Do baclofen extended‑release 20 mg twice daily and tizanidine 2 mg at bedtime cause bradycardia, and how should the heart rate be monitored?

Cardiovascular Effects of Baclofen ER 20mg Twice Daily and Tizanidine 2mg at Bedtime

Tizanidine 2mg at bedtime carries a significant risk of bradycardia and hypotension that requires baseline heart rate assessment and clinical monitoring, while baclofen ER 20mg twice daily has minimal direct cardiac effects but can cause effective bradycardia through ventricular ectopy. 1, 2, 3

Tizanidine-Specific Cardiac Risks

Tizanidine's central α2-adrenergic agonist mechanism directly causes bradycardia and hypotension, even at the low 2mg bedtime dose. 3

• A 37-year-old woman developed severe sinus bradycardia (30 bpm) and QT prolongation requiring temporary pacemaker placement after taking tizanidine 2mg nightly for two months, with heart rate normalizing 12 hours after discontinuation 3
• In hemodialysis patients, tizanidine 3mg daily produced symptomatic bradycardia (47 bpm average, maximum RR interval 3720 msec) that resolved upon discontinuation 4
• Among community-dwelling adults over 50 years, tizanidine demonstrated a 28.7% overall incidence of adverse cardiovascular effects in FDA adverse event reporting data 2
• Bradycardia and hypotension are particularly pronounced when tizanidine is combined with antihypertensive agents 1, 5

Critical Drug Interactions Affecting Heart Rate

Concomitant use of CYP1A2 inhibitors (oral contraceptives, cimetidine, famotidine, verapamil, amiodarone, propafenone) markedly decreases tizanidine clearance and significantly increases risk of hypotension and bradycardia. 1, 6

• Ciprofloxacin and fluvoxamine are absolutely contraindicated with tizanidine due to severe toxicity risk 1, 6, 7
• Combination with other antihypertensive medications can precipitate clinically significant hypotension requiring blood pressure and heart rate monitoring 6, 5
• A case report documented profound hypotension when tizanidine was combined with lisinopril, scoring 4 on the Naranjo Adverse Drug Reaction Probability Scale 5

Baclofen-Specific Cardiac Considerations

Baclofen ER 20mg twice daily does not directly cause bradycardia through cardiac mechanisms, but patients with bigeminy or trigeminy can present with effective bradycardia and apical-radial pulse deficit. 8

• Baclofen demonstrated a 12.1% overall incidence of adverse effects in FDA reporting, with falls being the predominant concern (27.8%) rather than direct cardiac effects 2
• Abrupt baclofen discontinuation can precipitate life-threatening withdrawal including tachycardia, hypertension, seizures, and potentially fatal outcomes 1
• Baclofen combined with tizanidine showed no clinically significant pharmacokinetic interaction in a controlled study of 15 subjects receiving baclofen 10mg TID plus tizanidine 4mg TID, with all parameter changes within 30% criterion 9

Monitoring Protocol

Baseline Assessment Required

• Obtain baseline heart rate and blood pressure before initiating tizanidine 1, 6
• Screen for all CYP1A2-inhibiting medications (oral contraceptives, cimetidine, famotidine, verapamil, amiodarone, propafenone, ciprofloxacin, fluvoxamine) 1, 6
• Document any antihypertensive medications that may potentiate hypotensive effects 6, 5
• Assess renal and hepatic function, as both conditions reduce tizanidine clearance and increase toxicity risk 1, 2

Ongoing Monitoring Strategy

• Monitor heart rate weekly during the first month of tizanidine therapy, either by pulse check, event recorder, or office ECG 8
• Educate patients about orthostatic hypotension risk and advise slow positional changes 6
• Instruct patients to report dizziness, lightheadedness, syncope, or excessive fatigue immediately 1, 3
• If heart rate drops below 50-55 bpm or patient develops symptomatic bradycardia, discontinue tizanidine immediately 3, 4

Special Population Precautions

In elderly patients with significant cardiovascular disease, tizanidine should be avoided due to heightened risk of hypotension and sedation. 1

• Older adults rarely tolerate tizanidine doses greater than 30-40mg daily and require starting doses of 2mg with gradual titration 1
• The American Geriatrics Society specifically warns against tizanidine-ciprofloxacin combination in older adults due to increased fall and sedation risk 7

Discontinuation Considerations

Never abruptly discontinue tizanidine after more than 1-2 weeks of therapy; gradual taper is necessary to prevent withdrawal phenomena including rebound tachycardia, hypertension, and increased muscle tone. 1, 6

• Baclofen requires even more cautious tapering, as abrupt discontinuation can cause seizures, hallucinations, hyperthermia, and potentially fatal outcomes 1
• Both medications are recommended for short-term use only (typically 7-14 days) in acute conditions 6