Norspan Transdermal Patch (2023)

Table of Contents
1 Name of Medicine 2 Qualitative and Quantitative Composition Norspan patch 5. Norspan patch 10. Norspan patch 15. Norspan patch 20. Norspan patch 25. Norspan patch 30. Norspan patch 40. 3 Pharmaceutical Form 4 Clinical Particulars 4.1 Therapeutic Indications 4.2 Dose and Method of Administration Adults. Titration. Opioid naïve patients. Conversion from opioid or fixed ratio opioid/ nonopioid combination drugs. Children. Renal and hepatic impairment. Discontinuation. Method of application. 4.3 Contraindications 4.4 Special Warnings and Precautions for Use Hazardous and harmful use. Respiratory depression. Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol. Use of opioids in chronic (long-term) non-cancer pain (CNCP). Tolerance, dependence and withdrawal. Accidental exposure. Hyperalgesia. Ceasing opioids. Use in surgery. Prolongation of QT interval. Gastrointestinal tract. Febrile illness. Opioid naïve patients. Application of external heat. Skin reactions at application site. Use in hepatic impairment. Use in renal impairment. Use in the elderly. Paediatric use. Effects on laboratory tests. General. Serotonin syndrome. 4.5 Interactions with Other Medicines and Other Forms of Interactions 4.6 Fertility, Pregnancy and Lactation Effects on fertility. 4.7 Effects on Ability to Drive and Use Machines 4.8 Adverse Effects (Undesirable Effects) Reporting suspected adverse effects. 4.9 Overdose Symptoms of overdose. Treatment of overdose. 5 Pharmacological Properties 5.1 Pharmacodynamic Properties Mechanism of action. Clinical trials. 5.2 Pharmacokinetic Properties Absorption. Distribution. Metabolism and excretion. 5.3 Preclinical Safety Data Genotoxicity. Carcinogenicity. 6 Pharmaceutical Particulars 6.1 List of Excipients 6.2 Incompatibilities 6.3 Shelf Life 6.4 Special Precautions for Storage 6.5 Nature and Contents of Container 6.6 Special Precautions for Disposal 6.7 Physicochemical Properties Chemical structure. CAS number. 7 Medicine Schedule (Poisons Standard) Summary Table of Changes FAQs Videos

1 Name of Medicine

Buprenorphine.

2 Qualitative and Quantitative Composition

Norspan patches are available in seven strengths: 5 microgram per hour, 10 microgram per hour, 15 microgram per hour, 20 microgram per hour, 25 microgram per hour, 30 microgram per hour and 40 microgram per hour. The composition of all seven strengths is identical except for patch size. The proportion of buprenorphine in the adhesive matrix is the same in each strength (10% by weight). The amount of buprenorphine released from each system per hour is proportional to the surface area of the patch. The skin is the limiting barrier to diffusion from the system into the bloodstream.

Norspan patch 5.

Each square patch releases buprenorphine 5 microgram per hour.
The area containing the active substance: 6.25 cm2.
Total buprenorphine content: 5 mg.

Norspan patch 10.

Each rectangular patch releases buprenorphine 10 microgram per hour.
The area containing the active substance: 12.5 cm2.
Total buprenorphine content: 10 mg.

Norspan patch 15.

Each rectangular patch releases buprenorphine 15 microgram per hour.
The area containing the active substance: 18.75 cm2.
Total buprenorphine content: 15 mg.

Norspan patch 20.

Each square patch releases buprenorphine 20 microgram per hour.
The area containing the active substance: 25 cm2.
Total buprenorphine content: 20 mg.

Norspan patch 25.

Each rectangular patch releases buprenorphine 25 microgram per hour.
The area containing the active substance: 31.25 cm2.
Total buprenorphine content: 25 mg.

Norspan patch 30.

Each rectangular patch releases buprenorphine 30 microgram per hour.
The area containing the active substance: 37.5 cm2.
Total buprenorphine content: 30 mg.

Norspan patch 40.

Each rectangular patch releases buprenorphine 40 microgram per hour.
The area containing the active substance: 50 cm2.
Total buprenorphine content: 40 mg.

3 Pharmaceutical Form

Norspan transdermal drug delivery system is a rectangular (10, 15, 25, 30 and 40 microgram per hour) or square (5 and 20 microgram per hour), beige coloured transdermal matrix patch with rounded corners.
Each Norspan patch is printed with the trade name and the strength in blue ink.
Norspan patches consist of a protective liner and functional layers. Proceeding from the outer surface towards the surface adhering to the skin, the layers are (1) a beige coloured web backing layer of polyester material; (2) an adhesive matrix rim without buprenorphine; (3) a separating layer ("foil") consisting of polyethylene terephthalate over the adhesive matrix; (4) the buprenorphine containing adhesive matrix; and (5) a release liner (see Figure 1). Before use the release liner covering the adhesive layer is removed and discarded.
Norspan Transdermal Patch (1)

(Video) How to Apply & Remove Transdermal Patch (Fentanyl) | Medication Administration for Nursing Students

4 Clinical Particulars

4.1 Therapeutic Indications

Norspan patches are indicated for the management of severe pain where:
other treatment options have failed, are contraindicated, not tolerated or are otherwise inappropriate to provide sufficient management of pain; and
the pain is opioid-responsive; and
requires daily, continuous, long-term treatment.
Norspan patches are not indicated for use in chronic non-cancer pain other than in exceptional circumstances.
Norspan patches are not indicated as an as-needed (PRN) analgesia.

