Components:
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Medically reviewed by Fedorchenko Olga Valeryevna, PharmD. Last updated on 26.06.2023
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Associated With Discontinuation Of Treatment
Twenty percent (1,199/6,145) of patients treated with Xet in worldwide clinical trials in major depressive disorder 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 Xet in worldwide trials in social anxiety disorder, OCD, panic disorder, GAD, and PTSD, respectively, discontinued treatment due to an adverse event. The most common events ( ≥ 1%) associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate approximately twice or greater for Xet compared to placebo) included the following:
| Major Depressive Disorder | OCD | Panic Disorder | Social Anxiety Disorder | Generalized Anxiety Disorder | PTSD | |||||||
| Xet | Placebo | Xet | Placebo | Xet | Placebo | Xet | Placebo | Xet | Placebo | Xet | Placebo | |
| CNS | ||||||||||||
| Somnolence | 2.3% | 0.7% | — | 1.9% | 0.3% | 3.4% | 0.3% | 2.0% | 0.2% | 2.8% | 0.6% | |
| Insomnia | — | — | 1.7% | 0% | 1.3% | 0.3% | 3.1% | 0% | — | — | ||
| Agitation | 1.1% | 0.5% | — | — | — | |||||||
| Tremor | 1.1% | 0.3% | — | 1.7% | 0% | 1.0% | 0.2% | |||||
| Anxiety | — | — | — | 1.1% | 0% | — | — | |||||
| Dizziness | — | — | 1.5% | 0% | 1.9% | 0% | 1.0% | 0.2% | — | — | ||
| Gastrointestinal | ||||||||||||
| Constipation | — | 1.1% | 0% | — | — | |||||||
| Nausea | 3.2% | 1.1% | 1.9% | 0% | 3.2% | 1.2% | 4.0% | 0.3% | 2.0% | 0.2% | 2.2% | 0.6% |
| Diarrhea | 1.0% | 0.3% | — | |||||||||
| Dry mouth | 1.0% | 0.3% | — | — | — | |||||||
| Vomiting | 1.0% | 0.3% | — | 1.0% | 0% | — | — | |||||
| Flatulence | 1.0% | 0.3% | — | — | ||||||||
| Other | ||||||||||||
| Asthenia | 1.6% | 0.4% | 1.9% | 0.4% | 2.5% | 0.6% | 1.8% | 0.2% | 1.6% | 0.2% | ||
| Abnormal Ejaculationa | 1.6% | 0% | 2.1% | 0% | 4.9% | 0.6% | 2.5% | 0.5% | — | — | ||
| Sweating | 1.0% | 0.3% | — | 1.1% | 0% | 1.1% | 0.2% | — | — | |||
| Impotencea | — | 1.5% | 0% | — | — | |||||||
| Libido | ||||||||||||
| Decreased | 1.0% | 0% | — | — | ||||||||
| Where numbers are not provided the incidence of the adverse events in patients treated with Xet was not > 1% or was not greater than or equal to 2 times the incidence of placebo. a Incidence corrected for gender. | ||||||||||||
Commonly Observed Adverse Events
Major Depressive Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for Xet at least twice that for placebo, derived from Table 2) were: Asthenia, sweating, nausea, decreased appetite, somnolence, dizziness, insomnia, tremor, nervousness, ejaculatory disturbance, and other male genital disorders.
Obsessive Compulsive Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for Xet at least twice that of placebo, derived from Table 3) were: Nausea, dry mouth, decreased appetite, constipation, dizziness, somnolence, tremor, sweating, impotence, and abnormal ejaculation.
Panic Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for Xet at least twice that for placebo, derived from Table 3) were: Asthenia, sweating, decreased appetite, libido decreased, tremor, abnormal ejaculation, female genital disorders, and impotence.
Social Anxiety Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for Xet at least twice that for placebo, derived from Table 3) were: Sweating, nausea, dry mouth, constipation, decreased appetite, somnolence, tremor, libido decreased, yawn, abnormal ejaculation, female genital disorders, and impotence.
