Instructions for Revival hard capsules with gastro-resistant granules 60 mg blister No. 30
Composition
active ingredient: duloxetine hydrochloride;
1 hard gastro-resistant capsule contains 33.68 mg of duloxetine hydrochloride, equivalent to 30 mg of duloxetine, or 67.35 mg of duloxetine hydrochloride, equivalent to 60 mg of duloxetine;
excipients: spherical sugar (sucrose, corn starch), hypromellose 2910/5mPa.s, crospovidone type A, sucrose, hypromellose acetate succinate, triethyl citrate (E 1505), talc, macrogol 8000, titanium dioxide (E 171);
capsule shell (for 30 mg capsules)
capsule shell composition: titanium dioxide (E 171), gelatin, patent blue V (E 131), sodium lauryl sulfate, carmoisine (E 122), purified water;
capsule shell (for 60 mg capsules)
capsule shell composition: titanium dioxide (E 171), gelatin, sodium lauryl sulfate, erythrosine (E 127), red iron oxide (E 172), black iron oxide (E 172), purified water.
Dosage form
Gastro-resistant hard capsules.
Main physicochemical properties:
30 mg capsules: hard gelatin capsules, size “3” with a white body and a blue cap, containing off-white pellets;
60 mg capsules: size “0” hard gelatin capsules with a light gray body and pink cap, containing off-white pellets.
Pharmacotherapeutic group
Other antidepressants. ATX code N06A X21.
Pharmacological properties
Pharmacodynamics.
Duloxetine is a combined serotonin (5-HT) and noradrenaline (NA) reuptake inhibitor. It has little dopamine reuptake inhibition and has no significant affinity for histamine, dopamine, cholinergic, or adrenergic receptors. Duloxetine dose-dependently increases extracellular levels of serotonin and noradrenaline in various brain regions of animals.
Pharmacodynamic effects: Duloxetine normalizes the pain threshold. Duloxetine also has analgesic effects, which are likely to result from slowing the transmission of pain impulses to the CNS.
Clinical efficacy and safety
Major depressive disorder (MDD): The efficacy of duloxetine has been demonstrated in fixed-dose studies in adult patients with major depressive disorder. Duloxetine was statistically superior to placebo. Response and remission rates were also statistically significantly higher with duloxetine compared to placebo. In a study investigating the efficacy of duloxetine in preventing relapse, it was found to be statistically significantly superior to placebo. Patients with recurrent MDD who received duloxetine had a significantly longer symptom-free period compared to patients who received placebo. A study of the efficacy of duloxetine in elderly patients with depression (≥65 years) showed a statistically significant difference compared to placebo.
Generalized Anxiety Disorder (GAD): In clinical trials, duloxetine demonstrated statistically significant superiority over placebo when used in the acute phase and for the prevention of relapse in adult patients with GAD.
Response and remission rates were also higher with duloxetine compared to placebo. In a study investigating the prevention of relapse in elderly patients (≥65 years) with GAD, duloxetine was shown to be more effective than placebo. The efficacy and safety of duloxetine in elderly patients were similar to those observed in younger adults.
Diabetic peripheral neuropathic pain: The efficacy of duloxetine has been demonstrated in studies investigating the treatment of diabetic neuropathic pain. Duloxetine significantly reduced pain compared with placebo. The effect was evident in some patients within the first week of treatment. The same studies also examined whether patients experienced drowsiness during treatment. Among patients who did not experience drowsiness, clinical response was more likely to occur with duloxetine than with placebo.
Children: Duloxetine has not been studied in patients under 7 years of age. Studies in children aged 7 to 17 years with ADHD showed that neither duloxetine nor the primary control group were statistically different from placebo.
Discontinuation of treatment due to adverse events was higher in patients receiving duloxetine compared to those receiving fluoxetine, mainly due to nausea. Suicidal behavior has also been reported with duloxetine. Treatment with duloxetine demonstrated statistically significant greater improvement in patients with GAD. Duloxetine did not demonstrate efficacy in reducing pain, as measured by the primary outcome measure of the mean pain score on the Brief Pain Inventory (BPI).
Pharmacokinetics.
