Drugs List

Therapeutic Indications

Uses

Ankylosing spondylitis
Gout - acute
Musculo-skeletal conditions
Osteoarthritis
Pain - mild to moderate
Rheumatoid arthritis
Treatment of post-operative pain

Administration

Where the symptoms are most pronounced during the night or in the morning, the dose should preferably be taken in the evening.

Contraindications

Children under 12 years
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
Renal impairment - glomerular filtration rate below 10ml/minute
Severe hepatic impairment
Third trimester of pregnancy

Precautions and Warnings

Allergic disposition
Children aged 12 to 18 years
Elderly
Females attempting to conceive
Risk factors for cardiovascular disorder
Asthma
Breastfeeding
Connective tissue disorder
Crohn's disease
First trimester of pregnancy
Galactosaemia
Glucose-galactose malabsorption syndrome
Haematological disorder
Hepatic impairment
Hereditary fructose intolerance
History of major gastrointestinal surgery
Hypertension
Lactose intolerance
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 ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all indications
Some formulations contain lactose
Some formulations contain sucrose
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

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

Elderly patients and patients of low body weight are more susceptible to the adverse reactions of NSAIDs, including gastrointestinal bleeding and perforation. As such, they should be started on and maintained on the lowest possible dose and monitored for gastrointestinal bleeding for 4 weeks after initiation of NSAID therapy. Concomitant gastro-protection (e.g. proton pump inhibitors) should be considered in these patients and those on other drugs, which increase gastrointestinal risk.

Patients with mixed connective tissue disorders such as systemic lupus erythematosus may be especially susceptible to aseptic meningitis.

Pregnancy and Lactation

Pregnancy

Diclofenac sodium is contraindicated in the third trimester of pregnancy.

Use diclofenac sodium with caution in the first trimester and second trimesters of pregnancy

The manufacturer does not recommend this product in pregnancy.

Studies suggest increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy.

Diclofenac should not be given in the first and second trimester unless necessary and the dose should be kept as low and duration of treatment as short as possible.

Diclofenac 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.

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

Lactation

Use diclofenac sodium with caution in breastfeeding.

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

Side Effects

Abdominal pain
Abnormal liver function
Acute renal insufficiency
Aggravation of existing asthma
Agranulocytosis
Anaphylactoid reaction
Anaphylaxis
Anorexia
Anxiety
Aphthous stomatitis
Aplastic anaemia
Arterial thrombosis
Aseptic meningitis
Asthma
Bronchospasm
Cerebrovascular accident
Chest pain
Colonic stricture
Confusion
Congestive cardiac failure
Constipation
Convulsions
Depression
Diarrhoea
Diarrhoea - bloody
Disorientation
Disturbances of sensation
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Eczema
Exacerbation of colitis or Crohn's proctocolitis
Fatigue
Flatulence
Gastritis
Gastro-intestinal perforation
Gastro-intestinal ulceration
Gastrointestinal bleeding
Glossitis
Haematemesis
Haematuria
Haemolytic anaemia
Hair loss
Hallucinations
Headache
Hearing disturbances
Hepatic failure
Hepatic impairment
Hepatic necrosis
Hepatitis
Hypersensitivity reactions
Hypertension
Hypotension
Impotence
Increases in hepatic enzymes
Insomnia
Interstitial nephritis
Irritability
Jaundice
Kounis syndrome
Leucopenia
Lyell's syndrome
Malaise
Melaena
Memory disturbances
Myocardial infarction
Nausea
Nephrotic syndrome
Neutropenia
Nightmares
Non-specific allergic reactions
Non-specific haemorrhagic colitis
Oedema
Oesophageal lesions
Palpitations
Pancreatitis
Papillary necrosis
Paraesthesia
Photosensitivity
Pneumonitis
Proteinuria
Pruritus
Psychotic symptoms
Purpura
Renal failure
Shock
Skin disorder
Stevens-Johnson syndrome
Taste disturbances
Thrombocytopenia
Tinnitus
Tiredness
Tremor
Ulcerative stomatitis
Vasculitis
Vertigo
Visual disturbances
Vomiting

Presentation

Modified release formulations of diclofenac sodium.

Drugs List

Therapeutic Indications

Uses

Ankylosing spondylitis
Gout - acute
Musculo-skeletal conditions
Osteoarthritis
Pain - mild to moderate
Rheumatoid arthritis
Treatment of post-operative pain

Dosage

Adults

Children

Administration

Where the symptoms are most pronounced during the night or in the morning, the dose should preferably be taken in the evening.

