Active ingredients: Mirtazapine
Remeron 15 mg orodispersible tablets
Remeron 30 mg orodispersible tablets
Remeron 45 mg orodispersible tablets
Remeron package inserts are available for pack sizes: - Remeron 15 mg orodispersible tablets, Remeron 30 mg orodispersible tablets, Remeron 45 mg orodispersible tablets
- Remeron 15 mg / ml oral solution
Why is Remeron used? What is it for?
Remeron belongs to a group of medicines called antidepressants.
Remeron is used to treat depression disorders in adults.
Remeron will take 1 to 2 weeks before starting to work. After a period of 2 to 4 weeks you may start to feel better. You should see your doctor if you do not feel better or if you feel worse after a period of between 2 and 4 weeks. More information can be found in paragraph 3, under the heading "When can you expect to feel better".
Contraindications When Remeron should not be used
Do not take Remeron:
- if you are allergic to mirtazapine or any of the other ingredients of this medicine (listed in section 6). In this case, you must talk to your doctor as soon as possible before taking Remeron.
- if you are taking or have recently taken (within the last 2 weeks) medicines called monoamine oxidase (MAO-I) inhibitors.
Precautions for use What you need to know before taking Remeron
Talk to your doctor or pharmacist before taking Remeron.
Children and adolescents
Remeron should not normally be used in children and adolescents under 18 years of age as efficacy has not been demonstrated. In addition, it should be known that in patients under 18 years of age this class of drugs is associated at an increased risk of side effects, such as suicide attempt, suicidal thoughts and hostility (particularly aggression, hateful behavior and anger). However, a doctor may decide to prescribe Remeron to patients under the age of 18 if it is in their best interest . If your doctor has prescribed Remeron for a patient under the age of 18 and you want to know more about this, please speak to him directly. Tell your doctor if any of the symptoms described above develop or worsen in patients under 18. years of age on Remeron therapy. In addition, the effects on the long-term safety of Remeron in this age group in terms of growth, maturation and development cognitive and behavioral, have not yet been demonstrated.In addition, significant weight gain was seen more often during treatment with Remeron than in adults in this age group.
Thoughts of suicide and worsening of depression
If you are depressed, you can sometimes think about harming yourself or taking your own life. These thoughts may increase soon after starting treatment with antidepressants, as these medicines take time to work, usually about two weeks but sometimes longer.
You are more likely to think like this if:
- you have already thought in the past about taking your own life or harming yourself.
- if you are a young adult. Information from clinical trials has shown an increased risk of suicidal behavior in adults under the age of 25 with psychic illnesses receiving antidepressants.
→ If at any time you find yourself thinking about killing yourself or harming yourself, contact your doctor or go to a hospital immediately.
You may find it helpful to confide in a relative or friend who is suffering from depression and ask them to read this leaflet. You can ask them to tell you if they think your depression is getting worse, or if they are worried about changes in your behavior.
Take special care with Remeron too
- if you have or have suffered in the past from any of the conditions listed below.
→ If you have not already done so, tell your doctor about these conditions before taking Remeron.
- convulsions (epilepsy). If you start to have seizures or if the seizures become more frequent, stop taking Remeron and contact your doctor immediately;
- liver disease, including jaundice. If you experience jaundice, stop taking Remeron and contact your doctor immediately;
- kidney diseases;
- heart disease or low blood pressure;
- schizophrenia. If psychotic symptoms, such as paranoid thoughts, become more frequent or severe, contact your doctor immediately;
- manic depression (alternating periods of euphoria / hyperactivity and depressed mood). If you start feeling elated or overexcited, stop taking Remeron and contact your doctor immediately;
- diabetes (the dose of insulin or other anti-diabetic medicines may need to be adjusted);
- eye diseases, such as increased pressure in the eye (glaucoma);
- difficulty urinating, which can be caused by an enlarged prostate;
- some types of heart conditions which can change the rhythm of the heart, a recent heart attack, heart failure or taking certain medicines which can affect the heart's rhythm.
- If you get any signs of infection, such as unexplained high fever, sore throat and mouth ulcers.
→ Stop taking Remeron and contact your doctor immediately for a blood test.
In rare cases, these symptoms may be signs of a disturbance in the production of blood cells in the marrow. Although rare, these symptoms most commonly occur after 4-6 weeks of treatment.
- if you are elderly. You may be more sensitive to the side effects of antidepressants.
Interactions Which drugs or foods can change the effect of Remeron
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Do not take Remeron in combination with:
- monoamine oxidase inhibitors (MAO inhibitors). Also, do not take Remeron for 2 weeks after stopping the MAO inhibitors. Likewise, if you stop taking Remeron, do not take MAO inhibitors for the next two weeks. Examples of MAO inhibitors are moclobemide, tranylcypromine (both are antidepressants) and selegiline (used in Parkinson's disease).
