Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use

Optalgin® Teva 1 g/2 ml solution for injection contains the pyrazolone derivative metamizole and carries the rare but life-threatening risks of shock and agranulocytosis (see section 4.8).

Patients who display anaphylactoid reactions to dipyrone are at particular risk of reacting in the same way to other non-narcotic analgesics.

Patients who display an anaphylactic or other immunologically mediated reaction (e.g.
agranulocytosis) to dipyrone are also at particular risk of reacting in the same way to other pyrazolones and pyrazolidines.

Patients who display an anaphylactic or other immunologically mediated reaction to other pyrazolones, pyrazolidines or other non-narcotic analgesics are also at high risk of having such a reaction to Optalgin Teva 1g/2 ml solution for injection.


Agranulocytosis
The treatment must be suspended immediately as soon as neutropenia (<1,500 neutrophils/mm3) occurs and the full blood count monitored until it returns to normal.
If the following signs and symptoms occur, patients should be instructed to stop using this medicinal product immediately and seek medical advice: unexpected deterioration in their general condition (such as fever, rigor, sore throat, difficulty swallowing), refractory or new-onset fever and painful mucosal changes, especially in the region of the mouth, nose and throat or in the genital or anal region.
The use of Optalgin Teva 1g/2ml solution for injection must be stopped immediately and the blood count (including differential blood count) checked. Do not wait for the results of the laboratory tests before stopping the treatment (see section 4.8).

Thrombocytopenia
If signs of thrombocytopenia occur such as an increased bleeding tendency and petechiae on the skin and mucosae (see section 4.8), the use of Optalgin Teva 1g/2ml solution for injection must be stopped immediately and the blood count (including differential count) checked. Do not wait for the results of the laboratory tests before stopping the treatment.

Pancytopenia
If pancytopenia occurs, the treatment must be stopped immediately and the full blood count monitored until it normalises (see section 4.8). All patients should be informed that they should consult the doctor immediately if signs and symptoms indicating blood dyscrasia occur during the treatment (e.g., general malaise, infection, persistent fever, bruising, bleeding, pallor).

Anaphylactic/Anaphylactoid reactions
In choosing the route of administration,
it must be borne in mind that parenteral administration of dipyrone is associated with a higher risk of anaphylactic or anaphylactoid reactions.

The risk of potentially serious anaphylactoid reactions to dipyrone is distinctly higher in patients with: -     analgesic asthma syndrome or urticaria/angio-oedema type intolerance of analgesics (see section 4.3).
-     bronchial asthma, especially if accompanied by rhinosinusitis and nasal polyps, -     chronic urticaria.
-     intolerance of dyes (e.g. tartrazine) and preservatives (e.g. benzoates).
-     alcohol intolerance. Such patients react even to small quantities of alcoholic drinks with symptoms such as sneezing, eye watering and pronounced facial reddening. An alcohol intolerance of this kind can be a sign of a previously undiagnosed analgesic asthma syndrome (see section 4.3).

Anaphylactic shock can occur, primarily in sensitive patients. Particular caution is therefore indicated in the case of administration to patients with asthma or atopy.
The patient must be asked about this before the administration of Optalgin Teva 1g/2ml solution for injection. In patients with an increased risk for anaphylactoid reactions, Optalgin Teva 1g/2ml solution for injection may be used only after carefully weighing the possible risks against the expected benefit (see also section 4.3). If Optalgin Teva 1g/2ml solution for injection is administered in such cases, the patient must be closely monitored by a doctor, ensuring emergency equipment is on standby.


Severe skin reactions
Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening, or fatal, have been reported in connection with dipyrone therapy.

The patients are to be informed about the signs and symptoms and monitored closely for skin reactions.

If signs and symptoms suggestive of thesse reactions occur, Optalgin® Teva 1 g/2 ml solution for injection should be discontinued immediately and dipyrone must not be resumed at any stage (see section 4.3).

Isolated hypotensive reactions
Dipyrone can trigger hypotensive reactions (see also section 4.8). These reactions are possibly dose- dependent. They are more likely in the case of parenteral than with enteral administration. The risk of such reactions is also higher in:
-      the case of too rapid intravenous injection (see section 4.2), -      patients with, for example, pre-existing hypotension, volume depletion or dehydration, unstable circulation or incipient circulatory failure (e.g. patients with myocardial infarction or multiple injuries),
-      patients with a high fever.


Careful verification of the indication (see also section 4.3) and close monitoring are therefore necessary in these patients. Preventive measures (e.g., stabilisation of the circulation) may be necessary to reduce the risk of hypotensive reactions.

Dipyrone may be used only with careful monitoring of the haemodynamic parameters in patients in whom a fall in blood pressure must be avoided at all costs, e.g. in severe coronary heart disease or relevant stenoses of the blood vessels supplying the brain.

Drug-induced liver damage
Cases of acute hepatitis with a predominantly hepatocellular pattern occurring within a few days to a few months of the start of treatment have been reported in patients treated with dipyrone . The signs and symptoms include raised serum levels of liver enzymes with or without jaundice, often in association with other drug hypersensitivity reactions (e.g., rash, blood count abnormalities, fever and eosinophilia) or accompanied by features of autoimmune hepatitis. Most patients recovered after the discontinuation of dipyrone treatment. In isolated cases, however, progression to acute liver failure with the need for liver transplantation has been reported.

The mechanism of dipyrone -induced liver damage has not been clearly elucidated. However, the data suggest an immunoallergic mechanism.

Patients should be told to consult their doctor if they develop symptoms that suggest liver damage.
Treatment with dipyrone should be discontinued in such patients and hepatic function checked.

Dipyrone should not be administered again if liver damage has previously occurred on treatment with dipyrone for which no other cause could be found.

Impaired renal or hepatic function
The risks should be weighed rigorously against the benefits and appropriate precautions taken before Optalgin® Teva 1 g/2 ml solution for injection is used in patients with renal or hepatic dysfunction (see section 4.2).

Optalgin® Teva 1 g/2 ml solution for injection
One ampoule contains 65 mg sodium, equivalent to 3.3% of the 2g WHO-recommended maximum daily sodium dietary intake for adults. This must be borne in mind for people on a sodium-controlled (low sodium/salt) diet.

Effects on Driving

4.7     Effects on ability to drive and use machines
In the recommended dose range, no impairment of concentration and reaction speeds is known.
Nevertheless, as a precaution, the possibility of impairment should be considered, at least in the case of higher dosages, and the use of machines, driving or other dangerous activities should be avoided.
This applies particularly if the product is taken with alcohol.