Active ingredients: Olanzapine
Olanzapine Apotex 2.5 mg film-coated tablets
Olanzapine 5 mg film-coated tablets
Olanzapine DOC Generici 7.5 mg film-coated tablets
OLANZAPINE DOC Generici 10 mg film-coated tablets
Olanzapine Apotex 15 mg film-coated tablets
Olanzapine 20 mg film-coated tablets
Why is Olanzapine used - Generic Drug? What is it for?
Olanzapine is part of a group of medicines called antipsychotics and is used to treat the following conditions:
- schizophrenia, a disease with symptoms such as hearing, seeing or feeling things that are not there, misconceptions, unwarranted suspiciousness, and social withdrawal. People with this disease may also feel depressed, anxious or tense.
- moderate to severe manic episode, a condition characterized by symptoms of arousal or euphoria
Olanzapine has been shown to prevent these symptoms from recurring in patients with bipolar disorder whose episode of mania has responded to treatment with olanzapine.
Contraindications When Olanzapine - Generic Drug should not be used
Do not take Olanzapine
- if you are allergic (hypersensitive) to olanzapine or any of the other ingredients of this medicine (listed in section 6). An allergic reaction can manifest itself as a rash, itching, swelling of the face, swelling of the lips, shortness of breath. If this has happened to you, please report it to your doctor.
- if you have previously been diagnosed with an eye problem such as certain types of glaucoma (increased pressure in the eye).
Precautions for use What you need to know before taking Olanzapine - Generic Drug
Talk to your doctor or pharmacist before taking Olanzapine.
- The use of Olanzapine in elderly patients with dementia is not recommended as it may cause serious side effects.
- Medicines of this type can cause unusual movements especially of the face and tongue. If this happens after you have been given Olanzapine, please tell your doctor.
- Very rarely, medicines of this type cause a 'combination of fever, faster breathing, sweating, muscle stiffness and drowsiness or sleepiness. If this happens, see your doctor right away.
- Weight gain has been observed in patients taking Olanzapine. You and your doctor need to monitor your weight regularly.
- High blood sugar and fat levels (triglycerides and cholesterol) have been observed in patients taking Olanzapine.Your doctor should order blood tests to check the sugars and certain fat values in the blood before you start taking Olanzapine and regularly during treatment.
- Tell your doctor if you or someone else in your family have had a previous blood clot formation, as medicines like this have been associated with the formation of blood clots.
If you have any of the following conditions, tell your doctor as soon as possible:
- Stroke or transient ischemic attack (transient stroke symptoms) (TIA)
- Parkinson's disease
- Prostate problems
- Intestinal blockage (paralytic ileus)
- Diseases of the liver or kidneys
- Diseases of the blood
- Heart disease
- Diabetes
- Convulsions
If you have dementia, you or your caregiver should tell your doctor if you have had a stroke or transient ischemic attack in the past.
As a routine precaution, if you are over the age of 65, get your blood pressure checked by your doctor periodically
Children and adolescents
Olanzapine is not indicated for patients under 18 years of age.
Interactions Which drugs or foods can modify the effect of Olanzapine - Generic Drug
Only take other medicines during treatment with Olanzapine if your doctor tells you that you can.
You may feel sleepy if Olanzapine is taken in combination with antidepressants or medicines taken for anxiety or to help you sleep (tranquilizers).
Tell your doctor if you are taking, have recently taken or might take any other medicines.
In particular, tell your doctor if you are taking:
- Parkinson's disease medicines.
- carbamazepine (an anti-epileptic and mood stabilizer), fluvoxamine (an antidepressant), or ciprofloxacin (an antibiotic) - your dose of Olanzapine may need to be adjusted.
OLANZAPINE DOC Generics and alcohol
Do not drink any type of alcohol during treatment with Olanzapine as taking Olanzapine and alcohol at the same time can make you drowsy.
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 for advice before taking this medicine. You should not take this medicine while breastfeeding, as small amounts of Olanzapine Accord may pass into breast milk.
The following symptoms may occur in newborn babies of mothers who have used Olanzapine in the last trimester (last three months of their pregnancy): shaking, muscle stiffness and / or weakness, sleepiness, agitation, breathing problems and difficulty in feeding. your child has any of these symptoms you may need to contact your doctor.
Driving and using machines
There is a risk of drowsiness when taking Olanzapine. If this happens do not drive or operate any tools or machines. Tell your doctor.
OLANZAPINE DOC Generici contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
OLANZAPINE DOC Generici contains soy lecithin.
If you are allergic to peanuts or soya, do not take this medicine.
Dose, Method and Time of Administration How to use Olanzapine - Generic Drug: Posology
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
Your doctor will tell you how many Olanzapine tablets to take and how long to continue taking them. The dose of OLANZAPINE DOC Generici to be taken varies from 5 to 20 mg per day. If your symptoms reappear, talk to your doctor but do not stop taking Olanzapine Unless your doctor tells you to.
You should take your Olanzapine tablets once a day, following your doctor's instructions. Try to take the tablets at the same time each day. It doesn't matter if you take them on a full stomach or on an empty stomach. Olanzapine Coated Tablets are for oral use. Swallow your Olanzapine tablets whole with water.
Overdose What to do if you have taken an overdose of Olanzapine - Generic Drug
If you take more Olanzapine than you should
Patients who took more Olanzapine than they should have experienced the following symptoms: rapid heart rate, agitation / aggression, speech problems, unusual movements (especially of the face or tongue) and a reduced level of consciousness . Other symptoms may be: acute confusion, seizures (epilepsy), coma, a combination of fever, faster breathing, sweating, muscle stiffness, drowsiness or sleepiness, slowed breathing rate, decreased cough reflex, high or low blood pressure, changes heart rhythm. Contact your doctor or hospital immediately if you get any of the above symptoms. Show your doctor your pack of tablets.
