Active ingredients: Fentanyl
Abstral 100 micrograms sublingual tablets
Abstral 200 micrograms sublingual tablets
Abstral 300 micrograms sublingual tablets
Abstral 400 microgram sublingual tablets
Abstral 600 micrograms sublingual tablets
Abstral 800 micrograms sublingual tablets
Why is Abstral used? What is it for?
Abstral is a treatment for adults who already have to take strong pain relieving medicines (opioids) regularly for persistent cancer pain, but who require treatment for breakthrough pain. If in doubt, consult your doctor.
Breakthrough pain is pain that occurs suddenly, even if you have already taken your usual opioid pain reliever medicine.
The active ingredient present in Abstral sublingual tablets is fentanyl. Fentanyl belongs to a group of powerful pain relieving medicines called opiates.
Contraindications When Abstral should not be used
Do not take Abstral
- if you are allergic to fentanyl or any of the other ingredients of this medicine (listed in section 6)
- if you have severe breathing problems
- if you do not regularly use an opioid medicine prescribed by your doctor (e.g. codeine, fentanyl, hydromorphone, morphine, oxycodone, pethidine), every day on a regular schedule, for at least one week, for the control of persistent pain. If you are not using these medicines you should not use Abstral as it may increase the risk that your breathing may become dangerously slow and / or difficult, or even stop.
- if you have short-term pain other than breakthrough pain.
Precautions for use What you need to know before taking Abstral
Talk to your doctor or pharmacist before taking Abstral if you have or have recently had any of the following events, as your doctor will need to take these into account when prescribing your dose:
- a head injury, as Abstral may hide the extent of the injury
- breathing problems or myasthenia gravis (condition characterized by muscle weakness)
- if you have heart problems, especially slow heart rate
- low blood pressure
- kidney or liver disease, as this may require your doctor to adjust your dose more carefully
- brain tumor and / or increased intracranial pressure (increased pressure in the brain causing severe headache, nausea / vomiting and blurred vision)
- sores in the mouth or mucositis (swelling and redness inside the mouth)
- if you take antidepressants or antipsychotics please refer to the section "Other medicines and Abstral"
During treatment with Abstral, if you are about to have surgery, please tell your doctor or dentist that you are taking this medicine.
For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Interactions Which drugs or foods can change the effect of Abstral
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines (other than the usual opioid pain reliever medicine).
The following medicines can intensify the effects of Abstral:
- some types of antifungal agents containing eg. ketoconazole or itraconazole (used to treat fungal infections);
- some types of antibiotic medicines used to treat infections (called macrolides, containing e.g. erythromycin
- some types of antiviral medicines called protease inhibitors containing eg. ritonavir (used to treat infections caused by viruses);
- alcohol-containing medicines;
- medicines called monoamine oxidase (MAO) inhibitors, which are used for severe depression and Parkinson's disease; tell your doctor if you have taken this type of medicine in the past two weeks.
The following medicines may reduce the effects of Abstral:
- Some types of potent pain relievers called partial agonists / antagonists, for example buprenorphine, nalbuphine and pentazocine (medicines to treat pain). In association with the use of these medicines, withdrawal symptoms (nausea, vomiting, diarrhea, anxiety, chills, tremor and sweat) may occur.
Abstral may intensify the effect of medicines that cause sleepiness, such as:
- other potent pain relievers (opioid-type medicines, e.g. for pain and cough)
- general anesthetics (used to fall asleep during operations)
- muscle relaxants
- sleeping pills
- medicines used to treat
- depression
- allergies
- anxiety and psychosis
- medicines containing clonidine (used to treat high blood pressure).
The risk of side effects increases if you are taking certain antidepressants or antipsychotics. Abstral may interact with these medicines and you may experience changes in your mental status (eg.agitation, hallucinations, coma) and other effects such as body temperature above 38 ° C, increased heart rate, unstable blood pressure and exaggerated reflexes, muscle stiffness, lack of coordination and / or gastrointestinal symptoms (eg. nausea, vomiting, diarrhea). Your doctor will tell you if Abstral is suitable for you.
Abstral with food, drink and alcohol
Abstral can cause drowsiness in some people. Do not take alcohol without consulting your doctor, as it may make you more sleepy than usual.
