Instructions Borizol film-coated tablets blister No. 60
Composition
active ingredient: riluzole;
1 tablet contains riluzole 50 mg;
excipients: calcium hydrogen phosphate, microcrystalline cellulose, colloidal anhydrous silicon dioxide, croscarmellose sodium, magnesium stearate;
film coating: hydroxypropylmethylcellulose, lactose monohydrate, titanium dioxide (E 171), macrogol, triacetin.
Dosage form
Film-coated tablets.
Main physicochemical properties: round tablets with a biconvex surface, coated, white or white with a creamy tint.
Pharmacotherapeutic group
Agents acting on the nervous system. Riluzole. ATX code N07X X02.
Pharmacological properties
Pharmacodynamics.
Riluzole is a benzothiazole derivative that has a multifaceted effect on the mechanism of glutamate neurotransmission. Riluzole affects the processes of nerve transmission in the brain structures that control the motor and sensory functions of the body. The mechanism of its action is not fully understood. It is assumed that riluzole blocks the process of glutamate release. Glutamate (the main neurotransmitter of the central nervous system excitation processes) plays a role in cell death. Activation of glutamate synthesis is of pathogenetic importance in neurodegenerative diseases of the brain, i.e. glutamate has a damaging effect on neurons and can mediate cell death in injuries of various etiologies. Activation of glutamate transmission leads to a weakening of spontaneous locomotion, and a decrease in glutamate effects enhances motor skills.
The use of riluzole promotes the ability to move independently, activates motor functions, and postpones the need for tracheotomy and artificial lung ventilation in patients with amyotrophic lateral sclerosis.
Pharmacokinetics.
Riluzole is rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations are reached 60-90 minutes after administration. Absorption of riluzole is 90%, absolute bioavailability is 60%.
The level and extent of absorption are reduced after taking the drug with a meal containing a large amount of fat.
Riluzole is distributed in all body tissues. It penetrates the blood-brain barrier and into breast milk. In the blood, 97% of riluzole binds to plasma proteins, mainly albumin and lipoproteins.
Riluzole is metabolized in the liver in two steps: hydroxylation by cytochrome P450 followed by glucuronidation.
The half-life is 9-15 hours.
About 90% of riluzole is excreted in the urine (60% of which is in the form of glucuronides), 10% in the feces.
Indication
To prolong life or delay the time of mechanical ventilation in patients with amyotrophic lateral sclerosis (ALS).
Contraindication
Hypersensitivity to riluzole and other components of the drug;
liver failure or 3 times the upper limit of normal for hepatic transaminase activity.
Interaction with other medicinal products and other types of interactions
Clinical studies to evaluate the interaction of riluzole with other drugs have not been conducted.
In vitro studies using human liver microsomes indicate that the major isoenzyme involved in the initial oxidative metabolism of riluzole is CYP1A2.
CYP1A2 inhibitors (e.g. caffeine, diclofenac, diazepam, nicergoline, clomipramine, imipramine, fluvoxamine, phenacetin, theophylline, amitriptyline and quinolones) have the potential to slow the elimination of riluzole and thus potentiate its effects and increase the risk of riluzole-associated adverse reactions.
CYP1A2 inducers (e.g. cigarette smoke, charred food, rifampicin, omeprazole) may accelerate its elimination and lead to a decrease in its effectiveness.
Application features
Clinical trials have shown that riluzole prolongs survival in patients with ALS (see Pharmacodynamics). Survival was determined for patients who were alive, did not undergo intubation for mechanical ventilation, and did not undergo tracheotomy.
There is no evidence that riluzole has a therapeutic effect on motor function, lung function, fasciculations, muscle strength, or motor symptoms. Riluzole has not been shown to be effective in late-stage ALS.
The safety and efficacy of riluzole have only been studied in patients with ALS. Therefore, the drug should not be used in patients with any other form of motor neurone disease.
Liver dysfunction.
Riluzole should be administered with caution to patients with a history of liver dysfunction or to patients with mild elevations in serum transaminase levels (ALT, AST 3 times the upper limit of normal) and bilirubin and/or gammaglutamyltransferase (GGT) levels.
Initial elevation of several liver function tests (especially bilirubin) should preclude the use of riluzole.
ALT levels should be measured more frequently in patients who develop elevated ALT levels.
Riluzole should be discontinued if ALT levels increase to 5 times the upper limit of normal. There is no experience with dose reduction or rechallenge in patients with ALT levels exceeding 5 times the upper limit of normal. Rechallenge in patients in this situation cannot be recommended.
Neutropenia.
Patients should be advised to report any illness accompanied by fever immediately to their physician. The presence of fever requires immediate blood count and leukocyte count determination and discontinuation of riluzole if neutropenia is detected.