Generalized Anxiety Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for Xet at least twice that for placebo, derived from Table 4) were: Asthenia, infection, constipation, decreased appetite, dry mouth, nausea, libido decreased, somnolence, tremor, sweating, and abnormal ejaculation.
Posttraumatic Stress Disorder: The most commonly observed adverse events associated with the use of paroxetine (incidence of 5% or greater and incidence for Xet at least twice that for placebo, derived from Table 4) were: Asthenia, sweating, nausea, dry mouth, diarrhea, decreased appetite, somnolence, libido decreased, abnormal ejaculation, female genital disorders, and impotence. Incidence in Controlled Clinical Trials: The prescriber should be aware that the figures in the tables following cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the populations studied.
Major Depressive Disorder: Table 2 enumerates adverse events that occurred at an incidence of 1% or more among paroxetine-treated patients who participated in short-term (6-week) placebo-controlled trials in which patients were dosed in a range of 20 mg to 50 mg/day. Reported adverse events were classified using a standard COSTART-based Dictionary terminology.
Table 2: Treatment-Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trials for Major Depressive Disordera
| Body System | Preferred Term | Xet (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 Disorderb | 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 Disturbancec,d | 13% | 0% |
| Other Male Genital Disordersc,e | 10% | 0% | |
| Urinary Frequency | 3% | 1% | |
| Urination Disorderf | 3% | 0% | |
| Female Genital Disordersc,g | 2% | 0% | |
| a Events reported by at least 1% of patients treated with Xet are included, except the following events which had an incidence on placebo ≥ Xet: Abdominal pain, agitation, back pain, chest pain, CNS stimulation, fever, increased appetite, myoclonus, pharyngitis, postural hypotension, respiratory disorder (includes mostly “cold symptoms” or “URI”), trauma, and vomiting. b Includes mostly “lump in throat” and “tightness in throat.” c Percentage corrected for gender. d Mostly “ejaculatory delay.” e Includes “anorgasmia,” “erectile difficulties,” “delayed ejaculation/orgasm,” and “sexual dysfunction,” and “impotence.” f Includes mostly “difficulty with micturition” and “urinary hesitancy.” g Includes mostly “anorgasmia” and “difficulty reaching climax/orgasm.” |
Obsessive Compulsive Disorder, Panic Disorder, And Social Anxiety Disorder
Table 3 enumerates adverse events that occurred at a frequency of 2% or more among OCD patients on Xet who participated in placebo-controlled trials of 12-weeks duration in which patients were dosed in a range of 20 mg to 60 mg/day or among patients with panic disorder on Xet who participated in placebo-controlled trials of 10-to 12-weeks duration in which patients were dosed in a range of 10 mg to 60 mg/day or among patients with social anxiety disorder on Xet who participated in placebo-controlled trials of 12-weeks duration in which patients were dosed in a range of 20 mg to 50 mg/day.
Table 3: Treatment-Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trials for Obsessive Compulsive Disorder, Panic Disorder, and Social Anxiety Disordera
| Body System | Preferred Term | Obsessive Compulsive Disorder | Panic Disorder | Social Anxiety Disorder | |||
| Xet (n = 542) | Placebo (n = 265) | Xet (n = 469) | Placebo (n = 324) | Xet (n = 425) | Placebo (n = 339) | ||
