Active ingredients: Metamizole
NOVALGINA 500 mg / ml oral drops, solution
NOVALGINA 500 mg tablets
NOVALGINA Adults 1 g suppositories
NOVALGINA Children 300 mg suppositories
Novalgina package leaflets are available for pack sizes: - NOVALGINA 500 mg / ml oral drops, solution, NOVALGINA 500 mg tablets, NOVALGINA Adults 1 g suppositories, NOVALGINA Children 300 mg suppositories
- NOVALGINA 1 g / 2 ml solution for injection
Why is Novalgina used? What is it for?
Pharmacotherapeutic group
Analgesics and antipyretics, pyrazolones.
Therapeutic indications
Severe or resistant painful or febrile states.
Contraindications When Novalgina should not be used
Hypersensitivity to the active substance or to any of the excipients.
Novalgina must not be used in patients with:
- hypersensitivity to other pyrazolones (eg phenazone, propiphenazone) or to pyrazolidines (eg phenylbutazone, oxifenbutazone);
- a history of agranulocytosis associated with the use of pyrazolones;
- impaired bone marrow function (e.g. after cytostatic therapy) or haematopoietic system disorders, such as granulocytopenia;
- patients who experience bronchospasm or other anaphylactoid reactions (e.g. urticaria, rhinitis, angioedema) to non-narcotic analgesics (e.g. salicylates, paracetamol, diclofenac, ibuprofen, indomethacin, naproxen);
- acute intermittent hepatic porphyria (risk of induction of porphyria attacks);
- congenital deficiency of glucose-6-phosphate-dehydrogenase (risk of hemolysis);
- infants under 3 months or body weight less than 5 kg.
In infants aged 3 to 11 months
Novalgina must not be administered intravenously. Novalgina should not be administered parenterally in patients with hypotension or circulatory instability.
It is recommended not to use Novalgina in the first three months of pregnancy and, if used in the following three months, this should only be done after carefully evaluating the risk-benefit ratio. Novalgina should not be used in the last three months of pregnancy. (See also Special Warnings: Pregnancy and Lactation).
Precautions for use What you need to know before you take Novalgina
Agranulocytosis caused by metamizole is an immune-allergic event that lasts at least one week. Such reactions are very rare, can be serious, life-threatening and fatal. They are not dose-dependent. and can occur at any time during therapy.
Patients should be advised of the need to discontinue treatment and to seek immediate medical attention if any of the following symptoms possibly related to neutropenia occur: fever, chills, sore throat, oral ulceration. In case of neutropenia (neutrophils / mm3 blood count should be performed urgently and monitored until the return to normal values.
Pantocytopenia
In the event of pancytopenia, treatment should be stopped immediately and complete blood counts monitored until normalized. All patients should be advised to contact their physician immediately if they experience signs and symptoms suggestive of blood dyscrasias (eg malaise). general, infections, persistent fever, bruising, bleeding, paleness) while being treated with metamizole.
Anaphylactic shock:
These reactions mainly occur in sensitive patients. Therefore metamizole should be used with caution in asthmatic or atopic patients (see "Contraindications").
Treatment should be discontinued immediately if any signs or symptoms of anaphylaxis (urticaria, angioedema, rash, dyspnoea, pallor or generalized hyperaemia, general malaise, hypotension, shock, laryngeal edema) or agranulocytosis (abrupt onset of severe associated neutropenia) appear. fever, marked asthenia, mouth ulcerations, pharynx and / or perineal ulcerations) or thrombocytopenia (tendency to bleed with or without petechiae).
Given the risks associated with metamizole, the drug should only be used after evaluating the possibility of resorting to therapeutic alternatives.
Patients who have already experienced a hypersensitivity reaction with metamizole should no longer take metamizole or other pyrazolone drugs.
Novalgina tablets and Novalgina suppositories for adults are not suitable for the treatment of children under the age of 15 years.
Novalgina Children 300 mg suppositories are not suitable for the treatment of children under the age of 4 years. For children under the age of 5, administration under medical supervision is recommended.
Avoid the use of the specialty in trivial disorders. In addition, pyrazolones should be used only for the period of time necessary to control painful or febrile symptoms; the use of analgesics at high doses or for prolonged periods must be evaluated by the doctor.
