Active ingredients: Duloxetine (Duloxetine hydrochloride)
CYMBALTA 30 mg gastro-resistant hard capsules
CYMBALTA 60 mg gastro-resistant hard capsules
Why is Cymbalta used? What is it for?
Cymbalta contains the active substance duloxetine. Cymbalta increases the levels of serotonin and norepinephrine in the nervous system. Cymbalta is used in adults to treat:
- the Depression
- generalized anxiety disorder (chronic feeling of anxiety or nervousness)
- diabetic neuropathic pain (often described as burning, cutting, stinging, stabbing, or oppressive or as an electric shock. In the affected area there may be loss of sensation, or sensations in which contact, heat, cold, or pressure can cause pain)
Cymbalta begins to work in most people with depression or anxiety within two weeks of starting treatment, but it may take 2-4 weeks before you feel better. Talk to your doctor if you don't start getting better after this time. Your doctor may continue to give you Cymbalta when you feel better to prevent depression or anxiety from returning. In people with diabetic neuropathic pain, it may take a few weeks to feel better. Tell your doctor if you feel no better after 2 months.
Contraindications When Cymbalta should not be used
DO NOT take Cymbalta if you:
- you are allergic to duloxetine or any of the other ingredients of this medicine (listed in section 6)
- have liver disease
- have severe kidney disease
- you are taking or have taken within the last 14 days another medicine known as a Monoamine Oxidase Inhibitor (MAOI) (see "Other medicines and Cymbalta")
- you are taking fluvoxamine which is usually used to treat depression, ciprofloxacin or enoxacin which are used to treat some infections
- you are taking other medicines that contain duloxetine (see "Other medicines and Cymbalta")
Tell your doctor if you have high blood pressure or heart disease. Your doctor will tell you if you can take Cymbalta.
Precautions for use What you need to know before taking Cymbalta
The reasons why Cymbalta may not be suitable for you are as follows. Talk to your doctor before taking Cymbalta if:
- are taking other medicines to treat depression (see "Other medicines and Cymbalta")
- you are taking St. John's wort (Hypericum perforatum), a herbal preparation
- have kidney disease
- have had seizures (fits)
- had a manic disorder
- suffer from bipolar disorder
- have eye problems, as well as some types of glaucoma (increased pressure in the eye)
- have a history of bleeding disorders (tendency to bruise)
- there is a risk for you of having low sodium levels (for example if you are taking diuretics, especially if you are an elderly person)
- you are being treated with another medicine which can cause liver damage
- you are taking other medicines that contain duloxetine (see "Other medicines and Cymbalta")
Cymbalta can cause a feeling of restlessness or an inability to sit or stand still. If this happens to you, you should tell your doctor.
Thoughts of suicide and worsening of depression and anxiety disorder
If you are depressed and / or have anxiety you may sometimes have thoughts of harming or killing yourself. These thoughts may be increased when you first start treatment with antidepressants, as these medicines take a period of time to be effective, usually about 2 weeks but sometimes even longer.
You may be more likely to think like this if you:
- have previously had thoughts about killing or harming yourself
- is a young adult. Data from clinical trials have shown an increased risk of suicidal behavior in adults under the age of 25 with psychiatric disorders who were treated with an antidepressant
If at any time you have thoughts of harming or killing yourself, contact your doctor or go to a hospital immediately.
You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You may ask them to tell you if they think your depression or anxiety is getting worse , or if they are concerned about changes in their behavior.
Children and adolescents under 18 years of age
Cymbalta should normally not be used in children and adolescents under 18 years of age.
Furthermore, you should be aware that patients under 18 have an increased risk of side effects such as suicide attempt, suicidal thoughts and hostile attitude (especially aggressive, oppositional and anger behavior) when taking these types of medicines. Despite this, the doctor may prescribe Cymbalta to patients under 18 if he / she feels this is the best solution for them. If your doctor has prescribed Cymbalta for a patient under 18 and you want clarification, please go back to your doctor. You should tell your doctor if any of the above symptoms appear or worsen when patients under 18 are taking Cymbalta. Furthermore, long-term safety effects of Cymbalta relating to growth, maturity and cognitive and behavioral development have not yet been demonstrated in this age group.
Interactions Which drugs or foods may change the effect of Cymbalta
Other medicines and Cymbalta
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.
The main component of Cymbalta, duloxetine, is found in other medicines for other conditions:
- diabetic neuropathic pain, depression, anxiety and urinary incontinence
Simultaneous use of more than one of these medicines should be avoided. Check with your doctor if you are already taking medicines that contain duloxetine.
Your doctor should decide whether you can take Cymbalta with other medicines. Do not start or stop taking any medicines, including those bought without a prescription and herbal preparations, before checking with your doctor.
Also tell your doctor if you are taking any of the following medicines:
Monoamine Oxidase Inhibitors (MAOIs): You should not take Cymbalta if you are taking, or have recently taken (within the last 14 days) another antidepressant medicine called a monoamine oxidase inhibitor (MAOI). Examples of MAOIs include moclobemide (an antidepressant) and linezolid (an antibiotic). Taking a MAOI together with many prescription medicines, including Cymbalta, can cause serious or even life-threatening side effects. You must wait at least 14 days after you stop taking a MAOI before you can take Cymbalta. . Also, you must wait at least 5 days after you stop taking Cymbalta before taking a MAOI.
Medicines that cause sleepiness: These include medications prescribed by the doctor, such as benzodiazepines, strong pain relievers, antipsychotics, phenobarbital and antihistamines.
Medicines that increase serotonin level: Triptans, tramadol, tryptophan, Selective Serotonin Reuptake Inhibitors (SSRIs) (such as paroxetine and fluoxetine), Selective Serotonin / Noradrenaline Reuptake Inhibitors (SNRIs) (such as venlafaxine), antidepressants clomipramine, amitriptyline), pethidine, St. John's wort (St. John's wort) and MAOIs (such as moclobemide and linezolid). These medicines increase the risk of side effects; if you get any unusual symptoms while taking any of these medicines together with Cymbalta, you should see your doctor.
