Acide Tolfenamique

Acide Tolfenamique Uses, Dosage, Side Effects, Food Interaction and all others data.

Acide Tolfenamique 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

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.

Trade Name Acide Tolfenamique
Generic Tolfenamic acid
Tolfenamic acid Other Names Acide tolfenamique, ácido tolfenámico, Acidum tolfenamicum, Tolfenamic acid
Type
Formula C14H12ClNO2
Weight Average: 261.704
Monoisotopic: 261.05565634
Protein binding

Tolfenamic acid presents high protein binding properties reaching 99.7% of the administered dose. Studies have studied the changes in protein binding depending on the presence of certain disorders that modify the dialysis equilibrium. These studies verify that modifications in blood creatinine, urea and bilirubin can significantly alter the concentration of unbound tolfenamic acid. The main binding structure is predicted to be related to lipid membrane structures.

Groups Approved, Investigational
Therapeutic Class Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs), Other drugs for migraine
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
Acide Tolfenamique
Acide Tolfenamique

Uses

Acide Tolfenamique is used specifically for relieving the pain of migraine headaches and also recommended for use as an analgesic in post-operative pain, and fever.

How Acide Tolfenamique works

Acide Tolfenamique 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.

Dosage

Acide Tolfenamique dosage

Acute migraine attacks:

  • Adult: 200 mg when 1st symptoms appear may be repeated once after 1-2 hr.
  • Renal impairment: Dose adjustments may be needed. Severe: Avoid.

Mild to moderate pain:

  • Children: A pediatric dosage regimen has not yet been established.
  • Adult: 100-200 mg tid.
  • Renal impairment: Dose adjustments may be needed. Severe: Avoid. It should be taken with food. Take water/ or immediately after meals.

Preclinical safety data: The therapeutic index for Acide Tolfenamique is high, and gastrointestinal ulceration and kidney changes have only been seen with oral doses approximately 6-10 times the maximum therapeutic dose recommended for tolfenamic acid.

Special Precautions: Asthma, bronchospasm, bleeding disorders, cardiovascular diseases, history of peptic ulceration, hypertension, patients with infections, liver, cardiac, or renal function impairment. Increase water intake or dose reduction to reduce dysuria. CHF; elderly; lactation.

Side Effects

Dysuria especially in males; diarrhoea, nausea, epigastric pain, vomiting, dyspepsia, erythema, headache. Tremor, euphoria, fatigue, pulmonary infiltration, & haematuria. Potentially Fatal: Blood dyscrasias, toxic hepatitis.

Toxicity

Acide Tolfenamique has a relatively low acute toxicity with LD50 values in 200-1000 mg/kg. The metabolites of tolfenamic acid are reported to have an even less important toxicity. Some of the expected toxicity is related to the presence of gastrointestinal effects such as gut ulceration and renal papillitis.

Precaution

As is the case with other NSAIDs, tolfenamic acid should be used with caution in patients with a history of gastrointestinal ulceration, or impaired liver or kidney function.

The therapeutic index for tolfenamic acid is high, and gastrointestinal ulceration and kidney changes have only been seen with oral doses approximately 6-10 times the maximum therapeutic dose recommended for tolfenamic acid. In human volunteers, tolfenamic acid did not affect renal function.

Interaction

The rate of absorption of Acide Tolfenamique increases with metoclopramide and magnesium hydroxide and decreases with aluminium hydroxide. Risk of bleeding with anticoagulants and other NSAIDs increases when use with Acide Tolfenamique. It decreases antihypertensive response to loop diuretics, β-blockers and ACE inhibitors. Co-administration increases plasma concentrations of lithium, methotrexate and cardiac glycosides. It also increases the risk of nephrotoxicity with ACE inhibitors, ciclosporin, tacrolimus or diuretics.

Volume of Distribution

The volume of distribution is of 1.79-3.2 L/kg. When tested intravenously, the reported steady-state volume of distribution was 0.33 L/kg.

Elimination Route

Acide Tolfenamique pharmacokinetic is marked by a short tmax of 0.94-2.04 h. It also presented a linear pharmacokinetic profile with an AUC from 13-50 mcg/ml.h if administered in a dose of 2-8 mg/kg respectively. The oral absorption is delayed and it gives a mean lag-time to absorption of 32 min. The peak plasma concentration of 11.1 mcg/ml. The bioavailability of tolfenamic acid is around 75%.

