Source: Medicines and Medical Devices Safety Authority (NZ) Revision Year: 2022 Publisher: Distributed on behalf of Mundipharma New Zealand Limited by: Pharmaco (N.Z.) Ltd, Fisher Crescent, Mt Wellington, Auckland 1060 Ph: (09) 377-3336 Toll Free [Medical Enquiries]: 0800 773 310
NORSPAN patch is contraindicated in patients with known hypersensitivity to buprenorphine or any components of the patch (see Section 6.1), including previous history of application site reactions suggestive of allergic contact dermatitis with buprenorphine transdermal patches, myasthenia gravis, delirium tremens and pregnancy.
NORSPAN patch is contraindicated in patients with severely impaired respiratory function and in patients concurrently receiving non-selective monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with non-selective MAOIs.
NORSPAN patch must not be used for the treatment of opioid dependence and opioid withdrawal.
NORSPAN should be used with caution in patients with:
Use with caution in patients with hypotension, hypovolaemia, biliary tract disease, pancreatitis, inflammatory bowel disorders, prostatic hypertrophy, adrenocortical insufficiency, chronic renal and hepatic disease and debilitated patients. As with all opioids, a reduction in dose may be advisable in hypothyroidism.
NORSPAN contains the opioid buprenorphine and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed NORSPAN at recommended doses. The risk of addiction is increased in patients with a personal or family history of substance abuse (including alcohol and prescription and illicit drugs) or mental illness. The risk also increases the longer the drug is used and with higher doses. Patients should be assessed for their risks for opioid abuse or addiction prior to being prescribed NORSPAN.
All patients receiving opioids should be routinely monitored for signs of misuse and abuse. Opioids are sought by people with addiction and may be subject to diversion. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the safe storage and proper disposal of any unused drug (see section 6.4 and section 6.6). Caution patients that abuse of oral or transdermal forms of opioids by parenteral administration can result in serious adverse events, which may be fatal.
Patients should be advised not to share NORSPAN with anyone else.
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. Caution should be exercised when prescribing NORSPAN to patients known to have, or suspected of having, problems with drug or alcohol abuse or serious mental illness.
Although the risk of addiction in any individual is unknown, it may occur in patients appropriately prescribed NORSPAN patch and in those who obtain the drug illicitly. Psychological and/or physical dependence may occur at recommended doses and if the drug is misused or abused.
Assess each patient’s risk for addiction to opioids, abuse, or misuse prior to prescribing NORSPAN patch and monitor all patients receiving NORSPAN patch for the development of these behaviours or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression).
The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids, but use in such patients necessitates comprehensive counselling about the risks and proper use of opioids, along with close monitoring for signs of addiction, abuse, or misuse.
NORSPAN patch, like other opioids, can be diverted for non-medical use into illicit channels of distribution. NORSPAN patch should therefore be prescribed and handled with a high degree of caution appropriate to the use of a drug with strong abuse potential.
NORSPAN patch is intended for transdermal use only. Abuse of opioids poses a risk of overdose and death. This risk is increased with concurrent abuse of opioids with alcohol and other substances including other opioids and benzodiazepines. Abuse or misuse in ways other than indicated or intentional compromise of transdermal delivery systems containing opioids will result in the uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death (see Section 4.9 OVERDOSAGE).
Serious, life-threatening or fatal respiratory depression can occur with the use of opioids even when used as recommended. It can occur at any time during the use of [Product] but the risk is greatest during initiation of therapy or following an increase in dose. Patients should be monitored closely for respiratory depression at these times.
The risk of life-threatening respiratory depression is also higher in elderly, frail, or debilitated patients and in patients with existing impairment of respiratory function (e.g. chronic obstructive pulmonary disease; asthma). Opioids should be used with caution and with close monitoring in these patients (see section 4.2). The use of opioids is contraindicated in patients with severe respiratory disease, acute respiratory disease and respiratory depression (see section 4.3 ).
