Consumer medicine information

Ponstan capsules

Mefenamic acid

BRAND INFORMATION

Brand name

Ponstan

Active ingredient

Mefenamic acid

Schedule

S4 | S2

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ponstan capsules.

What is in this leaflet

This leaflet answers some common questions about PONSTAN.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking PONSTAN against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What PONSTAN is used for

PONSTAN is used to relieve the symptoms of period pain and treat heavy periods.

It also provides short term relief of pain in conditions such as:

  • muscle and joint injuries such as sprains, strains and tendonitis
  • dental pain.

PONSTAN containing mefenamic acid belongs to a group of medicines called Non-Steroidal Anti-Inflammatory Drugs (or NSAIDs). These medicines work by relieving pain and inflammation.

Although PONSTAN can relieve the symptoms of pain and inflammation, it will not cure your condition.

Your doctor may have prescribed PONSTAN for another reason.

Ask your doctor if you have any questions about why PONSTAN has been prescribed for you.

PONSTAN is not addictive.

Before you take PONSTAN

When you must not take it

Do not take PONSTAN if:

  1. you have an allergy to:
  • mefenamic acid or any of the ingredients listed at the end of this leaflet
  • aspirin
  • any other NSAID medicine including COX-2 inhibitors.
Many medicines used to treat headache, period pain or other aches and pains contain aspirin or NSAID medicines.
If you are not sure if you are taking any of these medicines, ask your doctor or pharmacist.
Symptoms of an allergic reaction to these medicines may include:
- asthma, wheezing or shortness of breath
- swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
- hives, itching or skin rash
- fainting.
If you are allergic to aspirin or NSAID medicines and take PONSTAN, these symptoms may be severe.
  1. you had diarrhoea with this medicine in the past.
Diarrhoea may recur if you take PONSTAN again.
  1. you have a gastric ulcer (i.e. stomach or duodenal ulcer), a recent history of one, or have had gastric ulcers before.
  2. you have or have had inflammation and/or ulceration of the lining of the stomach or bowel.
Some examples of these conditions include Crohn's disease and ulcerative colitis.
  1. you have kidney disease.
  2. you have severe heart failure.
  3. you have liver failure.
  4. you are about to have coronary artery bypass surgery.
  5. children under 14 years of age.

Do not take PONSTAN if the packaging is torn or shows signs of tampering.

Do not take PONSTAN if the expiry date (EXP) printed on the pack has passed. If you take this medicine after the expiry date has passed, it may not work as well.

If you are not sure if you should start taking PONSTAN contact your doctor or pharmacist.

Before you start to take it

Tell your doctor or pharmacist if you have any allergies to:

  • any other medicines including aspirin or other NSAID medicines
  • any other substances, such as foods, preservatives or dyes.

Tell your doctor or pharmacist if you have or have had any medical conditions, especially the following:

  • vomiting blood or bleeding from the back passage
  • heart failure, heart attack, stroke
  • heart disease. Use of PONSTAN may increase your risk of developing cardiovascular events (e.g. heart attack) even if you don't have a history of heart disease.
  • high blood pressure
  • blood clots
  • a tendency to bleed or other blood problems such as anaemia
  • heartburn, indigestion, stomach ulcer or other stomach problems
  • bowel or intestinal problems such as ulcerative colitis
  • diarrhoea
  • asthma
  • pinkish, itchy swellings on the skin (also called hives) or any other skin rash.

Tell your doctor or pharmacist if you are using an intrauterine contraceptive device (IUCD).

Tell your doctor if you are pregnant or plan to become pregnant. PONSTAN may affect your developing baby if you take it during pregnancy. Pregnant woman taking PONSTAN should be closely monitored by their doctor.

Tell your doctor if you are breastfeeding. PONSTAN passes into breast milk and may affect your baby.

Your doctor will discuss with you the benefits and risks of taking this medicine.

