Instructions for Duloxent hard enteric-coated capsules 60 mg blister No. 30
Composition
active ingredient: duloxetine hydrochloride;
1 hard enteric-coated capsule contains 30 mg or 60 mg of duloxetine as duloxetine hydrochloride;
excipients: spherical sugar (sucrose, corn starch), hypromellose, sucrose, hypromellose phthalate, talc, triethyl citrate;
capsule shell for 30 mg dosage: titanium dioxide (E 171), indigotine (E 132), gelatin, printing ink (shellac, black iron oxide (E 172));
capsule shell for 60 mg dosage: titanium dioxide (E 171), indigotine (E 132), yellow iron oxide (E 172), gelatin, printing ink (shellac, black iron oxide (E 172)).
Dosage form
Enteric-coated hard capsules.
Main physicochemical properties:
30 mg dosage: white to off-white pellets in a size No. 3 hard gelatin capsule with a white body and a dark blue cap; 30 is printed in black on the body;
60 mg dosage: white to off-white pellets in a size No. 1 hard gelatin capsule with a yellowish-green body and a dark blue cap; 60 is printed in black on the body.
Pharmacotherapeutic group
Psychoanaleptics. Other antidepressants. ATX code N06A X21.
Pharmacological properties
Pharmacodynamics.
Mechanism of action
Duloxetine is a combined serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor. It weakly inhibits dopamine reuptake, with no significant affinity for histaminergic and dopaminergic, cholinergic, and adrenergic receptors.
Duloxetine dose-dependently increases extracellular levels of serotonin and norepinephrine in various areas of the animal brain.
Duloxetine normalized pain thresholds in several preclinical models of neuropathic and inflammatory pain and attenuated pain behavior in a model of persistent pain. The inhibitory effect of duloxetine on pain is thought to result from potentiation of descending inhibitory pain pathways in the central nervous system.
Pharmacokinetics.
Duloxetine is administered as a single enantiomer. Duloxetine is extensively metabolized by oxidative enzymes (CYP1A2 and polymorphic CYP2D6), with subsequent conjugation. The pharmacokinetics of duloxetine show a large inter-subject variability (generally 50-60%), partly due to gender, age, smoking status, and CYP2D6 metabolism status.
Absorption
Duloxetine is well absorbed after oral administration. Peak plasma concentrations are reached 6 hours after administration. Absolute oral bioavailability of duloxetine ranged from 32% to 80% (mean 50%). Food intake delays absorption, increasing the time to peak plasma concentrations from 6 to
10 hours, with a decrease in absorption (approximately 11%). These changes are not clinically significant.
Distribution
Duloxetine is highly bound to human serum proteins (approximately 96%), both albumin and alpha-1-acid glycoprotein. Protein binding is not affected by hepatic or renal impairment.
Biotransformation
Duloxetine is extensively metabolized, and the metabolites are excreted primarily in the urine. Both cytochromes P450-2D6 and 1A2 catalyze the formation of two major metabolites, the glucuronide conjugate of 4-hydroxyduloxetine and the sulfate conjugate of 5-hydroxy-6-methoxyduloxetine. Based on in vitro studies, the circulating metabolites of duloxetine are considered to be pharmacologically inactive. The pharmacokinetics of duloxetine in patients who are poor metabolizers of CYP2D6 have not been specifically studied. Limited data suggest that plasma levels of duloxetine are higher in these patients.
Breeding
The half-life of duloxetine is 12 hours. The mean plasma clearance of duloxetine is 101 l/h.
The elimination half-life of duloxetine ranges from 8 to 17 hours (mean 12 hours). After intravenous administration, plasma clearance of duloxetine ranges from 22 L/h to
46 l/h (mean 36 l/h). After oral administration, the apparent plasma clearance of duloxetine ranges from 33 to 261 l/h (mean 101 l/h).
Special population groups
Gender: Pharmacokinetic differences have been identified between men and women (apparent plasma clearance is approximately 50% lower in women). Based on the similarity in clearance ranges, pharmacokinetic differences based on gender do not justify a lower dose recommendation for female patients.