4.2 Dose and Method of Administration

For application to the skin (transdermal use) only over 7 days.

Adults.

The lowest dose, Norspan patch 5 microgram per hour, should be used as the initial dose. Consideration should be given to the previous opioid history of the patient, including opioid tolerance, if any, as well as current general condition and medical status of the patient. A maximum total dose of 40 microgram per hour Norspan should not be exceeded. No dosage adjustment is necessary in the elderly.

Titration.

Discontinue all other around the clock opioid drugs when Norspan therapy is initiated. During initiation and titration with Norspan patch, patients should take the usual recommended doses of short acting supplemental analgesics as needed until analgesic efficacy with Norspan patch is attained.
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 Norspan patch dosage may be individually titrated based on the need for supplemental when necessary (PRN) analgesia and the patient's response to Norspan patch.
To increase the dose, the patch that is currently being worn should be removed and a higher strength of Norspan patch or a combination of patches should be applied at a different skin site to achieve the required dose. A new patch should not be applied to the same skin site for three to four weeks. It is recommended that no more than two patches be applied at the same time, up to a maximum of 40 microgram/hr Norspan. If a 40 microgram patch is applied, no additional patches should be applied.
Patients should be carefully and regularly monitored to assess the optimum dose and duration of treatment. Titration should continue every three to seven days until adequate analgesia and improvement in function is achieved. If adequate pain relief cannot be achieved with maximal doses of Norspan patch, the patient should be converted to an around the clock strong opioid.

Opioid naïve patients.

In situations when it is clinically indicated to initiate opioid therapy with a maintenance (around the clock) opioid in an opioid naïve patient, clinical trials have shown that Norspan patch is an appropriate opioid product. The lowest dose available (Norspan patch 5 microgram per hour) should be used as the initial dose. If the patient is taking supplemental analgesics, these may be continued on a PRN basis as the dose of Norspan patch is adjusted.

Conversion from opioid or fixed ratio opioid/ nonopioid combination drugs.

Norspan patches have been used as an alternative in patients taking lower doses of opioids (up to 90 mg of oral morphine equivalents a day) and combination analgesics. Such patients should be started on a low dose of Norspan patch and continue with the same dose and dosing scheduling of their previous daily regimen during titration.

Children.

Use in children is not recommended due to lack of clinical safety and efficacy data in patients under 18 years of age.

Renal and hepatic impairment.

No dosage adjustment is required in patients with renal impairment or mild to moderate hepatic impairment. Patients with severe hepatic impairment may accumulate buprenorphine and Norspan patch should be used with caution, if at all, in such patients.

Discontinuation.

During chronic therapy, periodically reassess the continued need for opioid analgesics. After removal of a Norspan patch, buprenorphine serum concentrations decrease gradually, and the analgesic effect is maintained for a certain amount of time. This needs to be considered when use of Norspan patch is to be followed by other opioids. As a general rule, a subsequent opioid should not be administered within 24 hours of removal of a Norspan patch.
When the patient no longer requires therapy with Norspan, use a gradual downward titration of the dose every 7 days to prevent signs and symptoms of withdrawal in the physically dependent patient; consider introduction of an appropriate immediate release opioid medication.
Do not abruptly discontinue Norspan.

Method of application.

In order to ensure effective analgesia of buprenorphine and to minimise the potential of skin reactions (see Section 4.4 Special Warnings and Precautions for Use), the following directions of use should be followed:
Norspan patches should be applied to nonirritated, intact skin of the upper outer arm, upper chest, upper back or the side of the chest, but not to any parts of the skin with large scars. Application sites should be rotated whenever a patch is replaced or added. Application sites should be reused at no less than three week intervals. Norspan patches should be applied to a relatively hairless or nearly hairless skin site. If none are available, the hair at the site should be cut with scissors, not shaven.
If the application site must be cleaned, it should be done with clean water only. Soaps, alcohol, oils, lotions or abrasive devices should not be used. The skin should be dry before the patch is applied. Norspan patches should be applied immediately after removal from the sealed pouch packaging. Following removal of the release liner, the patch should be pressed firmly in place with the palm of the hand for approximately 30 seconds, making sure the contact is complete, especially around the edges. If the edges of the patch begin to peel off, they may be taped down with suitable skin tape. The patch should be worn continuously for 7 days.
Bathing, showering or swimming should not affect the patch. If a patch falls off, a new one should be applied.
While wearing the Norspan patch patients should be advised to avoid exposing the application site to direct external heat sources, such as heating pads, electric blankets, hot water bottles, heat lamps etc. as an increase in the absorption of buprenorphine may occur. The effects of use in hot tubs and sauna have not been studied.
When changing a patch, patients should be instructed to remove the used Norspan patch, fold it over on itself (bringing the adhesive sides together) and dispose of safely, out of reach of children.

4.3 Contraindications

Norspan patches are contraindicated in patients with known hypersensitivity to buprenorphine or any components of the patch, myasthenia gravis, delirium tremens and pregnancy.
Norspan patches are contraindicated in patients with severely impaired respiratory function, severe respiratory disease, acute respiratory disease and respiratory depression, and in patients concurrently receiving nonselective monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping treatment with nonselective MAOIs.
Norspan patches must not be used for the treatment of opioid dependence and opioid withdrawal.

(Video) BUPRENORPHINE (NORSPAN) - PHARMACIST REVIEW - #52

4.4 Special Warnings and Precautions for Use

Hazardous and harmful use.

