SYNTHESIS |
flavoring: orange flavoring , sodium
NDE without threshold dose: benzyl alcohol , sulfite
SHAPES AND PRESENTATIONS |
Orodispersible tablet (white, round, convex, 5 mm in diameter, debossed with “1” on one side and plain on the other side).
Box of 14, in individual pre-cut plates.
COMPOSITION |
For an orodispersible tablet :
Morphine sulfate: 1 mg
Corresponding to 0.75 mg of morphine
Excipients with known effect :
Each orodispersible tablet contains:
- Benzyl alcohol (0.1 microgram/orodispersible tablet)
- Sulphites (3.5 nanograms/orodispersible tablet)
Mannitol, hydroxypropyl cellulose, microcrystalline cellulose, crospovidone type A, acesulfame potassium, orange flavor (including benzyl alcohol, sodium and sulphites), silicon dioxide, magnesium stearate.
| DC | DIRECTIONS |
Severe pain that can only be adequately treated with opioids.
| DC | WARNINGS AND PRECAUTIONS FOR USE |
Particularly careful medical supervision and, if necessary, dose reduction are recommended in the following cases:
- Opioid addiction, history of substance abuse,
- Impaired respiratory function,
- Respiratory depression (see below),
- Sleep Apnea,
- Pulmonary Heart,
- Conditions associated with increased intracranial pressure, in the absence of ventilation,
- altered consciousness,
- Hypotension accompanied by hypovolemia,
- Prostatic hyperplasia with bladder stasis (risk of bladder rupture due to urinary retention),
- Narrowing of the urinary tract or renal colic,
- Bile Duct Disorders,
- Obstructive and inflammatory bowel disease,
- Constipation,
- Pheochromocytoma,
- Adrenocortical Insufficiency,
- Pancreatitis,
- Severe impairment of renal function,
- Severe impairment of liver function,
- Hypothyroidism,
- Seizure disorders or predisposition to convulsions,
- Elderly patients.
Respiratory depression
The main risk in opioid overdose is respiratory depression.
Sleep Disordered Breathing
Opioids can cause sleep-disordered breathing, 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.
Risk related to the concomitant use of sedatives such as benzodiazepines or related drugs
Concomitant use of ACTISKENAN and sedative drugs such as benzodiazepines or related drugs may lead to sedation, respiratory depression, coma and death. Because of these risks, concomitant prescription with these sedative drugs should be reserved for patients for whom there are no other therapeutic options. If the decision is made to prescribe Actiskenan concomitantly with sedative drugs, the lowest effective dose should be used, and the duration of treatment should be as short as possible.
Patients should be closely monitored for signs and symptoms of respiratory depression and sedation. In this regard, it is strongly recommended to inform patients and their carers about the symptoms to watch out for (see section Interactions ).
Morphine has a similar abuse potential as other strong opioid agonists and should be used with caution in patients with a history of alcohol or drug abuse.
Addiction and withdrawal syndrome (abstinence)
The use of opioid analgesics may be associated with the development of physical and/or psychological dependence or tolerance. The longer the drug is used, the greater the risk. Similarly, higher doses increase the risk involved. Symptoms can be reduced as much as possible by adjusting the dose or pharmaceutical form and by gradually withdrawing from morphine. For individual symptoms, see section Undesirable effects .
The misuse of oral forms by parenteral injection can lead to serious adverse events that can be fatal.
Pre and postoperative use
ACTISKENAN should be used with caution pre- and postoperatively due to the increased risk of ileus or respiratory depression during the postoperative period compared to non-operated patients. Due to the analgesic effect of morphine, serious intra-abdominal complications such as intestinal perforation may be masked.
Patients scheduled for other pain relieving procedures (eg nerve block) should not receive ACTISKENAN within 4 hours of the procedure. If treatment with ACTISKENAN is indicated, the dose should be adjusted according to the new postoperative needs.
Hyperalgesia
Hyperalgesia unresponsive to further increase in morphine dose may occur, especially at high doses. A reduction in the morphine dose or a change in opioid may be necessary.
Adrenal insufficiency
Opioid analgesics may cause reversible adrenal insufficiency requiring monitoring and glucocorticoid replacement therapy. Adrenal insufficiency can be manifested by the following symptoms: nausea, vomiting, loss of appetite, fatigue, weakness, dizziness or low blood pressure.
Decreased sex hormones and increased prolactin
Opioids, such as morphine, may have a pharmacological action on the hypothalamic-pituitary or gonadal axis.
Long-term use of opioid painkillers may be associated with decreased levels of sex hormones and increased prolactin. Symptoms include: decreased libido, impotence or amenorrhea.
Acute Chest Syndrome (ATS) in Patients with Sickle Cell Disease
Due to a possible association between ATS and morphine use in patients with sickle cell disease receiving morphine treatment for vaso-occlusive crisis, affected patients should be closely monitored for the symptoms of ATS.
Concomitant use with rifampicin
Plasma morphine concentrations may be reduced by rifampicin. The analgesic effect of morphine should be monitored and morphine doses adjusted during and after rifampicin treatment.
Oral P2Y12 inhibitor antiplatelet therapy
A reduction in the efficacy of treatment with a P2Y12 inhibitor has been observed, from the first day of concomitant treatment with a P2Y12 inhibitor and morphine (see section Interactions ).
Excipients
This medicinal product contains 0.1 microgram of benzyl alcohol per orodispersible tablet.
Benzyl alcohol can cause allergic reactions.
This medication should not be used for more than a week in young children (under 3 years old).
High amounts should be used with caution and only when needed, especially in pregnant or breastfeeding women and in people with hepatic or renal impairment due to the risk of benzyl alcohol accumulation and toxicity (acidosis metabolic).