If you forget to take Olanzapine
Take the tablets as soon as you remember. Do not take a double dose in one day.
If you stop taking Olanzapine
Do not stop taking the tablets as soon as you start to feel better. It is important that you continue taking Olanzapine for as long as your doctor feels it is necessary
If you suddenly stop taking Olanzapine, symptoms such as sweating, unable to sleep, tremor, anxiety or nausea and vomiting may occur. Your doctor may advise you to gradually reduce the dose before stopping treatment.
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 Olanzapine - Generic Drug
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor immediately if you get:
- unusual movements (a common side effect that may affect up to 1 in 10 people) mainly of the face or tongue;
- blood clots in the veins (an uncommon side effect that may affect up to 1 in 100 people), especially in the lower limbs (symptoms include swelling, pain and redness of the leg), which can circulate through blood vessels to the lungs causing the appearance of chest pain and difficulty in breathing. If you experience any of these symptoms, consult a doctor immediately;
- an "association of fever, faster breathing, sweating, muscle stiffness and confusion or sleepiness (the frequency of this side effect cannot be estimated from the available data).
Very common side effects (may affect more than 1 in 10 patients) include weight gain; drowsiness; increased levels of prolactin in the blood. In the early stages of treatment, some people may feel dizzy or faint (with a slow heart rate), especially when getting up from a lying or sitting position. These effects usually subside spontaneously, but if they don't, tell your doctor.
Common side effects (may affect up to 1 in 10 people) include changes in the levels of some blood cells, circulating fats and temporary increases in liver enzymes in the early stages of treatment; increases in the level of sugar in the blood and urine; increases in blood uric acid and creatine phosphokinase levels; feeling of increased hunger; dizziness; restlessness; tremor; unusual movements (dyskinesias); constipation; dry mouth; rash; loss of strength; extreme fatigue; water retention leading to swelling of the hands, ankles or feet; fever; joint pain and sexual dysfunction, such as decreased libido in males and females or erectile dysfunction in males.
Uncommon side effects (may affect up to 1 in 100 people) include hypersensitivity (eg swelling of the mouth and throat, itching, rash); diabetes or worsening of diabetes, occasionally associated with ketoacidosis (presence of ketone bodies in the blood and urine) or coma; seizures, usually associated with a history of seizures (epilepsy); muscle stiffness or spasms (including movement of the "eye); speech problems; slow heart rate; sensitivity to sunlight; nose bleeding; abdominal bloating; memory loss or forgetfulness; urinary incontinence; lack of the ability to urinate; hair loss; absence or reduction of menstrual cycles; and breast changes in males and females, such as abnormal growth or milk secretion.
Rare side effects (may affect up to 1 in 1,000 people) include a decrease in body temperature; changes in the rhythm of the heart; sudden unjustified death; inflammation of the pancreas causing severe stomach pain, fever and malaise; liver disease manifesting as yellowing of the skin and whites of the eyes; muscle disease presenting as unexplained tenderness and pain and prolonged and / or painful erection. Elderly patients with dementia may experience stroke, pneumonia, urinary incontinence, falls, extreme tiredness, visual hallucinations, a rise in body temperature, redness of the skin, walking disturbances during treatment with olanzapine. Some fatal cases have been reported in this particular patient group.
In patients with Parkinson's disease, Olanzapine Accord may worsen symptoms.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
Undesirable effects can also be reported directly through the national reporting system at the address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
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 package.
OLANZAPINE DOC Generici must be stored in its original packaging to keep it away from light and humidity.
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.
What OLANZAPINE DOC Generici contains
- The active ingredient is olanzapine. Each Olanzapine tablets contains 2.5 mg or 5 mg or 7.5 mg or 10 mg or 15 mg or 20 mg of the active ingredient. The exact quantity is indicated on the package of OLANZAPINE DOC Generici.
- The other components are
- (tablet core) anhydrous lactose, microcrystalline cellulose, crospovidone, magnesium stearate and
- (coating) polyvinyl alcohol, titanium dioxide (E171), talc, soy lecithin (E322) and xanthan gum (E415).
- In addition, the different concentrations of Olanzapine DOC Generici also contain the following excipients:
TABLET DOSAGE: OTHER EXCIPIENTS:
OLANZAPINE DOC Generici 15mg indigo carmine red film-coated tablet (E132)
OLANZAPINE DOC Generici 20mg film-coated tablet red iron oxide (E172)
What Olanzapine DOC Generici looks like and contents of the pack
2.5 mg film-coated tablet: Round, biconvex, white tablet with a diameter of 6 mm, debossed with "O" on one side.
5 mg film-coated tablet: Round, biconvex, white tablet with a diameter of 8 mm, debossed with "O1" on one side.
7.5 mg film-coated tablet: round, biconvex, white tablet with a diameter of 9 mm, debossed with "O2" on one side.
10 mg film-coated tablet: round, biconvex, white tablet with a diameter of 10 mm, debossed with "O3" on one side.
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
OLANZAPINA DOC GENERICI TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One film-coated tablet contains 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg or 20 mg olanzapine.
Excipients with known effects:
The 2.5 mg coated tablet contains 58.3 mg of anhydrous lactose and 0.064 mg of soy lecithin (E322).
The 5 mg coated tablet contains 116.6 mg of anhydrous lactose and 0.128 mg of soy lecithin (E322).
The 7.5 mg coated tablet contains 174.9 mg of anhydrous lactose and 0.192 mg of soy lecithin (E322).
The 10 mg coated tablet contains 233.2 mg of anhydrous lactose and 0.256 mg of soy lecithin (E322).
The 15 mg coated tablet contains 228.2 mg of anhydrous lactose and 0.256 mg of soy lecithin (E322).
The 20 mg coated tablet contains 304.3 mg anhydrous lactose 0.342 mg soy lecithin (E322).