Be careful when taking Remeron in combination with:
- antidepressants such as SSRIs, venlafaxine and L-tryptophan or triptans (used to treat "migraine), tramadol (for pain relief), linezolide (an antibiotic), lithium (used to treat some psychiatric conditions), methylene blue (used for treat high levels of methemoglobin in the blood) and preparations of St. John's wort - Hypericum Perforatum (a "medicinal herb for depression). Very rarely Remeron, alone or in combination with these medicines, can lead to the so-called serotonin syndrome. Some of the symptoms of this syndrome are: unexplained fever, sweating, increased heart rate, diarrhea, (uncontrollable) muscle twitching, tremor, overactive reflexes, restlessness, mood swings and loss of consciousness. If you experience any combination of these symptoms , speak to your doctor immediately.
- the antidepressant called nefazodone, which can increase the amount of Remeron in your blood. Tell your doctor if you are using this medicine as this may require a reduction in the dose of Remeron or, when the use of nefazodone is stopped, an increase in the dose of Remeron.
- medicines for anxiety or insomnia, such as benzodiazepines; medicines for schizophrenia, such as olanzapine; medicines for allergies, such as cetirizine; medicines for severe pain, such as morphine. In combination with these medicines, Remeron may increase the sleepiness caused by these medicines
- medicines to treat infections; medicines for bacterial infections (such as erythromycin), medicines to treat fungal infections (such as ketoconazole) and medicines to treat HIV / AIDS (such as HIV protease inhibitors) and medicines for stomach ulcer (such as cimetidine) These medicines, in combination with Remeron, can increase the amount of Remeron in your blood. Tell your doctor if you are using these medicines. It may be necessary to reduce the dose of Remeron or, when these medicines are stopped, to increase the dose of Remeron again.
- medicines for epilepsy, such as carbamazepine and phenytoin; medicines for tuberculosis, such as rifampicin. These medicines, in combination with Remeron, can decrease the amount of Remeron in your blood. Tell your doctor if you are using these medicines. It may need to be increased. the dose of Remeron or, when these medicines are stopped, decrease the dose of Remeron again.
- medicines that prevent blood clotting, such as warfarin.Remeron may increase the effects of warfarin on the blood. Tell your doctor if you are using this medicine. In case of a combination the doctor must monitor the blood closely.
- medicines that can affect the heart's rhythm such as some antibiotics and some antipsychotics.
Remeron with food and alcohol
You may get drowsy if you drink alcohol while you are taking Remeron.
It is advisable not to drink alcoholic beverages.
Remeron can be taken with or without food.
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.
Limited experience with the administration of Remeron to pregnant women does not indicate an increased risk. However, caution should be exercised when administering Remeron during pregnancy.
If you use Remeron until or immediately before delivery, the newborn baby should be carefully monitored for possible side effects.
When taken during pregnancy, similar medications (SSRIs) can increase the risk of a serious condition in babies, called persistent pulmonary hypertension of the newborn (PPHN), making the baby breathe faster and appear bluish. These symptoms usually occur during the first 24 hours after the baby is born.
If this happens to your baby, you should contact your midwife and / or doctor immediately.
Driving and using machines
Remeron can affect concentration or alertness. Make sure your abilities are not affected before driving or using machines. If your doctor has prescribed Remeron for a patient under the age of 18, make sure that concentration and alertness are not impaired before traveling on the street (e.g. by bicycle).
Remeron orodispersible tablets contain sugar spheres, containing sucrose.
Remeron orodispersible tablets contain sucrose-based sugar spheres.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Remeron orodispersible tablets contain aspartame, a source of phenylalanine.
Remeron orodispersible tablets contain aspartame, a source of phenylalanine. It can be harmful to people with phenylketonuria.
Dosage and method of use How to use Remeron: Dosage
Always take this medicine exactly as your doctor or pharmacist has told you.
If in doubt, consult your doctor or pharmacist.
How much Remeron to take
The recommended starting dose is 15 or 30 mg per day. Your doctor may advise you to increase the dose after a few days until you reach the right amount (between 15 and 45 mg per day). The dose is usually the same for all ages. However, your doctor may adjust the dose if you are elderly or if you have had kidney or liver disease.
When to take Remeron
→ Take Remeron at the same time each day.
It is best to take Remeron as a single dose before going to bed. In any case, your doctor may suggest that you split the dose of Remeron, once in the morning and once in the evening before going to bed. The higher dose should be taken before bedtime.
Take the orodispersible tablet as indicated below
Take the tablets orally.
Do not break the orodispersible tablet
To prevent rupture of the orodispersible tablet, do not press the tablet imprint on the blister (Figure A).
Remove a print from the tablet
Each blister contains 6 tablets (imprints), which are separated by perforated lines. Peel off a portion by tearing along the perforated lines (Figure 1).
Lift the cover sheet
Carefully lift the cover sheet, starting at the angle indicated by the arrow (Figures 2 and 3).
Take out the orodispersible tablet
The orodispersible tablet should be removed from its housing with dry hands and placed on the tongue (Figure 4).
It will disintegrate quickly and can be swallowed without water.
