Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Optalgin Drops contains the pyrazolone derivative Dipyrone (Metamizole) and are associated with rare but life-threatening risks of shock and agranulocytosis (see section 4.8).

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

Patients who experience an anaphylactic reaction or another immunologically mediated reaction to Optalgin (e.g., agranulocytosis) are also at particular risk of experiencing similar reactions to other pyrazolones and pyrazolidines.

Patients who experience anaphylactic or another immunologically mediated reaction to other pyrazolones, pyrazolidines or other non-narcotic analgesics are also at particular risk of experiencing similar reactions to Optalgin Drops.

Agranulocytosis
As soon as signs of neutropenia occur (< 1,500 neutrophils/mm3), treatment must be interrupted immediately and the complete blood count must be monitored until normalisation.

Patients should be told to stop use of this medicinal product immediately and to consult a doctor if the following signs and symptoms occur: unexpected deterioration in the general condition (such as fever, chills, pain in the throat, difficulties swallowing), fever that recurs or does not resolve, as well as painful changes to the mucous membranes, particularly in the mouth, nose and throat or genital and anal areas. The use of Optalgin Drops should be interrupted immediately and the blood count (including differential blood count) monitored. Treatment must be withdrawn even before the results of laboratory tests become available (see section 4.8).

Thrombocytopenia
If signs of thrombocytopenia occur, such as increased tendency to bleed or petechiae on the skin and mucous membranes (see section 4.8), the use of Optalgin Drops must be immediately interrupted and the blood count (including differential blood count) monitored. Discontinuation of treatment must not be withheld until laboratory test results are 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
When selecting the route of administration, it should be taken into account that parenteral administration of Optalgin Drops is associated with a higher risk of anaphylactic and 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).

An anaphylactic shock may occur, primarily in susceptible patients. Special care should therefore be taken when administered to patients with asthma or atopy.
Patients should be questioned accordingly prior to the administration of Optalgin Drops. In patients at increased risk of anaphylactoid reactions, Optalgin Drops should be used only after carefully weighing up potential risks against the expected benefit (see also section 4.3). If Optalgin Drops is administered in such cases, the patient should be closely monitored medically and emergency facilities should be available.


Severe cutaneous 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 with Dipyrone therapy.

Patients should be advised of the signs and symptoms and monitored closely for skin reactions.

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).

Drug-induced liver injury
Cases of acute hepatitis of predominantly hepatocellular pattern have been reported in patients treated with metamizole with an onset of few days to few months following treatment initiation. Signs and symptoms include elevated serum hepatic enzymes with or without jaundice, frequently in context of other drug hypersensitivity reactions (e.g. skin rash, blood dyscrasias, fever and eosinophilia) or accompanied by features of autoimmune hepatitis. Most patients recovered on discontinuation of metamizole treatment; nevertheless, in isolated cases, progression to acute liver failure requiring liver transplantation was reported.

The mechanism of metamizole-induced liver injury is not clearly elucidated, but data indicate an immuno-allergic mechanism.

Patients should be instructed to contact their doctor in case symptoms suggestive of liver injury occur.
In such patients metamizole should be discontinued and liver function should be assessed.

Metamizole should not be re-introduced in patients with an episode of hepatic injury during treatment with metamizole for which no other cause of liver injury has been determined.

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:
- 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., in patients with myocardial infarction or multiple trauma);
- Patients with high fever.

The indication should therefore be carefully established in such patients and they should be closely monitored.. Preventive measures (e.g., circulatory stabilization) may be required to reduce the risk of hypotensive reactions.

Optalgin Drops may be administered only if hemodynamic parameters are closely monitored 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.

Optalgin Drops should be only used 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).
Excipients:
• Sodium
Optalgin drops contains 37.5 mg sodium per 1 ml, equivalent to 1.9% of the maximum daily dietary sodium intake of 2 g recommended by the WHO for an adult.

• Benzyl alcohol
Benzyl alcohol has been associated with the risk of serious side effects including breathing problems (called “gasping syndrome”) in infants and toddlers. The medicinal product should not be used for more than a week in infants and toddlers (under 3 years old) because of accumulation.
Large quantities of benzyl alcohol should be used with caution and only when absolutely necessary because of the risk of accumulation and toxicity (metabolic acidosis), particularly in people with impaired hepatic or renal function, and during pregnancy and lactation.

• Propylene glycol
This medicinal product should be used with caution in infants under 4 weeks old, particularly if they are also receiving other medicinal products containing propylene glycol or alcohol.

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 in particular in conjunction with alcohol.