| Body as a Whole | Asthenia | 22% | 14% | 14% | 5% | 22% | 14% |
| Abdominal Pain | — | — | 4% | 3% | — | — | |
| Chest Pain | 3% | 2% | — | — | — | — | |
| Back Pain | — | — | 3% | 2% | — | — | |
| Chills | 2% | 1% | 2% | 1% | — | — | |
| Trauma | — | — | — | — | 3% | 1% | |
| Cardiovascular | Vasodilation | 4% | 1% | — | — | — | — |
| Palpitation | 2% | 0% | — | — | — | — | |
| Dermatologic | Sweating | 9% | 3% | 14% | 6% | 9% | 2% |
| Rash | 3% | 2% | — | — | — | — | |
| Gastrointestinal | Nausea | 23% | 10% | 23% | 17% | 25% | 7% |
| Dry Mouth | 18% | 9% | 18% | 11% | 9% | 3% | |
| Constipation | 16% | 6% | 8% | 5% | 5% | 2% | |
| Diarrhea | 10% | 10% | 12% | 7% | 9% | 6% | |
| Decreased Appetite | 9% | 3% | 7% | 3% | 8% | 2% | |
| Dyspepsia | — | — | — | — | 4% | 2% | |
| Flatulence | — | — | — | — | 4% | 2% | |
| Increased Appetite | 4% | 3% | 2% | 1% | — | — | |
| Vomiting | — | — | — | — | 2% | 1% | |
| Musculoskeletal | Myalgia | _ | — | — | — | 4% | 3% |
| Nervous System | Insomnia | 24% | 13% | 18% | 10% | 21% | 16% |
| Somnolence | 24% | 7% | 19% | 11% | 22% | 5% | |
| Dizziness | 12% | 6% | 14% | 10% | 11% | 7% | |
| Tremor | 11% | 1% | 9% | 1% | 9% | 1% | |
| Nervousness | 9% | 8% | — | — | 8% | 7% | |
| Libido Decreased | 7% | 4% | 9% | 1% | 12% | 1% | |
| Agitation | — | — | 5% | 4% | 3% | 1% | |
| Anxiety | — | — | 5% | 4% | 5% | 4% | |
| Abnormal Dreams | 4% | 1% | — | — | — | — | |
| Concentration Impaired | 3% | 2% | — | — | 4% | 1% | |
| Depersonalization | 3% | 0% | — | — | — | — | |
| Myoclonus | 3% | 0% | 3% | 2% | 2% | 1% | |
| Amnesia | 2% | 1% | — | — | — | — | |
| Respiratory System | Rhinitis | — | — | 3% | 0% | — | — |
| Pharyngitis | — | — | — | — | 4% | 2% | |
| Yawn | — | — | — | — | 5% | 1% | |
| Special Senses | Abnormal Vision | 4% | 2% | — | — | 4% | 1% |
| Taste Perversion | 2% | 0% | — | — | — | — | |
| Urogenital System | Abnormal | ||||||
| Ejaculationb | 23% | 1% | 21% | 1% | 28% | 1% | |
| Dysmenorrhea | — | — | — | — | 5% | 4% | |
| Female Genital Disorderb | 3% | 0% | 9% | 1% | 9% | 1% | |
| Impotenceb | 8% | 1% | 5% | 0% | 5% | 1% | |
| Urinary Frequency | 3% | 1% | 2% | 0% | — | — | |
| Urination Impaired | 3% | 0% | — | — | — | — | |
| Urinary Tract Infection | 2% | 1% | 2% | 1% | — | — | |
| a Events reported by at least 2% of OCD, panic disorder, and social anxiety disorder in patients treated with Xet are included, except the following events which had an incidence on placebo ≥ Xet: [OCD]: Abdominal pain, agitation, anxiety, back pain, cough increased, depression, headache, hyperkinesia, infection, paresthesia, pharyngitis, respiratory disorder, rhinitis, and sinusitis. [panic disorder]: Abnormal dreams, abnormal vision, chest pain, cough increased, depersonalization, depression, dysmenorrhea, dyspepsia, flu syndrome, headache, infection, myalgia, nervousness, palpitation, paresthesia, pharyngitis, rash, respiratory disorder, sinusitis, taste perversion, trauma, urination impaired, and vasodilation. [social anxiety disorder]: Abdominal pain, depression, headache, infection, respiratory disorder, and sinusitis. b Percentage corrected for gender. | |||||||
Generalized Anxiety Disorder And Posttraumatic Stress Disorder
Table 4 enumerates adverse events that occurred at a frequency of 2% or more among GAD patients on Xet 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 or among PTSD patients on Xet who participated in placebo-controlled trials of 12-weeks duration in which patients were dosed in a range of 20 mg/day to 50 mg/day.