If you have not told your doctor or pharmacist about any of the above, tell them before you take any PONSTAN.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with PONSTAN. These include:

  • aspirin including low doses of aspirin used to prevent your blood from clotting in certain heart conditions
  • warfarin or similar medicines including Eliquis, Xarelto or Pradaxa that are used to stop blood clots
  • some medicines used to treat high blood pressure
  • corticosteroids, medicines used to suppress the immune system or reduce inflammation
  • some medicines used to treat diabetes
  • lithium, a medicine used to treat mood swings in patients with bipolar disorder
  • cyclosporin or tacrolimus, medicines used to suppress the immune system
  • selective serotonin reuptake inhibitors, medicines used for depression
  • methotrexate, a medicine used to treat arthritis and some cancers.

These medicines may be affected by PONSTAN, or may affect how well it works. You may need to take different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while taking PONSTAN.

How to take PONSTAN

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

The usual dose of PONSTAN is 2 capsules (500 mg) three times daily with meals.

Your doctor may recommend a different dose. This may depend on your age, your condition and whether or not you are taking any other medicines.

Take PONSTAN exactly as your doctor has prescribed.

How to take it

Swallow PONSTAN capsules whole with a full glass of water.

Do not chew them.

Take PONSTAN with or after food. This may help reduce the possibility of stomach upset.

How long to take it

Do not take PONSTAN for longer than your doctor says.

Do not exceed the dosage recommended by your doctor.

If you are not sure how long to take PONSTAN, talk to your doctor or pharmacist.

If you need to take PONSTAN for a long time, see your doctor for regular check-ups so that he/she can monitor your condition and treatment.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as soon as you remember, and then go back to taking your capsules as you would normally.

Do not take a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone Australia 13 11 26 or New Zealand 0800 POISON or 0800 764 766) for advice, or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have taken too much PONSTAN. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much PONSTAN, you may experience pain or tenderness in the stomach, diarrhoea, muscle twitches, seizure (fit), confusion, dizziness or hallucination.

While you are taking PONSTAN

Things you must do

If you become pregnant while taking PONSTAN tell your doctor immediately.

If you are about to start taking any new medicine tell your doctor and pharmacist that you are taking PONSTAN.

Tell all of the doctors, dentists, and pharmacists that are treating you that you are taking PONSTAN.

If you are going to have surgery, tell your doctor you are taking PONSTAN.

If you get an infection while using PONSTAN, tell your doctor. PONSTAN may hide some of the signs of an infection and may make you think, mistakenly, that you are well or that it is not serious. Signs of an infection may include fever, pain, swelling and redness.

If you need to have any medical tests while you are taking PONSTAN, tell your doctor. PONSTAN may affect the results of some tests.

Things you must not do

Do not give PONSTAN to anyone else, even if they have the same condition as you.

Do not take PONSTAN to treat any other complaints unless your doctor tells you to.

Things to be careful of

Be careful driving or operating machinery until you know how PONSTAN affects you. As with other NSAID medicines, PONSTAN may cause dizziness or light-headedness in some people. Make sure you know how you react to PONSTAN before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed. If this occurs do not drive. If you drink alcohol, dizziness or light-headedness may be worse.

Be careful drinking alcohol whilst taking PONSTAN. As with other NSAID medicines, alcohol may increase your risk of developing gastro intestinal complications.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking PONSTAN.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

It can be difficult to tell whether side effects are the result of taking PONSTAN, effects of your condition or side effects of other medicines you may be taking. For this reason it is important to tell your doctor of any change in your condition.

If you are over 65 years of age you may have an increased chance of getting side effects.

Do not be alarmed by the list of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if...

Tell your doctor if you notice any of the following and they worry you:

  • stomach upset including nausea (feeling sick), vomiting, heartburn, indigestion, cramps
  • loss of appetite
  • constipation, diarrhoea, pain in the stomach, wind
  • fluid retention, swelling
  • dizziness, light-headedness
  • drowsiness
  • nervousness
  • headache
  • sleeplessness.

These are the more common side effects of PONSTAN.

Tell your doctor as soon as possible if...

