Lunaldin - instructions for use, dose, side effects, contraindications

Excipients: mannitol 59.440 mg, microcrystalline colloidal cellulose 9.350 mg (98% cellulose microcrystalline and 2% silicon colloidal anhydrous), croscarmellose sodium 0.730 mg, magnesium stearate 0.350 mg.

Dosage of 0.2 mg:

active substance: fentanyl citrate micronized 0.3142 mg (equivalent to fentanyl 0.2 mg);

Excipients: mannitol 59.280 mg, microcrystalline colloidal cellulose 9.350 mg (98% cellulose microcrystalline and 2% silicon colloidal anhydrous), croscarmellose sodium 0.730 mg, magnesium stearate 0.350 mg.

Dosage of 0.3 mg:

active substance: fentanyl citrate micronized 0.4713 mg (equivalent to fentanyl 0.3 mg);

Excipients: mannitol 59.120 mg, microcrystalline colloidal cellulose 9.350 mg (98% cellulose microcrystalline and 2% silicon colloidal anhydrous), croscarmellose sodium 0.730 mg, magnesium stearate 0.350 mg.

Dosage of 0.4 mg:

active substance: fentanyl citrate micronized 0.6284 mg (equivalent to fentanyl 0.4 mg);

Excipients: mannitol 58.960 mg, microcrystalline colloidal cellulose 9.350 mg (98% cellulose microcrystalline and 2% silicon colloidal anhydrous), croscarmellose sodium 0.730 mg, magnesium stearate 0.350 mg.

Dosage of 0.6 mg:

active substance: fentanyl citrate micronized 0.9426 mg (equivalent to fentanyl 0.6 mg);

Excipients: mannitol 88.440 mg, microcrystalline colloidal cellulose 14,030 mg (98% microcrystalline cellulose and 2% colloidal anhydrous silicon), croscarmellose sodium 1.095 mg, magnesium stearate 0.525 mg.

Dosage of 0.8 mg:

active substance: fentanyl citrate micronized 1,2570 mg (equivalent to fentanyl 0.8 mg);

Excipients: mannitol 117.90 mg Colloidal microcrystalline cellulose 18.70 mg (98% microcrystalline cellulose and 2% colloidal anhydrous silica), sodium croscarmellose 1.460 mg magnesium stearate 0.700 mg.

Description:

Dosage of 0.1 mg: White round flat pills.

Dosage of 0.2 mg: White oval shaped flat tablets.

Dosage of 0.3 mg: White triangular flat tablets.

Dosage of 0.4 mg: White diamond-shaped flat tablets.

Dosage of 0.6 mg: White "Dshaped "flat tablets.

Dosage of 0.8 mg: White capsular shaped flat tablets.

Pharmacotherapeutic group:Analgesic narcotic drug

ATX: & nbsp

N.01.A.H.01 Fentanyl

Pharmacodynamics:

Lunaldine® is an effective, fast-acting, short-acting p-opioid analgesic. The main therapeutic effects of Lunaldina® are analgesic and sedative. The analgesic activity of Lunaldine® is approximately 100 times higher than that of morphine. Lunaldin® has typical opioid analgesic effect on the central nervous system (CNS), respiratory and gastro-intestinal system, drugs which is characteristic for this class.

It was shown that in oncological patients with pain receiving constant maintenance doses of opioids, fentanyl significantly reduces the intensity of the pain attack (15 minutes after application), compared with placebo, which significantly reduces the need for emergency analgesic therapy. The safety and effectiveness of fentanyl was evaluated in patients who received the drug immediately after the onset of pain. Preventive use of fentanyl in predictable pain attacks during clinical trials has not been studied. Lunaldin®, like all agonists of the μ-opioid receptors, causes a dose-dependent depressant effect on the respiratory center. The risk of respiratory depression is higher in people who have not previously received opioids, compared to patients who have experienced severe pain and received long-term treatment with opioids.

Opioids usually increase the tone of the smooth muscles of the urinary tract, causing either an increase in the frequency of urination, or difficulty urinating. Opioids increase the tone of the smooth muscles of the gastrointestinal tract (GIT), reduce intestinal motility, which can be due to the fixing effect of fentanyl.

Pharmacokinetics:

Fentanyl has pronounced lipophilic properties, is rapidly absorbed through the mucous membrane of the oral cavity and slightly slower through the gastrointestinal tract. When administered orally, it undergoes pronounced "first pass" effects through the liver and GI tract.

Lunaldine® in the form of sublingual tablets dissolves well. Rapid absorption of fentanyl occurs within about 30 minutes after taking the drug. Bioavailability of fentanyl is not well understood, but it is estimated at about 70%. The maximum plasma concentration of fentanyl is 0.2 to 1.3 ng / ml (after the administration of 100 - 800 μg of the drug) and is achieved within 22.5 - 240 minutes.