The use of Novalgina, like any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant.
Novalgina should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
Interactions Which drugs or foods can modify the effect of Novalgina
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
In case of concomitant administration of cyclosporine and Novalgina there may be a reduction in the plasma levels of cyclosporine. Therefore it will be necessary to provide for regular checks of cyclosporinemia.
As with other analgesics, it is recommended to avoid the intake of alcohol during treatment with Novalgina, as interaction between the substances cannot be excluded.
The addition of metamizole to methotrexate may increase the haematotoxicity of methotrexate, particularly in elderly patients. Therefore this association must be avoided.
Metamizole when taken concomitantly with acetylsalicylic acid can reduce its effect on platelet aggregation. Therefore, this combination should be used with caution in patients taking low doses of acetylsalicylic acid for cardioprotection.
Metamizole can cause a decrease in the concentration of bupropion in the blood.Therefore caution is advised when metamizole and bupropion are administered concomitantly.
Warnings It is important to know that:
Anaphylactic / anaphylactoid reactions
When choosing the route of administration, it should be considered that the parenteral route is associated with an increased risk of anaphylactic / anaphylactoid reactions.
Patients with:
- analgesic asthma or intolerance to analgesics of the urticaria-angioedema type (see "Contraindications"),
- bronchial asthma, particularly if with concomitant polyposis rhinosinusitis,
- chronic urticaria,
- alcohol intolerance, meaning patients who react to minimal amounts of alcohol with symptoms such as sneezing, watery eyes or flushing of the face. Alcohol intolerance may indicate an undiagnosed analgesic asthma syndrome,
- intolerance to dyes (e.g. tartrazine) or preservatives (e.g. benzoates).
Prior to administration of Novalgina, specific questions should be asked of the patient. In cases at particular risk of anaphylactoid reactions, Novalgina should only be used after carefully weighing the possible risks versus the expected benefits. If Novalgina is to be administered in these circumstances, careful medical supervision and the availability of immediate emergency treatment are required.
Severe skin reactions
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), skin reactions that can be life threatening, have been reported with the use of metamizole. If you develop symptoms or signs of SJS or TEN (such as progressive rash, often with blistering or mucosal lesions) treatment with metamizole should be stopped immediately and not restarted. Patients should be informed of the type of signs and symptoms and the possibility of a skin reaction should be carefully monitored , particularly in the first weeks of treatment.
Isolated hypotensive reactions
Administration of metamizole may cause isolated cases of hypotensive reactions (see "Undesirable effects"). These reactions are possibly dose-dependent and more likely with parenteral administration.
Furthermore, the risk of severe hypotensive reactions of this type is increased:
- if intravenous administration is not done slowly,
- in patients with pre-existing hypotension, with dehydration or reduced volume, with circulatory instability or with incipient circulatory failure,
- in patients with high fever.
In these patients, the use of metamizole should be carefully considered and, if it is administered, careful medical supervision is required. Preventive measures (stabilization of the circulation) may be necessary to reduce the risk of a hypotensive reaction.
For patients with hypotension or circulatory instability see also "Contraindications". In patients in whom a reduction in blood pressure must be avoided, such as patients with severe coronary insufficiency or significant stenosis of the blood vessels supplying the brain, metamizole should only be used under close haemodynamic monitoring.
It is recommended to avoid the administration of high doses of metamizole in patients with renal or hepatic insufficiency, since the rate of elimination of the drug in such patients is reduced.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
Metamizole crosses the placenta. There are no data regarding a toxic effect on the fetus: metamizole did not demonstrate teratogenic effects in rats and rabbits, and foetotoxicity was observed only at high doses which were toxic to the mother. However, there are insufficient data on the use of metamizole during pregnancy.
Novalgina should not be used in the last three months of pregnancy.
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations was increased from less than 1% to to approximately 1.5%. The risk has been estimated to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased loss of pre- and post-implantation and embryo-fetal mortality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose
the fetus to:
- cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
- renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
the mother and the newborn, at the end of pregnancy, to:
- possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labor.