Tell your doctor as soon as possible if you notice any of the following:

  • severe dizziness
  • severe or persistent headache
  • severe pain or tenderness in the stomach
  • severe diarrhoea
  • eye problems such as blurred vision or loss of colour vision
  • ear pain
  • fast or irregular heartbeats, also called palpitations
  • excessive sweating
  • signs of frequent or worrying infections such as fever, severe chills, sore throat or mouth ulcers
  • bleeding or bruising more easily than normal, reddish or purplish blotches under the skin
  • worsening blood sugar levels in patients with diabetes
  • signs of anaemia, such as tiredness, being short of breath, and looking pale
  • a change in the colour of urine passed, blood in the urine
  • a change in the amount or frequency of urine passed, burning feeling when passing urine
  • bulky, grey or pale coloured stools
  • yellowing of the skin and eyes, also called jaundice
  • unusual weight gain, swelling of ankles or legs.

The above list includes serious side effects that may require medical attention.

Go to hospital if...

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if any of the following happen:

  • vomiting blood or material that looks like coffee grounds
  • bleeding from the back passage, black sticky bowel motions (stools) or bloody diarrhoea
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • asthma, wheezing, shortness of breath
  • sudden or severe itching, skin rash, hives
  • fainting, seizures or fits
  • pain or tightness in the chest
  • fever, nausea, vomiting, headache, stiff neck and extreme sensitivity to bright light
  • severe blisters and bleeding in the lips, eyes, mouth, nose and genitals.

These are very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare.

Other side effects not listed above may also occur in some patients.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell.

Ask your doctor or pharmacist if you don't understand anything in this list.

Some of the other possible side effects can only be found when your doctor does tests from time to time to check your progress.

After taking PONSTAN

Storage

Keep your capsules in the pack until it is time to take them. If you take the capsules out of the pack they will not keep well.

Keep the capsules in a cool dry place where the temperature stays below 30°C.

Do not store PONSTAN or any other medicine in the bathroom or near a sink. Do not leave it in the car or on window sills. Heat and dampness can destroy some medicines.

Keep PONSTAN where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking PONSTAN or the capsules have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

PONSTAN capsules have an ivory opaque body and an aqua blue opaque cap, and are marked in black with "Parke Davis" on the body and cap.

PONSTAN comes in blister packs of 50 capsules. This presentation is available only with a doctor's prescription.

Ingredients

Active ingredient:

Each PONSTAN capsule contains 250 mg mefenamic acid.

Inactive ingredients:

  • lactose monohydrate
  • titanium dioxide
  • iron oxide yellow
  • brilliant blue
  • gelatin
  • carbon black.

PONSTAN does not contain sucrose, gluten, tartrazine or any other azo dyes.

Distributor

PONSTAN is supplied in Australia by:

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

Australian Registration Number

AUST R 225658 - blister pack of 50

Date of preparation

This leaflet was prepared in May 2020.

® Registered Trademark.

© Pfizer Australia 2015.

Published by MIMS July 2020

BRAND INFORMATION

Brand name

Ponstan

Active ingredient

Mefenamic acid

Schedule

S4 | S2

 

1 Name of Medicine

Mefenamic acid.

6.7 Physicochemical Properties

Mefenamic acid is one of the fenamate series of nonsteroidal anti-inflammatory agents. It is a white or almost white, microcrystalline powder. The drug is almost insoluble in water, slightly soluble in ethanol (96 percent) and in methylene chloride. It dissolves in dilute solutions of alkali hydroxides.

Chemical structure.


Chemical name: N-(2,3, xylyl)-anthranilic acid.
Molecular formula: C15H15NO2.
Molecular weight: 241.3.

CAS number.

CAS Registry Number: 61-68-7.

2 Qualitative and Quantitative Composition

Ponstan capsules contain the active ingredient mefenamic acid 250 mg/capsule.

