Source: Web Search Revision Year: 2017 Publisher: Manufactured by Sanofi Egypt S.A.E under license from Sanofi-Aventis Germany
Novalgin contains the pyrazolone derivative metamizole and carries the rare but life-threatening risk of shock and agranulocytosis (see section 4.8).
Patients who show anaphylactoid reactions to Novalgin are also particularly at risk of reacting in the same way to other non-narcotic analgesics.
Patients who show an anaphylactic or other immunologically mediated reaction to Novalgin (e.g. agranulocytosis), are also particularly at risk of reacting in the same way to other pyrazolones and pyrazolidines.
Agranulocytosis :If signs of agranulocytosis or thrombocytopenia (see section 4.8) are observed, the use of Novalgin must be discontinued immediately and the blood count monitored (including dierential blood count). The treatment should be discontinued without waiting for the results of the laboratory tests.
Pancytopenia :In case of pancytopenia, treatment must be immediately discontinued and the complete blood count should be monitored until it normalizes (see section 4.8). All patients should be advised to seek immediate medical attention if they develop signs and symptoms during treatment which are suggestive of blood dyscrasias (e.g. general malaise, infection, persistent fever, bruising, bleeding, pallor).
Anaphylactic/anaphylactoid reactions :In selecting the method of administration it should be borne in mind that the parenteral administration of Novalgin is associated with a higher risk of anaphylactic and anaphylactoid reactions (see section 4.2 “Safety precautions for injection”).
The risk of possibly serious anaphylactoid reactions to Novalgin is clearly elevated for patients with:
An anaphylactic shock may predominantly occur in sensitive patients. Therefore, the administration in asthmatic or atopic patients is subject to particular caution.
Severe cutaneous reactions: The life-threatening cutaneous reactions of the Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) have been reported with the use of metamizole. If symptoms or sings of SJS or TEN (such as progressive skin rash often with blisters of mucosal lesions) develop, the treatment with Novalgin must be discontinued immediately, and must not be re-initiated at any time.
Patients should be advised of the signs and symptoms and monitored closely for skin reactions, particularly within the first weeks of treatment
Isolated hypotensive reactions: Novalgin can trigger hypotensive reactions (see also section 4.8). These reactions may be dose-related and should be expected more often in parenteral than in enteral administration. The risk of such reactions is also increased in the case of:
Careful examination of the indication (see also section 4.3) and close monitoring is therefore necessary in these patients. Preventive measures (e.g. stabilisation of the circulation) may be necessary to reduce the risk of hypotensive reactions.
The use of Novalgin must be accompanied by careful monitoring of the haemodynamic parameters in patients in whom a decrease in blood pressure must be avoided at all costs, e.g. in severe coronary heart disease or signicant stenosis of the blood vessels supplying the brain.
Novalgin should only be used after strict benet-to-risk analysis and with appropriate precautionary measures in patients with impaired renal or hepatic functions (see section 4.2). Before giving Novalgin, the patient must be questioned appropriately. In patients with a high risk of anaphylactoid reactions Novalgin should only be used after careful consideration of the possible risks, weighed against the expected benets.
If Novalgin is given in these cases, the patient should be subject to close medical monitoring and facilities for emergency treatment should be kept immediately to hand.
On external packaging: Warning: contains metamizole.
1 ml contains 1.42 mmol (32.7 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.
Metamizole may lead to a reduction in serum cyclosporin levels. These must therefore be monitored if Novalgin is used concomitantly.
During concomitant use of Novalgin and chlorpromazine, severe hypothermia may occur.
Adding metamizole to methotrexate may increase the hematotoxicity of methotrexate particularly in elderly patients. Therefore, this combination should be avoided.
Metamizole may reduce the effect of acetylsalicylic acid (aspirin) on platelet aggregation, when taken concomitantly. Therefore, this combination should be used with caution in patients taking low dose aspirin for cardioprotection.
Metamizole may cause a reduction in bupropion blood concentrations. Therefore, caution is advised when metamizole and bupropion are administered concurrently.
For the pyrazolones, it is known that interactions can occur with oral anticoagulants, captopril, lithium, and triamterene and the efficacy of antihypertensive drugs and diuretics may be modified. The extent to which metamizole also leads to these interactions is unknown.
Interference with laboratory tests: Interference with laboratory tests which use Trinder/Trinder-like reactions (e.g. tests to measure serum levels of creatinine, triglycerides, HDL cholesterol, and uric acid) has been reported in patients using metamizole.
No adequate data is available on the use of Novalgin in pregnant women. Metamizole crosses the placental barrier. In animal experimental studies metamizole showed no teratogenic effects (see section 5.3). Since no adequate information is available in humans, Novalgin should not be used during the first trimester of pregnancy and should be used only after strict medical analysis of the benefit-to-risk ratio in the second trimester.
