Thiozz-8
UkraineTable of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT THIOZZ-8 (THIOZZ-8)
Composition:
Active substance: thiocolchicoside;
One tablet contains thiocolchicoside 8 mg;
Excipients: mannite (E 421), aspartame (E 951), crospovidone, magnesium stearate.
Pharmaceutical form. Orodispersible tablets.
Main physico-chemical characteristics: round, flat on both sides, with bevelled edges, uncoated tablets ranging in colour from light yellow to dark yellow.
Pharmacotherapeutic group. Muscle relaxants with central mechanism of action.
ATC code M03B X05.
Pharmacological Properties
Pharmacodynamics
Tiocolchicoside is a semi-synthetic myorelaxant derived from the glycoside colchicoside. It exhibits selective affinity for gamma-aminobutyric acid (GABA) and glycine receptors.
The myorelaxant effect is predominantly manifested at the supraspinal level, due to complex regulatory mechanisms; a glycine-mediated mechanism of action is also not excluded.
Binding of tiocolchicoside to GABA is qualitatively and quantitatively distinct from that of its active metabolite—glucuronidated derivative.
Tiocolchicoside and its derivatives do not exhibit sedative effects.
Pharmacokinetics
Absorption
After a single 8 mg oral dose of tiocolchicoside, maximum concentration (Cmax) is reached within 30 minutes and reaches 175 ng/mL. The area under the concentration-time curve (AUC) is 417 ng·hour/mL.
The pharmacologically active metabolite SL18.0740 is also detected at a lower Cmax of 11.7 ng/mL, reached 5 hours after dose administration, with an AUC of 83 ng·hour/mL. No data are available for the inactive metabolite SL59.0955.
Following oral administration of tiocolchicoside, only two metabolites are detected in plasma: the pharmacologically active metabolite SL18.0740 and the inactive metabolite SL59.0955. The Cmax of both tiocolchicoside metabolites is reached approximately 60 minutes after administration. After a single 8 mg oral dose, the Cmax and AUC values for metabolite SL18.0740 are approximately 60 ng/mL and 130 ng·hour/mL, respectively. For metabolite SL59.0955, these values are much lower: Cmax is approximately 13 ng/mL, and AUC ranges from 15.5 ng·hour/mL (up to 3 hours) to 39.7 ng·hour/mL (up to 24 hours).
Distribution
The volume of distribution of tiocolchicoside is approximately 42.7 L after administration of an 8 mg dose. Data on the volume of distribution of metabolites are not available.
Metabolism
After oral administration, tiocolchicoside is rapidly metabolized to aglycone-3-dimethylthiocolchicoside, or SL59.0955. This occurs primarily via intestinal metabolism, which explains the absence of unchanged tiocolchicoside after oral administration. Metabolite SL59.0955 is glucuronidated to SL18.0740, which has equivalent pharmacological activity to tiocolchicoside and thus accounts for the pharmacological activity following oral administration of tiocolchicoside. SL59.0955 is also demethylated to form dimethylthiocolchicine.
Excretion
After oral administration of 14C-tiocolchicoside, the compound is primarily excreted in feces (79%), with only 20% excreted in urine. Unchanged tiocolchicoside is not excreted in urine or feces. Metabolites SL18.0740 and SL59.0955 are detected in both urine and feces, whereas didemethylthiocolchicine is excreted only in feces.
After oral administration of tiocolchicoside, the elimination half-life of metabolite SL18.0740 is 3.2–7 hours, and that of metabolite SL59.0955 is on average 0.8 hours.
Clinical characteristics.
Indications.
Adjuvant therapy for painful muscular contractures in cases of acute spinal disorders in adults and adolescents aged 16 years and older.
Contraindications.
Thiocolchicoside must not be used:
- in patients with hypersensitivity to the active substance or to any of the excipients of the medicinal product;
- in patients with peripheral paralysis and muscle hypotonia;
- in women during the entire pregnancy period or if pregnancy is planned;
- in women during breastfeeding;
- in women of childbearing age who are not using contraceptive methods.