For the full list of excipients see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablet.
2.5 mg film-coated tablet:
Round, white, biconvex film-coated tablet, 6 mm in diameter, marked "O" on one side.
5 mg film-coated tablet:
Round, white, biconvex film-coated tablet, 8 mm in diameter, marked "O1" on one side.
7.5 mg film-coated tablet:
Round, white, biconvex film-coated tablet 9 mm in diameter, marked "O2" on one side.
10 mg film-coated tablet:
Round, white, biconvex film-coated tablet, 10 mm in diameter, marked "O3" on one side.
15 mg film-coated tablet:
Oval, biconvex, light blue film-coated tablet, 7.35 x 13.35 in diameter, marked "O" on one side.
20 mg film-coated tablet:
Light pink, oval, biconvex, film-coated tablet, 7.5 x 14.5 mm in diameter, marked "O" on one side.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Adults
Olanzapine is indicated for the treatment of schizophrenia.
In patients who have demonstrated a positive response to initial treatment, continued olanzapine therapy allows clinical improvement to be maintained.
Olanzapine is indicated for the treatment of moderate to severe manic episode.
In patients whose manic episode has responded to olanzapine treatment, olanzapine is indicated for the prevention of new disease episodes in patients with bipolar disorder (see section 5.1).
04.2 Posology and method of administration
Adults
Schizophrenia: The recommended starting dose of olanzapine is 10 mg / day.
Episode of mania: The starting dosage is 15 mg to be administered as a single daily dose as monotherapy or 10 mg / day in combination therapy (see section 5.1).
Prevention of new disease episodes in bipolar disorder: The recommended starting dosage is 10 mg / day. In patients receiving olanzapine for the treatment of manic episode, continue therapy at the same dosage for prevention of new episodes of illness. If a new depressive, manic, or mixed episode occurs, olanzapine treatment should be continued ( optimizing the dose as needed), with additional therapy to treat mood disorders, as clinically indicated.
During the treatment of schizophrenia, the episode of mania and the prevention of new episodes of illness in bipolar disorder, according to the clinical condition of the patient the daily dosage can subsequently be adjusted within a range of 5-20 mg. a dose higher than the initially recommended dosage is recommended only after an adequate period of clinical observation and should generally take place at intervals of not less than 24 hours.Olanzapine can be given without regard for meals as absorption is not affected by food. Gradual dose reduction should be considered when discontinuing olanzapine.
Pediatric population
The use of olanzapine is not recommended in children and adolescents below 18 years of age due to a lack of safety and efficacy data. A greater magnitude of increase has been reported in short-term studies in adolescent patients. weight, lipid and prolactin alterations compared to studies in adult patients (see sections 4.4, 4.8, 5.1 and 5.2).
Elderly patients
Generally, a lower starting dose (5 mg / day) is not required, although dose reduction should be considered in patients 65 years of age and older when clinical situations advise (see also section 4.4). .
Patients with renal and / or hepatic insufficiency
A lower starting dose (5 mg) should be considered in these patients. In moderate hepatic insufficiency (Child-Pugh class A or B cirrhosis), the starting dose is 5 mg and any dose increase should be made with caution.
Dose variations related to the patient's sex
There is usually no need to make any changes to the starting dose and dose range for female versus male patients.
Smokers
Usually, there is no need to make changes to the starting dose and dosage range in smokers relative to non-smokers.
When there are multiple factors capable of slowing the metabolism (female patients, elderly, non-smokers), the possibility of decreasing the starting dose should be considered. Dosage increases when necessary should be done with caution in these patients (see sections 4.5 and 5.2).
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Patients at known risk of narrow-angle glaucoma.
04.4 Special warnings and appropriate precautions for use
During antipsychotic treatment, improvement in the patient's clinical condition may take several days to several weeks. During this period, patients should be closely monitored.
Psychosis and / or dementia-related behavioral disturbances
Olanzapine is not licensed for the treatment of dementia-related psychosis and / or behavioral disorders and is not recommended for this particular patient group due to an increased mortality and risk of cerebrovascular adverse events (ACV). In placebo-controlled clinical trials (6-12 weeks duration) in elderly patients (mean age 78 years) with dementia-related psychotic symptoms and / or behavioral disturbances, there was a two-fold increase in the incidence of deaths. among olanzapine-treated patients versus placebo-treated patients (3.5% vs. 1.5%, respectively). The highest incidence of death was not associated with olanzapine dose (mean daily dose of 4.4 mg) or duration of treatment. Risk factors that may predispose this patient population to increased mortality include age over 65, dysphagia, sedation, malnutrition and dehydration, lung disease (eg pneumonia including aspiration) or "concomitant use of benzodiazepines. However, the incidence of death was higher in olanzapine-treated patients than in placebo-treated patients regardless of these risk factors.
In the same clinical studies, cerebrovascular adverse events (EACV, e.g. stroke, transient ischemic attack (TIA)), some of them fatal, were reported. A 3-fold increase in EACV was found in olanzapine-treated patients compared to placebo-treated patients (1.3% and 0.4%, respectively). All olanzapine and placebo treated patients who presented EACV had pre-existing risk factors. Age over 75 years and vascular / mixed dementia were identified as risk factors for ACV on olanzapine treatment. The efficacy of olanzapine was not established in these studies.
Parkinson's disease
The use of olanzapine in the treatment of dopamine agonist-induced psychosis is not recommended in patients with Parkinson's disease. During clinical trials, worsening of parkinsonian symptoms and hallucinations were reported more commonly and more frequently with olanzapine than with placebo. (see section 4.8), furthermore olanzapine was no more effective than placebo in the treatment of psychotic symptoms. In these studies, patients were required to be initially stable on the lowest effective dose of anti-Parkinson drugs (dopamine agonists) and that this anti-Parkinson treatment remained the same for drugs and dosages used throughout the duration. of study. Olanzapine was initially administered at doses of 2.5 mg / day with dose escalation up to a maximum of 15 mg / day based on the physician's judgment.