Do not drink grapefruit juice if you have been prescribed treatment with Abstral, as it can increase the side effects of Abstral.
Warnings It is important to know that:
Pregnancy and breastfeeding
Do not use Abstral during pregnancy unless your doctor specifically tells you to.
Fentanyl can migrate into breast milk and cause side effects in the breastfed baby. Do not take Abstral while breastfeeding. You can only start breastfeeding again at least 5 days after taking the last dose of Abstral.
Ask your doctor or pharmacist for advice before taking any medicine during pregnancy or breastfeeding.
Driving and using machines
Abstral can affect your physical or mental ability to perform potentially dangerous activities, such as driving or operating machinery.
If you feel dizzy, sleepy or have blurred vision when taking Abstral, do not drive or use machines.
Dose, Method and Time of Administration How to use Abstral: Posology
Before you take Abstral for the first time, your doctor will explain how it should be taken to effectively treat breakthrough pain.
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
This product should ONLY be used by you, based on the instructions given by your doctor. It should not be used by anyone else as it can pose a SERIOUS risk to your health, especially for children.
Abstral is different from other medicines you may have used to treat breakthrough pain. You should always use the dose of Abstral prescribed by your doctor - this may be a different dose than you used with other medicines for breakthrough pain.
Initial treatment - find the most suitable dose
For Abstral to work, your doctor needs to identify the most suitable dose to treat your breakthrough pain. Abstral is available in a range of strengths. You may need to try different strengths of Abstral during different breakthrough pain manifestations to find the most suitable dose. Your doctor will help you find the best dose to use.
If you do not get adequate pain relief from a dose, your doctor may ask you to take an extra dose to treat a manifestation of breakthrough pain. Do not take a second tablet, unless your doctor tells you that you can, as it could result in an overdose.
Your doctor might advise you to take a dose consisting of more than one tablet at a time. Take this dose only as prescribed by your doctor.
Wait at least 2 hours after taking the last dose before treating a new breakthrough pain event with Abstral. Ongoing treatment - once you have found the right dose Once you and your doctor have found a dose of Abstral that can control breakthrough pain, you should take this dose no more than four times a day. A dose of Abstral may consist of more than one tablet. Wait at least 2 hours after taking the last dose before treating a new breakthrough pain event with Abstral.
If you feel that the dose of Abstral you are using does not control your breakthrough pain satisfactorily, please inform your doctor as he or she may need to adjust your dose.
You should not change your dose of Abstral unless your doctor tells you to.
Taking the medicine
Abstral is to be used sublingually. This means that the tablet should be placed under the tongue where it dissolves rapidly so that the fentanyl can be absorbed through the lining of the mouth. Once absorbed, fentanyl begins to act to carry out its pain relieving action.
When you have a breakthrough pain episode, take the dose your doctor tells you, as follows:
- if your mouth is dry, take a sip of water to moisten it. Spit or swallow the water;
- remove one or more tablets from the blister pack immediately before taking them, as follows:
- separate one of the squares of the blister from the packaging by cutting along the dotted lines (leave the remaining squares of the blister intact).
- Pull off the edge of the aluminum foil where the arrow is indicated and gently remove the tablet. Do not try to press Abstral sublingual tablets through the top aluminum layer, as this will damage them
- place the tablet under the tongue as deep as possible and let it dissolve completely;
- Abstral will dissolve rapidly under the tongue and be absorbed to carry out its pain relieving action. Therefore it is important that you do not suck, chew or swallow the tablet;
- do not drink or eat anything until the tablet has completely dissolved under the tongue.
If you stop taking Abstral
If you no longer have breakthrough pain, you should stop taking Abstral. However, you should continue to take your usual opioid-based analgesic medicine for the treatment of persistent tumor pain as directed by your doctor. If you stop taking Abstral you may experience drug withdrawal symptoms similar to the possible side effects of Abstral.
Talk to your doctor if you develop withdrawal symptoms or have concerns about the relief of painful symptoms. Your doctor will decide whether to prescribe a medicine to reduce or eliminate withdrawal symptoms.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Overdose What to do if you have taken too much Abstral
If you take more Abstral than you should
- remove any tablets from your mouth
- tell your caregiver or anyone else what happened
- you or your carer should immediately contact your doctor, pharmacist or local hospital and discuss what action to take
- while waiting for the doctor, the person should be kept awake by talking or shaking them continuously
Symptoms of an overdose include:
- extreme sleepiness
- slowing down and difficulty in breathing
If this happens, seek emergency medical treatment immediately.