When you can expect to feel better
Remeron usually takes 1-2 weeks to start working and after 2-4 weeks you may notice an improvement.
It is important that you tell your doctor about the effects of Remeron in the first few weeks of treatment.
→ 2-4 weeks after you start taking Remeron, discuss the effects the medicine has had on you with your doctor.
If you still do not notice any improvement, your doctor may prescribe a higher dose. In this case, talk to your doctor again after another 2-4 weeks.
Remeron usually needs to be taken for 4-6 months after symptoms of depression disappear.
Overdose What to do if you have taken too much Remeron
If you take more Remeron than you should
If you or someone else has taken too much Remeron, call your doctor right away The most likely signs of an overdose of Remeron (without other medicines or alcohol) are sleepiness, disorientation and increased heart rate. Symptoms of a possible overdose may include changes in heart rhythm (fast, irregular heartbeat) and / or fainting which could be symptoms of a life-threatening condition known as torsades de pointes.
If you forget to take Remeron
If you need to take your dose once a day
- Do not take a double dose to make up for a forgotten dose. Take the next dose at the usual time.
If you have to take the dose twice a day
- if you forget your morning dose, simply take this dose together with your evening dose.
- if you forget your evening dose, you should not take it together with the next morning dose; skip the dose and continue as normal with the morning and evening dose.
- if you have forgotten to take both doses, you should not try to make up for the missed dose. Skip both doses and continue the next day as normal with the morning and evening dose.
If you stop taking Remeron
→ You can only stop taking Remeron after consulting your doctor.
If you stop taking it too soon, your depression may return. When you feel better, talk to your doctor. Your doctor will decide when to stop treatment.
Do not suddenly stop taking Remeron, even if your depression is gone. If you suddenly stop taking Remeron you may feel sick, dizzy, agitated or anxious and have a headache. These symptoms can be avoided by stopping the treatment gradually. Your doctor will tell you how to decrease the dose gradually.
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 Remeron
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the following serious side effects, stop taking mirtazapine and tell your doctor immediately.
Uncommon (may affect up to 1 in 100 people)
- euphoria or emotional arousal (mania).
Rare (may affect up to 1 in 1,000 people)
- yellowing of the eyes or skin; this may indicate disturbances in liver function (jaundice).
Not known (frequency of which cannot be estimated from the available data)
- signs of infection such as a sudden and unexplained high fever, sore throat and ulceration in the mouth (agranulocytosis). In rare cases, mirtazapine can cause disturbances in the production of blood cells (bone marrow depression). Some people become less resistant to the infections because mirtazapine can cause a temporary shortage of white blood cells (granulocytopenia). In rare cases, mirtazapine can also cause a shortage of red and white blood cells, and platelets (aplastic anemia), a shortage of blood platelets (thrombocytopenia) or an increase in the number of white blood cells (eosinophilia).
- seizures (convulsions).
- a combination of symptoms such as unexplained fever, sweating, increased heart rate, diarrhea, (uncontrollable) muscle twitching, tremor, overactive reflexes, agitation, mood swings, loss of consciousness and increased salivation. Very rarely these may be symptoms of serotonin syndrome
- thinking about harming yourself or taking your own life
- severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
Other possible side effects with mirtazapine are:
Very common (may affect more than 1 in 10 people)
- increased appetite and body weight
- drowsiness or sleepiness
- headache
- dry mouth
Common (may affect up to 1 in 10 people)
- lethargy
- dizziness
- tremors
- nausea
- diarrhea
- He retched
- constipation
- rash or rash (exanthema)
- pain in the joints (arthralgia) or muscles (myalgia)
- backache
- feeling dizzy or faint when standing up suddenly (orthostatic hypotension)
- swelling (usually in the ankles and feet) caused by water retention (edema)
- tiredness
- vivid dreams
- confusion
- anxiety
- sleep problems
Uncommon (may affect up to 1 in 100 people)
- abnormal sensations on the skin, eg. burning, tingling, itching or tingling (paraesthesia)
- restless legs
- fainting (syncope)
- feeling of falling asleep in the mouth (oral hypoesthesia)
- low blood pressure
- nightmares
- agitation
- hallucinations
- need to move
Rare (may affect up to 1 in 1,000 people)
- muscle contraction (myoclonus)
- aggression
- abdominal pain and nausea; this may indicate "inflammation of the pancreas (pancreatitis)
Not known (frequency cannot be estimated from the available data)
- abnormal sensation in the mouth (oral paraesthesia)
- swelling in the mouth (mouth edema)
- swelling throughout the body (generalized edema)
- localized swelling
- hyponatremia
- inappropriate secretion of antidiuretic hormone
- severe skin reactions (bullous dermatitis, erythema multiforme)
- walking at night (sleepwalking)
- speech disorder
Additional side effects in children and adolescents
In children under 18 years of age, the following side effects were commonly observed in clinical studies: significant weight gain, hives and increased blood triglycerides.