The risk of respiratory depression is greater with the use of high doses of opioids, especially high potency and modified release formulations, and in opioid naïve patients. Initiation of opioid treatment should be at the lower end of the dosage recommendations with careful titration of doses to achieve effective pain relief. Careful calculation of equianalgesic doses is required when changing opioids or switching from immediate release to modified release formulations, (see section 4.2).
Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleeprelated hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. Opioids may also cause worsening of pre-existing sleep apnoea (see section 4.8). In patients who present with CSA, consider decreasing the opioid dosage using best practices for opiod taper.
Concomitant use of opioids and benzodiazepines or other CNS depressants, including alcohol, may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of NORSPAN with CNS depressant medicines, such as other opioid analgesics, benzodiazepines, gabapentinoids, cannabis, sedatives, hypnotics, tricyclic antidepressants, antipsychotics, antihistamines, centrally-active anti-emetics and other CNS depressants, should be reserved for patients for whom other treatment options are not possible. If a decision is made to prescribe NORSPAN concomitantly with any of the medicines, the lowest effective dose should be used, and the duration of treatment should be as short as possible. Patients should be followed closely for signs and symptoms of respiratory depression and sedation. Patients and their caregivers should be made aware of these symptoms. Patients and their caregivers should also be informed of the potential harms of consuming alcohol while taking NORSPAN.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of medicine-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics (see Section 4.5 Interactions with other medicines and other forms of interaction).
Advise both patients and caregivers about the risks of respiratory depression and sedation when NORSPAN patch is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs (see Section 4.5 Interactions with other medicines and other forms of interaction).
Opioid analgesics have an established role in the treatment of acute pain, cancer pain and palliative and end-of-life care. Current evidence does not generally support opioid analgesics in improving pain and function for most patients with chronic non-cancer pain. The development of tolerance and physical dependence and risks of adverse effects, including hazardous and harmful use, increase with the length of time a patient takes an opioid. The use of opioids for long-term treatment of CNCP is not recommended.
The use of an opioid to treat CNCP should only be considered after maximised non-pharmacological and non-opioid treatments have been tried and found ineffective, not tolerated or otherwise inadequate to provide sufficient management of pain. Opioids should only be prescribed as a component of comprehensive multidisciplinary and multimodal pain management. Opioid therapy for CNCP should be initiated as a trial in accordance with clinical guidelines and after a comprehensive biopsychosocial assessment has established a cause for the pain and the appropriateness of opioid therapy for the patient (see Hazardous and harmful use, above). The expected outcome of therapy (pain reduction rather than complete abolition of pain, improved function and quality of life) should be discussed with the patient before commencing opioid treatment, with agreement to discontinue treatment if these objectives are not met.
Owing to the varied response to opioids between individuals, it is recommended that all patients be started at the lowest appropriate dose and titrated to achieve an adequate level of analgesia and functional improvement with minimum adverse reactions. Immediate-release products should not be used to treat chronic pain, but may be used for a short period in opioid-naïve patients to develop a level of tolerance before switching to a modified-release formulation. Careful and regular assessment and monitoring is required to establish the clinical need for ongoing treatment. Discontinue opioid therapy if there is no improvement of pain and/or function during the trial period or if there is any evidence of misuse or abuse. Treatment should only continue if the trial has demonstrated that the pain is opioid responsive and there has been functional improvement. The patient’s condition should be reviewed regularly and the dose tapered off slowly if opioid treatment is no longer appropriate (see Ceasing Opioids).
Buprenorphine is a μ-opioid agonist.
Neuroadaptation of the opioid receptors to repeated administration of opioids can produce tolerance and physical dependence. Tolerance is the need for increasing doses to maintain analgesia. Tolerance may occur to both the desired and undesired effects of the opioid.
