Ponac Suspension. 50 mg per 5 ml SUSPENSION

PONAC SUSPENSION is indicated for the treatment of post traumatic conditions such as pain, swelling and inflammation, for a maximum period of five (5) days. PONAC SUSPENSION is also indicated as treatment of primary dysmenorrhoea, subject to a maximum daily dose of 500 mg three (3) times a day for a maximum of three (3) days.

Posology

Adults

Use the lowest effective dose for the shortest possible duration of treatment. PONAC SUSPENSION must be taken with meals.

Relief of mild to moderate pain: 500 mg three (3) times a day.

Acute pain: an initial dosage of 500 mg, thereafter 250 mg every six (6) hours for a maximum treatment period of five (5) days.

Primary dysmenorrhoea: a maximum daily dose of 500 mg three (3) times a day and a maximum treatment period of three (3) days.

Paediatric population

The dosage for children is 25 mg per kg body weight daily in divided doses. The following dose may be repeated as necessary, up to three (3) times daily:

• 6 months to 1 year: One (1) measureful (5 ml).
• 2 years to 4 years: Two (2) measureful (10 ml).
• 5 years to 8 years: Three (3) measureful (15 ml).
• 9 years to 12 years: Four (4) measureful (20 ml).

Method of administration

Oral use only.

PONAC SUSPENSION is contraindicated in patients:

• With hypersensitivity to mefenamic acid or any of the excipients of PONAC SUSPENSION (see section 6.1).
• With hypersensitivity to non-steroidal anti-inflammatory agents, with prostaglandin synthetase inhibiting activity. Since the possibility of cross-sensitivity among non-steroidal anti-inflammatory agents exists, PONAC SUSPENSION should not be given to patients in whom these medicines induce symptoms of bronchospasm, allergic rhinitis, or urticaria.
• With a history of gastrointestinal perforation, ulceration, or bleeding (PUBs) related to previous NSAIDs (including PONAC SUSPENSION) and/or an active or history of recurrent peptic and/or intestinal ulceration/haemorrhage/perforations.
• With chronic inflammation of either the upper or lower gastrointestinal tract such as inflammatory bowel disease.
• Who suffer from epilepsy (see section 4.4).
• With impaired hepatic or renal function (see section 4.4).
• With heart failure (see section 4.4).
• Requiring treatment for pain after coronary artery bypass graft (CABG) surgery.
• Pregnancy and lactation (see section 4.6).
• With the rare hereditary condition of sorbitol / maltitol / lactitol intolerance (see section 4.4).

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control the condition treated.

Patients on prolonged therapy with PONAC SUSPENSION should be kept under regular surveillance with particular attention to liver dysfunction, rash, blood dyscrasias or development of diarrhoea. Appearance of any of these symptoms should be regarded as an indication to stop therapy immediately.

Precaution should be taken in patients suffering from dehydration, particularly the elderly.

PONAC SUSPENSION and its metabolites may give a false positive reaction to certain urine tests for the presence of bile. Blood counts and liver function should be monitored during long-term therapy with PONAC SUSPENSION. PONAC SUSPENSION may enhance the effects of warfarin (see section 4.5).

Special Populations

Elderly

The elderly has an increased frequency of adverse reactions to NSAIDs including PONAC SUSPENSION, especially gastrointestinal perforation, ulceration and bleeding (PUBs) which may be fatal. The risk of gastrointestinal perforation, ulceration and bleeding (PUBs) is higher with increasing doses of PONAC SUSPENSION, in patients with a history of ulcers and the elderly. PONAC SUSPENSION should be avoided in elderly patients with dehydration or pre-existing renal disease.

Respiratory disorders

Caution is required if administered to patients suffering from, or with a previous history of bronchial asthma since NSAIDs such as PONAC SUSPENSION may precipitate bronchospasm in such patients. Bronchoconstriction may occur with PONAC SUSPENSION in asthmatic patients with aspirin sensitivity.

Cardiovascular, renal and hepatic impairment

The administration of PONAC SUSPENSION may cause a dose-dependent reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly (see section 4.3). PONAC SUSPENSION may enhance the effects of warfarin.

Toxicity has also been seen in patients with prerenal conditions leading to a reduction in renal blood flow or blood volume. Patients at greatest risk are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, and the elderly. Liver function tests must be carried out regularly to monitor elevation of enzymes and bilirubin.

Cardiovascular and cerebrovascular effects

Caution is required in patients with a history of hypertension as fluid retention and oedema have been reported in association with PONAC SUSPENSION therapy. In view of PONAC SUSPENSION inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients (see section 4.3).

