Active ingredients: Ziprasidone
Ziprasidone Sandoz 20 mg hard capsules
Ziprasidone Sandoz 40 mg hard capsules
Ziprasidone Sandoz 60 mg hard capsules
Ziprasidone Sandoz 80 mg hard capsules
Why is Ziprasidone used - Generic drug? What is it for?
Ziprasidone Sandoz contains the active substance ziprasidone and belongs to a group of medicines called antipsychotics.
Ziprasidone Sandoz is used to treat the following mental disorders:
- schizophrenia in adults. Schizophrenia is characterized by the following symptoms: hearing, seeing and hearing things that are not there, believing in something unreal, having unusual suspicions, being absent and having difficulty establishing social relationships, nervousness, depression or anxiety
- manic or mixed episodes of moderate severity in the context of bipolar disorder in adults and in children and adolescents aged 10 to 17. This mental illness is characterized by alternating phases of euphoric (mania) or depressive states. mania, the most characteristic symptoms are: euphoric behavior, excessive self-esteem, increased energy, decreased need for sleep, lack of concentration or hyperactivity and repeated high-risk behaviors.
Contraindications When Ziprasidone should not be used - Generic drug
Do not take Ziprasidone Sandoz
- if you are allergic to ziprasidone or any of the other ingredients of this medicine. Signs of an allergic reaction include skin rash, itching, swelling of the face or lips, difficulty in breathing
- if you have or have suffered in the past from heart problems or have recently had a heart attack
- if you are taking medicines to treat heart rhythm disturbances, or medicines that can alter the heart rhythm by prolonging the so-called QT interval, such as:
- class IA and III antiarrhythmics, medicines used to treat irregular heartbeat. Ask your doctor for advice if you are taking medicines to treat irregular heartbeat;
- arsenic trioxide - a medicine used to treat cancer;
- halofantrine - a medicine used to treat malaria;
- mefloquine - a medicine used to prevent and treat malaria;
- levacetylmethadol: a medicine used to combat addiction, such as that of morphine;
- mesoridazine, thioridazine, pimozide, sertindole: medicines for the treatment of mental disorders;
- sparfloxacin, gatifloxacin, moxifloxacin: medicines to treat bacterial infections;
- dolasetron - a medicine used to prevent and treat nausea and vomiting;
- cisapride: a medicine used to treat stomach and / or intestinal disorders.
Precautions for use What you need to know before taking Ziprasidone - Generic drug
Talk to your doctor or pharmacist before taking Ziprasidone Sandoz if any of the following apply to you:
- low resting heart rate
- fast or irregular heartbeat or abnormal heart rate functioning, which may be characterized by fainting, collapse or dizziness upon standing up. It is recommended that heart activity be measured before starting treatment
- salt depletion, resulting from severe and prolonged episodes of diarrhea and vomiting or the use of diuretics
- if you are elderly (over 65), have dementia and are at risk of having a stroke
- if you have or have had in the past from seizures or epilepsy
- liver disorders
- if you, or someone else in your family, have a 'history of blood clots, as this type of medication has been associated with the formation of blood clots.
Tell your doctor that you are taking Ziprasidone Sandoz before having any laboratory tests (such as blood, urine, liver function, heart rate etc), as this medicine can alter the test results.
Ziprasidone Sandoz is not recommended for children under 10 years of age.
Interactions Which drugs or foods can modify the effect of Ziprasidone - Generic drug
Other medicines and Ziprasidone Sandoz Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Medicines for heart rhythm disturbances or medicines which can alter the heart rhythm should not be taken concomitantly with Ziprasidone Sandoz. Refer to the list above in section 2 under the heading 'Do not take Ziprasidone Sandoz'.
Tell your doctor if you are taking or have recently taken medicines to treat the following conditions:
- bacterial infections; these medicines are known as antibiotics
- mood swings (ranging from depressed mood to euphoria), agitation and irritation; these medicines are known as mood stabilizers, such as lithium, carbamazepine, valproate
- depression, including some serotonergic drugs, for example selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, paroxetine, sertraline
- epilepsy, for example phenytoin, phenobarbital, carbamazepine, ethosuximide
- Parkinson's disease, for example levodopa, bromocriptine, ropinirole, pramipexole.
Ziprasidone Sandoz with food, drink and alcohol
Drinking alcohol while taking Ziprasidone Sandoz is not recommended as it may increase the risk of side effects.
Warnings It is important to know that:
Pregnancy and breastfeeding
Pregnancy: you should not take Ziprasidone Sandoz during pregnancy, unless specifically directed by your doctor, because there is a risk that this drug is harmful to the baby. The following symptoms may occur in newborn babies from mothers who have taken Ziprasidone Sandoz in the last trimester (the last three months of their pregnancy): shaking, muscle stiffness and / or weakness, sleepiness, agitation, trouble breathing and difficulty in eating. . If your baby shows any of these symptoms, it may be necessary to contact a doctor. Always use effective contraception. If you are pregnant, think you may be pregnant or are planning to become pregnant while taking Ziprasidone Sandoz, please tell your doctor immediately.
Breast-feeding: Do not breast-feed if you are taking Ziprasidone Sandoz, as small amounts of Ziprasidone Sandoz can pass into breast milk. If you are planning to breast-feed, consult your doctor before taking this medicine. 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.
Driving and using machines
It is recommended that you do not drive until your doctor has assessed your clinical response to Ziprasidone Sandoz.
Taking Ziprasidone Sandoz may cause drowsiness. If you experience this symptom, you should not drive or use any tools or machines until the sleepiness subsides.
Ziprasidone Sandoz contains lactose
If you have been told by your doctor that you have "intolerance to some sugars, consult your doctor before taking this medicine.
Dose, Method and Time of Administration How to use Ziprasidone - Generic drug: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
The recommended dose is:
Ziprasidone Sandoz 20 mg capsules.
Adults
- starting dose in acute cases: 40 mg of ziprasidone (2 capsules) twice a day
- maximum dose: 80 mg of ziprasidone (4 capsules) twice a day.
