Instructions for Duloxin capsules 60 mg No. 28
Composition
active ingredient: duloxetine hydrochloride;
1 capsule contains 33.7 mg of duloxetine hydrochloride, equivalent to 30 mg of duloxetine, or 67.4 mg of duloxetine hydrochloride, equivalent to 60 mg of duloxetine;
excipients: spherical sugar, hydroxypropyl methylcellulose, polyethylene glycol 6000, talc, sucrose, hydroxydipropyl methylcellulose acetate succinate, triethyl citrate;
hard gelatin capsule No. 3 (for 30 mg capsules);
capsule shell composition: titanium dioxide (E 171), indigotine blue (E 132), gelatin;
hard gelatin capsule No. 1 (for 60 mg capsules);
capsule shell composition: titanium dioxide (E 171), indigotine blue (E 132), quinoline yellow (E 104), erythrosine red (E 127), gelatin.
Dosage form
Enteric-coated hard capsules.
Main physicochemical properties:
30 mg: hard gelatin capsule No. 3, blue cap, white body. Capsule contents: white or almost white pellets;
60 mg: hard gelatin capsule No. 1, blue cap, ivory body. Capsule contents: white or almost white pellets.
Pharmacotherapeutic group
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 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. The inhibitory effect of duloxetine is thought to be the result of potentiation of descending pain-suppressing pathways in the central nervous system.
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 demonstrated statistical superiority over placebo. Response and remission rates were also statistically significantly higher with duloxetine compared to placebo.
In a study examining the efficacy of duloxetine in preventing relapse, the drug was found to have a statistically significant advantage over placebo. Patients with recurrent VDR 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, the efficacy of duloxetine was demonstrated compared to placebo. The efficacy and safety of duloxetine in elderly patients were similar to those observed in younger adult patients.
Diabetic peripheral neuropathic pain: The efficacy of duloxetine has been established in studies investigating the treatment of diabetic neuropathic pain.
Duloxetine significantly reduced pain compared with placebo, with the effect evident in some patients within the first week of treatment.
The same studies also looked at whether patients experienced drowsiness during treatment. Among patients who did not experience drowsiness, clinical response was more common with duloxetine than with placebo.
Children
Duloxetine has not been studied in patients under the age of 7. A study conducted in children aged 7 to 17 years with ADHD showed that the results of treatment with duloxetine and the control group were not statistically different from placebo.
Discontinuation of treatment due to adverse events was higher in patients taking duloxetine compared to those taking fluoxetine, mainly due to nausea. Suicidal behavior has also been reported with duloxetine.
Treatment with duloxetine demonstrated statistically more significant improvement in patients with GAD.
Duloxetine did not demonstrate efficacy in reducing pain as assessed 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, with peak plasma concentrations occurring 6 hours after dosing. The absolute oral bioavailability of duloxetine ranges from 32% to 80% (mean 50%). Food intake delays absorption, with the time to Cmax increasing from 6 to
10 hours, with a decrease in absorption (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 alpha1-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. Based on in vitro studies, circulating metabolites of duloxetine are considered 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.
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 do not justify the use of 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 on duloxetine in patients with mild to moderate renal impairment are limited.
Hepatic impairment. Moderate hepatic impairment (Child-Pugh class B) affected the pharmacokinetics of duloxetine. Compared to healthy subjects, 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 impairment. 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 disorders.
The drug Duloxin® is intended for adult patients.
For additional information, see the Pharmacological Properties section.
Contraindication
Hypersensitivity to the active substance or to any of the excipients of the drug.
The concomitant use of duloxetine with non-selective, irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated.
Liver diseases that can cause liver failure.
Duloxetine should not be used in combination with fluvoxamine, ciprofloxacin or enoxacin (strong CYP1A2 inhibitors) as the combination leads to increased plasma concentrations of duloxetine.
Severe renal failure (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
Monoamine oxidase inhibitors (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 started until 5 days after stopping duloxetine (see section 4.3).
The combined use of duloxetine 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 given to patients taking duloxetine (see section 4.4).
CYP1A2 inhibitors: Since CYP1A2 is involved in the metabolism of duloxetine, concomitant use of duloxetine with strong CYP1A2 inhibitors is likely to result in increased duloxetine concentrations. Fluvoxamine (100 mg once daily), a strong CYP1A2 inhibitor, reduces duloxetine plasma clearance by approximately 77% and increases AUC 0-t by 6-fold. Therefore, duloxetine should not be administered in combination with strong CYP1A2 inhibitors such as fluvoxamine (see section 4.4).
CNS-acting medicinal products. The risk of using duloxetine in combination with other CNS-acting medicinal products 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 and sedating antihistamines).
Serotoninergic drugs: Serotonin syndrome has been reported rarely in patients taking selective serotonin reuptake inhibitors/serotonin norepinephrine reuptake inhibitors (SSRIs/SNRIs) with serotonergic drugs. Caution is advised when duloxetine is used concomitantly with serotonergic drugs 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 medicinal products
Drugs metabolized by CYP1A2: The pharmacokinetics of theophylline, a CYP1A2 substrate, were not significantly affected by co-administration with duloxetine (60 mg twice daily).