Excipient(s) with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Hard capsule.
Ponstan capsules have an opaque aqua blue cap and opaque ivory body with "PARKE DAVIS" printed in black on both the body and cap.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Ponstan has demonstrated analgesic, anti-inflammatory and antipyretic properties in human clinical studies and in classical animal test systems. These effects may be due to Ponstan's dual action on prostaglandins. It inhibits the enzymes of prostaglandin synthetase 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. The pain of primary dysmenorrhoea is thought to be due to increased abnormal uterine activity and uterine ischaemia, probably induced by release of PGF or due to increase in the ratio of PGF:PGE2. Prostaglandins are also believed to be responsible, at least in some part, for the symptoms of menorrhagia.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Single and multiple studies have shown that Ponstan 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.

Metabolism.

Mefenamic acid metabolism is predominantly mediated via cytochrome P450 CYP2C9 in the liver. Patients who are known or suspected to be poor CYP2C9 metabolisers, based on previous history/ experience with other CYP2C9 substrates, should be administered mefenamic acid with caution as they may have abnormally high plasma levels due to reduced metabolic clearance.
Two distinct metabolic products, one a hydroxymethyl derivative and the other a carboxy derivative, have been identified in both plasma and urine. Mefenamic acid and its two metabolic derivatives become conjugated with glucuronic acid through an ester linkage which is alkali labile and are excreted principally in the urine, but also to some extent in the bile and faeces.

Excretion.

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.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of primary dysmenorrhoea and primary menorrhagia.
Short-term relief of mild to moderate pain such as dental pain and soft tissue pain.

4.3 Contraindications

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 non-steroidal anti-inflammatory drugs (NSAIDs) have induced symptoms of bronchospasm, allergic rhinitis or urticaria, because the potential exists for cross sensitivity.
3. Patients with impaired renal function.
4. Patients with severe hepatic impairment.
5. Patients previously experiencing diarrhoea on taking this drug.
6. Patients who have previously exhibited hypersensitivity to mefenamic acid or any of the components of Ponstan (see Section 6.1 List of Excipients).
7. Patients with severe heart failure.
8. Treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
9. Children under 14 years of age.

4.4 Special Warnings and Precautions for Use

The use of Ponstan with concomitant systemic nonaspirin NSAIDs, including cyclooxygenase-2 (COX-2) inhibitors, should be avoided. Concomitant use with one or more systemic NSAIDs may increase frequency of gastrointestinal ulcers and bleeding.

Cardiovascular effects.

Cardiovascular thrombotic events.

NSAIDs may cause an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction and stroke, which can be fatal. This risk may increase with dose or duration of use. The relative increase of this risk appears to be similar in those with or without known CV disease or CV risk factors. However, patients with CV disease, history of atherosclerotic CV disease or CV risk factors may also be at greater risk in terms of absolute incidence, due to their increased rate at baseline. To minimise the potential risk for an adverse CV event in patients treated with mefenamic acid, especially in patients with CV risk factors, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV toxicity and the steps to take if they occur (see Section 4.3 Contraindications).
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use.

Hypertension.

NSAIDs may lead to the onset of new hypertension or worsening of pre-existing hypertension and patients taking antihypertensives with NSAIDs may have an impaired antihypertensive response. Caution is advised when prescribing NSAIDs to patients with hypertension. Blood pressure should be monitored closely during initiation of NSAID treatment and at regular intervals throughout the course of therapy.

Heart failure.

Fluid retention and oedema have been observed in some patients taking NSAIDs, including mefenamic acid. Therefore, Ponstan should be used with caution in patients with compromised cardiac function and other conditions predisposing to, or worsened by, fluid retention. Patients with pre-existing heart failure or hypertension should be closely monitored.

Gastrointestinal effects.

NSAIDs, including mefenamic acid, can cause serious, potentially fatal, gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration and perforation of the stomach, small intestine or large intestine. The frequency of such events may increase with dose or duration of use, but can occur at any time without warning.
Upper GI ulcers, gross bleeding or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
Patients most at risk of developing GI complications with NSAIDs are the elderly; patients with CV disease; patients using concomitant corticosteroids, antiplatelet drugs (such as aspirin), or selective serotonin reuptake inhibitors (SSRIs); patients with a history of, or active, GI disease (such as ulceration, bleeding or inflammatory conditions); and patients ingesting alcohol or with a history of smoking and alcoholism. Mefenamic acid should be used with caution in these patients (see Section 4.3 Contraindications). When GI bleeding or ulceration occurs in patients receiving Ponstan, the drug should be withdrawn immediately. Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and what steps to take if they occur.
If diarrhoea occurs, Ponstan should be promptly discontinued. Symptoms may recur in certain patients following subsequent exposure.