Absorption: Duloxetine is well absorbed after oral administration. Peak plasma concentrations are reached 6 hours after dosing. The absolute oral bioavailability of duloxetine ranges from 32% to 80% (mean 50%). Food intake delays absorption, increasing the time to peak concentration from 6 to 10 hours and decreasing absorption (by approximately 11%). These changes are not clinically significant.
Distribution: Approximately 96% of duloxetine is bound to human plasma proteins. Duloxetine binds to both albumin and α1-acid glycoprotein. Protein binding is not affected by renal or hepatic impairment.
Metabolism: 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. Circulating metabolites of duloxetine are considered pharmacologically inactive based on in vitro studies. The pharmacokinetics of duloxetine in patients who are poor metabolisers of CYP2D6 have not been specifically studied. Limited data suggest that plasma levels of duloxetine are higher in these patients.
Elimination: The elimination half-life of duloxetine ranges from 8 to 17 hours (mean 12 hours). After oral administration, the apparent plasma clearance of duloxetine ranges from 33 to 261 L/h (mean 101 L/h).
Special patient groups
Gender: Pharmacokinetic differences have been observed between men and women (apparent plasma clearance is approximately 50% lower in women). Based on the overlap in the clearance range, pharmacokinetic differences due to gender are not justified in using a lower dose for female patients.
Age Pharmacokinetic differences have been observed between younger and older women (≥65 years) (AUC increases by approximately 25% and half-life is approximately 25% longer in older women), although the magnitude of these changes is not sufficient to justify dose adjustments. As a general recommendation, caution should be exercised when treating elderly patients (see sections 4.2 and 4.4).
Renal impairment: In patients with end-stage renal disease undergoing dialysis, duloxetine exposure and AUC were increased two-fold compared to healthy volunteers. Pharmacokinetic data for duloxetine are limited in patients with mild to moderate renal impairment.
Hepatic impairment. Moderate hepatic impairment (Child-Pugh 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 hepatic disease. The pharmacokinetics of duloxetine and its metabolites have not been studied in patients with mild or severe hepatic impairment.
Breastfeeding mothers. The disposition of duloxetine has been studied in breast-feeding women who were at least 12 weeks postpartum. Duloxetine is found in breast 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 when administered 40 mg twice daily. Lactation had no effect on the pharmacokinetics of duloxetine.
Children: The pharmacokinetics of duloxetine in pediatric patients aged 7 to 17 years with major depressive disorder following oral dosing of 20 to 120 mg once daily were characterized using population modeling analyses based on data from
Three studies. Model-predicted steady-state plasma concentrations of duloxetine in children were largely 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.
The Revival® drug is intended for adult patients.
For additional information, see the Pharmacological Properties section.
Contraindication
Hypersensitivity to duloxetine or to any of the excipients of the drug.
Concomitant use with non-selective, irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated. Liver disease that may cause liver failure.
Duloxetine should not be used in combination with fluvoxamine, ciprofloxacin or enoxacin (strong CYP1A2 inhibitors) due to increased plasma concentrations of duloxetine. Severe renal impairment (creatinine clearance < 30 ml/min). Initiation of duloxetine treatment is contraindicated in patients with uncontrolled hypertension as this may lead to a potential risk of hypertensive crisis.
Interaction with other medicinal products and other types of interactions
MAOIs. Due to the risk of serotonin syndrome, duloxetine should not be used in combination with non-selective irreversible MAOIs or within 14 days of stopping their use. Given the half-life of duloxetine, MAOIs should not be administered for at least 5 days after stopping duloxetine treatment (see section 4.3). Concomitant use of Revival® with selective reversible MAOIs such as moclobemide is not recommended (see section 4.4). The antibiotic linezolid is a reversible non-selective MAOI and should not be administered to patients receiving Revival® (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 AUC0-t by 6-fold. Therefore, duloxetine should not be co-administered with CYP1A2 inhibitors, including fluvoxamine (see section 4.4).
Medicinal products acting on the central nervous system. The risk of using duloxetine in combination with other medicinal products acting on the central nervous system has not been systematically evaluated, except as mentioned in this section. Therefore, caution should be exercised when taking duloxetine in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products (e.g. benzodiazepines, morphinomimetics, antipsychotics, phenobarbital, sedative antihistamines).
