Active ingredients: Levomepromazine
NOZINAN 25 mg film-coated tablets
NOZINAN 100 mg film-coated tablets
Why is Nozinan used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antipsychotic psycholeptics.
THERAPEUTIC INDICATIONS
In the treatment of schizophrenias, paranoid states and mania. In toxic psychoses (amphetamines, LSD, cocaine etc.). In organic mental syndromes accompanied by delirium. In vomiting and incoercible hiccups. In the treatment of intense pain generally in association with narcotic analgesics.
Contraindications When Nozinan should not be used
Hypersensitivity to the active substance or to any of the other components of this medicine; comatose states, especially those caused by substances with a depressive action on the central nervous system (alcohol, barbiturates, opiates, etc.); patients with suspected or recognized subcortical brain damage; severe states of depression; blood dyscrasias; liver and kidney diseases. The product is not indicated in infancy. Pheochromocytoma, myasthenia gravis and untreated epilepsy. Breastfeeding. The risk of harmful effects on the fetus following administration of Levomepromazine is not excluded; do not administer in the first trimester of pregnancy or during lactation, beyond this period the product should be used only when considered essential and always under direct medical supervision (see Special warnings).
Precautions for use What you need to know before taking Nozinan
As with all neuroleptics, patients treated with levomepromazine should be kept under direct medical supervision.
Due to its pharmacological properties, the product should be used with particular caution in the elderly, in subjects with cardiovascular diseases, acute and chronic lung diseases, glaucoma, prostatic hypertrophy, other stenosing diseases of the digestive and urinary tract and Parkinson's disease. of hypotension, do not use adrenaline, which can lead to a further lowering of blood pressure.
Prolonged doses lead to an increase in the plasma level of prolactin with possible effects on target organs. Products containing phenothiazines must therefore be used with appropriate caution in women with breast cancer. During therapy, especially if prolonged or at high doses, it is always necessary to keep in mind the possibility of side effects affecting the CNS, liver, bone marrow, eye and cardiovascular system and it is therefore necessary to perform periodic clinical checks. and laboratory.
In particular, since changes in the blood count have been described with phenothiazine derivatives, it is advisable to periodically perform a blood count during chronic therapy with NOZINAN, as well as repeated checks of renal and hepatic function. Patients treated with high doses of levomepromazine and who must undergo surgical interventions require lower doses of anesthetics and central nervous system depressant drugs. Risk of postural hypotension, particularly in people over 50 years of age.
The effects on the blood count must be particularly followed between the fourth and the twelfth week. However, the onset of dyscrasia can be sudden and therefore the onset of inflammatory manifestations affecting the mouth and upper airways must be immediately followed by appropriate haematological checks.
Phenothiazines increase the state of muscle stiffness in individuals with Parkinson's disease or similar forms or other motor disorders; they can also lower the seizure threshold and facilitate the onset of epileptic seizures. Levomepromazine may lower the seizure threshold (see section Undesirable effects) and should be used with caution in epileptic patients. Therapy should be discontinued if epileptic seizures occur. Patients treated with phenothiazines must avoid excessive exposure to sunlight, resorting, if necessary, to the use of special protective creams.
Use with caution in subjects exposed to particularly high or low temperatures as phenothiazines can compromise the ordinary mechanisms of thermoregulation.
Use with caution in patients with cardiovascular disease or a family history of QT prolongation.
Avoid concomitant therapy with other neuroleptics.
Neuroleptic phenothiazines can potentiate the prolongation of the QT interval thus increasing the risk of developing severe ventricular arrhythmias of the torsades de pointes, potentially fatal situation (sudden death). QT prolongation is exacerbated, in particular, by the presence of bradycardia. hypokalaemia and congenital or acquired (e.g. drug-induced) QT prolongation. If the clinical situation permits, medical and laboratory monitoring should be performed to rule out possible risk factors before initiating therapy with a neuroleptic drug and, as required, including during therapy (see also Undesirable Effects).
Hyperglycaemia or glucose intolerance has been observed in patients treated with NOZINAN.
In patients with a confirmed diagnosis of diatebe mellitus or with risk factors for the development of diabetes, who initiate therapy with NOZINAN, blood glucose levels should be monitored appropriately during treatment (see Undesirable effects).
Interactions Which drugs or foods can modify the effect of Nozinan
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
The association with other psychotropic drugs requires special caution and vigilance on the part of the physician to avoid unexpected and unwanted effects of interaction.
When neuroleptics are given concomitantly with QT-prolonging drugs, the risk of developing cardiac arrhythmias increases.
Do not administer concomitantly with drugs that cause electrolyte disturbances.
Given their fundamental properties, phenothiazines can variously interfere with numerous groups of drugs. Between these:
Substances that depress the CNS: barbiturates, anxiolytics, hypnotics, anesthetics, antihistamines, opiate analgesics. In case of combination avoid high dosages and carefully monitor the patient to avoid excessive sedation or central depression.
Anticonvulsants: due to the known effect of phenothiazines on the seizure threshold, an adjustment of specific therapy may be necessary in epileptic subjects. The respective dosage of the drugs in case of combination must be accurately determined since it is possible, among other things, that phenothiazines reduce the metabolism of phenylhydantoin, accentuating its toxicity, and that barbiturates, like other enzymatic inducers at the microsomal level, may accentuate the metabolism of phenothiazines.
