	4.0	2.9
Paresthesia	0	2.9	1.0	5.0	5.9
Somnolence	7.8	12.7	18.3	20.8	21.6
Tremor	0	0	7.7	7.9	14.7
Special Senses
Blurred Vision	2.0	2.9	2.9	2.0	7.8
Urogenital System
Abnormal Ejaculation	0	5.8	6.5	10.6	13.0
Impotence	0	1.9	4.3	6.4	1.9
Male Genital Disorders	0	3.8	8.7	6.4	3.7

 

In a fixed-dose study comparing placebo and paroxetine 20, 40, 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. No new adverse reactions were observed in the paroxetine 60 mg dose group compared to any of the other treatment groups.

In a fixed-dose study comparing placebo and paroxetine 10, 20, and 40 mg in the treatment of PD, there was no clear relationship between adverse reactions and the dose of paroxetine to which patients were assigned, except for asthenia, dry mouth, anxiety, libido decreased, tremor, and abnormal ejaculation. In flexible-dose studies, no new adverse reactions were observed in patients receiving 60 mg of paroxetine compared to any of the other treatment groups.

In a fixed-dose study comparing placebo and 20 and 40 mg of paroxetine in the treatment of GAD, for most of the adverse reactions, there was no clear relationship between adverse reactions and the dose of paroxetine to which patients were assigned, except for the following adverse reactions: asthenia, constipation, 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, 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 product labeling are likely to underestimate their actual incidence.

The percentage of patients reporting symptoms of sexual dysfunction in males and females with MDD, OCD, PD, , GAD, and two other indications are displayed in Table 6.

Table 6: Incidence of Sexual Adverse Reactions in Controlled Clinical Trials

	Paroxetine	Placebo
n (males)	1446	1042
	%	%
Decreased Libido	6 to 15	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

 

There are no adequate and well-controlled studies examining sexual dysfunction with paroxetine treatment.

Paroxetine treatment has been associated with several cases of priapism. In those cases with a known outcome, patients recovered without sequelae.

While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, healthcare providers should routinely inquire about such possible side effects.

Hallucinations

In pooled clinical trials of immediate-release paroxetine hydrochloride, hallucinations were observed in 0.2% of paroxetine-treated patients compared to 0.1% of patients receiving placebo.

Other Reactions Observed During the Premarketing Evaluation Of Paroxetine

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 one or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare adverse reactions are those occurring in fewer than 1/1000 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. Cardiovascular System: 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 infarction, myocardial ischemia, pallor, phlebitis, pulmonary embolus, supraventricular extrasystoles, thrombophlebitis, thrombosis, varicose vein, vascular headache, ventricular extrasystoles. Digestive System: 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, chlolelithiasis, 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. Endocrine System: 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. Musculoskeletal System: frequent: arthralgia; infrequent: arthritis, arthrosis; rare: bursitis, myositis, osteoporosis, generalized spasm, tenosynovitis, tetany. Nervous System: 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. Respiratory System: 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. Special Senses: 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. Urogenital System: infrequent: amenorrhea, breast pain, cystitis, dysuria, hematuria, menorrhagia, nocturia, pyuria, polyuria, 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.

Postmarketing Experience

The following reactions have been identified during post approval use of paroxetine. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Acute pancreatitis, elevated liver function tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction), Guillain-Barre syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, priapism, syndrome of inappropriate ADH secretion (SIADH), prolactinemia and galactorrhea; extrapyramidal symptoms which have included akathisia, bradykinesia, cogwheel rigidity, dystonia, hypertonia, oculogyric crisis which has been associated with concomitant use of pimozide; trismus; status epilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anaphylaxis, eclampsia, laryngismus, optic neuritis, porphyria, restless legs syndrome (RLS), ventricular fibrillation, ventricular tachycardia (including torsade de pointes), hemolytic anemia, events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis), vasculitic syndromes (such as Henoch-Schonlein purpura) and premature births in pregnant women. There has been a case report of severe hypotension when paroxetine was added to chronic metoprolol treatment.