Your doctor may adjust the starting dose on an individual basis up to the maximum dose. The latter can be achieved as early as day 3 of treatment. The maintenance dose in the treatment of schizophrenia should be the lowest effective dose. A dose of 20 mg ziprasidone (1 capsule) twice daily is often sufficient.
Elderly patients
In patients aged 65 and over the starting dose may be lower if so decided by the doctor.
Patients with liver disorders
Your doctor will prescribe a lower dose.
Patients with kidney disorders
Kidney disorders require no dose adjustment.
Children and adolescents aged 10 to 17 with bipolar mania
- starting dose: 20 mg of ziprasidone (1 capsule) as a single dose on the first day. Your doctor will increase the starting dose over 1 to 2 weeks to a twice daily regimen.
- maximum dose:
- 80 mg ziprasidone (4 capsules) twice daily in children weighing 45 kg or more
- 40 mg of ziprasidone (2 capsules) twice daily in children weighing less than 45 kg
The safety and efficacy of Ziprasidone Sandoz in the treatment of schizophrenia in children and adolescents have not been established.
Other strengths of this medicinal product are available for dosages not achievable / practicable with this strength.
Ziprasidone Sandoz 40 mg capsules
Adults
- starting dose in acute cases: 40 mg of ziprasidone (1 capsule) twice a day
- maximum dose: 80 mg of ziprasidone (2 capsules) twice a day.
Your doctor can adjust the starting dose on an individual basis up to the maximum dose. The latter can be achieved as early as day 3 of treatment. The maintenance dose in the treatment of schizophrenia should be the lowest effective dose. A dose of 20 mg ziprasidone twice daily is often sufficient.
Elderly patients
In patients aged 65 and over the starting dose may be lower if so decided by the doctor
Patients with liver disorders
Your doctor will prescribe a lower dose.
Patients with kidney disorders
Kidney disorders require no dose adjustment.
Children and adolescents aged 10 to 17 with bipolar mania
- starting dose: 20 mg of ziprasidone as a single dose on the first day. Your doctor will increase the starting dose over 1 to 2 weeks to a twice daily regimen.
- maximum dose:
- 80 mg ziprasidone (2 capsules) twice daily in children weighing 45 kg or more
- 40 mg of ziprasidone (1 capsule) twice daily in children weighing less than 45 kg
The safety and efficacy of Ziprasidone Sandoz in the treatment of schizophrenia in children and adolescents have not been established.
Other strengths of this medicinal product are available for dosages not achievable / practicable with this strength.
Ziprasidone Sandoz 60 mg capsules
Adults
- starting dose in acute cases: 40 mg of ziprasidone twice a day
- maximum dose: 80 mg of ziprasidone twice a day.
Your doctor can adjust the starting dose on an individual basis up to the maximum dose. The latter can be reached as early as the 3rd day of treatment.
The maintenance dose in the treatment of schizophrenia should be the lowest effective dose. A dose of 20 mg of ziprasidone twice a day is often sufficient.
Elderly patients
In patients aged 65 and over the starting dose may be lower if so decided by the doctor.
Patients with liver disorders
Your doctor will prescribe a lower dose.
Patients with kidney disorders
Kidney disorders require no dose adjustment.
Children and adolescents aged 10 to 17 with bipolar mania
- starting dose: 20 mg of ziprasidone as a single dose on the first day. Your doctor will increase the starting dose over 1 to 2 weeks to a twice daily regimen.
- maximum dose:
- 80 mg ziprasidone twice daily in children weighing 45 kg or more
- 40 mg of ziprasidone twice daily in children weighing less than 45 kg
The safety and efficacy of Ziprasidone Sandoz in the treatment of schizophrenia in children and adolescents have not been established.
Other strengths of this medicinal product are available for dosages not realizable / practicable with this strength.
Ziprasidone Sandoz 80 mg capsules
Adults
- starting dose in acute cases: 40 mg of ziprasidone twice a day
- maximum dose: 80 mg of ziprasidone (1 capsule) twice a day.
Your doctor can adjust the starting dose on an individual basis up to the maximum dose. The latter can be reached as early as the 3rd day of treatment.
The maintenance dose in the treatment of schizophrenia should be the lowest effective dose. A dose of 20 mg of ziprasidone twice a day is often sufficient.
Elderly patients
In patients aged 65 and over the starting dose may be lower if so decided by the doctor.
Patients with liver disorders
Your doctor will prescribe a lower dose.
Patients with kidney disorders
Kidney disorders require no dose adjustment.
Children and adolescents aged 10 to 17 with bipolar mania
- starting dose: 20 mg of ziprasidone as a single dose on the first day. Your doctor will increase the starting dose over 1 to 2 weeks to a twice daily regimen.
- maximum dose:
- 80 mg ziprasidone (1 capsule) twice daily in children weighing 45 kg or more
- 40 mg of ziprasidone twice daily in children weighing less than 45 kg
The safety and efficacy of Ziprasidone Sandoz in the treatment of schizophrenia in children and adolescents have not been established.
Other strengths of this medicinal product are available for dosages not realizable / practicable with this strength.
How to use
Oral use
Take the capsules whole, with a glass of water, during or shortly after a meal, in the morning and in the evening. You must take this medicine at the same time each day. It is important not to chew the capsules, as this may affect the amount of the "absorption by the intestine."
Duration of use
The duration of use will be determined by the doctor
Overdose What to do if you have taken an overdose of Ziprasidone - Generic Medication
In the event of an overdose, contact your doctor or pharmacist immediately and make the pack and any remaining capsules available.
If you have taken too many capsules you may experience sleepiness, tremor, seizures and involuntary movements of the head and neck.
Side Effects What are the side effects of Ziprasidone - Generic drug
Like all medicines, this medicine can cause side effects, although not everybody gets them. However, most side effects are transient in nature. It can often be difficult to distinguish the symptoms of the disease from those of the side effects.
If you experience any of the following serious side effects, STOP taking Ziprasidone Sandoz and contact your doctor immediately:
Uncommon side effects, may affect up to 1 in 100 patients:
- Fast or irregular heartbeat, dizziness on standing up, which may indicate abnormal heart function. These may be symptoms of a disorder known as postural hypotension.
