Diclofenac Sodium

Registered South African indications:

• Pain - mild to moderate
• Inflammation

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy (third trimester)
• Breastfeeding 
• Moderate to severe renal impairment (IV administration)
• Severe hepatic impairment
• Ischemic heart disease
• Peripheral arterial disease
• Cerebrovascular disease
• Congestive heart failure
• Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes)
• History of gastrointestinal bleeding or perforation relating to previous non-steroidal anti-inflammatory drugs (NSAIDs)
• History of hypersensitivity reactions to acetylsalicylic acid or other NSAIDs
• Confirmed or suspected cerebrovascular bleeding (IV)
• History of haemorrhagic diathesis (IV)
• Surgery associated with a high risk of haemorrhage (IV)
• Hypovolaemia or dehydration (IV)
• Patients in whom attacks of asthma, angioedema, urticaria or acute rhinitis are precipitated by ibuprofen, aspirin or other NSAIDs
• Asthma
• Coadministration with NSAIDs or anti-coagulant agents

Cautions

• Pregnancy (first trimester)
• Female patients of reproductive potential
• Mild to moderate renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Hepatic porphyria
• Hypertension 
• Mild to moderate congestive heart failure
• Uncontrolled hypertension
• Risk factors for cardiovascular events
• Gastrointestinal disorders
• Inflammatory bowel disease
• Ulcerative collitis
• Crohn's disease
• History of gastrointestinal toxicity
• Use after gastrointestinal surgery
• History of haematemesis or melaena
• Haematological abnormalities, or bleeding diathesis
• Seasonal allergic rhinitis
• Nasal polyps
• Chronic obstructive pulmonary diseases
• Chronic infections of the respiratory tract
• Systemic lupus erythematosus
• Mixed connective tissue disease
• Substantial extracellular volume depletion
• Masking of the signs and symptoms of infection
• Intramuscular administration
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• Prolonged use
• Appearance of skin rash or mucosal lesions

Forms avail. in SA and covered in this monograph: tab; cap; slow release tablet (SR tab); slow release capsule (SR cap); dsp; sac, inj

Pain - mild to moderate

• Oral (tab, caps, sac): Initial: 25-100mg, as a single dose; Maintenance: 25-50mg, 8hrly; Max: 150mg/24hrs
• Oral (SR tab, SR cap): 75mg, 12-24hrly OR 100mg, 24hrly
• Oral (dsp): 100-150mg, 8-12hrly; Max: 150mg/24hrs
• IM: 75 mg, Repeat 12hrly as needed; Max: 150mg/24hrs; Max duration: 2 days

Osteoarthritis

• Oral (tab): 50mg, 8-12hrly; Max 150mg/24hrs
• Oral (SR tablet): 75-100mg, dly; Max: 100mg/24hrs

Rheumatoid Arthritis

• Oral (tab): 50mg, 6-8hrly
• Oral (SR tab): 100mg, 12-24hrly; Max 200 mg/24hrs

Primary Dysmenorrhoea

• Oral (tab): 50mg  8hrly; Max 150mg/24hrs

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Dosage should be individually determined

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Treatment should be initiated at onset of symptoms and continued for a few days, depending on intensity of pain

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Migraine

• Oral (tab): Initial: 50mg; Repeat dose after 2hrs if needed; Then: repeat 4-6hrly if needed; Max: 150 mg/24hrs

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Long term use of NSAIDS (7-10 days) requires ongoing clinical review 

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Tab, cap, SR tab, SR cap: Do not cut/crush/chew/dissolve; Take with food

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Post-operative pain - moderate to severe

• IV: 75mg, as an infusion over 30 -120min; Repeat after 4-6hrs if needed; Max: 150mg/24hrs; Max duration: 2 days

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Dilute 1 amp with 100-500ml NaCl 0.9% or 5% glucose solution. Both solutions should be buffered with sodium bicarbonate solution (0.5ml 8.4% or 1ml 4.2%) 

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DO NOT administer as IV bolus 

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Prophylaxis of post-operative pain

• IV: Loading dose: 25-50mg, as an infusion over 15-60min; Maintenance: 5mg/hr, as an infusion; Max: 150mg/24hrs; Max duration: 2 days

