Source: European Medicines Agency (EU) Revision Year: 2013
Metamizole sodium contains the pyrazolone derivative metamizole sodium, and is associated with the rare but life-threatening risk of shock and agranulocytosis (see section 4.8).
Patients who experience anaphylactoid reactions to metamizole sodium are at particular risk of experiencing similar reactions to other non-narcotic analgesics.
Patients who experience an anaphylactic reaction or another immunologically mediated reaction (e.g. agranulocytosis) to metamizole sodium are at particular risk of experiencing similar reactions to other pyrazolones and pyrazolidines.
If signs of agranulocytosis or thrombocytopenia occur, administration of metamizole sodium must be discontinued immediately. Treatment must be withdrawn even before the results of laboratory tests become available.
If pancytopenia occurs, administration of metamizole sodium must be discontinued immediately and the blood count must be controlled until it is normal again (see section 4.8). All patients should be advised to seek help from their doctor, if during treatment signs and symptoms (e.g. deterioration in the general condition, infect, persistent fever, haematomas, bleeding, paleness) indicating a blood dyscrasia are observed.
The risk of possibly severe anaphylactoid reactions to metamizole sodium is markedly increased in patients with:
The life-threatening skin reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported during the use of metamizol sodium. If signs or symptoms (progressive rash, often combined with blisters or lesions of mucosa) of SJS or TEN develop, treatment with metamizole sodium must be discontinued immediately and must not be resumed.
Patients should be advised of signs and symptoms and should be closelyy monitored for skin reactions, especially in the first weeks of treatment.
Metamizole sodium can precipitate hypotensive reactions (see also section 4.8). These reactions may be dose dependent. The risk of such reactions is also increased in:
The indication should therefore be carefully established in such patients and they should be closely monitored. Preventative measures (e.g. circulatory stabilisation) may be necessary to reduce the risk of hypotensive reactions.
Metamizole sodium may be administered only if haemodynamic parameters are closely monitored in patients in whom a reduction in blood pressure must be avoided, e.g. patients with severe coronary heart disease or relevant cerebrovascularstenosis.
Metamizole sodium should be used only after careful consideration has been given to the benefit versus risk ratio and only if appropriate precautions are taken in patients with impaired renal or hepatic function (see section 4.2).
Patients should be questioned accordingly prior to the administration of metamizole sodium. In patients with increased risk of anaphylactoid reactions, metamizole sodium should be used only after carefully weighing up potential risks against the expected benefit. If metamizole sodium is administered in such cases, the patient should be closely monitored medically and emergency facilities should be available.
Metamizole sodium contains 1.5 mmol (or 35 mg) sodium per ml (20 drops). To be taken into consideration by patients on a controlled sodium diet.
Concurrent administration of metamizole sodium and chlorpromazine can lead to severe hypothermia. Metamizole sodium can reduce plasma ciclosporin levels. In combined administration, a dose adjustment may be required.
The pyrazolone class of active substances has a known potential to cause interactions with oral anticoagulants, captopril, lithium, methotrexate and triamterene and to influence the efficacy of antihypertensive agents and diuretics. It has not been established how far metamizole sodium leads to these interactions.
There are insufficient data available on the use of metamizole sodium in pregnant women. Metamizole sodium crosses the placental barrier. In animal studies, metamizole sodium showed no teratogenic effects (see section 5.3). Due to lack of adequate experience in humans, during the 1st and 2nd trimester of pregnancy metamizole sodium should only be taken after careful medical assessment of the benefit-risk balance.
Although metamizole sodium is only a weak inhibitor of prostaglandin synthesis, the possibility of premature occlusion of the ductus arteriosus (ductus Botalli) and perinatal complications due to a reduction in platelet aggregation in the mother and child cannot be excluded. Metamizole sodium is thus contraindicated during the last trimester of pregnancy (see section 4.3).
The metabolites of metamizole sodium are excreted into the breast milk, and breast-feeding must therefore be avoided during intake/administration and for at least 48 hours after the last intake/administration of metamizole sodium (see section 4.3).
Metamizole sodium can have influence on the ability to drive and use machines. In the recommended dose range, no impairment of the ability to concentrate or of responsiveness is known. As a central active component is postulated for metamizole sodium, and overdose can lead to central adverse reactions, the possibility of impairment should be considered, at least at higher doses, and operating machinery, driving vehicles and other hazardous activities should be avoided. This particularly applies in combination with alcohol.
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
The main undesirable effects of metamizole sodium are derived from hypersensitivity reactions. The most significant are shock and agranulocytosis. These reactions occur rarely or very rarely, but are life-threatening and may also occur if metamizole sodium was previously given without complications.
Rare: leukopenia
Very rare: agranulocytosis or thrombocytopenia.
Not known: panzytopenia, including cases with lethal outcome
These reactions can also occur even if previous administration of metamizole sodium was without complications.
The risk of agranulocytosis increases if metamizole sodium is administered for longer than one week. Agranulocytosis is typically characterised by inflammatory mucosal changes (e.g. in the mouth, nose, throat and genital and anal region), sore throat, swallowing difficulties, fever and chills. In patients receiving antibiotics, these signs may, however, be minimal. There is little or no swelling of the lymph nodes or spleen. The erythrocyte sedimentation rate (ESR) is markedly accelerated, the granulocytes are reduced considerably or completely absent. In general, haemoglobin, erythrocyte and platelet values are normal.
An unexpected deterioration in the general condition may indicate agranulocytosis.
Immediate discontinuation is essential for recovery. It is therefore strongly recommended to discontinue <Invented Name> immediately, without waiting for the results of laboratorydiagnostic tests, if signs of agranulocytosis occur.
Rare: anaphylactoid or anaphylactic reactions
Very rare: severe and life-threatening anaphylactoid or anaphylactic reactions
Such reactions to medicinal products may occur during the injection, immediately after administration or may also develop hours afterwards; in the majority of cases, however, they occur during the first hour post-administration.
Milder reactions typically take the form of skin and mucosal reactions (e.g. prorates, a burning sensation, redness, urticaria, swelling), dyspnoea and, more rarely, gastrointestinal complaints (e.g. nausea, dyspepsia, vomiting). Such mild reactions may become severe with generalised urticaria, severe angioedema (including laryngeal oedema), severe bronchospasm, cardiac arrhythmias, a fall in blood pressure (sometimes also with a preceding rise in blood pressure) and circulatory shock. In patients with analgesic asthma syndrome, intolerance reactions typically take the form of asthma attacks.
At the first signs of shock, such as a cold sweat, dizziness, light-headedness, skin discoloration, a sensation of discomfort around the heart, the necessary emergency measures should be initiated.
Rare: hypotensive reactions during or after administration.
These may be pharmacological in origin and not accompanied by other signs of an anaphylactoid or anaphylactic reaction. Such a reaction leads only rarely to a severe fall in blood pressure. Rapid intravenous injection increases the risk of such a hypotensive reaction.
Rare: fixed drug exanthema or other exanthemas (rash), in isolated cases, Stevens-Johnson syndrome or Lyell’s syndrome can occur. Metamizole sodium must therefore be discontinued immediately if skin reactions occur.
Very rare: particularly in patients with hypovolaemia or pre-existing renal disease and following overdose, renal impairment with anuria or oliguria, proteinuria and interstitial nephritis can occur.
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 the national reporting system listed in Appendix V.
Not applicable.
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