Drugs List

Therapeutic Indications

Uses

Acute musculoskeletal disorders
Ankylosing spondylitis
Gout - acute
Juvenile chronic arthritis
Relief of pain and inflammation due to trauma
Relief of pain and inflammation in osteoarthritis
Relief of pain and inflammation in rheumatoid arthritis
Treatment of post-operative pain

Contraindications

Children under 6 months
Cerebrovascular disorder
Gastrointestinal haemorrhage
Gastrointestinal perforation
Gastrointestinal ulcer
History of gastrointestinal haemorrhage
History of peptic ulcer
Ischaemic heart disease
New York Heart Association class II failure
Peripheral arterial circulatory disorder
Proctitis
Renal impairment - glomerular filtration rate below 10ml/minute
Severe hepatic impairment
Third trimester of pregnancy

Precautions and Warnings

Allergic disposition
Children aged 6 to 12 months
Elderly
Females attempting to conceive
Predisposition to haemorrhage
Risk factors for cardiovascular disorder
Asthma
Breastfeeding
Connective tissue disorder
Crohn's disease
First trimester of pregnancy
Haematological disorder
Hepatic impairment
History of cardiac failure
Hypertension
Renal impairment - glomerular filtration rate 10-20ml/minute
Second trimester of pregnancy
Systemic lupus erythematosus
Ulcerative colitis

May mask symptoms or signs of infections
May precipitate bronchospasm in patients with asthma or allergy
Advise patient dizziness may affect ability to drive or operate machinery
Not all available products are licensed for all age groups
Discontinue if signs of gastro-intestinal bleeding occur
May inhibit platelet aggregation - observe for signs of bleeding
Monitor hepatic function on long term therapy
Monitor renal function in patients with hepatic impairment
Monitor renal function on long term therapy
High dose/long term use may increase risk of arterial thrombotic events
Severe gastro-intestinal side effects may occur without warning
Discontinue if hepatic function deteriorates
Discontinue treatment if rash occurs
Maintain treatment at the lowest effective dose

Elderly patients have increased frequency of adverse reactions, especially gastrointestinal bleeding and perforation which may be fatal. These patients should commence treatment on the lowest dose available and be monitored for gastrointestinal bleeding for 4 weeks following initiation of therapy.

Patients with renal or hepatic impairment and the elderly should be kept under surveillance, since the use of NSAIDs may result in deterioration of renal function. The lowest effective dose should be used and renal function monitored.

If abnormal liver function tests persist or worsen, clinical signs or symptoms consistent with liver disease develop, or if other manifestations occur (eosinophilia, rash, etc) treatment should be discontinued. Hepatitis may occur without prodromal symptoms.

Diclofenac sodium may reversibly inhibit platelet aggregation. Patients with defects of haemostasis, bleeding diathesis or haematological abnormalities should be carefully monitored.

Pregnancy and Lactation

Pregnancy

The manufacturer does not recommend this product in pregnancy.

First trimester exposure to NSAIDs has been associated with an increased risk spontaneous abortions and of birth defects (notably cardiac septal defects). There is conflicting evidence, however, from various studies and the risk appears to be low.

When an NSAID is considered essential, a more established drug such as ibuprofen may be considered. Diclofenac should be used with caution in the first and second trimesters. Schaefer (2007) considers that use of NSAIDs in early pregnancy does not require termination of pregnancy or invasive diagnostic procedures.

Diclofenac is a prostaglandin synthetase inhibitor and may have the following effects during the second and third trimesters:
- Pulmonary and cardiac toxicity in the foetus/newborn (pulmonary hypertension with preterm closing of the ductus arteriosus). The risk exists from the beginning of the sixth month and increases if administration is close to full term.
- Functional renal injury in the foetus. From the twelfth week: oligohydramnios (usually reversible after the end of treatment) or anamnios (particularly with prolonged exposure). Following birth, renal failure may persist (especially with late and prolonged exposure).
- Inhibition of uterine contractions with delayed onset and prolongation of labour.
- Increased possibility of bleeding in mother and child.
- Increased risk of maternal oedema formation.
- When used in the peri-natal period, necrotising enterocolitis and intraventricular haemorrhages have been reported in very pre-term and very low birth weight infants.

Use of any NSAID is considered contraindicated during the third trimester of pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. The manufacturer recommends avoiding the use of diclofenac when breastfeeding.

When an NSAID is considered necessary during breastfeeding ibuprofen or flurbiprofen would be the drugs of choice although occasional use of diclofenac is permissible.