Norspan patches contain the opioid buprenorphine and is a potential drug of abuse, misuse and addiction. Addiction can occur in patients appropriately prescribed Norspan patches 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 patches.
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 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal). Caution patients that abuse of oral or transdermal forms of opioids by parenteral administration can result in serious adverse events, which may be fatal. A number of deaths have occurred when addicts have intravenously abused buprenorphine, usually with benzodiazepines concomitantly. Additionally, overdosage deaths due to ethanol and benzodiazepines in combination with buprenorphine have been reported.
Patients should be advised not to share Norspan patches with anyone else.

Respiratory depression.

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 Norspan patches, 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, in patients with hepatic impairment 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. The use of opioids is contraindicated in patients with severe respiratory disease, acute respiratory disease and respiratory depression (see Section 4.3 Contraindications).
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 Dose and Method of Administration), together with consideration of pharmacological differences between opioids. Consider starting the new opioid at a reduced dose to account for individual variation in response.
Opioids may cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia. 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 Adverse Effects (Undesirable Effects)). In patients who present with CSA, consider decreasing the total opioid dosage.

Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol.

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 patches 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 patches 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 using Norspan patches.

Use of opioids in chronic (long-term) non-cancer pain (CNCP).

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).

Tolerance, dependence and withdrawal.

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 patches in a person who may be physically-dependent, the drug should not be ceased abruptly but withdrawn by tapering the dose gradually (see Ceasing opioids).

Accidental exposure.

Accidental exposure to Norspan patches especially by children, can result in a fatal overdose of buprenorphine. Patients and their caregivers should be given information on safe storage and disposal of unused Norspan patches (see Section 6.4 Special Precautions for Storage; Section 6.6 Special Precautions for Disposal).

Hyperalgesia.

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.

Ceasing opioids.

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 Dose and Method of Administration). 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.

Use in surgery.

Norspan patches are not recommended for analgesia in the immediate postoperative period or in other situations characterised by a narrow therapeutic index or a 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 patches for at least 24 hours prior to surgery. Norspan patches should be used with caution following abdominal surgery, as opioids are known to impair intestinal motility.

Prolongation of QT interval.

In a positive controlled study of the effect of Norspan patches on the QTc interval in healthy subjects, therapeutic dosages (10 microgram per hour) had no effect on the QTc interval but higher dosages (40 microgram per hour) were associated with a mean prolongation of the QTc interval of 5.9 ms. Consider these observations in clinical decisions when prescribing Norspan to patients with electrolyte abnormalities and cardiac conditions that may elevate the risk of QT prolongation, patients with congenital QT prolongation, or those taking class IA antiarrhythmic medications (e.g. quinidine, disopyramide), class III antiarrhythmic medications (e.g. sotalol, amiodarone) or any other medication which prolongs the QT interval.

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 buprenorphine. Patients should be advised on measures to prevent constipation and prophylactic laxative use should be considered. Extra caution is advised in patients with chronic constipation. If paralytic ileus is present or suspected, treatment with Norspan should be stopped.

Febrile illness.

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.

Opioid naïve patients.

The lowest dose available, Norspan patch 5 microgram, should be used as the starting dose in opioid naïve patients.

Application of external heat.

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, 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.

Skin reactions at application site.

To minimise the risk of occurrence of application site skin reactions, it is important to follow the directions of use instructions (see Section 4.2 Dose and Method of Administration).
Application site reactions with Norspan patches 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 patches removal.
Norspan patches 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 Norspan patches 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 patches 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 Contraindications).
Continued Norspan patches 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.

Use in hepatic 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 patches should be used with caution, if at all, in such patients.

Use in renal impairment.

No dose adjustment is necessary in patients with renal impairment.

Use in the elderly.

See Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use, Respiratory depression.

Paediatric use.

The safety and efficacy of Norspan patches in patients under 18 years of age has not been established. Norspan is not recommended for use in children.

Effects on laboratory tests.

Increased alanine aminotransferase levels.

General.

Norspan patches should be used with particular caution in patients with convulsive disorders, head injury, shock, a reduced level of consciousness of uncertain origin, intracranial lesions or increased intracranial pressure. Buprenorphine may lower the seizure threshold in patients with a history of seizure disorder. Use with caution in patients with hypotension, hypovolaemia, biliary tract disease, pancreatitis, inflammatory bowel disorders (including constipation), prostatic hypertrophy, adrenocortical insufficiency, chronic renal and hepatic disease and debilitated patients. As with all opioids, a reduction in dosage may be advisable in hypothyroidism.

Serotonin syndrome.

Concomitant administration of buprenorphine and other serotonergic agents, such as 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 Interactions with Other Medicines and Other Forms of Interactions; Section 4.3 Contraindications).
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. If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Antiarrhythmic medications.

Higher doses (40 microgram per hour) of buprenorphine may increase the QTc interval. This should be considered when prescribing Norspan patches for patients with congenital QT prolongation or those taking antiarrhythmic medications in either class IA (e.g. quinidine, procainamide) or in class III (e.g. amiodarone, sotalol) or any other medication which prolongs the QT interval.

Anti-ulcer medication.

In clinical trial patients there were no apparent effects on Norspan patch exposure when used concomitantly with various H2-antagonists or proton pump inhibitors.

CNS depressants.

