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Cyclobenzaprine (sold under the brand name Flexeril, among others) is a medication used for
muscle spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle ...
s from musculoskeletal conditions of sudden onset. It is not useful in
cerebral palsy Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, stiff muscles, weak muscles, and tremors. There may be problems with sens ...
. It is taken by mouth. Use is not recommended for more than a few weeks. Common side effects include
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
, feeling tired, dizziness, and dry mouth. Serious side effects may include an
irregular heartbeat Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
. There is no evidence of harm in pregnancy, but it has not been well studied in this population. It should not be used with an
MAO inhibitor Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espec ...
. How it works is unclear. Cyclobenzaprine was approved for medical use in the United States in 1977. It is available as a generic medication. In 2020, it was the 39th most commonly prescribed medication in the United States, with more than 16million prescriptions. It was not available in the United Kingdom as of 2012.


Medical use

Cyclobenzaprine is used, in conjunction with physical therapy, to treat muscle spasms that occur because of acute musculoskeletal conditions. After sustaining an injury, muscle spasms occur to stabilize the affected body part, which may increase pain to prevent further damage. Cyclobenzaprine is used to treat such
muscle spasm A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder. A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle ...
s associated with acute, painful musculoskeletal conditions. It decreases pain in the first two weeks, peaking in the first few days, but has no proven benefit after two weeks. Since no benefit is proven beyond that, therapy should not be continued long-term. It is the best-studied muscle relaxer. It is not useful for spasticity due to neurologic conditions such as
cerebral palsy Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, stiff muscles, weak muscles, and tremors. There may be problems with sens ...
. A 2004 review found benefit for fibromyalgia symptoms, with a reported number needed to treat of 4.8 (meaning that 1 person out of every 4.8 benefits from treatment) for pain reduction, but no change in fatigue or tender points. A 2009 Cochrane review found insufficient evidence to justify its use in
myofascial pain syndrome Myofascial pain syndrome (MPS), also known as chronic myofascial pain (CMP), is a syndrome characterized by chronic pain in multiple myofascial trigger points ("knots") and fascial (connective tissue) constrictions. It can appear in any body part. ...
. It may also be used along with other treatments for
tetanus Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
.


Side effects

Cyclobenzaprine results in increased rates of drowsiness (38%), dry mouth (24%), and
dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...
(10%). Drowsiness and dry mouth appear to intensify with increasing dose. The sedative effects of cyclobenzaprine are likely due to its antagonistic effect on
histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discover ...
,
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...
, and
muscarinic receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...
s. Agitation is a common side effect observed, especially in the elderly. Some experts believe that cyclobenzaprine should be avoided in elderly patients because it can cause confusion, delirium, and cognitive impairment. In general, the National Committee for Quality Assurance recommends avoiding the use of cyclobenzaprine in the elderly because of the potential for more severe side effects.
Dysphagia Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or liq ...
, a life-threatening side-effect, may rarely occur. Treatment protocols and support should follow the same as for any structurally related tricyclic, such as
tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
s.


Overdose

The most common effects of overdose are drowsiness and
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
. Rare but potentially critical complications are
cardiac arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possi ...
, abnormal heart rhythms, severe low blood pressure,
seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...
s, and neuroleptic malignant syndrome. Life-threatening overdose is rare, however, as the
median lethal dose In toxicology, the median lethal dose, LD50 (abbreviation for " lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is ...
is about 338 milligrams/kilogram in mice and 425 mg/kg in rats. The potential harm is increased when central nervous system depressants and antidepressants are also used; deliberate overdose often includes alcohol among other drugs.


Interactions

Cyclobenzaprine has major contraindications with
monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, esp ...
s (MAOIs). At least one study also found increased risk of serotonin syndrome when cyclobenzaprine was taken with the serotonergic drugs duloxetine or phenelzine. These substances may interact with cyclobenzaprine: * Central nervous system depressants (e.g. alcohol,
opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
s, benzodiazepines, nonbenzodiazepines, phenothiazines,
carbamates In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formall ...
,
barbiturate Barbiturates are a class of depressant drugs that are chemically derived from barbituric acid. They are effective when used medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological addiction potential a ...
s, major tranquilizers) *
Monoamine oxidase inhibitor Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, esp ...
s taken within two weeks of cyclobenzaprine may result in serious, life-threatening side effects. Cyclobenzaprine may affect the medications used in surgical sedation and some surgeons request that patients temporarily discontinue its use prior to surgery.


Pharmacology

Cyclobenzaprine is a centrally acting muscle relaxant. Cyclobenzaprine is a 5-HT2 receptor antagonist; it relieves muscle spasm through action on the central nervous system at the brain stem, rather than targeting the peripheral nervous system or muscles themselves.


Pharmacodynamics


Pharmacokinetics

Cyclobenzaprine has an oral bioavailability of about 55% and approximately 93% is bound to proteins in plasma. The half-life of the drug is 18 hours and it has a plasma clearance of 0.7 litres per minute.


Comparison to other medications

Cyclobenzaprine has been found to be not inferior to tizanidine,
orphenadrine Orphenadrine (sold under many brand names) is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control i ...
, and carisoprodol in the treatment of acute lower back pain, although none have been proven to be effective for long-term use (beyond two weeks of treatment). No differences in pain or spasm scores were noted among these agents, nor when compared to benzodiazepines. However, nonbenzodiazepine (including cyclobenzaprine) treatment was found to have a lower risk of medication abuse and continuation of use against medical advice. Side effects such as sedation and
ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
are also less pronounced with nonbenzodiazepine antispasmodics. In a study on the treatment of musculoskeletal pain treatment with cyclobenzaprine alone or in combination with
ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus ar ...
, no significant differences in pain scores were noted among the three treatment groups. Peak benefit was found to occur on day seven of the treatment for all groups.


Formulations

By mouth, cyclobenzaprine is marketed as Apo-Cyclobenzaprin, Fexmid, Flexeril and Novo-Cycloprine. It is available in generic form. A once-a-day, extended-release formulation, Amrix, is available. Cyclobenzaprine is also used by compounding pharmacies in topical creams.


References


External links

* {{Authority control Dibenzocycloheptenes Dimethylamino compounds Drugs with unknown mechanisms of action Muscarinic antagonists Johnson & Johnson brands Muscle relaxants Wikipedia medicine articles ready to translate