MYOXERIL TABLETS

Indications

• Muscle spasms
• Acute musculoskeletal conditions

Dosage

Children: The safety and efficacy of cyclobenzaprine in children have not been established; therefore, it is not generally recommended for use in pediatric patients.

Adults: The usual recommended dose is 5 mg taken three times daily, which may be increased to a maximum of 10 mg three times daily if required.

Mechanism of action

The exact mechanism of action of cyclobenzaprine is not fully understood, but it is believed to act at the supraspinal level within the locus coeruleus of the brainstem. Cyclobenzaprine reduces activity of efferent alpha and gamma motor neurons through inhibition of coeruleus-spinal or reticulospinal pathways, leading to decreased spinal cord interneuron activity. Additionally, it may influence descending serotonergic pathways via 5-HT2 receptor action.

Pharmacodynamics

Cyclobenzaprine demonstrates muscle relaxant properties by acting on the central nervous system, particularly in the brainstem. Its typical duration of action is 4-6 hours, despite a relatively long half-life. Caution is advised as it may contribute to serotonin syndrome when used with other serotonergic agents, prompting immediate discontinuation if symptoms arise.

Pharmacokinetics

Cyclobenzaprine is absorbed from the gastrointestinal tract and is extensively metabolized in the liver. It has a long elimination half-life, which contributes to its prolonged effects. The pharmacokinetics can be influenced by factors such as age, liver function, and concurrent medications.

Contra-indications

• Concurrent use of monoamine oxidase inhibitors (MAOIs)
• Hyperthyroidism
• Acute recovery phase following myocardial infarction
• Heart block
• Arrhythmias

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Fatigue
• Nausea
• Constipation
• Blurred vision
• Confusion
• Serotonin syndrome

Interactions

• May enhance the effects of alcohol and other central nervous system depressants
• Risk of serotonin syndrome with other serotonergic agents
• May interact with tricyclic antidepressants, increasing their sedative effects

Precautions

• Use with caution in patients with a history of urinary retention or glaucoma
• Caution in elderly patients due to increased sensitivity and risk of sedation
• Monitor for signs of serotonin syndrome, especially when used with other serotonergic drugs

Pregnancy

Cyclobenzaprine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data are available on its safety in pregnant women.

Breast-feeding

Cyclobenzaprine is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Extended-release capsules

Mechanism of action

The exact mechanism of action of cyclobenzaprine has not been fully elucidated in humans, and much of the information available regarding its mechanism has been ascertained from early animal studies. There is some evidence that cyclobenzaprine exerts its effects at the supraspinal level, specifically within the locus coeruleus of the brainstem, with little-to-no action at neuromuscular junctions or directly on skeletal musculature. Action on the brainstem is thought to result in diminished activity of efferent alpha and gamma motor neurons, likely mediated by inhibition of coeruleus-spinal or reticulospinal pathways, and ultimately depressed spinal cord interneuron activity. More recently it has been suggested that inhibition of descending serotonergic pathways in the spinal cord via action on 5-HT2 receptors may contribute to cyclobenzaprine’s observed effects. The centrally acting muscle relaxant cyclobenzaprine was thought to be an alpha 2-adrenoceptor agonist that reduced muscle tone by decreasing the activity of descending noradrenergic neurons. In the present study, we examined the effects of cyclobenzaprine on descending neurons by measuring the monosynaptic reflex in rats. Cyclobenzaprine reduced the monosynaptic reflex amplitude dose dependently and this effect was not inhibited by the alpha 2-adrenoceptor antagonists idazoxan and yohimbine. Cyclobenzaprine-induced monosynaptic reflex depression was not attenuated by noradrenergic neuronal lesions produced by 6-hydroxydopamine. However, cyclobenzaprine inhibited monosynaptic reflex facilitation induced by (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane, a 5-HT2 receptor agonist, in spinalized rats markedly, and 5-HT depletion by DL-p-chlorophenylalanine inhibited the depressive effect of cyclobenzaprine on the monosynaptic reflex. These results suggest that cyclobenzaprine is a 5-HT2 receptor antagonist and that its muscle relaxant effect is due to inhibition of serotonergic, not noradrenergic, descending systems in the spinal cord.

Pharmacodynamics

Cyclobenzaprine is a skeletal muscle relaxant that works on areas of the brainstem to reduce skeletal muscle spasm, though its exact pharmacodynamic behaviour is currently unclear. Despite its long half-life, it is relatively short-acting with a typical duration of action of 4-6 hours. Cyclobenzaprine has been reported to contribute to the development of serotonin syndrome when used in combination with other serotonergic medications. Symptoms of serotonin syndrome may include autonomic instability, changes to mental status, neuromuscular abnormalities, or gastrointestinal symptoms - treatment with cyclobenzaprine should be discontinued immediately if any of these reactions occur during therapy.