CNS depressants, when used with Norspan patches, may produce additive depressant effects, e.g. respiratory depression, hypotension, profound sedation or potentially result in coma or death. Such agents include but are not limited to opioids, anaesthetics, sedatives (including benzodiazepines), anxiolytics, hypnotics, barbiturates, phenothiazines, antidepressants (including tricyclic antidepressants), chloral hydrate, antipsychotics, glutethimide, tranquilisers, muscle relaxants, antihypertensives, gabapentinoids, antihistamines, cannabis, centrally-acting anti-emetics and alcohol (see Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use of benzodiazepines or other CNS depressants, including alcohol).

CYP inhibitors and inducers.

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 CYP3A4 inhibiting properties to ketoconazole include fluconazole and itraconazole.
One drug interaction study with ketoconazole did not produce clinically relevant increases in mean maximum or total buprenorphine exposure; however, caution is advised when Norspan patches are administered concurrently with inhibitors of CYP3A4 (e.g. protease inhibitors, some drug classes of azole antimycotics, calcium channel antagonists and macrolide antibiotics) as this might lead to increased levels with increased efficacy of buprenorphine with concomitant increased toxicity.
Unlike Norspan patches, oral dose buprenorphine containing formulations refer to an interaction study of buprenorphine with ketoconazole (a potent inhibitor of CYP3A4) that resulted in increased Cmax and AUC of buprenorphine (approximately 50% and 70%, respectively) and, to a lesser extent, of norbuprenorphine. Patients should be closely monitored, and may require a dose reduction if combining oral dose buprenorphine containing formulations with CYP3A4 inhibitors.
The interaction between buprenorphine and CYP3A4 enzyme inducers has not been studied; however, coadministration of Norspan patches 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.

General anaesthetics.

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.

Monoamine oxidase inhibitors.

Nonselective MAOIs intensify the effects of opioid drugs which can cause anxiety, confusion and respiratory depression. Norspan patches must not be used concomitantly with nonselective MAOIs or in patients who have received nonselective MAOIs within the previous 14 days (see Section 4.3 Contraindications). As it is unknown whether there is an interaction between selective MAOIs (e.g. selegiline) and buprenorphine, caution is advised with this drug combination.

Serotonergic agents.

Buprenorphine should be used cautiously when co-administered with serotonergic medicinal products (e.g. SSRIs, SNRIs or tricyclic antidepressants) as the risk of serotonin syndrome, a potentially life-threatening condition, is increased.

Warfarin.

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.

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 is used concurrently with anticholinergic drugs.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No adverse effects on fertility or embryonic development were seen in rats when treated males were paired with treated females (≤ 20 mg patch every 3 days). Exposure (AUC) with these doses are up to 70 times greater than the expected daily systemic exposure (AUC) of buprenorphine in humans during treatment with Norspan 40 mg patch.
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 drugs. 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 patches in pregnant women.
No effects on embryofetal development were noted in studies with topically applied Norspan patches to pregnant rats (≤ 20 mg patch) and rabbits (80 mg patch), and in studies in rabbits that received daily SC injections of buprenorphine during the period of organogenesis (≤ 5 mg/kg/day). Exposures (AUC) at these doses were 47 and 74 times in rats and rabbits, respectively, the expected daily systemic exposure (AUC) of buprenorphine in humans during treatment with Norspan 40 mg patch.
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 postnatal 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 patches should not be used by breastfeeding women.

4.7 Effects on Ability to Drive and Use Machines

Norspan patch has a major influence on the ability to drive and use machines. Even when used according to instructions, buprenorphine may cause drowsiness and 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, tranquilisers, sedatives and hypnotics. If affected, patients should not drive or operate machinery nor for at least 24 hours after the patch has been removed.

4.8 Adverse Effects (Undesirable Effects)

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.

Cardiac disorders.

Uncommon: angina pectoris, palpitations, tachycardia.

Ear and labyrinth disorders.

Uncommon: tinnitus, vertigo.
Very rare: ear pain.

Eye disorders.

Uncommon: dry eye, blurred vision.
Rare: eyelid oedema, miosis, visual disturbance.

Gastrointestinal disorders.

Very common: constipation*, dry mouth, nausea*, vomiting*.
Common: abdominal pain*, diarrhoea*, dyspepsia*.
Uncommon: flatulence.
Rare: diverticulitis*, dysphagia, ileus, pyrosis (heartburn).
Very rare: retching.

General disorders and administration site conditions.

Very common: application site reaction (includes erythema, oedema, pruritus or rash at the application site).
Common: asthenic conditions* (including muscle weakness, lethargy, fatigue and malaise), chest pain*, pain, peripheral oedema, tiredness.
Uncommon: influenza-like illness, oedema, pyrexia*, rigors*, drug withdrawal syndrome.
Not known: drug withdrawal syndrome neonatal, drug tolerance.

Skin and subcutaneous tissue disorders.

Very common: application site skin reactions (includes common signs and symptoms of contact dermatitis (irritative or allergic) erythema, oedema, pruritus* or rash, vesicles, painful/burning sensation at the application site) (late onset local allergic reactions (allergic contact dermatitis) with marked signs of inflammation - in such cases, discontinue Norspan patch).
Common: exanthema, rash*, sweating*.
Uncommon: dry skin, face oedema, urticaria.
Very rare: pustules, vesicles.

Hepatobiliary disorders.

Rare: biliary colic.

Immune system disorders.

