Presentation and Status in Health Basket
56 x 20 mg
56 x 40 mg
Hepatic impairment: YENTREVE must not be used in women with liver disease resulting in hepatic impairment.
Renal impairmen: No dosage adjustment is necessary for patients with mild or moderate renal dysfunction (creatinine clearance 30 to 80 ml/min). YENTREVE must not be used in patients with severe renal impairment.
Elderly: Caution should be exercised when treating the elderly.
Children and adolescents: Duloxetine is not recommended for use in children and adolescents due to insufficient data on safety and efficacy.
Discontinuation of treatment: Abrupt discontinuation should be avoided. When stopping treatment with YENTREVE the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.
For full details see prescribing information
For women for the treatment of moderate to severe Stress Urinary Incontinence (SUI).
Hypersensitivity to the active substance or to any of the excipients. Liver disease resulting in hepatic impairment. YENTREVE should not be used in combination with nonselective, irreversible monoamine oxidase inhibitors – MAOIs. YENTREVE should not be used in combination with CYP1A2 inhibitors, like fluvoxamine, ciprofloxacin or enoxacin since the combination results in elevated plasma concentrations of duloxetine. Severe renal impairment (creatinine clearance <30 ml/min) . The initiation of treatment with YENTREVE is contraindicated in patients with uncontrolled hypertension that could expose patients to a potential risk of hypertensive crisis.
Mania and seizures: YENTREVE should be used with caution in patients with a history of mania or a diagnosis of bipolar disorder, and/or seizures.
Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions: The development of a potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including YENTREVE treatment, but particularly with concomitant use of serotonergic drugs (including triptans) with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms. The concomitant use of YENTREVE with MAOIs intended to treat depression is contraindicated. If concomitant treatment of YENTREVE with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. The concomitant use of YENTREVE with serotonin precursors (such as tryptophan) is not recommended. Treatment with duloxetine and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately if the above reactions occur and supportive symptomatic treatment should be initiated. Use with antidepressants: The use of YENTREVE in combination with antidepressants (especially with SSRI, SNRI and reversible MAOIs) is not recommended.
St John’s wort: Adverse reactions may be more common during concomitant use of YENTREVE and herbal preparations containing St John’s wort (Hypericum perforatum).
Mydriasis: Mydriasis has been reported in association with duloxetine, therefore, caution should be used when prescribing duloxetine in patients with increased intraocular pressure, or those at risk of acute narrow-angle glaucoma. Blood pressure and heart rate: Duloxetine has been associated with an increase in blood pressure and clinically significant hypertension in some patients. This may be due to the noradrenergic effect of duloxetine. Cases of hypertensive crisis have been reported with duloxetine, especially in patients with pre-existing hypertension. Therefore in patients with known hypertension and/or other cardiac disease, blood pressure monitoring is recommended, especially during the first month of treatment. Duloxetine should be used with caution in patients whose conditions could be compromised by an increased heart rate or by an increase in blood pressure. Caution should also be exercised when duloxetine is used with medicinal products that may impair its metabolism. For patients who experience a sustained increase in blood pressure while receiving duloxetine either dose reduction or gradual discontinuation should be considered. In patients with uncontrolled hypertension duloxetine should not be initiated.
Renal impairment: Increased plasma concentrations of duloxetine occur in patients with severe renal impairment on haemodialysis (creatinine clearance <30 ml/min). For patients with severe renal impairment,for information on patients with mild or moderate renal dysfunction see prescribing information. Haemorrhage: There have been reports of bleeding abnormalities, such as ecchymoses, purpura and gastrointestinal haemorrhage with selective serotonin reuptake inhibitors (SSRIs) and serotonin/noradrenaline reuptake inhibitors (SNRIs), including duloxetine. Caution is advised in patients taking, anticoagulants and/or medicinal products known to affect platelet function (e.g. NSAIDs or acetylsalicylic acid (ASA)), and in patients with known bleeding tendencies.
Discontinuation of treatment: Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt. In a clinical trial, adverse events seen on abrupt treatment discontinuation occurred in approximately 44% of patients treated with YENTREVE and 24% of patients taking placebo. The risk of withdrawal symptoms seen with SSRI’s and SNRI’s may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. The most commonly reported reactions are listed in section 4.8. Generally these symptoms are mild to moderate, however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose. Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that duloxetine should be gradually tapered when discontinuing treatment over a period of no less than 2 weeks, according to the patient’s needs.
Hyponatraemia: Hyponatraemia has been reported when administering YENTREVE, including cases with serum sodium lower than 110 mmol/l. Hyponatraemia may be due to a syndrome of inappropriate anti-diuretic hormone secretion (SIADH). The majority of cases of hyponatraemia were reported in the elderly, especially when coupled with a recent history of, or condition pre-disposing to, altered fluid balance. Caution is required in patients at increased risk for hyponatraemia, such as elderly, cirrhotic, or dehydrated patients or patients treated with diuretics.
