Matrifen

Matrifen is a category of opiate medicines.

[1], [2], [3], [4]

Indications of the matriphene

It is used to eliminate chronic pain syndrome (in severe form), which can be suppressed exclusively with the help of opiates.

Release form

The release takes place in the form of a patch (transdermal therapeutic system), which is packaged in special bags, 1, 3, 5, 10 or 20 such packets inside the pack.

Pharmacodynamics

Matryfen is a transdermal patch that ensures a constant penetration of the fentanyl substance into the body. This component belongs to the group of opiates, showing an affinity mainly for μ receptors. The main medicinal properties of the drug are sedative and analgesic.

Pharmacokinetics

The transdermal patch promotes the progressive systemic penetration of fentanyl into the body (this period takes more than 72 hours). The release time of the component in accordance with the processed area of the body is:

• 12.5 μg / h - 4.2 cm ²;
• 25 μg / h - 8.4 cm ²;
• 50 μg / hour - 16.8 cm ²;
• 75 μg / hour - 25.2 cm ²;
• 100 μg / hr - 33.6 cm ².

Absorption.

After the first application of the therapeutic patch, the serum fentanyl values increase gradually, often evening around 12-24 hours, and then remaining within these parameters throughout the remaining lifetime of the drug (the total period is 72 hours).

After using the second application inside the serum, the equilibrium parameters of the drug are observed, which persist until the new patch (the same size) is applied.

Absorption of fentanyl may be slightly different at different sites of application. A slightly reduced rate of absorption of the substance (about 25%) was noted during the tests performed with the participation of volunteers. The applications were made in the sternum, and compared with the absorption values for the treatment of the back and upper arm.

Distribution.

The protein synthesis of fentanyl in the blood plasma is 84%.

Biotransformation.

The active ingredient has linear pharmacokinetics, and its metabolism mainly occurs inside the liver with the participation of the element CYP3A4. The main product of decomposition is the inactive component of norfentanil.

Excretion.

After removing the therapeutic patch, the decrease in serum fentanyl values occurs gradually - approximately 50% for 13-22 hours (in an adult) or 22-25 hours (for a child). Continued absorption of the drug from the skin surface slows the process of removing the substance from the serum (compared to the same process after IV injection). Approximately 75% of drugs are excreted in urine (most are in the form of decay products, in unchanged form less than 10% is output). Approximately 9% of the dosage is excreted with feces (mainly as decay products).

Dosing and administration

During the first use of drugs, the dosage (the size of the system used) is selected taking into account the level of patient's tolerance to the drug and the state of its health, the previous use of opiates, and the severity of pathology and concomitant therapy with the use of drugs.

People who have not previously used narcotic analgesics, first prescribe a dosage that does not exceed 25 mcg / h.

During the transition from parenteral or internal use of opiates to therapy with fentanyl, the initial dosage should be selected. First you need to calculate the size of the dose of painkillers that have been used in the last 24 hours, and then transfer the resulting amount to a suitable portion of morphine, using the data given below.

Portions of drugs that are similar to analgesia in their effects:

• morphine: when administered in / m - 10 mg; with the introduction of p / o - 30 mg (if it is a regular procedure) and 60 mg (if it is a one-time or intermittent injection);
• hydromorphone: introduction in / m - 1.5 mg; introduction of p / o - 7.5 mg;
• methadone: intramuscular injection - 10 mg; n / o administration - 20 mg;
• oxycodone: IM injection - 10-15 mg; p / o administration - 20-30 mg;
• levorphanol: IM method - 2 mg; p / o method - 4 mg;
• oxymorhin: in the / m way - 1 mg; n / o method - 10 mg (rectal procedure);
• dimorphin: administration in / m - 5 mg; introduction p / o - 60 mg;
• pethidine: IM injection - 75 mg;
• codeine: administration of p / o - 200 mg;
• buprenorphine: IM injection - 0.4 mg; n / o administration - 0.8 mg (sublingual method);
• ketobemidone: IM method - 10 mg; p / o method - 30 mg.

