Cyclobenzaprine is available in pharmacy as brand name Amrix, Fexmid and Flexeril. Cyclobenzaprine is prescribed by physician and not available on shelf of any pharmacy in USA. Cyclobenzaprine is classified as muscle relaxants and does not fall into controlled substance.
Chemical Structure of Cyclobenzaprine
Cyclobenzaprine, N-dimethyl-3-(dibenzo-cyclohepten-5-ylidene) propylamine. Cyclobenzaprine is synthesized by reacting 5H-dibenzo cyclohepten-5-one with 3-dimethylaminopropylmagnesium chlorides and subsequently dehydrated to carbinol. Chemical structure is similar to tricyclic antidepressants.
How Does Cyclobenzaprine Work?
Cyclobenzaprine is widely used as muscle relaxants. Animal model has shown cyclobenzaprine does not act at neuromuscular junction or muscle actin-myosin complex.Multiple animal research studies areindicating cyclobenzaprine blocks reuptake of norepinephrine at locus ceruleus,mid brain and spinal cord. Similar animal research has also shown cyclobenzaprine blocks 5 HT receptor of serotonergic system. Serotonin receptors also known as 5 HT receptors are found in central and peripheral nervous system. Cyclobenzaprine increases synaptic concentration of norepinephrine molecule within serotonergic system in brain and ventral horn of spinal cord. Increase norepinephrine at level of spinal cord inhibits alpha motor neuron activities. Serotonergic system modulates anxiety and mood disorder. Inhibition of 5 HT receptors causes blocking of descending serotonergic system. Modulation and suppression of cerebral and spinal neurons eventually suppresses spinal reflexes causing muscle contraction. Comparableoutcomes were observed in animal research with tricyclic antidepressants.
Cyclobenzaprine reduces peripheral muscle spasm by inhibiting central modulation activities. Cyclobenzaprine is ineffective if spasm is secondary peripheral skeletal triggering disease causing muscle contraction.
Dosage – Cyclobenzaprine is marketed as-
- Apo-Cyclobenzaprine (10 mg tablets),
- Flexural (5 and 10 mg tablets), Generic form available.
- Femi (7.5 mg tablet), Generic forms available.
- Novo-Cyclosporine (10 mg tablets),
- Matrix is extended release and dose is once a day, available in 15- and 30-mg capsules.
Ten mg tablet is usually taken two to four times a day. The extended release capsule is usually taken one or two times a day. Cyclobenzaprine is often not prescribed beyond 3 weeks without talking to your doctor.
Absorption- Cyclobenzaprine is absorbed by intestinal mucosal membrane. Estimated mean oral bioavailability of cyclobenzaprine ranges from 33% to 55%.
Distribution- Cyclobenzaprine exhibits linear pharmacokinetics over the dose range 2.5 mg to 10 mg. Level of plasma depends on liver and kidney function. Free drugs available to act on receptors depend on protein binding. Cyclobenzaprine is highly protein bound and has low bioavailability. Cyclobenzaprine reaches therapeutic plasma steady state level within 3-4 days.
Metabolism- Cytochrome enzymes and oxidation metabolize cyclobenzaprine by demethylation of active molecule. Mode of metabolism is slow resulting in half-life of 18 hours.
Elimination- Cyclobenzaprine is excreted by kidney as glucuronides. Excretion depends on age and kidney function. Plasma clearance is 0.7 L/min. Concentration of cyclobenzaprine is higher in elderly and patient with borderline kidney function. Cyclobenzaprine is eliminated quite slowly, with an effective half-life of 18 hours (range 8-37 hours); plasma clearance is 0.7 L/min. The plasma concentration of cyclobenzaprine is generally higher in the elderly and in patients with hepatic impairment.
Indications For Use
- Muscle spasm
- Spasticity in Cerebral palsy
- Low back pain or neck pain
- Tension headache
- Myofascial pain syndrome
- Multiple sclerosis
Precautions: Cyclobenzaprine can cause severe life threatening complication if used in following diseases and in combination with following medications.
- Irregular heartbeats and arrhythmias
- Congestive heart failure
- Heart block
- Liver disease
- MAO inhibitor
- Medication use in treatment of allergies, cough and cold
- MAO inhibitors (phenelzine and tranylcypromine)
- Sedatives; sleeping pills; tranquilizers; and
Anaphylaxis and severe allergy is very rare, but probable complication with cyclobenzaprine.