Physical dependence, which can occur after several days to weeks of continued opioid usage, results in withdrawal symptoms if the opioid is ceased abruptly or the dose is significantly reduced.
Withdrawal symptoms can also occur following the administration of an opioid antagonist (e.g. naloxone) or partial agonist (e.g. buprenorphine). Withdrawal can result in some or all of the following symptoms: dysphoria, restlessness/agitation, lacrimation, rhinorrhoea, yawning, sweating, chills, myalgia, mydriasis, irritability, anxiety, increasing pain, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhoea, increased blood pressure, increased respiratory rate and increased heart rate.
When discontinuing NORSPAN in a person who may be physically-dependent, the drug should not be ceased abruptly but withdrawn by tapering the dose gradually (see section 4.2).
If NORSPAN patch is abruptly discontinued in a physically-dependent patient, an abstinence syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. Withdrawal may also may be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, or mixed agonist/antagonist analgesics(pentazocine).
Administration of buprenorphine to persons who are physically dependent on full μ-opioid agonists may precipitate an abstinence syndrome depending on the level of physical dependence, and the timing and dose of buprenorphine.
Accidental exposure of NORSPAN, especially by children, can result in a fatal overdose of NORSPAN. Patients and their caregivers should be given information on safe storage and disposal of unused NORSPAN (see section 6.4 and section 6.6).
Hyperalgesia may occur with the use of opioids, particularly at high doses. Hyperalgesia may manifest as an unexplained increase in pain, increased levels of pain with increasing opioid dosages or diffuse sensitivity not associated with the original pain. Hyperalgesia should not be confused with tolerance (see Tolerance, dependence and withdrawal). If opioid induced hyperalgesia is suspected, the dose should be reduced and tapered off if possible. A change to a different opioid may be required.
Abrupt discontinuation or rapid decreasing of the dose in a person physically dependent on an opioid may result in serious withdrawal symptoms and uncontrolled pain (see Tolerance, dependence and withdrawal). Such symptoms may lead the patient to seek other sources of licit or illicit opioids. Opioids should not be ceased abruptly in a patient who is physically dependent but withdrawn by tapering the dose slowly. Factors to take into account when deciding how to discontinue or decrease therapy include the dose and duration of the opioid the patient has been taking, the type of pain being treated and the physical and psychological attributes of the patient. A multimodal approach to pain management should be in place before initiating an opioid analgesic taper. During tapering, patients require regular review and support to manage any increase in pain, psychological distress and withdrawal symptoms.
There are no standard tapering schedules suitable for all patients and an individualised plan is necessary. In general, tapering should involve a dose reduction of no more than 10 percent to 25 percent every 2 to 4 weeks (see section 4.2). If the patient is experiencing increased pain or serious withdrawal symptoms, it may be necessary to go back to the previous dose until stable before proceeding with a more gradual taper.
When ceasing opioids in a patient who has a suspected opioid use disorder, the need for medication assisted treatment and/or referral to a specialist should be considered.
In chronic non-malignant pain, medication modifies the pain only to some extent. A comprehensive assessment is essential, and non-pharmacological options should be explored before starting pharmacological therapy. Patients should be advised about the expected outcome of therapy (i.e. pain reduction rather than complete abolition of pain, reduced suffering, improved function and quality of life). Opioid therapy should be initiated as a trial. Careful and regular assessment and monitoring is required to establish the clinical need for ongoing treatment with an opioid analgesic. Reassess or discontinue opioid therapy if there is no improvement of pain and/or function. NORSPAN patch should be ceased if there is any evidence of misuse or abuse, or if NORSPAN patch is having a detrimental effect.
NORSPAN is not recommended for analgesia in the immediate post-operative period or in other situations characterized by rapidly varying analgesic requirement. As with all opioid preparations patients who are to undergo cordotomy or other pain- relieving surgical procedures should not use NORSPAN patch for at least 24 hours prior to surgery. NORSPAN patch should be used with caution following abdominal surgery, as opioids are known to impair intestinal motility.