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 at: www.agenziafarmaco.gov.it/it/responsabili. 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 and blister. The expiry date refers to the last day of that month.
Store in the original package to protect from light and moisture.
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 Remeron contains
- The active ingredient is mirtazapine.
Remeron 15 mg orodispersible tablets contain 15 mg of mirtazapine per orodispersible tablet.
Remeron 30 mg orodispersible tablets contain 30 mg of mirtazapine per orodispersible tablet.
Remeron 45 mg orodispersible tablets contain 45 mg of mirtazapine per orodispersible tablet.
- The other ingredients are sugar spheres, hypromellose, povidone K30, magnesium stearate, butyl methacrylate basic copolymer, aspartame (E951), anhydrous citric acid, crospovidone (type A), mannitol (E421), microcrystalline cellulose, natural and artificial orange flavor (No. SN027512) and sodium bicarbonate.
What Remeron looks like and contents of the pack
Remeron are orodispersible tablets.
Remeron 15 mg orodispersible tablets are round, white, standard bevelled edge tablets, marked "TZ1" on one side.
Remeron 30 mg orodispersible tablets are standard round, white, bevelled edge tablets marked "TZ3" on one side.
Remeron 45 mg orodispersible tablets are round, white, standard bevelled edge tablets, marked "TZ4" on one side.
The orodispersible tablets are packaged in child-resistant blister packs with perforated unit doses.
The following pack sizes of Remeron 15, 30 and 45 mg orodispersible tablets are available: 6, 18, 30, 48, 90, 96 and 180 orodispersible tablets (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
REMERON ORODISPERSIBLE TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each Remeron 15 mg orodispersible tablet contains 15 mg of mirtazapine.
Each Remeron 30 mg orodispersible tablet contains 30 mg of mirtazapine.
Each Remeron 45 mg orodispersible tablet contains 45 mg of mirtazapine.
Excipent (s) with known effects:
Each Remeron 15 mg orodispersible tablet contains 4.65 mg of aspartame and 28 mg of sucrose.
Each Remeron 30 mg orodispersible tablet contains 9.3 mg of aspartame and 56 mg of sucrose.
Each Remeron 45 mg orodispersible tablet contains 13.95 mg of aspartame and 84 mg of sucrose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Orodispersible tablet.
15 mg orodispersible tablet:
round, white tablet with standard bevelled edge, marked on one side by the code "TZ1".
30 mg orodispersible tablet:
round, white tablet with standard bevelled edge, marked on one side by the code "TZ2".
45 mg orodispersible tablet:
round, white tablet with standard bevelled edge, marked on one side by the code "TZ4".
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Remeron is indicated for the treatment of major depressive episodes in adults.
04.2 Posology and method of administration
Dosage
Adults
The effective daily dose is usually between 15 and 45 mg; the starting dose is 15 or 30 mg.
Mirtazapine usually begins to work after 1-2 weeks of treatment. Treatment with an adequate dose should result in a positive response within 2-4 weeks. In case of insufficient response, the dose can be increased up to the maximum dose. If no response is observed within a further 2-4 weeks, treatment should be discontinued.
Patients with depression should be treated for a sufficient period of at least 6 months to ensure they are symptom-free.
It is recommended that mirtazapine treatment be discontinued gradually to avoid withdrawal symptoms (see section 4.4).
Older people
The recommended dose is the same as for adults. In elderly patients a dose increase should be made under close supervision to induce a satisfactory and safe response.
Renal impairment
The clearance of mirtazapine may be reduced in patients with moderate to severe renal impairment (creatinine clearance
Hepatic impairment
The clearance of mirtazapine may be reduced in patients with hepatic impairment. This should be considered when prescribing Remeron to this category of patients, particularly in the presence of severe hepatic impairment, as patients with severe hepatic impairment were not studied (see section 4.4).
Pediatric population
Remeron should not be used in children and adolescents below 18 years of age as efficacy has not been demonstrated in two short-term clinical studies (see section 5.1) and for safety reasons (see sections 4.4, 4.8 and 5.1). ).
Method of administration
Mirtazapine has an elimination half-life of 20-40 hours and therefore Remeron is suitable for once daily administration. The single dose should preferably be taken in the evening before bedtime. Remeron can also be administered in divided doses (one in the morning and one in the morning). one in the evening, the larger dose should be taken in the evening).
The tablets must be taken orally. The tablet breaks down quickly and can be swallowed without water.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Concomitant use of mirtazapine and monoamine oxidase (MAO) inhibitors (see section 4.5).
04.4 Special warnings and appropriate precautions for use
Pediatric population
Remeron should not be used to treat children and adolescents under 18 years of age. In clinical trials, suicidal behaviors (suicide attempts and suicidal ideation) and hostility (essentially aggression, hostile behavior and anger) were observed more frequently in children and adolescents treated with antidepressants than in those treated with placebo. If, based on medical needs, it is decided to carry out the treatment anyway, the patient should be carefully monitored to rule out the appearance of suicidal symptoms. In addition, long-term safety data for children and adolescents with regard to growth, maturation and cognitive and behavioral development are not available.
