Adverse reactions : תופעות לוואי

4.8     Undesirable effects

The most commonly reported undesirable effects during the clinical trials performed with the paracetamol/tramadol hydrochloride combination were nausea, dizziness and somnolence, observed in more than 10 % of the patients.

The frequencies are defined as follows:
Very common:       ≥1/10
Common:            ≥1/100 to <1/10
Uncommon:             ≥1/1000 to <1/100
Rare:                 ≥1/10 000 to <1/1000
Very rare:            <1/10 000
Unknown:          Frequency cannot be estimated from the available data Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Cardiac disorders:

• Uncommon: palpitations, tachycardia, arrythmia.
Eye disorders:
• Rare: vision blurred, miosis, mydriasis.


Ear and labyrinth disorders:
• Uncommon: tinnitus.
Gastro-intestinal disorders:

• Very common: nausea
• Common: vomiting, constipation, dry mouth, diarrhea, abdominal pain, dyspepsia, flatulence
• Uncommon: dysphagia, melaena.


General disorders and administration site conditions:
• Uncommon: chills, chest pain.


Investigations:
• Uncommon: transaminases increased.


Metabolism and nutrition disorders:
• Unknown: hypoglycaemia.


Nervous system disorders:
• Very common: dizziness, somnolence
• Common: headache, trembling
•      Uncommon: involuntary muscular contractions, paraesthesia, amnesia • Rare: ataxia, convulsions, syncope, speech disorders.


Psychiatric disorders:
• Common: confusional state, mood altered, anxiety, nervousness, euphoric mood, sleep disorders
• Uncommon: depression, hallucinations, nightmares

• Rare: delirium, drug dependence.

Post marketing surveillance

Very rare: abuse.


Renal and urinary disorders:

• Uncommon: albuminuria, micturition disorders (dysuria and urinary retention).

Respiratory, thoracic and mediastinal disorders:

• Uncommon: dyspnoea.
Skin and subcutaneous tissue disorders:
• Common: hyperhidrosis, pruritus
• Uncommon: dermal reactions (e.g. rash, urticaria).


Vascular disorders:
• Uncommon: hypertension, hot flush.



Although not observed during clinical trials, the occurrence of the following undesirable effects known to be related to the administration of tramadol or paracetamol cannot be excluded:

Tramadol
• Postural hypotension, bradycardia, collapse (tramadol).
• Post-marketing surveillance of tramadol has revealed rare alterations of warfarin effect, including elevation of prothrombin times.
•      Rare cases (≥ 1/10000 to < 1/1000) : allergic reactions with respiratory symptoms (e.g.
dyspnoea, bronchospasm, wheezing, angioneurotic oedema) and anaphylaxis
•      Rare cases (≥ 1/10000 to < 1/1000): changes in appetite, motor weakness, and respiratory depression
• Psychic side-effects may occur following administration of tramadol which vary individually in intensity and nature (depending on personality and duration of medication). These include changes in mood, (usually euphoric mood occasionally dysphoria), changes in activity (usually suppression occasionally increase) and changes in cognitive and sensorial capacity (e.g. decision behaviour perception disorders).
• Worsening of asthma has been reported though a causal relationship has not been established.
•       Nervous system disorders: Not known: Serotonin syndrome.
• Symptoms of drug withdrawal syndrome, similar to those occurring during opiate withdrawal may occur as follows: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal symptoms. Other symptoms that have very rarely been seen if tramadol hydrochloride is discontinued abruptly include: panic attacks, severe anxiety, hallucinations, paraesthesia, tinnitus and unusual CNS symptoms.
•   Respiratory, thoracic and mediastinal disorders: frequency not known: hiccups.
Paracetamol
• Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.
• There have been several reports that suggest that paracetamol may produce hypoprothrombinemia when administered with warfarin-like compounds. In other studies, prothrombin time did not change.
• Very rare cases of serious skin reactions have been reported.
•     Metabolism and nutrition disorders: cases of pyroglutamic acidosis (PGA) were reported with frequency not known, when paracetamol is used alone or with concomitant treatment of flucloxacillin, especially in patients with risk factors and prolonged treatment (see sections 4.4 and 4.5).

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 https://sideeffects.health.gov.il/.