If you think someone has accidentally taken Abstral, seek emergency medical treatment immediately.
Side Effects What are the side effects of Abstral
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you start to feel unusually or extremely sleepy or have slow or difficult breathing, you or your caregiver should immediately contact your doctor or local hospital for emergency medical intervention (see also section 3 "If you take more Abstral than he owes ").
Very common side effects (may affect more than 1 in 10 people) include:
- nausea
Common side effects (may affect up to 1 in 10 people) include:
- dizziness, headache, excessive sleepiness
- wheezing / wheezing
- inflammation of the oral mucosa, vomiting, constipation, dry mouth
- sweating, fatigue / tiredness / lack of energy
Uncommon side effects (may affect up to 1 in 100 people) include:
- allergic reaction, tremor / trembling, disturbed or blurred vision, fast or slow heartbeat, low blood pressure, memory loss
- depression, paranoia / unmotivated feeling of fear, feelings of confusion, disorientation, anxiety / unhappiness / restlessness, unusual feeling of happiness / well-being, mood swings
- feeling of always having a full stomach, stomach pain, indigestion
- mouth ulcers, tongue problems, pain in the mouth or throat, throat constriction, lip or gum ulcers
- loss of appetite, loss or alteration of the sense of taste / smell
- difficulty sleeping or disturbed sleep, disturbance in attention / ease of distraction, lack of energy / weakness / loss of strength
- skin abnormalities, rash, itching, night sweats, decreased sensitivity to touch, easy bruising
- joint pain or stiffness, muscle stiffness
- drug withdrawal symptoms (may occur if the following side effects appear: nausea, vomiting, diarrhea, anxiety, chills, tremors and sweat), accidental overdose, in men inability to achieve and / or maintain an erection, general feeling of malaise
Undesirable effects of unknown frequency: (frequency cannot be estimated from the available data)
- swelling of the tongue, severe breathing problems, falls, redness, feeling very hot, diarrhea, convulsions (seizures), swelling of the arms or legs, seeing or hearing things that are not there (hallucinations), fever.
Reporting of side effects
If you get any side effects, including any possible side effects not listed in this leaflet, contact your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
The pain reliever medicine in Abstral is very strong and could be life-threatening if accidentally taken by a child. Keep Abstral out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister after EXP. The expiry date refers to the last day of that month.
Do not store above 25 ° C.
Store in the original blister to protect from moisture.
It is recommended that Abstral be stored in a protected and locked storage place.
Any unused product should be given, if possible, to the pharmacist for safe disposal. Do not throw any medicines via wastewater or household waste. This will help protect the environment.
Deadline "> Other information
What Abstral contains
The active ingredient is fentanyl.
One sublingual tablet contains:
- 100 micrograms of fentanyl (citrate)
- 200 micrograms of fentanyl (citrate)
- 300 micrograms of fentanyl (citrate)
- 400 micrograms of fentanyl (citrate)
- 600 micrograms of fentanyl (citrate)
- 800 micrograms of fentanyl (citrate)
The other ingredients are mannitol (E421), silicated microcrystalline cellulose, croscarmellose sodium and magnesium stearate.
What Abstral looks like and contents of the pack
Abstral is a small white sublingual tablet that is inserted under the tongue. It comes in a range of different strengths and forms. Your doctor will prescribe the correct strength (form) and number of tablets for you.
- The 100 microgram tablet is white and round in shape
- The 200 microgram tablet is white and oval shaped
- The 300 microgram tablet is white and triangular in shape
- The 400 microgram tablet is white and pentagonal in shape
- The 600 microgram tablet is white and "D" shaped
- The 800 microgram tablet is white and capsule shaped
Abstral tablets are available in boxes of 10 or 30 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
ABSTRAL SUBLINGUAL TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Each sublingual tablet contains
100 mcg of fentanyl (as citrate)
200 mcg of fentanyl (as citrate)
300 mcg of fentanyl (as citrate)
400 mcg of fentanyl (as citrate)
600 mcg of fentanyl (as citrate)
800 mcg of fentanyl (as citrate)
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Sublingual tablet
The 100 mcg sublingual tablet is white in color and round in shape
The 200 mcg sublingual tablet is white in color and oval in shape
The 300 mcg sublingual tablet is white in color and triangular in shape
The 400 mcg sublingual tablet is white in color and rhomboid in shape
The 600 mcg sublingual tablet is white and "D" shaped
The 800 mcg sublingual tablet is white and capsule-shaped
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Management of breakthrough pain in adult patients using opioid therapy for chronic cancer pain. Breakthrough pain is a transient exacerbation of otherwise controlled chronic persistent pain.