Table 4: Treatment-Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trials for Generalized Anxiety Disorder and Posttraumatic Stress Disordera
| Body System | Preferred Term | Generalized Anxiety Disorder | Posttraumatic Stress Disorder | ||
| Xet (n = 735) | Placebo (n = 529) | Xet (n = 676) | Placebo (n = 504) | ||
| Body as a Whole | Asthenia | 14% | 6% | 12% | 4% |
| Headache | 17% | 14% | — | — | |
| Infection | 6% | 3% | 5% | 4% | |
| Abdominal Pain | 4% | 3% | |||
| Trauma | 6% | 5% | |||
| Cardiovascular | Vasodilation | 3% | 1% | 2% | 1% |
| Dermatologic | Sweating | 6% | 2% | 5% | 1% |
| Gastrointestinal | Nausea | 20% | 5% | 19% | 8% |
| Dry Mouth | 11% | 5% | 10% | 5% | |
| Constipation | 10% | 2% | 5% | 3% | |
| Diarrhea | 9% | 7% | 11% | 5% | |
| Decreased Appetite | 5% | 1% | 6% | 3% | |
| Vomiting | 3% | 2% | 3% | 2% | |
| Dyspepsia | — | — | 5% | 3% | |
| Nervous System | Insomnia | 11% | 8% | 12% | 11% |
| Somnolence | 15% | 5% | 16% | 5% | |
| Dizziness | 6% | 5% | 6% | 5% | |
| Tremor | 5% | 1% | 4% | 1% | |
| Nervousness | 4% | 3% | — | — | |
| Libido Decreased | 9% | 2% | 5% | 2% | |
| Abnormal Dreams | 3% | 2% | |||
| Respiratory System | Respiratory Disorder | 7% | 5% | — | — |
| Sinusitis | 4% | 3% | — | — | |
| Yawn | 4% | — | 2% | < 1% | |
| Special Senses | Abnormal Vision | 2% | 1% | 3% | 1% |
| Urogenital System | Abnormal Ejaculationb | 25% | 2% | 13% | 2% |
| Female Genital | 4% | 1% | 5% | 1% | |
| Disorderb | |||||
| Impotenceb | 4% | 3% | 9% | 1% | |
| a Events reported by at least 2% of GAD and PTSD in patients treated with Xet are included, except the following events which had an incidence on placebo ≥ Xet [GAD]: Abdominal pain, back pain, trauma, dyspepsia, myalgia, and pharyngitis. [PTSD]: Back pain, headache, anxiety, depression, nervousness, respiratory disorder, pharyngitis, and sinusitis. b Percentage corrected for gender. |
Dose Dependency Of Adverse Events
A comparison of adverse event rates in a fixed-dose study comparing 10, 20, 30, and 40 mg/day of Xet with placebo in the treatment of major depressive disorder revealed a clear dose dependency for some of the more common adverse events associated with use of Xet, as shown in Table 5:
Table 5: Treatment-Emergent Adverse Experience Incidence in a Dose-Comparison Trial in the Treatment of Major Depressive Disordera
Human Experience
Since the introduction of Xet in the United States, 342 spontaneous cases of deliberate or accidental overdosage during paroxetine treatment have been reported worldwide (circa 1999). These include overdoses with paroxetine alone and in combination with other substances. Of these, 48 cases were fatal and of the fatalities, 17 appeared to involve paroxetine alone. Eight fatal cases that documented the amount of paroxetine ingested were generally confounded by the ingestion of other drugs or alcohol or the presence of significant comorbid conditions. Of 145 non-fatal cases with known outcome, most recovered without sequelae. The largest known ingestion involved 2,000 mg of paroxetine (33 times the maximum recommended daily dose) in a patient who recovered.
Commonly reported adverse events 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 torsade 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.
Overdosage Management
No specific antidotes for paroxetine are known. Treatment should consist of those general measures employed in the management of overdosage with any drugs effective in the treatment of major depressive disorder.
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. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, or exchange transfusion are unlikely to be of benefit.
A specific caution involves patients who are taking or have recently taken paroxetine who might ingest excessive quantities of a tricyclic antidepressant. In such a case, accumulation of the parent tricyclic and/or an active metabolite may increase the possibility of clinically significant sequelae and extend the time needed for close medical observation (see PRECAUTIONS: Drugs Metabolized by Cytochrome CYP2D6).
In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the Physicians' Desk Reference (PDR).