Lithium: although rarely, the association with phenothiazines has resulted in acute encephalopathy. If fever of an undetermined nature is present together with side effects of an extrapyramidal nature, the administration of lithium and NOZINAN should be discontinued.
Antihypertensive: interaction with antihypertensive drugs leads to an increase in the hypotensive effect; however phenothiazines may antagonize the effects of guanethidine and similar drugs.
Anticholinergics: caution requires the association of phenothiazines and parasympatholytic drugs which can favor the appearance of characteristic side effects. Anticholinergics can reduce the antipsychotic action of NOZINAN.
Drugs with leukopenizing activity: due to the synergistic depressive effect on the blood crase, phenothiazines must not be associated with phenylbutazone, thiouracyl derivatives and other potentially myelotoxic drugs.
Metrizamide: this substance increases the risk of phenothiazine-induced seizures. It is therefore necessary to suspend the therapy at least 48 hours before a myelographic examination and the administration must not be resumed before 24 hours from the execution of this.
Alcohol: it is not advisable to drink alcohol during therapy as it can facilitate the central side effects of phenothiazines.
Lisuride, Pergolide and Levodopa: the effects of these substances are specifically antagonized by phenothiazines; this is taken into account in subjects with Parkinson's disease.
Antacids: avoid ingestion of the product together with antacids or other substances that can reduce the absorption of phenothiazines. Interaction with laboratory tests: the urinary metabolites of phenothiazines can impart a dark color to the urine and give false positive responses to the tests for amylase, urobilinogen, uroporphyrin, porphobilinogens and 5-hydroxy-indolacetic acid. False positive pregnancy tests have been reported in women receiving phenothiazines.
Antidiabetics: since levomepromazine can cause hyperglycaemia the dosage of oral hypoglycaemics or insulin must be carefully determined.
Antiarrhythmics: neuroleptics can induce alterations in the E.C.G. such as Q.T.interval prolongation, should therefore be used with caution in patients taking substances such as antiarrhythmics that have similar effects.
Antidepressants: the combination of phenothiazines and tricyclic antidepressants accentuates the antimuscarinic effects.
Deferoxamine: Administration of deferoxamine and prochlorperazine resulted in a transient metabolic encephalopathy. It is possible that this situation may also occur with levomepromazine, as it exhibits many of the pharmacological activities of prochlorperazine.
Cytochrome P450 2D6 metabolism: Levomepromazine and its non-hydroxylated metabolites have been reported to be inhibitors of cytochrome P450 2D6. Concomitant administration of levomepromazine with drugs mainly metabolised by cytochrome P450 2D6 may result in increased plasma levels of these drugs.
Warnings It is important to know that:
Fertility, pregnancy and breastfeeding
Pregnancy
Ask your doctor or pharmacist before taking any medicine.
Do not administer in the first trimester of pregnancy; beyond this period the product is not recommended and should only be taken when considered essential and always under the direct supervision of the doctor. In humans, the teratogenic risk of levomepromazine has not been evaluated.
Several prospective epidemiological studies conducted with other phenothiazines have been found to be contradictory as regards the teratogenic risk. The following symptoms have been observed in newborn babies of mothers who have taken conventional or atypical antipsychotics, including Nozinan, during the last trimester (last three months of pregnancy): shaking, muscle stiffness and / or weakness, sleepiness, agitation, breathing problems , slow or rapid heartbeat, bloating, constipation and difficulty in eating. If your child shows any of these symptoms, contact your doctor.
Feeding time
Levomepromazine is excreted in breast milk in small quantities. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue NOZINAN therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
Nozinan is not recommended for women of childbearing potential who are not using contraceptives.
In men, due to interactions with dopamine receptors, levomepromazine can cause hyperprolactinaemia, which may be associated with impaired fertility in women. Some studies suggest that levomepromazine treatment is associated with impaired male fertility.
Special attention requires the use of this substance in children, especially during an infectious disease or in the case of surgery or vaccination, as in such conditions a higher incidence of extrapyramidal reactions has been found.
The antiemetic effect of phenothiazines can mask the signs of overdosing of other drugs or can make it more difficult to diagnose concomitant diseases, especially of the digestive tract or CNS such as intestinal obstruction, brain tumors, Reye's syndrome. for this reason these substances must be used with caution in association with antiblastics which, at toxic doses, can cause vomiting.
Since the risk of persistent delayed dyskinesias has been correlated with the duration of therapy, chronic treatment with neuroleptics should be reserved for those patients with conditions that respond to the drug and for whom an appropriate alternative therapy is not possible. The doses and duration of treatment should be the minimum in order to obtain a satisfactory clinical response. If signs or symptoms of tardive dyskinesia appear (see Undesirable Effects) during therapy, discontinue administration.
In general, phenothiazines do not produce psychic dependence. However, as a result of abrupt interruption, nausea, vomiting, dizziness, tremors, motor restlessness may appear. Special attention should be paid to patients with psychic depression or during the manic phase of cyclical psychosis due to the possibility of a rapid change in mood towards depression.
A potentially fatal symptom complex called Neuroleptic Malignant Syndrome has been reported during treatment with antipsychotic drugs.