Caution is required in patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) and should only be treated with PONAC SUSPENSION after careful consideration.

Appropriate monitoring and advice are required for patients with a history of hypertension, as fluid retention and oedema have been reported in association with NSAID therapy such as PONAC SUSPENSION. Patients with uncontrolled hypertension, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with PONAC SUSPENSION after careful consideration.

As NSAIDs such as PONAC SUSPENSION can interfere with platelet function, they should be used in caution in patients with intracranial haemorrhage and bleeding diathesis.

Gastrointestinal bleeding, ulceration and perforation

When gastrointestinal perforation, ulceration or bleeding occurs in patients receiving PONAC SUSPENSION, treatment with PONAC SUSPENSION should be stopped. PONAC SUSPENSION should be given with caution to patients with a history of gastrointestinal disease (e.g. Crohnu2019s disease, hiatus hernia, gastro-oesophageal reflux disease, angiodysplasia) as the condition may be exacerbated. Gastrointestinal perforation, ulceration or bleeding (PUB) which can be fatal, has been reported with all NSAIDs such as PONAC SUSPENSION at any time during treatment, with or without warning symptoms, or a previous history of serious gastrointestinal events. Smoking and alcohol use are added risk factors.

The risk of gastrointestinal perforation, ulceration or bleeding is higher with increasing doses of PONAC SUSPENSION and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation and in the elderly. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for patients at risk of gastrointestinal bleeding such as the elderly and also for patients requiring concomitant low dose aspirin, or other medicines likely to increase gastrointestinal risk. Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of PONAC SUSPENSION treatment. Caution should be advised in patients receiving concomitant medications which could increase the risk of gastrointestinal side effects or bleeding such as corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as aspirin.

Diarrhoea may occur within 24 hours following usual PONAC SUSPENSION dosage. When diarrhoea occurs, PONAC SUSPENSION should be discontinued immediately. Temporary lowering of the white blood cell count has occurred but does not appear to be dose related. Blood counts should be performed at regular intervals during long-term administration of PONAC SUSPENSION.

SLE and mixed connective tissue disease

In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.

Dermatological effects

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Steven-Johnson syndrome, and toxic epidermal necrolysis, have been reported. PONAC SUSPENSION should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment.

Cross-sensitivity

Because of the possibility of cross-sensitivity due to structural relationships which exist among nonsteroidal anti-inflammatory medicines, acute allergic reactions may be more likely to occur in patients who have exhibited allergic reactions to these compounds. Occurrence of rash is a definite reason for stopping PONAC SUSPENSION because exfoliative dermatitis has been reported on continued use after development of a rash.

Dysmenorrhoea

In dysmenorrhoea and menorrhagia lack of response should alert the physician to investigate other causes.

Poor CYP2C9 metabolisers

In patients who are known or suspected to be poor CYP2C9 metabolisers based on previous history/experience with other CYP2C9 substrates, PONAC SUSPENSION should be administered with caution as they may have abnormally high plasma levels due to reduced metabolic clearance.

Hypokalaemia and renal tubular acidosis

Severe hypokalaemia and renal tubular acidosis have been reported due to prolonged use of NSAIDs as in PONAC SUSPENSION at higher than recommended doses. This risk is increased with the use of codeine/ mefenamic acid as patients may become dependent on the codeine component (section 4.8 c) Description of selected adverse reactions and section 4.9). Presenting signs and symptoms included reduced level of consciousness and generalised weakness. Mefenamic acid induced renal tubular acidosis should be considered in patients with unexplained hypokalaemia and metabolic acidosis.

Excipient warning

PONAC SUSPENSION contains sorbitol and may have a laxative effect. Patients with the rare hereditary condition of sorbitol / maltitol / lactitol intolerance should not take PONAC SUSPENSION.

NSAIDs: use of two or more NSAIDs concomitantly could result in an increase in side effects.

Corticosteroids: increased risk of gastrointestinal perforation, ulceration or bleeding (PUBs).

Anti-coagulants: PONAC SUSPENSION may enhance the effects of anti-coagulants such as warfarin (see section 4.4). Patients taking anti-coagulant medicine concurrently with PONAC SUSPENSION have had a prolongation of prothrombin time. PONAC SUSPENSION are contraindicated for patients taking an anticoagulant medicine if careful and continuous monitoring of the levels of prothrombin Factors VII, IX and X is not available.

Anti-platelet medicines and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.

Lithium: Patients receiving lithium concurrently with non-steroidal anti-inflammatory medicines, including PONAC SUSPENSION, have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. Thus, when PONAC SUSPENSION and lithium are administered concurrently, patients should be observed carefully for signs of lithium toxicity.