Symptoms of Anaphylaxis
- Skin reactions- itching, flushed or pale skin
- A feeling of warmth
- Bronchospasm– wheezing and difficult breathing
- Rapid heart beats
- Severe hypotension
- Dizziness and fainting
Symptoms Of Drug Allergies Other Than Hypersensitivity
- Skin rash
- Hives (urticaria)
- Facial swelling
- Shortness of breath
Pregnancy- Animal studies have failed to reveal evidence of teratogenicity. There are no controlled data in human pregnancy. Patient taking cyclobenzaprine prior to pregnancy and want to continued during pregnancy must consult obstetrician and neonatologist. There is no contraindication for cyclobenzaprine treatment during pregnancy. Results of animal lab studies suggest higher dosage of cyclobenzaprine in mice has not shown any impaired fertility or fetal abnormalities. There is no control human study or case report published regarding complication caused by cyclobenzaprine treatment in pregnancy.
Breast-feeding- Cyclobenzaprine is not excreted in human milk. There is no data of human research or any case report published in journal, indicating Flexeril excreted in in breast milk had caused side effects in infant following breast feeding.
Nursing Mothers- It is not known whether this drug is excreted in human milk. Metabolites of cyclobenzaprine are not studied in nursing mother. If mother has to feed child while taking cyclobenzaprine then consult neonatologist or pediatrician.
Pediatric Use- Safety and effectiveness of cyclobenzaprine in pediatric patients below 15 years of age have not been established.
Use in the Elderly- Plasma concentration of cyclobenzaprine was higher in elderly patients when compared with younger patient after same dosage in mg. Elderly patients is usually treated with 5 mg of Flexeril. Elderly patient are at risk for side effects like hallucination, drowsiness, confusion and cardiac side effects.
Storage- Store at 25 Degree C (77 Degree F); excursions permitted to 15-30 Degree C (59-86 Degree F). [See USP Controlled Room Temperature].
Side Effects of Cyclobenzaprine
General Side Effects:
- Dry mouth
- Skin rash
- Swelling of face and tongue
- Blurring vision
Cardiovascular Side Effects:
- Increase heart rate
- Irregular heart beats
- Chest pain
- Myocardial infarction
- Heart block
Central Nervous System:
- Drowsiness and dizziness
- Muscle twitching
- Abnormal gait
- Peripheral neuropathy
- Bell’s palsy
- Extrapyramidal symptoms
Digestive Side Effects:
- Loss of appetite
- Nausea and vomiting
- Gastric pain
- Jaundice – hepatitis
- Jaundice – cholestasis
- Tongue discoloration
- Paralytic Ileus
- Parotid adenoma
Respiratory Side Effects:
- Short of breath
Urogenital Side Effects:
- Urinary frequency and/or
- Impaired urination and urinary tract dilatation
- Testicular swelling
- Female breast enlargement
- Male Gynecomastia and galactorrhea
Hematic and Lymphatic Side Effects:
- Bone marrow depression
Musculoskeletal Side Effects:
- Local weakness
Endocrine Side Effects:
- Inappropriate ADH syndrome
Metabolic Side Effects:
- Elevation and lowering of blood glucose levels
- Weight gain or loss
- Loss of hair
Psychiatric Side Effects:
- Aggressive behavior.
Cyclobenzaprine has long half-life and withdrawal symptoms are not seen for 8 to 12 hours. If dose is missed then skip the dose and take the next dose at appropriate time. Do not take double dose to make up for the missed one.
- Flexeril is considered as non-habit forming drug.
Cyclobenzaprine Overdose Symptoms
- Persistent vomiting
- Cardiac arrest
- Slow or shallow breathing
- Severe Headache
- Feeling light-headed
Contact US National Poison Hotline at (USA) 1-800-222-1222 and (Health Canada) 1-866-234-2345.
In few cases patient may be dependent on Flexeril because of favorable effect of muscle relaxation and sedation. Patient may take few extra pills and may suffer with symptoms of overdose. Few patients may take few extra pills and run short of medications. Withdrawal symptoms will be seen if patient could not take pills for few days.
Inform Physician Immediately If You Have:
- Fast, pounding, or uneven heartbeats;
- Chest pain or heavy feeling, pain spreading to the arm or shoulder
- Nausea and vomiting
- Sudden numbness or weakness, especially on one side of the body
- Sudden headache
- Feeling light-headed, or fainting
Carcinogenesis, Mutagenesis, Impairment of Fertility
- Animal study has not indicated any signs of cancer inducing effect or enhancing growth of active cancer when treated with Flexeril at 5 to 40 times the maximum recommended dosage in human patient. Cyclobenzaprine did not affect the onset, incidence or distribution of neoplasia in an 81-week study in the mouse or in a 105-week study in the rat.
- Mutagenesis was not observed at dosage of up to 20 times.
- Impairment of fertility was not observed.