SYNTHESIS |
flavoring: berry artificial flavor , maltodextrin , propylene glycol , artificial flavor , triethyl citrate
printing ink: deionized water , bleached dewaxed shellac , brilliant blue FCF , tar , ammonium hydroxide
EEN without threshold dose: glucose , sucrose
SHAPES AND PRESENTATIONS |
COMPOSITION |
| p tablet | |
| Fentanyl citrate expressed as fentanyl | 200mcg |
| Where | 400mcg |
| Where | 600mcg |
| Where | 800mcg |
| Where | 1200 mcg |
| Where | 1600mcg |
Excipients with known effect: one tablet contains approximately 1.89 g of glucose and 20-36 mg of sucrose.
| DC | DIRECTIONS |
A paroxysmal pain attack is a transient exacerbation of chronic pain otherwise controlled by disease-modifying therapy.
Patients receiving morphine background therapy are those taking at least 60 mg of oral morphine per day, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg of oxycodone per day, at least 8 mg of hydromorphone orally daily or an equianalgesic dose of another opioid for at least one week.
| DC | WARNINGS AND PRECAUTIONS FOR USE |
- Accidental use in children:
- It is imperative to inform patients and their caregivers that Actiq contains an active substance at a dose which can be fatal for a child. Cases of death have been reported in children who had accidentally ingested Actiq.
- Patients and their caregivers should be instructed to keep all units out of the sight and reach of children and to carefully dispose of all units, used or unused. In any ambulatory patient, it is recommended to assess the possible risks of accidental exposure of children to the drug.
- Morphine long-term treatment:
- Actiq should under no circumstances be administered to patients not receiving disease-modifying opioid therapy, due to an increased risk of respiratory depression and death. Before starting treatment with Actiq, the background morphine treatment must be stabilized and the patient must continue treatment with morphine while taking Actiq.
- Drug dependence and risk of misuse:
- Addiction, physical dependence and psychological dependence are likely to appear during repeated administration of morphine. Iatrogenic addiction can occur after the administration of morphine. The risk of misuse may arise with fentanyl, as with other opioids, and all patients treated with opioids should be monitored for any signs misuse and addiction. Patients at increased risk of opioid misuse may still be treated with opioids, but the appearance of any signs of misuse, abuse or addiction should be closely monitored.
- Repeated use of ACTIQ can lead to opioid use disorder (OUD). Abuse or intentional misuse of ACTIQ can lead to overdose and/or death. The risk of occurrence of OUD is increased in patients with a personal or family history (parents or siblings) of substance use disorders (including alcoholism), in case of active smoking or in patients with a personal history of other mental health disorders (severe depression, anxiety disorders and personality disorders, for example).
- Patients should be monitored for signs of compulsive product-seeking behavior (eg, requesting a prescription refill too soon). In this context, opioids and psychoactive drugs (such as benzodiazepines) used concomitantly should be reviewed. For patients presenting with signs and symptoms of OUD, consultation with an addictologist should be considered.
- Hyperalgesia:
- As with other opioids, if there is insufficient pain control in response to a higher dose of fentanyl, the possibility of opioid-induced hyperalgesia should be considered. Fentanyl dose reduction, discontinuation of fentanyl therapy, or reassessment of therapy may be indicated.
- Endocrine effects:
- Opioids can have a pharmacological action on the hypothalamic-pituitary-adrenal axis or on the hypothalamic-pituitary-gonadal axis. An increase in serum prolactin and a decrease in plasma cortisol and testosterone can be observed. Clinical signs and symptoms may appear as a result of these hormonal changes.
- Cases of adrenal insufficiency have been reported more often with the use of opioids, including fentanyl tablets, after more than one month of use. The patient should gradually discontinue the opioid to allow recovery of adrenal function and should continue corticosteroid treatment until adrenal function is restored ( see Adverse Reactions ).
- Respiratory depression:
- As with all morphine, the use of Actiq exposes to a risk of clinically significant respiratory depression, therefore patients should be monitored. Particular caution is advised when titrating Actiq in patients with non-severe chronic obstructive pulmonary disease or any other pre-existing condition predisposing them to respiratory depression because, even at normal therapeutic doses, Actiq may aggravate respiratory disorders. to cause respiratory failure.
- Sleep-related breathing disorders:
- Opioids can cause sleep-related breathing disorders, including central sleep apnea (CSA) and sleep-related hypoxemia. The use of opioids increases the risk of CSA in a dose-dependent manner. In patients with CSA, a reduction in total opioid dose should be considered.
- Alcohol :
- Concomitant use of alcohol and fentanyl may induce an increase in depressant effects which may have a fatal outcome ( see Interactions ).
- Risks in case of concomitant administration of benzodiazepines:
- Concomitant use of opioids, including Actiq, and benzodiazepines can lead to profound sedation, respiratory depression, coma and death. Given these risks, the concomitant prescription of opioids and benzodiazepines should only be done in patients for whom there are no other adequate treatment options.
