Tiplito (Solution) Instructions for Use

Marketing Authorization Holder

Dr. Reddy’s Laboratories Ltd. (India)

ATC Code

M03BX05 (Thiocolchicoside)

Active Substance

Thiocolchicoside (Rec.INN registered by WHO)

Dosage Form

Tiplito

Solution for intramuscular injection 4 mg/2 ml

Dosage Form, Packaging, and Composition

Solution for intramuscular injection

2 ml – ampoules (6 pcs.) – cardboard packs – By prescription

Pharmacotherapeutic Group

Muscle relaxants; centrally acting muscle relaxants; other centrally acting muscle relaxants

Pharmacological Action

Thiocolchicoside is a semi-synthetic sulfide derivative of colchicoside, exhibiting muscle relaxant properties.

In vitro, it binds exclusively to GABA receptors and glycine strychnine-sensitive receptors. Since Thiocolchicoside acts as a GABA receptor antagonist, its muscle relaxant effect may be exerted at the supraspinal level, although glycinergic mechanisms of action cannot be excluded.

The characteristics of the interaction with GABA receptors are qualitatively and quantitatively distinct between thiocolchicoside and its main circulating metabolite – the glucuronic acid conjugate.

The muscle relaxant effect of thiocolchicoside and its main metabolite in vivo has been demonstrated in predictive modeling in rats and rabbits.

The absence of a muscle relaxant effect of thiocolchicoside in rats with damaged spinal cord indicates a predominance of supraspinal activity.

According to EEG study results, Thiocolchicoside and its main metabolite do not have a sedative effect.

Pharmacokinetics

After intramuscular administration, the C_max of thiocolchicoside in plasma is reached within 30 minutes and is 113 ng/ml after a 4 mg dose or 175 ng/ml after an 8 mg dose.

The corresponding AUC values are 283 and 417 ng×h/ml. The pharmacologically active metabolite SL18.0740 is detected at lower concentrations (C_max is 11.7 ng/ml) 5 hours after administration, with an AUC of 83 ng×h/ml.

Data on the inactive metabolite SL59.0955 are not available. The apparent V_d of thiocolchicoside is approximately 42.7 L after intramuscular administration of an 8 mg dose. Data on both metabolites are not available.

After oral administration, Thiocolchicoside is first metabolized to the aglycone 3-demethylthiocolchicine or SL59.0955.

This stage occurs mainly due to intestinal metabolism, which explains the absence of circulating unchanged thiocolchicoside with this route of administration.

SL59.0955 then undergoes conjugation with glucuronic acid, leading to the formation of metabolite SL18.0740. It has equipotent pharmacological activity with thiocolchicoside and thus maintains pharmacological activity after oral administration of thiocolchicoside.

SL59.0955 is also demethylated to didemethylthiocolchicine.

After intramuscular administration, the T_1/2 of thiocolchicoside is 1.5 hours, and the plasma clearance is 19.2 L/h.

Radioisotope studies have shown that after oral administration, the total dose is excreted mainly through the intestine (79%), renal excretion is only 20%.

Unchanged Thiocolchicoside is not excreted either through the intestine or through the kidneys.

SL18.0740 and SL59.0955 are excreted both through the intestine and the kidneys, while didemethylthiocolchicine is excreted only through the intestine.

Indications

As an adjuvant therapy for painful muscle spasms in acute spinal pathology.

Dosage Regimen

Administer Tiplito by intramuscular injection only.

The recommended single dose is 4 mg (one 2 ml ampoule).

Do not exceed the maximum single dose of 4 mg.

Administer the dose every 12 hours.

The maximum daily dose is 8 mg (two injections).

Limit the total duration of treatment to a maximum of 5 days.

Do not exceed the recommended dosage or treatment duration due to the risk of adverse effects, including potential hepatotoxicity and genotoxicity.

Observe the patient for several minutes post-injection for signs of vasovagal syncope.

Discontinue use if signs of allergic reaction or hepatotoxicity appear.

Avoid concomitant use with alcohol and other CNS depressants.

Adverse Reactions

Immune system disorders uncommon – allergic skin reactions; rare – urticaria; frequency unknown: angioedema, anaphylactic shock, anaphylactic reactions.

Cardiac and vascular disorders very rare – arterial hypotension.

Nervous system disorders common – drowsiness; rare – agitation and short-term confusion; unknown – malaise, accompanied or not accompanied by vasovagal syncope within a few minutes after intramuscular injection, convulsions.

Gastrointestinal disorders common – diarrhea, abdominal pain; uncommon – nausea, vomiting; rare – heartburn (after oral administration).

Hepatobiliary disorders unknown – cytolytic and cholestatic hepatitis.

Skin and subcutaneous tissue disorders uncommon – pruritus.

Contraindications

Hypersensitivity to thiocolchicoside; peripheral paralysis and muscle hypotonia; use in women of childbearing potential not using contraception; pregnancy, breastfeeding period; children under 16 years of age.

With caution

Impaired liver function.

Use in Pregnancy and Lactation

Contraindicated for use in women of childbearing potential not using contraception; during pregnancy and breastfeeding.

Patients should be informed about the potential risk in case of pregnancy and the need to use effective contraceptive methods.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Pediatric Use

Contraindicated for use in children under 16 years of age.

Special Precautions

Patients should be informed about the need to report any signs of hepatotoxicity.

When used concomitantly with alcohol, a significant increase in such side effects as drowsiness is possible. It is recommended to avoid alcohol consumption during the use of thiocolchicoside.

Thiocolchicoside may cause convulsions, especially in patients with epilepsy or in patients at risk of developing convulsions.

Observation of the patient after intramuscular injection of thiocolchicoside is necessary due to the possibility of vasovagal syncope.

Preclinical studies have shown that one of the metabolites of thiocolchicoside (SL59.0955) caused aneuploidy (a change in the number of chromosomes in dividing cells) at concentrations close to those observed in humans after oral administration of thiocolchicoside at a dose of 8 mg twice daily.

Aneuploidy is considered a risk factor for teratogenicity, embryo-/fetotoxicity, spontaneous abortion, reduced male fertility, and a potential risk factor for cancer development.

As a precautionary measure, the use of the drug in doses exceeding the recommended ones or long-term use should be avoided.

Effect on ability to drive vehicles and operate machinery

It should be taken into account that a common adverse reaction to Thiocolchicoside is drowsiness, therefore, if it occurs, caution should be exercised when driving vehicles, operating machinery, and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

It is not recommended to use Thiocolchicoside simultaneously with other drugs that have a muscle relaxant effect, as a mutually enhancing effect is possible, including a possible increase in the frequency of side effects. If it is necessary to use other muscle relaxants in combination with thiocolchicoside, patient monitoring should be ensured.

When used concomitantly with drugs that depress the central nervous system, including alcohol, antihypertensive agents, curare-like drugs, increased muscle relaxation and CNS depression, and the development of hypotension are possible.

When used concomitantly with anticoagulants, the risk of bleeding increases.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.