- Involuntary / unusual movements, especially of the face or tongue.
Not known, frequency cannot be estimated from the available data:
- Swelling of the face, lips, tongue or throat, swallowing or breathing problems, hives. These can be symptoms of a severe allergic reaction, such as angioedema.
- Fever, faster breathing, sweating, muscle stiffness, tremor, difficulty swallowing and decreased consciousness. These can be symptoms of a disorder known as neuroleptic malignant syndrome.
- Confusion, agitation, high temperature, sweating, lack of muscle coordination, muscle spasms. These can be symptoms of a disorder known as serotonin syndrome.
- Fast, irregular heartbeat and fainting, which can be symptoms of a potentially fatal disorder known as Torsades de Pointes.
- Swelling, pain and redness in the legs. These may be symptoms of blood clots in the veins, particularly those in the legs, which can travel through blood vessels and into the lungs, causing chest pain and difficulty in breathing.
You may experience any of the side effects listed below. These potential side effects are usually mild to moderate in nature and may resolve over time. However, if the side effect is severe or persistent you should contact your doctor.
Common side effects, may affect up to 1 in 10 patients:
- restlessness
- abnormal movements, including involuntary movements, muscle stiffness, slow movement, tremor, general weakness and tiredness, dizziness, sleepiness, headache
- constipation, nausea, vomiting and indigestion, dry mouth, increased salivation
- blurred vision.
Uncommon side effects, may affect up to 1 in 100 patients:
- increased appetite
- difficulty in controlling movements
- feeling agitated or anxious, throat tightness, nightmares
- seizures, involuntary eye movements in a fixed position, clumsiness, speech disturbances, numbness, tingling sensation, impaired ability to concentrate, saliva loss, excessive daytime sleepiness, exhaustion
- palpitations, feeling of faintness on getting up, shortness of breath
- sensitivity to light, ringing in the ears
- sore throat, difficulty swallowing, swollen tongue, diarrhea, wind, stomach upset
- itchy rash, acne
- muscle cramps, stiffness or swelling of the joints
- thirst, pain, chest discomfort, abnormal gait.
Rare side effects, may affect up to 1 in 1,000 patients:
- a runny nose
- decrease in blood calcium levels
- panic attacks, feelings of depression, slowed thoughts, lack of emotion
- unusual head position (stiff neck), paralysis, restless legs syndrome
- partial or complete loss of vision in one eye, itchy eyes, dry eyes, disturbed vision
- ear pain
- hiccup
- acid reflux
- loose stools
- hair loss, facial swelling, skin irritation
- inability to open the mouth
- urinary incontinence, pain or difficulty passing urine
- decreased or increased erection, decreased orgasm, abnormal breast milk production • breast enlargement in both men and women
- feeling of heat, fever
- decrease or increase in white blood cells (shown in blood tests)
- abnormal liver function test results
- high blood pressure
- abnormal blood or heart rate test results
- raised patches of red, inflamed skin covered with white scales known as psoriasis
Not known, frequency cannot be estimated from the available data:
- severe allergic reaction
- In the elderly population with dementia, a small increase in the number of deaths has been reported in patients taking antipsychotics compared to those not taking them
- sleep disturbances, involuntary urination
- state of mind characterized by an extremely high energy, abnormal thought patterns and hyperactivity
- dizziness, loss of consciousness
- large wheals (hives), with severe itching
- abnormal persistent and painful erection of the penis
- facial relaxation
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
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 blister, bottle and carton after EXP. The expiry date refers to the last day of that month.
Do not store above 30 ° C.
Bottles only:
Validity after first opening: 6 months.
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.
Other Information
If you forget to take Ziprasidone Sandoz
It is important to take the capsules regularly, at the same time each day. If you forget to take a dose, take it as soon as you remember, unless it is time for your next dose. In this case, just take the next dose at the usual time. Do not take a double dose to make up forgotten dose.
If you stop taking Ziprasidone Sandoz
Do not stop taking Ziprasidone Sandoz without your doctor's permission, even if you feel better, as this may reduce the therapeutic effect and your symptoms may return. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
The active ingredient is ziprasidone:
Each hard capsule contains 20 mg of ziprasidone (as ziprasidone hydrochloride monohydrate)
Each hard capsule contains 40 mg of ziprasidone (as ziprasidone hydrochloride monohydrate)
Each hard capsule contains 60 mg of ziprasidone (as ziprasidone hydrochloride monohydrate)
Each hard capsule contains 80 mg of ziprasidone (as ziprasidone hydrochloride monohydrate)
The other ingredients are:
Capsule contents: lactose monohydrate, pregelatinised maize starch, magnesium stearate.
20, 40 and 80 mg capsules Capsule shell: indigo carmine (E132), titanium dioxide (E171) and gelatin.
60 mg capsules
Capsule shell: titanium dioxide (E171) and gelatin.
What Ziprasidone Sandoz looks like and contents of the pack
Ziprasidone Sandoz comes in the form of hard gelatin capsules.
20 mg hard capsules, size 4 (length: 14.3 mm): opaque blue / opaque blue capsules
40 mg hard capsules, size 3 (length: 15.7 mm): opaque blue / opaque blue capsules
60 mg hard capsules, size 2 (length: 17.6 mm): white opaque / white opaque capsules
Hard capsules of 80 mg, size 1 (length: 19.4 mm): opaque blue / opaque blue capsules
Pack sizes
Ziprasidone Sandoz is packaged in blister packs in cardboard boxes containing 10, 14, 20, 30, 50, 56, 60, 98 or 100 capsules.
Ziprasidone Sandoz is packaged in bottles closed with caps, containing 200 capsules.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ZIPRASIDONE SANDOZ
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each hard capsule contains 20 mg of ziprasidone (as ziprasidone hydrochloride monohydrate)
Each hard capsule contains 40 mg of ziprasidone (as ziprasidone hydrochloride monohydrate)
Each hard capsule contains 60 mg of ziprasidone (as ziprasidone hydrochloride monohydrate)
Each hard capsule contains 80 mg of ziprasidone (as ziprasidone hydrochloride monohydrate)
Excipient (s) with known effect:
Each 20 mg capsule, hard contains 50.81 mg of lactose.