Feeding time
Metamizole metabolites are excreted in breast milk. Breastfeeding should be avoided during and for 48 hours after administration of Novalgina.
Effects on ability to drive and use machines
No harmful effects on the ability to concentrate and react at recommended doses have been reported. However, it must be taken into account, at least for higher doses, that the ability to concentrate and react may be altered thus constituting a risk in situations where these abilities are particularly important (e.g. driving cars or using machines) , especially if alcohol has been consumed.
Important information about some of the ingredients
Novalgina tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Dosage and method of use How to use Novalgina: Dosage
NOVALGINA oral drops, solution
Adults and children aged 15 and over:
20-40 drops up to 4 times a day.
Children aged 5 to 14:
10-15 drops up to 4 times a day.
Infants over 4 months and children up to 4 years:
2-6 drops up to 4 times a day.
NOVALGINA tablets
Adults and children aged 15 and over:
1-2 tablets up to 4 times a day.
NOVALGINA adults 1 g suppositories
Adults and children aged 15 and over:
1 suppository up to 3 times a day.
NOVALGINA children 300 mg suppositories
Children aged 4 to 14:
1 suppository up to 3 times a day.
The tablets should be swallowed with some liquid and without chewing.
The drops are taken diluted in a little liquid.
In patients with hepatic or renal insufficiency it is recommended not to administer high doses of metamizole, as the elimination rate is low in these patients. For short treatments it is not necessary to reduce the dosage. There are no data on long-term use in patients with renal or hepatic insufficiency.
The possibility of impaired hepatic and renal function should be considered in elderly patients and in patients with compromised general conditions.
Overdose What to do if you have taken too much Novalgina
Symptoms of overdose
Nausea, vomiting, abdominal pain, renal impairment / acute renal failure (e.g. due to interstitial nephritis) and more rarely central nervous system symptoms (dizziness, somnolence, coma, convulsions) have been reported following acute overdose. ), drop in blood pressure (sometimes progressing to shock) and also cardiac arrhythmias (tachycardia).
After administration of very high doses, the excretion of a harmless metabolite (rubazonic acid) can cause red urine.
Treatment of overdose
There is no known specific antidote for metamizole. If the intake has taken place recently, strategies can be tried to limit the further systemic absorption of the drug such as primary detoxification (gastric lavage) or means that reduce absorption (activated carbon). The main metabolite (4N-methylaminoantipyrine) can be eliminated by hemodialysis, haemofiltration, haemoperfusion or plasma filtration.
In case of accidental ingestion / intake of an excessive dose of Novalgina, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Novalgina, ask your doctor or pharmacist.
Side Effects What are the side effects of Novalgina
Like all medicines, Novalgina can cause side effects, although not everybody gets them.
- Cardiac pathologies
Kounis syndrome
- Disorders of the immune system
Metamizole can cause anaphylactic shock, anaphylactic / anaphylactoid reactions, which can be severe and life threatening and sometimes fatal. These reactions can appear at any stage of treatment, in a manner not related to the daily dose, even after repeated use in the past without complications.
Milder anaphylactic / anaphylactoid reactions typically manifest themselves with skin and mucosal symptoms (such as itching, burning, redness, hives, swelling), dyspnoea, and less frequently gastrointestinal symptoms. Milder reactions can progress to severe forms with generalized urticaria, severe angioedema (including laryngeal involvement), severe bronchospasm, cardiac arrhythmias, drop in blood pressure (sometimes preceded by a rise in blood pressure) and circulatory shock.
Such reactions may appear soon after the administration of metamizole or even after hours; however, they usually occur within the first hour of administration.
The risk of anaphylactic shock, however, appears to be higher with the parenteral forms. In patients with analgesic asthma syndrome, intolerance reactions usually manifest themselves in the form of asthmatic attacks.
- Skin and subcutaneous tissue disorders
In addition to the cutaneous and mucosal manifestations of the anaphylactic / anaphylactoid reactions mentioned above, fixed drug eruptions may occasionally occur, rarely rash and in isolated cases also Stevens-Johnson syndrome or Lyell syndrome, which can be life-threatening. .
In case of onset of such skin lesions it is necessary to immediately stop taking the drug and consult your doctor.
