Matrifen

Matrifen belongs to the opiate drug category.

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Indications Matrifena

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

Release form

It is released in the form of a patch (transdermal treatment system), which is packaged in special packages, 1, 3, 5, 10 or 20 such packages inside a pack.

Pharmacodynamics

Matrifen is a transdermal patch that provides continuous penetration of the substance fentanyl into the body. This component is part of the opiate group, demonstrating affinity mainly for µ-receptors. The main medicinal properties of the drug are sedative and analgesic.

Pharmacokinetics

The transdermal patch facilitates 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 treated area of the body is:

• 12.5 mcg/hour – 4.2 ^cm2;
• 25 mcg/hour – 8.4 ^cm2;
• 50 mcg/hour – 16.8 ^cm2;
• 75 mcg/hour – 25.2 ^cm2;
• 100 mcg/hour – 33.6 ^cm2.

Absorption.

After the first application of the medicated patch, serum fentanyl levels increase gradually, often leveling off at approximately 12-24 hours, and then remaining within these levels for the remainder of the drug's duration of action (the total period is 72 hours).

After using the 2nd application, equilibrium drug levels are observed within the serum, which remain until a new patch (of the same size) is applied.

Absorption of fentanyl may vary slightly at different application sites. A slightly lower absorption rate (about 25%) was observed in tests performed on volunteers. Applications were made to the sternum area and compared with absorption rates when treating the back and upper arm.

Distribution.

Protein synthesis of fentanyl in blood plasma is 84%.

Biotransformation.

The active component exhibits linear pharmacokinetics and its metabolism occurs mainly in the liver with the participation of the CYP3A4 element. The main breakdown product is the inactive component norfentanyl.

Withdrawal.

After removal of the medicated patch, serum fentanyl levels decrease gradually – by approximately 50% over 13-22 hours (in adults) or 22-25 hours (in children). Continued absorption of the drug from the skin surface slows down the process of elimination of the substance from the serum (compared to the same process after intravenous injection). Approximately 75% of the drug is excreted in the urine (most of it in the form of breakdown products; less than 10% is excreted unchanged). Approximately 9% of the dosage is excreted in the feces (mainly as breakdown products).

Dosing and administration

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

People who have not used narcotic analgesics before are initially prescribed a dosage that does not exceed 25 mcg/hour.

When switching from parenteral or oral opiates to fentanyl therapy, the initial dosage must be adjusted. First, calculate the dose of painkillers used in the last 24 hours and then convert this amount to the appropriate dose of morphine using the information below.

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

• morphine: when administered intramuscularly - 10 mg; when administered orally - 30 mg (if these are regular procedures) and 60 mg (if this is a single or intermittent injection);
• hydromorphone: intramuscular injection – 1.5 mg; oral injection – 7.5 mg;
• methadone: intramuscular injection – 10 mg; oral injection – 20 mg;
• oxycodone: intramuscular injection – 10-15 mg; oral injection – 20-30 mg;
• levorphanol: i/m method – 2 mg; p/o method – 4 mg;
• oxymorphine: intramuscular route – 1 mg; p/o route – 10 mg (rectal procedure);
• dimorphine: intramuscular injection – 5 mg; oral injection – 60 mg;
• pethidine: intramuscular injection – 75 mg;
• codeine: oral administration – 200 mg;
• buprenorphine: intramuscular administration – 0.4 mg; sublingual administration – 0.8 mg;
• ketobemidone: i/m method – 10 mg; p/o method – 30 mg.