Clinical manifestations of this syndrome are: hyperpyrexia, muscle stiffness, akinesia, vegetative disorders (irregularities in the pulse and blood pressure, sweating, tachycardia, arrhythmias); changes in consciousness which can progress to stupor and coma. The treatment of NMS consists in immediately suspending the administration of antipsychotic drugs and other non-essential drugs and in instituting intensive symptomatic therapy (particular care must be taken in reducing hyperthermia and in correcting dehydration). If the resumption of antipsychotic treatment is deemed essential, the patient should be carefully monitored.
An approximately three-fold increase in the risk of cerebrovascular events was observed in randomized clinical trials versus placebo in a population of patients with dementia treated with some atypical antipsychotics. The mechanism of this increased risk is unknown. An increased risk for other antipsychotics or other patient populations cannot be excluded. Nozinan should be used with caution in patients with a risk factor for stroke.
Effects on ability to drive and use machines
Since phenothiazines induce sedation and somnolence, this must be taken into account in those who drive vehicles or other machinery or who perform hazardous work.
Elderly patients with dementia:
Increased risk of death in elderly patients with dementia treated with antipsychotic drugs. Data from two large observational studies showed that older people with dementia treated with antipsychotics are subject to a moderate increased risk of death compared to those who are not treated. There are insufficient data to provide an accurate estimate of the size of the risk and the cause of the increased risk is unknown. Nozinan is not approved for the treatment of dementia-related behavioral disorders.
Venous thromboembolism
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE must be identified before and during treatment with NOZINAN and preventive measures taken.
Important information about some of the ingredients of the medicine
The medicine contains lactose, so if your doctor has told you that you have an intolerance to some sugars, contact your doctor before taking this medicine.
NOZINAN contains wheat starch. This medicine can be given to people with celiac disease.
People with wheat allergy (other than celiac disease) should not take this medicine.
Dosage and method of use How to use Nozinan: Dosage
The dosage varies according to the indications and objectives to be achieved; in general it is advisable to start treatment with low doses and gradually reach the optimal dosage. The recommended initial daily dose is 25 mg up to three times a day, to be gradually increased according to clinical judgment up to a maximum of 300 mg per day. Higher dosages can only be prescribed in exceptional cases and for short periods of time and under close medical supervision.
In the treatment of elderly patients, the posology must be carefully established by the physician who will have to evaluate a possible reduction of the dosages indicated above and apply a careful evaluation of the risk / benefit ratio in this patient population.
Overdose What to do if you have taken too much Nozinan
In case of accidental ingestion / intake of an excessive dose of NOZINAN, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of NOZINAN, ask your doctor or pharmacist.
Enhancement of undesirable effects: establish suitable antiparkinsonian, muscle relaxant and / or antihistamine therapy.
In the absence of a specific antidote, gastric lavage must be performed: in case of severe hypotension, lay the patient in a supine position with the head tilted down and carefully administer plasma expanders; possibly phenylephrine or noradrenaline by slow venous infusion and with particular caution, as NOZINAN can modify the normal response. Never use adrenaline.
Establish symptomatic treatment of nervous system depression such as in cases of acute barbiturate intoxication, including physiotherapy and antibiotic treatment to prevent bronchopneumonia. Hemodialysis is not effective. When the body temperature drops to particularly low levels, cardiac arrhythmias may appear. Particular surveillance must be exercised to control bowel and bladder distension phenomena.
Side Effects What are the side effects of Nozinan
Like all medicines, NOZINAN can cause side effects, although not everybody gets them.
Nervous system disorders: with the use of phenothiazines, sedation and somnolence may occur, especially during the first weeks of therapy, which mostly disappear with continued treatment or with an appropriate dose reduction. Other behavioral effects that occurred with varying frequency they are insomnia, restlessness, anxiety, euphoria, psychomotor agitation, mood depression or worsening of psychotic symptoms, confusional states, delirium. The possible appearance of dry mouth, mydriasis, vision disturbances, constipation, constipation and even paralytic ileus, urinary retention, and other signs of reduced parasympathetic activity is due to the anticholinergic activity of phenothiazines.
Convulsions and changes in body temperature are also possible. A significant and unexplained increase in body temperature may be due to intolerance towards the product; in this case it is necessary to interrupt the therapy. For depression of the cough center, ab ingestis affections can occur. Extrapyramidal-type reactions are common during treatment with phenothiazines. They are usually represented by muscular dystonias, akathisia, pseudo-parkinsonian syndromes and persistent late dyskinesias. Dystonias and akathisia are more frequent in children, while signs of parkinsonism prevail in the elderly, especially if they have organic brain lesions. Dystonias include spasms of the neck and trunk muscles up to stiff neck and opisthotonus, oculogyric crisis, trismus , protrusion of the tongue and carpal-breech spasms. These reactions appear very early and disappear within 24-48 hours of discontinuing therapy.
Very rarely, dystonia can cause laryngospasm associated with cyanosis and asphyxia.
Akathisia is characterized by motor restlessness and sometimes by insomnia. More frequent in the first days of therapy, it can also appear late. The disorders often regress spontaneously; otherwise they can be well controlled by reducing the dosage or by associating an antiparkinsonian anticholinergic. pseudo-parkinsonian (akinesia, rigidity, tremor at rest, etc ..) are mostly sensitive to specific drugs; in persistent cases it may be necessary to reduce the dosage or stop the treatment.
Late persistent dyskinesias occur mostly during long-term therapy and with high doses, even in the period following drug discontinuation.