Serotonin syndrome: Serotonin syndrome has been reported rarely in patients receiving selective serotonin reuptake inhibitors/serotonin norepinephrine reuptake inhibitors (SSRIs/SNRIs) in combination with serotonergic agents. Caution should be exercised when duloxetine is administered in combination with serotonergic agents such as SSRIs, SNRIs, tricyclic antidepressants such as clomipramine or amitriptyline, MAOIs such as moclobemide or linezolid, St. John's wort (Hypericum perforatum) or triptans, tramadol, pethidine and tryptophan (see section 4.4).
Effects of duloxetine on other drugs.
Medicinal products metabolized 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 its active 5-hydroxy metabolite and did not require dose adjustment. Caution is recommended when Revival® is administered with medicinal products that are primarily metabolized by CYP2D6 (risperidone, tricyclic antidepressants 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. Additionally, increases in international normalized ratio (INR) have been observed when patients were receiving warfarin concomitantly with duloxetine. However, co-administration of duloxetine and warfarin in a clinical pharmacology study in healthy volunteers did not result in a clinically meaningful change in INR from baseline or in the pharmacokinetics of R- or S-warfarin.
Effects of other drugs on duloxetine.
Antacids and H2 antagonists: Co-administration of duloxetine with antacids containing aluminum and magnesium or 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
Mania and seizures: Duloxetine should be used with caution in patients with a history of mania or a diagnosis of bipolar disorder and/or seizures.
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 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. Revival® should be used with caution in patients whose condition may be compromised by an increase in heart rate or blood pressure. Duloxetine should also be used with caution with medicinal products that may impair its metabolism (see section 4.5). For patients who experience a persistent increase in blood pressure while taking Revival®, consideration should be given to reducing the dose or gradually discontinuing its use (see section 4.8). Revival® should not be used in patients with uncontrolled hypertension (see section "Contraindications").
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.
Serotonin syndrome/neuroleptic malignant syndrome: As with other serotonergic agents, serotonin syndrome or neuroleptic malignant syndrome (NMS) may occur with duloxetine, which can be potentially life-threatening, especially with concomitant use of other serotonergic agents (including SSRIs, SNRIs, tricyclic antidepressants or triptans), agents that impair serotonin metabolism such as MAO inhibitors, or with antipsychotics or other dopamine antagonists that may affect serotonergic neurotransmitter systems (see sections 4.3 and 4.5).
Symptoms of serotonin syndrome may include altered mental status (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form, may resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, elevated serum creatine kinase, autonomic instability with possible rapid fluctuations in vital signs and altered mental status.
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.
St. John's wort (Hypericum perforatum). Adverse reactions may be more common with concomitant use of Revival® and herbal preparations containing St. John's wort (Hypericum perforatum).
Suicide.
Other psychiatric disorders for which duloxetine is indicated may also be associated with an increased risk of suicidal behaviour. In addition, these conditions may coexist with major depressive disorder. Therefore, the precautions recommended for patients with major depressive disorder should be applied to patients with other psychiatric disorders. Patients with a history of suicidal behaviour or patients who demonstrate a significant degree of suicidal ideation prior to initiation of treatment are at increased risk of suicidal thoughts or behaviour and should receive careful monitoring 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 with placebo in patients aged <25 years. Cases of suicidal ideation and behaviour have been reported during treatment with duloxetine or early after treatment discontinuation (see section 4.8). Patients, especially those at high risk, should be closely monitored during therapy, especially at the beginning of treatment and when changing the dose of the drug. Patients and caregivers should be informed of the need to monitor for any clinical worsening, the emergence of suicidal behavior or thoughts, and unusual changes in behavior, and to seek medical advice immediately if these symptoms appear.
Diabetic peripheral neuropathic pain. Isolated cases of suicidal ideation and suicidal behaviour have been reported during duloxetine therapy or early after discontinuation, as with other medicinal products with similar pharmacological effects (antidepressants). For risk factors for suicidality in depression, see section above. 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 the treatment of children under 18 years of age. Suicidal behaviour (suicide attempt and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were observed more frequently in clinical trials in children and adolescents treated with antidepressants compared to those treated with placebo.