Suicide / suicidal thoughts or clinical worsening
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 followed closely until improvement. According to general clinical experience, the risk of suicide may increase in the early stages of recovery.
Patients with a history of suicide-related events, or those with a significant degree of suicidal thoughts prior to initiation of treatment, are known to be at increased risk for suicidal thoughts or suicide attempts and should be followed closely during treatment. -analysis of placebo-controlled clinical trials conducted on the use of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behavior with antidepressants compared to placebo in patients younger than 25 years.
Antidepressant therapy should be accompanied by "careful supervision of patients, particularly those at high risk, especially early in treatment and following dose changes. Patients (and caregivers) should be informed about the need to monitor for any clinical worsening, suicidal behaviors or thoughts, and unusual changes in behavior and to seek medical advice immediately if these symptoms occur.
Regarding the possibility of suicide, particularly at the start of treatment, only the smallest amount of Remeron orodispersible tablets should be given to the patient in accordance with good patient management, in order to reduce the risk of overdose.
Medullary depression
Bone marrow depression, usually manifesting as granulocytopenia or agranulocytosis, has been reported during treatment with Remeron. Reversible agranulocytosis has been reported rarely in clinical trials with Remeron. Rare cases of agranulocytosis, mostly reversible, but fatal in some cases, have been reported with Remeron post-marketing. Fatal cases mostly involved patients over 65 years of age. The doctor should pay attention to symptoms such as fever, sore throat, stomatitis or other signs of infection; when these occur, treatment should be stopped and a complete blood count should be performed.
Jaundice
If jaundice occurs, treatment should be discontinued.
Conditions that require control
Patients with:
- epilepsy and organic brain syndrome. Although clinical experience shows that seizures are rare during treatment with mirtazapine, as well as with other antidepressants, Remeron should be used with caution in patients with a history of seizures. Treatment should be discontinued in patients who experience seizures. or when there is an increase in the frequency of seizures.
- Hepatic impairment: Following administration of a single 15 mg oral dose of mirtazapine, the clearance of mirtazapine was reduced by approximately 35% in patients with mild to moderate hepatic impairment compared to patients with normal hepatic function. The mean plasma concentration of mirtazapine was increased by approximately 55%.
- renal impairment: after administration of a single 15 mg oral dose of mirtazapine, in patients with moderate renal impairment (mean plasma creatinine clearance of mirtazapine was increased by approximately 55 and 115% respectively. patients with mild renal impairment (creatinine clearance
- heart diseases such as conduction defects, angina pectoris, recent myocardial infarction. In these cases, normal precautions should be taken and concomitant medication should be implemented with caution.
- hypotension.
- diabetes mellitus: in patients with diabetes, antidepressants can alter glycemic control. The dosage of insulin and / or oral hypoglycaemics may need to be adjusted and close monitoring is recommended.
As with other antidepressants, the following circumstances should be taken into account:
- Worsening of psychotic symptoms can occur when antidepressants are given to patients with schizophrenia or other psychotic disorders; paranoid thoughts can intensify.
- When dealing with the depressive phase of bipolar disorder, the transition to the manic phase can occur. Patients with a history of mania / hypomania should be closely monitored. Mirtazapine should be discontinued in all patients entering the manic phase.
- Although Remeron is not addictive, post-marketing experience shows that abrupt discontinuation of dosing after a long period of treatment can sometimes lead to withdrawal symptoms. Most withdrawal reactions are mild and self-limiting. Among others Withdrawal symptoms reported, the most frequent being dizziness, agitation, anxiety, headache and nausea. Although reported as withdrawal symptoms, these symptoms may be related to the underlying disease. As advised in section 4.2, it is recommended that treatment be discontinued with mirtazapine gradually.
- Caution should be observed in patients with urination disorders such as prostatic hypertrophy and in patients with acute narrow-angle glaucoma and ocular hypertension (although the possibility of problems with Remeron is low, as it has very weak anticholinergic activity ).
- Akathisia / psychomotor restlessness: The use of antidepressants has been associated with the development of akathisia, characterized by a subjectively unpleasant or stressful restlessness and need to move often accompanied by an inability to sit or stand still. This most likely occurs in the very first few weeks of Treatment In patients who develop these symptoms, increasing the dose may be harmful.
- Cases of QT prolongation, torsades de pointes, ventricular tachycardia and sudden death have been reported during post-marketing use of mirtazapine. Most reports have occurred in association with overdose or in patients with other risk factors. for QT prolongation, including concomitant use of QTc prolonging medicinal products (see section 4.5 and section 4.9). Caution should be exercised when prescribing Remeron in patients with known cardiovascular disease or family history of QT prolongation and who are concomitantly using other medicinal products believed to prolong the QTc interval.
Hyponatremia
Hyponatremia, possibly due to inappropriate antidiuretic hormone (SIADH) secretion, has been reported very rarely with the use of mirtazapine.