- Disorders of the blood and lymphatic system
Aplastic anemia, agranulocytosis and pancytopenia, including fatal outcome, leukopenia and thrombocytopenia. These reactions are considered immunological in nature. They can also occur after repeated use in the past without complications. Typical signs of agranulocytosis include inflammatory lesions of the mucous membranes ( e.g. oropharyngeal, anorectal, genitals), sore throat, fever (including persistent or recurrent fever). However, in patients receiving antibiotic therapy, the typical signs of agranulocytosis may be minimal. The erythrocyte sedimentation rate is considerably increased, while lymph node swelling is generally mild or absent.
Typical signs of thrombocytopenia include an "increased bleeding tendency and petechiae of the skin and mucous membranes.
- Vascular pathologies
Isolated hypotensive reactions
Occasionally, transient isolated hypotensive reactions (probably pharmacologically mediated and not accompanied by other signs of anaphylactic / anaphylactoid reactions) may occur after administration; in rare cases this reaction manifests itself as an acute drop in blood pressure.
- Renal and urinary disorders
It can occur in very rare cases, and particularly in patients with a history of kidney disease or, in case of overdose, acute worsening of renal function (acute renal failure), in some cases with oliguria, anuria or proteinuria. Acute interstitial nephritis has been reported in isolated cases.
- General disorders and administration site conditions
Local pain and reactions may occur at the injection site, sometimes with phlebitis.
Sometimes a red discoloration of the urine has been observed, which may be due to a metabolite present in low concentrations (rubazonic acid); the color disappears at the end of the treatment.
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 printed on the package. The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
NOVALGINA 500 mg / ml oral drops, solution
Do not store above 25 ° C.
NOVALGINA Adults 1 g suppositories
Do not store above 30 ° C.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
KEEP THIS MEDICINAL PRODUCT OUT OF THE SIGHT AND REACH OF CHILDREN.
Composition and pharmaceutical form
Composition
NOVALGINA 500 mg / ml oral drops, solution
1 ml of solution contains:
Active ingredient: sodium noramidopyrine methanesulfonate (metamizole) 500 mg
Excipients: sodium phosphate, monosodium sodium phosphate, citrus flavor and purified water.
NOVALGINA 500 mg tablets
One tablet contains:
Active ingredient: sodium noramidopyrine methanesulfonate (metamizole) 500 mg
Excipients: corn starch, lactose, talc, magnesium stearate, sodium bicarbonate.
NOVALGINA Adults 1 g suppositories
One suppository contains:
Active ingredient: sodium noramidopyrine methanesulfonate (metamizole) 1 g
Excipients: soy lecithin, solid semisynthetic glycerides.
NOVALGINA Children 300 mg suppositories
One suppository contains:
Active ingredient: sodium noramidopyrine methanesulfonate (metamizole) 300 mg
Excipients: soy lecithin, solid semisynthetic glycerides.
Pharmaceutical forms and content
Oral drops, solution: 20 ml bottle
Tablets: box of 20 tablets
Adult suppositories: box of 5 suppositories
Suppositories for children: box of 5 suppositories
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
NOVALGINA
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Novalgina 500 mg / ml oral drops, solution
1 ml of solution contains:
Active principle: noramidopyrine sodium methanesulfonate (metamizole) 500 mg
Excipients with known effects: sodium phosphate and monosodium sodium phosphate
Novalgina 500 mg tablets
One tablet contains:
Active principle: noramidopyrine sodium methanesulfonate (metamizole) 500 mg
Excipients with known effects: lactose
Novalgina Adults 1 g suppositories
One adult suppository contains:
Active principle: noramidopyrine sodium methanesulfonate (metamizole) 1 g
Novalgina Children 300 mg suppositories
A children's suppository contains:
Active principle: noramidopyrine sodium methanesulfonate (metamizole) 300 mg
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Oral drops, solution.
Suppositories.
Tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Severe or resistant painful or febrile states.
04.2 Posology and method of administration
Novalgina oral drops.
Adults and children aged 15 and over: 20-40 drops up to 4 times a day.
Children from 5 to 14 years: 10-15 drops up to 4 times a day.
