Tolpa

Approved Indications:

• Muscle Spasticity:
• Management of skeletal muscle spasms due to neurological conditions such as:
• Stroke (post-stroke spasticity)
• Multiple sclerosis
• Cerebral palsy
• Traumatic brain injury
• Spinal cord diseases
• Musculoskeletal Pain Syndromes:
• Relief of painful muscle spasm associated with:
• Cervical spondylosis
• Lumbar spondylosis
• Lumbago
• Spondylarthrosis
• Periarthritis of shoulder
• Fibromyalgia
• Postoperative Muscle Spasm:
• Adjunct therapy for muscle spasms following orthopedic or neurological surgeries.

Clinically Accepted (Off-Label) Uses:

• Vascular disorders involving muscle tension
• Tension-type headaches with cervical muscle hypertonia (investigational use)

Route of Administration: Oral (tablets)

Adults:

• Typical Dose: 150 to 450 mg/day, divided into 2 or 3 doses
• Start with 50 mg 3 times daily and increase based on response and tolerance
• Maximum dose: 150 mg three times daily

Pediatrics (Not routinely recommended):

• Safety and efficacy not well established in children under 18 years.

Elderly:

• Use with caution; start with lower doses due to possible hepatic or renal impairment

Hepatic Impairment:

• Use with caution; dose reduction may be necessary

Renal Impairment:

• Cautious use is advised; no specific adjustment guideline exists

Duration of Use:

• Treatment duration is individualized based on clinical response
• Usually short-term therapy; long-term use should be regularly reviewed

Tolperisone Hydrochloride is a centrally acting muscle relaxant that primarily acts on the brainstem and spinal cord. It stabilizes neuronal membranes by blocking voltage-gated sodium and calcium channels, reducing excessive neuronal excitability. Additionally, it inhibits spinal reflex arcs and polysynaptic transmission without affecting muscle tone or consciousness. The resultant decrease in motor neuron excitability leads to muscle relaxation, improved mobility, and reduced pain associated with spasticity or muscle spasm.

• Absorption: Rapid absorption from the gastrointestinal tract; peak plasma concentrations reached within 30–90 minutes post oral administration.
• Bioavailability: Low (approx. 20%) due to extensive first-pass metabolism
• Distribution: Widely distributed; crosses the blood-brain barrier
• Metabolism: Extensively metabolized in the liver via hydroxylation and conjugation pathways; enzymes involved are not fully characterized
• Active Metabolites: Pharmacologically inactive
• Elimination: Excreted primarily in urine (≥ 99%), mostly as metabolites
• Half-life: Approximately 2–3 hours

• Pregnancy: Not assigned by FDA; however, animal studies have shown adverse effects at high doses. Use only if the potential benefit justifies the potential risk to the fetus.
• Lactation: Unknown if excreted in human breast milk. Caution is advised during breastfeeding; a risk-benefit assessment should be made.
• General Advice: Avoid during the first trimester; consider alternatives in pregnant or lactating women if possible.

• Primary Class: Skeletal Muscle Relaxant
• Subclass: Centrally Acting Muscle Relaxant
• Generation: Non-sedative third-generation muscle relaxant

• Hypersensitivity to Tolperisone or any component of the formulation
• Myasthenia gravis
• Severe hepatic impairment
• Severe renal impairment
• Pregnancy (especially first trimester), unless absolutely necessary
• Lactation, unless under strict medical supervision

• Hypersensitivity Reactions: Rare but potentially serious allergic reactions reported; discontinue immediately if signs of hypersensitivity occur
• Neuromuscular Disorders: Use cautiously in patients with neuromuscular diseases (e.g., myasthenia gravis)
• Hepatic or Renal Impairment: Requires dose adjustment and monitoring
• Drowsiness or Dizziness: May impair ability to drive or operate machinery
• Monitoring: Monitor for allergic reactions and muscle tone; assess hepatic and renal function in long-term use

Common Side Effects (≥1%):

• Nervous System: Drowsiness, dizziness, headache
• Gastrointestinal: Nausea, vomiting, dyspepsia, abdominal discomfort
• General: Fatigue, dry mouth

Uncommon to Rare Side Effects:

• Allergic Reactions: Rash, pruritus, urticaria, anaphylactic shock (rare but serious)
• Hepatic: Elevated liver enzymes (rare)
• Cardiovascular: Hypotension, tachycardia (rare)
• Neuromuscular: Muscle weakness

Severity: Most side effects are mild to moderate and transient. Serious allergic reactions warrant discontinuation.

• CNS Depressants (e.g., benzodiazepines, opioids): Additive CNS depressant effects; monitor closely
• Other Muscle Relaxants: Risk of enhanced muscle relaxation; avoid or adjust dosing
• Anticholinergic Drugs: May enhance side effects like dry mouth, dizziness
• Enzyme Involvement: Though metabolic enzymes are not fully defined, hepatic metabolism implies possible interaction with other hepatically metabolized drugs

Food Interactions:

• Absorption may be enhanced when taken with food

Alcohol Interaction:

• Alcohol may increase CNS side effects like drowsiness and dizziness; avoid concurrent use

• EMA/FDA Advisory (Recent Years): No major changes in indication or black box warnings
• Updated Labeling in Some Countries: Reinforced caution for allergic reactions and emphasized use in short-term muscle spasm management only
• Clinical Guidelines: Considered an alternative to benzodiazepine-based muscle relaxants when sedation is undesirable

• Temperature: Store below 25°C (77°F)
• Humidity: Keep in a dry place
• Light Protection: Store in original packaging to protect from light
• Handling: Keep tightly closed; do not use expired medication
• Special Instructions: No refrigeration required. Keep out of reach of children