The secretion in maternal milk following oral administration is minimal and probably too low to affect the infant. Diclofenac has a short half-life of 1.1 hours and a number of active metabolites although the clinical significance of these is not known.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute renal insufficiency
Aggravation of existing asthma
Agranulocytosis
Anaemia
Anaphylactic reaction
Anaphylactoid reaction
Anorexia
Anxiety
Arterial thrombosis
Aseptic meningitis
Asthma
Blurred vision
Bronchospasm
Cerebrovascular accident
Chest pain
Colonic damage
Colonic stricture
Confusion
Congestive cardiac failure
Convulsions
Depression
Diarrhoea
Diplopia
Disorientation
Disturbances of sensation
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Eczema
Erythema multiforme
Exacerbation of colitis
Exacerbation of Crohn's disease
Exacerbation of haemorrhoids
Exfoliative dermatitis
Eye disorder
Flatulence
Gastro-intestinal disturbances
Gastro-intestinal ulceration and bleeding
Glossitis
Haematemesis
Haematuria
Hair loss
Hallucinations
Headache
Hearing disturbances
Hepatic disorders
Hypersensitivity reactions
Hypertension
Hypotension
Impotence
Increase of liver transaminases
Increased bowel action
Increases in hepatic enzymes
Insomnia
Interstitial nephritis
Irritability
Ischaemic colitis
Itching at application site
Jaundice
Leucopenia
Malaise
Melaena
Memory disturbances
Mouth ulcers
Myocardial infarction
Nausea
Nephrotic syndrome
Nightmares
Non-specific haemorrhagic colitis
Oedema
Oesophageal lesions
Pain
Palpitations
Pancreatitis
Papillary necrosis
Paraesthesia
Photosensitivity
Pneumonitis
Proteinuria
Psychosis
Purpura
Renal failure
Shock
Skin disorder
Stevens-Johnson syndrome
Taste disturbances
Thrombocytopenia
Tiredness
Toxic epidermal necrolysis
Tremor
Urinary abnormalities
Vasculitis
Vertigo
Visual disturbances
Vomiting

Presentation

Suppository formulations of diclofenac sodium.

Drugs List

Therapeutic Indications

Uses

Acute musculoskeletal disorders
Ankylosing spondylitis
Gout - acute
Juvenile chronic arthritis
Relief of pain and inflammation due to trauma
Relief of pain and inflammation in osteoarthritis
Relief of pain and inflammation in rheumatoid arthritis
Treatment of post-operative pain

Dosage

Adults

Children

Contraindications

Children under 6 months
Cerebrovascular disorder
Gastrointestinal haemorrhage
Gastrointestinal perforation
Gastrointestinal ulcer
History of gastrointestinal haemorrhage
History of peptic ulcer
Ischaemic heart disease
New York Heart Association class II failure
Peripheral arterial circulatory disorder
Proctitis
Renal impairment - glomerular filtration rate below 10ml/minute
Severe hepatic impairment
Third trimester of pregnancy

Precautions and Warnings

Allergic disposition
Children aged 6 to 12 months
Elderly
Females attempting to conceive
Predisposition to haemorrhage
Risk factors for cardiovascular disorder
Asthma
Breastfeeding
Connective tissue disorder
Crohn's disease
First trimester of pregnancy
Haematological disorder
Hepatic impairment
History of cardiac failure
Hypertension
Renal impairment - glomerular filtration rate 10-20ml/minute
Second trimester of pregnancy
Systemic lupus erythematosus
Ulcerative colitis

May mask symptoms or signs of infections
May precipitate bronchospasm in patients with asthma or allergy
Advise patient dizziness may affect ability to drive or operate machinery
Not all available products are licensed for all age groups
Discontinue if signs of gastro-intestinal bleeding occur
May inhibit platelet aggregation - observe for signs of bleeding
Monitor hepatic function on long term therapy
Monitor renal function in patients with hepatic impairment
Monitor renal function on long term therapy
High dose/long term use may increase risk of arterial thrombotic events
Severe gastro-intestinal side effects may occur without warning
Discontinue if hepatic function deteriorates
Discontinue treatment if rash occurs
Maintain treatment at the lowest effective dose

Elderly patients have increased frequency of adverse reactions, especially gastrointestinal bleeding and perforation which may be fatal. These patients should commence treatment on the lowest dose available and be monitored for gastrointestinal bleeding for 4 weeks following initiation of therapy.

Patients with renal or hepatic impairment and the elderly should be kept under surveillance, since the use of NSAIDs may result in deterioration of renal function. The lowest effective dose should be used and renal function monitored.

If abnormal liver function tests persist or worsen, clinical signs or symptoms consistent with liver disease develop, or if other manifestations occur (eosinophilia, rash, etc) treatment should be discontinued. Hepatitis may occur without prodromal symptoms.

Diclofenac sodium may reversibly inhibit platelet aggregation. Patients with defects of haemostasis, bleeding diathesis or haematological abnormalities should be carefully monitored.