Oral anticoagulants and antiplatelet agents: Medicines that thin the blood or prevent blood clots from forming. These medicines may increase the risk of bleeding.
Cymbalta with food, drink and alcohol
Cymbalta can be taken with or without meals. You should be careful if you drink alcohol while being treated with Cymbalta.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
- Tell your doctor if you are pregnant or planning to become pregnant while you are taking Cymbalta. You should only use Cymbalta after discussing the potential benefits and any potential risks to your unborn child with your doctor. Make sure your midwife and / or doctor know you are being treated with Cymbalta. When taken during pregnancy, similar drugs (SSRIs) may increase the risk of developing a serious condition in newborns, called persistent pulmonary hypertension of the newborn ( PPHN), which causes the newborn to breathe faster and have a bluish color. These symptoms usually occur during the first 24 hours after birth. If this happens to the newborn, contact your midwife or doctor immediately. If you take Cymbalta near the end of your pregnancy, your baby may have some symptoms as soon as it is born. These generally appear at birth or within a few days of birth. These symptoms may include flabby muscles, shaking, nervousness, difficulty in breastfeeding, a disturbed breathing and seizures. If the newborn has any of these symptoms after birth, or you are concerned about the health of the baby, contact your doctor. or the midwife who will be able to advise you.
- Tell your doctor if you are breastfeeding. The use of Cymbalta while breastfeeding is not recommended. Ask your doctor or pharmacist for advice.
Driving and using machines
Cymbalta may make you feel sleepy or dizzy. Do not drive or use any tools or machines until you are aware of how Cymbalta affects you.
Cymbalta contains sucrose
Cymbalta contains sucrose. If you have been told by your doctor that you have an "intolerance to some sugars, contact your doctor before taking this medicinal product.
Dose, Method and Time of Administration How to use Cymbalta: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Cymbalta is taken orally. Swallow the capsule without chewing, with the help of a glass of water.
For depression and diabetic neuropathic pain: The usual dose of Cymbalta is 60 mg once a day, but your doctor will prescribe the dose that is right for you.
For generalized anxiety disorder: The usual starting dose of Cymbalta is 30 mg once a day after which most patients will receive 60 mg once a day, but your doctor will prescribe the dose that they think is right for you. The dose can be adjusted up to 120 mg per day, based on your response to Cymbalta.
To help you remember to take Cymbalta, it may be easier for you to take it at the same time each day.
Talk to your doctor how long you need to continue taking Cymbalta. Do not stop taking Cymbalta, or change your dose, without talking to your doctor. Appropriate treatment of the disorder is important to help you get better. If left untreated, the disorder cannot improve and may become more severe and difficult to treat. to deal.
Overdose What to do if you have taken too much Cymbalta
If you take more Cymbalta than you should
Contact your doctor or pharmacist immediately if you have taken more Cymbalta than your doctor has prescribed. Symptoms of overdose include drowsiness, coma, serotonin syndrome (a rare reaction which can cause feelings of great happiness, sleepiness, clumsiness, restlessness, feeling of drunkenness, fever, sweating or muscle stiffness), fits, vomiting and rapid heart rate.
If you forget to take Cymbalta
If you forget a dose, take it as soon as you remember. However, if it is time for your next dose, skip the missed dose and just take a single dose as usual. Do not take a double dose to make up for a forgotten dose. Do not take more than the daily amount of Cymbalta that has been prescribed for you in one day.
If you stop taking Cymbalta
Even if you feel better, DO NOT stop taking the capsules without checking with your doctor. If your doctor thinks you no longer need Cymbalta, he will ask you to gradually reduce your dose over a period of at least 2 weeks before stopping the drug. all treatment.
Some patients who suddenly stop taking Cymbalta have experienced symptoms such as:
- dizziness, tingling sensations such as from pins and needles or sensations such as electric shock (particularly in the head), sleep disturbances (intense dreams, nightmares, inability to sleep), fatigue, sleepiness, feeling restless or agitated, feeling of anxiety, feeling sick or being sick (vomiting), shaking, headache, muscle pain, feeling irritable, diarrhea, excessive sweating or dizziness.
These symptoms are usually not serious and disappear within a few days, but if you experience symptoms that are bothersome you should consult with your doctor. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Cymbalta
Like all medicines, this medicine can cause side effects, although not everybody gets them. These effects are usually mild to moderate and often disappear after a few weeks.
Very common side effects (may affect more than 1 in 10 patients)
- headache, feeling sleepy
- feeling sick (nausea), dry mouth
Common side effects (may affect up to 1 in 10 people)
- lack of appetite
- difficulty falling asleep, feeling agitated, decreased sexual desire, anxiety, difficulty or inability to reach orgasm, unusual dreams
- dizziness, feeling of laziness, tremor, numbness, including a feeling of numbness, pricking or tingling of the skin
- blurred vision
- tinnitus (perception of a sound in the ear in the absence of an external sound stimulus)
- feel the heart beating in the chest
- increased blood pressure, flushing
- increased yawning
- constipation, diarrhea, stomach pain, retching (vomiting), heartburn, indigestion, accumulation of gas in the intestine
- increased sweating, rash (itchy)
- muscle pain, muscle spasm
- painful urination, frequent urination
- difficulty getting an erection, changes in ejaculation
- falls (especially in older people), fatigue
- weight loss
Children and adolescents under 18 years of age with depression treated with this medicine experienced some weight loss when they first started taking this medicine. After 6 months of treatment, the weight increased until it was equal to that of other children and adolescents of the same age and sex.