Interaction with other medicinal products and other forms of interaction.
There are no data available on drug interactions. However, caution is recommended when administering the medicinal product concomitantly with other muscle relaxants.
Concomitant use with agents that depress the central nervous system (CNS), including alcohol, antihypertensive agents, and curare-like drugs, may enhance muscle relaxation and CNS depression, leading to hypotension.
Concomitant use with anticoagulants may increase the risk of bleeding.
Special precautions for use.
Thiocolchicoside is not recommended for use in children under 16 years of age.
If nausea occurs, the dose of the drug should be reduced.
Thiocolchicoside may cause seizures in patients with a predisposition to seizures or epilepsy.
It is known that one of the metabolites of thiocolchicoside (SL59.0955) induces aneuploidy (i.e., an abnormal number of chromosomes in dividing cells) at concentrations close to those observed in human plasma when administered at a dose of 8 mg twice daily orally. Aneuploidy is a risk factor for teratogenicity, embryotoxicity/fetotoxicity, spontaneous abortion, impaired male fertility, and cancer development. Therefore, the use of the drug in doses exceeding the recommended ones and for prolonged periods should be avoided.
Women of childbearing potential should be informed about the potential risks during pregnancy and the necessity of using effective contraceptive methods.
The medicinal product contains aspartame, a phenylalanine derivative, which may be dangerous for patients with phenylketonuria.
Cases of cytolytic and cholestatic hepatitis have been reported with the use of thiocolchicoside. Severe cases (e.g., fulminant hepatitis) have been observed in patients who were concurrently taking paracetamol. Patients should be informed about the need to consult a physician if any signs of hepatic toxicity occur.
The maximum daily oral dose of 16 mg must not be exceeded. This dose should be divided into two equal parts administered at 12-hour intervals. If a patient misses a dose, it should be skipped to avoid taking several doses close together in time.
Use during pregnancy or breastfeeding.
The drug is contraindicated during pregnancy and breastfeeding.
Ability to affect reaction speed when driving or operating machinery.
During treatment, caution should be exercised when driving or engaging in other potentially hazardous activities requiring increased attention, as somnolence and dizziness are common adverse reactions. This should be taken into account when operating vehicles or working with automated systems.
Dosage and Administration.
The orally disintegrating tablet should be sucked in the mouth with or without water. The recommended and maximum dose is 8 mg every 12 hours (i.e., 16 mg per day). The duration of treatment is limited to 7 consecutive days.
Children.
Thiocolchicoside should not be administered to children and adolescents under 16 years of age for safety reasons.
Overdose.
Data regarding overdose are lacking.
Treatment: symptomatic and supportive therapy.
Adverse reactions.
The adverse reactions listed below are systematized according to MedDRA system organ classes and frequency: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency not known (frequency cannot be estimated from the available data).
Immune system disorders: uncommon – pruritus; rare – urticaria; very rare – anaphylactic reactions, arterial hypotension; frequency not known – angioedema and anaphylactic shock.
Nervous system disorders: common – somnolence, dizziness; rare – excitement and confusion.
Gastrointestinal disorders: common – diarrhea, abdominal pain; uncommon – nausea, vomiting; rare – heartburn.
Hepatobiliary disorders: frequency not known – cytolytic and cholestatic hepatitis.
Skin and subcutaneous tissue disorders: uncommon – skin allergic reactions.
Reporting suspected adverse reactions
Reporting suspected adverse reactions after medicinal product registration is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions through the national reporting system.
Shelf life.
2 years.
Storage conditions.
Store at a temperature not exceeding 30 °C. Keep out of reach and sight of children.
Packaging.
10 tablets in a blister pack, 1 blister pack in a cardboard box.
Prescription status.
Prescription only.
Manufacturer.
Ipca Laboratories Ltd.
Manufacturer's address and place of business.
P.O. Sajawta, District Ratlam – 457002 (M.P.), India.