Instructions for Depratal tablets 30mg No. 28
Composition
active ingredient: duloxetine hydrochloride;
1 enteric-coated tablet contains duloxetine hydrochloride, equivalent to duloxetine 30 mg or 60 mg;
excipients: pressed sugar, corn starch, magnesium stearate;
shell composition: methacrylic acid-ethyl acrylate copolymer (1:1), dispersion 30%; triethyl citrate; talc; titanium dioxide (E 171); simethicone emulsion.
Dosage form
Enteric-coated tablets.
Main physicochemical properties:
Dosage 30 mg: white to off-white, round, biconvex, film-coated tablets, engraved ')' on one side.
60 mg dosage: white to off-white, round, biconvex, film-coated tablets.
Pharmacotherapeutic group
Other antidepressants. ATX code N06A X21.
Pharmacological properties
Pharmacodynamics.
Duloxetine is a combined serotonin and norepinephrine reuptake inhibitor. It has little dopamine reuptake inhibition and has low affinity for histamine, dopamine, cholinergic, and adrenergic receptors. The mechanism of action of duloxetine in the treatment of depression is due to inhibition of serotonin and norepinephrine reuptake and, as a result, increased serotonergic and noradrenergic neurotransmission in the central nervous system (CNS). Duloxetine also has analgesic effects, which are likely to be the result of slowing the transmission of pain impulses in the CNS.
Pharmacokinetics.
Absorption
Duloxetine is well absorbed after oral administration. Peak concentrations are reached 6 hours after administration. Food intake delays absorption, increasing the time to peak concentration from 6 to 10 hours and decreasing absorption (by approximately 11%).
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.
Metabolism
Duloxetine is metabolized by CYP2D6 and CYP1A2 isoenzymes. The metabolites formed are pharmacologically inactive.
Breeding
The elimination half-life of duloxetine averages 12 hours. The mean plasma clearance of duloxetine is 101 l/h.
Preclinical safety data.
Duloxetine was not genotoxic in a standard battery of tests and was not carcinogenic in rats. Multinucleated cells were found in the liver in the absence of other histopathological changes in a rat carcinogenicity study. The underlying mechanism and clinical significance are unknown. In female mice treated with duloxetine for 2 years, an increased incidence of hepatocellular adenomas and carcinomas was observed only at the high dose (144 mg/kg/day), but these were considered secondary to induction of liver microsomal enzymes. The relevance of the findings in mice to humans is unknown.
In a study in female rats treated with duloxetine (45 mg/kg/day) prior to and during mating and early pregnancy, there were decreases in maternal food consumption and body weight, disruption of the estrous cycle, reduced live birth rates and offspring survival, and growth retardation in offspring at systemic exposure levels estimated to be the highest at the maximum clinical exposure (AUC). In an embryotoxicity study in rabbits, a higher incidence of cardiovascular and skeletal malformations was observed at systemic exposure levels below the maximum clinical exposure (AUC). No malformations were observed in another study testing a higher dose of another salt of duloxetine. In a prenatal/postnatal toxicity study in rats, duloxetine caused adverse behavioral effects in the offspring at doses below the maximum clinical exposure (AUC). Studies in juvenile rats showed transient neurobehavioral effects, as well as significant decreases in body weight and food consumption, induction of liver enzymes, and hepatocellular vacuolation at a dose of 45 mg/kg/day. The overall toxicity profile of duloxetine in juvenile rats was similar to that in adult rats. The no-effect level for duloxetine was determined to be 20 mg/kg/day.
Indication
Treatment of major depressive disorder.
Treatment of diabetic peripheral neuropathic pain.
Treatment of generalized anxiety disorder.
Contraindication
A contraindication for the use of the drug is hypersensitivity to duloxetine or to any excipients of the drug.
Duloxetine should not be administered with non-selective, irreversible monoamine oxidase inhibitors (MAOIs).
Duloxetine should not be prescribed to patients with unstable hypertension, as it may trigger a hypertensive crisis.
Duloxetine should not be prescribed to patients with end-stage renal disease (creatinine clearance < 30 ml/min).
Duloxetine should not be prescribed to patients with liver disease — it can cause liver failure.
Duloxetine should not be administered in combination with fluvoxamine, ciprofloxacin or enoxacin (strong CYP1A2 inhibitors) due to increased plasma concentrations of duloxetine.
Interaction with other medicinal products and other types of interactions
Medicinal products metabolised by CYP1A2: In a clinical study, there was no significant pharmacokinetic interaction when theophylline, a CYP1A2 substrate, was co-administered with duloxetine (60 mg twice daily).