Drugs 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) increases the steady-state exposure (AUC) of tolterodine (2 mg twice daily) by 71%, but does not affect the pharmacokinetics of its active 5-hydroxyl metabolite and does not require dose adjustment.
Caution is advised when duloxetine is used concomitantly with drugs that are predominantly metabolized by CYP2D6 (risperidone, tricyclic antidepressants such as nortriptyline, amitriptyline and imipramine), especially if they have a narrow therapeutic index (flecainide, propafenone and metoprolol).
Oral contraceptives and other steroids: In vitro studies indicate that duloxetine does not induce CYP3A catalytic activity. Specific in vivo drug interaction studies have not been conducted.
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 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 drugs on duloxetine
Antacids and H2 antagonists: Co-administration of duloxetine with aluminum- and magnesium-containing antacids or with famotidine did not affect the rate or extent of absorption of duloxetine following a 40 mg oral dose.
CYP1A2 inducer. Population pharmacokinetic analysis showed that smokers have almost 50% lower plasma concentrations of duloxetine compared to non-smokers.
Application features
Mania and epileptic seizures
Duloxetine should be used with caution in patients with a history of mania or a diagnosis of bipolar disorder and/or epileptic seizures.
Mydriasis
Cases of mydriasis have 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.
In some patients, duloxetine has been associated with increases in blood pressure and clinically significant hypertension. This may be related to the noradrenergic effects of duloxetine. Hypertensive crises have been reported with duloxetine, particularly in patients with pre-existing hypertension. Monitoring of blood pressure is recommended in patients with known hypertension and/or other heart failure, particularly during the first month of treatment. Duloxetine should be used with caution in patients whose underlying disease may be compromised by an increase in heart rate or blood pressure. Caution should be exercised when duloxetine is co-administered with medicinal products that may impair its metabolism (see section 4.5). For patients who experience persistent increases 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 unstable hypertension (see section 4.3).
Kidney failure
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
As with other serotonergic agents, serotonin syndrome, a potentially life-threatening condition, may occur with duloxetine treatment, especially when used concomitantly with other serotonergic agents (including SSRIs, SNRIs, tricyclic antidepressants or triptans), with 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 changes in the patient's 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).
If concomitant treatment with duloxetine and other serotonergic drugs that may affect the serotonergic and/or dopaminergic neurotransmitter systems is clinically warranted, close monitoring of patients is recommended, especially at the start of treatment and during dose increases.
St. John's wort (Hypericum perforatum)
Adverse reactions may occur more frequently 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 thoughts of harming oneself and of suicide (suicidality). The risk persists until significant remission occurs. As improvement may not occur during the first few weeks of treatment or longer, patients should be closely monitored until improvement occurs. It is common clinical experience that the risk of suicide may increase in the early stages of recovery.
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).
Close monitoring of patients, especially those at high risk, should be undertaken in conjunction with drug therapy, particularly early in treatment and after dose adjustments. Patients and caregivers should be informed of the need to monitor for any clinical worsening, suicidal behaviour or thoughts, and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.
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). For risk factors for suicidality in depression, see section above. Physicians should encourage patients to report any distressing thoughts or feelings at any time.
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
Haemostatic disorders such as ecchymosis, 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 known to affect platelet function (e.g. non-steroidal anti-inflammatory drugs or acetylsalicylic acid) and in patients with known bleeding diathesis.
Hyponatremia
Hyponatraemia has been reported in patients treated with duloxetine, including cases with serum sodium levels below 110 mmol/L. Hyponatraemia may be associated with the syndrome of inappropriate antidiuretic hormone secretion. Most cases of hyponatraemia have been observed in elderly patients, especially those with a recent history or condition causing fluid imbalance. Caution should be exercised in patients at increased risk of hyponatraemia (elderly patients, patients with cirrhosis and dehydration, patients taking diuretics).
Discontinuation of treatment
Withdrawal symptoms are common after discontinuation of treatment (especially if discontinued abruptly) (see section 4.8). In clinical trials, adverse events observed with 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 seen with SSRIs and SNRIs may depend on several factors, including duration of treatment and dose, and the rate of dose reduction. The most common adverse reactions are listed in section 4.8. These symptoms are usually mild to moderate in severity, but may be severe in some patients. Withdrawal symptoms usually occur within the first few days of discontinuation of 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 longer.
(from 2-3 months). Therefore, when discontinuing treatment, the dose of duloxetine should be gradually reduced over a period of at least two weeks, depending on the patient's needs (see section "Method of administration and dosage").
Elderly patients
Data on the use of 120 mg duloxetine in elderly patients with major depressive disorder and generalized anxiety disorder are limited. Therefore, caution should be exercised when treating elderly patients with the maximum dosage (see sections 5.2 and 5.2).
Akathisia/psychomotor agitation
Duloxetine has been associated with the development of akathisia, a subjectively unpleasant or distressing restlessness and need to move, 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 of the drug may be harmful.
Medicines containing duloxetine
Duloxetine is used under different brand names for different indications (treatment of diabetic neuropathic pain, major depressive disorder, generalized anxiety disorder, and stress urinary incontinence). The use of more than one of these drugs at the same time should be avoided.
