Pharmacodynamics

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

Pharmacokinetics

Absorption: Mefenamic acid is rapidly absorbed after oral administration. In two 500-mg single oral dose studies, the mean extent of absorption was 30.5 mcg/hr/mL (17%CV).1,2   The bioavailability of the capsule relative to an IV dose or an oral solution has not been studied.
      
Following a single 1-gram oral dose, mean peak plasma levels ranging from 10-20 mcg/mL3 have been reported. Peak plasma levels are attained in 2 to 4 hours and the elimination half-life approximates 2 hours. Following multiple doses, plasma levels are proportional to dose with no evidence of drug accumulation. In a multiple dose trial of normal adult subjects (n=6) receiving 1-gram doses of mefenamic acid four times daily, steady-state concentrations of 20 mcg/mL were reached on the second day of administration, consistent with the short half-life.
 
The effect of food on the rate and extent of absorption of mefenamic acid has not been studied. Concomitant ingestion of antacids containing magnesium hydroxide has been shown to significantly increase the rate and extent of mefenamic acid absorption (see PRECAUTIONS, Drug Interactions).1
 
Distribution: Mefenamic acid has been reported as being greater than 90% bound to albumin.9 The relationship of unbound fraction to drug concentration has not been studied. The apparent volume of distribution (Vzss/F) estimated following a 500-mg oral dose of mefenamic acid was 1.06 L/kg.2
 
Based on its physical and chemical properties, Ponstel is expected to be excreted in
human breast milk.
 
Metabolism: Mefenamic acid is metabolized by cytochrome P450 enzyme CYP2C9 to 3-hydroxymethyl mefenamic acid (Metabolite l). Further oxidation to a 3-carboxymefenamic acid (Metabolite ll) may occur.10 The activity of these metabolites has not been studied.  The metabolites may undergo glucuronidation and mefenamic acid is also glucuronidated directly. A peak plasma level approximating 20 mcg/mL was observed at 3 hours for the hydroxy metabolite and its glucuronide (n=6) after a single 1-gram dose. Similarly, a peak plasma level of 8 mcg/mL was observed at 6-8 hours for the carboxy metabolite and its glucuronide.3
 
 
Excretion: Approximately fifty-two percent of a mefenamic acid dose is excreted into the urine primarily as glucuronides of mefenamic acid (6%), 3 -hydroxymefenamic acid (25%) and 3-carboxymefenamic acid (21%). The fecal route of elimination accounts for up to 20% of the dose, mainly in the form of unconjugated 3-carboxymefenamic acid.
 
The elimination half-life of mefenamic acid is approximately two hours. Half-lives of metabolites I and II have not been precisely reported, but appear to be longer than the parent compound.3  The metabolites may accumulate in patients with renal or hepatic failure.  The mefenamic acid glucuronide may bind irreversibly to plasma proteins. Because both renal and hepatic excretion are significant pathways of elimination, dosage adjustments in patients with renal or hepatic dysfunction may be necessary. Ponstel should not be administered to patients with preexisting renal disease or in patients with significantly impaired renal function.

Why is this medication prescribed?

Mefenamic acid is used to relieve mild to moderate pain, including menstrual pain (pain that happens before or during a menstrual period). Mefenamic acid is in a class of medications called NSAIDs. It works by stopping the body's production of a substance that causes pain, fever, and inflammation.

How should this medicine be used?

Mefenamic acid comes as a capsule to take by mouth. It is usually taken with food every 6 hours as needed for up to 1 week. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take mefenamic acid exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Other uses for this medicine

This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

What special precautions should I follow?

Before taking mefenamic acid,

• tell your doctor and pharmacist if you are allergic to mefenamic acid, aspirin or other NSAIDs such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn), any other medications, or any of the inactive ingredients in mefenamic acid capsules. Ask your pharmacist for a list of the inactive ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: antacids; angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik); amiodarone (Cordarone, Pacerone); atazanavir (Reyataz); clopidogrel (Plavix); diuretics ('water pills'), efavirenz (Sustiva); fluconazole (Diflucan); fluvastatin (Lescol); metronidazole (Flagyl); lithium (Eskalith, Lithobid), lovastatin (Mevacor); methotrexate (Rheumatrex), ritonavir (Norvir, in Kaletra); sulfamethoxazole (in Bactrim, in Septra); sulfinpyrazone (Anturane); trimethoprim (Proloprim); and zarfirlukast (Accolate). Your doctor may need to change the doses of your medications or monitor you more carefully for side effects.
• tell your doctor if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section or asthma, especially if you also have frequent stuffed or runny nose or nasal polyps (swelling of the inside of the nose); swelling of the hands, feet, ankles, or lower legs (fluid retention); or liver or kidney disease.
• tell your doctor if you are pregnant, especially if you are in the last few months of your pregnancy, you plan to become pregnant, or you are breast-feeding. If you become pregnant while taking mefenamic acid, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking mefenamic acid.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What side effects can this medication cause?

Mefenamic acid may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• diarrhea
• constipation
• gas or bloating
• headache
• dizziness
• nervousness
• ringing in the ears

Some side effects can be serious. If you experience any of the following symptoms or those mentioned in the IMPORTANT WARNING section, call your doctor immediately. Do not take any more mefenamic acid until you speak to your doctor.

• blurred vision
• unexplained weight gain
• fever
• blisters
• rash
• itching
• hives
• swelling of the eyes, face, lips, tongue, throat, hands, arms, feet ankles, or lower legs
• difficulty breathing or swallowing
• pale skin
• fast heartbeat
• excessive tiredness
• unusual bleeding or bruising
• lack of energy
• upset stomach
• loss of appetite
• pain in the upper right part of the stomach
• flu-like symptoms
• yellowing of the skin or eyes
• cloudy, discolored, or bloody urine
• back pain
• difficult or painful urination

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at http://www.fda.gov/MedWatch/index.html] or by phone [1-800-332-1088].

What storage conditions are needed for this medicine?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

In case of emergency/overdose

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

• extreme tiredness
• upset stomach
• vomiting
• stomach pain
• vomiting a substance that is bloody or looks like coffee grounds
• black, tarry, or bloody stools
• slowed breathing
• coma (loss of consciousness for a period of time)

What other information should I know?

Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking mefenamic acid.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.