Infants over 4 months and children up to 4 years: 2-6 drops up to 4 times a day.
Novalgina tablets
Adults and children aged 15 and over: 1-2 tablets up to 4 times a day.
The tablets should be swallowed with some liquid and without chewing.
Novalgina adults 1 g suppositories
Adults and children aged 15 and over: 1 adult suppository up to 3 times a day.
Novalgina children 300 mg suppositories
Children from 4 to 14 years: 1 suppository for children up to 3 times a day.
In patients with hepatic or renal insufficiency it is recommended not to administer high doses of metamizole as the elimination rate is low in these patients. For short treatments it is not necessary to reduce the dosage. There are no data on long-term use in patients with renal or hepatic insufficiency.
The possibility of impaired hepatic and renal function should be considered in elderly patients and in patients with compromised general conditions.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1
Novalgina must not be used in patients with:
- hypersensitivity to other pyrazolones (eg phenazone, propiphenazone) or to pyrazolidines (eg phenylbutazone, oxifenbutazone);
- a history of agranulocytosis associated with the use of pyrazolones;
- impaired bone marrow function (eg after cytostatic therapy) or pathologies of the haematopoietic system, such as granulocytopenia;
- patients who experience bronchospasm or other anaphylactoid reactions (e.g. urticaria, rhinitis, angioedema) to non-narcotic analgesics (e.g. salicylates, paracetamol, diclofenac, ibuprofen, indomethacin, naproxen);
- acute intermittent hepatic porphyria (risk of induction of porphyria attacks);
- congenital deficiency of glucose-6-phosphate-dehydrogenase (risk of haemolysis);
- infants under 3 months or body weight less than 5 kg.
In infants aged 3 to 11 months Novalgina must not be administered intravenously.
Novalgina should not be administered parenterally in patients with hypotension or circulatory instability.
It is recommended not to use Novalgina in the first three months of pregnancy and, if used in the following three months, this should only be done after carefully evaluating the risk-benefit ratio. Novalgina must not be used in the last three months of pregnancy (see also section 4.6).
04.4 Special warnings and appropriate precautions for use
Agranulocytosis caused by metamizole is an immune-allergic event that lasts at least one week. Such reactions are very rare, can be serious, life-threatening and fatal. They are not dose-dependent. and can occur at any time during therapy.
Patients should be advised of the need to discontinue treatment and to seek immediate medical attention if any of the following symptoms possibly related to neutropenia occur: fever, chills, sore throat, oral ulceration. In case of neutropenia (neutrophils / mm3 blood count should be performed urgently and monitored until the return to normal values.
Pantocytopenia
In the event of pancytopenia, treatment should be stopped immediately and complete blood counts monitored until normalized.
All patients should be advised to contact their physician immediately if they experience signs and symptoms suggestive of blood dyscrasias (e.g. general malaise, infections, persistent fever, bruising, bleeding, paleness) while being treated with metamizole.
Anaphylactic shock: These reactions mainly occur in sensitive patients. Therefore metamizole should be used with caution in asthmatic or atopic patients (see section 4.3).
Given the risks associated with metamizole, the drug should only be used after evaluating the possibility of resorting to therapeutic alternatives.
Patients who have already experienced a hypersensitivity reaction with metamizole should no longer take metamizole or other pyrazolone drugs.
Novalgina tablets and Novalgina suppositories for adults are not suitable for the treatment of children under the age of 15 years.
Novalgina suppositories for children is not suitable for the treatment of children under the age of 4. For children under the age of 5, administration under medical supervision is recommended.
Anaphylactic / anaphylactoid reactions
When choosing the route of administration, it should be considered that the parenteral route is associated with an increased risk of anaphylactic / anaphylactoid reactions.
Patients with:
- analgesic asthma or intolerance to analgesics of the urticaria-angioedema type (see section 4.3),
- bronchial asthma, particularly if with concomitant polyposal rhinosinusitis,
- chronic urticaria,
- alcohol intolerance, meaning patients who react to minimal amounts of alcohol with symptoms such as sneezing, watery eyes or flushing of the face. Alcohol intolerance may indicate an undiagnosed analgesic asthma syndrome,
- intolerance to dyes (eg tartrazine) or preservatives (eg benzoates).