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, reduces duloxetine plasma clearance by approximately 77%. Therefore, duloxetine should not be co-administered with CYP1A2 inhibitors, particularly fluvoxamine.
Medicinal products metabolised 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 using duloxetine 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 (e.g. flecainide, propafenone and metoprolol).
CNS-acting medicinal products: Caution should be exercised when prescribing duloxetine in combination with other medicinal products and substances that act on the central nervous system, especially those with a similar mechanism of action, including alcohol and sedative medicinal products (e.g. benzodiazepines, opioid analgesics, antidepressants, phenobarbital, sedative antihistamines).
MAO inhibitors: Duloxetine should not be administered with non-selective, irreversible MAO inhibitors due to the risk of serotonin syndrome and for at least 14 days after discontinuation of MAO inhibitor treatment. Given the half-life of duloxetine, MAO inhibitors should not be administered for at least 5 days after discontinuation of duloxetine. When taking reversible, selective MAO inhibitors, such as moclobemide or triptans, tramadol, pethidine, tryptophan and buprenorphine, the risk of serotonin syndrome is lower, but the use of this combination is not recommended. The antibiotic linezolid is a reversible, non-selective MAO and should not be administered to patients taking duloxetine (see section 4.4).
Oral contraceptives and other steroidal agents: In vitro studies demonstrate that duloxetine does not induce CYP3A catalytic activity. Specific in vivo drug-drug interaction studies have not been performed.
Anticoagulants and antithrombotic agents. Caution should be exercised when duloxetine is co-administered with oral anticoagulants and antithrombotic agents due to an increased risk of bleeding due to pharmacodynamic interactions. Increases in international normalized ratio (INR) have been reported when patients receiving warfarin were started on duloxetine. However, concomitant administration of duloxetine and warfarin in a clinical pharmacology study in healthy volunteers in an inpatient setting did not result in a clinically significant change in INR from baseline or in the pharmacokinetics of R- or S-warfarin.
Medicinal products containing duloxetine: Concomitant use with other medicinal products containing duloxetine should be avoided.
Preparations containing St. John's wort herb. Adverse reactions often occur when used together with duloxetine.
Antacids and H2 antagonists: Co-administration of duloxetine with antacids containing aluminum and magnesium, or duloxetine with famotidine, did not affect the rate or extent of absorption of duloxetine following a 40 mg oral dose.
CYP1A2 inducers: Pharmacokinetic analyses have shown that smokers have almost 50% lower plasma concentrations of duloxetine compared to non-smokers.
Application features
Seizures and mania: Duloxetine should be prescribed with caution in patients with a history of seizures, mania, or bipolar disorder.
Blood pressure and palpitations. In some patients, duloxetine has been associated with an increase in blood pressure. This may be due to the noradrenergic effects of duloxetine. Hypertensive crisis has been reported with duloxetine, particularly in patients with hypertension. Monitoring of blood pressure is recommended in patients with hypertension and/or other cardiac disease, particularly during the first month of treatment. Duloxetine should be used with caution in patients who may have a history of cardiac arrhythmias or increased blood pressure. Caution should also be exercised when duloxetine is used with medicinal products that may impair its metabolism (see section 4.5). Patients with persistently elevated blood pressure should be given a dose reduction or gradual discontinuation. Treatment of patients with unstable hypertension is not advisable.
Renal impairment: Increased plasma concentrations of duloxetine have been observed in patients with end-stage renal disease (ESRD) on continuous hemodialysis (creatinine clearance < 30 mL/min). For patients with end-stage renal disease, see section 4.3; for patients with mild to moderate renal impairment, see section 4.4.
Serotonin syndrome: Potentially life-threatening serotonin syndrome may occur with duloxetine treatment, especially with concomitant use of other serotonergic agents (including selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants or triptans), agents that impair serotonin metabolism such as MAO inhibitors, antidepressants or other dopamine antagonists that may affect serotonergic neurotransmitter systems.
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). If concomitant treatment with duloxetine and other serotonergic agents that may affect the serotonergic and/or dopaminergic neurotransmitter systems is clinically warranted, close monitoring of the patient is recommended, especially at the start of treatment and with dose increases.
If serotonin syndrome is suspected, dose reduction or discontinuation of treatment should be considered depending on the severity of symptoms.