Uncommon side effects (may affect up to 1 in 100 people)
- throat inflammation causing a hoarse voice
- suicidal thoughts, difficulty falling asleep, forcefully grinding or rubbing the teeth, feeling disoriented, lack of motivation
- sudden and involuntary twitching or twitching of muscles, feeling restless or unable to sit or stand still, feeling jittery, difficulty concentrating, changes in the sense of taste, difficulty in controlling movements such as lack of coordination or involuntary movements of the muscles, restless legs syndrome, poor sleep quality
- dilation of the pupils (the dark center of the eye), visual disturbances
- feeling of dizziness or 'spinning' (vertigo), ear pain
- rapid or irregular heartbeat
- fainting, dizziness, light-headedness or fainting on standing, cold fingers and / or toes
- feeling of constriction in the throat, nosebleeds
- vomiting blood or black tarry stools, gastroenteritis, belching, difficulty swallowing
- inflammation of the liver which may cause abdominal pain and yellowing of the skin or whites of the eyes
- night sweats, hives, cold sweats, sensitivity to sunlight, increased tendency to bruise
- muscle stiffness, muscle contraction
- difficulty or inability to pass urine, difficulty starting urination, need to pass urine at night, need to pass more urine than normal, decreased urine flow
- abnormal vaginal bleeding, abnormal menstrual cycles, including heavy, painful, irregular or prolonged, unusually few or no periods, pain in the testicles or scrotum
- chest pain, feeling cold, thirsty, shaking, feeling hot, abnormal gait
- weight gain
- Cymbalta can cause effects that you may not be aware of, such as increases in liver enzymes, or blood levels of potassium, creatine phosphokinase, sugar or cholesterol.
Rare side effects (may affect up to 1 in 1,000 people)
- severe allergic reaction causing difficulty in breathing or dizziness with swelling of the tongue and lips, allergic reactions
- decreased activity of the thyroid gland which can lead to fatigue or weight gain
- dehydration, low levels of sodium in the blood (especially in older people; symptoms may include feeling dizzy, feeling faint, confused, sleepy or very tired, or feeling nauseous or about to vomit, more serious symptoms are loss of consciousness seizures or falls), syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
- suicidal behavior, mania (hyperactivity, racing thoughts and decreased need for sleep), hallucinations, aggressive behavior and anger
- "Serotonin syndrome" (a rare reaction which can cause feelings of great happiness, drowsiness, clumsiness, restlessness, feeling drunk, fever, sweating or muscle stiffness), seizures
- increased pressure inside the eye (glaucoma)
- inflammation of the mouth, bright red blood in the stool, bad breath
- hepatic (liver) failure, yellowing of the skin or whites of the eyes (jaundice)
- Stevens-Johnson syndrome (severe disease with blistering of the skin, mouth, eyes and genitals), severe allergic reaction which causes swelling of the face or throat (angioedema)
- contraction of the mouth muscles
- altered odor of urine
- symptoms of menopause, abnormal breast milk production in men and women
Very rare side effects (may affect up to 1 in 10,000 patients)
- Inflammation of the blood vessels in the skin (cutaneous vasculitis)
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children
Do not use this medicine after the expiry date which is stated on the carton.
Store in the original package to keep it away from moisture. Do not store above 30 ° C.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Cymbalta contains
The active ingredient is duloxetine. Each capsule contains 30 or 60 mg of duloxetine (as hydrochloride).
The other ingredients are:
Capsule contents: hypromellose, hypromellose acetate succinate, sucrose, sugar granules, talc, titanium dioxide (E171), triethyl citrate. (see at the end of section 2 for more information on sucrose)
Capsule shell: gelatin, sodium lauryl sulfate, titanium dioxide (E171), indigo carmine (E132), yellow iron oxide (E172) (for 60 mg only) and edible green ink (30 mg) or edible white ink (60 mg) ).
Edible green ink: synthetic black iron oxide (E172), yellow synthetic iron oxide (E172), propylene glycol, shellac.
Edible white ink: titanium dioxide (E171), propylene glycol, shellac, povidone.
What Cymbalta looks like and contents of the pack
Cymbalta is a gastro-resistant hard capsule. Each capsule of Cymbalta contains granules of duloxetine hydrochloride with a coating to protect them from stomach acid.
Cymbalta is available in 2 strengths: 30mg and 60mg.
The 30 mg capsules are blue and white imprinted with "30 mg" and the code "9543".
The 60 mg capsules are blue and green imprinted with "60 mg" and the code "9542".
Cymbalta 30 mg is available in packs of 7, 28 and 98 capsules.
Cymbalta 60 mg is available in packs of 28, 56, 84, 98, 100 and 500 capsules.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
CYMBALTA 30 MG HARD GASTRORESISTANT CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 30 mg of duloxetine (as hydrochloride).
Excipients:
Each capsule contains 8.6 mg of sucrose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Hard gastro-resistant capsule.
Opaque white body, imprinted with "30 mg" and an opaque blue cap, imprinted with "9543".
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of major depressive disorder.
Treatment of peripheral diabetic neuropathic pain.
Treatment of generalized anxiety disorder.
Cymbalta is indicated in adults.
For further information see section 5.1.
04.2 Posology and method of administration
Dosage
Major depressive disorder
The starting and recommended maintenance dosage is 60 mg once daily regardless of food intake. Dosages above 60 mg once daily, up to a maximum dose of 120 mg daily, have been evaluated in clinical studies since However, there is no clinical evidence to suggest that patients not responding to the recommended starting dose would benefit from further dose escalation.
Therapeutic response is usually observed after 2 - 4 weeks of treatment.
After consolidation of the antidepressant response, it is recommended to continue treatment for several months in order to avoid relapse. In patients with a history of repeated major depressive episodes and who respond to duloxetine, further long-term treatment with a dose of 60 to 120 mg per day may be considered.
Generalized anxiety disorder
The recommended starting dosage in patients with generalized anxiety disorder is 30 mg once daily regardless of food intake. In patients with insufficient response the dosage should be increased to 60 mg which is the usual maintenance dose in most patients.
In patients with co-morbidities for major depressive disorder, the starting and maintenance dosage is 60 mg once daily (see also dosing recommendations above).