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 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). There have been reports of long-term sexual dysfunction, with symptoms persisting despite discontinuation of SSRIs/SNRIs.
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 reproductive toxicity at systemic exposure levels (AUC) of duloxetine lower than the maximum clinical exposure level.
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, in particular heart defects.
It is known that the use of duloxetine in late pregnancy (any time from
20 weeks of pregnancy before delivery) was 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 the month before delivery.
Epidemiological data have shown that the use of SSRIs during pregnancy, especially in late pregnancy, may increase the risk of developing persistent pulmonary hypertension of the newborn (PPHN).
Although no studies have investigated the association of PLGN with SSRI treatment, this potential risk cannot be excluded for duloxetine, given its mechanism of action (serotonin reuptake inhibition).
As with other serotonergic drugs, withdrawal symptoms may occur in infants whose mothers have used duloxetine before delivery. Withdrawal symptoms seen with duloxetine 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.
Breast-feeding
Duloxetine is excreted in human milk in a study of six lactating mothers who did not breastfeed their infants. The established dose for the infant on a mg/kg basis is 0.14% of the maternal dose (see section 5.2). The safety of duloxetine in infants is unknown, and breastfeeding is not recommended while taking duloxetine.
Fertility
In animal studies, duloxetine did not affect male fertility, and effects in women were observed only at doses that caused maternal toxicity.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies on the effects on the ability to drive and use machines have been performed. Duloxetine may be associated with 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
Method of application
Duloxetine is for oral use.
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 in clinical trials. However, there is no clinical evidence that patients who do not respond to the initial recommended dose may benefit from an increase in dose.
Therapeutic results are usually observed after 2-4 weeks of treatment.
After consolidation of the antidepressant response, it is recommended to continue treatment for several months to avoid relapse. In patients who respond to duloxetine and have a history of previous recurrent major depressive episodes, further long-term treatment at a dose of 60-120 mg per day may be considered.
Generalized anxiety disorders
The recommended starting dose for patients with generalized anxiety disorder is 30 mg once daily, without regard to meals. In patients with inadequate response, the dose should be increased to 60 mg, 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 increases should be based on clinical response and tolerability.
After consolidation of the response, it is recommended to continue treatment for several months to avoid relapse.
The initial and recommended maintenance dose is 60 mg once daily, without regard to food intake. 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 the 60 mg dose may be given a higher dose.
The outcome of treatment should be assessed after 2 months. In patients with an inadequate initial response, an additional response is unlikely after this time.
Therapeutic benefit should be reassessed (at least every 3 months) (see section "Pharmacodynamics").
Special populations
Elderly patients
No dose adjustment is recommended for elderly patients based solely on age. However, caution should be exercised when treating the elderly, especially when using duloxetine at a dose of 120 mg/day in major depressive disorder or GAD, for which data are limited (see sections 5.2 and 4.4).
Liver failure
Duloxetine should not be used in patients with liver disease that may lead to hepatic failure (see sections 5.2 and 4.3).
Kidney failure
No dose adjustment is required for patients with mild to moderate renal impairment (creatinine clearance 30 to 80 ml/min). Duloxetine should not be used in patients with severe renal impairment (creatinine clearance < 30 ml/min, see section 4.3).
Treatment discontinuation
Abrupt discontinuation of treatment should be avoided. When discontinuing treatment with duloxetine, the dose should be gradually reduced over at least 1-2 weeks to reduce the risk of withdrawal symptoms (see sections 4.4 and 4.8). If intolerable symptoms develop after dose reduction or discontinuation, the previously prescribed dose may be resumed. Your doctor may then continue to reduce the dose more gradually.
Children
The drug should not be prescribed to children under 18 years of age.
Overdose
Cases of overdose with duloxetine alone or in combination with other drugs have been reported at a dose of 5400 mg. Fatal cases have been reported after overdose with duloxetine, mostly in combination with other drugs, and with duloxetine alone at a dose of approximately 1000 mg. Signs and symptoms of overdose (alone or in combination with other drugs) included drowsiness, coma, serotonin syndrome, seizures, vomiting, and tachycardia.
There are no specific antidotes to duloxetine; if serotonin syndrome occurs, specific treatment (cyproheptadine and/or temperature control) is necessary. A patent airway should be maintained. Cardiac monitoring and vital signs should be monitored, along with appropriate symptomatic and supportive measures. Gastric lavage may be considered immediately after ingestion or in symptomatic patients. Activated charcoal may be useful to limit absorption. Duloxetine has a large volume of distribution, and forced diuresis, hemoperfusion, and exchange perfusion are unlikely to be of benefit.
Side effects
Brief description of the safety profile
The most commonly reported adverse reactions in patients treated with duloxetine were nausea, headache, dry mouth, somnolence and dizziness. However, most of the common adverse reactions were mild or moderate in severity, usually occurred early in treatment, and most tended to resolve, even with continued therapy.
The following are adverse reactions reported from spontaneous reports and during placebo-controlled clinical trials.
Frequency estimate: very common (≥1/10), common (from
