tolfenamic acid

Action and Spectrum

Actions and spectrum: 

tolfenamic acid suppresses prostaglandin production and exerts inhibitory effects on prostaglandin receptors. tolfenamic acid’s mode of action is like that of NSAIDs, which is based on the inhibition of COX-1 and COX-2 pathways to suppress prostaglandin secretion and action, which is how NSAIDs exert their anti-inflammatory and pain-blocking effects. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Unpleasant urination in males 

Nausea 

Vomiting 

Diarrhea 

Hypertension 

Hepatic failure 

Renal failure 

Black Box Warning

Black Box Warning  

Avoid overdose. Take plenty of water when this drug is administered to overcome painful micturition. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

The use of tolfenamic acid is contraindicated in people suffering with peptic ulcer, allergic to NSAIDs or aspirin. 

Caution: 

This drug should be used with caution in patients with bleeding disorders, hepatic or liver disorders, cardiac diseases, peptic ulcers, asthma. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: not recommended 

Lactation:  

Use of tolfenamic acid in feeding mothers is not adviced as this drug can be excreted in breast milk and cause harmful effects in infants.  

Pregnancy category:   

Category A: Studies that were well-controlled and met expectations revealed no risk to the foetus `in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the foetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology: 

tolfenamic acid is suggested mostly in the treatment of migraine. The mode of action of tolfenamic acid is based on the primary mechanism of action of NSAIDs, which entails the inhibition of COX-1 and COX-2 pathways to suppress prostaglandin secretion and function and, consequently, to exert its anti-inflammatory and pain-blocking action.  

Pharmacodynamics: 

Studies have demonstrated that tolfenamic acid exhibits both a dose-dependent inhibition of cutaneous edema and a non-dose dependent partial inhibition of irritant-induced temperature rise. Prostaglandin E2 synthesis was observed to be inhibited along the same lines, which indicates a corresponding COX-2 inhibition. It has been demonstrated that thromboxane is a powerful prostaglandin E inhibitor with a maximum inhibition of thromboxane greater than 80%.  

Pharmacokinetics:  

Absorption  

The short tmax of 0.94–2.04 h characterizes the pharmacokinetics of tolfenamic acid. In addition to this, it had a linear pharmacokinetic profile with an AUC ranging from 2 to 8 mg/kg and an AUC of 13 to 50 mcg/ml/h. The average lag time to absorption caused by delayed oral absorption is 32 minutes. 11.1 mcg/ml was the peak plasma concentration. tolfenamic acid has a bioavailability of about 75%.  

Distribution 

The distribution volume ranges from 1.79 to 3.2 L/kg. The reported steady-state volume of distribution during intravenous testing was 0.33 L/kg. 

Metabolism 

20% of the tolfenamic acid dosage injected is metabolized in the first pass. Research on urine metabolites have shown the identification of five metabolites, of which three are monohydroxylated, one is monohydroxylated and hydroxylated, and the fifth and final metabolite presented and oxidized methyl group to produce a carboxyl group. N-(2-hydroxymethyl-3-chlorophenyl)-anthranilic acid and N-(2-hydroxymethyl-3-chloro-4-hydroxyphenyl)-anthranilic acid are two of these hydroxylated metabolites.  

Elimination and excretion 

tolfenamic acid undergoes hepatic metabolism, where its metabolites are then excreted through the kidneys as glucuronic acid conjugates. Only 8.8% of the administered dose—the unmodified drug and its glucuronide in urine—remains after most of the drug is eliminated by extrarenal processes.  

Half-life: 

tolfenamic acid has an estimated half-life of 8.01-13.50 hours. 6.1hours half-life was reported when tested intravenously. 

Adminstartion

Administration: 

tolfenamic acid is administered orally in the form of tablets. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: tolfenamic acid  

Why do we use tolfenamic acid? 

tolfenamic acid is a non-steroidal anti-inflammatory(NSAID) drug used to relieve pain and inflammation. It is used in the treatment of acute pain and migraine attacks.