In clinical studies, dosages up to 120 mg per day have been shown to be effective and have been evaluated from a safety point of view. In patients with insufficient response to 60 mg, increases up to 90 mg or 120 mg may therefore be considered. An increase in dosage should be made based on clinical response and tolerability.
After consolidation of the response, it is recommended to continue treatment for several months in order to avoid a relapse.
Peripheral diabetic neuropathic pain
The starting and recommended maintenance dosage is 60 mg per day regardless of food intake. Dosages above 60 mg once daily, up to a maximum dose of 120 mg per day administered in equally divided doses, were evaluated in clinical studies from a safety perspective. The plasma concentration of duloxetine shows a "wide variability from subject to subject (see section 5.2). Therefore, some patients who respond insufficiently to 60 mg may benefit with a higher dosage.
Response to treatment should be evaluated after 2 months. After this time, an additional response is unlikely in patients with an inadequate initial response.
Therapeutic benefit should be reassessed regularly (at least every three months) (see section 5.1).
Elderly patients
Dosage adjustment based on age alone is not recommended in elderly patients. However, as with any medicine, caution should be exercised when treating elderly patients, especially in major depressive disorder with Cymbalta 120 mg daily, for which patients data are limited (see sections 4.4 and 5.2).
Children and adolescents
Duloxetine is not recommended for use in children and adolescents due to the lack of sufficient data on safety and efficacy (see section 4.4).
Abnormal liver function
Cymbalta must not be used in patients with liver disease resulting in hepatic impairment (see sections 4.3 and 5.2).
Alteration of renal function
In patients with mild or moderate renal dysfunction (creatinine clearance 30 to 80 ml / min) no dosage adjustment is necessary. Cymbalta must not be used in patients with severe renal impairment (creatinine clearance
Suspension of treatment
Abrupt discontinuation should be avoided. When discontinuing treatment with Cymbalta 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 (see sections 4.4 and 4.8). If intolerable symptoms occur following a dose reduction or discontinuation of treatment, the possibility of resuming treatment with the previously prescribed dose should be considered. Thereafter, the doctor may continue to reduce the dose, but more gradually.
Method of administration
For oral use.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
The concomitant use of Cymbalta with non-selective and irreversible Monoamine Oxidase Inhibitors (MAOIs) is contraindicated (see section 4.5).
Liver disease resulting in impaired liver function (see section 5.2).
Cymbalta should not be used in combination with fluvoxamine, ciprofloxacin or enoxacin (potent CYP1A2 inhibitors) as the combination results in elevated plasma concentrations of duloxetine (see section 4.5).
Severe renal impairment (creatinine clearance
Initiation of Cymbalta treatment is contraindicated in patients with uncontrolled hypertension, which could expose patients to a potential risk of hypertensive crisis (see sections 4.4 and 4.8).
04.4 Special warnings and appropriate precautions for use
Mania and convulsions
Cymbalta should be used with caution in patients with a history of mania or a diagnosis of bipolar disorder, and / or seizures.
Mydriasis
Mydriasis has been reported in association with duloxetine, therefore caution should be used when prescribing Cymbalta to patients with increased intraocular pressure, or to those at risk of acute narrow-angle glaucoma.
Blood pressure and heart rate
In some patients, duloxetine has been associated with increased blood pressure and clinically significant hypertension. 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, monitoring of blood pressure is recommended. blood pressure, especially during the first month of treatment. Duloxetine should be used with caution in patients whose conditions may be compromised by an "increased heart rate or an increase in blood pressure. Caution should also be exercised when duloxetine is co-administered with medicinal products that may alter its metabolism (see section 4.5). In patients experiencing sustained increase in blood pressure during therapy with duloxetine either a dose reduction or gradual discontinuation of treatment should be considered (see section 4.8). Duloxetine therapy must not be initiated in patients with uncontrolled hypertension (see section 4.3).
Alteration of renal function
In patients with severe renal impairment on hemodialysis (creatinine clearance
Use with antidepressants
Caution should be observed when Cymbalta is used in combination with antidepressants. In particular, the association with selective and reversible MAOIs is not recommended.
St. John's wort
Adverse reactions may be more common when using Cymbalta in combination with herbal preparations containing St John's wort (Hypericum perforatum).
Suicide
Major depressive disorder and generalized anxiety disorder:
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant disease remission occurs. As improvement may not occur during the first or subsequent weeks of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide can increase early in the healing process.
Other psychiatric conditions for which Cymbalta is prescribed may also be associated with an increased risk of suicide-related events. Furthermore, these pathological situations can coexist with major depressive disorder. Therefore the same precautions taken when treating patients with major depressive disorder should be observed when treating patients with other psychiatric disorders.
Patients with a history of suicide-related events or those who have a significant degree of suicidal thoughts prior to initiation of treatment are known to be at higher risk for suicidal thoughts or suicide attempts, and should be closely monitored during treatment. Treatment: A meta-analysis of clinical trials of antidepressant medicinal products compared with placebo in the treatment of psychiatric disorders showed an increased risk of suicidal behavior in patients under 25 years of age treated with antidepressants compared to placebo.
Cases of suicidal thoughts and suicidal behaviors have been reported during duloxetine therapy or within short time after treatment discontinuation (see section 4.8).
Close surveillance of patients, and particularly those at high risk, should accompany drug therapy especially in the initial stages of treatment and after dose changes. Patients (or their carers) should be advised of the need to monitor and report immediately to the treating physician any worsening of the clinical picture, the onset of suicidal behavior or thoughts or unusual changes in behavior if these symptoms occur. .
Peripheral diabetic neuropathic pain:
As with other medicinal products with similar pharmacological action (antidepressants), isolated cases of suicidal ideation and suicidal behaviors have been reported during therapy with duloxetine or within a short time after treatment discontinuation. Regarding the risk factors for suicide in depression, please refer to the 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
No clinical studies have been performed with duloxetine in pediatric patients. Cymbalta should not be used in the treatment of children and adolescents under 18 years of age. Suicide-related behaviors (suicide attempts and suicidal thoughts) and hostile attitude (especially aggressive, oppositional and anger behavior) were observed more frequently in clinical trials of children and adolescents treated with antidepressants than in those treated with placebo. If, based on clinical need, a decision to treat is nevertheless made, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, there are no long-term safety data on growth, maturity and cognitive and behavioral development in children and adolescents.
