TOLFEDINE INJECTABLE

Indications

• Pain relief in osteoarthritis
• Pain relief in rheumatoid arthritis
• Management of dysmenorrhea
• Treatment of mild to moderate pain

Dosage

Children: Refer to the BNF for Children for paediatric dosing guidelines.

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Tolfenamic acid inhibits the biosynthesis of prostaglandins by blocking the cyclooxygenase (COX-1 and COX-2) pathways, leading to decreased prostaglandin secretion and action. Additionally, it exhibits inhibitory effects on leukotriene B4 chemotaxis in human polymorphonuclear leukocytes, contributing further to its anti-inflammatory action.

Pharmacodynamics

Tolfenamic acid demonstrates a non-dose dependent partial inhibition of irritant-induced temperature rise and a dose-dependent reduction in skin edema. It has been shown to inhibit serum thromboxane and prostaglandin E2 synthesis, indicating its effectiveness in modulating the inflammatory response by affecting COX-1 and COX-2 activity.

Pharmacokinetics

Tolfenamic acid is absorbed from the gastrointestinal tract and reaches peak plasma concentrations within a few hours. It is metabolized in the liver and has a half-life that allows for sustained therapeutic effects. The elimination is primarily via the kidneys, and it is important to monitor renal function during therapy.

Contra-indications

• Hypersensitivity to tolfenamic acid or any of its excipients
• Active or history of gastrointestinal bleeding or ulceration
• Severe heart failure
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Gastrointestinal disturbances such as nausea, vomiting, diarrhea, and dyspepsia
• Headache
• Dizziness
• Skin rashes and allergic reactions
• Renal impairment
• Hepatic impairment
• Cardiovascular events, including hypertension

Interactions

• Other non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of gastrointestinal toxicity
• Anticoagulants may have increased effects and risk of bleeding
• Diuretics and ACE inhibitors may have reduced efficacy due to NSAID-induced renal impairment
• Lithium levels may be increased with concurrent use

Precautions

• Use cautiously in patients with a history of peptic ulcer disease or gastrointestinal disorders
• Monitor renal function in patients with pre-existing renal impairment
• Caution in patients with cardiovascular disease due to potential for increased blood pressure
• Avoid use in late pregnancy due to potential effects on the fetal cardiovascular system

Pregnancy

Tolfenamic acid should be avoided during pregnancy, especially in the third trimester, due to potential risks to the fetus and complications during delivery.

Breast-feeding

Tolfenamic acid is excreted in breast milk; caution is advised when administered to nursing mothers.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Oral capsules
• Oral tablets
• Injection solution

Mechanism of action

Tolfenamic acid inhibits the biosynthesis of prostaglandins, and it also presents inhibitory actions on the prostaglandin receptors. As commonly thought, the mechanism of action of tolfenamic acid is based on the major mechanism of NSAIDs which consists of the inhibition of COX-1 and COX-2 pathways to inhibit prostaglandin secretion and action and thus, to exert its anti-inflammatory and pain-blocking action. Nonetheless, some report currently indicates that tolfenamic acid inhibits leukotriene B4 chemotaxis of human polymorphonuclear leukocytes leading to an inhibition of even 25% of the chemotactic response. This activity is a not ligand specific additional anti-inflammatory mechanism of tolfenamic acid.

Pharmacodynamics

Studies have shown that tolfenamic acid presents a non-dose dependent partial inhibition of irritant-induced temperature rise as well as a dose-dependent inhibition of skin edema. By studying its NSAID properties more closely, it was noted a dose-related inhibition of serum thromboxane which indicated the inhibition of COX-1. In the same line, there was noted a inhibition of prostaglandin E2 synthesis which marks a related COX-2 inhibition. The maximal inhibition of thromboxane was greater than 80% as well as is proven to be a potent prostaglandin E inhibitor.