ACTIQ is indicated for the treatment of paroxysmal pain attacks in patients already receiving a background treatment, morphine for chronic pain of origin, cancerous

A paroxysmal painful access is a temporary exacerbation of chronic pain by elsewhere controlled by a background treatment.

Patients receiving morphine-based treatment are those taking at least 60 mg of oral morphine daily, at least 25 micrograms of transdermal fentanyl per hour, at least 30 mg of oxycodone per day, at least 8 Mg of hydromorphone orally per day or equianalgesic dose of another opioid for at least one week

Reserved for the adult

In order to minimize the risks of morphine-related adverse effects and to determine the most "effective" dose adapted to a patient, it is essential that patients be closely monitored by health professionals during the Period of titration.

ACTIQ is not interchangeable on the basis of dose equivalence with other fast-acting fentanyls prescribed for painful, paroxysmal, cancerous access, since the pharmacokinetic profiles and / or patterns Dosages of these products are significantly different. Patients treated for paroxysmal painful access of cancer should be advised not to use several rapidly acting fentanyls and to discard any other fentanyl-containing products previously prescribed for painful, paroxysmal ( ADP) when switching to ACTIQ. The number of different ACTIQ assays made available to the patient at any time should be minimized to avoid errors and potential overdose


Any ACTIQ unit that has not been used and whose patient is no longer needed must be duly eliminated.

Patients should be reminded that ACTIQ must be kept out of the reach of children.

Mode of administration

ACTIQ is intended for oral administration, transmucosal, therefore, the tablet should be placed against the inner face of the cheek. With the aid of the applicator, it is then necessary to move the tablet against the mucosa of the cheeks in order to optimize the degree of exposure of the mucous membrane to the active product. The ACTIQ tablet should be allowed to melt on contact with the mucosa, without sucking, chewing or chewing, since the absorption of fentanyl from the oral mucosa is faster than systemic absorption by the gastrointestinal tract -intestinal.

Patients with dry mouth can moisten their oral mucosa by drinking a little water before taking the medication

The ACTIQ unit must be consumed in 15 minutes. If excessive morphine effects occur before the ACTIQ tablet is fully dissolved, it should be immediately removed from the mouth and consideration should be given to reducing subsequent doses.
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In the adult

Dosage adjustment and treatment, maintenance

The optimal dosage of ACTIQ should be determined for each patient, that is, the dose producing the desired analgesic effect with a minimum of adverse effects. In clinical studies, no relationship has been established between the effective dose of ACTIQ in painful and paroxysmal access and the dose of the background morphine treatment.

A) Titration

Before determining the dosage of ACTIQ in a patient, it is necessary to ensure that its chronic pain is controlled by a background morphine treatment and that it does not present more than 4 painful acute attacks per day .

The initial dose of ACTIQ should be 200 micrograms, with dosage increase, if necessary, according to the available dosage range (200, 400, 600, 800, 1200 and 1600 micrograms). Patients should be carefully monitored until the dose provides effective analgesia and undesirable side effects with a single ACTIQ unit per acute paroxysmal pain. This dose is defined as: being the effective dose.

During titration, if satisfactory analgesia is not obtained within 30 minutes of administration of a first unit of Actiq (ie 15 minutes after the end of dissolution; Of an ACTIQ unit), a second ACTIQ unit of the same assay may be used. In no case should more than two units of ACTIQ be used to treat the same paroxysmal pain. With the dosage of 1600 micrograms, it will probably be necessary to administer a second dose only in a minority of patients.

PRACTICAL TITRATION SCHEME

Start with a unit dosed at 200 μg

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1. Allow to melt in mouth 1 ACTIQ unit until complete dissolution (15 minutes)

2. Wait another 15 minutes, additional

3. If necessary, take a second unit to let it melt in 15 minutes

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Satisfactory relief with 1 unit?

(Test the same dose of ACTIQ during several acute attacks of paroxysmal)

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YES

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NO

Effective dose determined

Use the ACTIQ Assay

Immediately superior

(Available dosages: 200, 400, 600, 800, 1200, 1600 μg)
(B) Treatment, maintenance

Once the established effective dose (that is, acute paroxysmal access is effectively treated by a single unit on average), patients should use this dose and limit their intake to a maximum of four ACTIQ units per day.