Hemorrhages
Haemorrhagic manifestations such as ecchymosis, purpura and gastrointestinal haemorrhage have been reported with the intake of Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin / Noradrenaline Reuptake Inhibitors (SNRIs), including duloxetine, haemorrhagic manifestations, such as ecchymosis, purpura and gastrointestinal haemorrhage, have been reported. are taking anticoagulants and / or medicines known to affect platelet function [eg Non-Steroidal Anti-inflammatory Drugs (NSAIDs) or 'Acetylsalicylic Acid (ASA)], and in patients with known bleeding tendencies.
Hyponatremia
Hyponatremia has been reported during administration of Cymbalta, including cases with sodium levels below 110 mml / l. Hyponatremia may be due to a syndrome of inappropriate antidiuretic hormone secretion (SIADH). The majority of cases of hyponatremia have been reported in the elderly, especially when related to a recent history of, or a condition predisposing to, altered body fluid balance. Caution is warranted in patients at increased risk of hyponatremia, as well as in elderly, cirrhotic or dehydrated patients, or in patients treated with diuretics.
Suspension of treatment
Discontinuation symptoms are common when treatment is stopped, especially if discontinuation occurs abruptly (see section 4.8). In clinical trials, adverse events observed on abrupt discontinuation occurred in approximately 45% of patients treated with Cymbalta and in 23% of patients treated with placebo.
The risk of withdrawal symptoms seen with SSRIs and SNRIs 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 in intensity, however in some patients they may be severe in intensity. These symptoms usually occur within the first few days of stopping treatment, but there have been very rare reports of such symptoms in patients who have inadvertently forgotten to take a dose. Generally these symptoms are self-limiting and usually resolve within 2 weeks, although in some individuals they may be prolonged (2-3 months or more). Therefore, it is recommended that duloxetine be gradually reduced over a period of not less than 2 weeks prior to discontinuation of treatment, as needed by the patient (see section 4.2).
Elderly patients
There are limited data on the use of Cymbalta 120 mg in elderly patients with major depressive disorder. Therefore, caution should be exercised in treating elderly patients with the maximum dose (see sections 4.2 and 5.2). Data on the use of Cymbalta in elderly patients with generalized anxiety disorder are limited.
Akathisia / psychomotor restlessness
The use of 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 is more likely to occur within the first few years. weeks of treatment. In patients who develop these symptoms, increasing the dose may be harmful.
Medicines containing duloxetine
Duloxetine is used under different trade names for different indications (treatment of diabetic neuropathic pain, major depressive disorder, generalized anxiety disorder and stress urinary incontinence). Simultaneous use of more than one of these products should be avoided.
Hepatitis / increased liver enzyme values
Cases of hepatic injury have been reported with duloxetine (see section 4.8), including marked elevations in liver enzymes (> 10 times ULN), hepatitis and jaundice. Most cases occurred during the first months of treatment. The type of liver damage was essentially hepatocellular. Duloxetine should be used with caution in patients treated with other medicinal products that can cause liver damage.
Sucrose
Cymbalta 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.
04.5 Interactions with other medicinal products and other forms of interaction
Monoamine Oxidase InhibitorsDue to the risk of developing serotonin syndrome, duloxetine should not be used in combination with non-selective and irreversible MAOIs, or at least within 14 days immediately following discontinuation of treatment with a MAOI. Based on the half-life of duloxetine, you should wait at least 5 days after stopping Cymbalta before starting treatment with a MAOI (see section 4.3).
The risk of developing serotonin syndrome is lower with selective and reversible MAOIs, such as moclobemide. However, the use of Cymbalta in combination with a selective and reversible MAOI is not recommended (see section 4.4).
CYP1A2 inhibitors: Since CYP1A2 is involved in the metabolism of duloxetine, the use of duloxetine in combination with potent CYP1A2 inhibitors is likely to result in higher concentrations of duloxetine. Fluvoxamine (100 mg once daily), a potent inhibitor of CYP1A2, decreased the apparent plasma clearance of duloxetine by approximately 77% and increased AUC0-t 6-fold. Therefore Cymbalta should not be administered in combination with potent CYP1A2 inhibitors such as fluvoxamine (see section 4.3).
CNS medicines: The risk of using duloxetine in combination with other CNS-active medicinal products has not been systematically evaluated, except in the cases described in this section. Therefore, caution is advised when Cymbalta is taken in combination with other medicines or other centrally acting substances, including alcohol and sedative medicines (eg benzodiazepines, morphine mimetics, antipsychotics, phenobarbital, sedative antihistamines).
Serotonin syndrome: In rare cases, serotonin syndrome has been reported in patients taking SSRIs (eg paroxetine, fluoxetine) in combination with serotonergic medicinal products. Caution is advised if Cymbalta is used concomitantly with serotonergic antidepressants such as SSRIs, tricyclics such as clomipramine or amitriptyline, St. John's wort (Hypericum perforatum), venlafaxine or triptans, tramadol, pethidine and tryptophan.
Effects of duloxetine on other medicinal products
Medicinal products metabolised by CYP1A2: The pharmacokinetics of theophylline, a substrate of CYP1A2, were not significantly altered by co-administration with duloxetine (60 mg twice daily).
Medicinal products metabolised by CYP2D6: duloxetine is a moderate inhibitor of CYP2D6. When duloxetine was administered at a dose of 60 mg twice daily in combination with a single dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold. Co-administration with duloxetine (40 mg twice daily). day) increases the steady state AUC of tolterodine (2 mg twice daily) by 71% but does not affect the pharmacokinetics of its active 5-hydroxyl metabolite, and no dosage adjustment is recommended. Caution is advised if Cymbalta is administered in combination with medicinal products which are predominantly metabolised by CYP2D6 (risperidone, tricyclic antidepressants [TCA] such as nortriptyline, amitriptyline and imipramine) particularly if these have a low therapeutic index (such as flecainide, propafenone and metoprolol) .
