Mefenamic acid

Mefenamic acid (ponstan) pharmacokinetic ,adminstration ,dosage,side effect & contraindication,and general information

1. Pharmacology MEFENAMIC ACID By Younis Saad Ula S alih Noor Alhuda K halaf Ghufran J abbar Mefenamc acid

2. Introduction Pharmacodynamics Pharmacokinetics Uses Dosage & Administration Side Effects Brand names References & Sources CONTENTS

3. What is mefenamic acid? Mefenamic acid is a non- steroidal anti-inflammatory drug used to treat pain. It is typically prescribed for oral administration. Introduction

4. Mefenamic Acid is a white to greyish-white , odorless , microcrystalline powder with a melting point of 230° to 231°C and water solubility of 0.004% at pH 7.1 . The chemical name is N-2,3-xylylanthranilic acid . The molecular weight is 241.29 .

5. Its molecular formula is C15H15N02 and the structural formula of Mefenamic Acid is :

6. Mefenamic Acid is a non-steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of Mefenamic Acid, like that of other NSAIDs, is not completely understood but may be related to prostaglandin inhibition . Pharmacodynamics

7. Absorption usually reaches peak plasma levels 2 to 4 hours after oral administration with a half life of 2 hours . Distribution Mefenamic acid and its metabolites are firmly bound to plasma proteins. Pharmacokinetics

8. MEFENAMIC ACID has demonstrated analgesic , anti-inflammatory and antipyretic properties in human clinical studies and in classical animal test systems. These effects may be due to its dual action on prostaglandins. It inhibits the enzymes of prostaglandin syntheses and also antagonises the actions of prostaglandin at the receptor sites. These effects may also be responsible for its effectiveness in the treatment of primary dysmenorrhoea. Action & Metabolism

9. Mefenamic acid metabolism is predominantly mediated via cytochrome P450 CYP 2C9 in the liver. Patients who are known or suspected to be poor CYP2C9 metabolisers should be administered mefenamic acid with caution as they may have abnormally high plasma levels due to reduced metabolic clearance . Metabolism I 3-hydroxymethyl Mefenamic Acid Metabolism II 3-carboxy Mefenamic Acid

10. Elimination Following a single dose , 67% of the total dose is excreted in the urine as unchanged drug or as one of the two metabolites. 20% to 25% of the dose is excreted in the faeces during the first three days.

11. Mefenamic acid is used for : T reatment of primary dysmenorrhoea Inflammation and fever soft tissue and dental pain. Mefenamic acid is an NSAID, NSAIDs treat the symptoms of pain and inflammation. They do not treat the disease that causes those symptoms. Uses

12. Dysmenorrhoea ( 500 mg) three times daily from the onset of pain and continued for the usual duration of pain . Menorrhagia ( 500 mg) three times daily. Therapy should not be continued for more than 7 days except on the advice of a physician. Other Indications ( 500 mg) three times daily DOSAGE AND ADMINISTRATION

13. Dental pain or soft tissue 500 mg three times daily Children 250 mg three times daily Not recommended for children under 14 years of age. Food(before/after ) Should be taken with food.

14. Symptoms Symptoms of over dosage are related to the amount of drug ingested and range from gastrointestinal discomfort and diarrhea to seizures, acute renal failure, vertigo, hallucination, coma and death. Plasma levels of up to 210 μg/mL (therapeutic range 1 to 10 μg/mL ) have been reported resulting in repeated generalised convulsions, but are not generally useful for evaluation and management of over dosage. Over dosage

15. There is no specific antidote for mefenamic acid overdose. T reatment is symptomatic and supportive, including fluid replacement and IV access especially to patients who are dehydrated or unable to ingest adequate fluids . Because mefenamic acid and its metabolites are firmly bound to plasma proteins, haemodialysis, and peritoneal dialysis may be of little value. Treatment

16. All medicines may cause side effects, but many people have no, or minor, side effects . Constipation, diarrhea, dizziness, gas, Headache, heartburn, nausea, stomach upset. Severe allergic reactions Rash, Hives, Itching, trouble breathing, tightness in the chest, swelling of the mouth, face, lips, or tongue. Side Effects

17. Be careful if you are pregnant there a potential risk to the fetus . the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective). The inhibition of prostaglandin synthesis by NSAIDs may adversely affect pregnancy. Epidemiological studies suggest an increased risk of spontaneous abortion after use of prostaglandin synthesis inhibitors in early pregnancy. In animals, administration of prostaglandin synthesis inhibitors has been shown to result in increased pre- and post-implantation loss.

