Instructions for use Controlflex solution for injection 2mg/ml 2ml No. 5
Composition
active ingredient: thiocolchicoside;
1 ml of solution for injection contains 2 mg of thiocolchicoside;
Excipients: sodium chloride, diluted or concentrated hydrochloric acid, water for injection.
Dosage form
Solution for injection.
Main physicochemical properties: clear yellow liquid.
Pharmacotherapeutic group
Muscle relaxants. Muscle relaxants with a central mechanism of action. Other centrally acting agents. Thiocolchicoside. ATC code M0ZV X05.
Pharmacological properties
Pharmacodynamics
Thiocolchicoside is a semi-synthetic sulfide derivative of colchicoside with pharmacological activity as a muscle relaxant.
In vitro studies show that thiocolchicoside binds only to gamma-aminobutyric acid (GABA) and strychnine-sensitive glycinergic receptors. In autoradiographic studies, thiocolchicoside displaces [3H] strychnine binding, predominantly in the rat brainstem and spinal cord. In electrophysiological studies on native or recombinant GABA receptors, thiocolchicoside had no effect, but antagonized GABA-induced chloride channels.
Thiocolchicoside had no significant effect on glycine-induced motoneuron channels in spinal cord slices from young (10-day-old) rats.
Thiocolchicoside has been shown in vivo to antagonize the strychnine-induced linguo-mandibular reflex in anesthetized male rabbits. These results are consistent with the hypothesis of a glycinergic mechanism of action.
In an animal model, two intraperitoneal injections of thiocolchicoside reduced the startle reflex in spastic rats, and injections of 10 mg/kg intraperitoneally or 1 mg/kg intramuscularly or 10 mg/kg orally reduced the postsynaptic reflex by 60% in healthy rats. Thiocolchicoside has no sedative effect.
Pharmacokinetics
Absorption
After intramuscular administration of thiocolchicoside, the maximum concentration (Cmax) is reached within 30 minutes and is 113 ng/ml for a dose of 4 mg and 175 ng/ml for a dose of 8 mg. The values of the area under the pharmacokinetic curve "concentration-time" (AUC) are 283 ng/h/ml and 417 ng/h/ml.
The pharmacologically active metabolite SL18.0740 is also detected at a lower Cmax of 11.7 ng/mL, achieved 5 hours post-dose, and AUC of 83 ng/h/mL. No data are available for the inactive metabolite SL59.0955.
Distribution
The apparent volume of distribution of thiocolchicoside is approximately 42.7 L after intramuscular administration of 8 mg. Data are not available for either metabolite.
Breeding
After intramuscular administration, the expected half-life (T1/2) of thiocolchicoside is 1.5 hours and the plasma clearance is 19.2 l/h.
Indication
For adjuvant therapy of painful muscle contractures accompanying acute spinal pathologies in adults and adolescents aged 16 years and older.
Contraindication
The drug CONTROLFLEX is contraindicated for use:
patients with hypersensitivity to the active substance or to any of the excipients;
in case of flaccid paralysis, muscle hypotension;
throughout the entire period of pregnancy;
during breastfeeding;
women of reproductive age who are not using adequate contraception.
Interaction with other medicinal products and other types of interactions
There is no information on the interaction of thiocolchicoside with other drugs.
Application features
The drug CONTROLFLEX is not recommended for use in children and adolescents under 16 years of age.
If diarrhea occurs, treatment with CONTROLFLEX should be discontinued (see section "Adverse reactions").
Thiocolchicoside may cause epileptic seizures in patients suffering from epilepsy or diseases associated with the risk of epileptic seizures (see section "Adverse reactions").
Cases of vasovagal syncope have been reported. The patient should be monitored after intramuscular administration of the drug (see section "Adverse reactions").
The maximum recommended dose of thiocolchicoside of 16 mg per day should not be exceeded, which should be divided into 2 doses with an interval of 12 hours. If a dose is missed, the next dose should be administered at the usual time.
