Targin 40/20mg prolonged release tablets

Section 2 - Update to warning on use of MAOIs to include 2 week period. Addition of warning regarding sleep apnoea. Addition of warning on increased sensitivity to pain.

Section 4 - Addition of sleep apnoea as a possible side effect.

Section 6 - Deletion of UK manufacturer following Brexit.

Section 4.4 - Reorganisation of warnings into bullet point format. Addition of warnings on respiratory depression and sleep-related breathing disorders. Addition of warning advising caution in use for patients taking MAOIs or who have received MAOIs within the previous two weeks. Addition of warning regarding hyperalgesia.

Section 4.5 - Clarification of warning advising caution in use for patients taking MAOIs or who have received MAOIs within the previous two weeks.

Section 4.8 - Addition of sleep apnoea as a potential undesirable effect. Correction of anaphylactic responses to anaphylactic reaction.

Addition of warnings in section 2 regarding concomitant use of serotonin agents and gabapentinoids with Targin

Addition of warnings in section 4.5 regarding concomitant use of serotonin agents and gabapentinoids with Targin

Section 4.4

The text in bold has been added to the section below:

‘Caution is advised in patients taking MAO inhibitors or CNS depressants.

Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs:

Concomitant use of opioids, including oxycodone hydrochloride and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicines should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Targin concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible.

The patients should be followed closely for signs and symptoms of respiratory depression and sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware of these symptoms (see section 4.5).’

The text below has also been added to section 4.4:

‘Opioids such as oxycodone may influence the hypothalamic-pituitary-adrenal or –gonadal axes. Some changes that can be seen include an increase in serum prolactin, and decreases in plasma cortisol and testosterone. Clinical symptoms may manifest from these hormonal changes.’

‘total lactase deficiency’ has been added to replace ‘Lapp lactase deficiency’

Section 4.5

The text in bold has been added to the first paragraph of section 4.5 and text in strikethrough has been removed:

‘The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. The dose and duration of concomitant use should be limited (see section 4.4).

Substances having a Drugs which depress the CNS depressant effect include but are not limited to:(e.g. other opioids, anxiolytics, hypnotics and sedatives (including benzodiazepines), hypnotics, antidepressants, antipsychotics, antihistamines and antiemetics.) may enhance the CNS depressant effect (e.g. respiratory depression) of Targin.’

 Section 4.8

‘Rare:                    Drug dependence’ added underneath the subheading ‘Psychiatric disorders’

‘Aggression’ added to ‘Not known’ section beneath ‘Psychiatric disorders’

‘Drug dependence’ and ‘aggression’ removed from the ‘Psychiatric disorders’ subheading within the section ‘For the active substance oxycodone hydrochloride….’

‘Drug dependence’ and ‘Aggression’ added to ‘Not known’ section beneath ‘Psychiatric disorders’ under ‘Undesirable effects in the treatment of restless legs syndrome’

Section 5.1

‘Opioids such as oxycodone may influence the hypothalamic-pituitary-adrenal or –gonadal axes. Some changes that can be seen include an increase in serum prolactin, and decreases in plasma cortisol and testosterone. Clinical symptoms may manifest from these hormonal changes.’

The text above has been replaced with this text: ‘For effects of opioids upon the endocrine system, see section 4.4’

Section 10

The date of revision was updated to ‘June 2018’

Text from SPC: in italics
Added text: coloured in red
Removed test: crossed through

Section 2:
The order of naloxone hydrochloride strengths depiction has been rearranged to a more logical order.

Targin 5 mg/2.5 mg:
Each prolonged-release tablet contains 5 mg of oxycodone hydrochloride equivalent to 4.5 mg oxycodone and 2.5 mg naloxone hydrochloride as 2.73 mg of naloxone hydrochloride dihydrate equivalent to 2.5 mg naloxone hydrochloride and 2.25 mg naloxone.

Targin 10 mg/5 mg:
Each prolonged-release tablet contains 10 mg of oxycodone hydrochloride equivalent to 9 mg oxycodone and 5 mg naloxone hydrochloride as 5.45 mg of naloxone hydrochloride dihydrate equivalent to 5 mg naloxone hydrochloride and 4.5 mg naloxone.

Targin 20 mg/10 mg:
Each prolonged-release tablet contains 20 mg of oxycodone hydrochloride equivalent to 18 mg oxycodone and 10 mg naloxone hydrochloride as 10.9 mg of naloxone hydrochloride dihydrate equivalent to 10 mg naloxone hydrochloride and 9 mg naloxone.

Targin 40 mg/20 mg:
Each prolonged-release tablet contains 40 mg of oxycodone hydrochloride equivalent to 36 mg oxycodone and 20 mg naloxone hydrochloride as 12.8 mg of naloxone hydrochloride dihydrate equivalent to 20 mg naloxone hydrochloride and 18 mg naloxone.

The lactose content has also been revised to one decimal place.

Targin 5 mg/2.5 mg:    Each prolonged-release tablet contains 68.17 68.2 mg lactose anhydrous.
Targin 10 mg/5 mg:     Each prolonged-release tablet contains 61.04 lactose anhydrous.
Targin 20 mg/10 mg:   Each prolonged-release tablet contains 51.78 51.8 lactose anhydrous.
Targin 40 mg/20 mg:   Each prolonged-release tablet contains 103.55 103.6 lactose anhydrous.

