Mefenamic Acid

Registered South African indications:

• Post traumatic conditions such as pain, swelling and inflammation
• Fever
• Primary dysmenorrhoea

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• 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, mefenamic acid should not be given to patients in whom these medicines induce symptoms of bronchospasm, allergic rhinitis, or urticaria
• History of gastrointestinal perforation, ulceration, or bleeding (PUBs) related to previous NSAIDs (including mefenamic acid) and/or an active or history of recurrent peptic and/or intestinal ulceration/haemorrhage/perforations
• Chronic inflammation of either the upper or lower gastrointestinal tract such as inflammatory bowel disease
• Epilepsy
• Renal impairment
• Hepatic impairment
• Heart failure
• Treatment for pain after coronary artery bypass graft (CABG) surgery
• Pregnancy (from 20 weeks or later of gestation) (cap, sup, tab)
• Pregnancy (from 30 weeks gestation and later) (sus)
• Lactation (cap, sup, tab)
• Rare hereditary conditions of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption, or fructose intolerance (cap, tab) 

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Potential cross-sensitivity to aspirin, ibuprofen, or other non-steroidal anti-inflammatory drugs. Mefenamic acid must not be given to patients who have previously shown hypersensitivity reactions (e.g. asthma, bronchospasm, rhinitis, angioedema or urticaria) to these medicines
• Inflammatory bowel disease
• History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy
• Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding)
• Severe heart failure
• Hepatic failure
• Renal failure
• During the last trimester of pregnancy
• Treatment of pain after coronary artery bypass graft (CABG) surgery

• Pregnancy <20 weeks gestation (cap, sup, tab) (South African recommendations)
• Pregnancy <30 weeks gestation (sus) (South African recommendations)
• First and second trimester of pregnancy (Recommendations in other jurisdictions)
• Breastfeeding (sus) (South African recommendations)
• Breastfeeding (Recommendations in other jurisdictions) 
• Women of childbearing potential
• Elderly
• Debilitated patients
• Dehydration
• Asthma
• Hypertension
• Cardiac function impairment
• Established ischaemic heart disease
• Peripheral arterial disease
• Cerebrovascular disease  
• Hyperlipidaemia
• Diabetes mellitus
• Epilepsy
• Intracranial haemorrhage 
• Bleeding diathesis
• Systemic lupus erythematosus
• Mixed connective tissue disorders
• Smoking
• Alcohol use
• Coagulation disorder
• Galactose intolerance (cap, tab, sus) (Recommendations in other jurisdictions)
• Lapp lactase deficiency (cap, tab, sus) (Recommendations in other jurisdictions)
• Glucose-galactose malabsorption (cap, tab, sus) (Recommendations in other jurisdictions)

Forms avail. in SA and covered in this monograph: cap, tab

South African registered indications and dosages

Relief of mild to moderate pain

• Oral (cap, tab): 500mg, 3 times daily; Max duration: 5 days

Acute pain

• Oral (cap, tab): Initial: 500mg; Thereafter: 250mg, 6hrly; Max duration: 5 days

Primary dysmenorrhea

• Oral (cap, tab): 500mg, 3 times daily; Max duration: 3 days; Max: 1500mg/24hrs

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The lowest effective dose for the shortest possible duration should be used. Must be taken with meals

Paed. forms avail in SA and covered in this monograph: sus, sup

South African registered indications and dosages

Post-traumatic conditions such as pain, swelling and inflammation

Younger than 6 months

• No information available

Older than 6 months

• Oral (sus): 25mg/kg body-weight, daily in divided doses

Age	Dosage
6 months-1 year	50mg, up to 3 times daily if needed
2-4 years	100mg, up to 3 times daily if needed
5-8 years	150mg, up to 3 times daily if needed
9-12 years	200mg, up to 3 times daily if needed

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The lowest effective dose for the shortest possible duration should be used. Must be taken with meals

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Symptomatic treatment of pain and fever

Younger than 6 months

• No information available

Between 6 months - 2 years (≥10kg)

• Rectal (sup): Insert 1 sup (125mg), 3 times a day at intervals of 6-8hrs as needed

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The use of paediatric suppositories every 6-8 hours for longer than 24 hours is not recommended

Pregnancy

South African recommendations

Capsule, Tablet

• <20 weeks of gestation: Caution
• ≥20 weeks of gestation: Contraindicated
• Mefenamic acid is contraindicated in pregnant women from 20 weeks or later of gestation
• Regular use of non-steroidal anti-inflammatory medicines, such as mefenamic acid, 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
• When used during the second or third trimester of pregnancy, NSAIDs, including mefenamic acid, may cause foetal renal dysfunction
• This dysfunction may lead to a reduction in 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

