Tizanidine

Indications

Oral
Spasticity
Adult: >18 yr: Initially, 2 mg once daily increased according to response by 2-mg increments at intervals of at least 3-4 days up to 24 mg daily in 3-4 divided doses. Max: 8 mg/dose. Max: 24 mg/day.
Elderly: Not recommended.

CrCl (ml/min)	Dosage Recommendation
<25	Initially, 2 mg once daily, gradually increasing the dose before increasing the frequency of admin.

Hepatic impairment: Avoid or use with extreme caution.
Oral
Painful muscle spasm associated with musculoskeletal conditions
Adult: >18 yr: 2-4 mg tid.
Elderly: Not recommended.

CrCl (ml/min)	Dosage Recommendation
<25	Initially, 2 mg once daily, gradually increasing the dose before increasing the frequency of admin.

Hepatic impairment: Avoid or use with extreme caution.

Special Populations: Patients with renal impairment: Initially, 2 mg once daily, gradually increasing the dose before increasing the frequency of administration.

Contraindications

Severe hepatic dysfunction.

Warnings / Precautions

Hepatic or renal insufficiency. Children, elderly, pregnancy and lactation. Monitor LFT regularly. Stop treatment if liver enzymes are raised persistently >3 times upper limit of normal range. Avoid abrupt withdrawal of therapy.

Adverse Reactions

Drowsiness, fatigue, dizziness, insomnia, headache, anxiety, nausea, dryness of mouth, GI disturbances, hypotension, bradycardia, muscle pain and weakness, transient increase in serum transaminases, hallucinations.
Potentially Fatal: Hepatitis.

Overdose Reactions

Nausea, vomiting, hypotension, miosis, dizziness, respiratory distress, coma, restlessness and somnolence. Treatment is supportive and symptomatic. Gastric lavage or use activated charcoal to reduce drug absorption. Patient to be well hydrated.

Drug Interactions

Potentiates hypotensive effect of antihypertensives. Increased CNS effects with alcohol and CNS depressants. Increased bradycardia with β-blockers and digoxin. Increased serum concentration of tizanidine with CYP1A2 inhibitors e.g. zileuton, ciprofloxacin and other fluoroquinolones, antiarrhythmics, cimetidine, famotidine, oral contraceptives, aciclovir and ticlopidine. Decreased serum concentrations of tizanidine with rifampicin. Use with caution with drugs that may prolong QT interval.
See Below for More tizanidine Drug Interactions

Food Interactions

Tablets and capsules bioequivalent if taken under fasting conditions but differs when taken with food. Tablets: Food increases the median time to peak plasma concentration from about 60 min to about 85 min but increases the mean peak plasma concentration and extent of absorption by about 30%. Capsules: Food increases the median time to peak plasma concentration from about 1 hr to 3 hr; decreases mean peak plasma concentration by 20% while increases the extent of absorption by about 10%. Amount absorbed from capsule is 80% of amount absorbed from tablet when taken with food. Admin of the capsule contents sprinkled on applesauce: 15-20% increase in peak plasma concentration and amount absorbed and a 15-min decrease in median lag time and time to achieve peak plasma concentration, compared with admin of intact capsule under fasting.

Mechanism of Actions

Tizanidine, an α₂-adrenergic agonist, is a centrally acting muscle relaxant structurally related to clonidine. It reduces spasticity by increasing presynaptic inhibition of motor neurons and has no direct effect on skeletal muscle, the neuromuscular junction or on monosynaptic spinal reflexes.
Absorption: Absorbed from the GI tract (oral); peak plasma concentrations in 1-2 hr.
Distribution: Protein-binding: 30%. Elimination half-life: 2-4 hr.
Metabolism: Extensive hepatic first-pass metabolism mainly via the cytochrome P450 isoenzyme CYP1A2.
Excretion: Via urine (mainly as inactive metabolites).