Ponstel

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.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Consider potential benefits and risks of mefenamic acid therapy as well as alternative therapies before initiating therapy with the drug.125 b Use lowest possible effective dosage and shortest duration of therapy consistent with patient’s treatment goals.125 b

Pain

Relief of mild to moderate pain in patients ≥14 years of age when the duration of therapy ≤1 week.125 b

Dysmenorrhea

Treatment of primary dysmenorrhea.125 b

Fever

Has been used for reduction of fever† associated with infection in children; routine use as an antipyretic not recommended because of potential adverse effects.a

General

• Consider potential benefits and risks of mefenamic acid therapy as well as alternative therapies before initiating therapy with the drug.125 b

Administration

Oral Administration

Administer orally.125 May be administered in divided doses up to 4 times daily.125

Dosage

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.125 b Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.125 b

Pediatric Patients

Adolescents ≥14 years of age should receive dosage recommended for adults.125 (See Adult Dosage.)

Adults

For mild to moderate pain in adults, 500 mg initially followed by 250 mg every 6 hours as necessary.125

For relief of primary dysmenorrhea in adults, 500 mg initially followed by 250 mg every 6 hours as necessary.125 Initiate at onset of bleeding and associated symptoms; treatment should not be necessary for >2–3 days.125

Prescribing Limits

Pediatric Patients

Duration of therapy usually should not exceed 1 week.125

Adults

Duration of therapy usually should not exceed 1 week.125

Therapy should not be necessary for more than 2–3 days.125

Special Populations

Hepatic Impairment

Dosage reduction may be required.125

Renal Impairment

Dosage reduction may be required if used in patients with renal impairment.125

Use not recommended in patients with preexisting renal disease or substantial renal impairment.125

Geriatric Patients

Select dosage carefully since may be more likely to have decreased renal function.125 b

Use Ponstel 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 Ponstel is taken on an as needed basis. Do not take more often than told by the doctor.

Mechanism of Action

Mefenamic acid has analgesic, anti-inflammatory, and antipyretic properties.

The mechanism of action of Ponstel, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).

Mefenamic acid is a potent inhibitor of prostaglandin synthesis in vitro. Mefenamic acid concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because mefenamic acid is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

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). 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/mL 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).

Mefenamic acid has been reported as being greater than 90% bound to albumin. 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.

Based on its physical and chemical properties, Ponstel is expected to be excreted in human breast milk (see PRECAUTIONS; Nursing Mothers).

Metabolism

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. 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.

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. 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 excretions 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 pre-existing renal disease or in patients with significantly impaired renal function (see WARNINGS; Renal Toxicity and Hyperkalemia).

Pediatric

Ponstel 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 hours).

Race

Pharmacokinetic differences due to race have not been identified.

Hepatic Impairment

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 compared to patients with normal hepatic function (see WARNINGS; Hepatotoxicity).

Renal Impairment

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 should not be administered to patients with pre-existing renal disease or in patients with significantly impaired renal function (see WARNINGS; Renal Toxicity and Hyperkalemia).

Aspirin

When NSAIDs were administered with aspirin, the protein binding of NSAIDs were reduced, although the clearance of free NSAID was not altered. The clinical significance of this interaction is not known. See Table 2 for clinically significant drug interactions of NSAIDs with aspirin (see PRECAUTIONS; Drug Interactions).

Clinical Studies

In controlled, double-blind, clinical trials, Ponstel 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, 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 was significantly superior to placebo in all parameters, and both treatments (drug and placebo) were equally tolerated.

Ponstel is contraindicated in the following patients:

• Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to mefenamic acid or any components of the drug product (see WARNINGS; Anaphylactic Reactions, Serious Skin Reactions).
• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients (see WARNINGS; Anaphylactic Reaction, Exacerbation of Asthma Related to Aspirin Sensitivity).
• In the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS; Cardiovascular Thrombotic Events).

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Cardiovascular Thrombotic Events (see WARNINGS)
• GI Bleeding, Ulceration and Perforation (see WARNINGS)
• Hepatotoxicity (see WARNINGS)
• Hypertension (see WARNINGS)
• Heart Failure and Edema (see WARNINGS))
• Renal Toxicity and Hyperkalemia (see WARNINGS)
• Anaphylactic Reactions (see WARNINGS)
• Serious Skin Reactions (see WARNINGS)
• Hematologic Toxicity (see WARNINGS)

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In patients taking Ponstel or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1-10% of patients are:

Gastrointestinal experiences including - abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal), vomiting, abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes, tinnitus

Additional adverse experiences reported occasionally and listed here by body system include:

Body as a whole - fever, infection, sepsis

Cardiovascular system - congestive heart failure, hypertension, tachycardia, syncope

Digestive system - dry mouth, esophagitis, gastric/peptic ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice

Hemic and lymphatic system - ecchymosis, eosinophilia, leukopenia, melena, purpura, rectal bleeding, stomatitis, thrombocytopenia

Metabolic and nutritional - weight changes

Nervous system - anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness; insomnia, malaise, nervousness, paresthesia, somnolence, tremors, vertigo

Respiratory system - asthma, dyspnea

Skin and appendages - alopecia, photosensitivity, pruritus, sweat

Special senses - blurred vision

Urogenital system - cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure

Other adverse reactions, which occur rarely are:

Body as a whole - anaphylactoid reactions, appetite changes, death

Cardiovascular system - arrhythmia, hypotension, myocardial infarction, palpitations, vasculitis

Digestive system - eructation, liver failure, pancreatitis

Hemic and lymphatic system - agranulocytosis, hemolytic anemia, aplastic anemia, lymph-adenopathy, pancytopenia

Metabolic and nutritional - hyperglycemia

Nervous system - convulsions, coma, hallucinations, meningitis

Respiratory - respiratory depression, pneumonia

Skin and appendages - angioedema, toxic epidermal necrosis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, urticaria

Special senses - conjunctivitis, hearing impairment

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

After observing the response to initial therapy with Ponstel, the dose and frequency should be adjusted to suit an individual patient's needs.