Although metamizole is only a weak inhibitor of prostaglandin synthesis, the possibility of premature closure of the ductus arteriosus (duct of Botallo) and perinatal complications due to a reduction in foetal and maternal platelet aggregation cannot be ruled out. Novalgin is therefore contraindicated during the last trimester of pregnancy (see section 4.3).
The metabolites of metamizole are eliminated in breast milk, so that breast feeding should be discontinued when using metamizole and for at least 48 hours after taking the last dose of Novalgin (see section 4.3).
No impairment of concentration and the ability to react is known in the normal dose range. As a precautionary measure, however, at least at higher doses, the possibility of impairment should be considered and the use of machines, driving vehicles and other hazardous activities should be avoided. This is particularly the case in combination with alcohol.
The incidences of undesirable effects are based on the following categories: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1,000 to <1/100), rare (>1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Rare: Leucopenia
Very rare: Agranulocytosis, including fatal outcome, thrombocytopenia.
Not known: Aplastic anaemia, pancytopenia, including fatal outcome.
These reactions may also occur when metamizole has previously been given without complications.
There are occasional indications that the risk of agranulocytosis may be increased when Novalgin is used for more than one week.
This reaction is not dose dependant and may occur at any time during treatment. The signs are a high fever, chills, sore throat, swallowing difficulties and inflammation in the mouth, nose, throat and genital or anal area. In patients receiving antibiotics these signs may, however, be minimal. Swelling of lymph nodes or the spleen is slight or entirely absent. The erythrocyte sedimentation rate is greatly accelerated, granulocytes are considerably reduced or entirely absent. In general, but not invariably, values for haemoglobin, red cells and platelets are normal (see section 4.4).
Immediate discontinuation is crucial for recovery. It is therefore strictly recommended that Novalgin should be discontinued immediately without waiting for the results of diagnostic laboratory investigations, if the patient’s general condition unexpectedly deteriorates, fever does not abate or recurs, or if painful changes to the mucous membranes are observed, particularly in the mouth, nose and throat.
In case of pancytopenia, treatment must be immediately discontinued and the complete blood count should be monitored until it normalizes (see section 4.4).
Rare: Anaphylactic/anaphylactoid reactions*.
Very rare: Analgesic induced asthma syndrome. In patients with an analgesic asthma syndrome, intolerance reactions typically appear in the form of asthma attacks.
Not known: Anaphylactic shock*.
* These reactions may occur in particular after parenteral administration, may be severe and life-threatening, sometimes fatal. They may occur even after metamizole has previously been used on many occasions without complications.
These reactions may develop during the injection or immediately after administration but may also appear some hours later. However, they develop primarily during the first hour after administration. Milder reactions are typically seen in the skin and mucous membranes (such as itching, burning, reddening, urticaria, swelling), dyspnoea and – more rarely – gastrointestinal disorders. These milder reactions may progress to more severe forms with generalised urticaria, severe angioedema (also affecting the larynx), severe bronchospasm, disorders of cardiac rhythm, hypotension (sometimes also with a preceding increase in blood pressure), circulatory shock. Therefore, if skin reactions develop, Novalgin must be discontinued immediately.
Not known: Kounis syndrome
Uncommon: Hypotensive reactions during or after use, which may have a pharmacological cause and are not accompanied by other signs of anaphylactoid or anaphylactic reaction. A reaction of this kind can lead to a fall in blood pressure that may be serious. Rapid intravenous injection increases the risk of a hypotensive reaction.
In the event of a high fever, there may also be a critical fall in blood pressure related to dose, with no further sings of a hypersensitivity reaction.
Not known: Cases of gastrointestinal bleeding have been reported.
Uncommon: Fixed drug eruptions.
Rare: Rash (e.g. maculo-papular exanthema).
Very rare: Sevens-Johnson syndrome or Toxic Epidermal Necrolysis (discontinue treatment, see section 4.4).
Very rare: acute deterioration in renal function, very rarely involving development of proteinuria, oliguria or anuria, and/or acute renal failure; acute interstitial nephritis.
With injections, pain can occur at the injection site and there may be local reactions, very rarely even phlebitis.
A red coloration of the urine has been sometimes observed, which may be due to a harmless metamizole metabolite present at low concentration: rubazonic acid.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via pharmacovigilance.eg@sanofi.com.
In view of the possibility of incompatibility, it is recommended that the solution for injection should not be mixed with other therapeutic agents for injection or infusion (with respect to miscibility with solutions for infusion, see also section 4.2).
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