What is the recommended way to safely transition a patient with spasticity who is on baclofen to tizanidine, including tapering schedule, starting dose, monitoring, and considerations for hepatic or renal impairment?

Switching from Baclofen to Tizanidine

Baclofen must be tapered slowly while tizanidine is gradually introduced in a cross-titration approach, as abrupt baclofen discontinuation can cause life-threatening withdrawal symptoms including seizures, hallucinations, and potentially fatal hyperthermia. 1

Critical Safety Principle: Never Abruptly Stop Baclofen

• Abrupt baclofen withdrawal is dangerous and potentially fatal, causing visual and auditory hallucinations, anxiety, agitation, delirium, fever, tremors, tachycardia, and seizures 1
• Intrathecal baclofen withdrawal is particularly life-threatening, with high fever, altered mental status, rebound spasticity, and muscle rigidity leading to rhabdomyolysis, multiorgan failure, and death 1
• Even oral baclofen requires slow tapering in long-term users to prevent withdrawal 1

Recommended Cross-Titration Approach

Step 1: Initiate Tizanidine at Low Dose While Maintaining Full Baclofen Dose

• Start tizanidine at 2 mg up to three times daily (every 6-8 hours as needed, maximum 3 doses in 24 hours) 2, 3
• Continue the patient's current baclofen dose unchanged during initial tizanidine introduction 4
• Monitor closely for additive sedation and hypotension, as both drugs are CNS depressants with overlapping side effects 3

Step 2: Gradual Tizanidine Titration

• Increase tizanidine by 2-4 mg increments every few days to achieve optimal spasticity control 3
• Target effective dose is typically 8 mg per dose (single doses of 8 mg reduce muscle tone for several hours, with peak effect at 1-2 hours) 3
• Maximum single dose is 16 mg; maximum total daily dose is 36 mg 3
• Older adults rarely tolerate doses greater than 30-40 mg per day 2

Step 3: Begin Slow Baclofen Taper Only After Tizanidine is Established

• Once tizanidine reaches a therapeutic dose (typically 8 mg three times daily), begin reducing baclofen gradually 4
• Reduce baclofen by approximately 10-25% of the total daily dose every 3-7 days, monitoring for withdrawal symptoms 5
• The entire cross-titration process typically takes 2-4 weeks 6

Step 4: Monitor for Withdrawal and Adverse Effects

Watch for baclofen withdrawal symptoms:

• Seizures, psychic symptoms, hyperthermia, increased spasticity 5
• These symptoms improve with baclofen reintroduction if they occur 5

Monitor for tizanidine adverse effects:

• Hypotension (two-thirds of patients have 20% reduction in BP within 1-3 hours of 8 mg dose) 3
• Bradycardia and orthostatic hypotension 3
• Sedation (48% report sedation, 10% severe) 3
• Dry mouth and drowsiness 7, 6

Special Population Considerations

Hepatic Impairment

• Avoid tizanidine entirely or use with extreme caution in hepatic dysfunction due to risk of hepatotoxicity and reduced clearance 2, 8
• Tizanidine causes liver injury in approximately 5% of patients (ALT/AST >3x upper limit of normal) 3
• Three deaths from liver failure have been reported with tizanidine 3
• Monitor aminotransferase levels at baseline, 1,3, and 6 months, then periodically 3

Renal Impairment

• **Reduce individual tizanidine doses (not frequency) in patients with creatinine clearance <25 mL/min**, as clearance is reduced by >50% 3
• Baclofen also requires dose adjustment in renal disease and carries high risk in this population 5
• Monitor closely for dry mouth, somnolence, asthenia, and dizziness as indicators of tizanidine overdose 3

Elderly Patients

• Start with 2 mg tizanidine dosing and titrate more slowly 2
• Avoid tizanidine in elderly patients with significant cardiovascular disease due to hypotensive and sedative effects 1

Critical Drug Interactions to Screen Before Switching

Absolute Contraindications with Tizanidine

• Ciprofloxacin and fluvoxamine are absolutely contraindicated with tizanidine due to significantly reduced clearance 1, 8

Significant Interactions Requiring Caution

• CYP1A2 inhibitors (oral contraceptives, acyclovir, amiodarone, verapamil, mexiletine, propafenone, cimetidine, famotidine) cause significant hypotension, bradycardia, and sedation 1
• Women on oral contraceptives have 50% lower tizanidine clearance; reduce individual doses 3
• Alcohol increases tizanidine AUC by 20% and Cmax by 15%, with additive CNS depression 3
• Avoid concurrent use with other alpha-2 agonists or antihypertensive therapy 3

Monitoring Parameters During Transition

• Blood pressure and heart rate before each dose increase (watch for 20% reduction in BP, bradycardia) 3
• Orthostatic vital signs when moving from supine to standing 3
• Sedation level and ability to perform activities of daily living 3
• Spasticity control using objective measures (Ashworth scale, spasm frequency) 6
• Liver function tests at baseline, 1,3, and 6 months if continuing tizanidine 3
• Signs of baclofen withdrawal throughout the taper (fever, tachycardia, increased spasticity, mental status changes) 1, 5

Common Pitfalls to Avoid

• Never stop baclofen abruptly, even if the patient appears stable on tizanidine 1
• Do not assume equivalent efficacy between the two drugs; tizanidine and baclofen have similar efficacy but different tolerability profiles 6
• Tizanidine causes less subjective muscle weakness than baclofen (60-82% improvement vs 60-65% with baclofen), which may allow higher functional capacity 6
• Do not dose tizanidine more frequently than every 6-8 hours 3
• Warn patients about performing activities requiring alertness during titration 3
• Consider that pharmacokinetic studies show no interaction between baclofen and tizanidine when coadministered, making cross-titration pharmacologically safe 9