Depression, suicidal ideation and behaviour: Although YENTREVE is not indicated for the treatment of depression, its active ingredient (duloxetine) also exists as an antidepressant medicinal product. Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery. Patients with a history of suicide-related events or those exhibiting a significant degree of suicidal thoughts prior to commencement of treatment are known to be at a greater risk of suicidal thoughts or suicidal behaviour, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant medicinal products in psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old. Cases of suicidal thoughts and suicidal behaviours have been reported during duloxetine therapy or early after treatment discontinuation. Physicians should encourage patients to report any distressing thoughts or feelings or depressive symptoms at any time. If while on YENTREVE therapy, the patient develops agitation or depressive symptoms, specialised medical advice should be sought, as depression is a serious medical condition. If a decision to initiate antidepressant pharmacological therapy is taken, the gradual discontinuation of YENTREVE is recommended.
Use in children and adolescents under 18 years of age: No clinical trials have been conducted with duloxetine in paediatric populations. YENTREVE should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempts and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger), were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. Long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
Medicinal products containing duloxetine: Duloxetine is used under different trademarks in several indications (treatment of diabetic neuropathic pain, major depressive disorder, generalised anxiety disorder, fibromyalgia, chronic musculoskeletal pain and stress urinary incontinence). The use of more than one of these products concomitantly should be avoided.
Hepatitis/Increased liver enzymes: Cases of liver injury, including severe elevations of liver enzymes (>10 times upper limit of normal), hepatitis and jaundice have been reported with duloxetine. Most of them occurred during the first months of treatment. The pattern of liver damage was predominantly hepatocellular. Duloxetine should be used with caution in patients treated with other medicinal products associated with hepatic injury. Akathisia/psychomotor restlessness: The use of duloxetine has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
Sucrose: YENTREVE hard gastro-resistant capsules contain sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.
Very common: Insomnia, headache, dizziness. Nausea, dry mouth, constipation, fatigue. Common: Decreased appetite, sleep disorders, anxiety, decreased libido, anorgasma. Tremor, nervousness, lethargy, somnolence, blurred vision. Vertigo, palpitations, hot flush, diarrhea, vomiting, dyspepsia. Increased sweating, pruritus, weakness, rigors, feeling abnormal, hepatic lab related events. Symptoms reported upon abrupt discontinuation: Dizziness, nausea, insomnia, headache, anxiety.
For full details see prescribing information.
MAOIs (concomitantly or within at leat 14 days of discontinuing treatment with an MAOI), CNS drugs, including alcohol and sedatives (benzodiazepines, morphinomimetics, antipsychotics, phenobarbital, sedative antihistamine). Drugs metabolised by CYP1A2, CYP2D6. Potent inhibitors of CYP1A2, such as fluvoxamine.
Pregnancy and Lactation
Pregnancy: There are no adequate data on the use of duloxetine in pregnant women. Studies in animals have shown reproductive toxicity at systemic exposure levels (AUC) of duloxetine lower than the maximum clinical exposure. The potential risk for humans is unknown. Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Although no studies have investigated the association of PPHN to SNRI treatment, this potential risk cannot be ruled out with duloxetine taking into account the related mechanism of action (inhibition of the re-uptake of serotonin). As with other serotonergic medicinal products, discontinuation symptoms may occur in the neonate after maternal duloxetine use near term. Discontinuation symptoms seen with duloxetine may include hypotonia, tremor, jitteriness, feeding difficulty, respiratory distress and seizures. The majority of cases have occurred either at birth or within a few days of birth. YENTREVE should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus. Women should be advised to notify their physician if they become pregnant, or intend to become pregnant, during therapy.
Breast feeding: Duloxetine is very weakly excreted into human milk based on a study of 6 lactating patients, who did not breast feed their children. The estimated daily infant dose on a mg/kg basis is approximately 0.14% of the maternal dose. As the safety of duloxetine in infants is not known, the use of YENTREVE while breast-feeding is not recommended.
Cases of overdoses, alone or in combination with other medicinal products, with duloxetine doses of 5400 mg were reported. Some fatalities have occurred, primarily with mixed overdoses, but also with duloxetine alone at a dose of approximately 1000 mg. Signs and symptoms of overdose (duloxetine alone or in combination with other medicinal products) included somnolence, coma, serotonin syndrome, seizures, vomiting and tachycardia. No specific antidote is known for duloxetine but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/or temperature control) may be considered. A free airway should be established. Monitoring of cardiac and vital signs is recommended, along with appropriate symptomatic and supportive measures. Gastric lavage may be indicated if performed soon after ingestion or in symptomatic patients. Activated charcoal may be useful in limiting absorption. Duloxetine has a large volume of distribution and forced diuresis, haemoperfusion, and exchange perfusion are unlikely to be beneficial.