Haemorrhage: Abnormal bleeding such as ecchymoses, purpura, gastrointestinal bleeding and haemorrhage have been reported with SSRIs and serotonin/norepinephrine reuptake inhibitors (SNRIs), including duloxetine. Caution should be exercised in patients taking anticoagulants and/or medicinal products that affect platelet function (e.g. non-steroidal anti-inflammatory drugs or acetylsalicylic acid) and in patients with a predisposition to bleeding. Duloxetine increases the risk of postpartum haemorrhage (see section 4.6).
Hyponatremia. Hyponatremia has been reported with Depratal, including cases with serum sodium levels below 110 mmol/l. Hyponatremia may be caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Most of these cases have been reported in the elderly, especially in patients with a history of hyponatremia or conditions that may cause changes in body fluid balance. Caution should be exercised in elderly patients, patients with cirrhosis, and patients with dehydration or patients receiving diuretics.
Withdrawal symptoms: Withdrawal symptoms are common, especially when treatment is stopped abruptly (see section 4.8). In clinical trials, adverse reactions seen with abrupt treatment discontinuation occurred in approximately 45% of patients treated with duloxetine and 23% of patients treated with placebo.
Akathisia/psychomotor restlessness: Duloxetine has been associated with the development of akathisia, which is characterized by a subjectively unpleasant psychomotor restlessness and need to move, often accompanied by an inability to sit or stand still. This phenomenon occurs within the first few weeks of treatment. In patients who develop the above symptoms, increasing the dose may be harmful.
Hepatitis/increased liver enzymes. Cases of liver injury, including marked elevations of liver enzymes (up to 10 times the upper limit of normal), hepatitis and jaundice have been reported (see section 4.8). Most of these events occurred within the first month of treatment. Liver injury was most often hepatocellular in nature. Duloxetine should be used with caution in patients taking medicinal products that may cause liver injury.
Sexual dysfunction: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). Long-term sexual dysfunction has been reported, with symptoms persisting despite discontinuation of SSRIs and/or SNRIs.
Presence of sucrose. Depratal enteric-coated tablets should not be prescribed to patients with hereditary fructose intolerance, malabsorption syndrome, or sucrase-isomaltase insufficiency.
Suicide. Major depressive disorder and generalised anxiety disorder. Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). The risk persists until significant remission is achieved. The patient should be closely monitored until significant improvement is achieved, as remission may not occur within 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 is 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 disorders. 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 more 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 with placebo in patients under 25 years of age.
Cases of suicidal ideation and suicidal behaviour have been reported during treatment with duloxetine or early after treatment discontinuation.
During therapy, especially in the early stages of treatment and after dose changes, patients, especially those at high risk, should be closely monitored. Patients (and their 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 such symptoms 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 the treatment of 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, taking into account the clinical need, a decision to treat is made, the patient should be closely monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents with regard to growth, maturation and cognitive and behavioural development are not available (see section 4.8).
Elderly patients. Data on the use of Depratal 120 mg 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 dose.
Use during pregnancy or breastfeeding
Pregnancy
Results from two large observational studies (one conducted in the United States of America involving 2,500 women and one conducted in the European Union involving 1,500 women who took duloxetine during the first trimester of pregnancy) do not indicate an overall increased risk of major birth defects in their children. Analysis of individual defects, such as heart defects, was inconclusive.
In a study conducted in the European Union, use of duloxetine in patients in late pregnancy (any time from 20 weeks of gestation until delivery) was associated with an increased risk of preterm birth (almost 2-fold, corresponding to approximately 6 additional preterm births per 100 women). Most preterm births occurred between 35 and 36 weeks of gestation. No such association was observed in a study conducted in the United States.
Observational data from the United States of America show an increased risk (almost 2-fold) of postpartum hemorrhage when duloxetine is used within the month before delivery.
Epidemiological evidence suggests that the use of SSRIs during pregnancy, especially in late pregnancy, increases the risk of persistent pulmonary hypertension in the newborn.
Although no studies have examined the association between the risk of persistent pulmonary hypertension and SSRI treatment, this potential risk cannot be ruled out with duloxetine, given the related mechanism of action (serotonin reuptake inhibition).
As with other serotonergic drugs, withdrawal symptoms may occur in newborns shortly after maternal use of duloxetine. These symptoms may include hypotension, tremor, agitation, feeding difficulties, respiratory distress, and seizures. In most cases, withdrawal symptoms occurred either at birth or within a few days of birth.
Medicinal products containing duloxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus. Women should be advised to inform their doctor if they become pregnant or intend to become pregnant during therapy.
