ZANAFLEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZANAFLEX (ZANAFLEX).
Alpha-2 adrenergic receptor agonist; reduces sympathetic outflow from CNS, leading to decreased muscle tone and spasticity.
| Metabolism | Primarily hepatic via CYP1A2 to inactive metabolites; significant first-pass metabolism. |
| Excretion | Approximately 95% of a dose is eliminated via hepatic metabolism; renal excretion accounts for about 20% as unchanged drug and metabolites, with about 20% eliminated in feces. |
| Half-life | Terminal elimination half-life is approximately 2.5 hours in healthy adults; clinically, this short half-life necessitates multiple daily dosing for sustained effect and contributes to its use as needed for spasticity. |
| Protein binding | Approximately 30% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Volume of distribution is about 2.4 L/kg; this large Vd indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 40% due to extensive first-pass hepatic metabolism; bioavailability may be increased when taken with food. |
| Onset of Action | Oral: Onset of clinical effect (muscle relaxation) occurs within 30-60 minutes following a single dose. |
| Duration of Action | Duration of action (muscle relaxation) is 3-6 hours; clinical effect wanes as plasma concentrations decline, requiring repeat dosing every 6-8 hours for continuous spasticity control. |
| Molecular Weight | 253.3 |
Initial: 2 mg orally every 6-8 hours as needed, up to 3 times daily. Maximum: 36 mg per day.
| Dosage form | TABLET |
| Renal impairment | CrCl < 25 mL/min: Use with caution; reduce dose and increase interval. Specific guidelines not established; consider starting at 2 mg once daily. |
| Liver impairment | Child-Pugh Class A: No adjustment needed. Child-Pugh Class B: Use with caution; reduce dose, start at 2 mg once daily. Child-Pugh Class C: Contraindicated. |
| Pediatric use | Safety and efficacy not established for children < 18 years. |
| Geriatric use | Elderly patients may have reduced renal function; use low initial dose (2 mg) and titrate cautiously. Monitor for hypotension and sedation. |
| 1st trimester | Avoid. Teratogenic effects in animal studies; not recommended in pregnant women. |
| 2nd trimester | Avoid. Potential risk of fetal harm; use only if benefit outweighs risk. |
| 3rd trimester | Avoid. May cause neonatal withdrawal or hypotension. |
Clinical note
Comprehensive clinical and safety monograph for ZANAFLEX (ZANAFLEX).
| Placental transfer | Tizanidine crosses the placenta; quantitative data not established but molecular weight suggests transfer. |
| Breastfeeding | Tizanidine is excreted in human milk in low amounts; monitor infant for sedation and hypotension. Use with caution. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to tizanidine or any componentConcomitant use with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin)
| Precautions | Hypotension, bradycardia, hepatotoxicity (monitor LFTs), dry mouth, sedation, risk of withdrawal hypertension if abruptly discontinued. |
| Food/Dietary | Take with or without food consistently, but food increases bioavailability. Avoid alcohol and any products containing alcohol. Grapefruit juice may increase tizanidine levels; avoid concurrent use. |
| Clinical Pearls |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | Animal studies have shown no teratogenic effects. There are no adequate and well-controlled studies in pregnant women. Zanaflex (tizanidine) is categorized as Pregnancy Category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Fetal risks are not established for any trimester. |
| Fetal Monitoring | Monitor maternal blood pressure and heart rate due to hypotensive effects. No specific fetal monitoring is required, but standard prenatal care should be followed. Monitor for signs of maternal sedation or hypotension. |
| Fertility Effects | No human data on fertility effects. Animal studies did not show impaired fertility at doses up to 10 mg/kg/day (approximately 2.7 times the maximum recommended human dose on a mg/m² basis). |
| Titrate slowly to avoid hypotension; monitor liver function tests due to risk of hepatotoxicity; avoid abrupt withdrawal to prevent rebound hypertension and tachycardia; may cause significant sedation, especially at higher doses; use caution in elderly or renally impaired patients. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly without doctor's advice. · Avoid driving or operating heavy machinery until you know how this medicine affects you. · May cause drowsiness, dizziness, or low blood pressure; rise slowly from sitting or lying position. · Avoid alcohol and other central nervous system depressants. · Report signs of liver problems: yellowing of skin/eyes, dark urine, abdominal pain, persistent nausea. · Do not take more than three doses in 24 hours; maximum single dose is 8 mg if prescribed. |