Cyclobenzaprine is a muscle relaxant structurally very similar to the tricyclic antidepressant amitriptyline. Although cyclobenzaprine is clinically used as a muscle relaxant, in fact it has some of the pharmacological properties of tricyclic antidepressants.
Mechanism of action
Сiclobenzaprina shows some of the pharmacological effects of tricyclic antidepressants including anticholinergic effects, enhancement of norepinephrine and antagonism to reserpine. Cyclobenzaprine relieves muscle spasms through a central effect, probably in the brain stem, while having no effect on the neuromuscular junction or muscle. Nor is it a peripheral neuromuscular blocker. Cyclobenzaprine reduce pain associated with muscle spasms and contractions and improves mobility. Unlike dantrolene, cyclobenzaprine is ineffective in muscle spasms due to cerebral or spinal injuries.
After oral administration, cyclobenzaprine is well absorbed by the digestive tract. Probably the drug undergoes first pass metabolism and plasma levels vary greatly between patients. The first muscle relaxant effects shown within one hour and are maintained between 12 and 24 hours. To demonstrate a whole are required two days of treatment. The mean oral bioavailability ranging between 33 and 55%. Cyclobenzaprine shows linear kinetics, at least within the dose range of 2.5 to 10 mg. In healthy volunteers treated with 10 mg twice daily, the equilibrium concentrations at 3 or 4 days are reached.
Cyclobenzaprine is bound by 98% to plasma proteins. There is no evidence that this drug crosses the placental or that are excreted in breast milk barrier.
Cyclobenzaprine undergoes extensive metabolism to be excreted in the urine as inactive metabolites conjugates. The cytochrome P450 enzyme systems involved in metabolism are CYP3A4, CYP1A2 and to a lesser extent CYP2D6.
A small portion is excreted in the feces unchanged. The elimination half-life of 1-3 days. Plasma clearance is 0.7 L / min.
Plasma concentrations increase in the elderly and in patients with liver dysfunction, dose adjustments necessary being
Indications and dosing
Treatment of muscle spasms and painful musculoskeletal conditions
Adults and adolescents > 15 years old:
- recommended dosages are 20 to 40 mg per day, divided into 3 or 4 administrations. The maximum dose is 60 mg. The treatment should not continue beyond 2 to 3 weeks
Adolescents <15 years and children:
- The efficacy and safety of this drug have not been established
Treatment of fibromyalgia
- it is recommended to start treatment with doses of 10 mg to 10 mg increasing them 3 or 4 times daily. At these doses in a study in 208 patients, medication caused superior to placebo at 3 months results, but not at 6 months
Patients with renal dysfunction does not require dose adjustment.
Contraindications and Precautions
Tricyclic antidepressants may cause an allergic reaction in some people. It has been found that there is a cross-sensitivity between these drugs so precautions should be taken if a patient previously treated with a tricyclic antidepressant is prescribed cyclobenzaprine. In patients who have shown an allergy or hypersensitivity to tricyclic antidepressants should be considered an alternative to cyclobenzaprine.
Because of the potential risk of cardiac effects, cyclobenzaprine is contraindicated in patients with hypothyroidism. As in the case of tricyclic antidepressants, cyclobenzaprine should not be administered to patients recovering after an acute myocardial infarction: could cause a new heart attack or even death.
Cyclobenzaprine should not be given to patients who have prolonged or conduction defects (heart arrhythmias, AV block or congestive heart failure) QT interval. In patients who have had other heart problems, Cyclobenzaprine should be used with caution as rhythm disturbances may occur. Monitoring of all heart patients receiving cyclobenzaprine is recommended.
Because of their structural similarity with tricicílicos antidepressants, cyclobenzaprine should be used with caution in patients with psychological illnesses. Cyclobenzaprine is not effective in treating depression.
Cyclobenzaprine should not be used concomitantly with inhibitors monooxidasa. It is not known whether cyclobenzaprine can transform depression into mania or hypomania in susceptible patients (eg, in patients with bipolar disorder). Cyclobenzaprine should be used with caution in patients with psychotic disorders
Cyclobenzaprine lowers the seizure threshold and should be used with caution in patients with epilepsy. If seizures occur during treatment, cyclobenzaprine should be immediately withdrawn. Cyclobenzaprine can induce significant sedation, especially at the beginning of treatment. It should be advised of this fact to patients, particularly if they have to drive or operate heavy machinery.