The analgesic effect of the drug is related to the concentration of the active substance in the blood plasma. In patients who have not previously taken opioids, the minimum effective plasma concentrations of fentanyl, which cause analgesia, are 0.3-1.2 ng / ml. Levels of concentration of 10-20 ng / ml is the concentration of fentanyl in blood plasma at different types of anesthesia during surgical operations and concentration levels of 10-20 ng / ml can cause pronounced respiratory depression.

Approximately 80-85% of fentanyl binds to plasma proteins, mainly α1-glycoprotein, and to a lesser extent - albumins and lipoproteins.The volume of fentanyl distribution in the equilibrium state is 3-6 l / kg. Metabolised in the liver, mainly with the participation of enzymes CYP3A4 to metabolites. The main metabolite of fentanyl is norfentanil, which is not active.

It is excreted by the kidneys (75% - in the form of metabolites and 10% - in unchanged form) and with bile (9% - in the form of metabolites).

The total clearance of fentanyl is approximately 0.5 l / h / kg. The half-life of fentanyl is about 7 hours (from 3 to 12.5 hours), and the final half-life is about 20 hours (11.5 to 25 hours).

It was shown that fentanyl concentration in plasma is directly proportional to the dose of the drug in the range from 100 to 800 μg.

Impaired renal / hepatic function. Violation of the function of the liver or kidney can cause an increase in the concentration of the drug in the plasma.

In elderly, debilitated and debilitated patients fentanyl clearance can be reduced, which is the reason for an increase in the final half-life of the substance.

Indications:Treatment of pain episodes in patients with chronic pain syndrome caused by oncological disease, and receiving constant therapy with opioids.

Contraindications:

- Hypersensitivity to the active substance or to any of the auxiliary substances;

- andBecause of the risk of life-threatening respiratory depression, Lunaldine® is contraindicated in patients who have not previously received opioid therapy;

- fromConditions characterized by severe respiratory depression or severe obstructive pulmonary disease;

- atozrast to 18 years.

Carefully:

The use of all opioids, including Lunaldine®, is associated with a risk of clinically significant respiratory depression. Particular care should be taken when titrating the dose of Lunaldine® in patients with chronic obstructive pulmonary disease or other conditions contributing to respiratory depression (eg, myasthenia gravis), because of the risk of further respiratory depression, which can lead to respiratory failure.

Lunaldine® should be used with extreme caution in patients who may be particularly susceptible to hypercapnia: with increased intracranial pressure, impaired consciousness, coma, or brain tumor.

In patients with head injuries, the clinical picture can be masked by the use of opioids. In these cases, opioid drugs should be used only in absolute indications.

Determined that fentanyl can cause a bradycardia. Lunaldine® should be used with caution in patients with bradyarrhythmia.

Lunaldine® should be used with caution in patients with impaired hepatic or renal function, especially at the titration stage of the dose. The use of Lunaldine® in patients with hepatic or renal insufficiency can increase the bioavailability of fentanyl and reduce its systemic clearance, which can lead to its accumulation and increase / prolongation of action.

Care should be taken when treating patients with hypovolemia and arterial hypotension.

The use of Lunaldine® has not been studied in patients with damage or inflammation of the oral mucosa. In such patients, there is a risk of increased systemic exposure to the drug, therefore, it is recommended that special care be taken during the titration phase of the dose.

Pregnancy and lactation:

Safety of Lunaldine® during pregnancy is not established. Long-term treatment during pregnancy can cause symptoms of "cancellation" in a newborn. Lunaldine® should not be used during labor (including caesarean section) because it penetrates the placenta and can cause respiratory depression in the fetus or newborn.

During pregnancy, Lunaldin® can be used only if the potential benefit to the mother exceeds the possible risk to the fetus.

Lunaldine® is distributed into breast milk and may cause sedation and respiratory depression in children with breastfeeding: Lunaldine® may be used in nursing women only if the benefits of taking the drug are significantly greater than the potential risk to the mother and child. It is recommended to stop breastfeeding while taking the drug.

Dosing and Administration:

Lunaldine® should be given only to patients who are considered tolerant to opioid therapy, used for permanent pain caused by cancer. Patients are considered to be tolerant to opioids if they take at least 60 mg of morphine per day orally, 25 mcg of fentanyl per hour, percutaneously or an equivalent analgesic dose of another opioid for a week or more.

Lulandina® sublingual tablets are placed directly under the tongue as deep as possible. Lunaldine® tablets should not be swallowed, chewed, or absorbed; the drug must completely dissolve in the hyoid area.Patients are advised not to eat or drink until the sublingual tablet completely dissolves.

Patients experiencing dry mouth, before taking Lunaldina can use water to moisturize the oral mucosa.