Uncommon: allergic reaction (including oropharyngeal swelling and swollen tongue).
Rare: anaphylactic reactions.
Very rare: serious allergic reactions.

Injury, poisoning and procedural complications.

Uncommon: accidental injury (including fall).

Metabolism and nutrition disorders.

Common: anorexia.
Uncommon: dehydration*, weight decreased.

Musculoskeletal and connective tissue disorders.

Uncommon: muscle cramps, muscle spasm, myalgia.
Very rare: muscle fasciculation.

Nervous system disorders.

Very common: dizziness, headache*, somnolence*.
Common: dysgeusia (taste disturbance), paraesthesia, tremor.
Uncommon: concentration impairment, abnormal coordination, dysarthria, hypoaesthesia, memory impairment, migraine, restlessness, sedation, sleep disorder, syncope*.
Rare: dysequilibrium, numbness.
Unknown: seizure, hyperalgesia, sleep apnoea syndrome.

Psychiatric disorders.

Common: anxiety, confusion, depression*, insomnia, nervousness.
Uncommon: affect lability, agitation, aggression, depersonalisation, euphoric mood, hallucination, decreased libido, nightmare.
Rare: psychotic disorder.
Very rare: dependence, mood swings.

Renal and urinary disorders.

Uncommon: urinary incontinence, urinary retention.
Rare: urinary hesitation.

Reproductive system and breast disorders.

Rare: decreased erection, sexual dysfunction.

Respiratory, thoracic and mediastinal disorders.

Common: dyspnoea*.
Uncommon: asthma aggravated*, cough, hiccups, hyperventilation, hypoxia, rhinitis*, wheezing*.
Rare: respiratory depression, respiratory failure*.

Vascular disorders.

Common: vasodilatation.
Uncommon: circulatory disorders (such as hypotension or rarely even circulatory collapse), flushing, hypertension*, orthostatic hypotension.
Very common: ≥ 10%; common: ≥ 1% and < 10%; uncommon: ≥ 0.1% and < 1%; rare: ≥ 0.01% and < 0.1%; very rare: < 0.01% including isolated reports.
* At least one serious case.
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.

Application site skin reactions.

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 treatment. Instruct patients to promptly report the development of severe application site reactions and discontinue therapy.

Anaphylactic/ allergic reactions.

Cases of acute and chronic hypersensitivity to buprenorphine have been reported uncommonly both in clinical trials and in the postmarketing 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.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms of overdose.

Symptoms similar to other centrally acting analgesics are to be expected and are an extension of the pharmacological actions. These include respiratory depression including apnoea, sedation, drowsiness, nausea, vomiting, cardiovascular collapse and marked miosis although respiratory depression has been absent in some cases of buprenorphine overdosage.

Treatment of overdose.

Remove any patch in contact with the patient and dispose of it properly. Establish and maintain a patent airway, assist or 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 mu-agonists. Treatment with continuous intravenous naloxone should begin with the usual doses but high doses may be required. The onset of naloxone's effect may be delayed by 30 minutes or more. Please refer to naloxone hydrochloride injection product information for further information. There are literature which suggests that the dose response of buprenorphine induced respiratory depression to treatment with naloxone is bell shaped with higher doses of naloxone providing less effective treatment of respiratory depression than intermediate ones. Maintenance of adequate ventilation is more important than treatment with naloxone.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Buprenorphine is a partial opioid agonist, acting at mu-opioid receptors. The opioid agonist activities are dose related. Buprenorphine also has antagonistic activity at the kappa-opioid receptor. It is classified as a psychotropic substance under international convention.
Like other opioid agonists, buprenorphine produces dose related analgesia, however a ceiling effect to analgesia is well documented. Buprenorphine binds to and dissociates from the mu-receptor slowly, which may account for the prolonged duration of analgesia and, in part, for the limited physical dependence potential observed with the drug.
Buprenorphine produces similar effects to other opioids on the central nervous, cardiovascular, respiratory and gastrointestinal systems, although the intensity and duration of the effects may vary when compared with other opioids. Opioids may also influence the hypothalamic pituitary adrenal or gonadal axes, including an increase in serum prolactin and decreases in plasma cortisol and testosterone, which can manifest in clinical symptoms.
Since kappa receptor agonist activity is related to psychotomimetic and dysphoric effects, buprenorphine is expected to produce fewer psychotomimetic and dysphoric effects than drugs with kappa-agonist activities.
Like other opioid agonists, buprenorphine may produce increases in cerebrospinal fluid pressure, cause altered mentation, mental clouding or amnesia.
Buprenorphine acts to reduce blood pressure in a manner similar to other opioids. Norspan patch application resulted in transient decreases in blood pressure in healthy young and elderly subjects, without clinical adverse events.
Like other opioid analgesics, buprenorphine has a potential of respiratory depression. Respiratory depression is less common than with full mu-agonists, such as morphine, and there appears to be a ceiling effect. However, evidence suggests that buprenorphine is a partial agonist with respect to its respiratory depressant activity. When respiratory depression occurs it appears to have a slower onset and longer duration compared with morphine.
Administration of buprenorphine to persons who are physically dependent on full mu-opioid agonists may precipitate an abstinence syndrome depending on the level of physical dependence, and the timing and dose of buprenorphine.
Like other opioids buprenorphine may cause nausea, vomiting, constipation and an increase in biliary tract pressure. Effects on the immune system were seen with natural opioids like morphine in in vitro and animal studies, although the clinical significance of these is unknown. It is not known whether buprenorphine, a semisynthetic opioid, has immunological effects similar to morphine.
Buprenorphine can cause dose related miosis and urinary retention in some patients.