Interstitial lung disease.
Cases of interstitial lung disease have been reported in patients receiving riluzole, some of which were severe. If respiratory symptoms such as dry cough and/or dyspnoea develop, a chest x-ray should be performed.
If signs suggestive of interstitial lung disease (e.g. bilateral diffuse pulmonary opacities) occur, riluzole should be discontinued immediately. In most reported cases, symptoms resolved after discontinuation of riluzole and symptomatic treatment.
Patients with renal impairment.
Multiple-dose studies of riluzole have not been conducted in this category of patients.
Excipients.
Patients with carbohydrate intolerance, such as congenital galactosemia, glucose-galactose malabsorption syndrome, lactase deficiency, are not recommended to use the drug due to the lactose content in the tablet film coating.
Use during pregnancy or breastfeeding
The use of the drug during pregnancy or breastfeeding is contraindicated.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies of the effect of riluzole on the ability to drive or use machines have been conducted, but patients should be warned about the possibility of dizziness or loss of consciousness during treatment, so they should not drive or use machines during treatment with the drug.
Method of administration and doses
Treatment should only be prescribed by a doctor who has experience treating motor neuron diseases.
The recommended daily dose for adults or elderly patients is 100 mg (50 mg every 12 hours). No significant increase in therapeutic effect can be expected from increasing daily doses. The duration of treatment is determined by the doctor.
Patients with renal impairment: Borizol is not recommended for use in patients with renal impairment, as multiple dose studies of riluzole have not been conducted in this patient population (see section 4.4).
Elderly patients: based on pharmacokinetic data, there are no special recommendations for the use of the drug in this category of patients.
Patients with impaired liver function: Borizol is contraindicated in hepatic insufficiency or hepatic transaminase levels exceeding 3 times the upper limit of normal (see section "Contraindications"). The drug should be prescribed with caution to patients with liver disease (see section "Special instructions for use" and section "Pharmacokinetics").
There are no specific dosage recommendations for riluzole for patients of different races.
Children.
The safety and efficacy of riluzole in children have not been studied, so the drug should not be used in pediatric practice.
Overdose
Symptoms: in isolated cases of overdose, neurological and mental symptoms, acute toxic encephalopathy with stupor, coma, as well as methemoglobinemia were observed.
Treatment: There is no specific antidote. In case of overdose, symptomatic and supportive therapy is recommended.
Side effects
The most frequently observed adverse reactions were asthenia, nausea, and abnormal liver function tests.
Adverse reactions, information on which is provided below, are classified by organ and system and their frequency of occurrence: very common (≥ 10%); common (≥ 1% and < 10%); uncommon (≥ 0.1% and < 1%); rare (≥ 0.01% and < 0.1%); very rare (< 0.01%), with an unknown frequency (cannot be estimated from the available data).
Blood and lymphatic system: infrequently - anemia; with an unknown frequency - severe neutropenia.
Immune system: uncommon - anaphylactoid reactions, anaphylactic reactions, including angioedema.
Nervous system: often - headache, dizziness, perioral paresthesia, drowsiness, vertigo.
Cardiovascular system: often - tachycardia; infrequently - increased blood pressure.
Respiratory system: uncommon - decreased pulmonary function, interstitial lung disease, including hypersensitivity pneumonitis.
Hepatobiliary system: very common - increased levels of liver enzymes, including ALT, in the blood serum, usually in the first 3 months of treatment with riluzole; the increase in these indicators was usually transient. This increase may be associated with jaundice. With continuous use of the drug for 2-6 months, the level of ALT may gradually decrease to a level less than 2 times the upper limit of normal; with an unknown frequency - hepatitis.
In patients in clinical trials of riluzole who developed ALT levels greater than 5 times the upper limit of normal, treatment was discontinued. In most cases, these levels returned to values less than 2 times the upper limit of normal within 2 to 4 months.
Data from a riluzole study suggest that people of Mongoloid race are at greater risk of liver dysfunction, with abnormal liver function tests occurring in 3.2% (194/5995) of Mongoloid patients and 1.8% (100/5641) of Caucasian patients.
Skin and subcutaneous tissue disorders: frequency unknown - rash.
General disorders: very common - asthenia; common - pain of various localization; cases of muscle rigidity have been reported.
Expiration date
3 years.
Do not use after the expiry date stated on the packaging.
Storage conditions
In the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 tablets in a blister, 6 blisters in a pack.
Vacation category
According to the recipe.
Producer
Producer.
Public Joint Stock Company "Research and Production Center "Borshchagov Chemical and Pharmaceutical Plant".
Location of the manufacturer and its business address
Ukraine, 03134, Kyiv, Myru St., 17.