Suspension

• <30 weeks of gestation: Caution
• ≥30 weeks of gestation: Contraindicated
• Use of NSAIDs, including mefenamic acid suspension, can cause premature closure of the foetal ductus arteriosus, persistent pulmonary hypertension of the new-born, foetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
• Because of these risks, the use of mefenamic acid suspension dose and duration between 20 and 30 weeks of gestation should be limited and avoided at around 30 weeks of gestation and later in pregnancy. The onset of labour may be delayed and its duration increased

Suppository

• <20 weeks of gestation: Caution; positive evidence of risk
• ≥20 weeks of gestation: Contraindicated
• Mefenamic acid should not be used during the first 20 weeks of pregnancy. If there is a compelling need for NSAID treatment during this time, limit use to the lowest effective dose and shortest duration possible
• The inhibition of prostaglandin synthesis by NSAIDs, including mefenamic acid, may adversely affect pregnancy. Epidemiological studies suggest an increased risk of spontaneous abortion and congenital malformation 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. Regular use of NSAIDs 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 newborn
• The onset of labour may be delayed and its duration increased
• It is not known if mefenamic acid or its metabolites cross the placenta. However, because of the effects of medicines in this class (i.e. inhibitors of prostaglandin synthesis) on the foetal cardiovascular system, the use of mefenamic acid in pregnant women is not recommended and is contraindicated from 20 weeks or later from gestation

Recommendations in other jurisdictions

• First and second trimester: Caution
• Third trimester: Contraindicated
• Congenital abnormalities have been linked with NSAID use, but they are low in frequency and lack a discernible pattern
• Due to the known effects of NSAIDs on the foetal cardiovascular system, such as the risk of closing the ductus arteriosus, they are contraindicated in the last trimester of pregnancy
• The onset of labour might be delayed, and its duration might increase, leading to a heightened bleeding risk for both mother and child
• NSAIDs should not be taken during the first two trimesters or labour unless the benefits for the mother outweigh the potential risks to the foetus
• From the 20th week of pregnancy, mefenamic acid might cause oligohydramnios due to foetal renal dysfunction, which can start soon after beginning the treatment but is typically reversible upon stopping the medication
• There have been cases of ductus arteriosus constriction after using the drug in the second trimester; however, most cases resolved after discontinuing the treatment
• If mefenamic acid is used by a woman trying to conceive or during the first two trimesters, the dosage should be minimal and the treatment duration short
• After using mefenamic acid for several days from the 20th week of pregnancy, antenatal checks for oligohydramnios and ductus arteriosus constriction are advisable
• If oligohydramnios or ductus arteriosus constriction is detected, mefenamic acid should be stopped
• In the third trimester, all drugs that inhibit prostaglandin synthesis might expose the foetus to cardiopulmonary toxicity (like premature constriction/closure of the ductus arteriosus and pulmonary hypertension) and renal dysfunction
• Towards the end of pregnancy, these drugs can increase the bleeding time in both the mother and the newborn, even at low doses, and can inhibit uterine contractions, causing delayed or prolonged labour

Breastfeeding

South African recommendations

• Contraindicated (cap, sup, tab)
• Caution; not recommended (sus)
• Trace amounts of mefenamic acid may be present in breast milk and transmitted to the breastfeeding infant. Therefore, mefenamic acid should not be taken by mothers breastfeeding their infants

Recommendations in other jurisdictions

• Caution; not recommended
• Trace amounts of mefenamic acid may be present in breast milk and transmitted to the breastfeeding infant. Therefore, mefenamic acid should not be taken by breastfeeding mothers

Fertility

Recommendations below are applicable to South Africa and other jurisdictions

• The use of mefenamic acid 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 mefenamic acid should be considered

Recommendations below are applicable to South Africa and other jurisdictions

• Contraindicated
  The administration of mefenamic acid 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

Recommendations below are applicable to South Africa and other jurisdictions

• Contraindicated
  The administration of mefenamic acid 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

South African recommendations

• Caution; no dose adjustment recommended
  The elderly has an increased frequency of adverse reactions to NSAIDs, 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 mefenamic acid, in patients with a history of ulcers and the elderly. Mefenamic acid should be avoided in elderly patients with dehydration or pre-existing renal disease

Recommendations in other jurisdictions

• Caution; no dose adjustment recommended
  Whilst no pharmacokinetic or clinical studies specific to the elderly have been undertaken with mefenamic acid, it has been used at normal dosage in trials which included many elderly patients. The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy
  Mefenamic acid should be used with caution in elderly patients suffering from dehydration and renal disease. Non-oliguric renal failure and proctocolitis have been reported mainly in elderly patients who have not discontinued mefenamic acid after the development of diarrhoea