Each 40 mg hard capsule contains 101.61 mg of lactose.
Each 60 mg hard capsule contains 152.42 mg of lactose.
Each 80 mg hard capsule contains 203.22 mg of lactose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Hard capsule.
20 mg hard capsules, size 4 (length: 14.3 mm): opaque blue / opaque blue capsules.
40 mg hard capsules, size 3 (length: 15.7 mm): opaque blue / opaque blue capsules.
60 mg hard capsules, size 2 (length: 17.6 mm): white opaque / white opaque capsules.
Hard capsules of 80 mg, size 1 (length 19.4 mm): opaque blue / opaque blue capsules.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Ziprasidone is indicated for the treatment of schizophrenia in adults.
Ziprasidone is indicated for the treatment of manic or mixed episodes of moderate severity associated with bipolar disorder in adults and children and adolescents aged 10-17 years (efficacy in preventing episodes of bipolar disorder has not been established - see paragraph 5.1).
04.2 Posology and method of administration
Adults
The recommended dose in the acute treatment of schizophrenia and bipolar mania is 40 mg twice daily to be taken with food. The daily dose may subsequently be modified according to the clinical condition of the patient, up to a maximum of 80 mg twice a day. If indicated, the maximum recommended dose can be reached as early as the 3rd day of treatment.
It is particularly important not to exceed the maximum dose as the safety profile with doses above 160 mg / day has not been confirmed and ziprasidone is associated with a dose-related prolongation of the QT interval (see sections 4.3 and 4.4).
In maintenance therapy for schizophrenia, patients should be treated with the lowest effective dose of ziprasidone; in many cases, a dose of 20 mg twice daily may be sufficient.
Senior citizens
A lower starting dose is not usually indicated, but should be considered for those patients 65 years of age or older when needed based on clinical data.
Use in patients with renal impairment
No dose adjustment is required in patients with renal impairment (see section 5.2).
Use in patients with hepatic impairment
Lower doses should be considered in patients with hepatic impairment (see sections 4.4 and 5.2).
Pediatric population
Schizophrenia:
The safety and efficacy of ziprasidone in pediatric patients with schizophrenia have not been established (see section 4.4).
Bipolar mania:
The recommended dose in the treatment of acute episodes of bipolar mania in pediatric patients (aged 10-17 years) is a single 20 mg dose on the 1st day of treatment, to be taken with meals. Ziprasidone should subsequently be administered with meals in two divided daily doses and the dose should be titrated over 1-2 weeks to a target dose regimen of 120 - 160 mg / day in patients with body weight ≥45 kg or to a regimen target dose of 60 - 80 mg / day for patients with body weight
It is extremely important not to exceed the maximum dose calculated on the basis of body weight because the safety profile with doses higher than the maximum recommended dose (160 mg / day for children with body weight ≥45 kg and 80 mg / day for children of weight
Method of administration
The capsules should only be taken once a day for the first day in the case of treatment of acute bipolar mania in pediatric patients only and twice a day in all other cases. The capsules should be swallowed whole with water during or shortly after eating, without being chewed as this may affect the extent to which ziprasidone is absorbed from the intestine.
04.3 Contraindications
- Hypersensitivity to ziprasidone or to any of the excipients listed in section 6.1.
- Established prolongation of the QT interval.
- Congenital long QT syndrome.
- Recent acute myocardial infarction.
- Heart failure.
- Arrhythmias treated with class IA and III antiarrhythmic drugs.
- Concomitant treatment with medications that prolong the QT interval, such as Class IA and III antiarrhythmics, arsenic trioxide, halofantrine, levacetylmethadol, mesoridazine, thioridazine, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, dolasetron, serfloxine or mephlool.
(See sections 4.4 and 4.5)
04.4 Special warnings and appropriate precautions for use
Medical history, including assessment of family history, and physical examination should be done to identify patients for whom ziprasidone treatment is not recommended (see section 4.3).
QT interval
Ziprasidone causes mild to moderate prolongation of the dose related QT interval (see sections 4.8 and 5.1).
Ziprasidone should not be administered with medicinal products known to cause prolongation of the QT interval (see sections 4.3 and 4.5). Caution is advised in patients with significant bradycardia. Electrolyte imbalances, such as hypokalaemia and hypomagnesaemia, increase the risk of malignant arrhythmias and they must therefore be corrected before starting treatment with ziprasidone An ECG check is recommended before starting treatment in patients with stable heart disease.
If cardiac symptoms such as palpitations, dizziness, syncope or seizures occur, the possibility of a malignant cardiac arrhythmia should be considered and cardiac evaluation, including an ECG, should be performed. If the QTc interval is> 500 msec, then it is recommended to stop treatment (see section 4.3).
Rare episodes of torsades de pointes have been reported post-marketing in patients with multiple confounding risk factors taking ziprasidone.
Pediatric Patients
The safety and efficacy of ziprasidone in the treatment of schizophrenia have not been evaluated in pediatric and adolescent patients.
Neuroleptic Malignant Syndrome (NMS)
NMS is a rare but potentially fatal syndrome that has been reported in association with antipsychotic medicinal products, including ziprasidone. Treatment of NMS should include immediate withdrawal of all antipsychotic medicines.
Tardive dyskinesia
There is a possibility that tardive dyskinesia and other late-onset extrapyramidal syndromes may develop after long-term treatment with ziprasidone. It is known that patients with bipolar disorder are particularly vulnerable to this category of symptoms. This occurs more frequently as treatment duration and age increase. If signs and symptoms of tardive dyskinesia appear, a dose reduction or discontinuation of ziprasidone treatment should be considered.
Convulsions
Caution is recommended when treating patients with a history of seizures.
Impaired liver function
Experience in patients with severe hepatic impairment is limited and therefore ziprasidone should be used with caution in this patient population (see sections 4.2 and 5.2).
Increased risk of cerebrovascular adverse events in patients with dementia
An approximately three-fold increased risk of cerebrovascular adverse events was observed in randomized placebo-controlled clinical trials in dementia patients treated with some atypical antipsychotics. The mechanism of this increased risk is unknown. An increased risk cannot be excluded for other antipsychotic drugs or other patient populations. Ziprasidone should be used with caution in patients who have risk factors for stroke.
