Cyclobenzaprine

M03B - Muscle relaxants, centrally acting agents ATC M03BX08 Small molecule approved 1977 Oral Natural product

JFDA label: Xaprine 10mg Tab

Mechanism of Action

Centrally-acting skeletal muscle relaxant pharmacologically related to tricyclic antidepressants; reduces tonic somatic motor activity influencing both alpha and gamma motor neurons

Indications

Approved

Muscle spasm

Off-label

Acute jaw pain due to temporomandibular disorder

Contraindications

Source: Lexicomp

Hypersensitivity to cyclobenzaprine or any component of the formulation Absolute
acute recovery phase of MI Absolute
arrhythmias Absolute
during or within 14 days of MAO inhibitors Absolute
heart block or conduction disturbances Absolute
heart failure Absolute
hyperthyroidism Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (8)

Very Common dizziness · Drowsiness

Common confusion · decreased mental acuity · Fatigue · headache · irritability · nervousness

Gastrointestinal disorders (8)

Very Common Xerostomia

Common abdominal pain · acid regurgitation · constipation · diarrhea · Dyspepsia · nausea · unpleasant taste

Musculoskeletal and connective tissue disorders (1)

Common Weakness

Eye disorders (1)

Common Blurred vision

Respiratory, thoracic and mediastinal disorders (2)

Common Pharyngitis · upper respiratory tract infection

Dosing

Source: Lexicomp

Muscle spasm: Oral: Note: Do not use longer than 2 to 3 weeks Capsule, extended release: Usual: 15 mg once daily; some patients may require up to 30 mg once daily Tablet, immediate release: Initial: 5 mg 3 times daily; may increase up to 10 mg 3 times daily if needed

(For additional information see "Cyclobenzaprine: Pediatric drug information") Muscle spasm: Oral: Tablet, immediate release: Children ≥15 years: Refer to adult dosing.

Capsule, extended release: Use not recommended. Tablet, immediate release: Initial: 5 mg; titrate dose slowly and consider less frequent dosing.

There are no dosage adjustment provided in the manufacturer's labeling.

Capsule, extended release: Mild to severe impairment: Use not recommended. Tablet, immediate release: Mild impairment: Initial: 5 mg; use with caution; titrate slowly and consider less frequent dosing Moderate to severe impairment: Use not recommended.

Warnings & Precautions

Source: Lexicomp

Anticholinergic effects

Use with caution in patients with angle-closure glaucoma, increased intraocular pressure, or urinary frequency/hesitancy.

CNS depression

May cause CNS depression, which may impair physical or mental abilities; ethanol and/or other CNS depressants may enhance these effects. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Serotonin syndrome

Potentially life-threatening serotonin syndrome has occurred with cyclobenzaprine when used in combination with other serotonergic agents (eg, SSRIs, SNRIs, TCAs, buspirone, meperidine, tramadol, MAO inhibitors), bupropion, and verapamil. Monitor patients closely especially during initiation/dose titration for signs/symptoms of serotonin syndrome such as mental status changes (eg, agitation, hallucinations); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue cyclobenzaprine and any concomitant serotonergic agent immediately if signs/symptoms arise. Concomitant use or use within 14 days of discontinuing an MAO inhibitor is contraindicated.

Toxicity

Cyclobenzaprine shares the toxic potentials of the tricyclic antidepressants, including prolongation of conduction time, arrhythmias, and tachycardia; the usual precautions of tricyclic antidepressant therapy should be observed. Disease-related concerns:

Hepatic impairment

Use with caution in patients with mild hepatic impairment; plasma concentrations increased twofold in presence of mild impairment. Not recommended in moderate-to-severe hepatic impairment. Extended release capsules not recommended in patients with hepatic impairment of any severity (mild, moderate, or severe). Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Elderly

Extended release capsules not recommended for use in elderly. Other warnings/precautions:

Appropriate use

Limit therapy to 2-3 weeks; efficacy has not been established for longer periods of use.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events have not been observed in animal reproduction studies. The manufacturer recommends avoiding use during pregnancy unless clearly needed.

Lactation

It is not known if cyclobenzaprine is excreted in breast milk. Because cyclobenzaprine is closely related to tricyclic antidepressants, some of which are excreted in breast milk, the manufacturer recommends that caution be exercised when administering cyclobenzaprine to breastfeeding women.

LactMed: monitor the infant.

Monitoring

Clinical pearl	Signs/symptoms of serotonin syndrome (patients receiving other serotonergic drugs)

Chemistry & Properties

Formula	C20H21N
Molecular weight	275.4 g/mol
IUPAC name	N,N-dimethyl-3-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,9,11,13-heptaenylidene)propan-1-amine
CAS	303-53-7
PubChem CID	2895
InChIKey	`JURKNVYFZMSNLP-UHFFFAOYSA-N`
logP	4.55 (XLogP 5.2)
Polar surface area	3.24 Å²
H-bond acceptors / donors	1 / 0
Drug-likeness (QED)	0.68
Lipinski violations	0

SMILES

CN(C)CCC=C1c2ccccc2C=Cc2ccccc21

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes (logBB 1.06)

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2B6	Substrate	—
CYP2C19	Substrate	—
CYP2D6	Inhibitor	—
CYP2D6	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Bupropion	major
Codeine	major
Dexfenfluramine	major
Doxepin	major
Doxepin (topical)	major
Fenfluramine	major
Hydrocodone	major
Iohexol	major
Iopamidol	major
Methylene blue	major
Morphine	major
Morphine (liposomal)	major
Ozanimod	major
Potassium chloride	major
Potassium citrate	major
Procarbazine	major
Aclidinium	moderate
Acrivastine	moderate
Aldesleukin	moderate
Alimemazine	moderate
Anagrelide	moderate
Aprepitant	moderate
Atropine	moderate
Azatadine	moderate
Azelastine (nasal)	moderate
Brimonidine (ophthalmic)	moderate
Brimonidine (topical)	moderate
Brompheniramine	moderate
Carbinoxamine	moderate
Cetirizine	moderate
Chlorcyclizine	moderate
Chlorpheniramine	moderate
Clemastine	moderate
Clidinium	moderate
Clofedanol	moderate
Cyclizine	moderate
Cyproheptadine	moderate
Deferasirox	moderate
Dexbrompheniramine	moderate
Dicyclomine	moderate

Showing 40 of 100+.

Registered Products (4)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Destress 5 Tablets	Tablet 5 mg	30 tab	Sukhtian Pharma Company (SP)	3.200
Xaprine	Tablet 5 mg	30 tab	Sukhtian Group	4.000
DeStress 10 Tablets	Tablet 10 mg	30 tab	Sukhtian Pharma Company (SP)	4.500
Xaprine	Tablet 10 mg	30 tab	Sukhtian Group	5.640