- If the decision is made to prescribe Actiq together with benzodiazepines, the lowest effective dose and the minimum duration of concomitant use should be chosen. Patients should be closely monitored for signs and symptoms of respiratory depression and sedation ( see Interactions ).
- Cerebral effects of hypercapnia, impaired consciousness, head trauma:
- Actiq should be administered with extreme caution to patients who may be particularly sensitive to the cerebral effects of hypercapnia, for example in patients with signs of increased intracranial pressure or impaired consciousness. Since opioids can mask the clinical course in the event of head trauma, they should only be used in this context if absolutely clinically necessary.
- Bradyarrhythmias:
- Fentanyl can cause bradycardia. Therefore, fentanyl should be used with caution in patients with a history of bradyarrhythmia or pre-existing bradyarrhythmia.
- Renal or hepatic impairment:
- In addition, Actiq should be administered with caution to patients with hepatic or renal impairment, as the influence of hepatic and renal dysfunction on the pharmacokinetics of fentanyl is not known. However, when administered intravenously, fentanyl clearance is impaired by hepatic or renal impairment, due to impaired metabolic clearance and effects on plasma proteins. Hepatic or renal impairment may increase the bioavailability of orally absorbed fentanyl and decrease its systemic clearance, resulting in increased and prolonged opioid effects. Particular caution is therefore required during the titration phase in patients with moderate to severe hepatic or renal impairment.
- Hypovolemia, hypotension:
- Actiq treatment should be considered with caution in the presence of hypovolaemia or hypotension.
- Cavities :
- Normal oral hygiene is recommended to reduce any harmful effects to the teeth. Actiq containing approximately 2 grams of glucose, frequent consumption increases the risk of dental caries. Dry mouth associated with morphine therapy may increase this risk. During treatment with ACTIQ, it is advisable to visit the dentist regularly for check-ups.
- Serotonin Syndrome:
- Caution is advised when Actiq is co-administered with medicinal products that affect the serotonergic neurotransmitter systems.
- A potentially life-threatening serotonin syndrome may develop with the concomitant use of serotonergic medicinal products such as selective serotonin reuptake inhibitors (SSRIs) and serotonin reuptake inhibitors and norepinephrine (SNRI), as well as with drugs that alter the metabolism of serotonin (including monoamine oxidase inhibitors [MAO inhibitors]) ( see Contraindications ). This can occur at recommended doses.
- Serotonin syndrome may be accompanied by mental status alterations (eg, agitation, hallucinations, coma), autonomic nervous system instability (eg, tachycardia, labile blood pressure, hyperthermia), neuromuscular disorders (eg hyperreflexia, incoordination, rigidity) and/or gastrointestinal symptoms (eg nausea, vomiting, diarrhoea).
- If serotonin syndrome is suspected, treatment with Actiq should be discontinued.
- Anaphylaxis and hypersensitivity:
- Cases of anaphylaxis and hypersensitivity have been reported with the use of fentanyl-based drugs administered by the transmucosal buccal route ( see Adverse Reactions ).
- Pediatric population:
- The use of Actiq in children and adolescents under 16 years of age is not recommended due to a lack of data on safety and efficacy ( see Pharmacodynamics , Pharmacokinetics ).
- Excipients:
- Glucose:
- Contains 1.89 g of glucose per dose. This is to be taken into account for patients with diabetes mellitus.
- Patients with glucose-galactose malabsorption syndrome (a rare hereditary disease) should not take this medicine.
- May be harmful to teeth.
- Sucrose:
- Patients with fructose intolerance, glucose-galactose malabsorption syndrome or sucrase/isomaltase deficiency (rare hereditary diseases) should not take this medicine.
- May be harmful to teeth.
- Sodium:
- This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e. that it is essentially "sodium-free".
| DC | FERTILITY / PREGNANCY / BREASTFEEDING |
There are no data or limited data from the use of fentanyl during pregnancy. Animal studies have shown reproductive toxicity ( see Preclinical Safety ). Morphine analgesics can cause respiratory depression in the newborn. With prolonged use of fentanyl during pregnancy, there is a risk of opioid withdrawal syndrome in the neonate, which can be life-threatening if not identified and treated, and requires management in accordance with protocols developed by neonatology experts. Actiq should only be used in pregnant women if clearly needed.
If the use of opioids is necessary for a prolonged period in a pregnant woman, the patient must be informed of the risk of neonatal opioid withdrawal syndrome and appropriate treatment must be made available ( see Adverse effects ).
It is recommended that Actiq not be used during labor and delivery (including caesarean section) as fentanyl crosses the placental barrier and may cause respiratory depression in the foetus. The transplacental passage rate is 0.44 (foeto-maternal ratio: 1.00/2.27).
Feeding with milk :
Fentanyl is excreted in human milk, and may cause sedation and respiratory depression in nursing infants. Fentanyl should not be used while breastfeeding. Breast-feeding should not be resumed until at least 5 days after the last administration of fentanyl.