Increased mortality in elderly patients with dementia
Data from two large observational studies showed a small increased risk of death in elderly people with dementia treated with antipsychotics compared to untreated patients.
There are insufficient data to give an exact estimate of the precise magnitude of this risk and the cause of the increased risk is unknown.
Ziprasidone Sandoz is not licensed for the treatment of dementia-related behavioral disorders.
Venous thromboembolism
Cases of venous thromboembolism (VTE) have been reported with the use of antipsychotic drugs.
All possible risk factors for VTE should be identified before and during treatment with ziprasidone and preventive measures should be taken as patients treated with antipsychotics often develop risk factors for venous thromboembolism.
Lactose
Ziprasidone Sandoz contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Pharmacokinetic and pharmacodynamic interaction studies have not been conducted between ziprasidone and other QT prolonging medicinal products. An additive effect of ziprasidone and these medicinal products cannot be excluded; therefore, ziprasidone should not be administered in combination with medicinal products that prolong QT. QT interval, such as Class IA and III antiarrhythmics, arsenic trioxide, halofantrine, levacetylmetadol, mesoridazine, thioridazine, pimozide, sparfloxacin, gatifloxacin, moxifloxacin, dolasetron mesylate, mefloquine, sertindole or cisapride (see section 4.3).
No interaction studies of ziprasidone with other medicinal products have been conducted in children.
CNS-Affecting Medicines / Alcohol
Due to the primary effects of ziprasidone, care should be taken when the drug is taken together with other centrally acting medicinal products and alcohol.
Effects of ziprasidone on other medicinal products
A study in vivo with dextromethorphan showed no marked inhibition of CYP2D6 at plasma concentrations 50% lower than those obtained with the administration of ziprasidone 40 mg twice daily. The data in vitro indicate that ziprasidone may be a moderate inhibitor of CYP2D6 and CYP3A4. However, ziprasidone is unlikely to change the pharmacokinetics of medicinal products metabolised by these cytochrome P450 isoforms to a clinically relevant extent.
Oral contraceptives:
Administration of ziprasidone did not result in significant changes in the pharmacokinetics of the components of estrogen (ethinylestradiol, a substrate of CYP3A4) or progesterone.
Lithium:
Concomitant administration of ziprasidone did not cause alterations in the pharmacokinetics of lithium. Since ziprasidone and lithium are associated with cardiac conduction disturbances, the combination of the two drugs may pose a risk of pharmacodynamic interactions, including arrhythmias.
Carbamazepine and valproate:
Data on concomitant administration with mood stabilizers such as carbamazepine and valproate are limited.
Effects of other medicinal products on ziprasidone
The CYP3A4 inhibitor ketoconazole (400 mg / day) increased the serum concentrations of ziprasidone by a
Carbamazepine and valproate:
Carbamazepine 200 mg b.i.d. for 21 days caused an approximately 35% reduction in ziprasidone exposure.
There are no data on the concomitant use of valproate.
Antacids:
Multiple dose administration of aluminum and magnesium-containing antacids or cimetidine did not significantly alter the pharmacokinetics of ziprasidone under fed conditions.
Serotonergic medicines
Cases of serotonin syndrome have been reported in isolated cases temporally associated with the therapeutic use of ziprasidone in combination with other serotonergic medicinal products such as SSRIs (see section 4.8). Serotonin syndrome can be characterized by: confusion, agitation, fever , sweating, ataxia, hyperreflexia, myoclonus and diarrhea.
Protein binding
Ziprasidone is extensively bound to plasma proteins. The binding of ziprasidone to plasma proteins in vitro it was not altered by warfarin or propranolol, two highly protein bound drugs, nor did ziprasidone alter the binding of these drugs in human plasma. Therefore, the potential for drug displacement interaction with ziprasidone is unlikely.
04.6 Pregnancy and lactation
Reproductive toxicity studies have shown adverse reproductive effects at dosages associated with maternal toxicity and / or sedation. No signs of teratogenicity were found (see section 5.3).
Pregnancy
Studies in pregnant women have not been performed. Therefore, women of childbearing potential being treated with ziprasidone should be advised to use an adequate method of contraception. As clinical experience is limited, it is recommended not to administer ziprasidone during pregnancy unless the anticipated benefit to the mother justifies the potential risk to the fetus.
Infants exposed to antipsychotics (including ziprasidone) during the third trimester of pregnancy are at risk for side effects including extrapyramidal and / or withdrawal symptoms which may vary in severity and duration after birth. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, food intake disturbances. Infants should therefore be closely monitored.
Feeding time
It is not known whether ziprasidone is excreted in human milk. Therefore, patients on ziprasidone treatment should not breastfeed. If treatment is necessary, breastfeeding should be stopped.
04.7 Effects on ability to drive and use machines
Ziprasidone has minimal or moderate influence on the ability to drive or use machines as it may cause drowsiness. Patients who routinely drive vehicles or operate machinery should be adequately informed.
04.8 Undesirable effects
Oral ziprasidone has been administered in clinical studies (see section 5.1) to approximately 6,500 adult subjects. The most common adverse reactions in schizophrenia clinical studies were sedation and akathisia. In bipolar mania clinical trials the most common adverse reactions were sedation, akathisia, extrapyramidal disorders and dizziness.
The table below shows the adverse events that occurred in the short-term studies in schizophrenia (4 - 6 weeks) conducted with a fixed dose and in the short-term studies in bipolar mania (3 weeks) conducted with a flexible dose and for which a probable or possible correlation has been established with ziprasidone and occurred at an "incidence higher than placebo. Additional side effects reported in the post-marketing setting are italicized in the following list as frequency" not known ".
All adverse reactions are classified by class and frequency, as defined below:
very common (≥ 1/10)
common (≥1 / 100
uncommon (≥1 / 1,000
rare (≥ 1 / 10,000
very rare (
not known (frequency cannot be estimated from the available data).
The adverse reactions listed below may also be associated with the underlying disease and / or the use of concomitant medications.