Prior to administration of Novalgina, specific questions should be asked of the patient. In cases at particular risk of anaphylactoid reactions, Novalgina should only be used after carefully weighing the possible risks versus the expected benefits. If Novalgina is to be administered in these circumstances, careful medical supervision and the availability of immediate emergency treatment are required.
Treatment should be discontinued immediately if any signs or symptoms of anaphylaxis (urticaria, angioedema, rash, dyspnoea, pallor or generalized hyperaemia, general malaise, hypotension, shock, laryngeal edema) or agranulocytosis (abrupt onset of severe associated neutropenia) appear. fever, marked asthenia, mouth ulcerations, pharynx and / or perineal ulcerations) or thrombocytopenia (tendency to bleed with or without petechiae).
Severe skin reactions
Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), skin reactions that can be life threatening, have been reported with the use of metamizole. If you develop symptoms or signs of SJS or TEN (such as progressive rash, often with blistering or mucosal lesions) treatment with metamizole should be stopped immediately and not restarted. Patients should be informed of the type of signs and symptoms and the possibility of a skin reaction should be carefully monitored , particularly in the first weeks of treatment.
Isolated hypotensive reactions
Administration of metamizole may cause isolated cases of hypotensive reactions (see section 4.8). These reactions are possibly dose-dependent and more likely with parenteral administration.
Furthermore, the risk of severe hypotensive reactions of this type is increased:
- if intravenous administration is not done slowly,
- in patients with pre-existing hypotension, with dehydration or reduced volume, with circulatory instability or with incipient circulatory failure,
- in patients with high fever.
In these patients, the use of metamizole should be carefully considered and, if it is administered, careful medical supervision is required. Preventive measures (stabilization of the circulation) may be necessary to reduce the risk of a hypotensive reaction. For patients with hypotension. o circulatory instability see section 4.3.
In patients in whom a reduction in blood pressure must be avoided, such as patients with severe coronary insufficiency or significant stenosis of the blood vessels supplying the brain, metamizole should only be used under close haemodynamic monitoring.
It is recommended to avoid the administration of high doses of metamizole in patients with renal or hepatic insufficiency, since the rate of elimination of the drug in such patients is reduced.
The intravenous injection should be given very slowly (no more than 1 ml per minute) to ensure that the injection can be stopped at the first signs of anaphylactic / anaphylactoid reactions (see section 4.8) and to minimize the risk of isolated hypertensive reactions.
Avoid the use of the specialty in trivial disorders. In addition, pyrazolones should be used only for the period of time necessary to control painful or febrile symptoms; the use of analgesics at high doses or for prolonged periods must be evaluated by the doctor.
The use of Novalgina, like any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant.
Novalgina should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
Important information about some of the ingredients
The tablets contain 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
Metamizole can cause a reduction in the plasma levels of cyclosporine; therefore it will be necessary to provide for regular checks of the concentration of cyclosporine in case of concomitant treatment with metamizole.
As with other analgesics, it is recommended to avoid alcohol intake during treatment with Novalgina, as interaction between the substances cannot be excluded.
The addition of metamizole to methotrexate may increase the haematotoxicity of methotrexate, particularly in elderly patients. Therefore this association must be avoided.
04.6 Pregnancy and lactation
Pregnancy
Metamizole crosses the placenta. There are no data regarding a toxic effect on the fetus: metamizole did not demonstrate teratogenic effects in rats and rabbits and foetotoxicity was observed only at high doses which were toxic to the mother. However, there are insufficient data on the use of metamizole during pregnancy.
Novalgina should not be used in the last three months of pregnancy.
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations was increased from less than 1% to to approximately 1.5%. The risk has been estimated to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause increased loss of pre- and post-implantation and embryo-fetal mortality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose
the fetus to:
- cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
- renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
the mother and the newborn, at the end of pregnancy, to:
- possible prolongation of bleeding time, and antiplatelet effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labor.
Feeding time
Metamizole metabolites are excreted in breast milk. Breastfeeding should be avoided during and for 48 hours after administration of Novalgina.
