Centrally acting muscle relaxant (alpha-2 adrenergic agonist)
Tizanidine is a centrally acting muscle relaxant, used to relieve spasticity (muscle stiffness and spasms) in adults. It acts on the central nervous system, reducing the signals that cause excessive muscle tension. It can cause drowsiness, dry mouth and dizziness.
Also known as: Tizanidina, Sirdalud
Famotidine + tizanidine: famotidine may substantially increase tizanidine concentrations (CYP1A2) — avoid if possible.
The FDA tizanidine label documents that moderate or weak CYP1A2 inhibitors should be avoided concomitantly (section 7.2), as they may cause hypotension, bradycardia or excessive drowsiness; famotidine is a known CYP1A2 inhibitor. Tizanidine is metabolised predominantly by this enzyme (oral bioavailability of ~40% due to first-pass effect): CYP1A2 inhibition raises plasma concentrations of the muscle relaxant and potentiates its central and cardiovascular adverse effects. The combination is common in patients with spasticity and dyspepsia/GERD, so clinical vigilance is important in the first weeks. If adverse reactions occur, reduce the tizanidine dose or stop one of the drugs; avoid the combination whenever there is an alternative.
Tizanidine + famotidine: CYP1A2 inhibition by famotidine may increase tizanidine exposure — monitor for hypotension, bradycardia and drowsiness.
The FDA famotidine label documents: "Tizanidine (CYP1A2) Substrate: Potential for substantial increases in blood concentrations of tizanidine resulting in hypotension, bradycardia or excessive drowsiness; avoid concomitant use, if possible" (7.2). Famotidine inhibits CYP1A2, reducing tizanidine metabolism.
Monitor blood pressure, heart rate and level of sedation at the start of the combination.
Orthostatic hypotension, bradycardia or excessive sedation with the combination.
Avoid the combination; if unavoidable, reduce the tizanidine dose and monitor for hypotension, bradycardia and sedation.
DailyMed/FDA (NIH/NLM) — approved Tizanidine label (section 7.2): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d0b2b22-e1df-4ad5-92e6-f9a369108e4b ; approved Famotidine label (TEVA): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c6f4f9e-f3f5-4ecf-9f40-887e037e8847
FDA label (7.4): alcohol increases tizanidine exposure (associated with increased adverse reactions) and concomitant use with other CNS depressants may cause additive CNS depressant effects, including sedation. The CNS depressant effects of tizanidine and alcohol are additive (12.2).
Avoid alcohol during treatment; monitor for symptoms of excess sedation in patients taking tizanidine with another CNS depressant.
DailyMed/FDA (NIH/NLM) — approved Tizanidine label, section 7.4: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d0b2b22-e1df-4ad5-92e6-f9a369108e4b
FDA label (8.6): in renal insufficiency (creatinine clearance < 25 mL/min), tizanidine clearance is reduced — dose reduction is recommended and the risk of adverse reactions may be greater.
Reduce dose in renal impairment (CrCl < 25 mL/min); increase individual doses rather than dosing frequency; monitor closely (somnolence, hypotension).
DailyMed/FDA (NIH/NLM) — approved Tizanidine label, section 8.6: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d0b2b22-e1df-4ad5-92e6-f9a369108e4b
FDA label (8.7): use with caution in hepatic impairment — the extensive hepatic metabolism of the drug is expected to significantly affect pharmacokinetics; dose reduction recommended (2.4).
Reduce dose in hepatic impairment and monitor aminotransferases (risk of liver injury — 5.2).
DailyMed/FDA (NIH/NLM) — approved Tizanidine label, section 8.7: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d0b2b22-e1df-4ad5-92e6-f9a369108e4b
FDA label (8.1): no adequate data on the developmental risk in pregnant women; in animal studies, tizanidine during pregnancy resulted in developmental toxicity (embryofetal and postnatal offspring mortality, growth deficits) at doses lower than clinical.
Potential risk of fetal harm based on animal data; use only if benefit justifies risk.
No data on presence in human milk, effects on the breastfed infant or milk production; animal studies reported presence in the milk of lactating animals (8.2).
Not specifically documented in the label (no 8.3 section with requirements).
DailyMed/FDA (NIH/NLM) — approved Tizanidine label, section 8 Use in Specific Populations: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8d0b2b22-e1df-4ad5-92e6-f9a369108e4b
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Centrally acting muscle relaxant: central alpha-2 adrenergic agonist that increases presynaptic inhibition of motor neurons, with maximal effect on polysynaptic pathways and reduced facilitation of spinal motor neurons (FDA label 12.1). CNS depressant effects are additive with alcohol (12.2).
Central alpha-2 adrenergic agonist: the reduction of spasticity results from increased presynaptic inhibition of motor neurons (predominantly on polysynaptic pathways).
Oral absorption essentially complete; absolute systemic bioavailability of approximately 40% (CV = 24%) due to extensive first-pass hepatic metabolism (12.3). With food: ~30% increase in Cmax and extent of absorption (tablets); Tmax ~1 h fasting.
Extensive first-pass hepatic metabolism (hence oral bioavailability of ~40%); metabolised mainly by CYP1A2 — strong CYP1A2 inhibitors are contraindicated.
Elimination half-life of approximately 2 hours fasting (Tmax 1.0 h); with food, median Tmax increases by 25 min (to 1 h 25 min).