Tabular list of adverse reactions:
In short-term and long-term clinical trials with ziprasidone in schizophrenia and bipolar mania, the incidence of tonic-clonic seizures and hypotension was uncommon, and these events occurred in less than 1% of patients treated. with ziprasidone.
Ziprasidone causes a mild to moderate dose-related prolongation of the QT interval (see section 5.1). An increase of 30-60 msec in 12.3% (976/7941) of ECG traces was observed in clinical studies in schizophrenia. patients treated with ziprasidone and 7.5% (73/975) of the ECG tracings of patients on placebo. A prolongation> 60 msec was observed in 1.6% (128/7941) and 1, 2% (12/975) of the records of patients treated with ziprasidone and placebo, respectively. The incidence of QTc interval prolongation above 500 msec was detected in 3 patients out of a total of 3266 patients (0.1% ) treated with ziprasidone and in 1 patient out of a total of 538 patients (0.2%) on placebo. Comparable data were observed in clinical trials in bipolar mania.
During the schizophrenia clinical trials of long-term maintenance therapy, prolactin levels in patients treated with ziprasidone sometimes increased, but in the majority of cases they normalized without stopping the treatment. Furthermore, possible clinical manifestations (eg gynaecomastia and breast enlargement) have occurred only rarely.
Children and adolescents with bipolar mania
Ziprasidone orally was administered in clinical trials (see Section 5.1) to 267 pediatric patients with bipolar disorder. In a placebo-controlled study, the most frequent adverse reactions (reported with a frequency> 10%) were sedation, somnolence, headache, asthenia and nausea The frequency, type and severity of adverse reactions in these subjects were generally similar to that seen in adult subjects with bipolar disorder receiving ziprasidone.
In clinical trials of bipolar disorder in pediatric patients, ziprasidone was associated with a dose-related prolongation of the mild to moderate QT interval similar to that seen in the adult population. Tonic-clonic seizures and hypotension were not reported in the clinical trials in pediatric patients with bipolar disorder treated with placebo.
04.9 Overdose
Experience with overdose of ziprasidone is limited. The maximum known single dose of oral ziprasidone is 12,800 mg. In this case, extrapyramidal symptoms and a QTc interval of 446 msec (without cardiac consequences) were reported. In general, the most frequently reported symptoms following overdose are extrapyramidal symptoms, somnolence, tremor and anxiety.
The possibility of dullness, seizures, or dystonic reaction of the head and neck following overdose may pose a risk of aspiration with induced emesis. Cardiovascular monitoring should begin immediately and include continuous electrocardiographic monitoring in order to detect any arrhythmias. Not A specific antidote for ziprasidone is available.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: psycholeptics, antipsychotics, indole derivatives.
ATC code N05AE04.
Ziprasidone possesses a "high affinity for dopaminergic type 2 (D2) receptors and a" significantly higher affinity for serotonergic type 2A (5HT2A) receptors. With positron emission tomography (PET), 12 hours after administration of a single 40 mg dose, receptor blockade of greater than 80% for serotonin type 2A receptors and greater than 50% for serotonin receptors was detected. D2 type dopaminergic receptors. Ziprasidone also interacts with the 5HT2C, 5HT1D and 5HT1A serotonergic receptors and its affinity for these sites is equal to or greater than that for the D2 receptors. Ziprasidone has a "moderate affinity for neuronal transporters of serotonin and noradrenaline. and for H1 histamine receptors and receptors? 1. Ziprasidone has negligible affinity for the M1 muscarinic receptors.
Ziprasidone has been shown to be an antagonist of serotonergic type 2A (5HT2A) and dopaminergic type 2 (D2) receptors. Therapeutic activity is thought to be in part mediated by this combination of antagonistic activity. Ziprasidone also possesses strong antagonist activity against 5HT2C and 5HT1D receptors, strong agonist activity for 5HT1A receptor and inhibits neuronal reuptake of norepinephrine and serotonin. .
Learn more about clinical trials
Schizophrenia
In a 52-week study, ziprasidone was shown to be effective in maintaining clinical improvement during continued therapy in patients exhibiting an initial response to treatment: there was no clear evidence of a dose-response relationship between groups treated with ziprasidone. In this study, which included patients with positive and negative symptoms, the efficacy of ziprasidone was demonstrated on both positive and negative symptoms.
The incidence of body weight gain, reported as an adverse effect in short-term (4-6 week) schizophrenia studies, was low and was identical in ziprasidone-treated and placebo-treated patients (in both patients). 0.4% cases). In a 1-year placebo-controlled study, an average weight loss of 1-3 kg was observed in patients treated with ziprasidone compared to an average weight loss of 3 kg in patients treated with placebo.
In a double-blind comparison study in schizophrenia, metabolic parameters were evaluated, including fasting weight and insulin levels, total cholesterol and triglycerides, and insulin resistance index (IR). No significant changes from baseline were observed for any of these metabolic parameters in patients receiving ziprasidone.
Results of a post-marketing safety study
A randomized post-registration study in 18,239 patients with schizophrenia with an observational follow-up of 1 year was conducted to determine whether the effect of ziprasidone on the QTc interval is associated with an increased risk of non-suicide-related mortality. In this study, conducted under conditions of normal clinical practice, there was no difference in the overall non-suicide mortality rate between patients treated with ziprasidone and those treated with olanzapine (primary endpoint). In addition, the study found no differences in secondary endpoints of all-cause mortality, suicide-related mortality, and sudden death mortality; however, a "non-statistically higher incidence of cardiovascular mortality was found in the ziprasidone group. A statistically significant" higher incidence of hospitalizations for all causes was also observed in the ziprasidone group, mainly related to the difference in the number of psychiatric hospitalizations.