Neuroleptic Malignant Syndrome (NMS)
NMS is a potentially life-threatening condition associated with antipsychotic treatment. Rare cases reported as NMS have also been reported with the use of olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and autonomic nervous system instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmia) Additional manifestations may include increased creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure If a patient has signs and symptoms suggestive of NMS, or has unexplained high fever without other clinical manifestations of NMS, all medicines antipsychotics, including olanzapine, should be discontinued.
Hyperglycemia and diabetes
Hyperglycaemia and / or development or exacerbation of diabetes occasionally associated with ketoacidosis or coma has been reported uncommonly, including some fatal cases (see section 4.8). Some cases have been described in which a previous increase in body mass could be a predisposing factor. Appropriate clinical monitoring is suggested in accordance with guidelines used for antipsychotics, such as blood glucose measurement at baseline, 12 weeks after starting olanzapine treatment and annually thereafter. Patients treated with any antipsychotic, including olanzapine, should be monitored for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and weakness) and patients with diabetes mellitus and risk factors for diabetes mellitus should be monitored regularly for worsening glycemic control. Weight should be monitored regularly, eg at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and every three months thereafter.
Alterations of lipids
Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-controlled clinical trials (see section 4.8). Lipid changes should be treated as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipid-induced diseases. Patients treated with any antipsychotic, including olanzapine, should be monitored regularly for lipid values in accordance with the guidelines used for antipsychotics, eg at baseline, 12 weeks after starting olanzapine treatment and every 5 weeks thereafter. years.
Anticholinergic activity
Although olanzapine demonstrated anticholinergic activity in vitro, experience during clinical trials revealed a low incidence of related effects. However, in view of the lack of clinical experience with olanzapine in patients with concomitant diseases, caution is advised when prescribing patients. with prostatic hypertrophy, paralytic ileus and related pathologies.
Hepatic function
Transient and asymptomatic elevations of hepatic aminotransferases, alanine transferase (ALT) and aspartate transferase (AST) have frequently been observed, especially in the initial stages of treatment. Caution and periodic monitoring are advised in patients with elevated ALT and / or AST, in patients with signs and symptoms of hepatic insufficiency, in patients with pre-existing situations associated with limited hepatic functional reserve, as well as in cases of concomitant treatment with potentially hepatotoxic medicinal products. . In cases where a diagnosis of hepatitis (defined as hepatocellular injury, cholestatic, or both) has been made, olanzapine treatment should be discontinued.
Neutropenia
Caution is advised in patients with leukopenia and / or neutropenia of any origin, in patients taking medicinal products known to cause neutropenia, in patients with a history of iatrogenic myelotoxicity / myelosuppression, in patients with myelosuppression due to concomitant disease, radiotherapy or chemotherapy and finally in patients with hypereosinophilia situations or with myeloproliferative disease. Neutropenia has been reported frequently when olanzapine and valproate are co-administered (see section 4.8).
Discontinuation of treatment
When olanzapine is stopped abruptly, sweating, insomnia, tremor, anxiety, nausea or vomiting have been reported rarely (≥ 0.01%).
QT interval
In clinical studies, clinically significant prolongations of the corrected QT interval (Fridericia corrected QT interval [QTcF] ≥ 500 milliseconds [msec] at any time after baseline measurement in patients with baseline QTcF elderly in olanzapine treated patients , in patients with congenital long QT syndrome, congestive heart failure, cardiac hypertrophy, hypokalemia or hypomagnesaemia.
Thromboembolism
Uncommonly (≥0.1% and venous thromboembolism. A causal relationship between the occurrence of venous thromboembolism and treatment with olanzapine has not been established. However, since patients with schizophrenia often present with acquired risk factors for venous thromboembolism ( VTE), all possible risk factors for VTE such as patient immobilization must be identified and preventive measures taken.
General Central Nervous System (CNS) Activity
Due to the primary CNS effects of olanzapine, caution is recommended when the medicinal product is taken concomitantly with alcohol and other centrally acting medicinal products. As olanzapine is shown to have dopamine antagonist activity in vitro, this medicinal product may antagonize the effects of direct and indirect dopamine agonists.
Convulsions
Olanzapine should be used with caution in patients with a history of seizures or who are subject to factors that may lower the seizure threshold. Seizures were not commonly seen in these patients treated with olanzapine. In the majority of these cases, the seizures or risk factors for the onset of epilepsy were described in the history.
Tardive dyskinesia
In comparative studies lasting one year or less, olanzapine treatment resulted in a statistically significant "lower incidence of treatment-induced tardive dyskinesias. However, the risk of tardive dyskinesia increases with long-term treatment; therefore, if signs or symptoms of tardive dyskinesia occur in a patient receiving olanzapine, a reduction in dosage or discontinuation of the medicinal product should be considered.These symptoms may temporarily worsen or even arise after discontinuation of treatment.
Postural hypotension
Postural hypotension has sometimes been observed in clinical trials with olanzapine in elderly patients. As with other antipsychotics, it is recommended that blood pressure be checked periodically in patients over 65 years of age.
Sudden cardiac death
The event of sudden cardiac death was reported in postmarketing reports in olanzapine treated patients. In a retrospective observational cohort study, patients treated with olanzapine had an estimated 2-fold risk of presumed sudden cardiac death in patients treated with olanzapine. in treatment with antipsychotics. In the study, the risk with olanzapine was comparable to the risk assessed in an "analysis that pooled atypical antipsychotics.
Pediatric population
The use of olanzapine is not indicated in the treatment of children and adolescents. Studies in patients aged 13 to 17 years have shown the appearance of various adverse reactions, including weight gain, changes in metabolic parameters and increases in blood levels. prolactin The long-term outcomes associated with these events have not been studied and remain unknown (see sections 4.8 and 5.1).
