Loxfen

Indications

• Acute pain
• Chronic pain conditions
• Osteoarthritis
• Rheumatoid arthritis
• Post-operative pain
• Musculoskeletal disorders

Dosage

Children: Refer to BNF for Children for specific paediatric dosing guidelines as it may vary based on the child's age and weight.

Adults: Refer to BNF for specific adult dosing guidelines as it may vary based on the condition being treated.

Mechanism of action

Loxoprofen itself is a prodrug and carries little-to-no pharmacological activity. It is rapidly metabolized to its trans-alcohol form, which is a potent and non-selective inhibitor of cyclooxygenase. Cyclooxygenase (COX) is present in two forms, COX-1 and COX-2. COX-1 is constitutively expressed and performs cellular housekeeping functions, while COX-2 is induced post-injury and is responsible for mediating inflammation and pain. Loxoprofen's active metabolite inhibits both COX isoforms, leading to reduced levels of pain, inflammation, and fever mediators such as prostaglandins and thromboxane.

Pharmacodynamics

Loxoprofen acts as a non-selective inhibitor of cyclooxygenase enzymes, thereby decreasing the formation of biologically active mediators of pain, fever, and inflammation. This includes a reduction in prostaglandins, prostacyclin, and thromboxane, contributing to its analgesic and anti-inflammatory effects.

Pharmacokinetics

Loxoprofen is rapidly absorbed and metabolized into its active form. The pharmacokinetics of loxoprofen involve a high bioavailability due to its prodrug nature, and the active metabolite demonstrates a significant half-life, allowing for effective pain control. The drug is primarily excreted through the urine, with metabolites being eliminated from the body.

Contra-indications

• Hypersensitivity to loxoprofen or any of its components
• Active or history of peptic ulcer disease
• Severe heart failure
• Severe hepatic impairment
• Severe renal impairment
• Concurrent use with other NSAIDs

Adverse effects

• Gastrointestinal disturbances such as nausea and vomiting
• Diarrhea
• Dizziness
• Headache
• Rash
• Increased risk of cardiovascular events
• Kidney impairment

Interactions

• Concurrent use with anticoagulants may increase the risk of bleeding
• May enhance the effects of other NSAIDs
• Caution with diuretics, as loxoprofen may reduce their effectiveness
• May interact with antihypertensive agents, reducing their efficacy

Precautions

• Use with caution in patients with a history of gastrointestinal disorders
• Monitor renal function in patients with pre-existing kidney issues
• Consider cardiovascular risk factors in long-term use
• Use with caution in elderly patients and those with comorbid conditions

Pregnancy

Loxoprofen should be avoided during pregnancy, particularly in the third trimester, due to potential effects on fetal cardiovascular function and risk of premature closure of the ductus arteriosus.

Breast-feeding

Loxoprofen is excreted in breast milk, caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Oral suspension

Mechanism of action

Loxoprofen itself is a prodrug and carries little-to-no pharmacological activity - it is rapidly metabolized to its trans-alcohol form, which is a potent and non-selective inhibitor of cyclooxygenase. Cyclooxygenase (COX) is present in 2 forms, COX-1 and COX-2, with each serving different functions. COX-1 is present in human cells and is constitutively released, performing cellular housekeeping functions such as mucus production and platelet aggregation. COX-2 is induced in human cells post-injury or due to other stimuli, is triggered to appear in large quantities at the sites of injury/stimuli, and is ultimately responsible for the mediation of inflammation and pain. Loxoprofen's active metabolite inhibits both COX isoforms, resulting in reduced expression of several mediators of pain, inflammation, and fever (e.g. prostaglandins, prostacyclin, thromboxane, etc).

Pharmacodynamics

Loxoprofen is a non-selective inhibitor of cyclooxygenase enzymes, which are responsible for the formation of various biologically active pain, fever, and inflammatory mediators. These include prostaglandins, prostacyclin, thromboxane, and arachidonic acid.