Mefenamic Acid

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).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

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 the following:

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

Ponstel® (mefenamic acid) is a member of the fenamate group of nonsteroidal anti- inflammatory drugs (NSAIDs). Each blue-banded, ivory capsule contains 250 mg of mefenamic acid for oral administration. Mefenamic acid is a white to greyish-white, odorless, microcrystalline powder with a melting point of 230°-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. Its molecular formula is C15H15NO2 and the structural formula of mefenamic acid is:

Each capsule also contains lactose, NF. The capsule shell and/or band contains citric acid, USP; D&C yellow No. 10; FD&C blue No. 1; FD&C red No. 3; FD&C yellow No. 6; gelatin, NF; glycerol monooleate; silicon dioxide, NF; sodium benzoate, NF; sodium lauryl sulfate, NF; titanium dioxide, USP.

Pharmacodynamics

Ponstel (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 Ponstel (mefenamic acid) , like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.

Pharmacokinetics

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

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 (mefenamic acid) is expected to be excreted in human breast milk.

Mefenamic acid is metabolized by cytochrome P450 enzyme CYP2C9 to 3-hydroxymethyl mefenamic acid (Metabolite I). Further oxidation to a 3-carboxymefenamic acid (Metabolite II) 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

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.3

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 (mefenamic acid) should not be administered to patients with preexisting renal disease or in patients with significantly impaired renal function.

TABLE 1: Pharmacokinetic Parameter Estimates for Mefenamic Acid

Special Populations

Ponstel (mefenamic acid) has not been adequately investigated in pediatric patients less than 14 years of age. A study in 17 preterm infants administered 2 mg/kg indicated that the half-life was about five times as long as adults, consistent with the low activity of metabolic enzymes in newborn infants. The mean Cmax in this study was 4 mcg/mL (range 2.9-6.1). The mean time to maximum concentration (Tmax) was 8 hours (range 2-18 hrs).11

Pharmacokinetic differences due to race have not been identified.

Mefenamic acid pharmacokinetics have not been studied in patients with hepatic dysfunction. As hepatic metabolism is a significant pathway of mefenamic acid elimination, patients with acute and chronic hepatic disease may require reduced doses of Ponstel (mefenamic acid) compared to patients with normal hepatic function.

Mefenamic acid pharmacokinetics have not been investigated in subjects with renal insufficiency. Given that mefenamic acid, its metabolites and conjugates are primarily excreted by the kidneys, the potential exists for mefenamic acid metabolites to accumulate. Ponstel (mefenamic acid) should not be administered to patients with preexisting renal disease or in patients with significantly impaired renal function.

Clinical Studies

In controlled, double-blind, clinical trials, Ponstel (mefenamic acid) was evaluated for the treatment of primary spasmodic dysmenorrhea. The parameters used in determining efficacy included pain assessment by both patient and investigator; the need for concurrent analgesic medication; and evaluation of change in frequency and severity of symptoms characteristic of spasmodic dysmenorrhea. Patients received either Ponstel (mefenamic acid) , 500 mg (2 capsules) as an initial dose of 250 mg every 6 hours, or placebo at onset of bleeding or of pain, whichever began first. After three menstrual cycles, patients were crossed over to the alternate treatment for an additional three cycles. Ponstel (mefenamic acid) was significantly superior to placebo in all parameters, and both treatments (drug and placebo) were equally tolerated.

REFERENCES

1. Neuvonen PJ, Kivisto KT: Enhancement of drug absorption by antacids. An unrecognized drug interaction. Clin Pharmacokinet. 27:120-8, Aug 1994.

2. Tall AR, Mistilits SP: Studies on Ponstan (mefenamic acid): I. Gastro-intestinal blood loss; II. Absorption and excretion of a new formulation. J Int Med Res (UK). 1975, 3 (3) p176-82.

3. Winder CV, Kaump DH, Glazko et al: Experimental observations of flufenamic, mefenamic, and meclofenamic acids. AnnPhys Med (Eng), Suppl p7-49.1967.

9. Champion GD, Graham GG: Pharmacokinetics of non-steroidal anti-inflammatory agents. Aust NZ J Med. 8 (Supp 1): 94-100, Jun 1978.

10. McGurk KA, Remmel RP, Hosagrahara VP, Tosh D, Burchell B: Reactivity of mefenamic acid 1-o- acyl glucuronide with proteins in vitro and ex vivo. Drug Metab Dispos. Aug 1996, 24 (8) p842-9.

11. Ito K, Niida Y, Sato J et al: Pharmacokinetics of mefenamic acid in preterm infants with patent ductus arteriosus. Acta Paediatr JPN. 36 (4): 387-91, 1994.

Take mefenamic acid exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Mefenamic Acid dose your doctor recommends will be based on the following (use any or all that apply):

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Mefenamic Acid is available in the following doses:

• Mefenamic Acid 250 Mg Oral Capsule

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger amounts or for longer than recommended. Use the lowest dose that is effective in treating your condition.