04.7 Effects on ability to drive and use machines
No harmful effects on the ability to concentrate and react at recommended doses have been reported. However, it must be taken into account, at least for higher doses, that the ability to concentrate and react may be altered thus constituting a risk in situations where these abilities are particularly important (e.g. driving cars or using machines) , especially if alcohol has been consumed.
04.8 Undesirable effects
• Disorders of the immune system
Metamizole can cause anaphylactic shock, anaphylactic / anaphylactoid reactions, which can be severe and life threatening and sometimes fatal. These reactions can appear at any stage of treatment, in a manner not related to the daily dose, even after repeated use in the past without complications.
Milder anaphylactic / anaphylactoid reactions typically manifest themselves with skin and mucosal symptoms (such as itching, burning, redness, hives, swelling), dyspnoea, and less frequently gastrointestinal symptoms. Milder reactions can progress to severe forms with generalized urticaria, severe angioedema (including laryngeal involvement), severe bronchospasm, cardiac arrhythmias, drop in blood pressure (sometimes preceded by a rise in blood pressure) and circulatory shock.
Such reactions may appear soon after the administration of metamizole or even after hours; however, they usually occur within the first hour of administration.
The risk of anaphylactic shock, however, appears to be higher with the parenteral forms.
In patients with analgesic asthma syndrome, intolerance reactions usually manifest themselves in the form of asthmatic attacks.
• Skin and subcutaneous tissue disorders
In addition to the cutaneous and mucosal manifestations of the anaphylactic / anaphylactoid reactions mentioned above, fixed drug eruptions may occasionally occur, rarely rash and in isolated cases also Stevens-Johnson syndrome or Lyell syndrome, which can be life-threatening. . In case of onset of such skin lesions it is necessary to immediately stop taking the drug and consult your doctor.
• Disorders of the blood and lymphatic system
Aplastic anemia, agranulocytosis and pancytopenia, including fatal outcome, leukopenia and thrombocytopenia. These reactions are considered immunological in nature. They may also occur after repeated use in the past without complications.
Typical signs of agranulocytosis include inflammatory lesions of the mucous membranes (e.g. oropharyngeal, anorectal, genitals), sore throat, fever (including persistent or recurrent fever). However, in patients receiving antibiotic therapy, typical signs of agranulocytosis may be minimum. Erythrocyte sedimentation rate is significantly increased, while lymph node swelling is generally mild or absent.
Typical signs of thrombocytopenia include an "increased bleeding tendency and petechiae of the skin and mucous membranes.
• Vascular pathologies
Isolated hypotensive reactions.
Occasionally, transient isolated hypotensive reactions (probably pharmacologically mediated and not accompanied by other signs of anaphylactic / anaphylactoid reactions) may occur after administration; in rare cases this reaction manifests itself as an acute drop in blood pressure.
• Renal and urinary disorders
It can occur in very rare cases, and particularly in patients with a history of kidney disease or, in case of overdose, acute worsening of renal function (acute renal failure), in some cases with oliguria, anuria or proteinuria. Acute interstitial nephritis has been reported in isolated cases.
• General disorders and administration site conditions
Local pain and reactions may occur at the injection site, sometimes with phlebitis.
Sometimes a red discoloration of the urine has been observed, which may be due to a metabolite present in low concentrations (rubazonic acid); the color disappears at the end of the treatment.
04.9 Overdose
Symptoms of overdose
Nausea, vomiting, abdominal pain, renal impairment / acute renal failure (e.g. due to interstitial nephritis) and more rarely central nervous system symptoms (dizziness, somnolence, coma, convulsions) have been reported following acute overdose. ), drop in blood pressure (sometimes progressing to shock) and also cardiac arrhythmias (tachycardia).
After administration of very high doses, the excretion of a harmless metabolite (rubazonic acid) can cause red urine.
Treatment of overdose
There is no known specific antidote for metamizole. If the intake has taken place recently, strategies can be tried to limit the further systemic absorption of the drug such as primary detoxification (gastric lavage) or means that reduce absorption (activated carbon). The main metabolite (4N-methylaminoantipyrine) can be eliminated by hemodialysis, haemofiltration, haemoperfusion or plasma filtration.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: analgesics and antipyretics, pyrazolones.