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

• if the daily dose of morphine (orally) is less than 135 mg/day – Matrifen at a dosage of 25 mcg/hour;
• daily dose of morphine within 135-224 mg – the dose of Matrifen is 50 mcg/hour;
• daily dose of morphine within 225-314 mg – the dose of Matrifen is 75 mcg/hour;
• daily dose of morphine within the range of 315-404 mg – Matrifen at a dose of 100 mcg/hour;
• morphine dosages within 405-494 mg/day – the dose of Matrifen is 125 mcg/hour;
• when taking 495-584 mg of morphine per day, the dose of Matrifen is 150 mcg/hour;
• daily consumption of 585-674 mg of morphine – patch dose size is 175 mcg/hour;
• use of 675-764 mg of morphine per day – patch dose – 200 mcg/hour;
• use of 765-854 mg/day of morphine – patch dosage size is 225 mcg/hour;
• daily dose within 855-944 mg of morphine - patch at a dose of 250 mcg/hour;
• a dose of morphine within the range of 945-1034 mg/day – Matrifen at a rate of 275 mcg/hour;
• daily dose of morphine within 1035-1124 mg – Matrifen patch at a dose of 300 mcg/hour.

The initial indicators of the peak analgesic effect of the drug can be assessed 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 gradual.

To successfully switch from one medication to another, it is necessary to gradually discontinue the previous pain-relieving course after applying the initial dose of the patch – until its analgesic effect stabilizes.

Selection of dosage sizes and the process of maintenance treatment.

Transdermal patches must be changed at intervals of 72 hours. Dosages are selected for each individual patient, taking into account the indicators of achieving the required analgesic level. If the analgesic effect is noticeably weakened after 48 hours, the patch can be replaced during this period. If there is no adequate analgesic effect after using the first application, it is necessary to start increasing the dosage after 3 days, and do this until the desired analgesic effect is achieved.

Often, the single dose is increased by 12.5 or 25 mcg/hour, but the patient's condition and the need for additional therapy should be taken into account. To obtain a dose greater than 100 mcg/hour, several medicinal patches may be used simultaneously. Some patients may need additional or alternative methods of opiate administration if the patch dose exceeds 300 mcg/hour.

During the transition from long-term use of morphine to fentanyl, withdrawal syndrome may develop, even despite adequate analgesic effect. If such a disorder develops, it is necessary to use small doses of morphine with short-term action.

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Use Matrifena during pregnancy

There is no safety information on the use of transdermal fentanyl patches in pregnant women. Animal tests have shown reproductive toxicity. The potential risk to humans is unknown, but it has been noted that fentanyl, an IV anesthetic, can cross the human placenta.

Long-term use of Matrifen in pregnant women may cause the development of withdrawal syndrome in the newborn.

It is prohibited to apply the patch during contractions or during childbirth (this includes the cesarean section procedure), because the active substance penetrates the placenta and can cause respiratory depression in the fetus or newborn baby.

Fentanyl passes into breast milk and can cause a sedative effect on the infant or lead to respiratory depression. For this reason, breastfeeding should be discontinued while using Matrifen.

Contraindications

Among the contraindications:

• infants up to 2 years of age;
• increased sensitivity to the elements contained in the patch;
• It is prohibited to use it to relieve acute pain (or pain that occurs in the postoperative period), because it is impossible to select the dosage in a short time, and this increases the risk of suppression of respiratory function, which can be life-threatening;
• in severe forms of respiratory depression;
• in case of severe CNS lesions;
• in combination with MAOIs or if they are used in a period of less than 2 weeks before using Matrifen.

Side effects Matrifena

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

Psychiatric disorders: the most common is a feeling of drowsiness. Frequently, a feeling of anxiety, confusion, nervousness develops, as well as a state of depression, sedation, loss of appetite and hallucinations. Sometimes amnesia, a state of agitation, euphoria or insomnia occur. Asthenia, a state of delirium and problems with sexual function appear isolated;

CNS lesions: headaches and drowsiness most often occur. Sometimes paresthesia with tremor and speech problems develop. Myoclonic seizures of a non-epileptic nature, as well as ataxia, are noted sporadically;

Reactions from the visual organs: amblyopia occasionally develops;

Disorders of the cardiovascular system: sometimes tachycardia or bradycardia occurs, and blood pressure increases/decreases. Vasodilation or arrhythmia are occasionally observed;

Problems with the respiratory system: sometimes hypoventilation or dyspnea are noted. Apnea, pharyngitis or hemoptysis occur sporadically, and in addition, there is suppression of respiratory processes, laryngospasm and obstructive pulmonary damage;