Mefenamic acid should not be used for longer than 7 days. Follow your doctor's dosing instructions very carefully.

If you use this medicine long-term, you may need frequent medical tests.

Mefenamic acid can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using mefenamic acid.

Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Avoid drinking alcohol. It may increase your risk of stomach bleeding.

Avoid taking aspirin while you are taking mefenamic acid.

Ask a doctor or pharmacist before using any cold, allergy, or pain medication. Many medicines available over the counter contain aspirin or other medicines similar to mefenamic acid. Taking certain products together can cause you to get too much of this type of medication. Check the label to see if a medicine contains aspirin, ibuprofen, ketoprofen, or naproxen.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

In the U.S.

• Ponstel

Available Dosage Forms:

• Capsule

Therapeutic Class: Analgesic

Pharmacologic Class: NSAID

Chemical Class: Fenamate

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For mefenamic acid, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to mefenamic acid or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of mefenamic acid in children below 14 years of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of mefenamic acid in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution and an adjustment in the dose for patients receiving mefenamic acid.

Pregnancy

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking mefenamic acid, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using mefenamic acid with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Ketorolac

Using mefenamic acid with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Aceclofenac
• Acemetacin
• Acenocoumarol
• Aluminum Carbonate, Basic
• Aluminum Hydroxide
• Aluminum Phosphate
• Amiloride
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amtolmetin Guacil
• Anagrelide
• Apixaban
• Ardeparin
• Argatroban
• Aspirin
• Balsalazide
• Bemiparin
• Bendroflumethiazide
• Benzthiazide
• Betamethasone
• Betrixaban
• Bismuth Subsalicylate
• Bivalirudin
• Bromfenac
• Budesonide
• Bufexamac
• Bumetanide
• Calcium Carbonate
• Cangrelor
• Celecoxib
• Certoparin
• Chlorothiazide
• Chlorthalidone
• Choline Magnesium Trisalicylate
• Choline Salicylate
• Cilostazol
• Citalopram
• Clomipramine
• Clonixin
• Clopamide
• Clopidogrel
• Cortisone
• Cyclopenthiazide
• Cyclosporine
• Dabigatran Etexilate
• Dalteparin
• Danaparoid
• Deflazacort
• Desipramine
• Desirudin
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexibuprofen
• Dexketoprofen
• Diazoxide
• Dibenzepin
• Diclofenac
• Diflunisal
• Digoxin
• Dihydroxyaluminum Aminoacetate
• Dihydroxyaluminum Sodium Carbonate
• Dipyridamole
• Dipyrone
• Donepezil
• Dothiepin
• Doxepin
• Droxicam
• Duloxetine
• Edoxaban
• Enoxaparin
• Eplerenone
• Epoprostenol
• Eptifibatide
• Escitalopram
• Ethacrynic Acid
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Feverfew
• Floctafenine
• Flufenamic Acid
• Fluocortolone
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Fondaparinux
• Furosemide
• Ginkgo
• Gossypol
• Heparin
• Hydrochlorothiazide
• Hydrocortisone
• Hydroflumethiazide
• Ibuprofen
• Iloprost
• Imipramine
• Indapamide
• Indomethacin
• Ketoprofen
• Lepirudin
• Levomilnacipran
• Lithium
• Lofepramine
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Magaldrate
• Magnesium Carbonate
• Magnesium Hydroxide
• Magnesium Oxide
• Magnesium Salicylate
• Magnesium Trisilicate
• Meadowsweet
• Meclofenamate
• Mefenamic Acid
• Melitracen
• Meloxicam
• Mesalamine
• Methotrexate
• Methyclothiazide
• Methylprednisolone
• Metolazone
• Milnacipran
• Morniflumate
• Nabumetone
• Nadroparin
• Naproxen
• Nefazodone
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nortriptyline
• Olsalazine
• Opipramol
• Oxaprozin
• Oxyphenbutazone
• Paramethasone
• Parecoxib
• Parnaparin
• Paroxetine
• Pemetrexed
• Pentosan Polysulfate Sodium
• Pentoxifylline
• Phenindione
• Phenprocoumon
• Phenylbutazone
• Phenyl Salicylate
• Piketoprofen
• Piroxicam
• Polythiazide
• Pralatrexate
• Prasugrel
• Prednisolone
• Prednisone
• Proglumetacin
• Propyphenazone
• Proquazone
• Protein C
• Protriptyline
• Reboxetine
• Reviparin
• Rivaroxaban
• Rofecoxib
• Salicylamide
• Salicylic Acid
• Salsalate
• Sertraline
• Sibutramine
• Sodium Bicarbonate
• Sodium Salicylate
• Spironolactone
• Sulfasalazine
• Sulindac
• Tacrolimus
• Tenoxicam
• Tianeptine
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tinzaparin
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Torsemide
• Treprostinil
• Triamterene
• Trichlormethiazide
• Trimipramine
• Trolamine Salicylate
• Valdecoxib
• Venlafaxine
• Vilazodone
• Vorapaxar
• Vortioxetine
• Warfarin
• Xipamide