04.2 Posology and method of administration -
Abstral should only be given to patients considered tolerant to opioid therapy for persistent cancer pain. Patients may be considered opioid tolerant if they take at least 60 mg of morphine orally per day, at least 25 mcg of transdermal fentanyl per hour, at least 30 mg of oxycodone per day, at least 8 mg of hydromorphone per day or if they have taken an equianalgesic dose of another opioid for at least one week.
Method of administration:
Abstral sublingual tablets should be administered directly under the tongue, in the deepest part. Abstral sublingual tablets should not be swallowed, but should be allowed to dissolve completely in the sublingual cavity, without chewing or sucking them. Instruct patients not to eat or drink until the tablet is completely dissolved.
In patients with dry mouth, water can be used to moisten the mucosa before taking Abstral.
Dose titration:
The purpose of dose titration is to identify an optimal maintenance dose for the continued treatment of breakthrough pain manifestations. This optimal dose should provide adequate analgesia with an acceptable level of adverse reactions.
The optimal dose of Abstral will be determined for each individual patient by gradually increasing the dose. Several strengths are available for use during the titration step. The starting dose of Abstral should be 100 micrograms, increasing the dose as needed over the range of available strengths.
Patients should be carefully monitored until the optimal dose is reached.
Switching from other fentanyl-containing products to Abstral should not be done in a 1: 1 ratio due to the different absorption profiles. If patients switch from another fentanyl-containing product, a new titration with Abstral is required.
The following regimen is recommended for titration, although in all cases the physician should take into account the patient's clinical needs, age, and concomitant disease.
All patients should start therapy by taking a single 100 microgram sublingual tablet. If adequate analgesia is not achieved within 15-30 minutes of administration of a single sublingual tablet, an additional (second) sublingual tablet of 100 micrograms can be administered. If adequate analgesia is not obtained within 15-30 minutes of administering the first dose, a tablet of the next higher dosage should be considered for the subsequent manifestation of breakthrough pain (see the figure below).
Dose adjustment should continue gradually until adequate analgesia with tolerable adverse reactions is achieved. The dosage for the supplemental sublingual tablet (second tablet) should be increased from 100 to 200 micrograms to doses of 400 micrograms and above, as shown in the following diagram: During this titration phase, do not administer more than two doses for a single episode of breakthrough pain.
ABSTRAL TITRATION PROCEDURE
If adequate analgesia is obtained at the highest dose, but side effects are considered unacceptable, an intermediate dose (using the 100 microgram sublingual tablet, as needed) can be given.
During titration, patients may be instructed to take multiples of the 100 mcg and / or 200 mcg tablets for any single dose. More than four tablets should never be used at a time.
The efficacy and safety of doses above 800 micrograms have not been evaluated in clinical studies in patients.
In order to minimize the risk of opioid-related adverse reactions and to identify the appropriate dose, close monitoring of patients by healthcare professionals during the titration process is imperative.
During titration, patients should wait at least 2 hours before treating a new breakthrough pain manifestation with Abstral.
Maintenance therapy:
Once a suitable dose has been established, which may also consist of several tablets, patients should remain on this dose, and should limit consumption to a maximum of four doses of Abstral per day.
During the maintenance period, patients should wait at least 2 hours before treating a new breakthrough pain manifestation with Abstral.
Changes to dose adjustments:
If the response (analgesia or adverse reactions) to the titrated dose of Abstral changes markedly, adjustment may be necessary to ensure that an optimal dose is maintained.
If more than four episodes of breakthrough pain occur per day for more than four consecutive days, the dose of the long-acting opioid used for persistent pain should be re-evaluated. If the long-acting opioid or its dose is changed, the dosage of Abstral should be reassessed and titrated again to ensure that it is optimal for the patient.
