Cyrin

Approved Indications:

• Acute Musculoskeletal Conditions:
• Short-term adjunctive treatment (up to 2–3 weeks) for muscle spasm associated with acute, painful musculoskeletal conditions such as:
• Muscle strain
• Sprain
• Mechanical low back pain
• Cervical strain

Clinically Accepted Off-label Uses:

• Fibromyalgia Syndrome (FMS): For reduction of muscle tension, improvement of sleep quality, and pain relief.
• Temporomandibular Joint (TMJ) Dysfunction: Management of associated muscle spasms.
• Tension-type Headaches: As an adjunct in chronic cases linked with neck muscle tightness.
• Myofascial Pain Syndrome: As part of multimodal therapy in chronic musculoskeletal pain.
• Chronic back or neck pain: When associated with muscle tension unresponsive to first-line therapy.

Route of Administration: Oral

Adults:

• Initial dose: 5 mg orally three times daily
• May be increased to 7.5 mg or 10 mg three times daily based on individual response and tolerability
• Maximum recommended dose: 30 mg/day in divided doses
• Duration of therapy: Not to exceed 2 to 3 weeks, except in specific off-label chronic conditions under supervision

Elderly (≥65 years):

• Start with 5 mg once or twice daily
• Use with extreme caution due to increased sensitivity to anticholinergic effects and CNS depression

Pediatrics (<15 years):

• Not recommended due to lack of established safety and efficacy

Hepatic Impairment:

• Mild to moderate: Start with 5 mg once daily; titrate cautiously
• Severe hepatic impairment: Use contraindicated

Renal Impairment:

• No dose adjustment typically required, but monitor for adverse effects

Cyclobenzaprine is a centrally acting skeletal muscle relaxant structurally related to tricyclic antidepressants (TCAs). It acts primarily at the level of the brainstem rather than the spinal cord to reduce tonic somatic motor activity. It inhibits gamma and alpha motor neurons indirectly, leading to reduced muscle hyperactivity and spasm. Although its precise mechanism is not fully understood, cyclobenzaprine does not directly affect skeletal muscle fibers or neuromuscular junctions, distinguishing it from direct-acting muscle relaxants. Its tricyclic structure also contributes to mild sedative and anticholinergic properties.

• Absorption: Well absorbed orally
• Bioavailability: Approximately 33–55% (subject to first-pass metabolism)
• Onset of Action: Within 1 hour; peak effect in 3–8 hours
• Distribution: Widely distributed, protein binding ~93%
• Metabolism: Extensively metabolized in the liver via CYP3A4, CYP1A2, and CYP2D6
• Active Metabolites: Desmethylcyclobenzaprine and norcyclobenzaprine (pharmacologically active)
• Elimination Half-life:
• ~18 hours (immediate release)
• Up to 32–37 hours (extended release)
• Excretion: Mainly via urine (as metabolites)

• Pregnancy:
  Classified as Pregnancy Category B (no evidence of fetal harm in animal studies, but human data limited). Use only if clearly necessary, especially in the first trimester.
• Lactation:
  Unknown if excreted in human milk. Due to its structural similarity to TCAs and potential for sedation or anticholinergic effects in the infant, use with caution in nursing mothers.
• Recommendation:
  Avoid prolonged use during pregnancy or breastfeeding. Monitor infants if exposure occurs.

• Primary Class: Skeletal Muscle Relaxant
• Subclass: Centrally Acting, Tricyclic-structured agent

• Hypersensitivity to cyclobenzaprine or related compounds
• Use with or within 14 days of monoamine oxidase inhibitors (MAOIs)
• Hyperthyroidism
• Heart failure, arrhythmias, conduction disturbances, or recent myocardial infarction
• Severe hepatic impairment
• Use in pediatrics under 15 years of age

• Elderly patients may be more susceptible to sedation, confusion, or falls
• CNS depression: May impair mental or physical abilities; avoid driving or operating machinery
• Anticholinergic effects: Dry mouth, constipation, urinary retention—use cautiously in:
• Benign prostatic hyperplasia
• Glaucoma
• Cognitive impairment
• Serotonin syndrome risk when combined with SSRIs, SNRIs, or MAOIs
• Hepatic dysfunction: Use lower doses or avoid in moderate/severe liver disease
• Seizure risk: In rare cases with overdose or drug interactions
• Limit therapy duration due to lack of efficacy data beyond 2–3 weeks

Common:

• Central Nervous System: Drowsiness, dizziness, fatigue, headache
• Gastrointestinal: Dry mouth, nausea, constipation
• General: Malaise, blurred vision

Less Common:

• Tachycardia, palpitations
• Urinary retention
• Impaired coordination
• Increased appetite or weight gain

Rare but Serious:

• Confusion or hallucinations (especially in elderly)
• Cardiac arrhythmias
• Seizures (usually in overdose)
• Allergic reactions: Rash, angioedema, or anaphylaxis

Timing & Dose-dependence:

• Most side effects are dose-related and emerge within the first few days of therapy

• MAOIs: Risk of life-threatening serotonin syndrome or hypertensive crisis
• SSRIs, SNRIs, TCAs, tramadol, linezolid: May increase risk of serotonin syndrome
• Alcohol and CNS depressants (e.g., benzodiazepines, opioids): Potentiation of sedative effects
• CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin): May increase cyclobenzaprine levels
• Tramadol: Increased risk of seizures
• Anticholinergics (e.g., antihistamines, atropine): Additive anticholinergic burden

• Extended-release cyclobenzaprine (15–30 mg once daily) has become more available and is preferred for once-daily dosing in chronic muscle spasm
• Clinical practice guidelines continue to recommend cyclobenzaprine only for short-term use (≤2–3 weeks) for acute musculoskeletal conditions
• Off-label use in fibromyalgia remains common, though not guideline-endorsed
• New warnings highlight potential for serotonin syndrome and caution with polypharmacy in elderly

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C
• Humidity and Light: Protect from moisture and direct sunlight
• Handling: Keep in a tightly closed container; store away from children
• Oral Suspension (if compounded): Shake well before use; refrigerate if directed
• Shelf life: As per manufacturer’s packaging (typically 24–36 months)