Riluzole

Pharmacological properties

riluzole - a derivative of benzothiazole, has a multilateral effect on the mechanism of glutamate neurotransmission. riluzole affects the processes of nerve transmission in the structures of the brain that control motor and sensory functions of the body. the mechanism of its action is not fully understood. Riluzole is believed to block glutamate release. glutamate (the main neurotransmitter of central nervous system excitation processes) plays a role in cell death. activation of glutamate synthesis has pathogenetic significance in neurodegenerative diseases of the brain, that is, 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 influences enhances motility.

The use of Borizol promotes the ability to move independently, activates motor functions, postpones the need for tracheotomy, mechanical ventilation in patients with amyotrophic lateral sclerosis.

Pharmacokinetics Riluzole is rapidly absorbed in the digestive tract. C_max in blood plasma is achieved 60–90 minutes after administration. The absorbability of riluzole is 90%, the absolute bioavailability is 60%. The level and degree of absorption decreases after taking the drug with food containing a large amount of fat.

Riluzole is distributed in all body tissues. It penetrates the BBB and into breast milk. In the blood, 97% of riluzole binds to plasma proteins, mainly with albumin and lipoproteins. Riluzole metabolism is carried out in the liver in two stages: hydroxylation by cytochrome P450 followed by glucuronidation. T_½ is 9-15 hours. About 90% of riluzole is excreted in the urine (60% of them in the form of glucuronides), 10% with feces.

Indications

Amyotrophic lateral sclerosis.

Application

Use in adults 100 mg / day (50 mg every 12 hours). the duration of the course of treatment is determined individually.

Contraindications

Hypersensitivity to riluzole and other components of the drug;

renal failure;

liver failure;

increased activity of hepatic transaminases 3 times higher than the upper limit of normal.

Side effects

The most frequently observed adverse reactions such as asthenia, nausea, and abnormal liver function tests.

Adverse reactions, information on which is given below, are classified by organs and systems and by the frequency of their occurrence: very often (≥10%); often (≥1% and 10%); infrequently (≥0.1% and 1%); rarely (≥0.01% and 0.1%); very rarely (0.01%), with an unknown frequency (cannot be determined based on available data).

On the part of the blood: infrequently - anemia; There have been reports of the development of severe neutropenia.

On the part of the immune system: infrequently - anaphylactoid reactions, anaphylaxis reactions, including angioedema.

From the side of the nervous system: often - headache, dizziness, perioral paresthesia, drowsiness, vertigo.

From the cardiovascular system: often - tachycardia; reported cases of moderate increase in blood pressure.

From the respiratory system: infrequently - decreased pulmonary function, interstitial lung disease, including hypersensitive pneumonitis.

From the digestive system: very often - nausea; often - diarrhea, abdominal pain, vomiting; infrequently - pancreatitis. Anorexia is possible.

On the part of the hepatobiliary system: very often - an increase in the level of liver enzymes, including AlAT, in the blood serum, usually within 3 months from the start of treatment with riluzole; this increase may be associated with jaundice; with prolonged use of the drug for 2-6 months, the level of AlAT can gradually decrease to the initial values. Cases of hepatitis have been reported.

General disorders: very often - asthenia; often - pain of various localization; reported cases of muscle stiffness.

Most adverse reactions of riluzole are dose-dependent.

special instructions

Borizol should be used with caution in patients with acute liver disease, with elevated levels of transaminases or bilirubin in the blood serum, in people who have undergone an active form of hepatitis. with an initial increase in several indicators of liver function (especially bilirubin), riluzole should not be used.

It is recommended to determine the level of serum transaminases, including AlAT, before treatment, monthly during the first 3 months of therapy, then once every 3 months during the 1st year of treatment and periodically thereafter. In patients who have an elevated ALAT level, studies should be performed more often.

If the level of AlAT is 5 times higher than the upper limit of normal, the drug should be discontinued. Repeated use of Borizol in this situation is not recommended.

With the development of any febrile states, constant monitoring of the blood picture and cessation of the drug when neutropenia is detected is required.

Cases of interstitial lung disease have been reported in patients receiving riluzole; some of them were heavy. If symptoms like dry cough and / or shortness of breath appear, a chest x-ray should be taken. If there are signs of interstitial lung disease, riluzole should be discontinued immediately. In most cases, the symptoms disappeared after discontinuation of the drug and symptomatic treatment.

During the period of treatment with Borizol, you should not drink alcohol.

Pharmacokinetic data showed that there is no need to adjust the dosage of the drug in elderly patients, but it should be used with caution, given the age-related decrease in liver and kidney function.

There are no special recommendations for dose adjustment in patients with impaired renal function, however, patients with this group should use riluzole with caution. In renal failure, the use of the drug is contraindicated.

There are no specific recommendations for dosing riluzole for people of different racial affiliation.

Use during pregnancy and lactation

The use of Borizol during pregnancy is contraindicated.

Riluzole passes into breast milk, so it is recommended that you stop breast-feeding while treating women who are breast-feeding.

Children. The safety and effectiveness of riluzole in children and adolescents have not been studied, therefore, the drug is not used in pediatric practice.

The ability to influence the reaction rate when driving vehicles or working with mechanisms

You should refrain from driving vehicles or working with machinery, as dizziness and drowsiness may occur during treatment.

Interactions

Borizol may affect the pharmacodynamics of drugs that bind to albumin and lipoproteins. cytochrome p450 inhibitors (caffeine, diclofenac, diazepam, imipramine, fluvoxamine, phenacetin, theophylline, amitriptyline, quinolones) are potentially capable of slowing the elimination of riluzole. cytochrome p450 inducers (rifampicin, omeprazole) and smoking can accelerate the elimination of riluzole from the body.

Overdose

In case of an overdose, neurological and psychiatric symptoms, acute toxic encephalopathy with stupor, coma, and methemoglobinemia are possible.

There is no specific antidote. In case of an overdose, symptomatic and supportive therapy is recommended.

Storage conditions

At a temperature not exceeding 25 ° C.