Cyclobenzaprine should be used with caution in patients with a history of alcoholism or who are under treatment with other depressants of the central nervous system, because it can significantly reduce the mental alertness.
Due to its anticholinergic effects cyclobenzaprine should not be used in patients with paralytic ileus. It should be used with caution in patients with increased intraocular pressure, open-angle glaucoma, prostatic hypertrophy or urinatia retention. For their anticholinergic effects, cyclobenzaprine can reduce tear secretion which can cause discomfort to patients with lenses, being necessary the use of lubricating drops. All these effects are observed with greater intensity in the elderly.
Cyclobenzaprine should be used with caution in patients with liver disease because their metabolism may be affected. Cyclobenzaprine itself rarely impaired liver function.
Cyclobenzaprine is not effective in the treatment of spasticity associated with cerebral or spinal injuries or children with cerebral palsy.
Cyclobenzaprine is classified into risk category B in pregnancy. In laboratory animals, cyclobenzaprine has no effect on fertility or fetal development. However, there have been no controlled clinical studies performed during pregnancy so that this drug be used only if the benefits to the mother outweigh the possible risks to the fetus.
The American Academy of Pediatrics includes tricyclic antidepressants within the category of drugs whose effects in infants are not known, but may be potentially dangerous. Therefore, it is avoided to the extent possible the use of cyclobenzaprine during lactation.
Caution should be exercised in patients receiving cyclobenzaprine that are to be subjected to an X-ray using metrizamide as a contrast medium. As with other tricyclic drugs, the administration of metrizamide to patients receiving cyclobenzaprine can induce convulsions. Cyclobenzaprine should be discontinued at least 48 hours before the radiographic procedure with metrizamide, not resuming his business until at least 24 hours after myelography. During treatment with cyclobenzaprine patients are more sensitive to UV radiation so they avoid sun exposure, sunscreen used or suitable clothing.
As amitriptyline, cyclobenzaprine has antimuscarinic properties that may be additive with other anticholinergic drugs. Some of the drugs that should be used with caution if administered concomitantly with cyclobenzaprine are atropine, dicyclomine and other antimuscarinic; bupropion; clozapine; most tricyclic antidepressants; maprotiline; some phenothiazines (eg chlorpromazine, mesoridazine, promazine, thioridazine, triflupromazine); H1 antihistamines. Special attention should be paid to the digestive system and that co-administration of any of these drugs with cyclobenzaprine may cause paralytic ileus.
Cyclobenzaprine can show additive effects with other drugs that depress the central nervous system such as anxiolytics, sedatives, hypnotics, benzodiazepines, barbiturates, opioids, tricyclic antidepressants, phenothiazines, first generation H1 antihistamines and alcohol.
The antihypertensive effects of guanethidine guanadrel or can be reduced by cyclobenzaprine.
As a rule, cyclobenzaprine should not be used concomitantly with MAOIs due to possible adverse reactions that can be fatal. It must allow a washout period of 14 days between the withdrawal of treatment with MAOIs and the establishment of a treatment with cyclobenzaprine. Similarly, they are required between 5 and 7 days after treatment washing cyclobenzaprine before starting an MAOI therapy.
Cyclobenzaprine should be used with caution with tramadol. The tricyclic compounds that lower the seizure threshold increase the risk of seizures induced by tramadol.
It is not advisable to administer concomitantly with cisapride cyclobenzaprine because it can enhance the antiarrhythmic effects of the latter.
The herbs valerian (Valeriana officinalis) or kava kava (Piper methysticum) can cause additive effects of drowsiness and sedation, affecting the patient's ability to drive or perform tasks that require alertness. Possibly, it will be necessary to reduce the dose of medication or stop taking these plants.
The adverse reactions most frequently reported are cyclobenzaprine derive from their depressant effects on the central nervous system as well as its anticholinergic activity. In 39% of patients seen drowsiness, in 27% of cases xerostomia and dizziness in 11%.
Other adverse reactions observed in patients treated with cyclobenzaprine are fatigue or tiredness, weakness, nausea and vomiting, constipation, dyspepsia, dysgeusia, blurred vision, headache, and confusion. These adverse reactions occur in 1-3% of patients.