Pregnancy and Lactation

Pregnancy

The manufacturer does not recommend this product in pregnancy.

First trimester exposure to NSAIDs has been associated with an increased risk spontaneous abortions and of birth defects (notably cardiac septal defects). There is conflicting evidence, however, from various studies and the risk appears to be low.

When an NSAID is considered essential, a more established drug such as ibuprofen may be considered. Diclofenac should be used with caution in the first and second trimesters. Schaefer (2007) considers that use of NSAIDs in early pregnancy does not require termination of pregnancy or invasive diagnostic procedures.

Diclofenac is a prostaglandin synthetase inhibitor and may have the following effects during the second and third trimesters:
- Pulmonary and cardiac toxicity in the foetus/newborn (pulmonary hypertension with preterm closing of the ductus arteriosus). The risk exists from the beginning of the sixth month and increases if administration is close to full term.
- Functional renal injury in the foetus. From the twelfth week: oligohydramnios (usually reversible after the end of treatment) or anamnios (particularly with prolonged exposure). Following birth, renal failure may persist (especially with late and prolonged exposure).
- Inhibition of uterine contractions with delayed onset and prolongation of labour.
- Increased possibility of bleeding in mother and child.
- Increased risk of maternal oedema formation.
- When used in the peri-natal period, necrotising enterocolitis and intraventricular haemorrhages have been reported in very pre-term and very low birth weight infants.

Use of any NSAID is considered contraindicated during the third trimester of pregnancy.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. The manufacturer recommends avoiding the use of diclofenac when breastfeeding.

When an NSAID is considered necessary during breastfeeding ibuprofen or flurbiprofen would be the drugs of choice although occasional use of diclofenac is permissible.

The secretion in maternal milk following oral administration is minimal and probably too low to affect the infant. Diclofenac has a short half-life of 1.1 hours and a number of active metabolites although the clinical significance of these is not known.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute renal insufficiency
Aggravation of existing asthma
Agranulocytosis
Anaemia
Anaphylactic reaction
Anaphylactoid reaction
Anorexia
Anxiety
Arterial thrombosis
Aseptic meningitis
Asthma
Blurred vision
Bronchospasm
Cerebrovascular accident
Chest pain
Colonic damage
Colonic stricture
Confusion
Congestive cardiac failure
Convulsions
Depression
Diarrhoea
Diplopia
Disorientation
Disturbances of sensation
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Eczema
Erythema multiforme
Exacerbation of colitis
Exacerbation of Crohn's disease
Exacerbation of haemorrhoids
Exfoliative dermatitis
Eye disorder
Flatulence
Gastro-intestinal disturbances
Gastro-intestinal ulceration and bleeding
Glossitis
Haematemesis
Haematuria
Hair loss
Hallucinations
Headache
Hearing disturbances
Hepatic disorders
Hypersensitivity reactions
Hypertension
Hypotension
Impotence
Increase of liver transaminases
Increased bowel action
Increases in hepatic enzymes
Insomnia
Interstitial nephritis
Irritability
Ischaemic colitis
Itching at application site
Jaundice
Leucopenia
Malaise
Melaena
Memory disturbances
Mouth ulcers
Myocardial infarction
Nausea
Nephrotic syndrome
Nightmares
Non-specific haemorrhagic colitis
Oedema
Oesophageal lesions
Pain
Palpitations
Pancreatitis
Papillary necrosis
Paraesthesia
Photosensitivity
Pneumonitis
Proteinuria
Psychosis
Purpura
Renal failure
Shock
Skin disorder
Stevens-Johnson syndrome
Taste disturbances
Thrombocytopenia
Tiredness
Toxic epidermal necrolysis
Tremor
Urinary abnormalities
Vasculitis
Vertigo
Visual disturbances
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: July 2013

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Econac 100mg suppositories. Amdipharm Mercury Company Ltd. Revised September 2016.

Summary of Product Characteristics: Voltarol Suppositories. Novartis Pharmaceuticals UK Ltd. Revised February 2017.

'PRAC recommends the same cardiovascular precautions for diclofenac as for selective COX-2 inhibitors'
European Medicines Agency (EMA) 14th June 2013
Available at: www.ema.europe.eu
Last accessed: July 11, 2013

MHRA Drug Safety Update June 2013
Available at: https://www.mhra.gov.uk
Last accessed: July 11, 2013

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 28 June 2017.

The drug database for acute porphyria (NAPOS)
Available at: https://www.drugs-porphyria.org/monograph.php?id=3175
Diclofenac Last revised: June 30, 2010
Last accessed: July 11, 2013

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Diclofenac Last revised: March 1, 2012
Last accessed: July 11,2013