Severe skin reactions.

NSAIDs may very rarely cause serious cutaneous adverse events such as drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), exfoliative dermatitis, toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), which can be fatal and occur without warning. These serious adverse events are idiosyncratic and are independent of dose or duration of use. Patients should be advised of the signs and symptoms of serious skin reactions and to consult their doctor at the first appearance of a skin rash, mucosal lesion or any other sign of hypersensitivity. If this occurs, the drug should be promptly discontinued.
Ponstan may cause an exacerbation of chronic urticaria in patients with this disease.

Haematologic effects.

Ponstan 500 mg and aspirin 650 mg, four times a day, both caused significant further lowering of the prothrombin concentration (Ponstan 3.48% and aspirin 2.75%) in patients in whom the concentration has been initially lowered by anticoagulant therapy. Caution should therefore be exercised in administering Ponstan to patients on anticoagulant therapy, such as warfarin, and should not be given when prothrombin concentration is in the range of 10% to 20% of normal. Careful monitoring of blood coagulation factors is recommended (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Use with oral anticoagulants.

The concomitant use of NSAIDs, including Ponstan, with oral anticoagulants increases the risk of GI and non-GI bleeding and should be given with caution. Oral anticoagulants include warfarin/ coumarin type and novel oral anticoagulants (e.g. apixaban, dabigatran, rivaroxaban). Anticoagulation/ INR should be monitored in patients taking a warfarin/ coumarin type anticoagulant (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Other effects.

Ponstan should be used with caution in known asthmatics.
As no data presently exist concerning the effect of Ponstan, if any, on the efficacy of intrauterine contraceptive devices, physicians should be alert to the possibility of a reduction in contraceptive efficacy in women with an IUCD taking Ponstan.

Use in hepatic impairment.

Ponstan should be used with caution in patients with hepatic impairment.
As with other NSAIDs, borderline elevations of liver function tests may occur in up to 15% of patients. These elevations may progress, may remain essentially unchanged, or may be transient with continued therapy. Meaningful (3 times the upper limit of normal) elevations of SGPT or SGOT occurred in controlled clinical trials in less than 1% of patients.
Physicians and patients should remain alert for hepatotoxicity. Patients should be informed about the signs and/or symptoms of hepatotoxicity. A patient with symptoms and/or signs suggesting liver dysfunction (e.g. nausea, fatigue, lethargy, pruritus, jaundice, abdominal tenderness in the right upper quadrant and "flu-like" symptoms), or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with mefenamic acid.
Severe hepatic reactions, including jaundice and cases of fatal hepatitis, have been reported with other NSAIDs. Although such reactions are rare, if abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash, etc.), Ponstan should be discontinued.

Use in renal impairment.

As with other NSAIDs, long-term administration of Ponstan to animals has resulted in renal papillary necrosis and other abnormal renal pathology. In humans, there have been reports of acute interstitial nephritis with haematuria, proteinuria, glomerulitis, papillary necrosis and occasionally nephrotic syndrome.
A second form of renal toxicity has been seen in patients with prerenal conditions leading to a reduction in renal blood flow or blood volume, where the renal prostaglandins have a supportive role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and may precipitate overt renal decomposition. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, nephrotic syndrome, those taking diuretics and the elderly. Such patients should be carefully monitored while receiving Ponstan.
Discontinuation of NSAID therapy is typically followed by recovery to the pretreatment state. Since Ponstan is eliminated primarily by the kidneys, the drug should not be administered to patients with significantly impaired renal functions (see Section 4.3 Contraindications).

Use in the elderly.

See Section 4.4 Special Warnings and Precautions for Use, Gastrointestinal effects, Use in renal impairment.

Paediatric use.

Safety and effectiveness in children below the age of 14 years have not been established.