A kinetic study indicated no alteration of buprenorphine plasma concentrations in subjects with mild fever induced by endotoxin administration. However, because increased blood flow to the skin may enhance absorption, severe febrile illness may increase the rate of buprenorphine absorption from the patch and thus, patients with severe febrile illness should be monitored for side effects and may require dose adjustment.
Buprenorphine may lower the seizure threshold in patients with a history of seizure disorder.
The lowest dose available, NORSPAN patch 5 micrograms, should be used as the starting dose in opioid-naïve patients.
No dose adjustment is necessary in patients with renal impairment.
Buprenorphine is metabolised in the liver. No dose adjustment is necessary in patients with mild to moderate hepatic impairment, however, the intensity and duration of its action may be affected in patients with impaired liver function. Patients with severe hepatic impairment may accumulate buprenorphine during NORSPAN patch treatment. Consideration should be given to alternative therapy and NORSPAN patch should be used with caution, if at all, in such patients.
Increased alanine aminotransferase levels.
Advise patients and their caregivers to avoid exposing the application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, saunas, hot tubs, hot water bottles and heated water beds while wearing the patch because an increase in absorption of buprenorphine may occur. There is a potential for temperature-dependent increases in buprenorphine released from the patch, thereby increasing the risk of opioid reactions.
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 NORSPAN 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 NORSPAN removal.
NORSPAN may also cause skin sensitisation and subsequent allergic contact dermatitis (immunemediated, type IV hypersensitivity reaction). Allergic contact dermatitis may develop with a significant delay (it may take months after NORSPAN treatment initiation), and may manifest with symptoms similar to irritant contact dermatitis, or with more intense symptoms, such as “burn”-like lesions with bullae and discharge, which may spread outside the application site and which may not resolve rapidly after NORSPAN 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 NORSPAN 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.
The safety and efficacy of NORSPAN patch in patients under 18 years of age has not been established.
In clinical trial patients there were no apparent effects on NORSPAN patch exposure when used concomitantly with various H2-antagonists or proton pump inhibitors.
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). Such agents include sedatives or hypnotics, general anesthetic’s, other opioid analgesics, phenothiazines, centrally acting anti-emetics, benzodiazepines and alcohol.
Buprenorphine is both a substrate for, and an inhibitor of, CYP3A4. Specific inhibitors of CYP3A4 (ketoconazole, ritonavir, indinavir) have been shown to inhibit formation of the buprenorphine metabolite, norbuprenorphine, in human liver microsomes. Antifungal drugs with similar CY3A4 inhibiting properties to ketoconazole include fluconazole and itraconazole).
Buprenorphine 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 drug interaction study with the CYP3A4 inhibitor ketoconazole did not produce clinically relevant increases in mean maximum (Cmax) or total (AUC) buprenorphine exposure following NORSPAN with ketoconazole as compared to NORSPAN alone.
The interaction between buprenorphine and CYP3A4 enzyme inducers has not been studied; however, co-administration of NORSPAN patch and enzyme inducers (e.g. phenobarbitone, carbamazepine, phenytoin, rifampicin) could lead to increased clearance which might result in reduced efficacy. Buprenorphine has also been shown to be a CYP2D6 inhibitor in vitro. Patients receiving NORSPAN with CYP3A4 inhibitors should be closely monitored.
Reductions in hepatic blood flow induced by some general anaesthetics (e.g. halothane) and other drugs may result in a decreased rate of hepatic elimination of buprenorphine.
It is unknown whether there is an interaction between selective MAOIs (e.g. selegiline) and buprenorphine, hence, caution is advised with this drug combination.
The potential exists for international normalized ratio (INR) elevation in patients who are concomitantly taking warfarin. A retrospective safety analysis and benefit-risk assessment was performed evaluating the interaction between buprenorphine and warfarin. The analysis revealed very limited data was available and that there was a more likely interaction between buprenorphine and phenprocoumon than warfarin. However, there is not sufficient information for inclusion of the medicine interaction between buprenorphine and phenprocoumon.