Preclinical studies have shown that one of the metabolites of thiocolchicoside (SL59.0955) causes aneuploidy (a change in the number of chromosomes during cell division) at concentrations close to those observed in humans at 8 mg twice daily orally. Aneuploidy is considered a risk factor for teratogenicity, embryo/fetal toxicity, miscarriage, impaired male fertility and a potential risk factor for cancer. For prevention, exceeding the recommended dose of the drug or its prolonged use should be avoided (see section "Method of administration and dosage").
Postmarketing reports of hepatic dysfunction have been reported in association with thiocolchicoside. Serious cases of hepatic dysfunction (e.g. fulminant hepatitis) have been reported in patients receiving concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol. Patients should be advised to discontinue treatment and seek medical advice if signs of hepatic dysfunction develop (see section 4.8).
This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
Pregnancy
There is limited information on the use of thiocolchicoside in pregnant women. The potential risk to the embryo and fetus is unknown.
Animal studies have shown teratogenic effects of thiocolchicoside.
The drug CONTROLFLEX is contraindicated in pregnant women and women of reproductive age who do not use adequate contraceptive measures (see section "Contraindications").
Breast-feeding
The use of thiocolchicoside is contraindicated during breastfeeding, as it passes into breast milk (see section "Contraindications").
Fertility
Fertility studies in rats showed no changes in fertility at doses up to 12 mg/kg, i.e. at doses that did not cause clinical effects. Thiocolchicoside and its metabolites exhibit aneugenic activity at various concentration levels, which is a risk factor for impaired fertility in humans.
Ability to influence reaction speed when driving vehicles or other mechanisms
There are no data on the effects of thiocolchicoside on driving or operating complex machinery.
Clinical studies have shown that thiocolchicoside does not affect psychomotor skills. However, drowsiness may occur, which must be taken into account when driving or operating complex mechanisms.
Method of administration and doses
The drug CONTROLFLEX is administered intramuscularly.
The recommended maximum daily dose is 4 mg every 12 hours (i.e. 8 mg per day). Treatment should not exceed 5 consecutive days.
Do not exceed the recommended dose or duration of use (see section "Special instructions").
Children
The medicine is not recommended for use in children and adolescents under 16 years of age.
Overdose
No cases of overdose have been observed in patients using thiocolchicoside.
In case of overdose, close medical supervision and symptomatic therapy are recommended.
Side effects
The frequency of adverse reactions is defined as follows: very common (> 1/10), common (> 1/100 to < 1/10), uncommon (> 1/1000 to < 1/100), rare (> 1/10000 to < 1/1000), very rare (< 1/10000), frequency unknown (cannot be estimated from the available information).
Immune system disorders: uncommon - urticaria; very rare - hypotension; frequency unknown - angioedema and anaphylactic reactions, including anaphylactic shock.
Skin and subcutaneous tissue disorders: uncommon – erythema after intramuscular injection, itching, allergic reactions.
Nervous system: often - drowsiness; rarely - agitation or short-term confusion; frequency unknown - vasovagal syncope occurring within the first few minutes after intramuscular injection, convulsions (see section "Special instructions").
Gastrointestinal: often - diarrhea (see section "Special instructions for use"), stomach pain; infrequently - nausea, vomiting; rarely - heartburn.
On the part of the hepatobiliary system and biliary tract: frequency unknown - liver dysfunction (see section "Special instructions").
Reporting of suspected adverse reactions
Reporting suspected adverse reactions that occur after the registration of a medicinal product is very important. This allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national pharmacovigilance system.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
2 ml in ampoules, 5 ampoules in a blister, 1 or 2 blisters in a cardboard pack.
Vacation category
According to the recipe.
Producer
LLC NVF "MICROCHEM".
Location of the manufacturer and address of its place of business
Ukraine, 93400, Luhansk region, Severodonetsk, Promyslova st., building 24-v
Applicant
LLC NVF "MICROCHEM".
Applicant's location
Ukraine, 01013, Kyiv, Budindustrii St., 5.