Effects on laboratory tests.

A false positive reaction for urinary bile, using the diazo tablet test, may result after Ponstan administration. If biliuria is suspected, other diagnostic procedures, such as the Harrison spot test, should be performed.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Aspirin.

Mefenamic acid interferes with the anti-platelet effect of low dose aspirin, and thus may interfere with aspirin's prophylactic treatment of CV disease.

Anticoagulants.

The concurrent use of NSAIDs and warfarin has been associated with severe, sometimes fatal haemorrhage.
Mefenamic acid, like other nonsteroidal anti-inflammatory agents, can inhibit platelet aggregation and may prolong prothrombin time in patients on warfarin therapy. Mefenamic acid has been shown to displace warfarin from protein binding sites and may enhance the response to oral anticoagulants.
NSAIDs, such as Ponstan, should be used in combination with warfarin, only if absolutely necessary. Concurrent administration of Ponstan with oral anticoagulant drugs requires frequent prothrombin time monitoring (see Section 4.4 Special Warnings and Precautions for Use).

Antihypertensives.

NSAIDs, such as mefenamic acid, can reduce the efficacy of antihypertensive drugs including diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin II antagonists (AIIA) and beta-blockers.
In patients with impaired renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the coadministration of an ACE inhibitor or an AIIA and/or diuretics with a cyclooxygenase inhibitor can increase the deterioration of the renal function, including the possibility of acute renal failure, which is usually reversible. The occurrence of these interactions should be considered in patients taking mefenamic acid with an ACE inhibitor or an AIIA and/or diuretics.
Therefore, the concomitant administration of these drugs should be done with caution, especially in elderly patients. Patients should be adequately hydrated and the need to monitor renal function should be assessed before, and periodically during, concomitant treatment.

Corticosteroids.

Concurrent use with NSAIDs may increase the risk of gastrointestinal ulceration or bleeding.

Ciclosporin 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.

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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Based on the mechanism of action, the use of NSAIDs may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of NSAIDs, including Ponstan, should be considered.
(Category C)
Since there are no adequate and well-controlled studies in pregnant women, Ponstan should be used only if the potential benefits to the mother justify the possible risks to the fetus. It is not known if mefenamic acid or its metabolites crosses the placenta.
NSAIDs given during the latter part of pregnancy may cause closure of the fetal ductus arteriosus, fetal renal impairment, inhibition of platelet aggregation, and delay labour and birth.
Because of the effects of drugs in this class (i.e. inhibitors of prostaglandin synthesis) on the fetal CV system (i.e. premature closure of the ductus arteriosus), the use of mefenamic acid in pregnant women is not recommended and should be avoided during the third trimester of pregnancy, including the last few days before expected birth.
Mefenamic acid inhibits prostaglandin synthesis which may result in prolongation of pregnancy and interference with labour when administered late in the pregnancy. Women on mefenamic acid therapy should consult their physician if they decide to become pregnant.
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.
If used during second or third trimester of pregnancy, NSAIDs may cause fetal renal dysfunction which may result in reduction of amniotic fluid volume or oligohydramnios in severe cases. Such effects may occur shortly after treatment initiation. Pregnant women on mefenamic acid should be closely monitored for amniotic fluid volume.
Trace amounts of Ponstan may be present in breast milk and transmitted to the nursing infant. Thus Ponstan should not be taken by the nursing mother because of the effects of this class of drugs on the infant cardiovascular system.

4.8 Adverse Effects (Undesirable Effects)

Gastrointestinal disorders.

The most frequently reported adverse effects associated with the use of Ponstan involve the gastrointestinal tract. In controlled studies for up to eight months, the following disturbances were reported in decreasing order of frequency: diarrhoea (approximately 5% of patients), nausea with or without vomiting, other gastrointestinal symptoms and abdominal pain. In certain patients, the diarrhoea was of sufficient severity to require discontinuation of the medication. Diarrhoea is usually dose related. It generally subsides on reduction of dosage and rapidly disappears on termination of therapy.
Other less frequently reported gastrointestinal effects were anorexia, cholestatic jaundice, colitis, enterocolitis, mild hepatic toxicity, hepatitis, hepatorenal syndrome, pyrosis, pancreatitis, steatorrhoea, flatulence, constipation, gastrointestinal inflammation, gastrointestinal ulceration (with and without haemorrhage) and gastrointestinal perforation.