Half Life

The estimated half-life of tolfenamic acid is 8.01-13.50 hours. When tested intravenously, the reported half-life was 6.1h.

Clearance

The estimated clearance rate of tolfenamic acid is 0.142-0.175 L.h/kg. When tested intravenously, the reported clearance rate was 72.4 ml.h/kg.

Elimination Route

Acide Tolfenamique is cleared relatively fast and it undergoes by hepatic metabolism where the produced metabolites are renally cleared as glucuronic acid conjugates. Most of the elimination occurs by extrarenal mechanisms in which the unchanged drug together with its glucuronide in urine accounts for only 8.8% of the administered dose.

Pregnancy & Breastfeeding use

Pregnancy: This medicine is not recommended for use during pregnancy unless considered essential by your doctor. This is particularly important in the first and third trimesters. Not to be given during the third trimester of pregnancy.

Lactation: In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.

Contraindication

Not to be used in-

  • Children and adolescents under 18 years of age
  • People with an active peptic ulcer or bleeding in the gut
  • Severe heart failure, severe kidney failure, Severe liver failure
  • People taking other NSAIDs, including COX-2 inhibitors

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor if you have previously experienced such an allergy. If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately

Acute Overdose

Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhoea, excitation, coma, drowsiness, dizziness, tinnitus, fainting, and convulsions. In cases of significant poisoning acute renal failure and liver damage are possible. Patients should be treated symptomatically as required.

Storage Condition

Store in a cool and dry place. Keep out of reach of children

Innovators Monograph

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FAQ

What is Acide Tolfenamique used for?

Acide Tolfenamique is used as a potent pain reliever in the treatment of acute migraine attacks, and disorders like dysmenorrhea, rheumatoid, and osteoarthritis.

How safe is Acide Tolfenamique?

This medicine may cause severe gastrointestinal bleeding and perforation after prolonged usage. These adverse events may occur with or without warning symptoms. This risk is especially higher in the elderly population and in patients with a history of gastrointestinal diseases.

What are the common side effects of Acide Tolfenamique ?

The common side effects of Acide Tolfenamique are include: Headache, nausea, vomiting, epigastric pain, GI bleeding, diarrhoea, disorientation, excitation, coma, drowsiness, tinnitus, fainting, convulsions. Renal failure and liver damage may occur in cases of significant acute poisoning.

Is Acide Tolfenamique safe in pregnancy?

Acide Tolfenamique is contraindicated during the third trimester of pregnancy.

Is Acide Tolfenamique safe in breastfeeding?

This medicine is not recommended for use in breastfeeding women unless absolutely necessary. All the risks and benefits should be discussed with the doctor before taking this medicine. Your doctor may advise you to discontinue breastfeeding or to discontinue the medicine based on your clinical condition.

How long does Acide Tolfenamique take to work?

It is generally used as a once a day drug with peak levels occurring at two to four hours after administration.

Can I drink alcohol with Acide Tolfenamique?

Interaction with alcohol is unknown. It is advisable to consult your doctor before consumption.

Can I drive after taking Acide Tolfenamique ?

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking Acide Tolfenamique. If affected, patients should not drive or operate machinery.

How fast does Acide Tolfenamique work?

Acide Tolfenamique is absorbed quickly and almost completely after oral administration. Maximum plasma concentrations are reached after about 1-1½ hours. The half-life in plasma is about 2 hours.

How often can I take Acide Tolfenamique?

You may take a second tablet after 1-2 hours if needed.

What happen if I miss Acide Tolfenamique?

If you miss giving your pet a dose of Acide Tolfenamique, give the next dose as soon as you remember or, if it close to the next scheduled dose, return to the regular schedule. Do not double dose to catch up.

Who should not take Acide Tolfenamique?

This medicine is not recommended for use in patients with a known allergy to Acide Tolfenamique, other NSAIDs, or any other inactive ingredients present along with it

Does Acide Tolfenamique effect my kidney?

Acide Tolfenamique should be used with extreme caution in patients suffering from kidney diseases due to the increased risk of severe adverse effects.

Does Acide Tolfenamique affect my liver?

Acide Tolfenamique should be used with extreme caution in patients suffering from liver diseases due to the increased risk of severe adverse effects.

Does Acide Tolfenamique affect my heart?

Acide Tolfenamique should be used with extreme caution in patients suffering from heart diseases due to the increased risk of worsening of the patient's condition.

*** Taking medicines without doctor's advice can cause long-term problems.
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