Paed. forms avail. in SA and covered in this monograph: tabs; drp

Pain - mild to moderate

Younger than 2 years

• Not established for use

Older than 2 years

• Oral (tab): 1-3mg/kg; 8-12hrly
• Oral (drp): 0.5-2mg/kg; 8-12hrly

Pregnancy

• First trimester: Caution; not recommended
  Third trimester: Contraindicated
• 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, diclofenac should not be given unless clearly necessary. If diclofenac 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 oligohydramnios
• It may expose 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  

Breastfeeding

• Contraindicated
• Diclofenac passes into breastmilk in small amounts. Therefore, diclofenac should not be administered during breastfeeding in order to avoid undesirable effects in the infant 

Fertility 

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

Renal Impairment

• Mild to moderate: Caution; no information available
• Severe: Contraindicated

Hepatic Impairment

• Mild to moderate: Caution; no information available
• Severe: Contraindicated

Elderly

• Caution; no dose adjustment recommended
  The lowest effective dose is recommended for use in frail elderly patients or those with a low body weight

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders 

• Drowsiness
• Disorientation
• Depression
• Insomnia
• Nightmare
• Irritability
• Psychotic disorder
• Anxiety
• Confusional state
• Headache
• Dizziness
• Somnolence
• Paraesthesia
• Memory impairment
• Convulsion
• Tremor
• Aseptic meningitis
• Dysgeusia
• Cerebrovascular accident
• Hallucinations
• Fatigue

Cardiovascular Disorders 

• Palpitations
• Chest pain
• Cardiac failure
• Myocardial infarction
• Hypertension
• Vasculitis
• Hypotension
• Kounis syndrome

Respiratory Disorders 

• Asthma
• Pneumonitis

Gastrointestinal Disorders 

• Nausea and vomiting
• Diarrhoea
• Dyspepsia
• Abdominal pain
• Flatulence
• Anorexia
• Gastritis
• Gastrointestinal haemorrhage
• Haematemesis
• Haemorrhagic diarrhoea
• Malaena
• Gastrointestinal ulcer
• Colitis
• Constipation
• Stomatitis (including ulcerative stomatitis)
• Mouth ulceration
• Glossitis
• Oesophageal disorder
• Crohn's disease
• Large intestinal stricture
• Pancreatitis
• Ischaemic colitis

Hepatobiliary Disorders 

• Increased transaminases
• Hepatitis
• Jaundice
• Liver disorder
• Fulminant hepatitis
• Hepatic necrosis
• Hepatic failure

Genitourinary Disorders 

• Acute renal failure
• Haematuria
• Proteinuria
• Nephrotic syndrome
• Tubulointerstitial nephritis
• Renal papillary necrosis
• Impotence

Skin and Subcutaneous Tissue Disorders 

• Rash
• Urticaria
• Bullous eruptions
• Eczema
• Erythema
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis (Lyell's syndrome)
• Dermatitis exfoliative
• Alopecia
• Photosensitivity reaction
• Purpura
• Henoch-Schonlein purpura
• Pruritus
• Generalised oedema
• Injection site reactions

Immune, Blood and Lymphatic System Disorders 

• Hypersensitivity
• Anaphylactic and anaphylactoid reactions
• Angioneurotic oedema
• Thrombocytopenia
• Leukopenia
• Anaemia (including haemolytic and aplastic)
• Agranulocytosis

Sensory Disorders 

• Visual impairment
• Vision blurred
• Diplopia
• Optic neuritis
• Vertigo
• Tinnitus
• Impaired hearing

• CYP2C9 inhibitors
• Lithium
• Cardiac glycosides
• Digoxin
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids
• Diuretics
• Antihypertensive agents
• Beta-blockers
• Angiotensin converting enzyme (ACE) inhibitors
• Agents that increase serum potassium  
• Anticoagulants
• Warfarin
• Antiplatelet agents
• Acetylsalicylic acid
• Selective serotonin reuptake inhibitors
• Antidiabetic agents
• Methotrexate
• Ciclosporin
• Trimethoprim
• Mifepristone
• Quinolone antibacterials
• Phenytoin
• Tacrolimus
• Colestipol
• Cholestyramine