Caution should be exercised in patients at risk such as elderly patients or patients concomitantly treated with medicinal products known to cause hyponatremia.
Serotonin syndrome
Interaction with serotonergic active substances: Serotonin syndrome may arise when selective serotonin reuptake inhibitors (SSRIs) are administered concomitantly with other serotonergic drugs (see section 4.5). Symptoms of serotonin syndrome can be hyperthermia, rigidity, myoclonus, autonomic instability and possible rapid fluctuations in vital signs, changes in mental status including confusion, irritability and extreme agitation that progresses to delirium and coma. Caution and closer clinical monitoring is recommended when these active substances are administered in combination with mirtazapine. Treatment with mirtazapine should be discontinued upon the occurrence of these events and supportive symptomatic treatment initiated. From post-marketing experience, it appears that serotonin syndrome occurs very rarely in patients treated with Remeron alone (see section 4.8).
Older people
Older people are often more sensitive, especially to the side effects of antidepressants. During clinical trials with Remeron, no more frequent undesirable effects were reported in the elderly than in patients in other age groups.
Sucrose
Remeron contains sucrose-based sugar balls. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Aspartame
Remeron contains aspartame, a source of phenylalanine. Each tablet of 15 mg, 30 mg and 45 mg of mirtazapine corresponds to 2.6 mg, 5.2 mg and 7.8 mg of phenylalanine, respectively. It can be harmful to patients with phenylketonuria.
04.5 Interactions with other medicinal products and other forms of interaction
Pharmacodynamic interactions
- Mirtazapine should not be administered concomitantly with MAO inhibitors or during the two weeks following discontinuation of MAO inhibitor therapy. Conversely, approximately two weeks should elapse before patients treated with mirtazapine should be treated with MAO inhibitors (see section 4.3).
In addition, as with SSRIs, concomitant administration of other serotonergic active substances (L-tryptophan, triptans, tramadol, linezolide, methylene blue, SSRIs, venlafaxine, lithium and St. John's wort preparations - Hypericum perforatum) may result in an "incidence of serotonin-associated effects (serotonin syndrome: see section 4.4).
Caution should be advised and close clinical monitoring required when these active substances are administered in combination with mirtazapine.
- Mirtazapine may increase the sedative properties of benzodiazepines and other sedatives (particularly most antipsychotics, antihistamine H1 antagonists, opioids). Care should be taken if these medicines are prescribed together with mirtazapine.
- Mirtazapine may increase the depressing effects of alcohol on the central nervous system. Therefore, patients should be advised to avoid alcoholic beverages while taking mirtazapine.
- Mirtazapine, at a dose of 30 mg once daily, causes a slight but statistically significant increase in the international normalized ratio (INR) in subjects treated with warfarin. Since a more pronounced effect cannot be excluded at higher doses of mirtazapine, monitoring of the INR is advisable in case of concomitant treatment with warfarin and mirtazapine.
- The risk of QT prolongation and / or ventricular arrhythmias (eg torsades de pointes) may be increased with concomitant use of medications that prolong the QTc interval (eg some antipsychotics and some antibiotics).
Pharmacokinetic interactions
- CYP3A4 inducers carbamazepine and phenytoin increased the clearance of mirtazapine approximately twice, resulting in a 45% and 60% decrease in mean mirtazapine plasma concentration, respectively. When carbamazepine or any other inducer of hepatic metabolism (such as rifampicin) is added to mirtazapine therapy, the mirtazapine dose may need to be increased. If treatment with such a medicine is stopped, the dose of mirtazapine may need to be reduced.
- Concomitant administration of the potent CYP3A4 inhibitor ketoconazole increased the peak plasma and area under the curve (AUC) levels of mirtazapine by approximately 40 and 50%, respectively.
- When cimetidine (weak inhibitor of CYP1A2, CYP2D6 and CYP3A4) is co-administered with mirtazapine, the mean plasma concentration of mirtazapine may increase by more than 50%. Caution should be exercised and the dose may need to be reduced when mirtazapine is co-administered with potent CYP3A4 inhibitors, HIV protease inhibitors, azole antifungals, erythromycin, cimetidine or nefazodone.
- Interaction studies did not reveal any relevant pharmacokinetic effects associated with concomitant treatment of mirtazapine with paroxetine, amitriptyline, risperidone or lithium.
Pediatric population
Interaction studies have only been performed in adults.
04.6 Pregnancy and lactation
Pregnancy
Limited data from the use of mirtazapine in pregnant women do not indicate an increased risk of congenital malformations.
Studies in animals did not reveal any teratogenic effects of clinical relevance, however developmental toxicity was observed (see section 5.3).
Epidemiological data indicate that the use of SSRIs in pregnancy, particularly late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). Although there are no studies that have investigated an association of PPHN with treatment with mirtazapine, this potential risk cannot be ignored, taking into account its mechanism of action (increased serotonin concentrations).
