TORIXA MR

Indications

• Muscle spasms from musculoskeletal conditions
• Pain associated with muscle tension
• Skeletal muscle spasm relief

Dosage

Children: Refer to the BNF for Children for specific dosing guidance.

Adults: Refer to the BNF for specific dosing guidance.

Mechanism of action

Chlorzoxazone inhibits degranulation of mast cells, preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), which are mediators of type I allergic reactions. It may also reduce the release of inflammatory leukotrienes. The drug acts by inhibiting calcium and potassium influx, leading to neuronal inhibition and muscle relaxation. Primarily, it exerts its effects at the spinal cord and subcortical areas of the brain, inhibiting multisynaptic reflex arcs responsible for muscle spasms.

Pharmacodynamics

Chlorzoxazone is effective as a centrally-acting agent for managing painful musculoskeletal conditions. It works by inhibiting the reflex pathways in the central nervous system that contribute to muscle spasms, resulting in reduced spasticity, relief of pain, and improved mobility of the affected muscles.

Pharmacokinetics

Chlorzoxazone is absorbed from the gastrointestinal tract and is metabolized in the liver, primarily via cytochrome P450 enzymes. It has a relatively short half-life, which may necessitate multiple dosing throughout the day for sustained effect. The metabolites are primarily excreted in the urine.

Adverse effects

• Drowsiness
• Dizziness
• Nausea
• Vomiting
• Rash
• Hepatotoxicity

Interactions

• Alcohol may enhance the sedative effects of chlorzoxazone.
• Caution is advised when used with other CNS depressants.

Precautions

• Use with caution in patients with liver disease.
• Monitor for signs of hepatotoxicity during treatment.
• Caution in patients with a history of allergy to chlorzoxazone or similar agents.

Pregnancy

Chlorzoxazone should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus, as safety data is limited.

Breast-feeding

Chlorzoxazone is excreted in breast milk; caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Capsules

Indications

• Pain and inflammation in musculoskeletal disorders
• Acute gout
• Osteoarthritis
• Rheumatoid arthritis
• Ankylosing spondylitis

Dosage

Children: For children aged 16-17 years, the recommended dose is 120 mg once daily for a maximum of 8 days.

Adults: 120 mg once daily for a maximum of 8 days.

Mechanism of action

Etoricoxib selectively inhibits isoform 2 of the cyclo-oxygenase enzyme (COX-2), preventing the conversion of arachidonic acid to prostaglandins (PGs), which are mediators of inflammation and pain. This selective inhibition results in reduced inflammatory responses without significantly affecting the COX-1 pathway, which is important for maintaining gastrointestinal mucosal integrity.

Pharmacodynamics

Etoricoxib exhibits a high selectivity for COX-2, being about 106 times more selective for COX-2 than for COX-1. This selective action minimizes the gastrointestinal side effects commonly associated with non-selective NSAIDs, as COX-1 plays a protective role in the gastric mucosa. Etoricoxib provides analgesic and anti-inflammatory effects by lowering prostaglandin levels involved in the inflammatory process.

Pharmacokinetics

Etoricoxib is well-absorbed following oral administration, with peak plasma concentrations typically occurring about 1 to 2 hours after ingestion. The drug has a half-life of approximately 22 hours, allowing for once-daily dosing. It is extensively metabolized in the liver, primarily via CYP2C9 and CYP3A4 pathways, and is excreted mainly through urine as metabolites. The presence of food does not significantly affect its absorption.

Contra-indications

• Active gastrointestinal bleeding
• Active gastrointestinal ulceration
• Severe cutaneous adverse reactions (SCARs)
• Cerebrovascular disease
• Uncontrolled hypertension (persistently above 140/90 mmHg)
• Severe renal failure
• Hypersensitivity to aspirin or other NSAIDs
• Ischaemic heart disease
• Active inflammatory bowel disease

Adverse effects

• Hypertension
• Fluid retention
• Gastrointestinal discomfort
• Nausea
• Vomiting
• Headache
• Dizziness
• Chest pain
• Heart failure
• Palpitations
• Skin reactions
• Malaise
• Nephrotoxicity
• Insomnia
• Anemia
• Visual impairment
• Aseptic meningitis
• Tinnitus

Interactions

• Increased exposure when used with combined hormonal contraceptives
• Increased exposure when used with hormone replacement therapy
• May interact with other NSAIDs

Precautions

• Caution in patients with cardiac impairment
• Caution in patients with renal impairment
• Dehydration risk
• Caution in patients with allergic disorders
• May mask symptoms of infection

Pregnancy

Avoid unless the potential benefit outweighs the risk, especially during the third trimester due to risk of closure of the fetal ductus arteriosus.

Breast-feeding

Use with caution during breastfeeding; the manufacturer advises avoiding use if possible.

Storage

Store in a cool, dry place, away from direct sunlight, and out of reach of children.

Formulations

• Modified-release tablet
• Dispersible tablet
• Oral suspension
• Oral solution

Mechanism of action

Chlorzoxazone inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Chlorzoxazone also may reduce the release of inflammatory leukotrienes. Chlorzoxazone may act by inhibiting calcium and potassium influx which would lead to neuronal inhibition and muscle relaxation. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex arcs involved in producing and maintaining skeletal muscle spasm

Pharmacodynamics

Chlorzoxazone is a centrally-acting agent for painful musculoskeletal conditions. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex a.c. involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles.

Mechanism of action

Like any other COX-2 selective inhibitor Etoricoxib selectively inhibits isoform 2 of cyclo-oxigenase enzyme (COX-2), preventing production of prostaglandins (PGs) from arachidonic acid.

Pharmacodynamics

Etoricoxib is a COX-2 selective inhibitor (approximately 106 times more selective for COX-2 inhibition over COX-1).