Anticholinergics or other drugs with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when NORSPAN patch is used concurrently with anticholinergic drugs.
Buprenorphine has been shown to cross the placenta in humans and has been detected in newborn blood, urine and meconium. Opioid analgesics, including buprenorphine, may cause respiratory depression in the newborn infant. Withdrawal symptoms in newborn infants have been reported with prolonged use of this class of medicines. Neonatal withdrawal symptoms may include poor feeding, diarrhoea, irritability, tremor, rigidity, and seizures. Infants born to mothers physically dependent on opioids may also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms. There are no adequate and well-controlled studies of buprenorphine or NORSPAN patch in pregnant women.
In pregnant rabbits, buprenorphine produced statistically significant pre-implantation losses at PO doses ≥1mg/kg/day and post-implantation losses at intravenous (IV) doses ≥0.2mg/kg/day (medicine exposure in animals about 6 times the expected daily systemic dose of buprenorphine in humans during treatment with NORSPAN patch 20mg, on a surface area basis). Dystocia was noted in pregnant rats treated intramuscular (IM) with buprenorphine doses >1mg/kg/day (approximately 17 times the expected human daily dose during treatment with NORSPAN patch 20mg). Fertility and peri- and postnatal development studies with buprenorphine in rats showed increases in neonatal mortality after doses of 0.8mg/kg/day PO, 0.5mg/kg/day IM or 0.1mg/kg/day SC (approximately 14, 9 and 1.7 times, respectively, the human daily dose during treatment with NORSPAN patch 20mg on a mg/m² basis). No-effect doses for neonatal mortality were not established. Delays in the occurrence of righting reflex and startle response were noted in rat pups at a buprenorphine dose >8mg/kg/day PO (>100 times the expected human daily dose during treatment with NORSPAN patch 20mg on a mg/m² basis). No evidence for teratogenic activity was observed in animal studies at buprenorphine doses ranging from 14 to >100 times the expected human daily dose during treatment with NORSPAN patch 20mg, on a surface areabasis.
No effects on embryofetal development were noted in studies with topically applied NORSPAN patch in rats and rabbits (systemic exposure to buprenorphine up to about 30 and 6 times, respectively, the expected human daily dose during treatment with NORSPAN patch 20mg, on a surface area basis). However, systemic absorption was demonstrated only during late gestation in rabbits.
In a pre/postnatal study in pregnant and lactating rats, administration of ≥0.5 mg/kg/day SC buprenorphine caused an increase in the number of stillbirths and reduced pup survival. Exposures (AUC) at the no effect level (0.05 mg/kg/day SC) were subclinical.
Animal studies indicate buprenorphine has the potential to inhibit lactation or milk production. Decreases in post-natal survival, growth and development were also observed in animals treated with buprenorphine during lactation. Buprenorphine passes into mother’s milk at low concentrations and therefore, NORSPAN patch should not be used by breastfeedingwomen.
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).
NORSPAN patch has a major influence on the ability to drive and use machines. Even when used according to instructions, buprenorphine may modify patients' reactions to a varying extent depending on the dosage and individual susceptibility such that road safety and the ability to operate machinery may be impaired. This applies particularly in the beginning of treatment, during titration to a higher dose and in conjunction with other centrally acting substances including alcohol, tranquillisers, sedatives and hypnotics. If affected, patients should not drive or operate machinery for at least 24 hours after the NORSPAN patch has been removed.
Adverse reactions that may be associated with NORSPAN patch therapy in clinical use are similar to those observed with other opioid analgesics and tend to reduce with time, with the exception of constipation.