Central Nervous System Disorders

• Confusion
• Depression
• Hallucinations
• Nervousness
• Optic neuritis
• Headaches
• Paraesthesia
• Dizziness
• Drowsiness
• Aseptic meningitis
• Blurred vision
• Convulsions
• Insomnia
• Fatigue

Cardiovascular Disorders

• Oedema
• Hypertension
• Cardiac failure
• Arterial thrombotic events 
• Palpitations
• Hypotension

Respiratory Disorders

• Asthma
• Dyspnoea

Gastrontestinal Disorders

• Peptic ulcers
• Perforation 
• Gastrointestinal bleeding
• Nausea and vomiting
• Diarrhoea
• Flatulence
• Constipation
• Dyspepsia
• Abdominal pain
• Melaena
• Haematemesis
• Ulcerative stomatitis
• Exacerbation of colitis
• Crohn's disease
• Gastritis
• Anorexia
• Colitis
• Enterocolitis
• Gastric ulceration
• Pancreatitis
• Steatorrhea

Hepatobiliary Disorders

• Borderline elevations of one or more liver function tests
• Cholestatic jaundice
• Mild hepatotoxicity
• Hepatitis
• Hepatorenal syndrome  

Genitourinary Disorders

• Allergic glomerulonephritis
• Acute interstitial nephritis
• Dysuria
• Haematuria
• Nephrotic syndrome
• Non-oliguric renal failure 
• Proteinuria
• Renal failure including renal papillary necrosis

Endocrine and Metabolic Disorders

• Glucose intolerance in diabetic patients
• Hyponatraemia

Skin and Subcutaneous Tissue Disorders

• Angioedema
• Laryngeal oedema
• Erythema multiforme
• Face oedema
• Bullous reactions including Lyell's syndrome 
• Stevens-Johnson syndrome
• Perspiration
• Rash
• Photosensitivity reaction
• Pruritus
• Urticaria

Immune, Blood and Lymphatic System Disorders

• Anaemia
• Hypoplasia bone marrow
• Decreased haematocrit 
• Thrombocytopenic purpura
• Temporary lowering of the white blood cell count (leukopenia) with a risk of infection
• Sepsis
• Disseminated intravascular coagulation
• Agranulocytosis
• Aplastic anaemia
• Eosinophilia
• Neutropenia
• Pancytopenia
• Thrombocytopenia
• Hypersensitivity reactions
• Non-specific allergic reactions
• Anaphylaxis
• Respiratory tract reactivity comprising asthma
• Aggravated asthma
• Bronchospasm
• Dyspnoea
• Assorted skin disorders including rashes of various types, pruritus, urticaria, purpura, angioedema, and more rarely exfoliative or bullous dermatoses (including epidermal necrolysis and erythema multiforme)
• Pyrexia

Sensory Disorders

• Eye irritation
• Reversible loss of colour vision
• Visual disturbances
• Ear pain
• Tinnitus
• Vertigo 

Others

• Multi-organ failure
• A positive reaction in certain tests for bile

• Anticoagulants
• Lithium
• Cyclooxygenase-2 selective inhibitors
• Selective serotonin reuptake inhibitors  
• Antihypertensives 
• Diuretics
• Angiotensin-converting enzyme inhibitors 
• Angiotensin-II-receptor antagonists
• Aminoglycosides
• Antiplatelet agents
• Acetylsalicylic acid
• Cardiac glycosides
• Ciclosporin .
• Corticosteroids
• Sulfonylurea agents
• Methotrexate
• Mifepristone
• Probenecid
• Quinolone antibiotics
• Tacrolimus
• Zidovudine

None routine. Specific cases may require

• Renal function
• Hepatic function  
• Full blood count  

• Several studies have suggested that mefenamic acid or naproxen are particularly useful for pain associated with menstruation, and they should be considered first-line agents for short periods in the absence of contraindication.
• Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms. Do not exceed the maximum recommended dose

Inhibits prostaglandin synthesis by inhibition of cyclooxygenase.

Tablet 500mg

• Fenamin 500 (Pharmacare)
• Ponstel Forte (Adcock)
• Ponac Forte (Pharmacorp)
• Ponstan Forte (Pfizer) originator

Capsule 250mg

• Adco-Mefenamic acid (Adcock)
• Fenamin 250(Pharmacare)
• Pontel S (Adcock)
• Ponac (Pharmacorp)
• Ponstan (Pfizer) originator
• Sandoz Mefenamic (Sandoz)

Suspension (per 5ml) 50mg

• Adco-Mefenamic acid (Adcock)
• Fenamin Suspension (Pharmacare)
• Ponstel S (Adcock)
• Ponac (Pharmacorp)
• Ponstan (Pfizer) originator

Suppository 125mg

• Ponstan paediatric suppository (Pfizer) originator