Clinical trials.

The safety and efficacy of Norspan patches in the management of chronic pain has been studied in 30 clinical trials (4867 patients treated with Norspan patches). The active and placebo controlled clinical trials included patients with moderate to severe chronic pain of osteoarthritis, low back and noncancer pain requiring opioid analgesia. A single trial examined the safety of three doses of Norspan patches given for 72 hours to patients following orthopaedic surgery. No trials have been conducted in patients with cancer related pain.
BUPN.CLIN0001 was a randomised, double blind, double dummy, parallel, equivalence study comparing the efficacy and tolerability of Norspan patches 5, 10 and 20 mg applied every seven days with sublingual buprenorphine tablets 200 and 400 microgram (Temgesic) in 238 patients with moderate to severe pain due to osteoarthritis (hip and/or knee, 85% > one year). Patients were titrated to optimum pain control over 21 days, and continued at this level for 28 days. Paracetamol was permitted for breakthrough pain and all usage recorded. The primary efficacy variable was pain intensity recorded during the assessment period (days three and seven, BS-11 scale, see Table 1). The per protocol (PP) population mean reductions in pain scores ranged from 2.6 to 3.6 across the three daily rating assessments (morning, midday, evening) and the estimated mean difference between both active treatment arms was minimal (range 0.001 to 0.13). The 95% confidence intervals for the difference between treatments were within the range -1 to 1, compared with the prespecified equivalence margins of -1.5 to 1.5. This demonstrated equivalent efficacy. At study completion 70% (40/51) of patients on the patch and 75% (42/51) on tablets rated their pain relief as good or very good.
Norspan Transdermal Patch (2) There was no difference in escape medication usage and the incidence of discontinuation due to lack of efficacy was similar between the two treatment groups (9% Temgesic vs 14% Norspan patch). The most common adverse events reported were those commonly associated with the use of opioids (nausea, vomiting, dizziness, somnolence, headache and constipation).
BP98-1201 was a randomised, double blind trial comparing the efficacy and safety of Norspan patches 5, 10 and 20 mg, applied every seven days, with hydrocodone/ paracetamol (2.5 mg/250 mg) tablets four times a day (qid) in 270 patients with chronic moderate to severe back pain (pain intensity ≥ 5 BS-11 scale), not controlled by nonopioid analgesia alone (ibuprofen 400 mg qid). Patients were titrated to optimum pain control over 21 days and continued at this level for 35 days. The primary efficacy variables were average pain intensity (BS-11 scale*) and patient satisfaction with medication over days 21 to 56#, see Table 2. The intention to treat (ITT) population mean baseline pain intensity was 7.74 (Norspan patch group) compared with 7.65, which reduced through days 21 to 56 to 5.96 and 6.04, respectively. The difference (and 95% confidence interval) in average pain intensity between the two treatments was -0.08 (-0.06 to 0.44). The difference between the two treatments in patient global satisfaction was 0.16 (-0.08 to 0.39). Norspan patches were equally effective as hydrocodone/ paracetamol tablets in relieving pain and for patient satisfaction.
Norspan Transdermal Patch (3) The majority of adverse events reported were mild or moderate in severity and were typically associated with opioid therapy. Withdrawals due to lack of efficacy was similar for both groups (15% for Norspan patch and 14% for hydrocodone/ paracetamol). No changes in laboratory values were considered related to treatment and no clinically important changes were reported for pulse rate, respiratory rate or physical examinations.

5.2 Pharmacokinetic Properties

Each Norspan patch provides a steady delivery of buprenorphine for up to seven days. Steady state is achieved by day three following the first application. After removal of a Norspan patch, buprenorphine concentrations decline, decreasing approximately 50% in 12 hours (range 10 to 24 hours).
Norspan patches 5 microgram per hour, 10 microgram per hour, 15 microgram per hour, 20 microgram per hour, 25 microgram per hour, 30 microgram per hour and 40 microgram per hour provide dose proportional increases in total exposure (AUC) over the seven day application period. Dose proportional increases in plasma concentrations occur at steady state with Norspan patch application for up to 60 days. Accumulation of plasma buprenorphine did not occur during the 60 days.
The rate of buprenorphine release from each patch is proportional to the surface area. Each Norspan patch 5 microgram releases 5 microgram of buprenorphine per hour, and contains a total of 5 mg of buprenorphine. Each Norspan patch 10 microgram releases 10 microgram of buprenorphine per hour and contains a total of 10 mg of buprenorphine. Each Norspan patch 15 microgram releases 15 microgram of buprenorphine per hour and contains a total of 15 mg of buprenorphine. Each Norspan patch 20 microgram releases 20 microgram of buprenorphine per hour and contains a total of 20 mg of buprenorphine. Each Norspan patch 25 microgram releases 25 microgram of buprenorphine per hour and contains a total of 25 mg of buprenorphine. Each Norspan patch 30 microgram releases 30 microgram of buprenorphine per hour and contains a total of 30 mg of buprenorphine. Each Norspan patch 40 microgram releases 40 microgram of buprenorphine per hour and contains a total of 40 mg of buprenorphine.

(Video) Training Video For Application of Transdermal Patches

Absorption.