It is imperative that any new dose titration of the analgesic be monitored by a healthcare professional.
Discontinuation of therapy:
Abstral therapy should be discontinued immediately if the patient ceases to experience breakthrough pain. Treatment of persistent breakthrough pain should be continued as directed by the physician.
If it is necessary to discontinue the entire opioid therapy, the physician should closely monitor the patient in order to manage the risk of abrupt withdrawal effects.
Use in children and adolescents:
Abstral should not be used in patients below 18 years of age due to a lack of data on safety and efficacy.
Use in older people:
Dose titration should be approached with particular caution and patients should be carefully observed for signs of fentanyl toxicity (see section 4.4).
Use in patients with renal and hepatic insufficiency:
Patients presenting with hepatic or renal dysfunction should be carefully observed during dose titration of Abstral for signs of fentanyl toxicity (see section 4.4).
04.3 Contraindications -
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Patients without opioid maintenance therapy as there is an increased risk of respiratory depression.
Severe respiratory depression or severe obstructive lung disease.
Treatment of acute pain other than breakthrough pain.
04.4 Special warnings and appropriate precautions for use -
Patients and caregivers should be informed of the presence of an active substance in Abstral in such quantities as to be fatal to a child and therefore of the need for all tablets to be kept out of the reach and sight of children.
Because of the potentially serious side effects that can occur when taking opioid therapy such as Abstral, patients and their caregivers should be advised of the importance of taking Abstral correctly and what action to take if they do. overdose symptoms.
Before initiating therapy with Abstral, it is important that treatment with long-acting opioids is stabilized for the control of persistent pain.
With repeated administration of opioids, such as fentanyl, physical and / or psychological addiction and dependence may develop. Iatrogenic dependence following therapeutic use of opiates is rare.
As with all opioids, the use of Abstral is associated with a risk of clinically significant respiratory depression. Particular caution should be exercised when titrating the dose of Abstral in patients with chronic obstructive pulmonary disease or other conditions predisposing to respiratory depression (eg myasthenia gravis) due to the risk of further respiratory depression, which could lead to respiratory failure.
Abstral should only be administered with extreme caution in patients particularly susceptible to the intracranial effects of hypercapnia, i.e. in those in whom an increase in intracranial pressure, an altered state of consciousness, coma or brain tumors is evident. In patients with head injuries, the clinical course may be obscured by the use of opioids. In such an event, opioids should only be used when absolutely necessary.
Heart disease
Fentanyl can produce bradycardia. Fentanyl should be used with caution in patients with previous or ongoing bradyarrhythmias.
Data from intravenous studies on fentanyl use indicate that elderly patients may exhibit reduced clearance and prolonged half-life and may be more sensitive to the active substance than younger patients. Elderly, cachectic or debilitated patients should be monitored. careful observation for manifestations of fentanyl toxicity and, if necessary, doses should be reduced.
Abstral should be administered with caution to patients with hepatic or renal dysfunction, especially during the titration phase. The use of Abstral in patients with hepatic or renal insufficiency may increase the bioavailability of fentanyl and reduce its systemic clearance, resulting in an accumulation and increased or prolonged opioid effects.
Care should be taken when treating patients with hypovolaemia and hypotension.
Abstral has not been studied in patients with oral lesions or mucositis. In such patients there may be a risk of increased systemic drug exposure and therefore particular caution is recommended during titration.
There should be no obvious effects of stopping treatment with Abstral, but possible withdrawal symptoms are anxiety, tremor, sweating, paleness, nausea and vomiting.
Serotonin syndrome
• Caution is advised when Abstral is administered concomitantly with drugs that affect the serotonergic neurotransmission systems.
With concomitant use of serotonergic drugs such as Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), and with drugs that impair serotonin metabolism (including Monoamine Oxidase Inhibitors [MAOIs] ) development of a potentially life-threatening serotonin syndrome may occur. This may occur within the recommended dose range.
Serotonin syndrome may include changes in mental status (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g. hyperreflexia, lack of coordination, rigidity) and / or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea).
If serotonin syndrome is suspected, treatment with Abstral should be discontinued.