Patients must be monitored by a health professional to ensure that the maximum intake of four ACTIQ units per day is not exceeded. >
Readjustment of the dose

The maintenance dose of ACTIQ should be increased if treatment of several consecutive paroxysmal pain attacks requires more than one tablet per access. For the adjustment of the dose, the same principles as those described for titration apply (see above).
If patients have more than 4 paroxysmal pain per day, it may be necessary to re-evaluate the dosage of the background morphine treatment. If this is increased, it may be necessary to readjust the ACTIQ dose used to treat paroxysmal pain.


Stop processing

In patients continuing their background morphine analgesic treatment, ACTIQ treatment can generally be immediately stopped when it is no longer needed.

On the other hand, in the case of suspension of the whole morphine treatment, the protocol of progressive arrest of the morphine must take into account the ACTIQ dosage to avoid the appearance of symptoms of abrupt withdrawal. >

Use in the subject, aged

Elderly subjects were found to be more sensitive to the effects of fentanyl administered intravenously. Therefore, titration imposes special precautions in these patients. Fentanyl is eliminated more slowly in the elderly and has a longer terminal half-life, which may result in an accumulation of the active ingredient and increase the risk of undesirable effects. >

No specific clinical studies have been conducted with ACTIQ in the elderly. However, during clinical studies, ACTIQ doses for effective relief of paroxysmal pain have been lower in elderly patients over the age of 65.

Use in patients with hepatic or renal impairment

Caution should be exercised during the titration phase in patients with renal or hepatic impairment (see Warnings and Precautions for Use).

Pediatric population

For children aged 16 years and older: follow the adult dosage

In children aged 2 to 16 years, clinical experience with the use of ACTIQ in pediatric patients in patients already receiving a background morphine treatment is limited (see sections Pharmacodynamic Properties and Pharmacokinetic Properties ). Safety and efficacy in patients under the age of 16 years have not been established, therefore the use in this population of patients is not recommended.

ACTIQ is in the form of a white-to-white compressed powder matrix, fixed with food glue, to an unbreakable radiopaque plastic applicator on which the dosage is entered.

Pharmaco-therapeutic class, ANALGESICS, opioids, phenylpiperidine derivatives, ATC code: N02A B03

Fentanyl, an agonist, pure morphinomimetic, acts primarily on the brain, spinal cord, and smooth muscle morphine receptors. The therapeutic effect is exerted mainly at the level of the central nervous system (CNS). Analgesia is the most useful clinical pharmacological effect resulting from the interaction of fentanyl on the μ receptors. This effect is correlated with the circulating blood levels of fentanyl, provided that the CNS penetration time and CNS disappearance time (a phenomenon with a half-life of 3 to 5 minutes) is considered. In subjects who had never received a morphine treatment, the analgesic effect appeared at blood concentrations of 1 to 2 ng / ml, whereas the surgical anesthetic effect associated with a deep respiratory depression occurred at Concentrations of 10 to 20 ng / ml.

In patients with cancer whose chronic pain was controlled by regular administration of stable doses of morphine, ACTIQ-induced paroxysmal pain relief was significantly greater than that of placebo, 15, 30, 45 And 60 minutes after the commencement of administration.

The adverse effects of morphine are increased tone and decreased contractions of the smooth muscles of the gastrointestinal tract. These two phenomena prolong the transit time, intestinal and may be responsible for constipation, related to morphine.

Although the morphine levels increase, usually the tonus of the smooth muscles of the urinary tract, the overall effect is variable: in some cases they cause a urge to urinate and in other cases dysuria.

All μ-receptor agonists, including fentanyl, induce dose-dependent respiratory depression. The risk of respiratory depression is lower in patients with pain and in those receiving treatment, with background morphine because of tolerance, respiratory depression and other effects, and morphine. In patients not treated with morphine, the maximum respiratory depression is generally observed 15 to 30 minutes after the start of ACTIQ administration and can last several hours.

