Indications:
Muscoryl 8 is indicated as adjunctive treatment for painful muscle contractures in acute spinal disorders in adults and adolescents aged 16 years and older.
Dosage and administration:
Administration:
For oral use. Swallow the capsule whole after meals.
Dosage:
The maximum recommended dose is 8 mg every 12 hours (16 mg per day). The duration of treatment should be limited to 7 consecutive days.
Higher doses than recommended or prolonged use should be avoided.
This medicine should not be used in children and adolescents under 16 years of age due to safety concerns.
Some special attention on the handling of the medicine before and after use:
No special requirements for disposal after use.
Contraindications
Hypersensitivity to Thiocolchicoside or any excipients of the medicine.
Flaccid paralysis or muscle hypotonia.
Pregnancy and breastfeeding.
Women of childbearing potential not using appropriate contraceptive measures and for 1 month after discontinuation of treatment.
Men not using appropriate contraceptive measures during treatment with Thiocolchicoside and for 3 months after discontinuation of treatment (see details in Warnings and Precautions).
Warnings and precautions:
In patients with epilepsy or at risk of seizures, the benefit–risk balance of Thiocolchicoside should be carefully evaluated, and clinical monitoring should be reinforced. If seizures occur, treatment must be discontinued.
Cases of liver injury associated with Thiocolchicoside have been reported. Severe cases (acute hepatitis) have been reported in patients receiving concomitant treatment with NSAIDs or paracetamol. Patients should discontinue treatment and consult a physician if signs or symptoms of liver injury occur.
Preclinical studies have shown that one of the Thiocolchicoside metabolites (SL59.0955) induces aneuploidy (abnormal chromosome number in cells after cell division) at concentrations close to those observed in humans receiving 8 mg twice daily. Aneuploidy is considered a risk factor for teratogenicity, embryo/fetal toxicity, spontaneous abortion and impaired fertility in humans, as well as a potential cancer risk factor. Therefore, higher doses than recommended or prolonged use should be avoided.
Patients should be carefully informed about the potential risk of pregnancy and effective contraceptive methods.
The dose should be reduced in cases of diarrhea. If necessary, the medicine may be taken with a gastric protective agent.
Pregnancy and lactation:
Contraception in women and men:
Thiocolchicoside is contraindicated in women of childbearing potential and in men who are not using appropriate contraceptive methods.
Due to the aneugenic potential of Thiocolchicoside and its metabolites, women of childbearing potential must use effective contraception during treatment and for 1 month after discontinuation.
Men should use appropriate contraceptive methods and should not father a child during treatment and for 3 months after discontinuation.
Pregnancy:
Data on the use of Thiocolchicoside in pregnant women are limited.
Animal studies have demonstrated teratogenic effects.
The medicine is contraindicated during pregnancy.
Lactation:
Since Thiocolchicoside is excreted into breast milk, the medicine is contraindicated during breastfeeding.
Fertility:
Thiocolchicoside and its metabolites may have aneugenic potential at various concentrations, which may pose a risk factor for impairment of human fertility.
Effects on ability to drive and use machine:
Clinical studies have not shown any psychomotor impairment related to Thiocolchicoside. However, cases of drowsiness have been reported, caution should be exercised when driving or using machine.
Drug interactions and incompatibilities:
Drug interactions:
Concomitant use with non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol may increase the risk of acute hepatitis.
Incompatibilities:
In the absence of compatibility studies, this medicinal product should not be mixed with other medicinal products.
Undesirable effects:
Undesirable effects are classified according to frequency: Very common (ADR ≥ 1/10), common (1/100 ≤ ADR < 1/10), uncommon (1/1,000 ≤ ADR < 1/100), rare (1/10,000 ≤ ADR < 1/1,000), very rare (ADR < 1/10,000); cannot be estimated from the available data “Not known”.
Patients should be carefully monitored, appropriate methods including discontinuation of treatment should be taken if any abnormalities occur.
| Common | Uncommon | Rare | Not known | |
| Immune system | Hypersensitivity reactions such as urticaria | Hypersensitivity reactions such as Quincke’s edema and anaphylactic shock, anaphylactic reactions. | ||
| Skin and subcutaneous tissue | Pruritus, erythema, rash, maculopapular rash and particularly vesicular rash. | |||
| Gastrointestinal system | Diarrhea, epigastric pain | Nausea, vomiting | ||
| Hepatobiliary system | Liver injury | |||
| Nervous system | Drowsiness | Seizures or recurrent of seizures in patients with epilepsy |
Immediately report to doctor or pharmacist if the above undesirable effects occur during treatment, or report adverse drug reactions to the National Drug Information and Adverse Drug Reaction Monitoring Center (ADR).
Overdose and management:
Overdose: Possible symptoms may include diarrhea, vomiting.
Management: In case of overdose, medical monitoring and symptomatic treatment are recommended.
Pharmacodynamics:
Pharmacological group: Muscle relaxant
ATC code: M03BX05
Thiocolchicoside is a synthetic sulfur derivative of natural colchicum glucoside, which acts pharmacologically as a muscle relaxant in both humans and animals. It eliminates or significantly reduces muscle spasms of central origin: in spastic hypertonia, it reduces the passive resistance of muscles during stretching and reduces or abolishes residual muscle spasms. The muscle relaxant effect is also observed in visceral muscles, particularly the uterus.
The muscle relaxant effect results from the agonist action of the drug on glycinergic receptors mainly located in the brainstem and spinal cord. The drug does not act on voluntary muscles; therefore, it does not affect the respiratory system as well as the cardiovascular system.
Thiocolchicoside also acts as an antagonist of GABA A receptors (mainly located in the cerebral cortex); this pharmacological effect is known to have pro-convulsant properties.
Pharmacokinetics:
Absorption and distribution: After oral administration, Thiocolchicoside is not detected in plasma. Only two metabolites are observed: the pharmacologically active metabolite SL18.0740 and the inactive metabolite SL59.0955.
For these two metabolites, peak plasma concentrations are reached 1 hour after administration of Thiocolchicoside. After a single oral dose of 8 mg Thiocolchicoside, the Cmax and AUC of SL18.0740 are approximately 60 ng/mL and 130 ng.h/mL, respectively. For SL59.0955, these values are much lower: Cmax approximately 13 ng/mL and AUC ranging from 15.5 ng.h/mL (AUC calculated up to 3 hours) to 39.7 ng.h/mL (AUC up to 24 hours).
Metabolism: After oral administration, Thiocolchicoside is first metabolized into aglycone 3-demethyl-thiocolchicine or SL59.0955. This step occurs mainly due to intestinal metabolism, therefore unchanged Thiocolchicoside does not circulate after oral administration.
SL59.0955 is then glucuronidated to SL18.0740, which has pharmacological activity equivalent to Thiocolchicoside, or demethylated to didemethyl-thiocolchicine.
Elimination: It is mainly excreted in feces (79%), while urinary excretion accounts for only 20%. Thiocolchicoside is not excreted unchanged; SL18.0740 and SL59.0955 are found in urine and feces, whereas didemethyl-thiocolchicine is detected only in feces.
After oral administration of Thiocolchicoside, the metabolite SL18.0740 has a half-life ranging from 3.2 to 7 hours, while the metabolite SL59.0955 has a half-life of approximately 0.8 hours.