04.5 Interactions with other medicinal products and other forms of interaction -
Fentanyl is metabolised by CYP3A4. Drugs that inhibit CYP3A4 activity, such as macrolide antibiotics (e.g. erythromycin), azole antifungal agents (e.g. ketoconazole, itraconazole) or some protease inhibitors (e.g. ritonavir) may increase the bioavailability of fentanyl, reducing its systemic clearance and potentially intensifying or prolonging the opioid effects. Grapefruit juice is also a known inhibitor of CYP3A4. Fentanyl should therefore be administered with caution to patients concomitantly taking CYP3A4 inhibitors.
The concomitant use of other central nervous system depressants, such as other morphine derivatives (analgesics and antitussives), general anesthetics, musculoskeletal relaxants, sedative antidepressants, sedative H1 antihistamines, barbiturates, anxiolytics (eg benzodiazepines), hypnotics, antipsychotics, clonidine and related substances can produce an increased depressant effect on the central nervous system. Respiratory depression, hypotension, and profound sedation can occur.
Alcohol potentiates the sedative effects of morphine-based analgesics, therefore concomitant administration of alcoholic beverages or medicinal products containing alcohol is not recommended with Abstral.
Abstral is not recommended in patients who have taken monoamine oxidase (MAO) inhibitors in the past 14 days as severe and unpredictable potentiation by MAO inhibitors with opioid analgesics has been reported.
The concomitant use of partial opioid agonists / antagonists (for example, buprenorphine, nalbuphine, pentazocine) is not recommended. These drugs have a high affinity for opiate receptors with relatively low intrinsic activity and therefore produce a partially antagonistic effect than the analgesic effect of fentanyl and may induce drug withdrawal symptoms in opioid-dependent patients.
Serotonergic drugs
Concomitant administration of fentanyl with a serotonergic agent, such as a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) or a Monoamine Oxidase Inhibitor (MAO) may increase the risk of serotonin syndrome, a potentially life-threatening condition.
04.6 Pregnancy and breastfeeding -
The safety of fentanyl in pregnancy has not been established. Studies in animals have shown reproductive toxicity with impaired fertility in rats (see section 5.3). The potential risk for humans is unknown. Fentanyl should not be used during pregnancy unless absolutely necessary.
Long-term treatment during pregnancy can cause withdrawal symptoms in infants.
Fentanyl should not be used during labor and delivery (including caesarean section) as the drug crosses the placenta and can cause respiratory depression in the fetus or newborn.
Feeding time
Fentanyl migrates into breast milk and can cause sedation and respiratory depression in the breastfed baby. Fentanyl should not be used in breastfeeding women and breastfeeding can only be resumed at least 5 days after the last administration of fentanyl.
04.7 Effects on ability to drive and use machines -
No studies on the ability to drive and use machines have been performed with Abstral.
However, opioid analgesics affect the physical or mental ability to perform potentially dangerous activities, such as driving or operating machinery. Patients should be advised not to drive or operate machinery if they feel dizzy or sleepy or if they experience blurred or double vision while taking Abstral.
04.8 Undesirable effects -
Typical opioid side effects are to be expected with Abstral; they tend to decrease in intensity with prolonged use. The most serious potential adverse reactions associated with opioid use are respiratory depression (which could cause respiratory arrest), hypotension and shock.
Clinical studies of Abstral were aimed at evaluating the safety and efficacy of treating breakthrough pain in cancer patients. All patients were taking concomitant opioids such as prolonged-release morphine, prolonged-release oxycodone, or transdermal fentanyl for their persistent pain. Therefore it is not possible to conclusively identify the effects due to Abstral alone.
The most frequently observed adverse reactions with Abstral include typical opioid adverse reactions, such as nausea, constipation, somnolence and headache.
Tabulated list of adverse reactions observed with Abstral and / or other compounds containing fentanyl:
The following observed adverse reactions have been reported with Abstral and / or other fentanyl-containing compounds in clinical trials and in post-marketing experience. They are listed by system organ class and by frequency (very common ≥ 1/10; common from ≥ 1/100, a
* Opioid withdrawal symptoms such as nausea, vomiting, diarrhea, anxiety, shivering, shaking and sweating. have been observed with transmucosal administration of fentanyl
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose -
Symptoms of fentanyl overdose are an intensification of its pharmacological actions, the most serious effect of which is respiratory depression, which can cause respiratory arrest.