Experience in the use of ACTIQ in pediatrics in patients under the age of 16 years is limited. In one clinical study, 15 patients (out of 38) aged 5 to 15 years, already receiving a background morphine treatment, and having paroxysmal pain had been treated with ACTIQ. The study size was too small to allow conclusions on the safety and efficacy of ACTIQ in this patient population

No studies have evaluated the effects of ACTIQ on the ability to drive and use machines, however, morphine analgesics are likely to alter the mental and / or physical abilities required for Performing potentially dangerous tasks (such as driving vehicles or using machines). Patients should be advised not to drive or use machinery if ACTIQ treatment causes them to become drowsy, dizzy, or blurred or double vision.

· Hypersensitivity to fentanyl or to any of the excipients of ACTIQ.

Patients receiving no morphine-based treatment (see section Therapeutic indications) due to an increased risk of respiratory depression

Treatment of acute pain other than painful pain (eg postoperative pain, headache, migraine)

· Concomitant or discontinued administration of monoamine oxidase inhibitors (MAOIs) for less than 2 weeks

· Severe respiratory depression or obstruction, severe airways

It is imperative to inform patients and their caregivers that ACTIQ contains an active substance at a dose that can be fatal to a child. Cases of death have been reported in children who had accidentally ingested ACTIQ

Patients and their caregivers should be informed of the need to keep all units out of the reach of children and to dispose of all units, whether used or not, as indicated below. In any ambulatory patient, it is recommended to evaluate the possible risks of accidental exposure of children to the medication.

ACTIQ should not be administered to patients who are not undergoing morphine-based background therapy because of a risk of increased respiratory depression that may be fatal Before starting ACTIQ treatment Should be stabilized and the patient should continue treatment with the morphine during the intake of ACTIQ

As with all morphinics, an addiction, a physical and / or psychological dependence and abuse of fentanyl are likely to appear. However, iatrogenic drug addiction is rare in the strictly therapeutic use of morphine drugs, the risks are considered to be low in cancer patients with painful and paroxysmal but may be higher, A history of substance abuse or alcohol addiction

Patients treated with morphine drugs should be monitored for signs of abuse or addiction

As with all morphine drugs, the use of ACTIQ exposes to a risk of clinically significant respiratory depression. Special caution is advised when titrating ACTIQ in patients with chronic obstructive pulmonary disease, or any other pre-existing pathology predisposing them to respiratory depression, since, even when administered at normal therapeutic doses , ACTIQ may aggravate respiratory problems, leading to respiratory insufficiency

ACTIQ should be administered with extreme caution in patients who may be particularly sensitive to the cerebral effects of hypercapnia, for example in patients with signs of hypertension, intracranial or consciousness disorders. The morphinics which may mask the clinical course in the case of head trauma should be used in this context only in cases of absolute clinical necessity.
When administered intravenously, fentanyl may cause bradycardia. Therefore, ACTIQ should be used with caution in case of bradyarrhythmia.


Treatment with ACTIQ should be considered with caution in the presence of hypovolemia or hypertension.


This medicinal product contains sucrose. Its use is discouraged in patients with fructose intolerance, glucose-galactose malabsorption syndrome or sucrase / isomaltase deficiency

Normal oral hygiene is recommended to reduce any harmful effects to the teeth. ACTIQ containing about 2 grams of glucose, one frequent use increases the risk of caries, dental. Dry mouth associated with morphine therapy may increase this risk.

ANSM alert of 25/09/13

In order to minimize the risk of adverse effects by determining the minimum effective dose for each patient, it is essential that the patient be closely monitored during the titration period of the treatment. Moreover, these specialties are not equivalent to one another. When replacing one with another, it is necessary to repeat the procedure of titration.

Fentanyl is metabolized by the CYP3A4 isoenzyme in the liver and intestinal mucosa.
Potent inhibitors of the isoenzyme, CYP3A4, such as macrolides (such as erythromycin), azole antifungals (such as ketoconazole, itraconazole and fluconazole), and certain protease inhibitors (such as ritonavir) , Increasing the bioavailability of the absorbed fentanyl oral and also decreasing its systemic clearance, thus causing increased and prolonged morphine effects.