The following adverse reactions have been reported:
Uncommon: hypersensitivity(including oropharyngeal swelling and swollen tongue)
Rare: anaphylactic responses
Very rare: serious allergic reactions
Common: anorexia
Uncommon: dehydration*, weight decreased
Common: anxiety, confusional state, depression*, insomnia,nervousness
Uncommon: affect lability, agitation, depersonalisation, euphoric mood, hallucination, libido decreased, nightmare, aggression
Rare: psychotic disorder
Very rare: dependence, mood swings
Unknown: drug dependence
Very Common: dizziness, headache*, somnolence*
Common: dysgeusia (taste disturbance), paraesthesia,tremor
Uncommon: concentration impairment, coordination abnormal, dysarthria, hypoaesthesia, memory impairment, migraine, restlessness, sedation, sleep disorder, syncope*
Rare: dysequilibrium, numbness
Not Known: convulsions, hyperalgesia, sleep apnoea syndrome
Uncommon: dry eye, vision blurred
Rare: eyelid oedema, miosis, visual disturbance
Uncommon: tinnitus, vertigo
Very rare: ear pain
Uncommon: angina pectoris, palpitations, tachycardia
Common: vasodilatation
Uncommon: circulatory disorders (such as hypotension or rarely even circulatory collapse), flushing, hypertension*, orthostatichypotension
Common: dyspnoea*
Uncommon: asthma aggravated*, cough, hiccups, hyperventilation, hypoxia, rhinitis*, wheezing*
Rare: respiratory depression, respiratory failure*
Very Common: constipation*, dry mouth, nausea*, vomiting*
Common: abdominal pain*, diarrhoea*, dyspepsia*
Uncommon: flatulence
Rare: diverticulitis*, dysphagia, ileus, pyrosis(heartburn)
Very rare retching
Rare: billiary colic
Very Common: pruritus*
Common: exanthema, rash*,sweating*
Uncommon: dry skin, face oedema, urticaria
Very rare: pustules, vesicles
Uncommon: muscle cramps, muscle spasm, myalgia
Very rare: muscle fasciculation
Uncommon: urinary incontinence, urinary retention
Rare: urinary hesitation
Rare: decreased erection, sexual dysfunction
Very common: application site skin reaction†**
Common: asthenic conditions* (including muscle weakness, lethargy, fatigue and malaise), pain, peripheral oedema,tiredness
Uncommon: oedema, pyrexia*, rigors*, drug withdrawal syndrome, chest pain*,
Rare: influenza-like illness
Not known: Drug withdrawal syndrome neonatal, Drug tolerance
Uncommon: accidental injury (including fall)
Uncommon: Alanine aminotransferase increased, Weight decreased
Very Common ≥10%
Common ≥1% and <10%
Uncommon ≥0.1% and <1%
Rare ≥0.01% and <0.1% (isolated cases)
Very rare <0.01%
* at least one serious case
† Include common signs and symptoms of contact dermatitis (irritative or allergic): erythema, oedema, pruritus, rash, vesicles, painful/burning sensation at the application site.
** In some cases late onset local allergic reactions (allergic contact dermatitis) occurred with marked signs of inflammation. In such cases treatment with NORSPAN should be terminated (see sections 4.3 and 4.4).
The incidence of adverse events did not vary with age or race. The incidence of most adverse events was similar for males and females, but females reported nausea, vomiting, dizziness and headache 10% to 15% more frequently than males.
In rare cases, severe application site skin reactions with signs of marked inflammation including “burn,” “discharge,” and “vesicles” have occurred. Time of onset varies, ranging from days to months following the initiation of NORSPAN patch. Instruct patients to promptly report the development of severe application site reactions and discontinue therapy.
Cases of acute and chronic hypersensitivity to buprenorphine have been reported uncommonly both in clinical trials and in the post-marketing experience. The most common signs and symptoms include rashes, hives, and pruritus. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. A history of hypersensitivity to buprenorphine is a contraindication to the use of NORSPAN patch.
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/
None known.
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