Sovenor 5. 10. 20 5mg. 10mg. 20mg Transdermal patches.

SOVENOR u00c6 is indicated for the treatment of chronic musculoskeletal pain of the joints and the lower back, when that pain is of moderate to severe intensity sufficient to require an opioid to obtain adequate analgesia.

Posology
SOVENOR u00c6 Patch should be worn continuously for 7 days.
Patients aged 18 years and over: The lowest SOVENOR u00c6 dose available, SOVENOR u00c6 5 (5 u03bcg/h) should be used as the initial dose in all patients.
Titration
During initiation, titration, and treatment with SOVENOR u00c6 , patients may continue their existing NSAID or paracetamol regimen as needed. During the titration process, the dose may be adjusted every 3-days (72 hours). Thereafter, the 7-day dosing interval should be maintained. Changes in SOVENOR u00c6 dosage may be individually titrated based on the need for supplemental analgesia and the patientu2019s analgesic response to SOVENOR u00c6 .
To increase the dose, a larger patch should replace the patch that is currently being worn, or a combination of patches should be applied in different places to achieve the desired dose. It is recommended that no more than two patches be applied at the same time, regardless of patch strength. Titration should continue every 3 - 7 days until adequate analgesia is achieved. If adequate pain control cannot be achieved with SOVENOR u00c6 , therapy with SOVENOR u00c6 should be discontinued and the patient converted to an appropriate analgesic regimen as determined by a physician.
Special populations
Paediatric population
The safety and efficacy of SOVENOR u00c6 in patients under 18 years of age has not been established.
Renal impairment
No special dose adjustment of SOVENOR u00c6 is necessary in patients with renal impairment.
Hepatic impairment
There is no need for dosage adjustment when using SOVENOR u00c6 in patients with mild to moderate hepatic impairment. Patients with severe hepatic impairment may accumulate buprenorphine during SOVENOR u00c6 treatment. SOVENOR u00c6 should not be used in such patients (see section 4.3).
Method of administration
In order to minimise the potential of skin reactions (see Section 4.4). SOVENOR u00c6 should be applied to non-irritated, intact skin of the upper outer arm, upper chest, upper back or the side of the chest. SOVENOR u00c6 should be applied to a relatively hairless or nearly hairless skin site. If none are available, the hair at the site should be clipped, not shaven. Application sites should be rotated whenever a transdermal patch is replaced or added. Application sites should be re-used at no less than 3-week intervals. If the application site must be cleaned, it should be done with clear water only. Soaps, alcohol, oils, lotions, or abrasive devices should not be used. The skin must be dry before the transdermal patch is applied. SOVENOR u00c6 should be pressed firmly in place at the application site, making sure contact is complete, especially around the edges. If the edges of the patch begin to peel off, the edges may be taped down with suitable skin tape. If a transdermal patch falls off, a new one should be applied. Bathing, showering, or swimming should not affect the system. While wearing SOVENOR u00c6 , patients should be advised to avoid exposing the SOVENOR u00c6 site to direct external heat sources such as heating pads, electric blankets, heat lamps, hot water bottles etc., as an increase in absorption of buprenorphine may occur. The effects of the use of SOVENOR u00c6 in hot tubs and saunas have not been studied.
Application directions
Open the pouch just before applying the patch by cutting the pouch along the dotted line with scissors. Be careful not to damage the transdermal patches with the scissors. Take off the thin cover sheet. Attach the patch to the upper arm, upper chest, upper back, or sides of the chest. Press the patch with the hand for approximately 30 seconds and check that it is properly attached. The patch should not be used if the seal is broken.
Discontinuation
After removal of SOVENOR u00c6 , plasma concentrations decrease gradually. This should be considered when therapy with SOVENOR u00c6 is to be followed by other opioids. As a general rule, a subsequent opioid should not be administered within 24 hours after removal of SOVENOR u00c6 .

SOVENOR u00c6 is contraindicated in:
u2022 patients with known hypersensitivity to buprenorphine or to any of the excipients (see section 6.1), including previous history of application site reactions, suggestive of contact dermatitis with buprenorphine transdermal patches;
u2022 patients suffering from delirium tremens;
u2022 patients with severe hepatic impairment;
u2022 patients suffering from myasthenia gravis.
SOVENOR u00c6 should not be used in patients with head injury, intracranial lesions or increased intracranial pressure, shock or a reduced level of consciousness of uncertain origin.