Fertility:There are no data on fertility in humans. In animal studies, male fertility was impaired ( see Preclinical Safety ).
| DC | DRIVING AND USING MACHINES |
| DC | OVERDOSAGE |
- Symptoms :
- The symptoms to be expected in the event of an overdose by fentanyl are of the same nature as those observed after the intravenous administration of fentanyl or other opioids, and result from its pharmacological action. The most serious adverse effects are mental impairment, loss of consciousness, coma, cardio-respiratory arrest, respiratory depression, respiratory distress and respiratory failure leading to death.
- Cases of Cheyne Stokes respiration have been observed with fentanyl overdose, particularly in patients with a history of heart failure.
- Supported :
- The measures to be taken immediately in the presence of a morphine overdose consist of immediately removing the unit of Actiq from the patient's mouth if it is still there using the applicator, ensuring the permeability of the respiratory tract, perform physical and verbal stimulation of the patient and determine his level of consciousness as well as his ventilatory and circulatory status. Institute assisted ventilation if necessary.
- Overdose (accidental ingestion) in a person who has never received morphine treatment:
- Treatment of overdose in a person who has never received opioid therapy (accidental ingestion) requires the establishment of a venous access and the administration of naloxone or another opioid antagonist, depending on the clinical condition. . The duration of respiratory depression due to overdose may be longer than the effects of the morphine antagonist (e.g. the half-life of naloxone is between 30 and 81 minutes) and therefore it may be necessary to repeat the administration of the antidote.
- For more details on the instructions for use of the opioid antagonist used, refer to the Summary of Product Characteristics of the product in question.
- Overdose in patients receiving opioid maintenance therapy:
- In patients receiving well-tolerated morphine treatment, set up an intravenous line. In some cases, the judicious use of naloxone or other opioid antagonists may be warranted, but it runs the risk of triggering an acute withdrawal syndrome.
- Although muscle rigidity associated with respiratory depression has never been described after administration of Actiq, such a phenomenon is possible with fentanyl or other opioids. If such muscular rigidity appears, it will be necessary to establish assisted ventilation, administer a morphine antagonist and, as a last resort, a muscle relaxant.
| PP | PRECLINICAL SAFETY |
Non-clinical data from conventional studies of safety pharmacology, repeated dose toxicology, genotoxicity and carcinogenicity did not reveal any particular risk for humans.
Embryofetal developmental toxicity studies conducted in rats and rabbits revealed no malformations or developmental changes when administered during the period of organogenesis.
In a study of fertility and early embryonic development in rats, a male-mediated effect was observed at high doses (300 µg/kg/day, subcutaneous route), consistent with the sedative effects of fentanyl.
In pre- and postnatal development studies in rats, offspring survival was significantly reduced at doses causing severe maternal toxicity. The effects of maternal toxic doses on the first generation are: a delay in physical development, sensory functions, reflex and behavior. These effects may be indirect effects of maternal neglect and/or decreased breastfeeding or a direct effect of fentanyl.
Carcinogenicity studies (alternative dermal test in transgenic Tg AC mice for 26 weeks, subcutaneous carcinogenicity study in rats for two years) with fentanyl do not show any results suggesting an oncogenic potential. Analysis of brain sections from the rat carcinogenicity study showed brain damage in animals given high doses of fentanyl citrate. The clinical relevance of these results is not known.
| DP | STORAGE CONDITIONS |
- The duration of the conversation :
- 3 years.
Store at a temperature not exceeding 30°C.
Store in the protective blister until use.
| DP | HANDLING/DISPOSAL PROCEDURES |
All units, used or not, should be kept out of the reach of children and disposed of carefully as outlined below. Partially used units are particularly dangerous for children.
After the total consumption of Actiq, the applicator must be immediately stored in the container provided for this purpose which will be placed out of reach of children.
If the medicine has only been partially consumed, the rest of the tablet should be dissolved under a hot water tap, then the applicator should be immediately stored in the container provided for this purpose, which will be placed out of reach of children.
PRESCRIPTION/ISSUE/CARE |
Delivery limited to 7 days.
Prescription on prescription meeting the specifications set by the decree of March 31, 1999.
| MA | 3400935806307 (2002, SPC rev 10.05.2022) 200 µg. |
| 3400935806826 (2002, SPC rev 10.05.2022) 400 µg. | |
| 3400935807366 (2002, SPC rev 10.05.2022) 600 µg. | |
| 3400935843494 (2002, SPC rev 10.05.2022) 800 µg. | |
| 3400935843845 (2002, SPC rev 10.05.2022) 1200 µg. | |
| 3400935844217 (2002, SPC rev 10.05.2022) 1600 µg. |
| Price : | 20.51 euros (boxes of 3 tablets). |
| 65% Sec Remb. Collect. | |
Marketing Authorization Holder: Teva Pharma BV, Swensweg 5, 2031 GA Haarlem, The Netherlands.