18. NSAIDs given during the latter part of pregnancy may cause closure of the fetal ductus arteriosus , fetal renal impairment, inhibition of platelet aggregation . Continuous treatment with NSAIDs during the last trimester of pregnancy should only be given on sound indications. During the last few days before expected birth, agents with an inhibitory effect on prostaglandin synthesis should be avoided. It is not known if mefenamic acid or its metabolites crosses the placenta. Since there are no adequate and well-controlled studies in pregnant women

19. Use in Lactation Trace amounts of mefenamic acid may be present in breast milk and transmitted to the nursing infant. Thus mefenamic acid should not be taken by the nursing mother because of the effects of this class of drugs on the infant cardiovascular system.

20. 1. Patients showing evidence of chronic inflammation and/or active ulceration of either the upper or lower gastrointestinal tract and patients with pre-existing renal disease. 2. Patients in whom aspirin and/or other NSAIDs have induced symptoms of bronchospasm, allergic rhinitis because the potential exists for cross-sensitivity. 3 . Patients with impaired renal function or hepatic failure. CONTRAINDICATIONS

21. 4. Patients previously experiencing diarrhea on taking this drug. 5 . Patients who have previously exhibited hypersensitivity to mefenamic acid . 6 . Patients with severe heart failure.

22. Aspirin Mefenamic acid interferes with the anti-platelet effect of low-dose aspirin, and thus may interfere with aspirin’s prophylactic treatment of cardiovascular disease. Corticosteroids Concurrent use with NSAIDs may increase the risk of gastrointestinal ulceration or bleeding. INTERACTIONS

23. Cyclosporin or Tacrolimus Concomitant administration with NSAIDs increases the risk of nephrotoxicity. Hypoglycaemic agents There have been reports of changes in the effects of oral hypoglycaemic agents in the presence of NSAIDs. Therefore, mefenamic acid should be administered with caution in patients receiving insulin or oral hypoglycaemic agents.

24. Lithium Mefenamic acid has produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. Thus, when mefenamic acid and lithium are administered concurrently, patients should be observed carefully for signs of lithium toxicity. Methotrexate Caution is advised when methotrexate is administered concurrently with NSAIDs, including mefenamic acid, because NSAID administration may result in increased plasma levels of methotrexate, especially in patients receiving high doses of methotrexate.

25. Mefenamic acid is internal administration solid formulation : supplied in PVC/Al blister packs of 20 or 50 capsules and in bottles of 50 capsules. liquid formulation : 120 ml Examples: Beafemic , Mefalth , Mefivan , Ponstel , Ponstan , Ponstal , Parkemed , Revalan , Mafepain , Brand names

26. Mefamed, Potalon , Dolfenal, Meyerdonal, Alfoxan, Fenamin, Pangesic, Mefanorm , Meftal,

27. References : 1 .  http:// www.ncbi.nlm.nih.gov/pmc/articles/PMC2720641/ 2 .   "Side effects for Mefenamic Acid". Medline Plus. National Institutes of Health . 3.   http://www.drugs.com/ppa/mefenamic-acid.html 4.  http://www.eci2012.net/ References & Sources

28. 5.  http://www.drugs.com/ppa/mefenamic-acid.html 6.  http:// www.drugsupdate.com/generic/view/285 Sources : MedlinePlus Drug Information: Mefenamic Acid . Last accessed September 28, 2005 . Ponstel Pharmacology, Pharmacokinetics, Studies, Metabolism - Mefenamic Acid - RxList Monographs . Last accessed September 28, 2005 .

29. THANKS