Care should be taken when prescribing mirtazapine to pregnant women. If Remeron is used until delivery or shortly before delivery, postnatal monitoring of the neonate is recommended for possible withdrawal effects.
Feeding time
Animal studies and limited human data have shown that mirtazapine is excreted in breast milk only in small amounts. The decision to continue / discontinue breastfeeding or to continue / discontinue Remeron therapy should be based on evaluation the benefit of breastfeeding for the baby and the benefit of Remeron therapy for the woman.
Fertility
Non-clinical reproductive toxicity studies in animals showed no effect on fertility.
04.7 Effects on ability to drive and use machines
Remeron has minor or moderate influence on the ability to drive or use machines. Remeron can impair concentration and alertness (particularly in the initial stages of treatment). Patients should avoid potentially dangerous jobs that require alertness and concentration, such as driving a motor vehicle or operating machinery, if they experience these effects.
04.8 Undesirable effects
Depressed patients exhibit a number of symptoms that are due to the disease itself. It is therefore sometimes difficult to ascertain which symptoms are an expression of the disease itself and which are the result of treatment with Remeron.
The most commonly reported side effects, which occurred in more than 5% of patients treated with Remeron in the randomized, placebo-controlled trials (see below) are sleepiness, sedation, dry mouth, weight gain, increased appetite, dizziness. and fatigue.
The undesirable effects of Remeron have been evaluated in all randomized placebo-controlled studies in patients (including those with indications other than major depression). The meta-analysis included 20 studies, with a planned treatment duration of up to 12 weeks, with 1,501 patients (134 person years) treated with mirtazapine doses up to 60 mg and 850 patients (79 person years) treated with placebo. The extension phases of these studies were excluded to maintain comparability with placebo treatment.
Table 1 shows the incidence by category of undesirable effects that occurred statistically significantly more frequently in clinical trials during treatment with Remeron than with placebo, and in addition to undesirable effects reported spontaneously. of side effects from spontaneous reporting is based on the reporting rate of these events in clinical trials. The frequency of spontaneous reporting side effects for which no cases were observed with mirtazapine in randomized placebo-controlled trials was classified as "not Note".
Table 1. Undesirable effects of Remeron
1 In clinical trials, these events occurred statistically significantly more frequently during treatment with Remeron than during treatment with placebo.
2 In clinical trials, these events occurred with a greater frequency, but not statistically significant, during treatment with Remeron compared to treatment with placebo.
3 In clinical trials, these events occurred statistically significantly more frequently during treatment with Remeron than during treatment with placebo.
4 N.B. dose reduction generally does not lead to less somnolence / sedation, but may compromise antidepressant efficacy.
5 Treatment with antidepressants can usually lead to the onset or worsening of anxiety and insomnia (which may be symptoms of depression). Development or worsening of anxiety and insomnia have been reported during treatment with mirtazapine.
6 Cases of suicidal ideation and suicidal behaviors have been reported during mirtazapine therapy or early after treatment discontinuation (see section 4.4).
Transient elevations in transaminases and gamma-glutamyltransferase were observed in laboratory analyzes conducted in clinical trials (however, associated adverse events were not reported with a statistically significant frequency with Remeron compared to placebo).
Pediatric population
The following undesirable effects were commonly observed in clinical trials in children: weight gain, urticaria and hypertriglyceridaemia (see also section 5.1).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address: www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Current experience with overdose with Remeron alone indicates that symptoms are usually mild. Central nervous system depression with disorientation and prolonged sedation have been reported, along with tachycardia and mild hyper- or hypotension. However, there is a possibility of hypotension. more severe outcomes (including death) at higher doses than the therapeutic dose, especially with mixed overdoses, QT prolongation and torsades de pointes have also been reported in these cases.
Cases of overdose should be treated with appropriate symptomatic and life support therapy. ECG monitoring should be performed. Administration of activated charcoal or gastric lavage should also be considered.
Pediatric population
Appropriate actions, as described for adults, should be taken in the event of overdose in pediatric patients.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: other antidepressants.
ATC code: N06AX11.
Mechanism of action / pharmacodynamic effects
Mirtazapine is a centrally active presynaptic a2-antagonist, capable of inducing an increase in central noradrenergic and serotonergic neurotransmission. The increase in serotonergic neurotransmission is specifically mediated by the 5-HT1 receptors, as the 5-HT2 and 5-HT3 receptors are blocked by mirtazapine. It is assumed that both enantiomers of mirtazapine contribute to antidepressant activity by blocking the S enantiomer ( +) the a2 and 5-HT2 receptors and the R (-) enantiomer the 5-HT3 receptors.
Clinical efficacy and safety
The antagonistic activity of mirtazapine towards H1-histaminergic receptors is associated with its sedative properties. Mirtazapine is almost devoid of anticholinergic activity and, at therapeutic doses, has only limited effects (eg orthostatic hypotension) on the cardiovascular system.