SOVENOR u00c6 should be used with caution in patients with impaired respiratory function and in patients concurrently receiving serotonergic agents including monoamine oxidase inhibitors (MAOIs) or who have received MAOIs within the previous two weeks (see section 4.5). SOVENOR u00c6 should be used with caution in patients with constipation. Caution should be exercised in patients suffering from sleep apnoea. SOVENOR u00c6 may lower the seizure threshold in patients with a history of seizure disorder. Severe febrile illness may increase the rate of buprenorphine absorption from SOVENOR u00c6 .
Respiratory depression
The primary risk of opioid excess is respiratory depression. Opioids may cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxaemia. Opioid use may increase the risk of CSA in a dose- dependent manner in some patients. Opioids may also cause worsening of pre-existing sleep apnoea (see section 4.8). In patients who present with CSA, consider decreasing the total opioid dosage.
CNS depressants co-administration
Concomitant use of buprenorphine and sedative medicines such as benzodiazepines or related medicines 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 opioids concomitantly with sedative medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible. It is unknown if such severity can be expected from transdermal formulations of buprenorphine.
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).
Serotonin syndrome
Concomitant administration of buprenorphine and other serotonergic agents, such as MAOIs, selective serotonin re-uptake inhibitors (SSRIs), serotonin norepinephrine re-uptake inhibitors (SNRIs) or tricyclic antidepressants may result in serotonin syndrome, a potentially life-threatening condition (see section 4.5). Caution is also advised in patients who have received MAOIs within the previous two weeks. If concomitant treatment with other serotonergic agents is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Symptoms of serotonin syndrome may include mental-status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms.
Medicine dependence, tolerance and potential for abuse
For all patients, prolonged use of SOVENOR u00c6 may lead to medicine dependence (addiction), even at therapeutic doses. The risks are increased in individuals with current or past history of substance misuse disorder (including alcohol misuse) or mental health disorder (e.g. major depression). Additional support and monitoring may be necessary when prescribing for patients at risk of opioid misuse. A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained online, and past and present medical and psychiatric conditions.
Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of pain control as initially experienced. Patients may also supplement their treatment with additional pain relievers. These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient. Overuse or misuse may result in overdose and/or death. It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else. Patients should be closely monitored for signs of misuse, abuse, or addiction. The clinical need for analgesic treatment should be reviewed regularly.
Significant respiratory depression has been associated with buprenorphine, particularly by the intravenous route. A number of deaths have occurred when addicts have intravenously abused buprenorphine, usually with benzodiazepines concomitantly. Additional overdose deaths due to ethanol and benzodiazepines in combination with buprenorphine have been reported (see section 4.5).
Caution should be exercised when prescribing SOVENOR u00c6 to patients known to have, or suspected of having, problems with drug or alcohol abuse or serious mental illness.
Medicine withdrawal syndrome
Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with SOVENOR u00c6 . Medicine withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months. Withdrawal syndrome, when it occurs, is generally mild, begins after 2 days and may last up to 2 weeks. The opioid medicine withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.
If women take this medicine during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome.
Hyperalgesia
Hyperalgesia may be diagnosed if the patient on long-term opioid therapy presents with increased pain. This might be qualitatively and anatomically distinct from pain related to disease progression or to breakthrough pain resulting from development of opioid tolerance. Pain associated with hyperalgesia tends to be more diffuse than the pre-existing pain and less defined in quality. Symptoms of hyperalgesia may resolve with a reduction of opioid dose.
SOVENOR u00c6 should not be used at higher doses than recommended.
Skin reactions at application site
To minimise the risk of occurrence of application site skin reactions, it is important to follow the posology instructions (see section 4.2). Application site reactions with SOVENOR u00c6 are usually presented by a mild or moderate skin inflammation (contact dermatitis), and their typical appearance may include erythema, oedema, pruritus, rash, small blisters (vesicles), and painful/burning sensation at the application site. Most commonly the cause is skin irritation (irritant contact dermatitis), and these reactions resolve spontaneously after SOVENOR u00c6 removal. SOVENOR u00c6 may also cause skin sensitisation and subsequent allergic contact dermatitis (immune mediated, type IV hypersensitivity reaction). Allergic contact dermatitis may develop with a significant delay (it may take months after SOVENOR u00c6 treatment initiation) and may manifest with symptoms similar to irritant contact dermatitis, or with more intense symptoms, such as u201cburnu201d -like lesions with bullae and discharge, which may spread outside the application site and which may not resolve rapidly after SOVENOR u00c6 removal. Patients and caregivers should be instructed accordingly to monitor the application sites for such reactions. If allergic contact dermatitis is suspected, relevant diagnostic procedures should be performed to determine if sensitisation has occurred and its actual cause (buprenorphine and/or other ingredients of the patch). If allergic contact dermatitis has been confirmed, treatment should be discontinued (see section 4.3). Continued SOVENOR u00c6 treatment in individuals experiencing allergic contact dermatitis may lead to complications, including blistering of the skin, open wound, bleeding, ulceration, and subsequent infections. Mechanical injuries during patch removal (e.g. laceration) are also possible in patients with fragile skin. Chronic inflammation may lead to long-lasting sequelae, such as post inflammatory hyper- and hypopigmentation, as well as dry and thick scaly skin lesions, which may closely resemble scars.
Endocrine system
Opioids 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 be manifest from these hormonal changes.
SOVENOR u00c6 is not recommended for analgesia in the immediate post-operative period or in other situations characterised by rapidly varying analgesic requirement. SOVENOR u00c6 produces morphine-like effects, including euphoria and physical dependence.
Administration of SOVENOR u00c6 to persons who are physically dependent on full u03bc-opioid agonists may precipitate an abstinence syndrome.