Blood and lymphatic system.

Cases of autoimmune haemolytic anaemia have been associated with the continuous administration of Ponstan for 12 months or longer. In such cases the Coombs test results are positive with evidence of both accelerated RBC production and RBC destruction. The process is reversible upon termination of Ponstan administration.
Decreases in haematocrit have been noted in 2% to 5% of patients and primarily in those who have received prolonged therapy. Leukopoenia, eosinophilia, thrombocytopoenia purpura, agranulocytosis, pancytopoenia, aplastic anaemia, bone marrow hypoplasia and platelet aggregation inhibition have also been reported.

Immune system.

Anaphylaxis.

Metabolism and nutrition.

Glucose intolerance in diabetic patients, hyponatraemia and fluid retention.

Psychiatric disorders.

Nervousness.

Nervous system.

Aseptic meningitis, convulsions, drowsiness, dizziness, headache, blurred vision and insomnia.

Eye and ear disorders.

Eye irritation, reversible loss of colour vision and ear pain.

Cardiovascular system.

Hypotension, hypertension and palpitations.

Respiratory and thoracic system.

Asthma and dyspnoea.

Skin and subcutaneous tissue disorders.

Angioedema, oedema of the larynx, erythema multiforme, perspiration, Lyell's syndrome (toxic epidermal necrolysis), Stevens-Johnson syndrome, dermatitis exfoliative, pruritus, urticaria, rash and facial oedema.

Renal and urinary disorders.

As with other NSAIDs, renal failure including papillary necrosis has been reported. In elderly patients renal failure has occurred after taking Ponstan for 2 to 6 weeks. The renal damage may not be completely reversible. Haematuria, dysuria, tubulointerstitial nephritis, glomerulonephritis and nephrotic syndrome have also been reported.

General disorders and administration site conditions.

Oedema.

Investigations.

Urobilinogen urine (false positive) and liver function test abnormal.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
Patients on long term treatment should be reviewed regularly with regards to efficacy, risk factors and ongoing need for treatment.

Dysmenorrhoea.

2 capsules (500 mg) three times daily with meals from the onset of pain and continued for the usual duration of pain.

Menorrhagia.

2 capsules (500 mg) three times daily with meals and from the onset of menses and continued according to the judgement of the physician. Therapy should not be continued for more than 7 days except on the advice of a physician.

Other indications.

2 capsules (500 mg) three times daily, with meals.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration. However, adverse effects of Ponstan include dizziness, drowsiness and blurred vision which could affect the ability to drive or use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.9 Overdose

Symptoms.

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

Treatment.

There is no specific antidote for mefenamic acid overdose. Treatment is symptomatic and supportive, including fluid replacement and IV access especially to patients who are dehydrated or unable to ingest adequate fluids. Avoiding intravascular fluid depletion will help prevent development of renal failure.
In cases of severe toxicity, activated charcoal may reduce absorption of the drug if given within one to two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube ensuring that the airway is protected.
In clinically severe overdoses, full blood count, electrolytes, glucose, renal function, liver function tests, arterial blood gases and coagulation studies should be monitored for abnormalities.
Because mefenamic acid and its metabolites are firmly bound to plasma proteins, haemodialysis, haemoperfusion and peritoneal dialysis may be of little value.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

Pack of 20s: Schedule 2 (Pharmacy Medicine).
Pack of 50s: Schedule 4 (Prescription Only Medicine).

6 Pharmaceutical Particulars

6.1 List of Excipients

Lactose monohydrate, titanium dioxide, gelatin, brilliant blue FCF, iron oxide yellow, carbon black.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Ponstan 250 mg capsules are available in PVC/Al blister packs of 20 or 50 capsules and bottles of 50 capsules.
Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes