The white, round tablet debossed with 503 on one side and a cross/quadrisecting score on the reverse is an oral prescription skeletal muscle relaxant containing Tizanidine Hydrochloride (4 mg). It is the generic equivalent to brand-name Zanaflex 4 mg.
Pill Identification
Attribute – Specification
- Active Ingredient – Tizanidine Hydrochloride, USP (4 mg base equivalent)
- Imprint – 503 on one side; quadrisecting score lines on the reverse
- Color & Shape – White to off-white, round, flat-faced, beveled-edge tablet
- Size – Approximately 8 mm to 9 mm
- Primary Manufacturers / Distributors – Caraco Pharmaceutical Laboratories / Sun Pharmaceutical Industries
- Drug Class – Centrally acting adrenergic receptor agonist / Antispastic agent
- (Note: Other formulations bearing the number “503” include Metformin ER 500 mg [white oval], Omeprazole/Sodium Bicarbonate [white capsule], and Watson 503 [hydrocodone/acetaminophen 10/650 mg oval]. The debossed “503” flat, round tablet with a quadrisecting score specifically identifies generic Tizanidine 4 mg).
Mechanism of Action
Tizanidine is a centrally acting adrenergic agonist structurally related to clonidine, but with roughly one-tenth to one-fiftieth of clonidine’s blood-pressure-lowering potency at equivalent muscle-relaxant doses:
- Presynaptic Activation: Tizanidine selectively binds to and stimulates presynaptic adrenergic receptors located primarily in the superficial dorsal horn and interneuronal pathways of the spinal cord.
- Inhibition of Excitatory Neurotransmission: Receptor activation inhibits voltage-gated calcium influx into presynaptic terminals, which blocks the release of excitatory amino acid neurotransmitters – chiefly glutamate and aspartate.
- Suppression of Spinal Reflexes: By reducing excitatory synaptic input, tizanidine selectively suppresses polysynaptic reflex arcs responsible for excess muscle tone, involuntary spastic contractions, and clonus without causing widespread flaccidity or substantial reduction in voluntary muscle strength.
Indications and Clinical Uses
- Management of Spasticity: First-line treatment for the reduction of increased muscle tone, severe spasms, and spasticity associated with:
- Multiple Sclerosis (MS)
- Spinal Cord Injury (SCI)
- Non-progressive spinal cord pathology
- Off-Label Uses: Short-term management of acute musculoskeletal pain, chronic tension-type headaches, myofascial pain syndrome, and refractory back/neck muscle spasms.
Dosage and Administration
- Tizanidine has a rapid onset (1 to 2 hours) and a short duration of action (3 to 6 hours), making dosing targeted to times when relief of spasticity is most critical (such as before physical therapy or sleep).
- Initial Adult Dosing: 2 mg to 4 mg orally as a single dose.
- Titration Schedule: Dose may be gradually increased by 2 mg to 4 mg per dose every 1 to 4 days until optimal clinical efficacy is achieved.
- Maintenance & Frequency: Doses may be repeated every 6 to 8 hours as needed, up to a maximum of 3 doses in 24 hours.
- Maximum Daily Dose: Do not exceed 36 mg per day. Single doses should not exceed 16 mg.
- Food Effect (Consistency Rule): Food significantly increases peak plasma concentration of tizanidine tablets by approximately 30%. Patients must choose to consistently take tizanidine either with food or on an empty stomach, avoiding switching between states to prevent sudden fluctuations in sedation or hypotension.
- Renal Impairment: In patients with renal insufficiency , clearance is reduced by more than 50%. Reduce starting doses and monitor closely for excessive sedation and hypotension.
Side Effects
Common Adverse Reactions:
- Central Nervous System: Extreme somnolence/sedation (up to 48%), dizziness (16%), fatigue, asthenia (weakness), and ataxia
- Gastrointestinal / Autonomic: Dry mouth / xerostomia (up to 49%), constipation, nausea
- Cardiovascular: Dose-dependent hypotension and bradycardia
Serious Adverse Reactions:
- Profound Hypotension & Syncope: Clinically significant drops in systolic and diastolic blood pressure, particularly when standing.
- Hepatotoxicity / Liver Injury: Dose-related transaminase elevations (ALT/AST), occasionally manifesting as symptomatic drug-induced hepatitis or jaundice.
- Hallucinations & Psychosis: Visual hallucinations or paranoid ideation occurring in approximately 3% of patients.
- Severe Sedation & Motor Impairment: Sedation typically peaks 1 to 2 hours post-ingestion and can impair reaction times.
Key Drug Interactions
- Absolute Contraindication: Strong CYP1A2 Inhibitors
- Tizanidine is extensively metabolized by the cytochrome P450 CYP1A2 enzyme. Concomitant use with potent CYP1A2 inhibitors – specifically ciprofloxacin and fluvoxamine – is strictly contraindicated. Co-administration causes up to a 33-fold increase in tizanidine AUC and a 12-fold increase in peak concentrations, precipitating severe hypothermia, profound hypotension, coma, or fatal respiratory depression.
- Moderate CYP1A2 Inhibitors: Other inhibitors (e.g., zileuton, oral contraceptives containing ethinyl estradiol, fluoroquinolones like levofloxacin, amiodarone, cimetidine) require extreme caution and dose reductions.
- Antihypertensive Agents: Concurrent administration with beta-blockers, ACE inhibitors, calcium channel blockers, or clonidine significantly enhances hypotensive and bradycardic effects.
- CNS Depressants and Alcohol: Alcohol increases tizanidine blood levels by approximately 20% and produces additive central depression.
Warnings and Precautions
- Rebound Hypertension and Tachycardia: Abrupt cessation after chronic use can cause severe rebound hypertension, tachycardia, tremor, anxiety, and hypertonia. Treatment must be discontinued gradually by tapering the dose by 2 mg to 4 mg per day under medical supervision.
- Hepatic Function Monitoring: Baseline and periodic liver function tests (serum transaminases) are recommended during the first 6 months of therapy (at 1, 3, and 6 months) to monitor for drug-induced hepatic injury. Discontinue immediately if ALT/AST levels exceed 3 times the upper limit of normal.
- Orthostatic Hypotension and Syncope: Monitor blood pressure regularly during dose titration, especially in patients taking concomitant cardiovascular medications.
- Operating Heavy Machinery: Due to high rates of somnolence, patients should avoid driving or performing hazardous tasks until their response to tizanidine is known.