Presentation and Status in Health Basket
30 X 100 mcg
30 X 200 mcg
30 X 400 mcg
30 X 600 mcg
30 X 800 mcg
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, or at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg of oral 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: Sub-lingual tablets should be administered directly under the tongue at the deepest part. 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.Over Dosage 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.
Discontinuation of therapy: For patients no longer requiring any opioid therapy, the Abstral dose should be taken into consideration before a gradual downward titration of opioids to minimise possible withdrawal effects. In patients who continue to take their chronic opioid therapy for persistent pain but no longer require treatment for breakthrough pain, Abstral therapy may usually be discontinued immediately.
Use in children and adolescents: Abstral must not be used in patients less than 18 years of age due to a lack of data on safety and efficacy.
Use in elderly patients: Dose titration needs to be approached with particular care and patients observed carefully for signs of fentanyl toxicity.
Use in patients with renal and hepatic impairment: Patients with kidney or liver dysfunction should be carefully observed for signs of fentanyl toxicity during the Abstral titration phase.
Management of breakthrough pain in adult patients using opioid therapy for chronic cancer pain. Breakthrough pain is a transient exacerbation of otherwise controlled chronic background pain.
Hypersensitivity to the active substance, Opioid-naïve patients because of the risk of life, Threatening respiratory depression, Severe respiratory depression or severe obstructive lung conditions, contraindicated in the management of acute or postoperative pain, including headache/migraine, dental pain, or use in the emergency room.
Life-Threatening Respiratory Depression: Serious, life-threatening and/or fatal respiratory depression has occurred in patients treated with ABSTRAL, including following use in opioid non-tolerant patients and improper dosing.
Monitor for respiratory depression, especially during initiation of ABSTRAL or following a dose increase. The substitution of ABSTRAL for any other fentanyl product may result in fatal overdose.
Due to the risk of respiratory depression, ABSTRAL is contraindicated in the management of acute or postoperative pain including headache/migraine and in opioid non-tolerant patients.
Accidental Ingestion: Accidental ingestion of even one dose of ABSTRAL, especially by children, can result in a fatal overdose of fentanyl.
Death has been reported in children who have accidentally ingested transmucosal immediaterelease fentanyl products. ABSTRAL must be kept out of reach of children.
Cytochrome P450 3A4 Interaction: The concomitant use of ABSTRAL with all cytochrome P450 3A4 inhibitors may result in an increase in fentanyl plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a
concomitantly used cytochrome P450 3A4 inducer may result in an increase in fentanyl plasma concentration. Monitor patients receiving ABSTRAL and any CYP3A4 inhibitor or inducer.
Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
– Reserve concomitant prescribing of ABSTRAL and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
– Limit dosages and durations to the minimum required.
– Follow patients for signs and symptoms of respiratory depression and sedation.
Risk of Medication Errors: Substantial differences exist in the pharmacokinetic profile of ABSTRAL compared to other fentanyl products that result in clinically important differences in the extent of absorption of fentanyl and that could result in fatal overdose.
– When prescribing, do not convert patients on a mcg per mcg basis from any other fentanyl products to ABSTRAL.
– When dispensing, do not substitute an ABSTRAL prescription for other fentanyl products.
Addiction, Abuse, and Misuse: ABSTRAL exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing ABSTRAL, and monitor all patients regularly for the development of these behaviors and conditions.
Neonatal Opioid Withdrawal Syndrome: Prolonged use of ABSTRAL during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
See prescribing information for full details.
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.
For full details see prescribing information.
Fentanyl is metabolised by CYP3A4. Active substances that inhibit CYP3A4 activity such as macrolide antibiotics (e.g. erythromycin), azole antifungal agents (e.g. ketoconazole, itraconazole) or certain protease inhibitors (e.g. ritonavir) may increase the bioavailability of fentanyl by decreasing its systemic clearance, potentially enhancing or prolonging opioid effects. Grapefruit juice is also known to inhibit CYP3A4.