The elderly and women are more frequently affected.
They manifest themselves with involuntary rhythmic movements of the tongue, lips and face, more rarely of the extremities and are generally preceded by fine vermicular movements of the tongue. Discontinuation of therapy can prevent the development of symptoms, for which a specific therapy is not known. Periodic reduction of neuroleptic dosage if clinically possible can help to recognize the onset of tardive dyskinesia early.
Tardive dystonia: Tardive dystonia not associated with tardive dyskinesia may occur very rarely. It is characterized by choreic movements or dystonic movements with delayed onset, often persistent and can potentially become irreversible.
Cardiac disorders: levomepromazine, more easily than other phenothiazines, causes hypotension, tachycardia, dizziness, syncopal manifestations. The hypotensive effects can lead to particular problems in people with mitral insufficiency and heart disease. Alterations of the electrocardiographic trace are possible.
Cases of prolongation of the QT interval have been reported very rarely.
Rare cases of QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest have been observed with Nozinan as with other drugs of the same class.
Very rare cases of sudden death.
Cardiac arrhythmias may occur such as: atrial arrhythmias, A-V block, ventricular tachycardia, possibly related to dosage.
Vascular disorders: Frequency not known: Venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis (see section Special Warnings).
Blood and lymphatic system disorders: Effects on blood count are quite rare, but serious. They include leukopenia, agranulocytosis, thrombocytopenia, purpura, haemolytic anemia and aplastic anemia.
Skin and subcutaneous tissue disorders: hypersensitivity reactions (general or contact) and photosensitivity are possible, which are mostly represented by erythema, urticaria, eczema, exfoliative dermatitis. In long-term therapies, brown pigmentations have been reported, especially in the photo-exposed areas.
Endocrine system and effects on metabolism: phenothiazines can cause hyperprolactinemia, reduction of estrogen, progesterone and pituitary gonadotropins. As a consequence, breast enlargement and tenderness, abnormal lactation, amenorrhea may appear in women and gynecomastia and testicular volume reduction in men, impotence. Other possible effects are an increase in body weight, peripheral edema. Priapism has been reported very rarely.
Glucose intolerance, hyperglycemia (see Precautions for use) and glucosuria. Hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Hypersensitivity reactions: in addition to skin and haematological reactions, cholestatic jaundice can occur with varying frequency, clinically similar to infectious hepatitis and characterized by hyperbilirubinemia, hypertransaminasemia, increased alkaline phosphatase and eosinophilia. In case of signs or symptoms of hepatic suffering therapy must be discontinued immediately Other hypersensitivity reactions are represented by laryngeal or angioneurotic edema, laryngospasm, bronchospasm, anaphylactic reactions, systemic lupus erythematosus-like syndromes.
Eye disorders: in the case of protracted therapy, the appearance in the cornea and in the lens of particle material of an undetermined nature has been reported which in some patients caused visual impairment. Pigmentary retinopathy. dosage and duration of therapy it is suggested that patients on high dose or long-term treatment be monitored periodically.
Hepatobiliary disorders Hepatocellular, cholestatic and mixed liver damage.
Other: Necrotising enterocolitis, which can be fatal, has been reported very rarely in patients receiving levomepromazine. There have been isolated cases of sudden death of possible cardiac origin in patients receiving neuroleptic phenothiazines. as well as cases of sudden death from an unknown cause.
Neuroleptic Malignant Syndrome (see Special warnings).
Kidney damage.
As with all phenothiazines, "silent pneumonia" may develop in patients on prolonged treatment with levomepromazine.
Pregnancy, puerperium and perinatal conditions Frequency not known: neonatal withdrawal syndrome, extrapyramidal symptoms (see section Special Warnings - Pregnancy).
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at “www.agenziafarmaco.gov.it/it/responsabili.” By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Expiry: see the expiry date indicated on the package
The expiry date indicated refers to the product in intact packaging, correctly stored.
WARNING: do not use the medicine after the expiry date indicated on the package.
Keep this medicine out of the sight and reach of children.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use.This will help protect the environment.
Composition and pharmaceutical form
COMPOSITION
NOZINAN 25 mg film-coated tablets
Each tablet contains:
Active ingredient: levomepromazine maleate 33.8 mg
equal to levomepromazine base 25 mg
Excipients:
Core: wheat starch; lactose monohydrate; magnesium stearate; colloidal hydrated silica; dextrin.
Coating: hypromellose; macrogula; titanium dioxide; yellow iron oxide.
NOZINAN 100 mg film-coated tablets
Each tablet contains:
Active ingredient: levomepromazine maleate 135 mg
equal to levomepromazine base 100 mg
Excipients:
Core: wheat starch; lactose monohydrate; magnesium stearate; colloidal hydrated silica; dextrin.
Coating: hypromellose; macrogula; titanium dioxide, yellow iron oxide.
PHARMACEUTICAL FORM AND CONTENT
Film-coated tablets
- 20 tablets of 25 mg
- 20 tablets of 100 mg
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
NOZINAN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
NOZINAN 25 mg film-coated tablets
Each tablet contains:
Active principle: levomepromazine maleate 34 mg equal to levomepromazine base 25 mg.
Excipients:
Lactose 60 mg
Castor oil 0.6 mg
NOZINAN 100 mg film-coated tablets
Each tablet contains:
Active principle: levomepromazine maleate 136 mg equal to levomepromazine base 100 mg.