Bipolar mania
The efficacy of ziprasidone in the treatment of mania in adults was established in two 3-week double-blind placebo-controlled studies comparing ziprasidone with placebo and one 12-week double-blind study comparing ziprasidone. with haloperidol and placebo. These studies included approximately 850 patients who met DSM-IV criteria for bipolar I disorder with an acute manic or mixed episode, with and without psychotic manifestations. The presence at baseline of psychotic traits in the study setting was 49.7%, 34.7% or 34.9%. Efficacy was assessed using the Mania Rating Scale (MRS). The Clinical Global Impression-Severity (CGI-S) scale was either a co-primary efficacy variable or a key secondary efficacy variable in these studies. treatment with ziprasidone (40-80 mg BID, mean daily dose 120 mg) caused a statistically significant improvement in both MRS and CGI-S scales at the last visit (3 weeks) compared to placebo. In the 12-week study, haloperidol treatment (mean daily dose 16 mg) resulted in significantly greater reductions in MRS scores than ziprasidone (mean daily dose 121 mg). Ziprasidone demonstrated comparable efficacy to that of haloperidol in terms of the proportion of patients who maintained a response to treatment from week 3 to week 12.
The efficacy of ziprasidone in the treatment of Bipolar I Disorder in pediatric patients (aged 10-17 years) was evaluated in a 4-week placebo-controlled study (n = 237) in inpatient or outpatient returning patients. in the DSM IV criteria for manic or mixed bipolar I disorder episodes, with or without psychotic components, and with a baseline Y-MRS score ≥17. This double-blind, placebo-controlled study compared oral ziprasidone administered in flexible doses (80-160 mg / day (40-80 mg BID) in two divided doses in patients with body weight ≥45 kg; 40-80 mg / day (20-40 mg BID) in patients with body weight titration over 1-2 weeks, with the administration of two daily doses, to a target dose of 120-160 mg / day for patients weighing ≥45 kg, or 60-80 mg / day for patients with body weight
The safety of ziprasidone was evaluated in 267 pediatric patients (aged 10-17 years) enrolled in multiple-dose clinical trials in bipolar mania; a total of 82 pediatric patients with Bipolar I Disorder were treated with oral ziprasidone for at least 180 days.
In a 4-week study in pediatric patients (10-17 years) with bipolar mania, no differences were observed between patients treated with ziprasidone and those in the placebo group, in the mean change from baseline of the following parameters: body weight, fasting glucose levels, total cholesterol, LDL cholesterol or triglycerides.
Long-term double-blind clinical studies have not been conducted to evaluate the efficacy and tolerability of ziprasidone in children and adolescents.
Long-term clinical studies have not been conducted to evaluate the efficacy of ziprasidone in preventing relapse of manic-depressive symptoms.
05.2 Pharmacokinetic properties
Absorption
After oral administration of multiple doses of ziprasidone taken with food, peak serum concentrations are generally reached within 6-8 hours of administration. The absolute bioavailability of a 20 mg dose administered with food is 60%. Pharmacokinetic studies have shown that the bioavailability of ziprasidone increases up to 100% in the presence of food. Therefore, it is recommended that ziprasidone be taken with food.
Distribution
The volume of distribution is approximately 1.1 l / kg. Ziprasidone is more than 99% bound to serum plasma proteins.
Metabolism and elimination
The mean terminal half-life of ziprasidone after oral administration is 6.6 hours. Steady state is achieved within 1-3 days. The mean clearance of ziprasidone administered intravenously is 5 ml / min / kg. Approximately 20% of the dose is excreted in the urine and approximately 66% is excreted in the faeces.
Ziprasidone exhibits linear kinetics in relation to the therapeutic dose range of 40-80 mg administered twice daily with food.
Ziprasidone is extensively metabolised after oral administration and only a small percentage is excreted in the urine (drug-related total serum.
A study in vivo suggests that conversion to S-methyl dihydroziprasidone represents the major metabolic pathway of ziprasidone. Studies in vitro indicate that this metabolite is formed through reduction catalyzed by aldehyde oxidase, resulting in S-methylation. Oxidative metabolism is also involved, mainly via CYP3A4, with the potential contribution of CYP1A2.
When tested in vitro, ziprasidone and the metabolites S-methyl-dihydroziprasidone and ziprasidone sulfoxide have some common properties that may lead to the hypothesis of a prolongation of the QTc interval. The metabolite S-methyl-dihydroziprasidone is eliminated mainly in the faeces via biliary excretion, with a minimal contribution of metabolism catalysed by CYP3A4. Ziprasidone sulfoxide is eliminated by renal excretion and by secondary metabolism catalysed by CYP3A4.
Other special patient populations
Pharmacokinetic screening of patients did not reveal any significant pharmacokinetic differences between smokers and nonsmokers.
No clinically significant differences in ziprasidone pharmacokinetics were observed between subjects of different ages or sex. The pharmacokinetics of ziprasidone in pediatric patients aged 10-17 years were similar to that seen in adult patients after correction for body weight differences.
According to the fact that renal clearance contributes little to total clearance, no increase in ziprasidone exposure was observed when administered to subjects with varying degrees of renal function. Exposure in subjects with mild impairment (creatinine clearance 30-60 mL / min), moderate (creatinine clearance 10-29 mL / min) and severe (requiring hemodialysis) were 146%, 87% and 75% of that found in healthy subjects (clearance creatinine> 70 ml / min) following oral administration of 20 mg BID for seven days It is not known whether serum concentrations of the metabolites are increased in these patients.
In patients with mild to moderate hepatic impairment (Child-Pugh A or B) caused by cirrhosis, there was a 30% increase in serum concentrations after oral administration and a prolongation of the terminal half-life of approximately 2 hours compared to that found in healthy subjects. The effect of liver disease on serum concentrations of metabolites is unknown.
05.3 Preclinical safety data
Preclinical safety data did not reveal any particular hazard for humans as demonstrated by conventional studies of safety pharmacology, genotoxicity and carcinogenic potential. In reproductive studies conducted in rats and rabbits, the administration of ziprasidone showed no evidence of teratogenicity. Adverse fertility events and decreased body weight of pups have been observed with doses that cause maternal toxicity, such as decreased weight gain. The increase in perinatal mortality and the reduction in the functional development of the offspring occurred at maternal plasma concentrations considered similar by extrapolation to the maximum concentrations reached in humans with the use of therapeutic doses.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Capsule contents:
Lactose monohydrate
Pregelatinised maize starch
Magnesium stearate
Capsule shell
20 mg hard capsules
Indigo carmine (E132)
Titanium dioxide (E171)
Jelly
Hard capsules of 40 mg
Indigo carmine (E132)
Titanium dioxide (E171)
Jelly
Hard capsules of 60 mg
Titanium dioxide (E171)
Jelly
Hard capsules of 80 mg
Indigo carmine (E132)
Titanium dioxide (E171)
Jelly
06.2 Incompatibility
Not relevant.
