Adverse reactions : תופעות לוואי

4.8     Undesirable effects
Clinical trials with this product have not indicated any other undesirable effects other than those for paracetamol alone or ibuprofen alone.
Adverse reactions have been ranked under headings of frequency using the following convention: 1. Very common (≥ 1/10)
2. Common (≥ 1/100, < 1/10(
3. Uncommon (≥ 1/1000, < 1/100(
4. Rare (≥ 1/10000, < 1/1000)
5. Very rare (< 1/10000(
6. Not known (cannot be estimated from the available data).
Blood and lymphatic               Uncommon: Decrease in haemoglobin and haematocrit.
system disorders                  Although a causal relationship has not been established, bleeding episodes (e.g. epistaxis, menorrhagia) have been reported in during therapy with the drug.
Very Rare: Haematopoietic disorders (agranulocytosis, anaemia,
aplastic anaemia, haemolytic anaemia leukopenia, neutropenia,
pancytopenia and thrombocytopenia with or without purpura) have been reported following paracetamol use, but were not necessarily causally related to the drug.
Cardiac disorders                 Common: Oedema, fluid retention; fluid retention generally responds promptly to discontinuation of the drug.
Very Rare: Palpitations; tachycardia; arrhythmia and other cardiac dysrhythmias have been reported. Hypertension and cardiac failure have been reported in association with NSAID treatment.
Ear and labyrinth                 Very Rare: Vertigo.
disorders                         Common: Tinnitus (for medicines containing ibuprofen) Eye disorders                     Uncommon: Amblyopia (blurred and/or diminished vision, scotomata and/or changes in colour vision) have occurred but is usually reversed after cessation of therapy. Any patient with eye complaints should have an ophthalmological examination which includes central vision fields.
Gastrointestinal Disorders   Common: Abdominal pain, diarrhoea, dyspepsia, nausea, stomach discomfort and vomiting
Uncommon: Flatulence and constipation, peptic ulcer, perforation or gastrointestinal haemorrhage, with symptoms of melaena haematemesis sometimes fatal, particularly in the elderly.
Ulcerative stomatitis and exacerbation of ulcerative colitis and
Crohn's disease have been reported following administration. Less frequently gastritis has been observed and pancreatitis reported.
General disorders and        Very Rare: Fatigue and malaise.
administration site conditions
Hepatobiliary disorders      Very Rare: Abnormal liver function, hepatitis and jaundice.
In overdose paracetamol can cause acute hepatic failure, hepatic failure, hepatic necrosis and liver injury.
Immune system disorders      Very Rare: Hypersensitivity reactions including skin rash and cross-sensitivity with sympathomimetics have been reported.
Uncommon: Other allergic reactions have been reported but a causal relationship has not been established: Serum sickness, lupus erythematosus syndrome, Henoch-Schönlein vasculitis,
angioedema.
Investigations               Common: Alanine aminotransferase increased, gamma- glutamyltransferase increased and liver function tests abnormal with paracetamol.
Blood creatinine increased and blood urea increased.
Uncommon: Aspartate aminotransferase increased, blood alkaline phosphatase increased, blood creatine phosphokinase increased.
haemoglobin decreased and platelet count increased.
Metabolic and nutrition      Very Rare: In the case of metabolic acidosis, causality is disorders                    uncertain as more than one drug was ingested. The case of metabolic acidosis followed the ingestion of 75 grams of paracetamol, 1.95 grams of acetylsalicylic acid, and a small amount of a liquid household cleaner. The patient also had a history of seizures which the authors reported may have contributed to an increased lactate level indicative of metabolic acidosis.
Metabolic side effects have included hypokalaemia. Metabolic side effects including metabolic acidosis have been reported following a massive overdose of acetaminophen.
Uncommon: Gynaecomastia, hypoglycaemic reaction.
Nervous system disorders     Common: Dizziness, headache, nervousness Uncommon: Depression, insomnia, confusion, emotional lability,
somnolence, aseptic meningitis with fever and coma
Rare: Paraesthesias, hallucinations, dream abnormalities
Very Rare: Paradoxical stimulation, optic neuritis, psychomotor impairment, extrapyramidal effects, tremor and convulsions.
Renal and urinary            Uncommon: Urinary retention disorders                    Very Rare: Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and acute and chronic renal failure.
Adverse renal effects are most often observed after overdose, after chronic abuse (often with multiple analgesics), or in association with paracetamol-related hepatotoxicity.
Acute tubular necrosis usually occurs in conjunction with liver failure, but has been observed as an isolated finding in rare cases.
A possible increase in the risk of renal cell carcinoma has been associated with chronic paracetamol use as well.
One case-control study of patients with end-stage renal disease suggested that long term consumption of paracetamol may significantly increase the risk of end-stage renal disease particularly in patients taking more than 1000 mg per day.
Respiratory and thoracic        Uncommon: Thickened respiratory tract secretions and mediastinal disorders       Very Rare: Respiratory reactivity including: asthma, exacerbation of asthma, bronchospasm and dyspnoea.
Skin and subcutaneous           Common: Rash (including maculopapular type), pruritus.
tissue disorders                Very Rare: Hyperhidrosis, purpura and photosensitivity. Very rare cases of serious skin reactions have been reported, such as exfoliative dermatoses and bullous reactions including erythema multiforme, Stevens Johnson Syndrome and Toxic Epidermal
Necrolysis.
Not Known: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Acute generalised exanthematous pustulosis (AGEP).

Clinical studies suggest that use of ibuprofen, particularly at a high dose (2400 mg/day) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

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