Pediatric population
Two randomized, double-blind, placebo-controlled clinical trials in children aged 7-18 years with major depressive disorder (n = 259) who used a flexible dose for the first 4 weeks (15-45 mg of mirtazapine) followed by a fixed dose (15, 30 or 45 mg mirtazapine) for an additional 4 weeks failed to demonstrate significant differences between mirtazapine and placebo for primary and secondary endpoints. Significant weight gain (≥ 7%) was observed in 48.8% of subjects treated with Remeron compared with 5.7% of subjects treated with placebo. Urticaria (11.8% vs 6.8%) and hypertriglyceridemia (2.9% vs 0%) were also commonly observed.
05.2 Pharmacokinetic properties
Absorption
After oral administration of Remeron, the active substance mirtazapine is well and rapidly absorbed (bioavailability ≈ 50%), peak plasma levels are reached after approximately two hours. Food intake does not affect the pharmacokinetics of mirtazapine.
Distribution
The plasma protein binding of mirtazapine is approximately 85%.
Biotransformation
Biotransformation occurs essentially by demethylation and oxidation, followed by conjugation. Data in vitro on human liver microsomes indicate that the cytochrome P450, CYP2D6 and CYP1A2 enzymes are involved in the formation of the 8-hydroxy metabolite of mirtazapine, while CYP3A4 is considered to be responsible for the formation of the N-demethyl and N-oxide metabolites. The demethylated metabolite is pharmacologically active and appears to have the same pharmacokinetic profile as the parent compound.
Elimination
Mirtazapine is extensively metabolised and eliminated via the urine and faeces within a few days. The mean elimination half-life is 20-40 hours; longer half-lives, up to 65 hours, have occasionally been recorded, and shorter half-lives have been observed in young people. The elimination half-life is sufficient to warrant treatment with one dose. only daily. The steady state is reached after 3-4 days, after which there is no further accumulation.
Linearity / Non-linearity
Mirtazapine exhibits linear pharmacokinetics over the recommended dose range.
Special populations
The clearance of mirtazapine may be reduced in patients with renal or hepatic impairment.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive and developmental toxicity.
No teratogenic effects were observed in reproductive toxicity studies in rats and rabbits. At a systemic exposure equal to twice the maximum therapeutic exposure for humans, there was an increase in post-implantation abortion, a reduction in pup weight at birth and a reduction in pup survival during the first three. days of breastfeeding.
In a series of gene mutation tests for chromosomal DNA damage, mirtazapine was not genotoxic. Thyroid tumors found in a rat carcinogenicity study and hepatocellular neoplasms found in a mouse carcinogenicity study are considered species-specific and non-genotoxic responses associated with long-term treatment with high doses of hepatic enzyme inducers.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Sugar balls;
hypromellose;
povidone K30;
magnesium stereate;
basic butyl methacrylate copolymer;
aspartame (E951);
anhydrous citric acid;
crospovidone (type A);
mannitol (E421);
microcrystalline cellulose;
natural and artificial orange flavoring (N ° SN027512);
sodium bicarbonate.
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 from light and moisture.
06.5 Nature of the immediate packaging and contents of the package
Rigid, child-resistant blister, to be opened by lifting one side, consisting of a laminated aluminum foil and plastic film sealed to a laminated aluminum foil based on paper, coated with heat-sealed lacquer.
Plastic films contain: PVC (polyvinyl chloride), polyamide and polyester.
The blisters each contain 6 orodispersible tablets. The following pack sizes are available for each strength: 6 (1x6), 18 (3x6), 30 (5x6), 48 (8x6), 90 (15x6) and 96 (16x6) and 180 (10x18 (3x6)) orodispersible tablets.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
N.V. Organon
Kloosterstraat 6
5349 AB Obs
Netherlands
Representative in Italy:
MSD Italia S.r.l.
Via Vitorchiano, 151
00189 Rome
08.0 MARKETING AUTHORIZATION NUMBER
6 orodispersible tablets of 15 mg: AIC N. 029444116
18 orodispersible tablets of 15 mg: AIC N. 029444128
30 orodispersible tablets of 15 mg: AIC N. 029444130
48 orodispersible tablets of 15 mg: AIC N. 029444142
96 orodispersible tablets of 15 mg: AIC N. 029444155
6 orodispersible tablets of 30 mg: AIC N. 029444167
18 orodispersible tablets of 30 mg: AIC N. 029444179
30 orodispersible tablets of 30 mg: AIC N. 029444181
48 orodispersible tablets of 30 mg: AIC N. 029444193
96 orodispersible tablets of 30 mg: AIC N. 029444205
6 orodispersible tablets of 45 mg: AIC N. 029444217
18 orodispersible tablets of 45 mg: AIC N. 029444229
30 orodispersible tablets of 45 mg: AIC N. 029444231
48 orodispersible tablets of 45 mg: AIC N. 029444243
96 orodispersible tablets of 45 mg: AIC N. 029444256
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 23 September 2003
Date of last renewal: February 2013
10.0 DATE OF REVISION OF THE TEXT
April 2015
