FLEXERIL
Clinical safety rating
cautionComprehensive clinical and safety monograph for FLEXERIL (FLEXERIL).
Cyclobenzaprine is a centrally acting muscle relaxant that acts primarily at the brainstem, reducing tonic somatic motor activity via inhibition of descending serotonergic pathways. It is structurally related to tricyclic antidepressants and exhibits anticholinergic, sedative, and analgesic effects.
| Metabolism | Primarily hepatic via CYP3A4, CYP1A2, and CYP2D6; undergoes N-demethylation and glucuronidation. Active metabolite: norcyclobenzaprine. |
| Excretion | Primarily hepatic; approximately 50% excreted in urine as metabolites, less than 1% unchanged; 40% excreted in feces via bile. |
| Half-life | Terminal elimination half-life is 18 hours (range 8–37 hours) with clinical context: requires dose adjustment in hepatic impairment; steady-state reached in ~3–5 days. |
| Protein binding | ~93% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | ~14 L/kg (range 10–20 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral: ~33% due to extensive first-pass metabolism. |
| Onset of Action | Oral: 1 hour. No parenteral route approved. |
| Duration of Action | 12–24 hours; clinical note: muscle relaxant effects may persist beyond half-life due to redistribution. |
| Molecular Weight | 275.39 |
10 mg to 15 mg orally three times a day; maximum daily dose: 30 mg.
| Dosage form | TABLET |
| Renal impairment | No specific dosage adjustment guidelines; use with caution in renal impairment due to potential for increased side effects. |
| Liver impairment | Contraindicated in hepatic impairment; Child-Pugh class A, B, C: no safe dosage established. |
| Pediatric use | Not recommended for use in children under 15 years old; safety and efficacy not established. |
| Geriatric use | Use lower starting dose (e.g., 5 mg) and titrate slowly; increased risk of sedation and anticholinergic effects. May not be well tolerated; consider alternative therapy. |
| 1st trimester | There are no adequate and well-controlled studies in pregnant women. Flexeril should be used during the first trimester only if the potential benefit justifies the potential risk to the fetus. |
| 2nd trimester | No evidence of fetal harm in animal studies; however, human data are limited. Use only if clearly needed. |
| 3rd trimester | Use during the third trimester may cause neonatal effects such as lethargy, hypotonia, and respiratory depression if used near term. Avoid use, especially during labor. |
Clinical note
Comprehensive clinical and safety monograph for FLEXERIL (FLEXERIL).
| Placental transfer | Cyclobenzaprine crosses the placenta in rats; human data are not available. Given its molecular weight and lipophilicity, placental transfer is expected. |
| Breastfeeding | Cyclobenzaprine is excreted into breast milk in small amounts. The American Academy of Pediatrics considers it compatible with breastfeeding, but caution is advised due to potential for sedation and hypotonia in the infant. Monitor the infant for drowsiness and poor feeding. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate human studies in pregnant women. Use only if clearly needed. First trimester: no known risk. Second trimester: no known risk. Third trimester: potential for neonatal adverse effects such as respiratory depression and withdrawal if used near term. |
| Fetal Monitoring | Monitor for maternal sedation, dizziness, and anticholinergic effects. Neonatal monitoring for signs of respiratory depression, hypotonia, and withdrawal if used near term. |
| Fertility Effects | No adequate studies on fertility effects. Cyclobenzaprine does not appear to affect fertility in animal studies, but no human data available. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to cyclobenzaprine or any component of the formulationConcomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI therapyAcute recovery phase of myocardial infarctionArrhythmias, including heart block and conduction disturbancesHyperthyroidism
| Precautions | Should not be used for longer than 2-3 weeks (acute use only), May impair mental or physical abilities required for driving or operating machinery, Central nervous system depression additive with alcohol and other CNS depressants, Anticholinergic effects: caution in patients with angle-closure glaucoma, urinary retention, or prostatic hypertrophy, Cardiovascular effects: risk of arrhythmias, especially in patients with preexisting cardiac disease (tachycardia, QT prolongation), Serotonin syndrome risk when used with MAOIs, SSRIs, SNRIs, or other serotonergic drugs, Hepatic impairment: lower doses recommended |
| Food/Dietary | Alcohol should be avoided due to additive CNS depression. No specific food interactions; take with or without food. Grapefruit juice does not significantly interact, but caution with high-fat meals may alter absorption slightly. |
| Clinical Pearls | Flexeril (cyclobenzaprine) is structurally related to tricyclic antidepressants (TCAs) and shares similar anticholinergic and sedative properties. It should not be used longer than 2-3 weeks due to lack of evidence for efficacy beyond that duration. Avoid in patients with hyperthyroidism, heart block, or recent MI. Concomitant use with MAOIs can cause hypertensive crisis. Onset of muscle relaxation is delayed; therapeutic effect may not be apparent until after 2-4 days. Sedation is the most common side effect and can be used to aid sleep. |
| Patient Advice | Do not take for longer than 3 weeks unless directed by your doctor. · This medication may cause drowsiness or dizziness; avoid driving or operating heavy machinery until you know how it affects you. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, opioids) as they may increase sedation. · Do not stop suddenly if taken regularly; taper dose to avoid withdrawal symptoms like headache or nausea. · Inform your doctor if you have glaucoma, urinary retention, or are taking MAO inhibitors (e.g., phenelzine, tranylcypromine). · Take exactly as prescribed; do not increase dose or frequency. · May cause dry mouth; use sugar-free gum or candy for relief. |
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