NIFLURIL 400MG

Indications

• Rheumatoid arthritis
• Osteoarthritis
• Gout
• Pain management in inflammatory conditions
• Fever reduction

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Morniflumate works by inhibiting cyclooxygenase and 5-lipoxygenase pathways, which are crucial for the synthesis of inflammatory prostaglandins and leukotrienes. This inhibition reduces the production of these mediators, leading to decreased inflammation and pain. Additionally, it acts as a calcium-activated chloride channel blocker, influencing calcium channel activity in the body.

Pharmacodynamics

Morniflumate has been shown to significantly reduce the synthesis of leukotriene B4 (LTB4) and thromboxane B2 (TXB2) in both purified polymorphonuclear neutrophils and whole blood. It inhibits LTB4 synthesis by approximately 50% following administration, while TXB2 levels are reduced by over 85%. These effects indicate a potent reduction in arachidonic acid metabolism, contributing to its anti-inflammatory action.

Pharmacokinetics

Morniflumate is absorbed after oral administration, and its pharmacokinetics are characterized by the formation of a bioactive metabolite (M1), which correlates with therapeutic effects. The drug demonstrates biphasic behavior on calcium channels, suggesting the presence of distinct binding sites that mediate its action. Detailed pharmacokinetic parameters such as half-life, distribution, and excretion are not provided, and further studies may be needed to elucidate these aspects.

Pregnancy

There is limited information on the safety of morniflumate during pregnancy. Caution is advised.

Breast-feeding

Morniflumate is excreted in breast milk. Caution is advised when administering to breastfeeding women.

Storage

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

Formulations

• Oral tablet
• Powder for oral suspension

Mechanism of action

The primary mechanism of niflumic acid and its ester is action is inhibition of enzymes involved in the synthesis of inflammatory prostaglandins. This medication inhibits cyclooxygenase and 5-lipoxygenase pathways, which lead to fever and inflammation. Niflumic acid, a calcium-activated Cl- channel blocker, is an analgesic and anti-inflammatory agent used in the treatment of inflammatory conditions. Niflumic acid does directly inhibit calcium channels or activate potassium channels. Niflumic acid selectively reduces noradrenaline- and 5-HT-induced pressor responses by inhibiting a mechanism which leads to the opening of voltage-gated calcium channels. Niflumic acid (NFA) produces biphasic behavior on human CLC-K channels that suggests the presence of two functionally different binding sites: an activating site and a blocking site.

Pharmacodynamics

Morniflumate, given at therapeutic dosages to healthy human volunteers, on leukotriene B4 (LTB4) and thromboxane (TXB2) synthesis, both in purified PMNs (polymorphnuclear neutrophils) and in whole blood. In whole blood experiments, morniflumate reduced blood leukotriene B4 (LTB4) synthesis induced by Ca-ionophore A23187 Bx approximately 50%, both after a single dose and at steady state; the level of inhibition showed a pattern similar to the plasma levels of the bioactive metabolite of morniflumate (M1). The inhibition of serum thromboxane B2 (TXB2) levels was higher than 85%. Hence, morniflumate is demonstrated to reduce arachidonic acid metabolism, by exerting its effects on cyclooxygenase and 5-lipoxygenase. This characteristic might provide a better approach for anti-inflammatory therapy. In several animal models orally administered morniflumate, the beta-morpholinoethyl ester of niflumic acid, proved almost equal to the parent compound in anti-inflammatory, analgesic and antipyretic activity with the absence of gastric irritating/ulcerogenic effects of its acidic parent compound.