Lactose
Olanzapine tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this drug.
Soy lecithin
Olanzapine tablets contain soy lecithin. This drug should not be used by patients who are hypersensitive to peanuts or soy.
04.5 Interactions with other medicinal products and other forms of interaction
Pediatric population
Interaction studies have only been performed in adults.
Potential interactions involving olanzapine
Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this isoenzyme may affect the pharmacokinetics of olanzapine.
Induction of CYP1A2
The metabolism of olanzapine can be accelerated by smoking and carbamazepine, which can lead to decreased olanzapine concentrations. Only a mild to moderate increase in olanzapine clearance was observed. Clinical consequences are likely to be limited, but clinical monitoring is recommended and an increase in olanzapine dosage may be considered if necessary (see section 4.2).
CYP1A2 inhibition
Fluvoxamine, a specific inhibitor of CYP1A2 activity, has been shown to significantly inhibit the metabolism of olanzapine. After administration of fluvoxamine the mean increase in olanzapine Cmax was 54% in non-smoking females and 77% in males. smokers, while the mean increase in olanzapine AUC was 52% in non-smoking females and 108% in smoking males, respectively. In patients who are using fluvoxamine or any other CYP1A2 inhibitor, as well as ciprofloxacin, olanzapine treatment should start at lower doses. If treatment with a CYP1A2 inhibitor is initiated, a dose reduction of olanzapine should be considered.
Decreased bioavailability
Activated charcoal reduces the bioavailability of oral olanzapine by 50-60% and should be taken at least 2 hours before or after olanzapine.
Fluoxetine (a CYP2D6 inhibitor), single doses of an antacid (aluminum, magnesium) or cimetidine do not significantly affect the pharmacokinetics of olanzapine.
Potential for olanzapine to affect other medicines
Olanzapine can oppose the effects of direct and indirect dopamine agonists.
Olanzapine does not inhibit the major CYP450 isoenzymes (e.g. 1A2, 2D6, 2C9, 2C19, 3A4) in vitro. Therefore no particular interaction is to be expected as verified by in vivo studies in which no inhibition of the metabolism of the following active substances was found: tricyclic antidepressant (mostly representing the CYP2D6 pathway), warfarin (CYP2C9), theophylline (CYP1A2 ) or diazepam (CYP3A4 and 2C19).
Olanzapine showed no drug interaction when administered concomitantly with lithium or biperidene.
Therapeutic monitoring of valproate plasma levels did not indicate that an adjustment of the valproate dose is required after co-administration with olanzapine.
General CNS activity
Caution should be exercised in patients who consume alcohol or receive medicinal products that can cause CNS depression.
In patients with Parkinson's disease and dementia the concomitant use of olanzapine with anti-Parkinson medicinal products is not recommended (see section 4.4).
QT interval
Caution should be exercised if olanzapine is administered concomitantly with medicinal products known to cause an increase in the QT interval (see section 4.4).
04.6 Pregnancy and lactation
Pregnancy
There are no adequate and well-controlled studies in pregnant women. Patients should be advised of the need to inform their physician in the event of an existing or planned pregnancy while being treated with olanzapine. However, as experience in humans is limited, olanzapine should only be used in pregnancy if the potential benefit justifies a potential risk to the fetus.
Neonates exposed to antipsychotics (including olanzapine) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and / or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of restlessness, hypertonia, hypotonia, tremor, somnolence, difficulty breathing, or eating disorders.Consequently, infants need to be monitored closely.
Feeding time
In a study in healthy breastfeeding women, olanzapine was excreted in breast milk. At the steady statethe mean infant exposure (in mg / kg) was estimated to be 1.8% of the maternal dose of olanzapine (in mg / kg). Patients should be advised not to breastfeed while on olanzapine therapy.
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed. Since olanzapine may cause somnolence and dizziness, patients should be advised that caution should be exercised when operating machinery, including motor vehicles.
04.8 Undesirable effects
Adults
In clinical trials the most frequently reported adverse reactions associated with the use of olanzapine (observed in ≥ 1% of patients) were somnolence, weight gain, eosinophilia, increased prolactin, cholesterol, glucose and triglyceride levels. (see section 4.4), glycosuria, increased appetite, dizziness, akathisia, parkinsonism, leukopenia, neutropenia (see section 4.4), dyskinesia, orthostatic hypotension, anticholinergic effects, transient and asymptomatic increases in hepatic aminotransferases (see section 4.4), rash skin, asthenia, fatigue, fever, arthralgia, increased alkaline phosphatase, elevated gamma glutamyltransferase, uric acid, creatine phosphokinase and edema.
Table of adverse reactions
The following table lists the adverse reactions and laboratory tests observed following spontaneous reports and during clinical trials. For each frequency group, adverse reactions are reported in order of decreasing severity. The listed frequency parameters are defined as follows: very common (≥ 1/10), common (≥ 1/100,
1 Clinically significant weight gain was observed in all Body Mass Index (BMI) categories present at baseline. After short-term treatment (mean duration 47 days), an increase in body weight ≥ 7% from baseline was very common (22.2%), an increase in body weight ≥ 15% from baseline was common (4.2 %) and ≥ 25% body weight gain from baseline was uncommon (0.8%). With long-term exposure (at least 48 weeks), patients whose body weight had increased by ≥ 7%, ≥ 15% and ≥ 25% from baseline were very common (64.4%, 31.7% and 12.3%, respectively). %).
2 Mean increases in fasting lipid values (total cholesterol, LDL cholesterol and triglycerides) were greater in those patients who did not show evidence of lipid changes at baseline.