Contraindications

Children under 12 years
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
Renal impairment - glomerular filtration rate below 10ml/minute
Severe hepatic impairment
Third trimester of pregnancy

Precautions and Warnings

Allergic disposition
Children aged 12 to 18 years
Elderly
Females attempting to conceive
Risk factors for cardiovascular disorder
Asthma
Breastfeeding
Connective tissue disorder
Crohn's disease
First trimester of pregnancy
Galactosaemia
Glucose-galactose malabsorption syndrome
Haematological disorder
Hepatic impairment
Hereditary fructose intolerance
History of major gastrointestinal surgery
Hypertension
Lactose intolerance
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 ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all indications
Some formulations contain lactose
Some formulations contain sucrose
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

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

Elderly patients and patients of low body weight are more susceptible to the adverse reactions of NSAIDs, including gastrointestinal bleeding and perforation. As such, they should be started on and maintained on the lowest possible dose and monitored for gastrointestinal bleeding for 4 weeks after initiation of NSAID therapy. Concomitant gastro-protection (e.g. proton pump inhibitors) should be considered in these patients and those on other drugs, which increase gastrointestinal risk.

Patients with mixed connective tissue disorders such as systemic lupus erythematosus may be especially susceptible to aseptic meningitis.

Pregnancy and Lactation

Pregnancy

Diclofenac sodium is contraindicated in the third trimester of pregnancy.

Use diclofenac sodium with caution in the first trimester and second trimesters of pregnancy

The manufacturer does not recommend this product in pregnancy.

Studies suggest increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy.

Diclofenac should not be given in the first and second trimester unless necessary and the dose should be kept as low and duration of treatment as short as possible.

Diclofenac 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.

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

Lactation

Use diclofenac sodium with caution in breastfeeding.

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

Counselling

Advise patients that they should report any unusual abdominal symptoms (especially gastrointestinal bleeding).

Advise patients that the ability to drive or operate machinery may be affected by side effects such as dizziness, vertigo, somnolence, central nervous system disturbances, drowsiness and fatigue.

Side Effects

Abdominal pain
Abnormal liver function
Acute renal insufficiency
Aggravation of existing asthma
Agranulocytosis
Anaphylactoid reaction
Anaphylaxis
Anorexia
Anxiety
Aphthous stomatitis
Aplastic anaemia
Arterial thrombosis
Aseptic meningitis
Asthma
Bronchospasm
Cerebrovascular accident
Chest pain
Colonic stricture
Confusion
Congestive cardiac failure
Constipation
Convulsions
Depression
Diarrhoea
Diarrhoea - bloody
Disorientation
Disturbances of sensation
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Eczema
Exacerbation of colitis or Crohn's proctocolitis
Fatigue
Flatulence
Gastritis
Gastro-intestinal perforation
Gastro-intestinal ulceration
Gastrointestinal bleeding
Glossitis
Haematemesis
Haematuria
Haemolytic anaemia
Hair loss
Hallucinations
Headache
Hearing disturbances
Hepatic failure
Hepatic impairment
Hepatic necrosis
Hepatitis
Hypersensitivity reactions
Hypertension
Hypotension
Impotence
Increases in hepatic enzymes
Insomnia
Interstitial nephritis
Irritability
Jaundice
Kounis syndrome
Leucopenia
Lyell's syndrome
Malaise
Melaena
Memory disturbances
Myocardial infarction
Nausea
Nephrotic syndrome
Neutropenia
Nightmares
Non-specific allergic reactions
Non-specific haemorrhagic colitis
Oedema
Oesophageal lesions
Palpitations
Pancreatitis
Papillary necrosis
Paraesthesia
Photosensitivity
Pneumonitis
Proteinuria
Pruritus
Psychotic symptoms
Purpura
Renal failure
Shock
Skin disorder
Stevens-Johnson syndrome
Taste disturbances
Thrombocytopenia
Tinnitus
Tiredness
Tremor
Ulcerative stomatitis
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: December 2020

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Diclomax Retard. Galen Ltd. Revised June 2020.
Summary of Product Characteristics: Diclomax SR. Galen Ltd. Revised October 2020.

Summary of Product Characteristics: Diclo-SR. Strides Pharma UK Ltd. Revised November 2020.

Summary of Product Characteristics: Enstar XL 100mg tablets. Ennogen Pharma Ltd. Revised October 2019.

Summary of Product Characteristics: Motifene 75mg. Daiichi-Sankyo UK Ltd. Revised September 2020.

The Renal Drug Handbook. 5th edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed : 15 December 2020