Palexia Oral Solution 20 mg/ml

To update the PIL according to the position of CMDh (637158/2022) derived from PSUSA/00002849/202111 for tapentadol. This change also includes QRD updates and editorial changes.

To update the SmPC according to the position of CMDh (637158/2022) derived from PSUSA/00002849/202111 for tapentadol. This change also includes QRD updates and editorial changes.

RMS BfArM approval regarding composition change - addition of Sodium Benzoate as an excipient to the drug product. 

RMS - BfArM approval regarding compositon change - addition of Sodium Benzoate as an excipient to the drug product. 

addition of information on sleep-related breathing disorders

Information on sleep-related breathing disorders added

Section 4.8:

Added Delirium** as an adverse event of unknown frequency

** Post marketing cases of delirium were observed in patients with additional risk factors such as cancer and advanced age.

Section 4:

addition of Delirium as an adverse event of unknown frequency

Correction to date of revision of text (section 10) of the update published on 23-Jul-2019

Section 4.1 (new text underlined, deleted text strike through)

PALEXIA is indicated for the relief of moderate to severe acute pain in children from 2 years of age with a body weight of more than 16 kg and in adults, which can be adequately managed only with opioid analgesics.

Section 4.2

For dosages of 20 mg or more (patients with a body weight of more than 16 kg) PALEXIA 20 mg/ml should be used, for dosages of less than 20 mg (patients with a body weight of 16 kg or less) PALEXIA 4 mg/ml is recommended.

PALEXIA 20 mg/ml is not recommended for children with a body weight of 16 kg or less due to the high concentration of tapentadol.

Section 4.4:

PALEXIA is not recommended in children with a body weight of 16 kg or less (see section 4.2)

Section 4.4

Text added on Risk from concomitant use of sedating medicinal products such as benzodiazepines or related substances.

Section 4.5

Text updated in line with CMDh recommendation on ‘Sedative medicines such as benzodiazepines or related drugs’

Section 4.4: Special warnings and precautions

Seizures: The following is included 'In addition, tapentadol may increase the  seizure risk in patients taking other medicinal products that lower the seizure threshold (see section 4.5)'

 Section 4.5: Interaction with other medicinal products and other forms of interaction

The following changes made:

​​PALEXIA can induce convulsions and increase the potential for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and other medicinal products that lower the seizure threshold to cause convulsions.

In isolated cases there have been reports of serotonin syndrome in a temporal connection with the therapeutic use of tapentadol in combination with serotinergic medicinal products such as selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants. Signs of serotonin syndrome may be for example confusion, agitation, fever, sweating, ataxia, hyperreflexia, myoclonus and diarrhea. Serotonin syndrome is likely when one of the following is observed:

• Spontaneous clonus
• Inducible or ocular clonus with agitation or diaphoresis
• Tremor and hyperreflexia
• Hypertonia and body temperature > 38oC and inducible ocular clonus

Section 2: Qualitative and quantitative composition

- propylene glycol and sodium added as excipients with known effect

Section 4.1: Therapeutic Indications

- indication extended to paediatric population. Approved indication is 'Palexia is indicated for the relief of moderate to severe acute pain in children from 2 years of age and in adults, which can be adequately managed only with opioid analgesics.'

Section 4.2: Posology and method of administration

- added 'The use of Palexia in children is restricted to hospital use where appropriate equipment to enable respiratory support is available'.

- dosing recommendations and dose by body weight is provided for the paediatric population.

- the oral syringe is referred to as the dosing pipette

- added ' Palexia may be administered through a nasogastric tube made of polyurethane, silicone, or polyvinyl chloride (these materials were tested and showed no interactions or degradation of tapentadol)'.

Section 4.4: Special precautions for use

- Added details of quantities of propylene glycol and sodium

- precautions in relation to paediatric dosing is added

Section 4.5: Interactions with other medicinal products and other forms of interaction

- added ' Due to the major elimination pathway being glucuronide conjugation the potential for interactions in adults is low. additionally, in vitro, tapentadol was found not to induce or inhibit any of the main CYP enzymes, including CYP 3A4.'

- For the paediatric population, added 'Due to the major elimination pathway being glucuronide conjugation the potential for interactions in children aged more than 5 months is low (see section 4.2).

Section 4.6: Fertility, pregnancy and lactation

- the title 'Lactation' is changed to 'Breast-feeding'

Section 4.8: Undesirable effects

- added 'The most severe adverse drug reactions are sedation, respiratory depression and allergic reactions'

- adverse event information relevant to the paediatric population is added

Section 5.1: Pharmacodynamic properties

- the summary for paediatric population is updated.

Section 5.2 Pharmacokinetic properties

- pharmacokinetic information relevant to the paediatric population is added

Section 5.3: Preclinical safety data

- preclinical data in juvenile animals is included

Section 6.1 List of excipients

- E number for propylene glycol is added (E 1520)

Section 6.5 Nature and contents of container

- description of the oral syringe is changed from 'Each bottle of the oral solution is provided with an oral syringe and an adapter. The syringe is scaled in 0.25 millilitre increments with a minimum volume of 0.25ml and a maximum volume of 5 ml' to ' Each bottle of the oral solution is provided with a dosing pipette and an adapter attached to the dosing pipette. The scale of the 5mL dosing pipette is subdivided in 0.1ml intervals. Additionally, the right scale shows the single doses for adults' 

Section 6.6 Special precautions for use and other handing.

- cross reference added to section 4.2

Section 10: Date of the revision of the text

- July 2018

Section 2: Excipients with known effect added - propylene glycol and sodium

Section 4.1: Indication extended to paediatric population - Palexia is indicated for the relief of moderate to severe acute pain in children from 2 years of age and in adults, which can be adequately managed only with opioid analgesics.

Section 4.2: Use in children is restricted to hospital use. Information on paediatric dosing and use is included. Section on method of administration is updated in relation to administration through nasogastric tubes.

Section 4.4: Details on excipient propylene glycol and sodium added. Warning and precautions in relation to the paediatric population added.

Section 4.5: Added ' due to the major elimination pathwas being conjugation the potential for interactions in adults in low. Additionally, in vitro, tapentadol was found not to induce or inhibit any of the main CYP enzymes, including CYP 3A4'. Added information on potential for iteraction in paediatric population.

Section 4.6: title ' Lactation' changed to 'Breast-feeding'

Section 4.8: added details on adverse reaction in children.

Section 5.1: section on paediatric population is updated

Section 5.2: Details on paediatric population included

Section 5.3: preclinical data in juvenile animal included

Section 6.1: E 1520 added for propylene glycol

Section 6.5: Details of the dosing pipette is updated.

Section 6.6: title amended to ' Special precautions for disposal and other handling'. Reference made to section 4.2

Section 10: Date updated - July 2018

update to marketing authorisation holder and number

·         Update to SPC following renewal of marketing authorisation

·         In section 10, date of revision of text changed