Concomitant administration of CYP3A4 inducers may reduce the effectiveness of ACTIQ.

Concomitant administration of ACTIQ and other CNS depressants (other morphine, sedative or hypnotic, anesthetics, general, phenothiazines, tranquillizers, muscle relaxants, sedative antihistamines or alcohol) may potentiate the depressant effects of each product. >

Symptoms of withdrawal may occur in patients treated with ACTIQ after administration of morphine antagonists (such as naloxone), or mixed antagonist agonists / antagonists (eg, pentazocine, butorphanol, buprenorphine, nalbuphine).

Not applicable.

The symptoms to be expected in the case of overdose with ACTIQ are of the same nature as those observed after the intravenous administration of fentanyl or other morphine and result from its pharmacological action. The most serious adverse reactions are mental impairment, loss of consciousness, coma, cardiopulmonary arrest, respiratory depression, respiratory distress, and respiratory failure, which can result in death .

Measures to be taken immediately in the presence of a morphine overdose include the immediate removal of the ACTIQ unit from the patient's mouth if it is still with the applicator, Permeability of the respiratory tract, performing physical and verbal stimulations of the patient and determining his level of consciousness, as well as his ventilatory and circulatory state. Insert, if necessary, assisted ventilation.

Treatment of overdose in a person who has never received morphine therapy (accidental ingestion) requires a venous approach and administer naloxone or other morphine antagonist, Clinical condition. The duration of respiratory depression due to overdosage may be longer than the effects of the antagonist: morphine (eg, the half-life of naloxone is between 30 and 81 minutes) Necessary to repeat administration of the antidote.

For more details on the use of the morphine antagonist used, refer to the Summary of Product Characteristics in question.

In patients receiving treatment, well tolerated morphine, set up a route, first venous. In some cases, the judicious use of naloxone or other morphine antagonists may be warranted, but it is at risk of triggering an acute withdrawal syndrome.

Although it has never been described of muscular rigidity associated with respiratory depression after administration of ACTIQ, such a phenomenon is possible, with fentanyl or other morphinic. If such muscular stiffness occurs, it will be necessary to provide assisted ventilation, administer a morphine antagonist and, as a last resort, a curarizer.
There are no relevant data on the safety of fentanyl during pregnancy Animal studies have shown reproductive toxicity (see section Preclinical safety data). Morphine analgesics may cause respiratory depression in the newborn. Prolonged treatment during pregnancy is associated with a risk of withdrawal symptoms in the newborn. ACTIQ should only be used in pregnant women if it is clear that it is necessary

ACTIQ should not be used during delivery as fentanyl crosses the placental barrier and may cause respiratory depression in the fetus. The transplacental passage rate is 0.44 (feto-maternal ratio: 1.00 / 2.27) .Fentanyl is excreted in breast milk, therefore women should not breastfeed during Treatment with ACTIQ, due to the possibility of sedation and / or depression, respiratory in the infant. Breast-feeding should not be resumed for at least 24 hours after the last administration of fentanyl.
Typical side effects of morphine may be observed when taking ACTIQ. Most often, they disappear or decrease, intensity with the continuation of the treatment and the obtaining of the appropriate dosage

However, the most serious adverse effects are respiratory depression (which may result in apnea or respiratory arrest), circulatory depression, hypotension and shock, and patients should be carefully monitored to detect these Unwanted effects

Site-level administration reactions such as bleeding gums, local irritations, pain and ulcers have been reported since the marketing of ACTIQ.
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Clinical studies conducted with ACTIQ to evaluate the efficacy and tolerability of the product in the treatment of paroxysmal pain were included at the same time with other morphine-releasing morphine Prolonged or transdermal fentanyl) to treat their chronic pain. Therefore, it is not possible to isolate with certainty the adverse effects due to ACTIQ treatment alone

The following adverse reactions have been reported during clinical trials with ACTIQ and data reported since commercialization. The undesirable effects are listed below according to the MedDRA classification by organ class and frequency (frequencies are defined as follows: very common ≥ 1/10, common ≥; 1/100 to