The initial dosage of Matryfen, which is calculated taking into account the daily oral portion of morphine:

• with a daily portion of morphine (orally) less than 135 mg / day - Matryfen at a dosage of 25 mcg / h;
• The daily portion of morphine in the range of 135-224 mg - the dose of Matryfen is 50 μg / h;
• a daily portion of morphine within 225-314 mg - the dose size of Matryfen is equal to 75 μg / h;
• a daily portion of morphine within the limits of 315-404 mg - Matryfen in a dose of 100 mcg / h;
• dosage of morphine within 405-494 mg / day - the dose of Matryfen is 125 μg / h;
• at reception for a day within 495-584-мг mg of morphine - the size of a dose of Matriphenum is equal 150 mkg / hour;
• consumption per day 585-674-mg mg of morphine - the size of the dose of the patch - 175 mcg / h;
• use per day 675-764-mg mg of morphine - a dose of plaster - 200 mcg / h;
• use of 765-854 mg / day of morphine - the size of the dosage of the patch is 225 μg / h;
• dose per day within 855-944 mg of morphine - patch at a dose of 250 mcg / h;
• a portion of morphine within 945-1034 mg / day - Matryfen in the amount of 275 μg / h;
• a daily dose of morphine in the range 1035-1124 mg - Matryfen patch at a dose of 300 mcg / h.

Assess the initial peak analgesic effect of the drug can be at least 24 hours after the application. This is due to the fact that the increase in serum fentanyl values during the first 24 hours is carried out gradually.

To make a successful transition from one medication to another, it is required to cancel the previous anesthetic course gradually after the application of the initial dosage of the patch - until the stabilizing of its analgesic effect occurs.

Selection of dosage sizes and the process of maintenance treatment.

Change transdermal patches is required at intervals of 72 hours. Dosages are selected for each individual patient, taking into account the indices of achieving the required analgesic level. With a noticeable weakening of the analgesic effect after 48 hours, the patch can be replaced in this time interval. In the absence of an adequate analgesic effect after using the first application, it is necessary to begin increasing the dosage 3 days later, and do this until the right analgesic effect is achieved.

Often, a single dose is increased by 12.5 or 25 mcg / h, but the condition in which the patient is present should be taken into account, as well as the need for additional therapy. To obtain a dosage greater than 100 μg / h, several medical patches can be applied simultaneously. In some patients, there may be a need for additional or alternative methods of administering opiates in the case of a dosage of the patch exceeding 300 μg / h.

During the transition from prolonged use of morphine to fentanyl, the development of withdrawal syndrome is possible, even despite the adequate analgesic effect. When developing such a disorder, small doses of morphine with short-term exposure are required.

[5]

Use of the matriphene during pregnancy

There is no information on the safety of the use of transdermal patches with fentanyl in pregnant women. Tests on animals have revealed the presence of toxic effects on the reproductive system. A possible risk for a person is not known, but it was noted that an anesthetic IV fentanyl is able to pass through the human placenta.

Continued use of Matryfen in pregnant women can lead to the development of a newborn abstinence syndrome.

It is forbidden to apply the plaster during fights or during the delivery (this includes the procedure of caesarean section), because the active substance penetrates the placenta and can provoke the inhibition of respiratory processes in the fetus or the newborn baby.

Fentanyl falls into the mother's milk and can provoke a sedative effect on the baby or lead to the suppression of its respiratory activity. Because of this, you must stop breastfeeding while you use Matryfen.

Contraindications

Among the contraindications:

• infants up to 2 years of age;
• increased sensitivity to elements contained in the patch;
• it is forbidden to use to eliminate acute pain (or arising in the postoperative period), therefore, how to choose a dosage in a short time will not work, and this increases the risk of suppression of respiratory function, which can be life-threatening;
• with severe forms of respiratory depression;
• with lesions of the central nervous system in a severe degree;
• in combination with MAOI or in the case of their use in a period of less than 2 weeks before using Matryfen.

Side effects of the matriphene

The most dangerous side effect of the drug is the suppression of respiratory activity. In addition, there may appear:

Disorders of the psyche: most often there is a feeling of drowsiness. Often, a feeling of anxiety, confusion, nervousness develops, and in addition, a state of depression, sedation, impaired appetite and hallucinations. Sometimes there is amnesia, a state of agitation, euphoria or insomnia. There is a single appearance of asthenia, a state of delusions and problems with sexual function;

Lesions of central nervous system: most often there are headaches and a feeling of drowsiness. Sometimes paresthesia develops with tremors and problems with speech. Single mark myoclonic seizures of a non-epileptic nature, as well as ataxia;

Reactions from the visual organs: occasionally develops amblyopia;

Disturbances of function SSS: sometimes there is a tachycardia or a bradycardia, and also pressure increases / decreases. Occasionally, vasodilation or arrhythmia is noted;

Problems in the work of the respiratory system: sometimes mark hypoventilation or dyspnea. Apnea, pharyngitis or hemoptysis occurs sporadically, and in addition to this there is suppression of respiratory processes, laryngospasm and pulmonary obstruction;

Disorders of the digestive tract: most often noted vomiting with nausea and constipation. Often there are dyspeptic manifestations or xerostomia. Sometimes diarrhea begins. Occasionally hiccups develop. Single swelling or intestinal obstruction is observed;