For the relief of acute pain in adults and adolescents ≥14 years of age, the recommended dose is 500 mg as an initial dose followed by 250 mg every 6 hours as needed, usually not to exceed one week.

For the treatment of primary dysmenorrhea, the recommended dose is 500 mg as an initial dose followed by 250 mg every 6 hours, given orally, starting with the onset of bleeding and associated symptoms. Clinical studies indicate that effective treatment can be initiated with the start of menses and should not be necessary for more than 2 to 3 days.

Ponstel (mefenamic acid) is available as 250 mg blue-banded, ivory capsules, imprinted with " FHPC 400" and "Ponstel®".

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].

Manufactured for:
Shionogi Inc.
Florham Park, NJ 07932

Manufactured by:
Halo Pharmaceutical Inc.
Whippany, NJ 07981

Rev. 05/2016

For inquires call 1-800-849-9707

NDC 59630-400-30

Ponstel®
(Mefenamic Acid Capsules, USP)
250 mg

Rx Only

30 CAPSULES

PHARMACIST: PLEASE DISPENSE
WITH MEDICATION GUIDE

SHIONOGI INC.

Applies to mefenamic acid: oral capsule

Gastrointestinal

Common (1% to 10%): Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, gastric ulcers, duodenal ulcers, vomiting
Rare (less than 0.1%): Eructation, pancreatitis
Frequency not reported: Peptic ulcer, dry mouth, esophagitis, gastritis, GI bleeding, glossitis, hematemesis, melena, rectal bleeding, stomatitis, anorexia, colitis, enterocolitis, pyrosis, steatorrhea, GI inflammation, ulcerative stomatitis, exacerbation of Crohn's disease, gastritis[Ref]

General

The most frequently reported side effects were gastrointestinal (GI) in nature and included abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, vomiting, and gastric or duodenal ulcers.[Ref]

Cardiovascular

Rare (less than 0.1%): Hypotension, arrhythmia, myocardial infarction, palpitations, vasculitis
Frequency not reported: Congestive heart failure, tachycardia, hypertension, cardiac failure, arterial thrombotic events[Ref]

Hematologic

Cases of autoimmune hemolytic anemia have been reported with continuous use of this drug for 12 months or longer. In such cases, the Coombs tests were positive for both accelerated RBC production and destruction. The process was reversible upon discontinuation of therapy.[Ref]

Common (1% to 10%): Anemia, bleeding time increased
Rare (less than 0.1%): Agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia
Frequency not reported: Eosinophilia, leukopenia, thrombocytopenia, bone marrow hypoplasia, hematocrit decreased, thrombocytopenic purpura, disseminated intravascular coagulation, neutropenia, autoimmune hemolytic anemia, eosinophilia, platelet aggregation inhibition[Ref]

Metabolic

Rare (less than 0.1%): Hyperglycemia
Frequency not reported: Hyponatremia, glucose intolerance, anorexia[Ref]

Nervous system

Common (1% to 10%): Dizziness, headache, drowsiness
Rare (less than 0.1%): Convulsions, coma
Frequency not reported: Syncope, paresthesia, somnolence, tremors, optic neuritis[Ref]

Respiratory

Rare (less than 0.1%): Respiratory distress, pneumonia
Frequency not reported: Asthma, dyspnea, bronchospasm, aggravated asthma, laryngeal edema[Ref]

Dermatologic

Common (1% to 10%): Rash, pruritus
Rare (less than 0.1%): Angioedema, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, urticaria
Frequency not reported: Ecchymosis, purpura, alopecia, photosensitivity, sweating[Ref]

Hepatic

Common (1% to 10%): Elevated liver enzymes
Rare (less than 0.1%): Liver failure
Frequency not reported: Hepatitis, jaundice, cholestatic jaundice, hepatorenal syndrome, mild hepatic toxicity[Ref]

Ocular

Rare (less than 0.1%): Conjunctivitis
Frequency not reported: Blurred vision, eye irritation, reversible loss of color vision, visual disturbances[Ref]

Genitourinary

Frequency not reported: Cystitis, dysuria, hematuria, oliguria, polyuria, proteinuria, false positive urobilinogen urine[Ref]

Renal

Common (1% to 10%): Abnormal renal function
Frequency not reported: Interstitial nephritis, renal failure, allergic/non-allergic glomerulonephritis, nephrotic syndrome, non-oliguric renal failure, renal papillary necrosis, tubulointerstitial nephritis[Ref]

Psychiatric

Rare (less than 0.1%): Hallucinations
Frequency not reported: Anxiety, confusion, depression, dream abnormalities, insomnia, nervousness[Ref]

Hypersensitivity

Rare (less than 0.1%): Anaphylactoid/anaphylactic reaction
Frequency not reported: Hypersensitivity reaction, non-specific allergic reaction[Ref]

Other

Common (1% to 10%): Edema, tinnitus
Rare (less than 0.1%): Death, meningitis, appetite changes, hearing impairment
Frequency not reported: Fever, infection, sepsis, weight changes, asthenia, malaise, vertigo, aseptic meningitis, ear pain, face edema, fatigue, malaise, multi-organ failure, pyrexia, fluid retention, edema of the larynx[Ref]

Some side effects of Ponstel may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.