Excipients:
Lactose 111.5 mg
Castor oil 1.2 mg
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
In the treatment of schizophrenias, paranoid states and mania. In toxic psychoses (amphetamines, LSD, cocaine etc.). In organic mental syndromes accompanied by delirium. In vomiting and incoercible hiccups. In the treatment of intense pain generally in association with narcotic analgesics.
04.2 Posology and method of administration
The dosage varies according to the indications and objectives to be achieved; in general it is advisable to start treatment with low doses and gradually reach the optimal dosage. The recommended initial daily dose is 25 mg up to three times a day, to be gradually increased according to clinical judgment up to a maximum of 300 mg per day. Higher dosages can only be prescribed in exceptional cases and for short periods of time and under close medical supervision.
In the treatment of elderly patients, the posology must be carefully established by the physician who will have to evaluate a possible reduction of the dosages indicated above and apply a careful evaluation of the risk / benefit ratio in this patient population.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients; comatose states, especially those caused by substances with a depressive action on the central nervous system (alcohol, barbiturates, opiates, etc ..); patients with suspected or recognized subcortical brain damage; severe states of depression; blood dyscrasias; liver and kidney diseases. The product is not indicated in infancy. Pheochromocytoma, myasthenia gravis and untreated epilepsy. Breastfeeding. The risk of harmful effects on the fetus following administration of Levomepromazine is not excluded; do not administer in the first trimester of pregnancy or during lactation, beyond this period the product should be used only when considered essential and always under direct medical supervision (see section 4.6).
04.4 Special warnings and appropriate precautions for use
Special attention requires the use of this substance in children, especially during an infectious disease or in the case of surgery or vaccination, as in such conditions a higher incidence of extrapyramidal reactions has been found.
The antiemetic effect of phenothiazines can mask the signs of overdosing of other drugs or can make it more difficult to diagnose concomitant diseases, especially of the digestive tract or CNS such as intestinal obstruction, brain tumors, Reye's syndrome. for this reason these substances must be used with caution in association with antiblastics which, at toxic doses, can cause vomiting.
Since the risk of persistent delayed dyskinesias has been correlated with the duration of therapy, chronic treatment with neuroleptics should be reserved for those patients with conditions that respond to the drug and for whom an appropriate alternative therapy is not possible. The doses and duration of treatment should be the minimum in order to obtain a satisfactory clinical response. If signs or symptoms of tardive dyskinesia (see section 4.8) appear during therapy, discontinue administration.
In general, phenothiazines do not produce psychic dependence. However, as a result of abrupt interruption, nausea, vomiting, dizziness, tremors, motor restlessness may appear. Special attention should be paid to patients with psychic depression or during the manic phase of cyclical psychosis due to the possibility of a rapid change in mood towards depression.
A potentially fatal symptom complex called Neuroleptic Malignant Syndrome has been reported during treatment with antipsychotic drugs. Clinical manifestations of this syndrome are: hyperpyrexia, muscle stiffness, akinesia, vegetative disorders (irregularities in the pulse and blood pressure, sweating, tachycardia, arrhythmias); changes in consciousness which can progress to stupor and coma. The treatment of NMS consists in immediately suspending the administration of antipsychotic drugs and other non-essential drugs and in instituting intensive symptomatic therapy (particular care must be taken in reducing hyperthermia and in correcting dehydration). If the resumption of antipsychotic treatment is deemed essential, the patient should be carefully monitored.
During therapy, inform your doctor if you are pregnant; it is also necessary to consult it if you wish to proceed to breastfeeding or to become pregnant. In breastfeeding patients, it is necessary to decide whether to give up breastfeeding the infant and start the treatment or vice versa, continue breastfeeding avoiding the administration of the medicine.
As with all neuroleptics, patients treated with Levomepromazine should be kept under direct medical supervision.
Due to its pharmacological properties, the product should be used with particular caution in the elderly, in subjects with cardiovascular diseases, acute and chronic lung diseases, glaucoma, prostatic hypertrophy, other stenosing diseases of the digestive and urinary tract and Parkinson's disease. hypotension, do not use adrenaline, which can cause a further lowering of blood pressure.
Prolonged doses lead to an increase in the plasma level of prolactin with possible effects on target organs. Products containing phenothiazines must therefore be used with appropriate caution in women with breast cancer. During therapy, especially if prolonged or at high doses, it is always necessary to keep in mind the possibility of side effects affecting the CNS, liver, bone marrow, eye and cardiovascular system and it is therefore necessary to perform periodic clinical checks. and laboratory.
In particular, since changes in the blood count have been described with phenothiazine derivatives, it is advisable to periodically perform a blood count during chronic therapy with NOZINAN, as well as repeated checks of renal and hepatic function.
Patients treated with high doses of Levomepromazine and who must undergo surgical interventions require lower doses of anesthetics and central nervous system depressant drugs.
Risk of postural hypotension, particularly in people over 50 years of age.
The effects on the blood count must be particularly followed between the fourth and the twelfth week. However, the onset of dyscrasia can be sudden and therefore the onset of inflammatory manifestations affecting the mouth and upper airways must be immediately followed by appropriate haematological checks.
