Having considered the available evidence and analyzed the data submitted by the registration certificate holders, the PRAC agreed that the information on medicinal products containing tramadol should be updated to take into account the risk of serotonin syndrome.
All registration certificate holders of medicinal products containing tramadol, including the fixed combinations tramadol-paracetamol and tramadol-dexketoprofen, must make changes within two months of the publication of the PRAC recommendation to amend the instructions for the medicinal products.
Amendments to be included in the relevant sections of the package insert (new text underlined in bold, deleted text struck through).
Section “Special warnings and precautions for use”
Serotonin syndrome
Serotonin syndrome, a potentially life-threatening condition, has been reported in patients receiving tramadol in combination with other serotonergic medicinal products or tramadol alone (see sections “Interaction with other medicinal products and other forms of interaction”, “Adverse reactions”, and “Overdose”).
If concomitant treatment with other serotonergic medicinal products is clinically warranted, careful monitoring of the patient is recommended, particularly during treatment initiation and dose increases.
Symptoms of serotonin syndrome may include changes in mental status, autonomic instability, neuromuscular abnormalities, and gastrointestinal symptoms.
If serotonin syndrome is suspected, consideration should be given to reducing the dose or discontinuing therapy, depending on the severity of symptoms. Discontinuation of serotonergic medicinal products usually leads to rapid improvement.
Section “Interaction with other medicinal products and other forms of interaction”
Concomitant therapeutic use of tramadol and serotonergic medicinal products, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs) (see section “Contraindications”), tricyclic antidepressants, and mirtazapine, may cause toxicity serotonin syndrome, a potentially life-threatening condition (see sections “Special warnings and precautions for use” and “Adverse reactions”). Serotonin syndrome is likely when one of the following is observed:
Spontaneous clonus Inducible or ocular clonus with agitation or diaphoretic pathology Tremor and hyperreflexia Hypertonia and body temperature > 38 ° C and inducible or ocular clonus
Discontinuation of serotonergic drugs usually leads to rapid improvement. Treatment depends on the type and severity of symptoms.
“Adverse reactions” section
Nervous system disorders
Serotonin syndrome: frequency “not known” :
“Overdose” section
Serotonin syndrome has also been reported
Перелік лікарських засобів, що містять tramadol і дозволені до медичного застосування в Україні (за даними Державного реєстру лікарських засобів станом на 28.05.2021)
Link
https://www.ema.europa.eu/en/documents/prac-recommendation/new-product-information-wording-extracts-prac-recommendations-signals-adopted-3-6-may-2021-prac_en.pdf
https://www.ema.europa.eu/en/documents/prac-recommendation/prac-recommendations-signals-adopted-3-6-may-2021-prac-meeting_en.pdf