Following Norspan patch application, buprenorphine diffuses from the patch through the skin. In clinical pharmacology studies, the median time for Norspan patch 10 microgram to deliver detectable buprenorphine concentrations (25 picogram/mL) was approximately 17 hours. The mean bioavailability of buprenorphine from a Norspan patch relative to intravenous (IV) dosing is between 13-15% (for all strengths).

Accidental oral ingestion.

Measurable systemic levels of buprenorphine were demonstrated in dogs given Norspan patches by oral administration.

Distribution.

Buprenorphine is approximately 96% bound to plasma proteins.
In a study of IV buprenorphine in healthy subjects, the volume of distribution at steady state was 430 L, which is indicative of the high lipophilicity of the drug.
Following IV administration, buprenorphine and its metabolites are secreted into bile, and within several minutes distribute into the cerebrospinal fluid (CSF). CSF concentrations appear to be approximately 15% to 25% of concurrent plasma concentrations.

Metabolism and excretion.

Buprenorphine metabolism in the skin following Norspan patch application is negligible. Buprenorphine is eliminated via hepatic metabolism, with subsequent biliary excretion and renal excretion of soluble metabolites. Hepatic metabolism through CYP3A4 and UGT1A1/1A3 enzymes results in two primary metabolites, norbuprenorphine and buprenorphine 3-O-glucuronide, norbuprenorphine is also glucuronidated prior to elimination. Buprenorphine is eliminated in the faeces within seven days.
Norbuprenorphine is the only known active metabolite of buprenorphine. It has been shown to be a respiratory depressant in rats at concentrations at least 50-fold those seen following application of Norspan patch 20 microgram per hour.
In a study in postoperative patients the total clearance of buprenorphine was 55 L/h.

Application site.

A study in healthy subjects demonstrated that the pharmacokinetic profile of buprenorphine delivered by Norspan patch is similar when applied to the upper outer arm, upper chest, upper back or the side of the chest (midaxillary line, 5th intercostal space).
In a study of healthy subjects applying Norspan patches repeatedly to the same site, immediate reapplication caused increased absorption, without clinical adverse events. For this reason, rotation of application sites is recommended (see Section 4.2 Dose and Method of Administration).
In another study in healthy subjects application of a heating pad directly on the Norspan patch caused a transient 26 to 55% increase in blood concentrations of buprenorphine. Concentrations returned to normal within five hours after the heat was removed. For this reason, applying heat sources such as hot water bottles, heat pads or electric blankets directly to the Norspan patch is not recommended. A heating pad applied to a Norspan patch site directly after patch removal did not alter absorption from the skin depot.

5.3 Preclinical Safety Data

Genotoxicity.

Buprenorphine showed no evidence of genotoxic activity in assays for gene mutations (reverse mutations in bacterial cells, forward mutations in mammalian cells and yeast), chromosomal damage (human lymphocytes, mouse micronucleus test, Chinese hamster cell in vivo and in vitro) or gene conversion (yeast). However, in other assays, buprenorphine was positive for frame shift mutations in Ames test and caused inhibition of normal DNA synthesis and increases in unscheduled DNA synthesis in studies using mouse testes.

Carcinogenicity.

No evidence of carcinogenicity was seen in Tg.AC transgenic mice treated with dermal doses of buprenorphine up to 600 mg/kg/day for 6 months or female rats treated with daily dermal doses of buprenorphine up to 200 mg/kg/day for approximately 100 weeks. These doses resulted in exposures (AUC) at least 160 times the expected daily systemic dose of buprenorphine in humans during treatment with Norspan 40 mg patch. In male rats, however, an increased incidence of benign testicular interstitial tumours was observed in animals treated dermally with ≥ 60 mg/kg/day buprenorphine for approximately 100 weeks. Exposure (AUC) at the NOEL was 96 times greater than the expected daily systemic exposure of buprenorphine in humans during treatment with Norspan 40 mg patch.

6 Pharmaceutical Particulars

6.1 List of Excipients

The inactive ingredients in Norspan transdermal drug delivery system (patch) are levulinic acid, oleyl oleate, povidone, Duro Tak 387-2051, Duro Tak 387-2054 and polyethylene terephthalate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

(Video) What are pain patches? London Pain Clinic

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Norspan patch 5, 10 and 20 is supplied in cartons containing one*, two or four* individually packaged patches.
Norspan patch 15, 25, 30 and 40 is supplied in cartons containing two* or four* individually packaged patches.
Each patch is contained in an aluminium sachet laminated with LDPE/paper.
* Not all pack sizes are currently marketed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

(Video) Treating Acute Pain When Buprenorphine is in the Room

6.7 Physicochemical Properties

Buprenorphine is a white or almost white powder and is very slightly soluble in water, freely soluble in acetone, soluble in methanol and ether and slightly soluble in cyclohexane. The pKa is 8.5. The chemical name of buprenorphine is (2S)-2-[17-(cyclopropylmethyl)-4, 5α-epoxy-3-hydroxy-6-methoxy-6α, 14-ethano-14α-morphinan-7α-yl]-3, 3-dimethylbutan-2-ol. The molecular weight is 467.6 and the empirical formula is C29H41NO4.

Chemical structure.

The structural formula is:
Norspan Transdermal Patch (4)

CAS number.

52485-79-7.

7 Medicine Schedule (Poisons Standard)

S8.

Summary Table of Changes

Norspan Transdermal Patch (5)

(Video) "Buprenorphine for Pain Management" - Michael M. Miller, MD, DFASAM, DLFAPA

FAQs

Can I just stop using NORSPAN patches? ›

Do not stop using this medicine suddenly. If you stop taking NORSPAN patches suddenly, your pain may worsen and you may experience withdrawal symptoms.

