Indomethacin

Registered South African indications:

• Pain
• Inflammation

Indomethacin may predispose to cardiovascular events, gastrointestinal events, or cutaneous reactions which may be fatal.

 

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy >30 weeks
• History of active peptic ulcer
• History of gastrointestinal lesions
• Nasal polyps associated with angioneurotic oedema
• History of acute asthmatic attacks, urticaria or rhinitis as a result of therapy with aspirin or other non-steroidal anti-inflammatory drugs
• History of proctitis or recent rectal bleeding (sup)
• Coronary artery bypass graft surgery

Caution

• Pregnancy <30 weeks
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Gastrointestinal bleeding
• Asthma
• Cardiac dysfunction
• Hypertension
• Fluid retention  
• Existing or controlled infection
• Coagulation defects
• Diabetes mellitus
• Psychiatric disorders
• Epilepsy
• Parkinsonism
• Dehydration  
• May affect ability to drive and operate machinery

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

Rheumatoid arthritis
Ankylosing spondylitis
Osteo­arthritis
Chronic musculoskeletal disorders
Joint disorders

• Oral (cap): Initial: 25mg, 8-12hrly; Titrate by 25-50mg at intervals of 1 week; Max: 200mg/24hrs
• Rectal (sup): 100mg, 12-24hrly; Max: 200mg/24hrs 

Acute disorders

• Oral (cap): 50mg, 8-12hrly; Treatment duration: 10 days; Max: 200mg/24hrs
• Rectal (sup): 100mg, 12-24hrly; Max: 200mg/24hrs 

Acute gout
Acute gouty arthritis

• Oral (cap): 50mg, 6-8hrly; Max: 200mg/24hrs; Titrate to lowest effective dose once stable
• Rectal (sup): 100mg, 12-24hrly; Max: 200mg/24hrs 

Bursitis/Tendonitis of the shoulder

• Oral (cap): 25-50mg, 8hrly; Max: 150mg/24hrs; Max duration: 2 weeks
• Rectal (sup): 100mg, 12-24hrly; Max: 200mg/24hrs 

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Use lowest effective dose for the shortest duration possible

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Take with food, an antacid or milk

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Labour suppression - gestation <32 weeks (patients in whom nifedipine is contraindicated)

• Oral (cap): 50mg, immediately; Repeat dosage: 25mg, 4hrly for up to 48hrs

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See additional prescribing points

Not established for use in children

Pregnancy

• Contraindicated in pregnancy >30 weeks
• Caution in pregnancy <30 weeks
• Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of therapy
• In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, indomethacin should not be given unless clearly necessary. If indomethacin is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible
• During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:
  - cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
  - renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;
  The mother and the neonate, at the end of pregnancy, to:
  - possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses
  - inhibition of uterine contractions resulting in delayed or prolonged labour
• Consequently, indomethacin is contraindicated during the third trimester of pregnancy. Studies in animals have shown reproductive toxicity

Breastfeeding

• Caution; not recommended
• Administration of indomethacin is not recommended in breastfeeding mothers. Indomethacin is excreted in breast milk

Fertility

• Indomethacin may have a reversible inhibitory effect on women's ovulation. The use of indomethacin may impair female fertility and is not recommended in women attempting to conceive
• In women who have difficulties conceiving or who are undergoing an investigation of infertility, withdrawal of indomethacin should be considered

Renal Impairment

• Caution; no dose adjustment recommended
  Lower daily dosage should be used to avoid excessive drug accumulation
• Not recommended in severe renal impairment

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended
  Initiate at lower end of dosage range

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headaches
• Dizziness
• Depression
• Vertigo
• Fatigue 
• Mental confusion
• Anxiety
• Syncope
• Drowsiness
• Convulsions
• Coma
• Peripheral neuropathy
• Involuntary muscle movements
• Insomnia
• Psychiatric disturbances
• Depersonalisation
• Paraesthesia
• Dysarthria
• Parkinsonism