06.3 Period of validity
Blister:
18 months.
Bottle:
18 months.
After first opening: 6 months
06.4 Special precautions for storage
Do not store above 30 ° C
06.5 Nature of the immediate packaging and contents of the package
Aluminum / aluminum blister
HDPE bottle with PP cap
Pack sizes:
Blisters: 10, 14, 20, 30, 50, 56, 60, 98, 100 hard capsules
Bottle: 200 hard capsules
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Sandoz S.p.A., L.go U. Boccioni 1, 21040 Origgio (VA)
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 041339019 / M - "20 MG HARD CAPSULES" 10 CAPSULES IN BLISTER AL / AL
AIC n. 041339021 / M - "20 MG HARD CAPSULES" 14 CAPSULES IN BLISTER AL / AL
AIC n. 041339033 / M - "20 MG HARD CAPSULES" 20 CAPSULES IN BLISTER AL / AL
AIC n. 041339045 / M - "20 MG HARD CAPSULES" 30 CAPSULES IN BLISTER AL / AL
AIC n. 041339058 / M - "20 MG HARD CAPSULES" 50 CAPSULES IN BLISTER AL / AL
AIC n. 041339060 / M - "20 MG HARD CAPSULES" 56 CAPSULES IN BLISTER AL / AL
AIC n. 041339072 / M - "20 MG HARD CAPSULES" 60 CAPSULES IN BLISTER AL / AL
AIC n. 041339084 / M - "20 MG HARD CAPSULES" 98 CAPSULES IN BLISTER AL / AL
AIC n. 041339096 / M - "20 MG HARD CAPSULES" 100 CAPSULES IN BLISTER AL / AL
AIC n. 041339108 / M - "20 MG HARD CAPSULES" 200 CAPSULES IN HDPE BOTTLE
AIC n. 041339110 / M - "40 MG HARD CAPSULES" 10 CAPSULES IN BLISTER AL / AL
AIC n. 041339122 / M - "40 MG HARD CAPSULES" 14 CAPSULES IN BLISTER AL / AL
AIC n. 041339134 / M - "40 MG HARD CAPSULES" 20 CAPSULES IN BLISTER AL / AL
AIC n. 041339146 / M - "40 MG HARD CAPSULES" 30 CAPSULES IN BLISTER AL / AL
AIC n. 041339159 / M - "40 MG HARD CAPSULES" 50 CAPSULES IN BLISTER AL / AL
AIC n. 041339161 / M - "40 MG HARD CAPSULES" 56 CAPSULES IN BLISTER AL / AL
AIC n. 041339173 / M - "40 MG HARD CAPSULES" 60 CAPSULES IN BLISTER AL / AL
AIC n. 041339185 / M - "40 MG HARD CAPSULES" 98 CAPSULES IN BLISTER AL / AL
AIC n. 041339197 / M - "40 MG HARD CAPSULES" 100 CAPSULES IN BLISTER AL / AL
AIC n. 041339209 / M - "40 MG HARD CAPSULES" 200 CAPSULES IN HDPE BOTTLE
AIC n. 041339211 / M - "60 MG HARD CAPSULES" 10 CAPSULES IN BLISTER AL / AL
AIC n. 041339223 / M - "60 MG RIGID CAPSULES" 14 CAPSULES IN BLISTER AL / AL
AIC n. 041339235 / M - "60 MG RIGID CAPSULES" 20 CAPSULES IN BLISTER AL / AL
AIC n. 041339247 / M - "60 MG HARD CAPSULES" 30 CAPSULES IN BLISTER AL / AL
AIC n. 041339250 / M - "60 MG RIGID CAPSULES" 50 CAPSULES IN BLISTER AL / AL
AIC n. 041339262 / M - "60 MG HARD CAPSULES" 56 CAPSULES IN BLISTER AL / AL
AIC n. 041339274 / M - "60 MG HARD CAPSULES" 60 CAPSULES IN BLISTER AL / AL
AIC n. 041339286 / M - "60 MG RIGID CAPSULES" 98 CAPSULES IN BLISTER AL / AL
AIC n. 041339298 / M - "60 MG HARD CAPSULES" 100 CAPSULES IN BLISTER AL / AL
AIC n. 041339300 / M - "60 MG RIGID CAPSULES" 200 CAPSULES IN HDPE BOTTLE
AIC n. 041339312 / M - "80 MG HARD CAPSULES" 10 CAPSULES IN BLISTER AL / AL
AIC n. 041339324 / M - "80 MG RIGID CAPSULES" 14 CAPSULES IN BLISTER AL / AL
AIC n. 041339336 / M - "80 MG RIGID CAPSULES" 20 CAPSULES IN BLISTER AL / AL
AIC n. 041339348 / M - "80 MG RIGID CAPSULES" 30 CAPSULES IN BLISTER AL / AL
AIC n. 041339351 / M - "80 MG RIGID CAPSULES" 50 CAPSULES IN BLISTER AL / AL
AIC n. 041339363 / M - "80 MG RIGID CAPSULES" 56 CAPSULES IN BLISTER AL / AL
AIC n. 041339375 / M - "80 MG RIGID CAPSULES" 60 CAPSULES IN BLISTER AL / AL
AIC n. 041339387 / M - "80 MG RIGID CAPSULES" 98 CAPSULES IN BLISTER AL / AL
AIC n. 041339399 / M - "80 MG HARD CAPSULES" 100 CAPSULES IN BLISTER AL / AL
AIC n. 041339401 / M - "80 MG RIGID CAPSULES" 200 CAPSULES IN HDPE BOTTLE
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 15/03/2013
10.0 DATE OF REVISION OF THE TEXT
02/2013