Phenothiazines increase the state of muscle stiffness in individuals with Parkinson's disease or similar forms or other motor disorders; they can also lower the seizure threshold and facilitate the onset of epileptic seizures. Levomepromazine may lower the seizure threshold (see section 4.8) and should be used with caution in epileptic patients. Therapy should be discontinued if epileptic seizures occur. Patients treated with phenothiazines must avoid excessive exposure to sunlight, resorting, if necessary, to the use of special protective creams. Use with caution in subjects exposed to particularly high or low temperatures as phenothiazines can compromise the ordinary mechanisms of thermoregulation.
Use with caution in patients with cardiovascular disease or a family history of QT prolongation.
Avoid concomitant therapy with other neuroleptics.
Neuroleptic phenothiazines can potentiate the prolongation of the QT interval thus increasing the risk of developing severe ventricular arrhythmias of the torsades de pointes, potentially fatal situation (sudden death). QT prolongation is exacerbated, in particular, by the presence of bradycardia. hypokalaemia and congenital or acquired (e.g. drug-induced) QT prolongation. If the clinical situation permits, medical and laboratory monitoring should be performed to rule out possible risk factors before initiating therapy with a neuroleptic drug and, as required, including during therapy (see also section 4.8).
An approximately three-fold increase in the risk of cerebrovascular events was observed in randomized clinical trials versus placebo in a population of patients with dementia treated with some atypical antipsychotics. The mechanism of this increased risk is unknown. An increased risk for other antipsychotics or other patient populations cannot be excluded. NOZINAN should be used with caution in patients with stroke risk factors.
Hyperglycaemia or glucose intolerance has been observed in patients treated with NOZINAN.
In patients with a confirmed diagnosis of diabetes mellitus or with risk factors for the development of diabetes who initiate therapy with NOZINAN, blood glucose levels should be monitored appropriately during treatment (see section 4.8).
Elderly patients with dementia:
Increased risk of death in elderly patients with dementia treated with antipsychotic drugs.
Data from two large observational studies showed that older people with dementia treated with antipsychotics are subject to a moderate increased risk of death compared to those who are not treated. There are insufficient data to provide an accurate estimate of the size of the risk and the cause of the increased risk is unknown.
Nozinan is not approved for the treatment of dementia-related behavioral disorders.
Venous thromboembolism
Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs.
Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE must be identified before and during treatment with Nozinan and preventive measures taken.
NOZINAN contains lactose therefore patients with rare inherited problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
NOZINAN contains castor oil, which can cause stomach upset and diarrhea.
04.5 Interactions with other medicinal products and other forms of interaction
The association with other psychotropic drugs requires special caution and vigilance on the part of the physician to avoid unexpected and unwanted effects of interaction.
When neuroleptics are given concomitantly with QT-prolonging drugs, the risk of developing cardiac arrhythmias increases.
Do not administer concomitantly with drugs that cause electrolyte disturbances.
Given their fundamental properties, phenothiazines can variously interfere with numerous groups of drugs. Between these:
Substances that depress the CNS: barbiturates, anxiolytics, hypnotics, anesthetics, antihistamines, opioid analgesics. In case of combination avoid high dosages and carefully monitor the patient to avoid excessive sedation or central depression.
AnticonvulsantsDue to the known effect of phenothiazines on the seizure threshold, an adjustment of specific therapy may be necessary in epileptic subjects. The respective dosage of the drugs in case of combination must be accurately determined since it is possible, among other things, that phenothiazines reduce the metabolism of phenylhydantoin, accentuating its toxicity, and that barbiturates, like other enzymatic inducers at the microsomal level, may accentuate the metabolism of phenothiazines.
Lithium: although rarely, the association with phenothiazines has resulted in acute encephalopathy.
If fever of an undetermined nature is present together with side effects of an extrapyramidal nature, the administration of lithium and NOZINAN should be discontinued.
Antihypertensives: the interaction with antihypertensive drugs leads to an increase in the hypotensive effect; however phenothiazines may antagonize the effects of guanethidine and similar drugs.
Anticholinergics: caution requires the association of phenothiazines and parasympatholytic drugs which can favor the appearance of characteristic side effects. Anticholinergics can reduce the antipsychotic action of NOZINAN.
Drugs with leukopenizing activity: for the synergistic depressive effect on the blood crase, phenothiazines must not be associated with phenylbutazone, thiouracyl derivatives and other potentially myelotoxic drugs.
Metrizamide: this substance increases the risk of phenothiazine-induced convulsions. It is therefore necessary to suspend the therapy at least 48 hours before a myelographic examination and the administration must not be resumed before 24 hours from the execution of this.
AlcoholAlcohol intake during therapy is not recommended as it may facilitate the central side effects of phenothiazines.
Lisuride, Pergolide and Levodopa: the effects of these substances are specifically antagonized by phenothiazines; this is taken into account in subjects with Parkinson's disease.
Antacids: avoid ingestion of the product together with antacids or other substances that can reduce the absorption of phenothiazines.
Interaction with laboratory tests: The urinary metabolites of phenothiazines can impart a dark color to the urine and give false positive responses to the tests for amylase, urobilinogen, uroporphyrins, porphobilinogens and 5-hydroxy-indolacetic acid. In women treated with phenothiazines they are False positive pregnancy tests have been reported.
Antidiabetics: since Levomepromazine can cause hyperglycaemia the dosage of oral hypoglycemic agents or insulin must be carefully determined.