Age: Pharmacokinetic differences have been observed between young and elderly women (≥ 65 years) (AUC increases by approximately 25% and half-life is approximately 25% longer in elderly patients), although the magnitude of these changes is not sufficient to justify a dose adjustment. As a general recommendation, caution should be exercised when treating elderly patients (see sections 4.2 and 4.4).
Hepatic impairment. Moderate liver disease (Child-Pugh Class B) affected the pharmacokinetics of duloxetine. Compared to healthy volunteers, the apparent plasma clearance of duloxetine was 79% lower, the apparent terminal half-life was 2.3-fold longer, and the AUC was 3.7-fold higher in patients with moderate liver disease. The pharmacokinetics of duloxetine and its metabolites have not been studied in patients with mild or severe hepatic impairment.
Breastfeeding mothers. Duloxetine has been studied in 6 lactating women who were at least 12 weeks postpartum. Duloxetine is excreted in human milk, and steady-state concentrations in breast milk are approximately one-quarter of those in plasma. The amount of duloxetine in breast milk is approximately 7 mcg/day at a dose of 40 mg twice daily. Lactation had no effect on the pharmacokinetics of duloxetine.
Paediatric population: The pharmacokinetics of duloxetine in children aged 7 to 17 years with major depressive disorder following oral administration of 20 to 120 mg once daily were characterized using population modeling analyses based on data from
3 studies. Model-predicted plasma concentrations of duloxetine in pediatric patients were generally within the range of concentrations observed in adult patients.
Indication
- Treatment of major depressive disorder.
- Treatment of diabetic peripheral neuropathic pain.
- Treatment of generalized anxiety disorder.
- Duloxetine® is indicated for adults.
- For additional information, see the Pharmacological Properties section.
Contraindication
A contraindication for the use of the drug is hypersensitivity to duloxetine or to any of the drug's excipients.
Duloxetine should not be administered concomitantly with non-selective, irreversible monoamine oxidase inhibitors (MAOIs) (see section “Interaction with other medicinal products and other forms of interaction”).
Duloxetine should not be prescribed to patients with liver disease, as it may cause liver failure (see section "Pharmacokinetics").
Duloxetine should not be administered in combination with fluvoxamine, ciprofloxacin or enoxacin (strong CYP1A2 inhibitors) due to increased plasma concentrations of duloxetine (see section 4.5).
Duloxetine should not be prescribed to patients with end-stage renal disease (creatinine clearance <30 ml/min) (see section 4.4).
Duloxetine should not be prescribed to patients with unstable hypertension, as this may precipitate a hypertensive crisis (see sections "Special warnings and precautions for use" and "Adverse reactions").
Interaction with other medicinal products and other types of interactions
MAO inhibitors: Duloxetine should not be used in combination with non-selective, irreversible monoamine oxidase (MAO) inhibitors or for at least 14 days after discontinuation of MAO inhibitor treatment due to the risk of serotonin syndrome. Based on the half-life of duloxetine, at least 5 days should elapse after discontinuation of Duloxetine before starting MAO inhibitors (see section 4.4).
Reversible selective MAO inhibitors, such as moclobemide, reduce the risk of serotonin syndrome, but this combination is not recommended. The antibiotic linezolid is a reversible non-selective MAO inhibitor and should not be given to patients receiving Duloxetine (see section 4.4).
CYP1A2 inhibitors. Since CYP1A2 is involved in the metabolism of duloxetine, concomitant use of duloxetine with potent CYP1A2 inhibitors is likely to result in increased duloxetine concentrations. Fluvoxamine (100 mg once daily), a potent CYP1A2 inhibitor, decreased duloxetine plasma clearance by approximately 77% and increased AUCo-t by 6-fold. Therefore, duloxetine should not be co-administered with CYP1A2 inhibitors, including fluvoxamine.
Drugs that act on the central nervous system.
The risk of using duloxetine in combination with other drugs that act on the central nervous system has not been systematically evaluated, except as described in this section. Therefore, caution should be exercised when using Duloxetine in combination with other drugs or substances that act on the central nervous system, including alcohol and sedative drugs (e.g. benzodiazepines, morphinomimetics, neuroleptics, phenobarbital, sedative antihistamines).