Gastrointestinal disorders: vomiting with nausea and constipation are most often observed. Dyspeptic manifestations or xerostomia are often observed. Sometimes diarrhea begins. Hiccups develop occasionally. Bloating or intestinal obstruction is observed isolatedly;

Immune manifestations: anaphylaxis develops occasionally;

Lesions of the subcutaneous layer and skin surface: most often, hyperhidrosis or itching develops. In addition, local skin manifestations are often observed. Sometimes erythema or rash is noted. Erythema with itching, as well as rash, usually disappear within 24 hours after removing the patch;

Disorders of the urinary system and kidneys: urinary retention is sometimes observed. Pain in the bladder or oliguria are observed sporadically;

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

Other disorders: in case of prolonged use of the patch, tolerance to the drug may develop, as well as mental and physical dependence. Signs of withdrawal 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 prolongation of its medicinal effect - symptoms such as a state of coma, a feeling of lethargy and suppression of respiratory activity with periodic breathing or cyanosis. Among other manifestations - weakening of muscle tone, hypothermia with hypotension, and bradycardia. Symptoms of toxicity - the development of deep sedation, miosis, ataxia, convulsions, and in addition suppression of respiratory function (this is the main symptom).

To cope with the suppression of respiratory activity, immediate measures are required, which include removing the patch, and in addition, verbal or physical pressure on the victim. Then he needs to administer the substance naloxone, which is a specific opiate antagonist.

Adults should initially receive 0.4-2 mg of naloxone hydrochloride intravenously. If necessary, this dose can be given every 2-3 minutes, or a continuous injection of 2 mg of the drug diluted in 0.9% sodium chloride (500 ml) or 5% dextrose (0.004 mg/ml) can be given instead. The rate of injection should be adjusted based on previous bolus infusions and the patient's response.

If it is impossible to perform an intravenous injection, it is allowed to administer the drug subcutaneously or intramuscularly. When administering naloxone by such methods, the onset of its effect will be slower compared to an intravenous injection. However, intramuscular administration prolongs the duration of the drug's effect.

Respiratory depression due to fentanyl intoxication may last longer than the effects of naloxone. Acute pain may increase as the drug wears off, and catecholamines may be released. It is important to provide adequate intensive treatment when needed.

In case of significant pressure reduction (lasting for a long time), it is necessary to take into account hypovolemia and monitor the health condition by introducing the required volumes of fluid parenterally.

Interactions with other drugs

When used in combination with other drugs that depress the central nervous system (including tranquilizers, sedatives and hypnotics, opioids, muscle relaxants with systemic anesthetics, sedative-type antihistamines and phenothiazines with alcoholic beverages), an additive sedative effect may develop. In addition, hypotension with hypoventilation, as well as deep sedation or coma may occur. Therefore, when using the above drugs simultaneously with Matrifen, it is necessary to constantly monitor the patient's condition.

Fentanyl is a substance with a high clearance rate. It is rapidly and extensively metabolized (primarily by the hemoprotein CYP3A4).

When combining the transdermal form of fentanyl with drugs that inhibit the activity of the CYP3A4 element (including ketoconazole, voriconazole and fluconazole with ritonavir, as well as itraconazole, clarithromycin, diltiazem with troleandomycin, nefazodone with amiodarone and nelfinavir with verapamil), the plasma level of the active substance Matrifen may increase. Because of this, the medicinal effect of the drug may be potentiated or prolonged. In addition, such a reaction may be demonstrated by side effects that can cause severe respiratory depression. In such cases, it is necessary to provide the best care and very carefully monitor the person's condition. It is prohibited to combine such drugs if it is not possible to ensure constant close monitoring of the patient.

The transdermal patch should not be administered to individuals who require concomitant use of an MAOI. There is evidence that MAOIs potentiate the effects of opiates, especially in individuals with heart failure. For this reason, fentanyl should not be used for 2 weeks after discontinuing MAOI therapy.

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

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Storage conditions

Matrifen must be kept in a place inaccessible to small children. The temperature mark should not exceed 25°C.

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Shelf life

Matrifen can be used for 2 years from the date of manufacture of the medicinal patch.