Cardiovascular Disorders

• Oedema
• Hypertension
• Tachycardia
• Chest pain
• Arrhythmia
• Palpitation
• Hypotension
• Congestive heart failure
• Blood urea elevation
• Rapid fall in blood pressure resembling a shock-like state

Respiratory Disorders

• Acute respiratory distress
• Bronchospasm

Gastrointestinal Disorders

• Nausea and vomiting
• Anorexia
• Abdominal pain
• Constipation
• Diarrhoea
• Gastrointestinal ulceration
• Stomatitis
• Gastritis
• Flatulence
• Bleeding from the sigmoid colon
• Intestinal strictures 
• Intestinal ulceration followed by stenosis and obstruction
• Ulcerative stomatitis

Hepatobiliary Disorders

• Hepatitis
• Jaundice

Genitourinary Disorders

• Haematuria
• Proteinuria
• Nephrotic syndrome
• Interstitial nephritis
• Renal insufficiency
• Renal failure
• Vaginal bleeding

Endocrine and Metabolic Disorders

• Hyperglycaemia
• Glycosuria
• Hyperkalaemia
• Breast changes
• Gynaecomastia
• Flushing

Musculoskeletal Disorders

• Muscle weakness

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Urticaria
• Angioneurotic oedema
• Angiitis
• Erythema nodosum
• Skin rash 
• Photosensitivity
• Exfoliative dermatitis
• Stevens-Johnson syndrome
• Erythema multiforme
• Toxic epidermal necrolysis
• Sweating
• Loss of hair

Immune, Blood and Lymphatic System Disorders

• Blood dyscrasias
• Purpura
• Aplastic anaemia
• Haemolytic anaemia
• Agranulocytosis
• Bone-marrow depression
• Disseminated intravascular coagulation
• Thrombocytopenia
• Acute anaphylaxis
• Epistaxis

Sensory Disorders

• Blurred vision
• Diplopia
• Orbital and peri-orbital pain
• Corneal deposits
• Retinal disturbances
• Tinnitus
• Hearing disturbances
• Deafness

• Aspirin
• Diflunisal
• Anticoagulants
• Probenecid
• Methotrexate
• Cyclosporin
• Lithium
• Diuretics
• Triamterene
• Cardiac glycosides
• Alpha blockers
• Angiotensin-converting enzyme inhibitors
• Beta blockers
• Diuretics
• Hydralazine
• Losartan  
• Phenylpropanolamine
• Corticosteroids
• Quinolone antibiotics

None routine. Specific cases may require

• Ophthalmological examinations
• Renal function
• Hepatic function

Labour suppression

There are a number of studies that demonstrated indomethacin’s efficacy in suppressing preterm labor, but at increased risk of oligohydramnios, premature closure of the ductus arteriosus and periventricular leucomalacia. Thus, because of it’s safety profile and the availability of safer and effective agents, it's use is not promoted. However, short-term use may be considered in gestation <32 weeks AND when nifedipine is contraindicated.

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Capsule 25mg - EML (Hospital)

Capsule 50mg, Suppository 100mg - Non-EML 

Indomethacin is a non-steroidal anti-inflammatory agent with antiinflammatory, analgesic and antipyretic activity. Its pharmacological effect is thought to be mediated through inhibition of the enzyme cyclooxygenase, the enzyme responsible for the rate-limiting step in prostaglandin synthesis via the arachidonic acid pathway.

Capsule 25mg

• Adco-Indomethacin (Adcock Ingram)
• Aflamin 25 (Sandoz)
• Amdocin (Innovata)
• Arthrexin (Pharmacare)
• Betacin (Ranbaxy Pharmaceuticals)
• Famethacin (Thebe)
• Flamecid (Adcock Ingram)
• Gulf-indomethacin (Gulf Drug)
• Mediflex (Medicine Dev)
• Methocaps (Caps Pharmaceticals)
• Nisaid (Alliance)
• Sandoz-indomethacin (Sandoz)

Capsule 50mg

• Arthrexin (Pharmacare) originator

Suppository 100mg

• Arthrexin (Pharmacare) originator

Also available in the following forms: Gel and spray.