Caution in the use of SOVENOR u00c6 in patients taking MAOIs or who have received MAOIs within the previous two weeks is appropriate. SOVENOR u00c6 should be used with caution in patients who are concurrently taking other central nervous system (CNS) depressants or other medicines that may cause respiratory depression, hypotension, profound sedation, or potentially result in coma and death. Such medicines include sedatives or hypnotics, general anaesthetics, other opioid analgesics, phenothiazines, centrally acting anti-emetics, benzodiazepines and alcohol.
Buprenorphine should be used cautiously when co-administered with serotonergic medicinal products, such as MAOIs, SSRIs, SNRIs or tricyclic antidepressants as the risk of serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4).
Reductions in hepatic blood flow induced by some general anaesthetics ( e.g. halothane) and other medicines may result in a decreased rate of hepatic elimination of the medicine buprenorphine.
Buprenorphine, as in SOVENOR u00c6 , is primarily metabolised by glucuronidation and to a lesser extent (about 30 %) by CYP3A4. Concomitant treatment with CYP3A4 inhibitors may lead to elevated plasma concentrations with intensified efficacy of buprenorphine. A medicine interaction study with the CYP3A4 inhibitor ketoconazole did not produce clinically relevant increases in mean maximum (C max ) or total (AUC) buprenorphine exposure following SOVENOR u00c6 with ketoconazole as compared to SOVENOR u00c6 alone. The interaction between buprenorphine and CYP3A4 enzyme inducers has not been studied. Co-administration of buprenorphine and enzyme inducers (e.g. phenobarbitone, carbamazepine, phenytoin and rifampicin) could lead to increased clearance which might result in reduced efficacy.

SOVENOR u00c6 should not be used during pregnancy or lactation.
Pregnancy
Buprenorphine, as contained in SOVENOR u00c6 , has been shown to cross the placenta in humans. Prolonged used of SOVENOR u00c6 during pregnancy can result in neonatal opioid withdrawal syndrome.
Breastfeeding
Buprenorphine, as contained in SOVENOR u00c6 , has been detected in newborn blood, urine and meconium and also in motheru2019s milk at low concentrations.
Fertility
No human data on the effect of buprenorphine on fertility are available. In animal studies, no effect on fertility has been observed with buprenorphine (see section 5.3).

SOVENOR u00c6 may impair the ability to drive and operate machinery.

a) Summary of safety profile
Serious adverse reactions that may be associated with SOVENOR u00c6 therapy in clinical use are similar to those observed with other opioid analgesics, including respiratory depression (especially when used with other CNS depressants) and hypotension (see section 4.4).
b) Tabulated list of adverse reactions
The following side effects have been reported during the use of SOVENOR u00c6 :
The table lists adverse reactions reported from 9 completed studies with SOVENOR u00c6 . The reactions are listed as MeDRA preferred term by system organ class and absolute frequency. Very common (u2265 1/10); common (u2265 1/100 to < 1/10); uncommon (u2265 1/1 000 to < 1/100); rare (u2265 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).
Immune System disorders
Uncommon allergic reaction (including oropharyngeal swelling and swollen tongue)
Very rare anaphylactic response
Metabolism and nutrition disorders
Common a norexia
Rare dehydration*
Psychiatric disorders
Common confusional state, depression*, insomnia, nervousness, anxiety
Uncommon affect lability, agitation, euphoric mood, hallucination, decreased libido, nightmare, aggression
Rare psychotic disorder
Very rare depersonalisation, medicine dependence (see section 4.4)
Nervous system disorders
Very common dizziness, headache*, somnolence*
Common T remor
Uncommon concentration impairment, abnormal co - ordination, dysarthria, dysgeusia, hypoaesthesia, memory impairment, migraine, syncope*, paraesthesia
Very rare C onvulsions
Not known hyperalgesia, sleep apnoea syndrome
Eye disorders
Uncommon dry eye, blurred vision
Rare M iosis
Ear and labyrinth disorders
Uncommon tinnitus, vertigo
Cardiac disorders
Uncommon palpitations, tachycardia
Rare angina pectoris
Vascular disorders
Uncommon flushing, hypertension*
Rare vasodilatation, orthostatic hypotension
Very rare H ypotension
Respiratory, thoracic and mediastinal disorders
Common dyspnoea*
Uncommon cough, hiccups, wheezing
Rare asthma aggravated*, hyperventilation, hypoxia, respiratory failure, rhinitis
Very rare respiratory depression
Gastrointestinal disorders
Very Common constipation*, nausea*, vomiting*
Common abdominal pain*, diarrhoea*, dry mouth, dyspepsia*
Uncommon F latulence
Rare dysphagia, ileus
Not known diverticulitis*
Hepatobiliary disorders
Not known biliary colic*
Skin and subcutaneous tissue disorders
Very Common pruritus*
Common rash*, sweating*
Uncommon dry skin, urticaria, dermatitis contact
Rare face oedema
Musculoskeletal and connective tissue disorders
Uncommon muscle spasm, myalgia
Renal and urinary disorders
Uncommon urinary incontinence, urinary retention, urinary hesitation
Reproductive system and breast disorders
Rare sexual dysfunction
General disorders and administration site conditions
Very Common application site reaction u2020
Common asthenic conditions (including muscle weakness), peripheral oedema
Uncommon oedema, pyrexia*, rigors*, withdrawal syndrome, chest pain, application site dermatitis**
Rare influenza - like illness
Not known withdrawal syndrome neonatal, tolerance
Investigations
Uncommon alanine amino - transferase increased, weight decreased
Injury and poisoning
Uncommon accidental injury (including fall)
* At least one serious case
u2020 Includes: application site erythema, application site oedema, application site pruritus, application site rash.
** In some cases late onset local allergic reactions occurred with marked signs of inflammation. In such cases treatment with SOVENOR u00c6 should be terminated.
Adverse events identified through post marketing experience
Rare Increased risk of abdominal pain, including pancreatitis has been reported
c) Description of selected adverse reactions
Mechanical injuries during patch removal (e.g. laceration) are also possible in patients with fragile skin. Chronic inflammation may lead to long-lasting sequelae, such as post inflammatory hyper- and hypopigmentation, as well as dry and thick scaly skin lesions, which may closely resemble scars. In such cases treatment with SOVENOR u00c6 should be terminated (see sections 4.3 and 4.4). After discontinuation of SOVENOR u00c6 , withdrawal symptoms are uncommon. This may be due to the very slow dissociation of buprenorphine from the opioid receptors and to the gradual decrease of buprenorphine plasma concentrations (usually over a period of 30 hours after removal of the last patch).
Reporting suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

The manifestations of SOVENOR u00c6 overdose is an extension of its pharmacological actions. Respiratory depression has been absent in some cases of buprenorphine overdose. Respiratory depression, including apnoea, may occur in other overdose situations. Additional symptoms include sedation, drowsiness, nausea, vomiting, cardiovascular collapse and marked miosis.
Remove any SOVENOR u00c6 in contact with the patient and dispose of it properly. Establish and maintain a patent airway, assist and control respiration as indicated, and maintain adequate body temperature and fluid balance. Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. A specific opioid antagonist such as naloxone may reverse the effects of buprenorphine, although naloxone may be less effective in reversing the effects of buprenorphine than other u03bc-opioid agonists. Treatment with continuous intravenous naloxone should begin with the usual doses but high doses may be required. Maintenance of adequate ventilation is essential when managing a SOVENOR u00c6 overdose and more important than specific antidote treatment with a narcotic antagonist such as naloxone.