3 Observed for fasting normal values at baseline (borderline fasting cholesterol at baseline (≥ 5.17 -
4 Observed for fasting normal values at baseline (borderline fasting blood glucose at baseline (≥ 5.56 -
5 Observed for normal fasting values at baseline (
6 In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not statistically significantly different from placebo. Olanzapine-treated patients had a lower "incidence" Parkinsonism, akathisia and dystonia compared to patients treated with fractional doses of haloperidol. In the absence of detailed anamnestic information regarding the presence of acute and late movement disorders of an extrapyramidal nature, it is not currently possible to conclude that olanzapine causes a minor occurrence of tardive dyskinesia and / or other late onset extrapyramidal syndromes.
7 Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine was stopped abruptly.
8 In clinical studies of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of the normal range in approximately 30% of olanzapine-treated patients who had normal baseline prolactin values. In most of these patients the increases were generally mild, and remained 2 times below the upper limit of the normal range.
9 Adverse event identified in clinical trials in the Integrated Database for olanzapine.
10 Established based on values measured in clinical trials in the Integrated Database for olanzapine.
11 Adverse event identified in post-marketing spontaneous reports and with frequency determined using the Olanzapine Integrated Database.
12 Adverse event identified in post-marketing spontaneous reporting and with frequency estimated at the upper 95% confidence interval using the Olanzapine Integrated Database.
Long-term exposure (at least 48 weeks)
The percentage of patients who had clinically significant adverse changes in weight, glucose, total cholesterol / LDL / HDL or triglyceride gain increased over time. In adult patients who completed 9-12 months of therapy, the percentage increase average blood glucose decreased after about 6 months.
Additional information on particular categories of populations
In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher incidence of death and cerebrovascular adverse reactions than placebo (see section 4.4). In this group of patients, very common adverse reactions associated with the use of olanzapine were walking disturbances and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and urinary incontinence were commonly observed.
In clinical trials of patients with iatrogenic psychosis (dopamine agonists) associated with Parkinson's disease, worsening of parkinsonian symptoms and hallucinations were reported very commonly and more frequently than with placebo.
In a clinical study in patients with bipolar mania, combination therapy of valproate and olanzapine resulted in an "incidence of neutropenia of 4.1%; elevated plasma levels of valproate could be a potential contributing factor. Olanzapine given with lithium or valproate has resulted in an increased incidence (≥ 10%) of tremor, dry mouth, increased appetite and weight gain. Speech disturbance has also been reported frequently. During treatment with olanzapine in combination with lithium or valproate, in case of acute treatment (up to 6 weeks) there was a ≥ 7% increase in starting body weight in 17.4% of patients. In patients with bipolar disorder, long-term treatment with olanzapine (up to 12 months) for prevention of new disease episodes was associated with a ≥ 7% increase in baseline body weight in 39.9% of patients.
Pediatric population
Olanzapine is not indicated for the treatment of children and adolescents under 18 years of age. Although no clinical studies designed to compare adolescents with adults have been performed, the data obtained from studies in adolescent subjects were compared with those obtained from adult studies.
The following table summarizes the adverse reactions reported with a higher frequency in adolescent patients (aged 13-17 years) than in adult patients or adverse reactions reported only during short-term clinical trials in adolescent patients. Clinically significant weight gain (≥ 7%) appears to occur more commonly in the adolescent population than in adults for similar exposures. The magnitude of weight gain and the percentage of adolescent patients who had clinically significant weight gain were greater in long-term exposure (at least 24 weeks) than in short-term exposure.
For each frequency group, adverse reactions are reported in order of decreasing severity. The listed frequency parameters are defined as follows: very common (≥ 1/10), common (≥ 1/100,
13 After short-term treatment (mean duration of 22 days), an increase in body weight (kg) ≥ 7% from baseline was very common (40.6%), an increase in body weight ≥ 15% from baseline baseline was common (7.1%) and ≥ 25% body weight gain from baseline was common (2.5%). With long-term exposure (at least 24 weeks), body weight from baseline increased by ≥ 7% in 89.4% of patients, by ≥ 15% in 55.3% of patients and of a value ≥ 25% in 29.1% of patients.
14 Observed for normal fasting values at baseline (
15 Changes in total fasting cholesterol levels from normal to baseline (total fasting cholesterol levels from borderline to baseline (≥ 4.39 mmol / L -
16 Elevated prolactin levels were reported in 47.4% of adolescent patients.
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 https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
Signs and symptoms
Very frequent symptoms of overdose (with incidence> 10%) include tachycardia, agitation / aggression, dysarthria, extrapyramidal manifestations of various types and a reduction in the level of consciousness ranging from sedation to coma.
Other clinically important sequelae of overdose include delirium, convulsion, coma, possible neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, cardiac arrhythmias (
Treatment
There is no specific antidote for olanzapine. Induction of vomiting is not recommended. Standard procedures for the management of overdose may be indicated (eg gastric lavage, administration of activated charcoal). Concomitant administration of activated charcoal reduces the oral bioavailability of olanzapine by 50-60% .
Based on the clinical picture, symptomatic treatment and monitoring of vital functions should be performed, including treatment of hypotension and circulatory collapse and maintenance of respiratory function. Do not use adrenaline, dopamine, or other sympathomimetic agents with beta-agonist activity. since stimulation of beta receptors can cause a worsening of the hypotensive state. Cardiovascular activity should be monitored to recognize any arrhythmias. Monitoring and careful medical surveillance must continue until the patient is cured.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: diazepines, oxazepines and thiazepines.
ATC code: N05A H03.
Pharmacodynamic effects
Olanzapine is an antipsychotic, antimanic and mood stabilizing agent with a broad pharmacological profile on numerous receptor systems.