Antiarrhythmics: neuroleptics can induce alterations in the E.C.G. such as Q.T.interval prolongation, should therefore be used with caution in patients taking substances such as antiarrhythmics that have similar effects.
Antidepressants: the combination of phenothiazines and tricyclic antidepressants accentuates the antimuscarinic effects.
Deferoxamine: administration of deferoxamine and prochlorperazine resulted in a transient metabolic encephalopathy. It is possible that this situation may also occur with levomepromazine, as it exhibits many of the pharmacological activities of prochlorperazine.
Cytochrome P450 2D6 metabolism: Levomepromazine and its non-hydroxylated metabolites have been reported to be inhibitors of cytochrome P450 2D6. Concomitant administration of levomepromazine with drugs mainly metabolised by cytochrome P450 2D6 may result in increased plasma levels of these drugs.
04.6 Pregnancy and lactation
Do not administer in the first trimester of pregnancy or during breastfeeding (read carefully section 4.3): beyond this period, the product should only be used when considered essential and always under the direct supervision of the doctor.
When used as an antiemetic, the product should be used during pregnancy only in cases of overt symptoms for which an alternative intervention is not possible and not in the frequent and simple cases of emesis gravidarum and even less for its preventive purposes.
Infants exposed to conventional or atypical antipsychotics including Nozinan during the third trimester of pregnancy are at risk for side effects including extrapyramidal or withdrawal symptoms which may vary in severity and duration after birth. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, bradycardia, tachycardia, disturbed food intake, meconium ileus, delayed meconium passage, abdominal bloating. Therefore, neonates should be carefully monitored in a manner to plan an appropriate treatment.
04.7 Effects on ability to drive and use machines
Since phenothiazines induce sedation and drowsiness, this must be taken into account in those who drive vehicles or other machinery or who perform dangerous work.
04.8 Undesirable effects
Nervous system disorders: with the use of phenothiazines, sedation and somnolence may occur, especially during the first weeks of therapy, which mostly disappear with continued treatment or with an appropriate dose reduction. Other behavioral effects that occurred with varying frequency are insomnia, restlessness, anxiety, euphoria, psychomotor agitation, mood depression or worsening of psychotic symptoms, confusional states, delirium. The possible appearance of dry mouth, mydriasis, vision disturbances, constipation, constipation and even paralytic ileus, urinary retention, and other signs of reduced parasympathetic activity is due to the anticholinergic activity of phenothiazines. Convulsions and changes in body temperature are also possible. A significant and unexplained increase in body temperature may be due to intolerance towards the product; in this case it is necessary to interrupt the therapy. For depression of the cough center, ab ingestis affections can occur. Extrapyramidal-type reactions are common during treatment with phenothiazines. They are usually represented by muscular dystonias, akathisia, pseudo-parkinsonian syndromes and persistent late dyskinesias. Dystonias and akathisia are more frequent in children, while signs of parkinsonism prevail in the elderly, especially if they have organic brain lesions. Dystonias include spasms of the neck and trunk muscles up to stiff neck and opisthotonus, oculogyric crisis, trismus , protrusion of the tongue and carpal-breech spasms. These reactions appear very early and disappear within 24-48 hours of discontinuing therapy. Very rarely, dystonia can cause laryngospasm associated with cyanosis and asphyxia.
Akathisia is characterized by motor restlessness and sometimes by insomnia. More frequent in the first days of therapy, it can also appear late. The disorders often regress spontaneously; otherwise they can be well controlled by reducing the dosage or by combining an anti-parkinson anticholinergic. The pseudo-parkinsonian syndromes (akinesia, rigidity, tremor at rest, etc.) are mostly sensitive to specific drugs; in persistent cases it may be necessary to reduce the dosage or to suspend the treatment.
Late persistent dyskinesias occur mostly during long-term therapy and with high doses, even in the period following drug discontinuation.
The elderly and women are more frequently affected.
They manifest themselves with rhythmic movements of the tongue, lips and face, more rarely of the extremities and are generally preceded by fine vermicular movements of the tongue. Discontinuation of therapy can prevent the development of symptoms, for which a specific therapy is not known. Periodic reduction of neuroleptic dosage if clinically possible can help to recognize the onset of tardive dyskinesia early.
Tardive dystonia: Tardive dystonia not associated with tardive dyskinesia may occur very rarely. It is characterized by choreic movements or dystonic movements with delayed onset, often persistent and can potentially become irreversible.
Cardiac pathologies: Levomepromazine, more easily than other phenothiazines, causes hypotension, tachycardia, dizziness, syncopal manifestations. The hypotensive effects can lead to particular problems in people with mitral insufficiency and heart disease. Alterations of the electrocardiographic trace are possible.
Cases of prolongation of the QT interval have been reported very rarely.
Rare cases of QT prolongation, ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation and cardiac arrest have been observed with Nozinan as with other drugs of the same class.
Very rare cases of sudden death.
Cardiac arrhythmias may occur such as: atrial arrhythmias, A-V block, ventricular tachycardia, possibly related to dosage.
Vascular pathologies:
Frequency not known:
Venous thromboembolism, including pulmonary embolism, sometimes fatal, and deep vein thrombosis (see section 4.4).
Disorders of the blood and lymphatic systemEffects on blood count are quite rare, but serious. They include leukopenia, agranulocytosis, thrombocytopenia, purpura, haemolytic anemia and aplastic anemia.