Oral contraceptives and other steroid agents: the results of studies in vitro show that duloxetine does not induce the catalytic activity of CYP3A. No specific drug interaction studies have been performed in vivo.
Anticoagulants and antiplatelet agents: Caution should be used when duloxetine is administered in combination with oral anticoagulants or with antiplatelet agents due to a potential increased risk of bleeding attributable to a pharmacodynamic interaction. In addition, increases in INR values have been reported when duloxetine was administered to patients receiving warfarin. However, administration of duloxetine in combination with warfarin in equilibrium conditions in healthy volunteers as part of a clinical pharmacology study did not result in a clinically significant change in INR from baseline or in R- or S pharmacokinetics. -warfarin.
Effects of other medicinal products on duloxetine
Antacids and H2 receptor antagonists: Administration of duloxetine in combination with aluminum and magnesium-containing antacids or duloxetine with famotidine had no significant effect on the rate or extent of duloxetine absorption following administration of an oral dose of 40 mg.
CYP1A2 inducers: Population pharmacokinetic analysis studies have shown that smokers have almost 50% lower plasma concentrations of duloxetine than non-smokers.
04.6 Pregnancy and lactation
Pregnancy
There are insufficient data on the use of duloxetine in pregnant women. Studies in animals have shown reproductive toxicity from exposure to systemic concentrations (AUC) of duloxetine lower than the maximal clinical exposure (see section 5.3).
The potential risk for humans is unknown.
Epidemiological data have suggested that the use of SSRIs in pregnancy, especially late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Although no studies have investigated the association of PPHN with SNRI treatment, this A potential risk cannot be excluded with duloxetine when taking into account its mechanism of action (inhibition of serotonin reuptake).
As with other serotonergic medicinal products, withdrawal symptoms may occur in the newborn after maternal use of duloxetine close to delivery. Withdrawal symptoms seen with duloxetine may include hypotonia, tremor, nervousness, difficulty in breastfeeding, difficulty in breathing and convulsions. Most cases occurred both at birth and within days of birth.
Cymbalta should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus. Women should be advised to report to their physician if they become pregnant or intend to become pregnant during therapy.
Feeding time
Based on a study of 6 lactating women who were not breastfeeding their infants, duloxetine is poorly excreted in breast milk. Calculated in mg / kg, the estimated daily infant dose is approximately 0.14% of the maternal dose (see section 5.2). Since the safety of duloxetine in infants is unknown, the use of Cymbalta while breastfeeding is not recommended.
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed. Taking Cymbalta may be associated with a sedative action and dizziness. Patients should be warned to avoid performing potentially dangerous tasks such as driving or operating machinery if they experience sedation or dizziness.
04.8 Undesirable effects
to. Summary of the safety profile
The most commonly reported adverse reactions in patients treated with Cymbalta were nausea, headache, dry mouth, somnolence and dizziness. However, the majority of common adverse reactions were mild to moderate, generally they started early during therapy and most tended to subside with continued therapy.
b. Summary table of adverse reactions
Table 1 shows the adverse reactions observed in spontaneous reports and in placebo-controlled clinical trials (for a total of 7,819 patients, including 4,823 with duloxetine and 2,996 with placebo) in depression, generalized anxiety disorder and diabetic neuropathic pain. .
Table 1: Adverse reactions
Frequency assessment: very common (≥ 1/10), common (≥ 1/100,
For each frequency class, undesirable effects are reported in descending order of severity.
1 Cases of seizures and cases of tinnitus have also been reported after discontinuation of treatment.
2 Cases of orthostatic hypotension and syncope have been reported mainly at the start of treatment.
3 See section 4.4.
4 Cases of aggressive behavior and anger have been reported especially in the early stages of treatment or after its discontinuation.
5 Cases of suicidal ideation and suicidal behaviors have been reported during duloxetine therapy or early after treatment discontinuation (see section 4.4).
6 Assessment of the frequency of adverse reactions reported during the post-marketing surveillance period; not observed in placebo-controlled clinical trials.
7 No statistically significant difference from placebo.
8 Falls were more common in elderly subjects (> 65 years of age)
c. Description of selected adverse reactions
Discontinuation of duloxetine therapy (especially when it occurs abruptly) commonly leads to withdrawal symptoms. The most commonly reported reactions are dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), fatigue, somnolence, agitation or anxiety, nausea and / or vomiting, tremor, headache, irritability, diarrhea, hyperhidrosis and dizziness.
Generally, for SSRIs and SNRIs, these events are mild to moderate and self-limiting, however, in some patients they may be severe and / or prolonged. Therefore, when treatment with duloxetine is no longer required, gradual discontinuation of therapy by progressive dose reduction is recommended (see sections 4.2 and 4.4).
In three 12-week acute phase clinical trials with duloxetine in patients with diabetic neuropathic pain, a small but statistically significant increase in fasting blood glucose was observed in patients treated with duloxetine. The HbA1c value was stable in both duloxetine-treated and placebo-treated patients. In the extension phase of these studies, which lasted up to 52 weeks, there was an increase in HbA1c in both duloxetine and routine treatment groups, but the mean increase was greater than 0.3% in the duloxetine group. There was also a small increase in fasting glucose and total cholesterol in patients treated with duloxetine while laboratory tests showed a slight decrease in the routine treatment group.
In patients treated with duloxetine, the QT interval corrected for heart rate did not differ from that observed in patients treated with placebo. No clinically significant differences in QT measurements were observed in patients treated with duloxetine and those treated with placebo. , PR, QRS, or QTcB.
