Durogesic DTrans 25 micrograms/hour Transdermal Patch

Addition of new warning under section 4.4:

Endocrine effects

Opioids such as fentanyl may influence the hypothalamic-pituitary-adrenal or –gonadal axes, especially after long-term use. Some changes that can be seen include an increase in serum prolactin, and decreases in plasma cortisol and testosterone. Clinical signs and symptoms may manifest from these hormonal changes. If an endocrine effect such as hyperprolactinaemia or adrenal insufficiency is suspected, appropriate laboratory testing is recommended and discontinuation of treatment with DUROGESIC should be considered.

Addition of new warning under section 2:

DUROGESIC, like other opioids, may affect the normal production of hormones in the body such as cortisol, prolactin, or sex hormones, particularly if you have taken DUROGESIC for long periods of time. The effects of these hormonal changes may include feeling or being sick (including vomiting), loss of appetite, tiredness, weakness, dizziness, low blood pressure, infertility, or decreased sex drive. In addition, female patients may experience changes in menstrual cycle, while male patients may experience impotence or enlarged breasts. If you notice any of these signs, speak to your doctor.

Summary of Product Characteristics Section 4.8

The following adverse reaction should be added under the SOC Gastrointestinal disorders with a frequency uncommon:

Dysphagia

Package Leaflet Section 4

The following adverse reaction should be listed under the adverse reactions with a frequency uncommon:

Difficulty in swallowing.

Changes to sections 2, 3 and 4 corresponding to SmPC changes

Changes to sections 4.2, 4.4, 4.8 and 4.9

• SmPC section 4.5 Interaction with other medicinal products and other forms of interaction and corresponding PIL section, to add additive effect of gabapentinoids on CNS depression

Please note there will be no update to the CCDS in relation to this, since gabapentinoids are already covered by the drug interaction for CNS depressants and therefore would only be another example of a CNS depressant and not a separate drug interaction in the table. The drug interaction table is not meant to be an exhaustive list of CNS depressants, as such it isn’t necessary to update the CCDS with another example of CNS depressants.

• PIL section 3.0 How to use DUROGESIC to add information about lack of efficacy if patch falls off

Please note there will be no update to the CCDS in relation to this, since gabapentinoids are already covered by the drug interaction for CNS depressants and therefore would only be another example of a CNS depressant and not a separate drug interaction in the table. The drug interaction table is not meant to be an exhaustive list of CNS depressants, as such it isn’t necessary to update the CCDS with another example of CNS depressants.

The following changes to section 6:

-  What the product looks like and pack contents - "The patches come in individually wrapped heat-sealed (acrylonitrile film or cyclic olefin copolymer) pouches, and come in cartons containing 3, 4, 5, 8, 10, 16, 20 or 30 patches."

- Last date of revision of the text

Changes to sections:

- 6.5 Nature and contents of container

- 10 Date of revision of the text

4.4       Special warnings and precautions for use

Respiratory depression

Some patients may experience significant respiratory depression with Durogesic DTrans; patients must be observed for these effects.  Respiratory depression may persist beyond the removal of the Durogesic DTrans patch.  The incidence of respiratory depression increases as the Durogesic DTrans dose is increased (see section 4.9).  Central nervous system depressants may increase the respiratory depression (see section 4.5).

Central Nervous System (CNS) Depressants, including Alcohol and CNS Depressant Narcotic Drugs

Concomitant use of Durogesic DTrans with CNS depressants, including alcohol and CNS depressant narcotic drugs, may increase the undesirable effects of Durogesic DTrans; concomitant use should be avoided (see section 4.5). If concomitant use of Durogesic DTrans with a CNS depressant is clinically necessary, prescribe the lowest effective dosages and minimum duration for both drugs, and follow patients closely for signs of respiratory depression and sedation.

4.5       Interaction with other medicinal products and other forms of interaction

Pharmacodynamic-related interactions

Centrally-acting medicinal products/Central Nervous System (CNS) depressants, includingand alcohol and CNS depressant narcotic drugs

The concomitant use of Durogesic DTrans with other central nervous system depressants (including benzodiazepines and other sedatives/ hypnotics, opioids, sedatives, hypnotics, general anaesthetics, phenothiazines, tranquilisers, sedating antihistamines, and alcoholic beverages and CNS depressant narcotic drugs) and skeletal muscle relaxants may produce additive disproportionately increase the CNS depressant effects such as respiratory depressionhypoventilation, hypotension, profound sedation, coma or death may occur. Therefore, the use of any of these medicinal products concomitantly with Durogesic DTrans requires special patient care and observation.

Cytochrome P450 3A4 (CYP3A4) Inhibitors

Fentanyl, a high clearance active substance, is rapidly and extensively metabolised mainly by CYP3A4.

.

Cytochrome P450 3A4 (CYP3A4) Inducers

Change due to harmonisation of Summary of Product Characteristics in Europe (implementation of the outcome of a referral procedure under Article 30 of Directive 2001/83/EC).

Change due to harmonisation of Summary of Product Characteristics in Europe (implementation of the outcome of a referral procedure under Article 30 of Directive 2001/83/EC).

Durogesic DTrans combined SmPC is no longer published, SmPC for each strength is now available

Changes to the SmPC

Section 4.4: Special warnings and precautions for use

Gastrointestinal tract

Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. The resultant prolongation in gastrointestinal transit time may be responsible for the constipating effect of fentanyl. Patients should be advised on to take measures to prevent constipation and prophylactic laxative use should may be considered in some situations. Extra caution should be used in patients with chronic constipation. If paralytic ileus is present or suspected, treatment with Durogesic DTrans should be reviewed taking into account the overall risk-benefit for the patient.

Durogesic DTrans combined SmPC is no longer published, SmPC for each strength is now available

Changes to the SmPC

Section 4.4: Special warnings and precautions for use

Gastrointestinal tract

Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. The resultant prolongation in gastrointestinal transit time may be responsible for the constipating effect of fentanyl. Patients should be advised on to take measures to prevent constipation and prophylactic laxative use should may be considered in some situations. Extra caution should be used in patients with chronic constipation. If paralytic ileus is present or suspected, treatment with Durogesic DTrans should be reviewed taking into account the overall risk-benefit for the patient.