Adverse reactions : תופעות לוואי

4.8    Undesirable effects

The frequency of undesirable effects is stated on the basis of the following categories: 
Very common         ≥ 1/10
Common              ≥ 1/100, < 1/10
Uncommon            ≥ 1/1000, < 1/100
  Rare                ≥ 1/10,000, < 1/1000
Very rare           ≤ 1/10,000
Not known           Frequency cannot be estimated from the available data 

Blood and lymphatic system disorders
Rare:                         Leucopenia.
Very rare:                    Agranulocytosis, including cases with a fatal outcome, thrombocytopenia.
Not known:                    Aplastic anaemia, pancytopenia, including cases with a fatal outcome.

These reactions can occur even if dipyrone has previously been administered without complications.

There are isolated reports suggesting that the risk of agranulocytosis may possibly be increased if Optalgin® Teva 1 g/2 ml solution for injection is administered for longer than a week.

This reaction is not dose-dependent and can occur at any time during treatment. It manifests as high fever, shivering, sore throat, swallowing difficulties and inflammation of the mouth, nose, throat, genitals or anal regions. In patients receiving antibiotics, however, these signs may be minimal.
Swelling of lymph nodes or the spleen is minor or completely absent. The erythrocyte sedimentation rate is greatly increased and granulocytes are considerably reduced or completely absent. In general, but not always, haemoglobin, erythrocyte and platelet values are normal (see section 4.4).

Immediate cessation is crucial to recovery. It is therefore urgently recommended to stop Optalgin® Teva 1 g/2 ml solution for injection immediately, without waiting for the laboratory results, if an unexpected deterioration in the patient’s general condition occurs, the fever does not subside or recurs, or painful changes occur in the mucosa, especially in the mouth, nose and throat.

Typical signs of thrombocytopenia include an increased bleeding tendency and petechiae on the skin and mucosae.

If pancytopenia occurs, the treatment must be stopped immediately and the full blood count monitored until it normalises (see section 4.4).

Immune system disorders
Rare:                           Anaphylactoid or anaphylactic reactions*.
Very rare:                      Analgesic-induced asthma syndrome.
In patients with analgesic asthma syndrome, intolerance reactions typically appear in the form of asthma attacks.
Not known:              Anaphylactic shock*.
*These reactions can occur especially after parenteral administration, can be serious and life- threatening, and in some cases have a fatal outcome. They can occur even if dipyrone has previously been administered without complications.

Such reactions can develop during the injection or immediately after ingestion, but also hours later.
However, in the majority of cases, they occur during the first hour after administration. Milder reactions typically manifest as skin and mucous membrane reactions (e.g., itching, burning, reddening, urticaria, swelling), dyspnoea and rare gastrointestinal symptoms. Milder reactions of this kind can transition into more severe forms with generalised urticaria, severe angio-oedema (including laryngeal), severe bronchospasm, arrhythmias, hypotension (sometimes preceded by a rise in blood pressure) or circulatory shock.

Optalgin® Teva 1 g/2 ml solution for injection must therefore be stopped immediately if skin reactions occur.

 Cardiac disorders
Not known:                          Kounis syndrome.

Vascular disorders
Uncommon:                           Hypotensive reactions during or after administration which are possibly pharmacological in origin and not accompanied by other signs of an anaphylactoid or anaphylactic reaction. Such a reaction can lead to severe hypotension. Rapid intravenous injection increases the risk of a hypotensive reaction.

Even in cases of hyperpyrexia, dose-dependent critical hypotension can occur without other signs of a sensitivity reaction.

Gastrointestinal disorders
Not known: Cases of gastrointestinal bleeding have been reported.

Hepatobiliary disorders
Not known:              Drug-induced liver damage including acute hepatitis, jaundice, raised liver enzymes (see section 4.4).

Skin and subcutaneous tissue disorders
Uncommon:                      Fixed drug eruption.
Rare:                          Rash (e.g. maculopapular rash).
Very rare:                     Stevens-Johnson syndrome or toxic epidermal necrolysis (see section 4.4).
Not known:                     Drug reaction with eosinophilia and systemic symptoms (DRESS, see section 4.4).

Renal and urinary disorders
Very rare:                          Acute deterioration of kidney function in which, very rarely, proteinuria, oligo- or anuria or acute kidney failure can develop; acute interstitial nephritis.

General disorders and administration site conditions
If the product is injected, pain and local reactions, and very rarely even phlebitis, can occur at the injection site.

Red discoloration of the urine has been reported; this may be caused by the harmless dipyrone metabolite rubazonic acid, which is present at a low concentration.

Reporting of suspected adverse reactions
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. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form http://sideeffects.health.gov.il/