Tizanidine

Oral
Spasticity

CrCl (mL/min)	Dosage
<25	Initially, 2 mg once daily, increase in increments of no more than 2 mg, according to patient’s tolerability and response.

Contraindicated.

Concomitant use with potent CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin). Hepatic impairment.

Patient with psychiatric disorder, CV disorder, coronary artery disease. Renal impairment. Elderly. Pregnancy and lactation. Avoid abrupt dose reduction and withdrawal.

Significant: Hepatotoxicity, hypersensitivity reactions, hypotension, sedation, hallucinations.
Gastrointestinal disorders: Xerostomia.
General disorders and administration site conditions: Weakness, fatigue, withdrawal hypertension.
Infections and infestations: Infection.
Investigations: Increased liver enzymes.
Nervous system disorders: Dizziness, drowsiness.
Cardiac disorders: Bradycardia, tachycardia.

PO: C

This drug may cause drowsiness, dizziness, and hypotension, if affected, do not drive or operate machinery.

Monitor LFT at baseline and monthly for the first 4 months of therapy; blood pressure, renal function, and ECG periodically.

Symptoms: Nausea, vomiting, hypotension, bradycardia, QT prolongation, dizziness, miosis, respiratory distress, coma, restlessness, somnolence. Management: Symptomatic and supportive treatment. Employ gastric lavage or administer high doses of activated charcoal. Maintain adequate hydration.

Enhanced CNS effects with sedatives and other CNS depressants (e.g. benzodiazepines, opioids, TCA). Increased hypotensive effects, rebound hypertension and tachycardia with β-adrenoceptor blockers, digoxin. Increased plasma concentration with oral contraceptives.
Potentially Fatal: Increased serum concentration with potent CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin).

Enhanced CNS effects with alcohol.

Description:
Mechanism of Action: Tizanidine is an α₂-adrenergic agonist that acts on the spinal and supraspinal levels to block excitatory interneurons. It reduces spasticity by increasing presynaptic inhibition and has great effects in the polysynaptic pathways. It also possesses a moderate central analgesic effect.
Onset: 1-2 hours.
Duration: 3-6 hours.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract. Food alters absorption and bioequivalence. Bioavailability: Approx 40% (oral). Time to peak plasma concentration: Approx 1 hour.
Distribution: Volume of distribution: 2.4 L/kg. Plasma protein binding: Approx 30%.
Metabolism: Undergoes extensive first-pass hepatic metabolism by CYP1A2 to inactive metabolites.
Excretion: Mainly via urine (60%); faeces (20%). Elimination half-life: Approx 2.5 hours.

Source: National Center for Biotechnology Information. PubChem Database. Tizanidine, CID=5487, https://pubchem.ncbi.nlm.nih.gov/compound/Tizanidine (accessed on Jan. 23, 2020)

Store at 25°C.

Muscle Relaxants

M03BX02 - tizanidine ; Belongs to the class of other centrally-acting muscle relaxants.

Anon. Tizanidine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/11/2017.

Buckingham R (ed). Tizanidine Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/11/2017.

Joint Formulary Committee. Tizanidine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/11/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Tizanidine Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 18/01/2018.

Tizanidine Hydrochloride (Par Pharmaceutical, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 20/11/2017.