Bleeding: Haemostasis disorders such as bruising, including purpura, and gastrointestinal bleeding have been reported with SSRIs and SNRIs, including duloxetine. Duloxetine may increase the risk of postpartum haemorrhage (see section 4.6). Caution should be exercised in patients taking anticoagulants and/or medicinal products that may affect platelet function (e.g. NSAIDs or acetylsalicylic acid) and in patients with known bleeding diathesis.
Hyponatremia: Cases of hyponatremia, including cases with serum sodium levels below 110 mmol/L, have been reported with duloxetine. Hyponatremia may be associated with the syndrome of inappropriate antidiuretic hormone secretion. Most cases of hyponatremia have been reported in elderly patients, especially in combination with conditions that lead to changes in fluid balance. Caution should be exercised in patients at increased risk of hyponatremia (elderly patients, patients with cirrhosis and dehydration, patients receiving diuretics).
Withdrawal symptoms. Withdrawal symptoms are common, particularly when treatment is stopped abruptly (see section 4.8). 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 common adverse reactions are listed in the section on Adverse Reactions. These symptoms are usually mild to moderate in severity, but may be severe in some patients. They usually occur within the first few days of stopping treatment, but there have been isolated reports of such symptoms in patients who inadvertently missed a dose. These symptoms generally resolve spontaneously within two weeks, although in some patients they may persist for longer (2-3 months or longer). Therefore, it is recommended that the dose of duloxetine be tapered gradually when stopping treatment over a period of at least 2 weeks, depending on the patient's needs (see section 4.8).
Akathisia/psychomotor restlessness. Duloxetine has been associated with the development of akathisia, characterized by a subjectively unpleasant or distressing restlessness and need to move, often accompanied by an inability to sit or stand still. This phenomenon is more likely to occur during the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be harmful.
Hepatitis/increased liver enzymes: Cases of liver injury, including marked elevations of liver enzymes (>10 times the upper limit of normal), hepatitis and jaundice have been reported with duloxetine (see section 4.8). Most of these have occurred within the first few 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.
Elderly patients: Data on the use of duloxetine 120 mg in elderly patients with major depressive disorder and generalized anxiety disorder are limited. Therefore, caution should be exercised when using the maximum dose in elderly patients (see section 4.2).
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.
Presence of sucrose: This medicinal product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose or galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.
Use during pregnancy or breastfeeding
Fertility: In animal studies, duloxetine had no effect on male fertility, and effects in females were observed only at doses that caused maternal toxicity.
Pregnancy. Animal studies have shown reproductive toxicity at systemic exposure (AUC) levels of duloxetine lower than the maximum clinical exposure. Studies investigating the effects of duloxetine on the fetus during the first trimester of pregnancy have not yielded conclusive results regarding an increased risk of serious specific congenital malformations, including cardiac malformations. It is known that the use of duloxetine in late pregnancy (any time from 20 weeks of gestation until delivery) has been associated with an increased risk of preterm birth. Observational data suggest an increased risk (less than 2-fold) of postpartum hemorrhage when duloxetine is used within one month of delivery. Epidemiological data suggest 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 PLGN with SSRI treatment has not been studied, this potential risk cannot be excluded for 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, respiratory depression, and seizures. In most cases, these symptoms have occurred immediately after birth or within the first few days of life. Duloxetine should be used during pregnancy only if the expected benefit to the mother justifies the potential risk to the fetus. Women taking duloxetine should inform their doctor if they are pregnant or plan to become pregnant.
Breastfeeding. According to a study conducted in six lactating mothers who did not breastfeed their children, duloxetine is very poorly excreted in human milk. The established dose for a child based on 1 mg per 1 kg of body weight is approximately 0.14% of the maternal dose (see section "Pharmacokinetics"). The safety of duloxetine in children is unknown, therefore the use of Revival® during breastfeeding is not recommended.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies of the effect of duloxetine on the speed of reaction when driving vehicles or using other mechanisms have not been conducted. Revival® may cause sedation and dizziness. Therefore, if sedation or dizziness occurs, patients should avoid potentially hazardous activities, such as driving or operating machinery.
