Acidum Tolfenamicum

Uses

Acidum Tolfenamicum 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 Acidum Tolfenamicum works

Acidum Tolfenamicum 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

Acidum Tolfenamicum 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 Acidum Tolfenamicum 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

Acidum Tolfenamicum 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 Acidum Tolfenamicum increases with metoclopramide and magnesium hydroxide and decreases with aluminium hydroxide. Risk of bleeding with anticoagulants and other NSAIDs increases when use with Acidum Tolfenamicum. 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

Acidum Tolfenamicum 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

Acidum Tolfenamicum 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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