Serotonin syndrome: Serotonin syndrome has been reported rarely in patients taking selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) with serotonergic agents. Caution should be exercised when prescribing duloxetine in combination with serotonergic and tricyclic antidepressants such as clomipramine or amitriptyline, MAO inhibitors such as moclobemide or linezolid, St. John's wort (Hypericum perforatum) or triptans, buprenorphine, tramadol, peptidyne, tryptophan.
Medicinal products metabolised by CYP1A2: The pharmacokinetics of theophylline, a CYP1A2 substrate, were not significantly affected by co-administration with duloxetine (60 mg twice daily).
Medicinal products metabolized by CYP2D6. Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine 60 mg twice daily was administered with a single dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold. Co-administration of duloxetine (40 mg twice daily) increased the steady-state AUC of tolterodine (2 mg twice daily) by 71% but did not affect the pharmacokinetics of the 5-hydroxy metabolite, and no dosage adjustment is recommended. Caution is advised when administering duloxetine with medicinal products that are primarily metabolized by CYP2D6 (risperidone, tricyclic antidepressants [TCAs] such as nortriptyline, amitriptyline and imipramine), especially if they have a narrow therapeutic index (e.g. flecainide, propafenone and metoprolol).
Oral contraceptives and other steroidal agents: In vitro studies indicate that duloxetine does not induce CYP3A catalytic activity. Specific in vivo drug interaction studies have not been performed.
Anticoagulants and antithrombotic agents. Duloxetine should be administered with caution with oral anticoagulants and antithrombotic agents due to the potential for increased bleeding risk due to pharmacodynamic interactions. In addition, increases in INR have been observed when duloxetine was administered to patients receiving warfarin. However, coadministration of duloxetine and warfarin in a clinical pharmacology study in healthy volunteers under inpatient conditions did not result in a clinically meaningful change in INR from baseline or in the pharmacokinetics of R- or S-warfarin.
Effects of other medicinal products on duloxetine
Antacids and H2 antagonists: Coadministration of duloxetine with aluminum- and magnesium-containing antacids or duloxetine with famotidine did not affect the rate or extent of absorption of duloxetine following a 40 mg oral dose.
CYP1A2 inducers: A population pharmacokinetic analysis showed that smokers have almost 50% lower plasma concentrations of duloxetine compared to non-smokers.
Application features
Seizures and mania: As with other drugs acting on the central nervous system, duloxetine should be used with caution in patients with a history of seizures, mania, or bipolar disorder.
Mydriasis: Mydriasis has been reported in association with duloxetine, therefore duloxetine should be used with caution in patients with elevated intraocular pressure or at risk of acute narrow-angle glaucoma.
Blood pressure and palpitations. In some patients, duloxetine has been associated with an increase in blood pressure and clinically significant hypertension. This may be due to the noradrenergic effects of duloxetine. Hypertensive crisis has been reported with duloxetine, particularly in patients with pre-existing hypertension. Therefore, monitoring of blood pressure is recommended in patients with known hypertension and/or other cardiac disease, particularly during the first month of treatment. Duloxetine should be used with caution in patients who may be at risk from increased heart rate or blood pressure. Duloxetine should also be used with caution with medicinal products that may impair its metabolism (see section 4.5).
In patients who experience persistent elevations in blood pressure while taking duloxetine, dose reduction or gradual discontinuation should be considered (see section 4.8). Duloxetine should not be initiated in patients with uncontrolled hypertension (see section 4.3).
Renal impairment: Increased plasma concentrations of duloxetine have been observed in patients with severe renal impairment on haemodialysis (creatinine clearance <30 ml/min). For patients with severe renal impairment, see section 4.3. For patients with mild to moderate renal impairment, see section 4.4.
If concomitant treatment with duloxetine and other serotonergic/neuroleptic agents that may affect serotonergic and/or dopaminergic neurotransmitter systems is clinically warranted, close patient monitoring is recommended, particularly during treatment initiation and dose increases.
Symptoms of serotonin syndrome may include altered mental status (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoherence), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome in its most severe form may resemble CNS depression, including hyperthermia, muscle rigidity, elevated serum creatine kinase, autonomic instability with possible rapid fluctuations in vital signs, and changes in mental status.