Dose titration

The optimal dose of Lunaldine® is determined for each patient individually by selection with a gradual increase in dose. To select the dose you can use tablets with different contents of the active substance. The initial dose of Lunaldine® should be 100 μg, during titration it is gradually increased as needed in the range of existing doses.

During the titration of the dose, patients should be carefully monitored until the optimal dose is reached, i.e., before the proper analgesic effect is achieved.

Transition from other fentanyl-containing preparations to Lunaldine® should not be carried out at a ratio of 1: 1 due to different absorption profiles of the drugs. If patients are switching from other fentanyl-containing drugs, titration with Lunaldine® should be performed.

For the choice of doses, the following regimen is recommended, although in all cases the attending physician should take into account the patient's clinical needs, age and concomitant diseases.

All patients should begin treatment with one sublingual tablet of 100 mcg.

If a sufficient analgesic effect is not achieved within 15-30 minutes after taking one sublingual tablet, a second tablet of 100 μg can be taken. If after taking 2 tablets of 100 mcg enough anesthesia is not achieved, consider increasing the dose to the next dose of the drug at the next episode of pain. Increase the dose should be carried out gradually until sufficient pain relief is achieved. Titration of the dose should begin with the administration of a sublingual tablet. The second additional sublingual tablet should be taken after 15-30 minutes if sufficient anesthesia is not achieved. The dose of an additional sublingual tablet should be increased from 100 to 200 μg and then to a dose of 400 μg or more. This is illustrated in the diagram below. At the stage of dose selection by titration, no more than two (2) sublingual tablets should be used for one episode of a pain attack.

The dose (μg) of the first sublingual tablet for an episode of a pain attack	The dose (μg) of an additional (second) sublingual tablet, which, if necessary, should be taken 15-30 minutes after the first tablet
100	100
200	100
300	100
400	200
600	200
800	-

If sufficient anesthesia is achieved at a higher dose, but unwanted effects are considered unacceptable, an intermediate dose can be given (using a sublingual tablet of 100 μg).

Doses of more than 800 μg in clinical trials have not been evaluated.

To minimize the risk of adverse reactions associated with taking opioids and determining the optimal dose, careful medical observation of the patient's condition during titration of the dose is necessary.

Supportive treatment

After determining the optimal dose, which may be more than one tablet, patients undergo maintenance treatment with a selected dose and limit the use of the drug to a maximum of four doses of Lunaldine® per day.

Correction of dose

If the reaction (anesthesia or unwanted reactions) to a matched dose of Lunaldine® is significantly altered, dose adjustment may be required to maintain the optimal dose. If there are more than four episodes of pain per day for more than four consecutive days, the dose of opioids of prolonged action used to relieve persistent pain should be adjusted.If a long-acting opioid drug is substituted or its dose is changed, recalculate and titrate the dose of Lunaldina® to select the optimal dose for the patient.

Repeated titration and selection of a dose of pain medication should be done under the supervision of a doctor.

Discontinuation of treatment

If the patient no longer needs to take opioids, the dose of Lunaldine® should be taken into account before starting a gradual reduction in the dose of opioids to minimize possible "cancellation" effects.

If patients continue to take opioids permanently for the treatment of chronic pain, but no longer need treatment for pain, Lunaldine® may be discontinued immediately.

Application in children and adolescents

Lunaldine® should not be used in patients younger than 18 years due to insufficient safety and efficacy data.

Application in elderly patients

Titration of the dose should be carried out with extreme caution. Patients should carefully monitor the appearance of signs of fentanyl toxicity.

Application the patients with impaired renal or hepatic function

Patients with impaired liver or kidney function should be carefully observed for signs of fentanyl toxicity during the titration phase of Lunaldina®.

Instructions for the use of tablets Lunaldin®

In case of an attack of pain, take the drug as prescribed by your doctor. To do this, follow the recommendations below for opening the package:

- Do not try to squeeze Lunaldin's tablet through the foil, as this will destroy it. Tablets should be removed from the package only with dry hands.

Important: Do not open the packaging unnecessarily.

- The drug Lunaldii comes packed in a blister for 10 tablets, each of which is in a separate cell. In order to remove the tablet, you need to tear off one cell. For convenience, the tear lines are perforated.

- After the cell with the tablet is torn off, carefully peel off the foil, starting from the side with the red stripe. Then gently take the tablet with your fingers.

Side effects:

When applying Lunaldina®, undesirable reactions typical for opioids should be expected; The intensity of these reactions, as a rule, tends to decrease with prolonged use.

The most serious potential adverse reactions associated with the use of opioids are respiratory depression (which can lead to the stopping of breathing), lowering of blood pressure and shock.

From the respiratory system: more often - respiratory depression, hypoventilation, until the respiratory arrest.