Immediate management of opioid overdose includes removal of any remaining Abstral sublingual tablets from the mouth, physical and verbal stimulation of the patient, and assessment of level of consciousness. A patent airway must be established and maintained. If necessary, insert an oropharyngeal airway or endotracheal tube, administer oxygen, and initiate mechanical ventilation as needed. Maintain adequate body temperature and parenteral fluid administration.
For the treatment of accidental overdose in opioid-naïve individuals, naloxone or other opioid antagonists should be used as clinically indicated and based on the relevant Summary of Product Characteristics. Repeated administration of opioid antagonists may be necessary if the duration of respiratory depression is prolonged.
Caution should be exercised in the use of naloxone or other opioid antagonists to treat overdose in patients on opioid therapy, as there is a risk of acute withdrawal syndrome.
If severe or persistent hypotension occurs, hypovolemia should be assessed and the problem should be managed with appropriate parenteral fluid therapy.
Muscle stiffness that interferes with breathing has been reported with fentanyl and other opiates. In this situation, endotracheal intubation, assisted ventilation, and administration of opioid antagonists and muscle relaxants may be necessary.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: analgesics, opiates; phenylpiperidine derivatives.
ATC code: N02AB03.
Fentanyl is a potent mc-opioid analgesic with rapid onset of analgesia and short duration of action. As an analgesic, fentanyl is approximately 100 times more potent than morphine. The secondary effects of fentanyl on the central nervous system (CNS) and on respiratory and gastrointestinal function are typical of opioid analgesics and are considered class effects. These can include respiratory depression, bradycardia, hypothermia, constipation, myosis, physical dependence and euphoria.
The analgesic effects of fentanyl are related to the blood levels of the active substance; in opioid-naïve patients, minimal effective analgesic serum concentrations of fentanyl are between 0.3 and 1.2 ng / mL, while blood levels of 10-20 ng / mL produce surgical anesthesia and profound respiratory depression.
In patients with chronic cancer pain taking stable maintenance doses of opioids, there was a statistically significant improvement in the difference in pain intensity with Abstral versus placebo 10 minutes after dosing, with significantly less need for therapy. analgesic "as needed".
The safety and efficacy of Abstral have been evaluated in patients taking the drug at the onset of breakthrough pain. Preventive use of Abstral to prevent predictable pain episodes has not been studied in clinical studies.
Fentanyl, like all opiate mc receptor agonists, produces dose-dependent respiratory depression. This risk is higher in opioid-naïve subjects than in patients who have experienced severe pain or are receiving chronic opioid therapy. Long-term opioid treatment usually causes addiction to their side effects.
While opiates typically increase the smooth muscle tone of the urinary tract, the end effect tends to be variable, in some cases producing urgency, in others, difficulty passing urine.
Opiates increase tone and reduce propulsive contractions of the smooth muscle of the gastrointestinal tract, causing prolongation of the gastrointestinal transit time, which may be behind the constipating effect of fentanyl.
05.2 "Pharmacokinetic properties -
Fentanyl is a highly lipophilic drug, absorbed very quickly through the oral mucosa and more slowly through the gastrointestinal tract. Orally administered fentanyl results in pronounced hepatic and intestinal first pass effects.
Abstral is a fast dissolving sublingual tablet formulation. Rapid absorption of fentanyl occurs within approximately 30 minutes of Abstral administration. The absolute bioavailability of Abstral was 54%. Mean maximum plasma concentrations of fentanyl range from 0.2 to 1.3 ng / ml ( after administration of 100-800 mcg of Abstral) and are reached within 22.5-240 minutes.
Approximately 80-85% of fentanyl is bound to plasma proteins, mainly to a1-glycoprotein and to a lesser extent to albumin and lipoprotein. The steady-state volume of distribution of fentanyl is approximately 3-6 L / kg.
Fentanyl is primarily metabolised via CYP3A4 to several pharmacologically inactive metabolites, including norfentanil. Within 72 hours of intravenous fentanyl administration, approximately 75% of the dose is excreted in the urine, primarily as metabolites, with less than 10% as unchanged drug. Approximately 9% of the dose is present in the faeces, mainly as metabolites. Total plasma clearance of fentanyl is approximately 0.5 L / h / kg.
Following administration of Abstral, the primary elimination half-life of fentanyl is approximately 7 hours (range 3-12.5 hours) and the terminal half-life is approximately 20 hours (range 11.5-25 hours).