Breast-feeding
Duloxetine is poorly excreted in breast milk. The established dose for the infant at the rate of 1 mg per 1 kg of body weight is approximately 0.14% of the maternal dose. The safety of duloxetine in infants is unknown, therefore breastfeeding while taking duloxetine is not recommended.
Fertility
In animal studies, duloxetine did not affect male fertility. Effects in females were seen only at doses that caused maternal toxicity.
Ability to influence reaction speed when driving vehicles or other mechanisms
Studies of the effect of duloxetine on the speed of reactions when driving vehicles or using other mechanisms have not been conducted. The use of duloxetine may be associated with sedation and dizziness. During treatment, patients may experience a sedation reaction or dizziness. In this case, you should refrain from potentially hazardous activities that require increased attention and speed of psychomotor reactions.
Method of administration and doses
For major depressive disorder. The initial and recommended maintenance dose is 60 mg once daily, regardless of food intake.
The safety of dosing from 60 mg once daily to a maximum dose of 120 mg daily has been evaluated in clinical trials. However, there is no clinical evidence that patients who do not respond to the initial recommended dose may benefit from increasing the dose.
The therapeutic effect of treatment appears within 2–4 weeks.
After consolidation of response to antidepressant treatment, it is recommended to continue treatment for several months to avoid relapse. For patients who respond to duloxetine and have a history of recurrent episodes of major depressive disorder, further long-term treatment at a dosage of 60–120 mg/day should be considered.
For generalized anxiety disorder, the recommended starting dose is 30 mg once daily without regard to meals. If the treatment effect is insufficient, the dose should be increased to 60 mg daily, which is the usual maintenance dose for most patients. For patients with comorbid major depressive disorder, the recommended starting and maintenance dose is 60 mg once daily (see also dosage recommendations above).
Doses up to 120 mg have been shown to be effective and safe in clinical trials. Therefore, for patients with an inadequate response to the 60 mg dose, an increase in dose to 90 mg or 120 mg may be considered. Dose increases should be based on clinical response and tolerability.
After obtaining a therapeutic effect, it is recommended to continue treatment for several months to avoid relapse.
The therapeutic effect of treatment is manifested within 2 months.
In patients with an inadequate initial response, further dose increases are unlikely to be justified. Therapeutic benefit should be assessed regularly (at least every 3 months).
Patients with renal impairment. No dose adjustment is required for patients with mild to moderate renal impairment (creatinine clearance 30 to 80 mL/min). This medicinal product is not recommended for patients with end-stage renal disease (creatinine clearance < 30 mL/min).
Patients with liver failure. Depratal should not be prescribed to patients with liver disease.
Elderly patients. There is no need to change the dose of the drug when prescribing to elderly patients. However, as with any drug, Depratal should be used with caution in the treatment of elderly people, especially when using duloxetine 120 mg per day for major depressive disorder or generalized anxiety disorder, for which data are limited (see section "Special instructions").
Treatment discontinuation
Abrupt discontinuation of the drug should be avoided. When discontinuing treatment with duloxetine, the dose should be gradually reduced over a period of at least 1 to 2 weeks to reduce the risk of withdrawal symptoms (see sections 4.4 and 4.8). If the patient develops intolerable symptoms after dose reduction or after discontinuation of treatment, it may be advisable to resume the previously prescribed dose. Subsequently, the doctor may continue to gradually reduce the dose, but at a slower rate.
Children.
The drug is not used in pediatric practice.
Overdose
Symptoms: Overdoses of duloxetine 5400 mg have been reported, either alone or in combination with other medicinal products. Several fatalities have occurred, primarily with mixed overdoses, but there have also been fatalities following duloxetine alone at doses of approximately 1000 mg. Signs and symptoms of overdose (duloxetine alone or in combination with other medicinal products) have included somnolence, coma, serotonin syndrome, convulsions, vomiting and tachycardia. Symptoms of overdose (predominantly with other medicinal products) 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 clear 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 commonly reported adverse reactions with duloxetine were dizziness, nausea, headache, dry mouth, and somnolence. However, most adverse reactions were mild to moderate, usually began early in therapy, and most resolved with continued treatment. The table below lists the adverse reactions observed with duloxetine, based on spontaneous reports and placebo-controlled clinical trials.