Fertility

The use of PONAC SUSPENSION may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of PONAC SUSPENSION should be considered.

Pregnancy

PONAC SUSPENSION should not be used during the first two trimesters of pregnancy or during labour. Regular use of non-steroidal anti-inflammatory medicines during the third trimester of pregnancy, may result in premature closure of the foetal ductus arteriosus in utero, and possibly, in persistent pulmonary hypertension of the new-born. The onset of labour may be delayed, and its duration increased.

Breastfeeding

Trace amounts of mefenamic acid may be present in breast milk and transmitted to the breastfeeding infant. Therefore, PONAC SUSPENSION should not be taken by mothers breastfeeding their infants.

PONAC SUSPENSION may affect the mental and/or physical abilities to perform or execute tasks or activities requiring mental alertness, judgment and/or sound coordination and vision since PONAC SUSPENSION may cause adverse reactions such as dizziness, drowsiness, fatigue and visual disturbances. Therefore, patients should not drive, use machinery or participate in dangerous activities until they are certain that PONAC SUSPENSION does not adversely affect their ability to do so safely (see section 4.8).

a) Summary of adverse effects

The most frequent observed adverse events are gastrointestinal in nature.

b) Tabulated summary of adverse reactions

Frequencies defined as frequent, less frequent and frequency unknown.

MedDRA system organ class Frequency Adverse reactions

Gastrointestinal disorders Frequent Diarrhoea Nausea with or without vomiting Abdominal pain Less frequent Anorexia Pyrosis Flatulence Enterocolitis Colitis Steatorrhea Cholestatic jaundice Hepatitis Pancreatitis Hepato-renal syndrome Mild hepatic toxicity Constipation Peptic ulceration, perforation with or without gastrointestinal haemorrhage (sometimes fatal) Frequency unknown Dyspepsia Melaena Haematemesis Ulcerative stomatitis Exacerbation of colitis and Chronu2019s disease Gastritis Blood and lymphatic system disorders Less frequent Haemolytic anaemia Decreased haematocrit Leukopenia Eosinophilia Thrombocytopenia or Thrombocytopenic purpura, Agranulocytosis Pancytopenia Aplastic anaemia Bone marrow aplasia Immune system disorders Less frequent Acute hypersensitivity reactions (urticaria, bronchospasm, anaphylaxis) Metabolism and nutrition disorders Less frequent Glucose intolerance in diabetic patients Hyponatraemia Frequency unknown Hypokalaemia* Psychiatric disorders Less frequent Nervousness Nervous system disorders Less frequent Drowsiness Dizziness Headache Visual disturbances Convulsions Insomnia Eye disorders Frequency unknown Visual disturbances Ear and labyrinth disorders Less frequent Ear pain Cardiac disorders Less frequent Palpitations Oedema Hypertension Cardiac failure Vascular disorders Less frequent Hypotension Respiratory, thoracic and mediastinal disorders Less frequent Asthma may be precipitated Bronchospasm Dyspnoea Skin and subcutaneous tissue disorders Less frequent Angioedema Oedema of the larynx Steven-Johnson syndrome Lyellu2019s syndrome (toxic epidermal necrolysis) Erythema multiforme Perspiration Pruritis Urticaria Skin rash Facial oedema Frequency unknown Bullous reactions Renal and urinary disorders Less frequent Renal failure Papillary necrosis Acute interstitial nephritis with haematuria Dysuria Proteinuria Allergic glomerulonephritis Frequency unknown Nephrotic syndrome, elevation in blood urea Renal tubular acidosis*

c) Description of Selected Adverse Reactions

* Renal tubular acidosis and hypokalaemia have been reported in the post-marketing setting typically following prolonged use of the NSAID component at higher than recommended doses, usually due to dependence on the codeine component of a co-formulation.

Reporting of suspected adverse events

Reporting suspected adverse reactions after authorisation of medicine is important. It allows continued monitoring of the benefit/risk balance of medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/

Mefenamic acid such as in PONAC SUSPENSION has a marked tendency to induce tonic-clonic (grand mal) convulsions in overdosage. Dyskinesia, acute renal failure and coma have been reported. Overdose has led to fatalities. Prolonged use at higher than recommended doses may result in severe hypokalaemia and renal tubular acidosis. Symptoms may include reduced level of consciousness and generalised weakness (see section 4.4 and section 4.8). Treatment is symptomatic and supportive. Following accidental overdosage, the stomach should be emptied immediately by inducing emesis followed by administration of activated charcoal. Vital functions should be monitored and supported. Haemodialysis is of little value since mefenamic acid and its metabolites are firmly bound to plasma proteins.