Preparations containing St. John's wort. Adverse reactions may be more common when Duloxetine® is used concomitantly with herbal preparations containing St. John's wort (Hypericum perforatum).
Suicide.
Major depressive disorder and generalized anxiety disorder.
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). The risk exists until significant remission is achieved. The patient should be closely monitored until significant improvement is achieved, as remission may not occur during the first few weeks or more of treatment. It is general clinical experience that the risk of suicide is increased in the initial stages of treatment.
Other psychiatric conditions for which Duloxetine® should be prescribed may also be associated with an increased risk of suicidal behaviour. In addition, these psychiatric conditions may be comorbid if they accompany major depressive disorder. Therefore, the same precautions should be taken when treating patients with major depressive disorder as when treating other psychiatric conditions. Patients with a history of suicidal behaviour or a significant level of suicidal ideation are at greater risk of suicidal behaviour and should be monitored closely during treatment.
A meta-analysis of placebo-controlled clinical trials of antidepressants in psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients under 25 years of age. Cases of suicidal ideation and behaviour have been reported during duloxetine therapy or early after treatment discontinuation (see section 4.8).
During therapy, especially in the early stages and when changing the dosage, patients, especially those at risk, should be closely monitored and the dosage adjusted accordingly. Patients and caregivers should be informed of the need to monitor for any clinical worsening, suicidal behavior or thoughts, and unusual changes in behavior and to seek medical advice immediately if they present.
Diabetic peripheral neuropathic pain: Isolated cases of suicidal ideation and suicidal behaviour have been reported during or early after treatment with duloxetine, as with other medicinal products with similar pharmacological effects (antidepressants). Physicians should advise patients to report any feelings of distress.
Use in children and adolescents under 18 years of age.
Duloxetine should not be used in children and adolescents under 18 years of age. Suicide-related behaviour (suicide attempt and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were observed more frequently in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If a decision to treat is made based on clinical need, the patient should be closely monitored for suicidal symptoms (see section 5.1). In addition, long-term safety data on growth, maturation and cognitive and behavioural development in children and adolescents are not available (see section 4.8).
Hyponatremia: Cases of hyponatremia, including cases of serum sodium below 110 mmol/L, have been reported with duloxetine. Hyponatremia may be caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Most cases of hyponatremia have been reported in the elderly, especially in combination with conditions that lead to changes in fluid balance. Caution should be exercised in patients at increased risk of hyponatremia (e.g., the elderly), patients with cirrhosis, dehydrated patients, and patients receiving diuretics.
Withdrawal symptoms. Withdrawal symptoms are quite common, especially when treatment is stopped abruptly (see section 4.8). In clinical trials, adverse events observed after abrupt discontinuation of treatment occurred in approximately 45% of patients treated with duloxetine and 23% of patients treated with placebo. The risk of withdrawal symptoms with SSRIs and SNRIs depends on several factors, including the duration and dose of therapy and the rate of dose reduction. The most frequently reported reactions are listed in the section on Adverse Reactions. These symptoms are usually mild or moderate, but in some patients they may be severe, usually occurring within the first few days after discontinuation of treatment. Very rarely, such symptoms have been observed in patients who accidentally missed a dose. These symptoms subside spontaneously and usually disappear within 2 weeks, although in some individuals they may be prolonged (2-3 months or more). Therefore, it is recommended that the dose of duloxetine be gradually reduced when discontinuing treatment over a period of at least 2 weeks, according to the patient's needs (see section 4.2).
Elderly patients: Data on the use of duloxetine at a dosage of 120 mg in elderly people with major depressive disorder and generalized anxiety disorder are limited. Therefore, caution should be exercised when using the drug in elderly patients at the maximum dosage (see sections “Method of administration and dosage” and “Pharmacokinetics”).
Akathisia/psychomotor restlessness: Duloxetine has been associated with the development of akathisia, a subjectively unpleasant or distressing restlessness and need to move, often accompanied by an inability to sit or stand still. These symptoms occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be harmful.