Immune manifestations: anaphylaxis develops sporadically;

Lesions of the subcutaneous layer and skin surface: most often develops hyperhidrosis or itching. In addition, local skin manifestations are often observed. Sometimes there is erythema or rash. Erythema with pruritus, as well as the rash mainly pass after the day after removal of the plaster;

Disorders of the function of the urination system and kidneys: sometimes notice a delay in urination. Single pains in urea or oliguria are observed;

Systemic lesions: occasionally a feeling of cold or swelling develops;

Other violations: in the case of prolonged use of the patch, there may be tolerance in relation to drugs, and in addition dependence of a mental and physical nature. Symptoms of abstinence caused by opiates (such as vomiting, tremor, nausea, diarrhea and anxiety) appear as a result of switching from previously used narcotic analgesics to Matrifen.

Overdose

Signs of poisoning: an overdose of the drug develops in the form of prolonging its medicinal effects - such symptoms as a coma, a feeling of inhibition and suppression of respiratory activity with periodic breathing or cyanosis. Among other manifestations - weakened muscle tone, hypothermia with hypotension, as well as bradycardia. Symptoms of toxicity - the development of deep sedation, miosis, ataxia, convulsions, and in addition suppression of respiratory function (this is the main feature).

To cope with the suppression of respiratory activity, immediate measures are required, which include the removal of the band-aid, and in addition a verbal or physical effect on the victim. Further, he is required to administer a substance called naloxone, which is a specific antagonist of opiates.

Adults first need to enter 0.4-2 mg of naloxone hydrochloride intravenously. If there is such a need, this dose is administered every 2-3 minutes, or instead a long injection of 2 mg of the drug is made, which is diluted in a 0.9% solution of sodium chloride (500 ml) or 5% dextrose solution (volume 0.004 mg / ml). The speed of the ongoing injection should be adjusted, taking into account previously performed bolus infusions, as well as the reaction of the victim.

If it is not possible to perform an IV injection, it is permitted to administer the agent n / c or in the / m way. When naloxone is administered by such methods, the onset of its effect will be slowed down in comparison with the intravenous injection. But at the same time, the IM prolongs the time of exposure to the drug.

Suppression of respiratory function due to intoxication with fentanyl may last longer than that of naloxone. When removing the narcotic effect, acute pain may increase, and in addition to this, release of catecholamines begins. It is very important to conduct the correct intensive treatment, if such a need arises.

With a significant decrease in pressure (lasting for a long time), it is necessary to take into account hypovolemia, and monitor the health by injecting the required volumes of liquid parenterally.

Interactions with other drugs

When combined with other drugs that depress the function of the central nervous system (this includes tranquilizers, sedative and hypnotic drugs, opioids, muscle relaxants with systemic anesthetics, antihistamines of sedative type and fentiazines with alcoholic beverages), it is possible to develop an additive sedative effect. In addition, hypotension with hypoventilation may occur, as well as deep sedation or a coma condition. Therefore, with the simultaneous use of the above medicines with Matryfen it is necessary to constantly monitor the patient's condition.

Fentanyl is a substance with a high level of clearance. It is rapidly and in large amounts subjected to metabolism (mainly with the participation of hemoprotein CYP3A4).

When combining the transdermal form of fentanyl with LS, which slows the activity of the element CYP3A4 (amongst such ketoconazole, voriconazole and fluconazole with ritonavir, and besides itraconazole, clarithromycin, diltiazem with trolleandomisin, nefazodone with amiodarone and nelfinavir with verapamil), the plasma level of the active ingredient of Matryfen may increase. Because of this, the drug effect of the drug may be potentiated or lengthened. In addition, a similar reaction can show side effects, which can cause suppression of respiratory activity in severe degree. In such cases, you need to provide the best care and very carefully monitor the condition of a person. It is forbidden to combine such medicines if there is no possibility to provide constant close monitoring of the patient.

The transdermal patch is forbidden to appoint to persons who need simultaneous application of MAOI. There is evidence that MAOIs are potentiating the effects of opiates, especially in people with heart failure. Because of this, it is forbidden to use fentanyl for 2 weeks after the abolition of therapy with the use of MAOI.

It is forbidden to combine Matryfen with nalbuphine and buprenorphine, as well as pentazocine. These substances act as partial antagonists of individual drug effects (such as analgesia) and can lead to the appearance of withdrawal symptoms in people who are addicted to opiates.

[6]

Storage conditions

Matrifen is required to be kept out of reach of small children. The temperature should not exceed 25 ° C.

[7]

Shelf life

Matryfen is allowed to be used for 2 years from the date of manufacture of the medical plaster.