ABSTRAL

Abstral should only be administered to patients who are considered tolerant to their opioid therapy for persistent cancer pain. Patients can be considered opioid tolerant if they take at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.

Method of administration:

Abstral sublingual tablets should be administered directly under the tongue at the deepest part. Abstral sublingual tablets should not be swallowed, but allowed to completely dissolve in the sublingual cavity without chewing or sucking.

Patients should be advised not to eat or drink anything until the sublingual tablet is completely dissolved. In patients who have a dry mouth water may be used to moisten the buccal mucosa before taking Abstral.

Dose titration:

The object of dose titration is to identify an optimal maintenance dose for ongoing treatment of breakthrough pain episodes. This optimal dose should provide adequate analgesia with an acceptable level of adverse reactions. The optimal dose of Abstral will be determined by upward titration, on an individual patient basis.

Several doses are available for use during the dose titration phase. The initial dose of Abstral used should be 100 micrograms, titrating upwards as necessary through the range of available dosage strengths. Patients should be carefully monitored until an optimal dose is reached.

Switching from other fentanyl containing products to Abstral must not occur at a 1:1 ratio because of different absorption profiles. If patients are switched from another fentanyl containing product, a new dose titration with Abstral is required.

The following dose regimen is recommended for titration, although in all cases the physician should take into account the clinical need of the patient, age and concomitant illness. All patients must start therapy with a single 100 microgram sublingual tablet.

If adequate analgesia is not obtained within 15-30 minutes of administration of a single sublingual tablet, a supplemental (second) 100 microgram sublingual tablet may be administered. If adequate analgesia is not obtained within 15-30 minutes of the first dose an increase in dose to the next highest tablet strength should be considered for the next episode of breakthrough pain (Refer to figure below).

Dose escalation should continue in a stepwise manner until adequate analgesia with tolerable adverse reactions is achieved. The dose strength for the supplemental (second) sublingual tablet should be increased from 100 to 200 micrograms at doses of 400 micrograms and higher.

This is illustrated in the schedule below. No more than two (2) doses should be administered for a single episode of breakthrough pain during this titration phase. ABSTRAL Titration Process Strength (micrograms) of first sublingual tablet per episode of breakthrough pain Strength (micrograms) of supplemental (second) sublingual tablet to be taken 15- 30 minutes after first tablet, if required 100 100 200 100 300 100 400 200 600 200 800 - If adequate analgesia is achieved at the higher dose, but undesirable effects are considered unacceptable, an intermediate dose (using the 100 microgram sublingual tablet where appropriate) may be administered.

Starting dose 100 μg Adequate pain relief achieved within 15-30 minutes? Yes No Take a second tablet (See table to determine strength of second tablet) Increase first tablet to next higher strength for next breakthrough pain episode Use this dose for subsequent breakthrough pain During titration, patients can be instructed to use multiples of 100 microgram tablets and/or 200 microgram tablets for any single dose.

No more than four (4) tablets should be used at any one time. The efficacy and safety of doses higher than 800 micrograms have not been evaluated in clinical studies in patients. In order to minimise the risk of opioid–related adverse reactions and to identify the appropriate dose, it is imperative that patients be monitored closely by health professionals during the titration process.

During titration patients should wait at least 2 hours before treating another episode of breakthrough pain with Abstral.

Maintenance therapy:

Once an appropriate dose has been established, which may be more than one tablet, patients should be maintained on this dose and should limit consumption to a maximum of four Abstral doses per day. During the maintenance period patients should wait at least 2 hours before treating another episode of breakthrough pain with Abstral.

Dose re-adjustment:

If the response (analgesia or adverse reactions) to the titrated Abstral dose markedly changes, an adjustment of dose may be necessary to ensure that an optimal dose is maintained. If more than four episodes of breakthrough pain are experienced per day over a period of more than four consecutive days, then the dose of the long acting opioid used for persistent pain should be re-evaluated.

If the long acting opioid or dose of long acting opioid is changed the Abstral dose should be re-evaluated and re-titrated as necessary to ensure the patient is on an optimal dose. It is imperative that any dose re-titration of any analgesic is monitored by a health professional.

4). Treatment duration and goals Before initiating treatment with Abstral, a treatment strategy including treatment duration and treatment goals, and a plan for end of the treatment, should be agreed together with the patient, in accordance with pain management guidelines.

During treatment, there should be frequent contact between the physician and the patient to evaluate the need for continued treatment, consider discontinuation and to adjust dosages if needed. In absence of adequate pain control, the […]

Undesirable effects typical of opioids are to be expected with Abstral; they tend to decrease in intensity with continued use. The most serious potential adverse reactions associated with opioid use are respiratory depression (which could lead to respiratory arrest), hypotension and shock.

The clinical trials of Abstral were designed to evaluate safety and efficacy in treating patients with breakthrough cancer pain; all patients were taking concomitant opioids, such as sustained-release morphine, sustained-release oxycodone or transdermal fentanyl, for their persistent pain.

Therefore, it is not possible to definitively separate the effects of Abstral alone. The most frequently observed adverse reactions with Abstral include typical opioid adverse reactions, such as nausea, constipation, somnolence and headache.

Tabulated Summary of Adverse Reactions with Abstral and/or other fentanyl- containing compounds: The following adverse reactions have been reported with Abstral and/or other fentanyl-containing compounds during clinical studies and from post-marketing experience.

They are listed below by system organ class and frequency (very common ≥ 1/10; common ≥ 1/100 to < 1/10; uncommon ≥1/1,000 to <1/100; not known (cannot be estimated from available data)). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System Organ Class Adverse Reaction by Frequency Very common ≥ 1/10 Common ≥ 1/100 to < 1/10 Uncommon ≥1/1,000 to <1/100 Not known (cannot be estimated from available data) Immune system disorders Hypersensitivity Metabolism and nutrition disorders Anorexia Decreased appetite System Organ Class Adverse Reaction by Frequency Very common ≥ 1/10 Common ≥ 1/100 to < 1/10 Uncommon ≥1/1,000 to <1/100 Not known (cannot be estimated from available data) Psychiatric disorders Depression Paranoia Confusional state Disorientation Mental status changes Anxiety Euphoric mood Dysphoria Emotional lability Disturbance in attention Insomnia Hallucination Drug dependence (addiction) Drug abuse Delirium Nervous system disorders Dizziness Headache Somnolence Amnesia Parosmia Dysgeusia Tremor Lethargy Hypoaesthesia Sleep disorder Convulsion Depressed level of consciousness Loss of consciousness Eye disorders Vision blurred Cardiac disorders Tachycardia Bradycardia Vascular disorders Hypotension Respiratory, thoracic and mediastinal disorders Dyspnoea Oropharyngeal pain Throat tightness Respiratory depression Gastrointestinal disorders Nausea Stomatitis Vomiting Constipation Dry mouth Mouth ulceration Gingival ulceration Lip ulceration Impaired gastric emptying Abdominal pain Dyspepsia Stomach discomfort Tongue disorder Aphthous stomatitis Swollen tongue Diarrhoea Skin and subcutaneous tissue disorders Hyperhidrosis Skin lesion Rash Pruritus allergic Pruritus Night sweats Increased tendency to bruise Urticaria Musculoskeletal and connective tissue disorders Arthralgia Musculoskeletal stiffness Joint stiffness Reproductive system and breast disorders Erectile dysfunction General disorders and administration site conditions Fatigue *Drug withdrawal syndrome Asthenia Malaise Flushing and hot flush Peripheral oedema Pyrexia Neonatal System Organ Class Adverse Reaction by Frequency Very common ≥ 1/10 Common ≥ 1/100 to < 1/10 Uncommon ≥1/1,000 to <1/100 Not known (cannot be estimated from available data) withdrawal syndrome Drug tolerance Injury, poisoning and procedural complications Accidental overdose Fall * opioid withdrawal symptoms such as nausea, vomiting, diarrhoea, anxiety, chills, tremor, and sweating have been observed with transmucosal fentanyl Description of selected adverse reactions Tolerance Tolerance can develop on repeated use.

Drug dependence Repeated use of Abstral can lead to drug dependence, even at therapeutic doses. 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

Because of the risks, including fatal outcome, associated with accidental exposure, misuse, and abuse, patients and their carers must be advised to keep Abstral in a safe and secure place, not accessible by others. Patients and their carers must be instructed that Abstral contains an active substance in an amount that can be fatal to a child, and therefore to keep all tablets out of the sight and reach of children.

Due to the potentially serious undesirable effects that can occur when taking an opioid therapy such as Abstral, patients and their carers should be made fully aware of the importance of taking Abstral correctly and what action to take should symptoms of overdose occur.

Before Abstral therapy is initiated, it is important that the patient’s long-acting opioid treatment used to control their persistent pain has been stabilised. Tolerance and Opioid Use Disorder (abuse and dependence) Tolerance and physical and/or psychological dependence may develop upon repeated administration of opioids such as fentanyl.

Repeated use of Abstral may lead to Opioid Use Disorder (OUD). A higher dose and longer duration of opioid treatment, can increase the risk of developing OUD. Abuse or intentional misuse of Abstral may result in overdose and/or death.

g. major depression, anxiety and personality disorders). 2). Before and during treatment the patient should also be informed about the risks and signs of OUD. Patients should be advised to contact their physician if these signs occur. g.

too early requests for refills). This includes the review of concomitant opioids and psycho- active drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.

Respiratory Depression In common with all opioids, there is a risk of clinically significant respiratory depression associated with the use of Abstral. g. myasthenia gravis) because of the risk of further respiratory depression, which could lead to respiratory failure.

Increased intracranial pressure Abstral should only be administered with extreme caution in patients who may be particularly susceptible to the intracranial effects of hyperkapnia, such as those showing evidence of raised intracranial pressure, reduced consciousness, coma or brain tumours.

In patients with head injuries, the clinical course may be masked by the use of opioids. In such a case, opioids should be used only if absolutely necessary. Hyperalgesia As with other opioids, in case of insufficient pain control in response to an increased dose of fentanyl, the possibility of opioid-induced hyperalgesia should be considered.

A fentanyl dose reduction or discontinuation of fentanyl treatment or treatment review may be indicated. Cardiac disease Fentanyl may produce bradycardia. Fentanyl should be used with caution in patients with previous or pre-existing bradyarrhythmias.

Elderly, cachectic or debilitated population Data from intravenous studies with fentanyl suggest that older patients may have reduced clearance, a prolonged half-life and they may be more sensitive to the active substance than younger patients.

Older, cachectic, or debilitated patients should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary. Impaired hepatic or renal function Abstral should be administered with caution to patients with liver or kidney dysfunction, especially during the titration phase.

The use of Abstral in patients with hepatic or renal impairment may increase the bioavailability of fentanyl and decrease its systemic clearance, which could lead to accumulation and increased and prolonged opioid effects. Hypovolaemia and hypotension Care should be taken in treating patients with hypovolaemia and hypotension.

Use in patients with mouth wounds or mucositis Abstral has not been studied in patients with mouth wounds or mucositis. There may be a risk of increased systemic drug exposure in such patients and therefore extra caution is recommended during dose titration.

Abstral withdrawal There should be no noticeable effects on cessation of treatment with Abstral, but possible symptoms of withdrawal are anxiety, tremor, sweating, paleness, nausea and vomiting. Serotonin Syndrome Caution is advised when Abstral is co-administered with drugs that affect the serotoninergic neurotransmitter systems.

The development of a potentially life-threatening serotonin syndrome may occur with the concomitant use of serotonergic drugs such as Selective Serotonin Re-uptake Inhibitors (SSRIs) and Serotonin Norepinephrine Re-uptake Inhibitors (SNRIs), and with drugs which impair metabolism of serotonin (including Monoamine Oxidase Inhibitors [MAOIs]).

This may occur within the recommended dose. , nausea, vomiting, diarrhoea). If serotonin syndrome is suspected, treatment with Abstral should be discontinued. Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and […]

1. Patients without maintenance opioid therapy as there is an increased risk of respiratory depression. Severe respiratory depression or severe obstructive lung conditions. Treatment of acute pain other than breakthrough pain. Patients being treated with medicinal products containing sodium oxybate.