Frequency assessment: 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).
| Very often | Often | Infrequently | Rarely | Very rare |
| Infections and infestations |
| | Laryngitis | | |
| From the endocrine system |
| | | Hypothyroidism | |
| On the part of the immune system |
| | | Anaphylactic reactions, hypersensitivity | |
| Metabolic disorders |
| Decreased appetite | Hyperglycemia, (especially in patients with diabetes) | Dehydration, hyponatremia, ADH6 deficiency | |
| From the psyche |
| Insomnia, agitation, decreased libido, anxiety, abnormal visions and abnormal orgasm | Sleep disorders, bruxism, disorientation, apathy, suicidal ideation5,7 | Mania, hallucinations, aggression and anger4, suicidal behavior5,7 | |
| From the nervous system |
| Headache, drowsiness | Tremor, paresthesia, dizziness, lethargy | Myoclonus, akathisia7, nervousness, disturbance in attention, dyskinesia, dysgeusia, restless legs syndrome, poor sleep | Serotonin syndrome6, seizures1, psychomotor restlessness6, extrapyramidal disorders6 | |
| From the organs of vision |
| Image blur | Mydriasis, visual disturbances | Glaucoma | |
| From the side of the organs of hearing and labyrinth |
| Ringing in the ears1 | Dizziness, earache | | |
| Palpitation | Tachycardia, supraventricular arrhythmia, ventricular arrhythmia, fibrillation most often atrial | | |
| From the vascular side |
| Increased blood pressure3, tides | Arterial hypertension3,7, orthostatic hypotension2, loss of consciousness2, feeling of coldness in extremities | Hypertensive crisis3,6 | |
| From the respiratory system |
| Yawn | Feeling of tightness in the throat, nosebleeds | Eosinophilic pneumonia, interstitial lung diseases | |
| From the digestive tract |
| Nausea, dry mouth | Constipation, diarrhea, vomiting, dyspepsia, flatulence, abdominal pain | Gastrointestinal bleeding 7, gastroenteritis, eructation, gastritis, dysphagia | Stomatitis, bad breath, blood in stool, microscopic colitis | |
| Hepatobiliary system |
| | Elevated liver enzymes (ALT, AST, alkaline phosphatase), hepatitis3, acute liver injury | Jaundice6, liver failure6 | |
| Skin and skin derivatives |
| Increased sweating, rash | Night sweats, contact dermatitis, urticaria, cold sweat, photosensitivity, increased tendency to bruise | Angioedema6, Stevens-Johnson syndrome6 | Skin vasculitis |
| Musculoskeletal and connective tissue disorders |
| Musculoskeletal pain, muscle spasm | Muscle twitching, feeling of muscle stiffness | Trismus | |
| Kidney and bladder |
| Dysuria, frequent urination | Urinary retention, difficulty initiating urination, nocturia, polyuria, decreased urine flow | Abnormal urine odor | |
| From the reproductive system |
| Erectile dysfunction, ejaculation disorder, delayed ejaculation | Menstrual disorders, sexual disorders, gynecological bleeding, testicular pain | Menopausal symptoms, galactorrhea, hyperprolactinemia, postpartum hemorrhage | |
| General disorders |
| Fall8, fatigue | Chest pain7, malaise, feeling cold, tingling sensation, thirst, malaise, feeling hot, gait disturbance | | |
| Research results |
| Weight loss | Weight gain, increased blood creatinine phosphokinase levels, increased potassium levels in the blood | Increased blood cholesterol levels | |
1 Cases of seizures and tinnitus have been observed after discontinuation of treatment.
2 Cases of orthostatic hypotension and loss of consciousness were observed mainly at the beginning of treatment.
3 See section "Application features".
4 Cases of aggression and anger have been reported at the start of treatment and after treatment discontinuation.
5 Cases of suicidal ideation and suicidal behaviour have been reported early in treatment and early after treatment discontinuation.
6 The frequency of adverse reactions identified from post-marketing studies that were not observed in placebo-controlled clinical trials.
7 Statistically not significantly different from placebo.
8 Falls were more common in elderly patients (≥ 65 years).
9 The estimated frequency is based on all clinical trial data.
10 Estimated frequency based on placebo-controlled clinical trials.
Description of selected adverse reactions
Discontinuation of duloxetine (especially abrupt) has been associated with withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia or electric shock sensations, particularly in the head), sleep disturbances (including insomnia and abnormal dreams), fatigue, somnolence, agitation or anxiety, nausea and/or vomiting, tremor, headache, myalgia, irritability, diarrhoea, hyperhidrosis and dizziness are the most common reactions.
Usually, with SSRIs and SNRIs, these reactions are mild or moderate and resolve on their own, but in some patients they may be severe and/or prolonged. Therefore, if
