What is the safety profile of thiocolchicoside?

Thiocolchicoside Safety Profile

Thiocolchicoside has significant safety concerns including genotoxicity, reproductive toxicity, seizure risk, and lacks proven efficacy beyond placebo effect, making it an unfavorable choice for muscle relaxation therapy.

Major Safety Concerns

Neurological Effects

• Seizures: Thiocolchicoside has powerful epileptogenic activity, with multiple case reports of seizures even in patients without prior seizure history 1
• A case report documented generalized tonic-clonic seizures in a hemodialysis patient after taking thiocolchicoside 8 mg twice daily for just four days 2
• Central nervous system effects include confusion, drowsiness, and dizziness

Reproductive Toxicity

• Thiocolchicoside is teratogenic in experimental animals and damages chromosomes 3
• Associated with altered spermatogenesis, including cases of azoospermia 3
• The European Medical Agency has restricted its use due to risk of aneuploidy from its metabolite M2 4
• Should not be injected for more than 5 days or taken orally for longer than 7 days 4

Hepatic and Other Systemic Effects

• Liver injury and elevated hepatic enzymes have been reported 3
• Other documented adverse effects include:
  • Pancreatitis
  • Blood cell disorders
  • Severe cutaneous disorders
  • Rhabdomyolysis 3

Pharmacokinetics and Metabolism

• After oral administration, thiocolchicoside itself is not detectable in plasma 5
• It undergoes rapid metabolism to:
  1. M2 (aglycone derivative) - pharmacologically inactive
  2. M1 (3-O-glucuronidated aglycone) - pharmacologically active 5
• After intramuscular administration, both thiocolchicoside and M1 are present in plasma 5
• Oral bioavailability is approximately 25% compared to intramuscular administration 5

Special Populations

Renal Impairment

• Increased risk in patients with renal impairment, particularly those on hemodialysis 2
• Case reports document seizures in hemodialysis patients taking standard doses 2

Pregnancy and Fertility

• Contraindicated in pregnancy due to teratogenic effects in animal studies 3
• Limited human data (follow-up of approximately 30 pregnant women) showed no major malformations, but sample size is insufficient to draw definitive conclusions 3
• Associated with male fertility issues including altered spermatogenesis 3

Efficacy Concerns

• Lacks proven efficacy beyond placebo effect for muscle relaxation 3
• Recent comparative study in Wistar rats showed no skeletal muscle relaxant properties at both 2 mg/kg and 4 mg/kg doses 4
• Did not potentiate the muscle relaxant activity of diazepam when used in combination 4

Clinical Recommendations

• Avoid use in patients with:

  • History of epilepsy or seizures 1
  • Acute brain injury 1
  • Renal impairment, especially those on hemodialysis 2
  • Pregnancy or when trying to conceive 3

• For muscle pain, safer alternatives should be considered:

  • Paracetamol is recommended as a first-line agent 3
  • Other well-established muscle relaxants with better safety profiles may be considered

Monitoring

If thiocolchicoside must be used (which is rarely justified):

• Limit duration to less than 7 days for oral administration and less than 5 days for injection 4
• Monitor for neurological symptoms, particularly seizure activity
• Monitor liver function tests
• Avoid use in patients with compromised blood-brain barrier 1

In conclusion, given its significant safety concerns and questionable efficacy, there is little justification for exposing patients to the adverse effects of thiocolchicoside when safer and more effective alternatives are available.