The pharmacokinetics of Abstral were dose proportional over the dose range of 100 to 800 micrograms. Pharmacokinetic studies have shown that multiple tablets are bioequivalent to single tablets of the equivalent dose.
Renal / hepatic insufficiency
Insufficient liver or kidney function can cause increased serum concentrations. Elderly, cachectic or generally debilitated patients may have lower fentanyl clearance, which could cause a longer "final half-life" (see sections 4.2 and 4.4).
05.3 Preclinical safety data -
Pharmacology data on safety and repeated dose toxicity do not reveal a particular hazard for humans, which is not already covered in other sections of this Summary of Product Characteristics. Animal studies have shown reduced fertility and increased mortality in fetuses of rats. The teratogenic effects, however, have not been demonstrated.
Mutagenicity tests in bacteria and rodents yielded negative results. Like other opiates, fentanyl has shown mutagenic effects in vitro on mammalian cells. A mutagenic risk with therapeutic use seems unlikely, since the effects were only induced at very high concentrations.
Carcinogenicity studies (26-week dermal alternative bioassay in TgAC transgenic mice; 2-year subcutaneous carcinogenicity study in rats) with fentanyl did not reveal results suggestive of oncogenic potential. Evaluation of brain slides from the carcinogenesis study in rats revealed brain lesions in animals treated with high doses of fentanyl citrate. The relevance of these findings to humans is unknown.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Mannitol (E421)
Silicified microcrystalline cellulose
Croscarmellose sodium
Magnesium stearate
06.2 Incompatibility "-
Not relevant.
06.3 Period of validity "-
2 years.
06.4 Special precautions for storage -
Do not store above 25 ° C.
Store in the original package to protect from moisture.
06.5 Nature of the immediate packaging and contents of the package -
Abstral sublingual tablets are packaged in child-resistant blister packs with OPA / aluminum / PVC pockets lined with paper / polyester / aluminum, contained in an outer carton. The packaging of each strength of Abstral sublingual tablets is color coded according to a particular identifying color.
Pack sizes: packs of 10 or 30 sublingual tablets. Not all pack sizes may be marketed.
06.6 Instructions for use and handling -
Waste materials must be disposed of safely. Patients and caregivers should be encouraged to return any unused product to the pharmacy, where it should be disposed of according to national and local regulations.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Kyowa Kirin Ltd
Galabank Business Park
Galashiels
TD1 1QH
UK
08.0 MARKETING AUTHORIZATION NUMBER -
AIC n 038736031 - "100 Mcg Sublingual Tablets" 10 Tablets In Blister Opa / Pvc / Al / Al
AIC n 038736043 - "100 Mcg Sublingual Tablets" 30 Tablets In Blister Opa / Pvc / Al / Al
AIC n 038736056 - "200 Mcg Sublingual Tablets" 10 Tablets In Blister Opa / Pvc / Al / Al
AIC n 038736068 - "200 Mcg Sublingual Tablets" 30 Tablets In Blister Opa / Pvc / Al / Al
AIC n 038736070 - "300 Mcg Sublingual Tablets" 10 Tablets In Blister Opa / Pvc / Al / Al
AIC n 038736082 - "300 Mcg Sublingual Tablets" 30 Tablets In Blister Opa / Pvc / Al / Al
AIC n 038736094 - "400 Mcg Sublingual Tablets" 10 Tablets In Blister Opa / Pvc / Al / Al
AIC n 038736106 - "400 Mcg Sublingual Tablets" 30 Tablets In Blister Opa / Pvc / Al / Al
AIC n 038736118 - "600 Mcg Sublingual Tablets" 10 Tablets In Blister Opa / Pvc / Al / Al
AIC n 038736120 - "600 Mcg Sublingual Tablets" 30 Tablets In Blister Opa / Pvc / Al / Al
AIC n 038736132 - "800 Mcg Sublingual Tablets" 10 Tablets In Blister Opa / Pvc / Al / Al
AIC n 038736144 - "800 Mcg Sublingual Tablets" 30 Tablets In Blister Opa / Pvc / Al / Al
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Date of first authorization: 29-02-2008
Date of last renewal: 28-02-2013
10.0 DATE OF REVISION OF THE TEXT -
May 2016