Method of administration and doses
Major depressive disorder. 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, have been evaluated for safety. However, there is no clinical evidence that patients who do not respond to the initial recommended dose may benefit from an increase in dose.
A therapeutic response is usually observed after 2-4 weeks of treatment.
Generalized anxiety disorder. The recommended starting dose is 30 mg once daily without regard to meals. In patients with insufficient response, the dose should be increased to 60 mg daily, which is the usual maintenance dose in most patients.
In patients with comorbid major depressive disorder, both the initial and maintenance dose is 60 mg once daily (see dosing recommendations above).
Doses up to 120 mg/day have been shown to be effective and are being evaluated for safety in clinical trials. Therefore, for those patients who do not respond adequately to the 60 mg dose, an increase in dose to 90 or 120 mg may be considered.
Dose escalation should be based on clinical response and tolerability. After consolidation of response, it is recommended to continue treatment for several months to avoid relapse.
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 of 120 mg daily, given in equally divided doses, have been evaluated for safety in clinical trials. Duloxetine plasma concentrations show wide interindividual variability (see Pharmacokinetics). Therefore, some patients who do not respond adequately to 60 mg may be given a higher dose. The outcome of treatment should be assessed after 2 months. In patients with an inadequate initial response, further response after this period is unlikely.
Therapeutic benefit should be assessed regularly (at least every 3 months) (see section "Pharmacodynamics").
Elderly patients: No dose adjustment based on age alone is recommended for elderly patients. However, caution should be exercised when treating the elderly, especially when using Revival® at a dose of 120 mg per day for major depressive disorder or generalized anxiety disorder, for which data are limited (see sections 5.2 and 4.4).
Patients with hepatic impairment: Revival® should not be administered to patients with liver disease that may cause hepatic impairment (see sections 5.2 and 5.3).
Patients with renal impairment. No dosage adjustment is required for patients with mild or moderate renal impairment (creatinine clearance 30–80 ml/min). Revival® should not be used in patients with severe renal impairment (creatinine clearance <30 ml/min, see section “Contraindications”).
Discontinuation of treatment. Abrupt discontinuation of treatment should be avoided. The dose should be gradually reduced over a period of at least one to two weeks to reduce the risk of withdrawal symptoms. If intolerable symptoms occur after dose reduction or discontinuation, the drug may be resumed at the previously prescribed dose. Subsequently, the doctor may continue to reduce the dose, but more gradually.
Children.
The safety and efficacy of duloxetine in children (under 18 years of age) have not been studied, so the drug should not be prescribed to this age group of patients.
Overdose
Symptoms: Cases of overdose have been reported with duloxetine at a dose of 5400 mg as monotherapy or in combination with other drugs. Fatal cases have been recorded, primarily with mixed overdose, and with duloxetine at a dose of approximately 1000 mg. Signs and symptoms of overdose (duloxetine alone or in combination with other drugs): drowsiness, coma, serotonin syndrome, seizures, vomiting and tachycardia.
Treatment. Specific antidotes are not known. If serotonin syndrome occurs, specific treatment (cyproheptadine and/or temperature control) is necessary. The airway should be checked. Cardiac monitoring and vital signs are recommended, along with appropriate symptomatic and supportive measures. Gastric lavage may be appropriate if performed immediately after ingestion or for symptomatic purposes. Activated charcoal reduces the absorption of the drug. Duloxetine has a large volume of distribution in the body, so forced diuresis, hemoperfusion, and exchange perfusion are unlikely to be useful.
Side effects
The most commonly reported adverse reactions were nausea, headache, dry mouth, drowsiness, and dizziness. Most of the common adverse reactions were mild to moderate in intensity. They usually occurred during treatment, and most of them tended to disappear, even with prolonged therapy.
The following adverse reactions have been reported in spontaneous reports and in placebo-controlled clinical trials. Frequency estimates: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Infections and infestations: uncommon - laryngitis.
On the part of the endocrine system: rarely - hypothyroidism.
From the immune system