None routine. Specific cases may require

• Renal function
• Hepatic function
• Full blood count

Cardiovascular and significant cardiovascular risk factors

• Diclofenac is contraindicated in patients with established congestive heart failure (NYHA II-IV), ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease
• Patients with congestive heart failure (NYHA-I) or significant risk factors for CVS should be treated with diclofenac only after careful consideration. Since CV risks with diclofenac may increase with dose and duration exposure, the lowest effective daily dose should be used and for the shortest duration possible

Administration

• IM: carries the risk of severe pain, thrombus and/or formation of a sterile abscess
• Avoid administration in patients with dehydration or hemorrhagic shock due to increased risk of renal injury

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Diclofenac 25mg/3ml vial - EML (Hospital) 

All other forms - NON-EML 

Diclofenac is a nonsteroidal agent with marked analgesic/anti-inflammatory properties. It is an inhibitor of prostaglandin synthetase, (cyclo-oxygenase). Diclofenac sodium in vitro does not suppress proteoglycan biosynthesis in cartilage at concentrations equivalent to the concentrations reached in human beings. 

Tablet 12.5mg

• Voltaren Acti-Go (Novartis) originator

Tablet 25mg

• A-Lennon diclofenac (Pharmacare Limited)
• Adco-diclofenac (Adcock)
• Diclofenac Biotech (Biotech)
• Diclohexal (Sandoz)
• Mylan Diclofenac (Mylan)
• Panamor (Pharmacare)
• Voltaren (Novartis) originator

Tablet 50mg

• A-Lennon diclofenac (Pharmacare Limited)
• Adco-Diclofenac (Adcock Ingram)
• Diclohexal 50 T (Sandoz)
• Diclofenac 50 Oethmaan ( Oethmaan Biosims)
• Mylan Diclofenac (Mylan)
• Panamor AT (Pharmacare Limited)
• Voltaren GT (Novartis) originator

Tablet 75mg 

• Voltaren (Novartis) originator

Tablet dispersible 50mg

• Cataflam D (Novartis) originator
• Catafast D (Novartis)
• Dicloflam (Pharmacare)
• Dicloflam Blackcurrent (Pharmacare Limited)
• Panamor 50mg Dispersible tablet (Pharmacare Limited)

Tablet sr 75mg

• Panamor (Pharmacare)

Tablet sr 100mg

• Difen (Gulf Drug)
• Diclofenac SR Biotech (Biotech)
• Panamor (Pharmacare)
• Sandoz Diclofenac Sodium (Sandoz)
• Voltaren (Novartis) originator

Capsule 12.5mg

• Voltaren Acti-Go Soft Gel (Novartis) originator

Capsule 25mg

• Voltaren Acti-Go Soft Gel (GlaxoSmithKline) originator

Capsule 75mg

• Motifine (Biotech)

 Capsule sr 75mg

• Veltex (Adcock) originator

Capsule sr 100mg

• Fortfen (Pharmacare Limited)
• Veltex (Adcock)

Sachet 50mg

• Cataflam (Novartis) originator

Injection (per 3ml) 75mg

• Adco-Diclofenac (Adcock Ingram)
• Austell-Diclofenac (Austell)
• Bio Diclofenac (Biotech)
• Diclofenac Injection (Unimed Healthcare)
• Difenject (Medicine Dev)
• Fortfen (Pharmacare Limited)
• Panamor (Pharmacare Limited)
• Pharma-Q Diclofenac (Pharma Q)
• Q Care Diclofenac (Pharma Q)
• Trio-Diclofenac (Innovata )
• Voltaren (Novartis) originator

Oral drops (per ml) 15mg 

• Voltaren (Novartis) originator

Also available in the following forms: Suppository, gel, patch and lotion.

COMBINATION PREPARATIONS

Diclofenac/ Misoprostol

Tablet 50mg/200μg

• Arthrotec 50 (Pfizer) originator

Tablet 75mg/200μg

• Arthrotec 75 (Pfizer) originator