Skin and subcutaneous tissue disorders: hypersensitivity reactions (general or contact) and photosensitivity are possible, which are mostly represented by erythema, urticaria, eczema, exfoliative dermatitis. In long-term therapies, brown pigmentations have been reported, especially in the photo-exposed areas.
Endocrine system and effects on metabolism: phenothiazines can cause hyperprolactinemia, reduction of estrogens, progesterone and pituitary gonadotropins. As a consequence, breast enlargement and tenderness, abnormal lactation, amenorrhea may appear in women and gynecomastia and testicular volume reduction in men, impotence. Other possible effects are an increase in body weight, peripheral edema. Priapism has been reported very rarely.
Glucose intolerance, hyperglycaemia (see section 4.4) and glucosuria.
Hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Hypersensitivity reactions: in addition to cutaneous and haematological ones, cholestatic jaundice can occur with varying frequency, clinically similar to infectious hepatitis and characterized by hyperbilirubinemia, hypertransaminasemia, increased alkaline phosphatase and eosinophilia. In case of signs or symptoms of hepatic distress, therapy should be discontinued immediately. Other hypersensitivity reactions are represented by laryngeal or angioneurotic edema, laryngospasm, bronchospasm, anaphylactic reactions, systemic lupus erythematosus-like syndromes.
Eye disorders: in the case of prolonged therapy, the appearance in the cornea and in the lens of particle material of an undetermined nature has been reported, which in some patients caused visual impairment. Pigmentary retinopathy. Since ocular damage appears to be related to dosage and duration of therapy, it is suggested that patients on high dose or long-term treatment should be monitored periodically.
Hepatobiliary disorders
Hepatocellular, cholestatic and mixed liver damage.
Other:
Necrotising enterocolitis, which can be fatal, has been reported very rarely in patients receiving levomepromazine.
There have been isolated cases of sudden death of possible cardiac origin in patients receiving neuroleptic phenothiazines. as well as cases of sudden death from an unknown cause.
Neuroleptic Malignant Syndrome (see section 4.4).
Kidney damage.
As with all phenothiazines, "silent pneumonia" may develop in patients on prolonged treatment with levomepromazine.
Pregnancy, puerperium and perinatal conditions
Frequency not known: neonatal withdrawal syndrome, extrapyramidal symptoms (see section 4.6).
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
Enhancement of undesirable effects: establish suitable antiparkinsonian, muscle relaxant and / or antihistamine therapy.
In the absence of a specific antidote, gastric lavage must be performed: in case of severe hypotension, lay the patient in a supine position with the head tilted down and carefully administer plasma expanders; possibly phenylephrine or noradrenaline by slow venous infusion and with particular caution, as NOZINAN can modify the normal response. Never use adrenaline.
Establish symptomatic treatment of nervous system depression such as in cases of acute barbiturate intoxication, including physiotherapy and antibiotic treatment to prevent bronchopneumonia. Hemodialysis is not effective. When the body temperature drops to particularly low levels, cardiac arrhythmias may appear. Particular surveillance must be exercised to control bowel and bladder distension phenomena.
Convulsions.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: psycholeptics, antipsychotics.
A.T.C code: N05AA02.
Nozinan contains as the active ingredient levomepromazine, a phenothiazine neuroleptic, which has some specific pharmacological activities. It antagonizes dopaminergic synaptic transmission; it has a strong alpha-adrenergic blocking action and anticholinergic and adrenergic properties, the latter by reducing the recovery of sympathetic-mimetic amines at the level of presynaptic neuronal membranes. Administered to humans and animals, phenothiazines show evident effects on behavior, motor activity, sleep and conditioned reflexes.
The exact mechanism by which phenothiazines carry out their antipsychotic effect is not known. The pharmacological properties, however, explain well the extrapyramidal, cardiovascular, endocrine and autonomic nervous system effects that usually accompany the therapeutic use of these drugs.
05.2 "Pharmacokinetic properties
Absorption
Maximum serum concentrations are reached on average 1-3 hours after oral administration and 30-90 minutes after intramuscular injection.
Elimination
The half-life of levomepromazine has a wide individual variability (from 15 to 78 hours).
The metabolites of levomepromazine are sulfo-oxidized derivatives and an active demethylated derivative.
The product is eliminated by both urinary and faecal routes.
05.3 Preclinical safety data
The preclinical data have little clinical relevance in the light of the vast experience acquired with the use in humans of the active ingredient contained in the medicinal product.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Nucleus:
cornstarch; lactose; microcrystalline cellulose (AVICEL); magnesium stearate; anhydrous colloidal silica (AEROSIL).
Coating:
zein; castor oil; titanium dioxide.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
4 years.
06.4 Special precautions for storage
To protect the medicine from light, keep the blister in the outer carton.
06.5 Nature of the immediate packaging and contents of the package
Tablets in aluminum / PVC heat-sealed blister packs:
- Box of 20 tablets of 25 mg
- Box of 20 tablets of 100 mg
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
sanofi-aventis S.p.A. - Viale L Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
NOZINAN 25 mg film-coated tablets AIC n °. 015228012
NOZINAN 100 mg film-coated tablets AIC n °. 015228024
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
06.06.1959 / 01.06.2010
10.0 DATE OF REVISION OF THE TEXT
AIFA determines of June 2014