This medicine contains sulphites.
Sulfites can, in rare cases, cause severe hypersensitivity reactions and bronchospasm.
This medicinal product contains less than 1 mmol sodium (23 mg) per orodispersible tablet, i.e. essentially 'sodium free'.
| DC | FERTILITY / PREGNANCY / BREASTFEEDING |
Pregnancy
There are insufficient data in humans to assess a potential teratogenic risk. A possible link with an increased incidence of inguinal hernias has been reported. Morphine crosses the placental barrier. Animal studies have shown a risk of toxicity in offspring throughout gestation (see section Preclinical safety ). Morphine should therefore only be used during pregnancy if the benefit to the mother clearly outweighs the risk to the child.
Given the mutagenic properties of morphine, it should not be administered to men and women of childbearing potential in the absence of effective contraception.
Newborns whose mothers received opioid analgesics during pregnancy should be monitored for signs of neonatal withdrawal (abstinence) syndrome. Treatment may include the use of an opioid and supportive care.
Childbirth
Morphine can prolong or shorten the duration of labour. Newborns whose mothers received opioid analgesics during delivery should be observed for signs of respiratory depression or withdrawal syndrome and (if necessary) they should be treated with a specific opioid antagonist.
Feeding with milk
Morphine is excreted in breast milk, where it reaches concentrations higher than those found in maternal plasma. As clinically relevant concentrations may be achieved in breast-fed children, breast-feeding is not advised.
Fertility
Animal studies have shown that morphine may reduce fertility (see section Preclinical safety ).
| DC | DRIVING AND USING MACHINES |
Treatment with ACTISKENAN may cause sedation and it is not recommended to drive vehicles and use machines in case of drowsiness. This medicinal product may impair cognitive function and affect the ability to drive safely, mainly at the initiation of treatment, during dose modification and in combination with other central nervous system depressants such as alcohol or sedatives.
When the treatment is stable, driving is not strictly prohibited.
| DC | OVERDOSAGE |
Symptoms
Toxic doses vary widely from person to person, with a single dose leading to poisoning while regular users can tolerate high doses.
Signs of morphine toxicity and overdose are: pinpoint pupils (miosis), skeletal muscle flaccidity, bradycardia, hypotension, hypothermia, respiratory depression, aspiration pneumonitis, drowsiness, and nervous system depression center that may progress to a state of stupor or coma. Death may occur from respiratory failure. Circulatory failure and deep coma may occur in more severe cases. An overdose can be fatal. Rhabdomyolysis progressing to renal failure has been reported in the setting of opioid overdose.
Treatment of morphine overdose
The first measures should consist of opening the airways and initiating assisted or controlled ventilation.
Pure opioid antagonists are specific antidotes against the effects of opioid overdose. Other supportive measures should be used as needed.
In unconscious patients in respiratory arrest, ventilation, intubation, and intravenous administration of an opioid antagonist (eg, naloxone 0.4-2 mg IV) are indicated.
If respiratory failure persists, the dose should be repeated 1-3 times at three-minute intervals until the respiratory rate is normalized and the patient responds to painful stimuli.
Strict monitoring (at least 24 hours) is necessary because the effect of the opioid antagonist is shorter than that of morphine, and a resurgence of respiratory failure is therefore to be expected.
The dose of the opioid antagonist in children is 0.01 mg per kg body weight per dose.
Measures to prevent the risk of hypothermia and hypovolaemia may also be necessary.
Naloxone should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to morphine overdose. Naloxone should be administered with caution to persons with known or suspected physical dependence on morphine. In these cases, a sudden or complete reversal of the effects of the opioid can favor the appearance of an acute withdrawal syndrome.
Oral administration of activated charcoal (50 g for adults, 1 g/kg for children) may be considered in the event of ingestion of a large quantity less than one hour previously, provided that it is possible to protect the respiratory tracts.
| PP | PRECLINICAL SAFETY |
Non-clinical data from conventional studies of safety pharmacology and repeated-dose toxicology reveal no special hazard for humans.
Effects have been observed in animals at the level of genotoxicity and reproductive and developmental functions.
Mutagenic and tumorigenic potential
The results of the mutagenicity tests are clearly positive, indicating that morphine has a clastogenic effect and that this effect has an impact on gametes. Morphine must therefore be considered as a mutagenic substance and it can be assumed that this effect is also applicable to the human species.
No long-term studies have been conducted in animals on the tumorigenic potential of morphine.
Reproductive toxicity
Animal studies have shown a risk of toxicity in offspring throughout gestation (CNS malformations, growth retardation, testicular atrophy, changes in neurotransmitter systems and behavioral profiles, dependence).
In male rats, decreased fertility and chromosomal damage in gametes have been reported.
| DP | THE DURATION OF THE CONVERSATION |
36 months
| DP | SPECIAL STORAGE CONDITIONS |
Store in the original packaging in order to protect from light.
| DP | SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING |
Any unused medication or waste should be disposed of in accordance with applicable regulations.
PRESCRIPTION/ISSUE/CARE |
Prescription on secure prescriptions.
Prescription limited to 28 days.
| MA |
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| Price : |
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Remb Sec soc at 65% and Collect in the indications:
- intense pain and/or pain resistant to weaker analgesics, severe pain of cancerous origin, severe acute non-cancerous pain (post-operative pain), and severe chronic pain of neuropathic origin;
- intense and/or stubborn pain encountered in osteoarthritis of the knee or hip and in chronic low back pain, as a treatment of last resort, at a stage when surgical solutions are being considered and in non-candidate patients (refusal or counter- indication) to prosthetic replacement surgery (coxarthrosis or gonarthrosis), for the shortest possible duration due to the risk of serious adverse effects and the absence of long-term data.