ATC code: N02BB02.
Noramidopyrine methanesulfonate (metamizole / dipyrone) sodium has high analgesic, antipyretic and antispastic activity.
The analgesic activity occurs both centrally and peripherally.
After i.v. the effect occurs in 5-15 minutes, while after the i.m. it occurs in 15-30 minutes; the duration of the effect is generally 6 hours.
The antipyretic activity is all the more marked the higher the fever, the normal temperature is not affected.
Several experimental models highlight the anti-inflammatory activity, while other studies, both "in vivo" and "in vitro" on intestinal, bronchial and uterine smooth muscles, highlight the spasmolytic one.
05.2 Pharmacokinetic properties
In humans, after oral administration of 480 mg of metamizole the blood peak is reached in 1.5 hours (13.4 ± 0.8 mcg / ml); the plasma half-life is 6.9 ± 0.9 hours.
By the urinary route, metamizole is eliminated in the first 24 hours for 71 ± 6% of the administered dose and in the following 24 hours for 18 ± 7% (tests carried out with the labeled product).
05.3 Preclinical safety data
The LD50 (mg / kg) of metamizole is 4,351 (os), 2,389 (s.c.) and 2,081 (s.c.) in the rat and 4,161 (s.c.), 2,389 (s.c.) and 2,338 (s.c.) in the mouse.
The i.v. and s.c. of 150 mg / kg / day, continued for 4 weeks, do not induce any toxic effect in rats and dogs; the same animal species tolerate well the oral administration of 100 and 300 mg / kg / day for 6 months.
Mutagenicity tests are negative at all concentrations considered.
The results of specific tests conducted in rats, administering 1,000 and 3,000 ppm of metamizole combined with 1,000 ppm of NaNO2 in the diet for 18 months, demonstrate that metamizole has no carcinogenic potential.
There is no further information on preclinical data other than that already reported elsewhere in this Summary of Product Characteristics (see section 4.6).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Oral drops, solution
citrus flavor, sodium phosphate, monosodium sodium phosphate and purified water.
Tablets
corn starch, lactose, talc, sodium bicarbonate and magnesium stearate.
Adult suppositories
solid semisynthetic glycerides and soy lecithin.
Suppositories for children
solid semisynthetic glycerides and soy lecithin.
06.2 Incompatibility
No chemical-physical incompatibilities are known.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
Novalgina 500 mg tablets
Novalgina Children 300 mg suppositories
This medicine does not require any special storage conditions.
Novalgina 500 mg / mL oral drops, solution.
Do not store above 25 ° C.
Novalgina Adults 1 g suppositories
Do not store above 30 ° C.
06.5 Nature of the immediate packaging and contents of the package
Novalgina 500 mg / mL oral drops, solution.
Colored type III glass bottle, with dropper and screw cap in high density polyethylene; bottle of 20 ml.
Novalgina 500 mg tablets
Blister packs in opaque white PVC and aluminum, heat-sealed; 20 tablets.
Novalgina Adults 1 g suppositories
Blisters with PVC and polyethylene pockets, opaque white; 5 adult suppositories.
Novalgina Children 300 mg suppositories
Blisters with PVC and polyethylene pockets, opaque white; 5 suppositories for children.
06.6 Instructions for use and handling
Novalgina 500 mg / ml oral drops, solution
The bottle has the "Childproof closure'.
To open, press on the cap and at the same time unscrew it, turning it anticlockwise. Close after use. The bottle is closed if you hear a click when unscrewing the cap without pressing.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
sanofi-aventis S.p.A. - Viale L. Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
Novalgina 500 mg / ml oral drops, solution, 20 ml bottle: A.I.C. n. 008679033
Novalgina 500 mg tablets, 20 tablets: A.I.C. n. 008679019
Novalgina Adults 1 g suppositories, 5 suppositories: A.I.C. n. 008679045
Novalgina Children 300 mg suppositories, 5 suppositories: A.I.C. n. 008679058
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Tablets: December 1968 / June 2010
Drops and suppositories: February 1954 / June 2010
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination of April 2013
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