Section 3:
'Prolonged-release tablet' has been added as a description of the pharmaceutical form.

Section 4.2:
The wording has been amended: the trade name 'Targin' has been replaced by 'these tablets' or by 'these prolonged-release tablets'.

Text regarding use of Targin 5 mg/2.5 mg for dose titration has been removed.

Targin 5 mg/2.5 mg is intended for dose titration when initiating opioid therapy and individual dose adjustment.

'of Targin' has been removed when referring to doses in this section.

Text has been added regarding elevated peak plasma concentrations.

Slightly elevated (dose corrected) peak plasma concentrations should be taken into account when the 2.5 mg/1.25 mg tablet is used.

Reference to section 4.4 has been added regarding the method of administration.

Targin These tablets must be swallowed whole, and not broken, chewed or crushed (see section 4.4).

Section 4.3:
'Any situation in which opioids are indicated' has been removed.

Section 4.4:
The wording has been amended: the trade name 'Targin' has been replaced by 'these tablets'.

The reference to higher doses has been removed regarding long-term opioid treatment.

In patients under long-term opioid treatment with higher doses of opioids, the switch to Targin can initially provoke withdrawal symptoms.

A cross reference to section 4.2 has been added to provide clarification regarding the occurrence of withdrawal syndrome.

Other minor editorial changes have been made to ensure harmonization across this product range:

A careful Careful medical monitoring is particularly necessary for patients with severe renal impairment.

Section 4.5:
The wording has been amended: the trade name 'Targin' has been replaced by 'these tablets'.

Section 4.6:
The wording has been amended: the trade name 'Targin' has been replaced by 'these tablets'.

Section 4.7:
'with Targin' has been removed in reference to the beginning of treatment.

The wording has been amended: the trade name 'Targin' has been replaced by 'these tables'.

Section 4.8:
The format of this section has changed from tabular form to text.

'Asthenic conditions' has been updated to 'lethargy, fatigue and asthenia'.

The terms 'decreased libido', 'dysgeusia' and 'thirst' have been moved from the undesirable effects section for the single active substance, oxycodone hydrochloride, to the undesirable effects section for pain for the combination product.

For the undesirable effects section for the single active substance, oxycodone hydrochloride, the following changes have been made:

'Hyperalgesia' has been added with a frequency of not known under the classification 'nervous system disorders'.

'Hypogonadism' has been added with a frequency of uncommon under the classification 'reproductive system and breast disorders'.

'Dental caries' has been added with a frequency of not known under the classification 'gastrointestinal disorders'.

The frequency of 'cholestasis' has been updated from not known to uncommon.

'Drug withdrawal system neonatal' has been added with a frequency of not known under the classification 'general disorders and administration site conditions'.

'Aggression' has been added with a frequency of not known under the classification 'psychiatric disorders'.

Section 4.9:
The term 'skeletal muscle flaccidity' has been replaced by 'hypotonia'.

Symptoms of oxycodone overdose include miosis, respiratory depression, somnolence progressing to stupor, skeletal muscle flaccidity hypotonia, bradycardia as well as hypotension.

Section 6.1:
'Hydroxypropylcellulose' has been added as an ingredient of the 5 mg/2.5 mg tablet only.
The description of Povidone K30 has been updated to state that it is an ingredient of the 10 mg/5 mg, 20 mg/10 mg and 40 mg/20 mg tablets only.
The description of Polyvinyl alcohol has been updated
Several colourants have been added as ingredients of the tablet coat for several strengths.

Tablet core:
Ethylcellulose,
Stearyl alcohol,
Lactose monohydrate,
Talc,
Magnesium stearate,
Hydroxypropylcellulose, (5 mg/2.5 mg tablets only)
Povidone K30, (10 mg/5 mg, 20 mg/10 mg, 40 mg/20 mg tablets)

Tablet coat:
Poly(vinylalcohol), partially hydrolysed,
Titanium dioxide (E171),
Macrogol 3350,
Talc,
Brilliant Blue FCF aluminium lake (E133), (5 mg/2.5 mg tablets only)
Iron oxide red (E172), (20 mg/10 mg tablets only)
Iron oxide yellow (E172), (40 mg/20 mg tablets only)

Section 6.3:
The descriptions of the packaging components has been updated.
The shelf life after opening has been added for the bottles.

Polyvinylchloride (PVC)/aluminium foil bBlisters: 3 years
HDPE bBottles: 2 years        Shelf life after first opening: 6 months

Section 6.5:
The description of the packaging components and the pack size has been updated.

Child resistant PVC/aluminium foil blisters containing 56 prolonged release tablets.
Pack sizes: 10, 14, 20, 28, 30, 50, 56, 60, 98
Hospital pack: 100 (10 x 10) tablets
HDPE bottles with a child resistant PP closure:
Pack size: 100 tables

Section 10:
The date of revision of the text has been updated to 'January 2017' from 'December 2015'.

The prolonged‑release tablets may be taken with or without food with sufficient liquid. Targin must be swallowed whole, and not broken, chewed or crushed.