Medicines containing duloxetine. Duloxetine is used under different brand names for several indications (diabetic neuropathic pain, major depressive disorder, generalised anxiety disorder and stress urinary incontinence). The use of more than one of these medicines at the same time should be avoided.
Elevated liver enzymes. Severe elevations of liver enzymes (>10 times the upper limit of normal) or liver injury with cholestasis or severe elevations of enzymes together with liver injury have been reported rarely (see section 4.8). These events have been most commonly reported during the first months of treatment. Liver injury is most often hepatocellular in nature. Caution should be exercised when prescribing duloxetine to patients taking medicinal products that may cause liver injury.
Sexual dysfunction: Selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). Long-term sexual dysfunction has been reported where symptoms persist despite discontinuation of SSRIs/SNRIs.
Presence of sucrose. Duloxent® contains sucrose. Duloxent® hard enteric-coated capsules should not be administered to patients with hereditary fructose intolerance, malabsorption syndrome, sucrase-isomaltase insufficiency. If the patient has been diagnosed with an intolerance to some sugars, contact your doctor before taking this medicinal product.
Use during pregnancy or breastfeeding
Pregnancy
Animal studies have shown that reproductive toxicity at systemic exposure (AUC) of duloxetine is lower than the maximum clinical exposure.
Two large observational studies suggest no increased overall risk of major birth defects (one in the US involving 2,500 individuals exposed to duloxetine in the first trimester, and the other in the EU involving 1,500 individuals exposed to duloxetine in the first trimester). Analysis of specific birth defects, such as heart defects, has been inconclusive.
Observational data suggest an increased risk (less than 2-fold) of postpartum hemorrhage following exposure to duloxetine within the month before birth.
Epidemiological evidence suggests that the use of SSRIs during pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension of the newborn (PPHN). Although the association of PPHN with SSRI treatment has not been studied, this potential risk cannot be excluded with duloxetine given its mechanism of action (inhibition of serotonin reuptake).
As with other serotonergic drugs, withdrawal symptoms may occur in infants whose mothers have used duloxetine before delivery. Symptoms of withdrawal syndrome include hypotension, tremor, hyperexcitability, difficulty swallowing and sucking, respiratory distress, and seizures. In most cases, these symptoms have been observed immediately after birth or within the first few days of life.
Use of the drug during pregnancy is recommended only if the expected benefit outweighs the potential risk to the fetus. Women taking duloxetine should be advised to inform their doctor if they become pregnant or plan to become pregnant.
Breast-feeding
Duloxetine is poorly excreted in human milk, based on a study of 6 lactating patients who did not breastfeed their infants. The established dose for the infant is 1 mg per kg of body weight, which is approximately 0.14% of the maternal dose. The safety of duloxetine in infants is unknown, so breastfeeding is not recommended while taking duloxetine.
Fertility
In animal studies, duloxetine did not affect male fertility, and effects in women were only seen at doses that caused maternal toxicity.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies on the effect of duloxetine on the speed of reaction when driving or using other mechanisms have not been conducted. Duloxenta® may cause sedation and dizziness. Patients should be informed that if they experience sedation or dizziness, they should refrain from potentially hazardous activities, such as driving or using other mechanisms.
Method of administration and doses
For oral use
In major depressive disorder, the initial and recommended maintenance dose of duloxetine is 60 mg once daily without regard to meals. Doses above 60 mg once daily may be increased to a maximum dose of 120 mg daily in divided doses. The feasibility of prescribing doses above 120 mg has not been systematically evaluated in terms of clinical data. However, there is no clinical data to suggest that dose escalation would be effective in patients who do not respond to the initial recommended dose.
The therapeutic effect of treatment is evident within 2–4 weeks.
After a sustained antidepressant effect, it is recommended to continue treatment for several months to avoid relapse. For patients who respond to duloxetine and have a history of recurrent major depressive episodes, further long-term treatment at a dose of 60-120 mg per day should be considered.
For generalized anxiety disorder, the recommended starting dose is 30 mg once daily with or without food. In patients with insufficient response, the dose should be increased to 60 mg, which is the usual maintenance dose for most patients.
For patients with comorbid major depressive disorder, the initial and maintenance dose is 60 mg once daily (see also dosing recommendations above).