The efficacy of paroxetine in the treatment of major depressive disorder, social anxiety disorder, obsessive compulsive disorder (OCD), panic disorder (PD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin (5-hydroxy-tryptamine, 5-HT). 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 potent and highly selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. In vitro radioligand binding studies indicate that paroxetine has little affinity for muscarinic, alpha1-, alpha2-, beta-adrenergic-, dopamine (D2)-, 5-HT1-, 5-HT2-, and histamine (H1)-receptors; antagonism of muscarinic, histaminergic, and alpha1-adrenergic receptors has been associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs.
Because the relative potencies of paroxetine's major metabolites are at most 1/50 of the parent compound, they are essentially inactive.
Paroxetine hydrochloride is completely absorbed after oral dosing of a solution of the hydrochloride salt. The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets of Xet daily for 30 days. Paroxetine is extensively metabolized and the metabolites are considered to be inactive. Nonlinearity in pharmacokinetics is observed with increasing doses. Paroxetine metabolism is mediated in part by CYP2D6, and the metabolites are primarily excreted in the urine and to some extent in the feces. Pharmacokinetic behavior of paroxetine has not been evaluated in subjects who are deficient in CYP2D6 (poor metabolizers).
In a meta-analysis of paroxetine from 4 studies done in healthy volunteers following multiple dosing of 20 mg/day to 40 mg/day, males did not exhibit a significantly lower Cmax or AUC than females.
Absorption And Distribution
Paroxetine is equally bioavailable from the oral suspension and tablet.
Paroxetine hydrochloride is completely absorbed after oral dosing of a solution of the hydrochloride salt. In a study in which normal male subjects (n = 15) received 30 mg tablets daily for 30 days, steady-state paroxetine concentrations were achieved by approximately 10 days for most subjects, although it may take substantially longer in an occasional patient. At steady state, mean values of Cmax, Tmax, Cmin, and T½ were 61.7 ng/mL (CV 45%), 5.2 hr. (CV 10%), 30.7 ng/mL (CV 67%), and 21.0 hours (CV 32%), respectively. The steady-state Cmax and Cmin values were about 6 and 14 times what would be predicted from single-dose studies. Steady-state drug exposure based on AUC0-24 was about 8 times greater than would have been predicted from single-dose data in these subjects. The excess accumulation is a consequence of the fact that 1 of the enzymes that metabolizes paroxetine is readily saturable.
The effects of food on the bioavailability of paroxetine were studied in subjects administered a single dose with and without food. AUC was only slightly increased (6%) when drug was administered with food but the Cmax was 29% greater, while the time to reach peak plasma concentration decreased from 6.4 hours post-dosing to 4.9 hours.
Paroxetine distributes throughout the body, including the CNS, 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 400 ng/mL. Paroxetine does not alter the in vitro protein binding of phenytoin or warfarin.
Metabolism And Excretion
The mean elimination half-life is approximately 21 hours (CV 32%) after oral dosing of 30 mg tablets daily for 30 days of Xet. In steady-state dose proportionality studies involving elderly and nonelderly patients, at doses of 20 mg to 40 mg daily for the elderly and 20 mg to 50 mg daily for the nonelderly, some nonlinearity was observed in both populations, again reflecting a saturable metabolic pathway. In comparison to Cmin values after 20 mg daily, values after 40 mg daily were only about 2 to 3 times greater than doubled.
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 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 PRECAUTIONS: Drugs Metabolized by CYP2D6).
Approximately 64% of a 30-mg oral solution dose 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% 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.
- R52.1 – Chronic intractable pain
- R52.2 – Other chronic pain
- R52.9 – Unspecified pain
- R52.1 – Chronic intractable pain
- R52.2 – Other chronic pain
- R52.9 – Unspecified pain
Available in countries
| Body System/ Preferred Term | Placebo n = 51 | Xet | |||
| 10 mg n = 102 | 20 mg n = 104 | 30 mg n = 101 | 40 mg n = 102 | ||
| Body as a Whole | |||||
| Asthenia | 0.0% | 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 | 0.0% | 2.0% | 5.8% | 5.9% | 5.9% |
| Dizziness | 3.9% | 6.9% | |||