04.9 Overdose
There have been reports of overdose of duloxetine with doses of 5,400 mg, alone or in combination with other medicinal products. Some deaths have occurred, essentially in association with the overdose of various medicinal products, but also with duloxetine alone at a dose of approximately 1,000 mg. Signs and symptoms of overdose (with duloxetine alone or in combination with other medicinal products) included somnolence, coma, serotonin syndrome, convulsions, vomiting and tachycardia.
There is no known specific antidote for duloxetine, but specific treatment (such as cyproheptadine and / or temperature control) may be considered if serotonin syndrome occurs. A patent airway must be maintained. Monitoring for cardiac and vital signs is recommended, along with appropriate supportive and symptomatic measures. Gastric lavage may be indicated if performed shortly after ingestion or in symptomatic patients. Activated charcoal may be helpful in reducing absorption. Duloxetine has a large volume of distribution and forced diuresis, haemoperfusion and exchange perfusion are unlikely to be of benefit.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other antidepressants.
ATC code: N06AX21.
Mechanism of action
Duloxetine is a combined serotonin (5-HT) and norepinephrine (NA) reuptake inhibitor. Duloxetine weakly inhibits dopamine reuptake with no significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors. Duloxetine dose-dependently increases the extracellular levels of serotonin and noradrenaline in various brain areas of animals.
Pharmacodynamic effects
Duloxetine normalized the pain threshold in various preclinical models of neuropathic and inflammatory pain and attenuated the attitude towards pain in a persistent pain model. The inhibitory action of duloxetine on pain is believed to be the result of an enhancement of the descending pathways. pain inhibitors present in the central nervous system.
Clinical efficacy and safety
Major depressive disorder:
Cymbalta was studied in a clinical program involving 3,158 patients (1,285 patient-years of exposure) who met DSM-IV criteria for major depression. The efficacy of Cymbalta at the recommended dose of 60 mg once daily was demonstrated in all three acute, fixed-dose, randomized, double-blind, placebo-controlled clinical trials in adult outpatients with major depressive disorder. Overall, the efficacy of Cymbalta has been demonstrated with daily dosages between 60 and 120 mg in five out of seven acute, fixed-dose, randomized, double-blind, placebo-controlled clinical trials in adult outpatients with major depressive disorder.
Cymbalta demonstrated statistical superiority over placebo as measured by improvement in total score on the Hamilton Depression Rating Scale (HAM-D) at 17 items (which includes both somatic and emotional symptoms of depression). Response and remission rates were also statistically and significantly higher with Cymbalta than with placebo. Only a small fraction of the patients included in the pivotal clinical trials had severe depression (baseline HAM-D> 25).
In a relapse prevention study, patients responding to acute 12-week treatment with open-label Cymbalta 60 mg once daily were randomized to receive both Cymbalta 60 mg once daily and placebo for an additional period of 6 months. Cymbalta 60 mg once daily demonstrated statistically significant superiority compared to placebo (p = 0.004) in the main outcome, the prevention of depressive relapse, measured as time to relapse. The incidence of relapse during the 6-month double-blind follow-up period was 17% and 29% for duloxetine and placebo, respectively.
During a 52-week double-blind placebo-controlled treatment, patients with recurrent major depressive disorder treated with duloxetine had a significantly longer symptom-free time (p depressive symptoms (p
The effect of Cymbalta 60 mg once daily in elderly depressed patients (> 65 years) was specifically tested in a study showing a statistically significant difference in the reduction of HAM-D 17 score in patients treated with duloxetine compared to those with placebo. The tolerability of Cymbalta 60 mg once daily in elderly patients was comparable to that seen in younger adults. However, data on elderly patients treated with the maximum dose (120 mg daily) are limited and therefore Caution is recommended when treating this patient population.
Generalized anxiety disorder:
Cymbalta demonstrated statistically significant superiority over placebo in five out of five studies including 4 acute randomized, double-blind, placebo-controlled studies and one relapse prevention study in adult patients with generalized anxiety disorder.
Cymbalta demonstrated statistically significant superiority to placebo as measured by improvement in Hamilton Anxiety Scale (HAM-A) total score and Sheehan Disability Scale (SDS) global dysfunction score. Response and remission rates were also higher with Cymbalta than with placebo. Cymbalta showed comparable efficacy results to venlafaxine in terms of improvement in HAM-A total score.
In a relapse prevention study, patients who responded to acute treatment with open-label Cymbalta at 6 months were randomized to receive both Cymbalta and placebo for an additional 6 months. The use of Cymbalta 60 mg to 120 mg once daily demonstrated statistically significant superiority compared to placebo (p
Peripheral diabetic neuropathic pain:
The efficacy of Cymbalta as a treatment for diabetic neuropathic pain was established in 2 randomized, 12-week, double-blind, placebo-controlled, fixed-dose studies in adult patients (aged 22 to 88 years) suffering from pain. diabetic neuropathic for at least 6 months. Patients who met the diagnostic criteria for major depressive disorder were excluded from these studies. The primary clinical outcome was the mean weekly mean pain over 24 hours, measured on a Likert scale of 11 points in a daily diary compiled by patients.
In both studies, Cymbalta 60 mg once daily and 60 mg twice daily significantly reduced pain compared to placebo. In some patients the effect was evident in the first week of treatment. The difference in mean improvement between the two active treatment arms was not significant. Approximately 65% of patients treated with duloxetine, compared with 40% of those treated with placebo, recorded a reduction in referred pain of at least 30%. The values corresponding to a pain reduction of at least 50% were 50% and 26% respectively. The clinical response rates (pain improvement of 50% or greater) were analyzed based on whether or not the patient experienced somnolence during treatment. . Clinical response rates in patients who experienced somnolence were 60% with duloxetine and 30% with placebo. pain reduction of 30% within 60 days were unlikely to reach this level during further treatment.
In an open-label long-term uncontrolled study, the reduction in pain in patients who responded to the eighth week of acute treatment with Cymbalta 60 mg in a single daily dose was maintained over the next six months as measured by changes in the range. of the mean pain in the 24 hours of the BPI (Brief Pain Inventory) questionnaire.
Pediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with Cymbalta in all subsets of the pediatric population for the treatment of major depressive disorder, diabetic neuropathic pain and generalized anxiety disorder. See section 4.2 for information on pediatric use.
05.2 Pharmacokinetic properties
Duloxetine is administered as a single enantiomer. Duloxetine is extensively metabolised by oxidation enzyme systems (CYP1A2 and the polymorph CYP2D6), followed by those of conjugation. The pharmacokinetics of duloxetine demonstrate large subject-to-subject variability (generally 50-60%), partly due to gender, age, smoking status and CYP2D6 metabolite status.
Absorption: Duloxetine is well absorbed after oral administration with a Cmax occurring 6 hours post dose. The absolute oral bioavailability of duloxetine ranges from 32% to 80% (on average 50%). Food slows the time to reach peak concentration from 6 to 10 hours and marginally decreases the extent of absorption (approximately 1 hour). "11%). These variations have no clinical relevance.
Distribution: duloxetine is approximately 96% bound to human plasma proteins. Duloxetine binds to both albumin and alpha-1 acid glycoprotein. Protein binding is not affected by impaired renal or hepatic function.
Biotransformation: Duloxetine is extensively metabolised and the metabolites are eliminated mainly in the urine. Both cytochromes P450-2D6 and 1A2 catalyze the formation of the two major metabolites, 4-hydroxy glucuronide conjugate duloxetine and 5-hydroxy 6-methoxy conjugate sulphate duloxetine Based on studies in vitro, the circulating metabolites of duloxetine are considered pharmacologically inactive. The pharmacokinetics of duloxetine in patients who metabolize poorly with 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 an intravenous dose, the plasma clearance of duloxetine ranges from 22 l / h to 46 l / h (mean, 36 l Apparent plasma clearance of duloxetine ranges from 33 to 261 L / h (mean, 101 L / h) following an oral dose.
Particular populations
SexPharmacokinetic differences have been identified between males and females (apparent plasma clearance is approximately 50% lower in females). Based on the overlap in the variability of clearance, gender-related pharmacokinetic differences do not justify the recommendation to use a lower dose in female patients.
Age: Pharmacokinetic differences were found between younger and older women (≥ 65 years) (in the elderly, the AUC increases by approximately 25% and the half-life is approximately 25% longer), although the magnitude of these variations is not sufficient to justify dosage adjustments As a general recommendation, caution should be exercised in the treatment of elderly patients (see sections 4.2 and 4.4).
Alteration of renal function: Patients with end stage renal disease (ESRD) undergoing dialysis have 2-fold higher duloxetine Cmax and AUC values than healthy subjects. Pharmacokinetic data in patients with mild or moderate renal impairment of duloxetine are limited.
Abnormal liver function: Moderate liver disease (Child-Pugh class B) affects the pharmacokinetic properties of duloxetine. In patients with moderate liver disease, the apparent plasma clearance of duloxetine is 79% lower, the half-life apparent terminal is 2.3 times longer and the AUC is 3.7 times higher than in healthy subjects. The pharmacokinetics of duloxetine and its metabolites have not been studied in patients with mild or severe hepatic impairment.
Women while breastfeeding: The distribution of duloxetine was studied in 6 lactating women who had been postpartum for at least 12 weeks. Duloxetine was found in breast milk, and steady-state concentrations in breast milk were approximately ¼ of those in plasma. The amount of duloxetine in breast milk was approximately 7 mcg / day for a daily dosage of 40 mg twice daily. Breastfeeding had no influence on the pharmacokinetics of duloxetine.
05.3 Preclinical safety data
Duloxetine was not genotoxic in a series of standard tests and was not carcinogenic in rats. In rat carcinogenicity studies, multinucleated cells were observed in the liver in the absence of other histopathological changes. The underlying mechanism and clinical significance are unknown. Female mice receiving duloxetine for 2 years had an increased incidence of hepatocellular adenomas and carcinomas at only the highest dose (144 mg / kg / day), but these were considered secondary to induction of the hepatic microsomal system. The relevance of these mouse data to humans is unknown.Female rats treated with duloxetine (45 mg / kg / day) before and during mating and early pregnancy had a decrease in maternal food consumption and body weight, an interruption of the estrus cycle, a decrease indices of viability at birth and progeny survival and progeny growth retardation for systemic exposure levels believed to be at least equal to the maximum clinical exposure (AUC) levels. In an embryotoxicity study performed in rabbits, a higher incidence of cardiovascular and skeletal malformations was observed for systemic exposure levels below the maximum clinical exposure (AUC). In another study performed to test a higher dose of a different salt than duloxetine, no malformations were observed. In pre-natal and post-natal toxicity studies in rats, duloxetine induced adverse behavioral effects in offspring at systemic exposure levels below the maximum clinical exposure (AUC ).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Capsule contents:
Hypromellose
Hypromellose acetate succinate
Sucrose
Sugar granules
Talc
Titanium dioxide (E171)
Triethyl citrate
Capsule shell:
30 mg:
Jelly
Sodium lauryl sulfate
Titanium dioxide (E171)
Indigo carmine (E132)
Edible green ink
Edible green ink contains:
Synthetic black iron oxide (E172)
Synthetic yellow iron oxide (E172)
Propylene glycol
Shellac
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store in the original package to protect the medicine from moisture.
Do not store above 30 ° C.
06.5 Nature of the immediate packaging and contents of the package
Polyvinyl chloride (PVC), polyethylene (PE) and polychlorotrifluoroethylene (PCTFE) blister sealed with aluminum foil.
Cymbalta 30 mg is available in packs of 7, 28 and 98 capsules.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Eli Lilly Nederland BV, Grootslag 1-5, NL-3991 RA Houten, The Netherlands.
08.0 MARKETING AUTHORIZATION NUMBER
EU / 1/04/296/001
036683011
EU / 1/04/296/006
036683062
EU / 1/04/296/009
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 17 December 2004
Date of last renewal: June 24, 2009