In pre-clinical studies olanzapine has been shown to possess an affinity spectrum (Ki serotonin 5-HT2A / 2C, 5-HT3, 5-HT6; dopamine D1, D2, D3, D4, D5; for muscarinic-type cholinergic receptors M1-M5; for those α1 adrenergic and H1 histamines. Animal behavioral studies with olanzapine indicated serotonergic, dopaminergic and cholinergic antagonism, which confirms the receptor affinity profile described above. Olanzapine showed greater affinity in vitro and increased activity in models in vivo for 5-HT2 serotonergic receptors compared to D2 dopaminergic receptors. Electrophysiological studies have shown that olanzapine selectively reduces the activity of mesolimbic dopaminergic neurons (A10), while having little effect on the striatal circuits (A9 neurons) involved in motor function. Olanzapine reduced the response in conditioned avoidance behavior (predictive test of " antipsychotic activity) at doses lower than those capable of inducing catalepsy (predictive test of motor side effects). Unlike other antipsychotic agents, olanzapine increases response in an "anxiolytic" test.
In a PET (Positron Emission Tomography) study conducted in healthy volunteers with single oral doses (10 mg), olanzapine demonstrated a higher degree of affinity for 5HT2A receptors than for dopamine D2 receptors. In addition, a single photon emission computed tomography (SPECT) study conducted in schizophrenic patients showed that patients who respond to olanzapine exhibit lesser degree of striatal D2 receptor blockade than patients who respond to some other antipsychotics and risperidone, and comparable to that of patients responding to clozapine.
Clinical efficacy
In controlled clinical trials, 2 versus placebo and 2 versus an active comparator conducted in over 2,900 schizophrenic patients who presented with both positive and negative symptoms, olanzapine was statistically superior in improving both positive and negative symptoms.
In a double-blind, international comparative study of schizophrenia, schizoaffective manifestations and related disorders, which included 1,481 patients with associated depressive symptoms of varying severity (with mean score of 16.6 detected at the start of the study according to the for Montgomery-Asberg depression), a "secondary prospective analysis of the change in mood score between the start and end of the study showed a statistically significant improvement (p = 0.001) obtained with olanzapine (-6.0). compared to that observed with haloperidol (-3.1).
In patients with mania or a mixed episode of bipolar disorder, olanzapine demonstrated superior efficacy to both placebo and valproate in reducing symptoms of mania for more than 3 weeks. Olanzapine also demonstrated comparable efficacy results to haloperidol in terms of ratio of patients who achieved symptomatic remission of mania and depression after 6 and 12 weeks.In a combination therapy study in patients treated with lithium or valproate for a minimum of 2 weeks, the addition of 10 mg olanzapine (combination therapy with lithium or valproate) was superior in reducing the symptoms of mania after 6 weeks. compared to lithium or valproate monotherapy.
In a 12-month re-disease prevention study in manic episode patients who achieved remission on olanzapine and who were then randomized to olanzapine or placebo, olanzapine demonstrated statistically significant superiority over placebo at the primary endpoint. useful for the evaluation of new bipolar episodes Olanzapine also demonstrated a statistically significant advantage over placebo in terms of onset of both new manic episode and new depressive episode.
In a second 12-month study on the prevention of re-episodes of disease in manic episode patients who achieved remission on a combination of olanzapine and lithium and were subsequently randomized to olanzapine or lithium alone, olanzapine was statistically unsatisfactory. lower than lithium at the primary endpoint useful for evaluating new bipolar episodes (olanzapine 30.0%, lithium 38.3%; p = 0.055).
In an 18-month study in manic or mixed episode patients stabilized with a combination therapy of olanzapine and a mood stabilizer (lithium or valproate), long-term combination therapy of olanzapine and lithium or valproate was not superior in statistically significant to lithium or valproate monotherapy in delaying the onset of new bipolar episodes, defined on the basis of diagnostic criteria.
Pediatric population
Experience in adolescents (aged 13-17 years) is limited to short-term efficacy data in schizophrenia (6 weeks) and mania associated with bipolar I disorder (3 weeks), involving less than 200 adolescents. Olanzapine was used in flexible dosing, starting with 2.5 mg / day and increasing to 20 mg / day. During treatment with olanzapine, adolescents gained significantly more weight than adults. changes in total fasting cholesterol, LDL cholesterol, triglyceride and prolactin levels had been greater in adolescents than in adults. There are no data on maintenance of effect and long-term safety data are limited (see sections 4.4 and 4.8).
05.2 "Pharmacokinetic properties
Absorption
Olanzapine is well absorbed after oral administration, reaching peak plasma concentrations within 5-8 hours. Absorption is not affected by food intake.
The absolute bioavailability following intravenous administration has not been determined.
Distribution
At serum concentrations ranging from 7 to 1,000 ng / ml, olanzapine is 93% bound to plasma proteins, mainly albumin and α1 acid glycoprotein.
Biotransformation
Olanzapine is metabolised in the liver mainly through conjugation and oxidation processes. The major circulating metabolite is 10-N-glucuronide, which does not cross the blood-brain barrier. Cytochromes P450-CYP1A2 and P450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl metabolites, both of which demonstrate lower in vivo pharmacological activity than olanzapine in animal studies. unmetabolized olanzapine molecule.
Elimination
After oral administration, the mean elimination half-life of olanzapine in healthy volunteers varies with age and gender.
The mean half-life in elderly healthy volunteers (65 years and over) is increased (51.8 hours compared to 33.8 hours) and clearance reduced (17.5 vs 18.2 l / hour) compared to non-elderly subjects. The range of variability of the kinetic parameters in the elderly is similar to that found in the non-elderly. In 44 schizophrenic patients over 65 years of age, daily doses of 5 to 20 mg did not cause any particular adverse reaction profile.
The mean half-life in females is somewhat prolonged compared to males (36.7 versus 32.3 hours) and clearance is reduced (18.9 versus 27.3 l / h). Nevertheless olanzapine (5-20 mg) demonstrated the same safety profile in female (n = 467) and male (n = 869) patients.
Renal impairment
In patients with renal impairment (urine creatinine clearance, mainly in metabolised form.