Coadministration with agents that induce CYP3A4 activity such as antimycobacterials (e.g. rifampin, rifabutin), anticonvulsants (e.g. carbamazepine, phenytoin, and phenobarbital), herbal products (e.g. St John’s wort, Hypericum perforatum) may reduce the efficacy of fentanyl. CYP3A4 inducers exert their effect in a time-dependent manner, and may take at least 2 weeks to reach maximal effect after introduction. Conversely, on discontinuation, CYP3A4 induction may take at least 2 weeks to decline. Patients receiving fentanyl who stop therapy with, or decrease the dose of CYP3A4 inducers may be at risk of increased fentanyl activity or toxicity.
Fentanyl should therefore be given to patients with caution if administered concomitantly with CYP3A4 inhibitors and/or inducers.
Concomitant use of other CNS depressants, such as other morphine derivatives (analgesics and antitussives), general anaesthetics, skeletal muscle relaxants, sedative antidepressants, sedative H1 antihistamines, barbiturates, anxiolytics (ie benzodiazepines), hypnotics, antipsychotics, clonidine and related substances may produce increased CNS depressant effects. Respiratory depression, hypotension and profound sedation may occur.
Alcohol potentiates the sedative effects of morphine-based analgesics, therefore concomitant administration of alcoholic beverages or medicinal products containing alcohol with Abstral is not recommended.
Abstral is not recommended for use in patients who have received monoamine oxidase (MAO) inhibitors within 14 days because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.
The concomitant use of partial opioid agonists/antagonists (e.g. buprenorphine, nalbuphine, pentazocine) is not recommended. They have high affinity to opioid receptors with relatively low intrinsic activity and therefore partially antagonise the analgesic effect of fentanyl and may induce withdrawal symptoms in opioid dependent patients.
Serotoninergic Drugs: Co-administration of fentanyl with a serotoninergic agent, such as a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin Norepinephrine Re-uptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor (MAOI), may increase the risk of serotonin syndrome, a potentially life-threatening condition.
Pregnancy and Lactation
Pregnancy: The safety of fentanyl in pregnancy has not been established. Studies in animals have shown reproductive toxicity, with impaired fertility in rats. The potential risk for humans is unknown. Fentanyl should only be used during pregnancy when clearly necessary.
Long-term treatment during pregnancy may cause withdrawal symptoms in the new-born infant.
Lactation: Fentanyl is excreted into breast milk and may cause sedation and respiratory depression in the breast-fed child. Fentanyl should only be used by breast-feeding women if the benefits clearly outweigh the potential risks for both mother and child.
The symptoms of fentanyl overdose are an extension of its pharmacological actions, the most serious effect being respiratory depression, which may lead to respiratory arrest. Management of opioid overdose in the immediate term includes removal of any remaining Abstral sublingual tablets from the mouth, physical and verbal stimulation of the patient and an assessment of the level of consciousness. A patent airway should be established and maintained. If necessary an oropharyngeal airway or endotracheal tube should be inserted, oxygen administered and mechanical ventilation initiated, as appropriate. Adequate body temperature and parenteral fluid intake should be maintained.
For the treatment of accidental overdose in opioid-naïve individuals, naloxone or other opioid antagonists should be used as clinically indicated and in accordance with their Summary of Product Characteristics. Repeated administration of the opioid antagonist may be necessary if the duration of respiratory depression is prolonged.
Care should be taken when using naloxone or other opioid antagonists to treat overdose in opioid-maintained patients, due to the risk of precipitating an acute withdrawal syndrome.
If severe or persistent hypotension occurs, hypovolaemia should be considered, and the condition should be managed with appropriate parenteral fluid therapy.
Muscle rigidity interfering with respiration has been reported with fentanyl and other opioids. In this situation, endotracheal intubation, assisted ventilation and administration of opioid antagonists as well as muscle relaxants may be requested.
Storage: Do not store above 25°C. Store in the original blister package in order to protect from moisture.