Using mefenamic acid with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Alacepril
• Atenolol
• Azilsartan
• Azilsartan Medoxomil
• Benazepril
• Betaxolol
• Bisoprolol
• Candesartan
• Captopril
• Carteolol
• Carvedilol
• Celiprolol
• Cilazapril
• Delapril
• Enalapril
• Enalaprilat
• Eprosartan
• Esmolol
• Fosinopril
• Imidapril
• Irbesartan
• Labetalol
• Levobunolol
• Lisinopril
• Losartan
• Metipranolol
• Metoprolol
• Moexipril
• Nadolol
• Nebivolol
• Olmesartan
• Oxprenolol
• Penbutolol
• Pentopril
• Perindopril
• Pindolol
• Practolol
• Propranolol
• Quinapril
• Ramipril
• Sotalol
• Spirapril
• Telmisartan
• Temocapril
• Timolol
• Trandolapril
• Valsartan
• Zofenopril

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of mefenamic acid. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Asthma or
• Bleeding problems or
• Blood clots or
• Congestive heart failure or
• Dehydration or
• Edema (fluid retention or body swelling) or
• Heart attack, history of or
• Hyperkalemia (high potassium in the blood) or
• Hypertension (high blood pressure) or
• Kidney disease or
• Liver disease (eg, hepatitis) or
• Stomach or intestinal ulcers or bleeding, history of or
• Stroke, history of—Use with caution. May make these conditions worse.

• Aspirin-sensitive asthma or
• Kidney disease, severe or
• Stomach ulcers, active—Should not be used in patients with these conditions.

• Heart surgery (including coronary artery bypass graft [CABG] surgery)—Should not be used for pain right before or after surgery.

Use mefenamic acid as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food. Take with food if it causes an upset stomach.
• Take with a full glass of water.

What do I do if I miss a dose?

• If you take this medicine on a regular basis, take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• Many times mefenamic acid is taken on an as needed basis. Do not take more often than told by the doctor.

Carefully consider the potential benefits and risks of Mefenamic Acid and other treatment options before deciding to use Mefenamic Acid. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals ( seeWARNINGS; Gastrointestinal Bleeding, Ulceration, and Perforation).

Mefenamic Acid is indicated:

• For relief of mild to moderate pain in patients ≥ 14 years of age, when therapy will not exceed one week (7 days).
• For treatment of primary dysmenorrhea.

Mefenamic Acid Capsules USP 250 mg are Size ‘1’ yellow-yellow capsules with ‘ML’ imprinted on the cap & ‘250’ imprinted on the body. They are supplied as follows:

Bottles of 30 NDC                                          42571-258-30

Bottles of 100 NDC                                        42571-258-01

Dispense in a tight container as defined in the USP.

Storage

Store at room temperature 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

Made in India

Manufactured for:

Micro Labs USA Inc.

Princeton, NJ 08540

Revised: 12/2016

NDC 42571-258-30
Mefenamic Acid Capsules, USP
250 mg
PHARMACIST: PLEASE DISPENSE WITH MEDICATION GUIDE PROVIDED SEPARATELY
Rx Only
30 Capsules
MICRO LABS LIMITED

• Analgesic, Nonopioid
• Nonsteroidal Anti-inflammatory Drug (NSAID), Oral

Refer to adult dosing. Use with caution; initiate dose at lower end of the dosing range.

Pain, mild to moderate: Adolescents ≥14 years: Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, adjustment may be necessary due to extensive hepatic metabolism.

CBC, chemistry profile, occult blood loss, and periodic liver function tests; renal function (urine output, serum BUN and creatinine); signs or symptoms of GI bleeding; blood pressure.

Mefenamic acid crosses the placenta (Mackenzie 1985). Birth defects have been observed following in utero NSAID exposure in some studies; however, data is conflicting (Bloor 2013). Nonteratogenic effects, including prenatal constriction of the ductus arteriosus, persistent pulmonary hypertension of the newborn, oligohydramnios, necrotizing enterocolitis, renal dysfunction or failure, and intracranial hemorrhage have been observed in the fetus/neonate following in utero NSAID exposure. In addition, nonclosure of the ductus arteriosus postnatally may occur and be resistant to medical management (Bermas 2014; Bloor 2013). Because NSAIDs may cause premature closure of the ductus arteriosus, product labeling for mefenamic acid specifically states use should be avoided starting at 30 weeks' gestation.

The chronic use of NSAIDs in women of reproductive age may be associated with infertility that is reversible upon discontinuation of the medication. Consider discontinuing use in women having difficulty conceiving or those undergoing investigation of fertility. The use of NSAIDs close to conception may be associated with an increased risk of miscarriage (Bloor 2013; Bermas 2014).

More frequently reported side effects include: abdominal pain, diarrhea, and nausea. See below for a comprehensive list of adverse effects.

Due to lack of published clinical experience in nursing mothers and the potential for toxicity, other agents may be preferred.

Use is not recommended. Excreted into human milk: Yes (in trace amounts) Comments: The effects in the nursing infant are unknown.