Doses up to 120 mg/day have been shown to be effective and have been evaluated for safety in clinical trials. Therefore, for patients who do not respond adequately to 60 mg, an increase in dose to 90 mg or 120 mg may be considered. Dose increases should be based on clinical response and tolerability.
After achieving a stable therapeutic effect, it is recommended to continue treatment for several months to avoid relapse.
For diabetic peripheral neuropathic pain, the initial and recommended maintenance dose is 60 mg once daily, without regard to meals. Doses above 60 mg once daily, up to a maximum dose of 120 mg daily, given in divided doses, have been evaluated for safety in clinical studies. Duloxetine plasma concentrations vary considerably between individuals (see section 5.2). Therefore, some patients with inadequate response to the dose of duloxetine may benefit from a higher dose of duloxetine.
60 mg may benefit from a higher dose.
The therapeutic effect of treatment is evident within 2 months. In patients with an inadequate initial response, additional response after this period is unlikely. The therapeutic effect should be reassessed regularly (at least every 3 months) (see section "Pharmacodynamics").
Elderly patients: No dose adjustment based solely on age is recommended for elderly patients. However, as with all medicinal products, caution should be exercised when treating elderly patients, especially when using Duloxetine at a dose of 120 mg/day for the treatment of major depressive disorder or generalized anxiety disorder, for which data are limited (see sections 4.4 and 5.2).
Patients with hepatic impairment: Duloxent® should not be administered to patients with liver disease causing hepatic dysfunction (see sections 4.3 and 4.4).
Patients with renal impairment. No dose adjustment is required for patients with mild to moderate renal impairment (creatinine clearance 30 to 80 ml/min). Not indicated for the treatment of patients with end-stage renal disease (creatinine clearance <30 ml/min) (see Contraindications).
Children.
Duloxetine should not be used in children and adolescents under 18 years of age for the treatment of major depressive disorder due to safety and efficacy concerns (see sections 4.4, 4.8 and 5.1).
The safety and efficacy of duloxetine for the treatment of generalized anxiety disorder in children aged 7 to 17 years have not been established. Currently available data are described in sections 4.8, 5.1, and 5.2.
The safety and efficacy of duloxetine for the treatment of diabetic peripheral neuropathic pain have not been studied. Data are not available.
Discontinuation of treatment.
Abrupt discontinuation of treatment should be avoided. After discontinuation of Duloxetine®, the dose should be gradually reduced over a period of at least one to two weeks to reduce the risk of withdrawal reactions (see sections 4.4 and 4.8). If intolerable symptoms occur after dose reduction or after discontinuation of treatment, reintroduction of the previously prescribed dose may be considered. Your doctor may then continue to reduce the dose, but more gradually.
Children
Clinical studies on the use of duloxetine in children have not been conducted, therefore it is not used in pediatric practice.
Overdose
Large doses (up to 5400 mg) have been reported as monotherapy or in combination with other drugs. There have been some fatalities, mostly from mixed overdoses, but also with duloxetine alone at doses of approximately 1000 mg. Symptoms of overdose (duloxetine alone or in combination with other drugs) have included somnolence, coma, serotonin syndrome, seizures, vomiting, and tachycardia.
Specific antidotes are not known, and specific treatment (cyproheptadine and/or temperature control) is necessary if serotonin syndrome occurs. A patent airway should be checked. Cardiac monitoring and vital signs should be monitored, along with appropriate symptomatic and supportive measures. Gastric lavage may be appropriate if administered immediately after ingestion or for symptomatic purposes. Activated charcoal reduces absorption. Duloxetine has a large volume of distribution, so forced diuresis, hemoperfusion, and exchange perfusion are unlikely to be useful.
Side effects
The most common adverse reactions in patients treated with duloxetine were nausea, headache, dry mouth, somnolence, and dizziness. However, most of the common adverse reactions were mild to moderate in severity, usually began early in therapy, and most tended to resolve even with continued therapy.
The table below lists the adverse reactions observed with duloxetine, based on data obtained from spontaneous reports and placebo-controlled clinical trials.
Frequency estimate: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10000 and <1/1000), very rare (<1/10000), unknown (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