From the nervous system and sense organs: more often - headache, drowsiness; less often - CNS depression (including after surgery), paradoxical CNS excitation, delirium, convulsions, blurred vision, diplopia, bright dreams, memory loss; frequency not established - confusion, euphoria, hallucinations, headache, intracranial hypertension.

From the digestive system: more often - nausea, vomiting; less often - flatulence, spasm of the sphincter of Oddi, slowing the emptying of the stomach, constipation, biliary colic (in patients who had them in history).

From the cardiovascular system: more often - a bradycardia, lowering of arterial pressure; less often - oppression of the cardiovascular system, right up to cardiac arrest.

From the side of the urinary system: spasm of ureters, retention of urine.

Allergic reactions: less often - allergic dermatitis, laryngospasm, chills, pruritus, bronchospasm.

Other: short-term stiffness of the muscles (including breast), increased sweating, drug dependence, withdrawal syndrome (vague pain, diarrhea, palpitation, rhinitis, sneezing, goose, skin, sweating, anorexia, nausea, vomiting, nervousness, fatigue , irritability, trembling, dilated pupils, general weakness), tolerance.

Overdose:

Symptoms: dizziness, drowsiness, nervousness, general weakness, oppression of the cardiovascular system, lowering of arterial pressure, bradycardia, sticky sweat, miosis, rigidity of muscles, respiratory center depression, bradypnoea, apnea.

Treatment: introduction of a specific antagonist - naloxone; symptomatic and supporting vital functions of therapy (including, the introduction of muscle relaxants, artificial ventilation of the lungs (IVL), with bradycardia - the introduction of atropine, with a marked decrease in blood pressure - replenishment of the volume of circulating blood).

Interaction:

Dinitrogen oxide increases muscle rigidity; tricyclic antidepressants, opioids, sedatives and hypnotics drugs (PM), phenothiazines, antianxiety drugs (anxiolytics), drugs for general anesthesia and peripheral muscle relaxants, antihistamines drug having sedative effects, ethanol deprimiruyuschie and other drugs increase the likelihood of side effects (CNS depression, hypoventilation, hypotension, bradycardia, suppression of the respiratory center and others).

Strengthens the effect of antihypertensive drugs. Beta-adrenoblockers can reduce the frequency and severity of hypertensive reaction in cardiac surgery (including sternotomy), but increase the risk of bradycardia.

Buprenorphine, nalboufine, pentazocine, naloxone, naltrexone reduce the analgesic effect of fentanyl and eliminate its depressing effect on the respiratory center.

Benzodiazepines prolong the yield of neuroleptanalgesia.

It is necessary to reduce the dose of fentanyl with simultaneous use with insulin, glucocorticosteroids, hypotensive drugs.

MAO inhibitors increase the risk of serious complications.

Muscle relaxants prevent or eliminate muscle rigidity; muscle relaxants withm-cholinoblocking activity (including pancuronium bromide) reduce the risk of bradycardia and hypotension (especially when using beta-blockers and other vasodilators) and may increase the risk of tachycardia and hypertension; muscle relaxants that do not possess m-cholinoblocking activity (including suxamethonium) do not reduce the risk of bradycardia and arterial hypotension (especially in the background of an aggravated cardiological history) and increase the risk of serious side effects from the cardiovascular system.

Special instructions:

Because of the possible serious side effects that can occur with treatment with opioids such as Lunaldine®, patients and caregivers should be fully aware of the importance of the correct administration of Lunaldine®, and also know what actions should be taken when symptoms of an overdose appear.

Before starting treatment with Lunaldin®, it is important to stabilize the use of long-acting opioids, used to relieve persistent pain.

With the repeated use of opioids, such as Lunaldin®, tolerance and physical and / or psychological dependence may develop.

Cases of iatrogenic dependence after the therapeutic use of opioids are extremely rare.

Data from studies of fentanyl indicate a decrease in its clearance, an increase in the half-life and greater sensitivity to fentanyl in elderly patients compared with young people. Fentanyl toxicity in elderly, debilitated or debilitated patients should be monitored continuously and, if necessary, lowered.

Effect on the ability to drive transp. cf. and fur:

Lunaldine® may adversely affect the ability to perform potentially dangerous operations, such as driving a vehicle or using mechanisms.

Patients should be advised to refrain from driving and controlling machinery, as dizziness, drowsiness, or visual impairment may occur when taking Lunaldin®.

Form release / dosage:

Tablets are sublingual, 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.6 mg and 0.8 mg.

Packaging:

For 10 tablets per blister of PA / PVC / Al / PE / paper.

For 1 or 3 blisters together with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

List II.In accordance with the Federal Law of the Russian Federation "On Narcotic Drugs and Psychotropic Substances".

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000265

Date of registration:16.02.2011

Expiration Date:16.02.2016

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

RESYFARM AB Sweden

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp20.03.2018

Illustrated instructions

Instructions

Lunaldin® (Lunaldin® )