Smokers
In smokers with mild hepatic impairment, the mean half-life is increased (39.3 hours) and drug clearance reduced (18.0 l / hour), similar to that found in healthy non-smokers (48.8 hours, respectively). and 14.1 l / hour).
In non-smokers, compared to smokers (males and females), the mean half-life is increased (38.6 versus 30.4 hours) and clearance reduced (18.6 versus 27.7 l / hour).
Plasma clearance of olanzapine appears to be lower in elderly than in young people, in female subjects than in males, and in non-smokers than in smokers. However, the influence of factors such as age, sex or smoking on the clearance and plasma half-life of olanzapine is minimal compared to the range of variability found in the population.
In a study of Caucasian, Japanese and Chinese subjects, no differences in pharmacokinetic parameters were found between the three populations.
Pediatric population
Adolescents (13-17 years of age): The pharmacokinetic profile of olanzapine is similar in adolescents and adults. In clinical studies, the mean olanzapine exposure period was approximately 27% higher in adolescents. Demographic differences between adolescents and adults include lower average body weight and fewer adolescents were smokers. These factors likely contribute to a higher average exposure period observed in adolescents.
05.3 Preclinical safety data
Acute toxicity (single dose)
In rodents, signs of toxicity after oral administration were those typical of substances with high neuroleptic activity: hypoactivity, coma, tremors, clonic convulsions, salivation, decreased weight gain. The mean lethal dose observed in mice and rats was approximately 210 mg / kg and 175 mg / kg, respectively. In dogs, single oral doses up to 100 mg / kg were not fatal; clinical manifestations such as sedation, ataxia, tremors, increased heart rate were observed , difficulty breathing, miosis and anorexia In monkeys, single oral doses up to 100 mg / kg resulted in prostration and, with higher doses, in a state of semi-unconsciousness.
Repeated dose toxicity
In studies lasting up to 3 months in mice and up to 1 year in rats and dogs, the main effects observed were central nervous system depression, anticholinergic manifestations and peripheral haematological disorders. Tolerance has developed towards the depressive effects on the central nervous system. At high doses, growth parameters were decreased. Reversible effects, related to an increase in prolactin in rats, led to a decrease in the weight of the uterus and ovaries and morphological alterations of the vaginal epithelium and mammary gland.
Hematological toxicity
Effects on haematological parameters were found in each of the aforementioned animal species, including the reduction of circulating leukocytes which was found to be dose-related and non-specific in mice and rats, respectively; however, no signs of bone marrow toxicity were found. Reversible neutropenia, thrombocytopenia and anemia developed in some dogs treated with 8-10 mg / kg per day (the area under the curve - AUC - is 12 to 15 times larger than that seen in a man treated with 12 mg In cytopenic dogs, no adverse effects on stem and proliferative elements of the bone marrow were observed.
Reproductive toxicity
Olanzapine has no teratogenic effects. Sedation interferes with the mating abilities of male rats. Cycles of estrus were altered at doses of 1.1 mg / kg (3 times the maximum human dose) and reproduction parameters were affected in rats given 3 mg / kg (9 times the dose). maxim in man). The offspring of rats treated with olanzapine presented delayed fetal development and a transient reduction in activity levels.
Mutagenesis
Olanzapine is neither mutagenic nor capable of promoting cell division in a complete series of standard tests, including mutagenicity tests performed on both bacteria and mammalian tissues in vivo and in vitro.
Carcinogenesis
Based on the results of studies carried out in mice and rats, it was concluded that olanzapine does not possess carcinogenic activity.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Core of the tablet:
Anhydrous lactose
Microcrystalline cellulose
Crospovidone
Magnesium stearate
Tablet coating:
Polyvinyl alcohol
Titanium dioxide (E171)
Talc
Soy lecithin (E322)
Xanthan gum (E415)
Indigotine red (E 132) (in 15 mg film-coated tablet only)
Red iron oxide (E172) (in 20 mg film-coated tablet only)
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2.5 mg film-coated tablets:
2 years.
5 mg, 7.5, 10 mg, 15 mg, 20 mg film-coated tablets:
3 years.
06.4 Special precautions for storage
Blister:
Store in the original package to keep it away from light and moisture.
06.5 Nature of the immediate packaging and contents of the package
Aluminum / aluminum blister.
Packs:
Olanzapine 2.5 mg film-coated tablets: 28 tablets
Olanzapine 5 mg film-coated tablets: 28 tablets
OLANZAPINE DOC Generici 7.5 mg film-coated tablets: 28 and 56 tablets
OLANZAPINE DOC Generici 10 mg film-coated tablets: 28 and 56 tablets
OLANZAPINE DOC Generici 15 mg film-coated tablets: 28 and 56 tablets
OLANZAPINE DOC Generici 20 mg film-coated tablets: 28 and 56 tablets
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
DOC Generici Srl, Via Turati 40, 20121 Milan
08.0 MARKETING AUTHORIZATION NUMBER
2.5 mg film-coated tablets 28 tablets in blister AL / AL AIC 039949019
5 mg film-coated tablets 28 tablets in blister AL / AL AIC 039949021
7.5 mg film-coated tablets 28 tablets in blister AL / AL AIC 039949033
7.5mg film-coated tablets 56 tablets in blister AL / AL AIC 039949072
10 mg film-coated tablets 28 tablets in blister AL / AL AIC 039949045
10 mg film-coated tablets 56 tablets in blister AL / AL AIC 039949084
15 mg film-coated tablets 28 tablets in blister AL / AL AIC 039949058
15 mg film-coated tablets 56 tablets in blister AL / AL AIC 039949096
20 mg film-coated tablets 28 tablets in blister AL / AL AIC 039949060
20 mg film-coated tablets 56 tablets in blister AL / AL AIC 039949108
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
July 2011
10.0 DATE OF REVISION OF THE TEXT
May 2015
