Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Optalgin contains the pyrazolone derivative Dipyrone and are associated with rare but life-threatening risks of shock and agranulocytosis (see section 4.8).

Patients who experience anaphylactoid reactions to Dipyrone are at particular risk of experiencing similar reactions to other non-narcotic analgesics.

Patients who experience an anaphylactic reaction or other immunologically mediated reaction to Dipyrone (e.g., agranulocytosis) are at particular risk of experiencing similar reactions 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.

Agranulocytosis

Optalgin Caplets/Tablets SPC, SZ, 6/2022 NOTIFICATION
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.

Patients should be instructed to stop using this medicinal product immediately if the following signs and symptoms occur and to seek medical advice: unexpected deterioration in their general condition (such as fever, chills, sore throat, difficulty swallowing), refractory or recurrent 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 must be stopped immediately and the blood count (including differential blood count) checked. Treatment must be discontinued even before laboratory test results become available (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), administration of Optalgin must be discontinued immediately and blood count (including differential blood count) must be monitored. Treatment must be discontinued even before laboratory test results become available.


Pancytopenia
If pancytopenia occurs, treatment must be discontinued immediately and complete blood count must be monitored until it normalizes (see section 4.8). All patients should be instructed to consult their doctor immediately if signs and symptoms occur during treatment which may indicate blood dyscrasia (e.g., malaise, infection, persistent fever, bruising, bleeding, pallor).

Anaphylactic/anaphylactoid reactions
The risk of potentially severe anaphylactoid reactions to Optalgin is significantly increased in patients with:
- Analgesic-asthma-syndrome or analgesic-intolerance of urticaria-angioedema type (see section 4.3).
- Bronchial asthma, particularly with concurrent rhinosinusitis and nasal polyps.
- Chronic urticaria.
- Intolerance to coloring agents (e.g., tartrazine) or preservatives (e.g., benzoates).
- Alcohol intolerance. Such patients react to even minimal amounts of alcohol with symptoms such as sneezing, watery eyes and severe flushing. Alcohol intolerance of this kind may be indicative of as yet undiagnosed analgesic-asthma-syndrome (see section 4.3).

Anaphylactic shock may occur, primarily in susceptible patients. Special care should therefore be taken when administered to patients with asthma or atopy.

The patient must be asked about this before the administration Optalgin. In patients with an increased risk of anaphylactoid reactions, Optalgin may be used only after carefully weighing up the possible risks against the expected benefit (see also section 4.3). If Optalgin 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.


Optalgin Caplets/Tablets SPC, SZ, 6/2022 NOTIFICATION
If signs and symptoms suggestive of these reactions occur, dipyrone should be discontinued immediately and dipyrone therapy must not be resumed at any stage (see section 4.3) 
Isolated hypotensive reactions
Optalgin may induce hypotensive reactions (see also section 4.8).
These reactions may be dose-dependent. This is more likely with parenteral than enteral administration.
The risk of such reactions is also increased in:
- Patients with, for example, pre-existing hypotension, volume depletion or dehydration, unstable circulation or incipient circulatory failure (e.g., in patients with myocardial infarction or multiple trauma).
- Patients with high fever.

Careful indication testing and close monitoring are therefore required in such patients. Preventive measures (e.g., circulatory stabilization) may be required to reduce the risk of hypotensive reactions.

Optalgin should only be used with careful monitoring of hemodynamic parameters in patients in whom a reduction in blood pressure must be avoided at all costs, e.g., patients with severe coronary heart disease or relevant cerebrovascular stenosis.

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 immune-allergic 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 is used in patients with renal or hepatic dysfunction (see section 4.2).

Effects on Driving

4.7 Effects on ability to drive and use machines

Within the recommended dosage range there is no known impairment of the ability to concentrate and react. As a precaution, however, at least at higher dosages, the possibility of impairment of the ability to concentrate and react should be taken into account, and patients should avoid using machines, driving or other hazardous activities. This applies particularly in conjunction with alcohol.