What are the side effects of transdermal patch? ›

Less common
  • Acid or sour stomach.
  • anxiety.
  • back pain.
  • headache, severe and throbbing.
  • irritation at the patch site.
  • itching skin or rash.
  • muscle spasms.
  • neck pain.
Aug 1, 2022

What is transdermal patches used for? ›

What Are Transdermal Patches? Transdermal patches adhere to the skin as a way to deliver drugs. They provide a specific, predetermined dose of medication that is absorbed through the skin and into the bloodstream.

How does NORSPAN make you feel? ›

Some people may experience side effects such as unsteadiness, dizziness, drowsiness or confusion which may increase the risk of a fall. Tell your doctor if you suffer from nausea or vomiting when using NORSPAN patches. Your doctor may prescribe some medicine to help.

Is buprenorphine a good painkiller? ›

Sublingual buprenorphine, with and without naloxone, is indicated for the treatment of opioid use disorders. Although not approved for pain, some evidence suggests it may be a safe and effective alternative to conventional opioid analgesics, particularly for those with addiction problems.

Can I shower with a transdermal patch? ›

You may take a bath, shower, or swim while using this medicine. Doing so will not affect the patch. If a patch falls off, just put it back on a different area. If the patch does not stick completely, put on a new patch but continue to follow your original schedule for changing your patch.

How long does it take for a transdermal patch to work? ›

Up to a full day (24 hours) may pass before the first dose begins to work. Your doctor may need to adjust the dose during the first few weeks before finding the amount that works best for you.

Where is the best place to put a buprenorphine patch? ›

Apply the patch to a dry, flat skin area on your upper arm, chest, back, or side of the chest. Choose a place where the skin is not very oily and is free of scars, cuts, burns, or any other skin irritations. The patch will stay in place better if it is applied to an area with little or no hair.

What should you avoid when applying transdermal patches? ›

Don't use a drug patch if the seal is broken, altered, cut, or damaged in any way. Don't use soaps, oils, lotions, alcohol, or other agents that might irritate or alter the skin site. Don't expose the application site to direct external heat sources, such as heating pads.

What are three benefits of using the patch? ›

The patch is a safe, simple, and convenient way to prevent pregnancy. It also has other benefits, like helping with acne, making your periods lighter and more regular, and easing menstrual cramps.

How effective is the transdermal patch? ›

If you follow directions perfectly, the patch works 99% of the time. That means 1 person out of 100 who use the patch might get pregnant in a year. But in real life, people make mistakes, like not changing the patch on the right day. That can drop the effectiveness to about 91%.

Why would a doctor prescribe buprenorphine? ›

Although there is limited research about the illicit use of buprenorphine, several studies suggest that the main reasons people buy illicit buprenorphine are to self-manage withdrawal from opioids or to self-treat their opioid use disorder.

How well does buprenorphine work on chronic pain? ›

A 2014 review also found that sublingual buprenorphine is effective for the treatment of chronic pain, though most of the studies included in the review were low-quality. Additionally, the authors noted that buprenorphine could be more effective at treating certain kinds of pain and have fewer dangerous side effects.

How long can you use pain patches? ›

patches – apply a new patch every 3, 4 or 7 days, depending on the strength and the brand you've been prescribed. tablets – taken when you need them for pain relief – each dose will usually last 6 to 8 hours. Talk to your doctor if this is not controlling your pain.

How long does buprenorphine patch take to work? ›

The opioid painkiller in the buprenorphine patch is released slowly into your body. Your first buprenorphine patch may take up to two days to begin to have any noticeable effect but further patches will maintain this effect.

What are the side effects of buprenorphine? ›

Common side effects of buprenorphine include:
  • Constipation, headache, nausea, and vomiting.
  • Dizziness.
  • Drowsiness and fatigue.
  • Sweating.
  • Dry mouth.
  • Tooth decay.
  • Muscle aches and cramps.
  • Inability to sleep.
Jul 14, 2022

Videos

1. "Buprenorphine for Pain Management" - Michael M. Miller, MD, DFASAM, DLFAPA
(UW - Department of Family Medicine and Community Health)
2. Buprenorphine: Indications Beyond Addiction?
(PAINWeek)
3. How to Properly Apply a Transdermal Patch
(Apotex Inc.)
4. How to Use an Opioid Patch for Pain
(ACPFoundation)
5. Buprenorphine | Javery Pain Institute
(Javery Pain Institute)
6. ♡ Starting a Pain Patch! (07.11.18) | Amy's Life ♡
(Amy's Life)
Top Articles
Latest Posts
Article information

Author: Lakeisha Bayer VM

Last Updated: 01/27/2023

Views: 6173

Rating: 4.9 / 5 (49 voted)

Reviews: 88% of readers found this page helpful

Author information

Name: Lakeisha Bayer VM

Birthday: 1997-10-17

Address: Suite 835 34136 Adrian Mountains, Floydton, UT 81036

Phone: +3571527672278

Job: Manufacturing Agent

Hobby: Skimboarding, Photography, Roller skating, Knife making, Paintball, Embroidery, Gunsmithing

Introduction: My name is Lakeisha Bayer VM, I am a brainy, kind, enchanting, healthy, lovely, clean, witty person who loves writing and wants to share my knowledge and understanding with you.