Drugs List

Therapeutic Indications

Uses

Ankylosing spondylitis
Control of pain/inflammation after orthopaedic surgery
Dysmenorrhoea
Gout - acute
Musculo-skeletal conditions
Osteoarthritis
Rheumatoid arthritis

Contraindications

Children under 18 years
Haemorrhagic diathesis
Breastfeeding
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History of gastrointestinal haemorrhage
History of gastrointestinal haemorrhage secondary to NSAID
History of gastrointestinal perforation
History of gastrointestinal ulceration
History of peptic ulcer
Peptic ulcer
Renal impairment - glomerular filtration rate below 10ml/minute
Severe cardiac failure
Severe hepatic impairment
Third trimester of pregnancy

Precautions and Warnings

Allergic disposition
Elderly
Females attempting to conceive
Risk factors for cardiovascular disorder
Asthma
Cardiac impairment
Cerebrovascular disorder
Coagulopathy
Connective tissue disorder
First trimester of pregnancy
History of asthma
History of cardiac failure
History of gastrointestinal disorder
Hypertension
Inflammatory bowel disease
Ischaemic heart disease
Mild hepatic impairment
Peripheral arterial circulatory disorder
Renal impairment - glomerular filtration rate 10 - 50ml/minute
Second trimester of pregnancy
Systemic lupus erythematosus

May mask symptoms or signs of infections
NSAIDs may provoke or exacerbate asthma
Advise ability to drive/operate machinery may be affected by side effects
Consider other first line treatment options in the elderly
Not all available brands are licensed for all indications
Preparation contains sucrose
Discontinue if signs of gastro-intestinal bleeding occur
Monitor closely any patient who develops new infection while on treatment
Monitor renal function in patients with cardiac impairment
Monitor renal function in patients with hepatic impairment
Discontinue if signs of gastro-intestinal ulceration occur
High dose/long term use may increase risk of arterial thrombotic events
NSAIDs may provoke bronchospasm/urticaria in susceptible patients
Risk of gastro-intestinal bleeding increased in the elderly
Severe gastro-intestinal side effects may occur without warning
Discontinue if any kind of visual disturbance occurs
Discontinue if hypersensitivity reactions occur
Discontinue if severe skin reaction occurs
Maintain treatment at the lowest effective dose
Start treatment at lowest recommended dose
May cause impaired fertility

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. Ketoprofen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Elderly patients 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 should be mointored for gastrointestinal bleeding throughout treatment during 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

Ketoprofen is contraindicated in the third trimester of pregnancy.

Use Ketoprofen 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.

Ketoprofen 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.

Ketoprofen 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 ketoprofen with caution in breastfeeding.

The manufacturer recommends avoiding the use of ketoprofen when breastfeeding.Although the level of excretion of ketoprofen in breast milk is unknown, some sources report adverse effects on breastfed infants such as gastrointestinal and renal effects.

Ibuprofen is considered a preferable choice in breastfeeding (Briggs 2015, Schaefer 2015).

Side Effects

Abdominal discomfort
Abdominal pain
Abnormal liver function
Aggravation of existing asthma
Agranulocytosis
Alopecia
Alterations in renal function tests
Anaemia
Anaphylaxis
Angioedema
Aplastic anaemia
Arterial thrombosis
Aseptic meningitis
Asthma
Blurred vision
Bone marrow aplasia
Bronchospasm
Bullous dermatoses
Cardiac failure
Confusion
Constipation
Convulsions
Depression
Diarrhoea
Disorientation
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Epidermal necrolysis
Erythema multiforme
Exacerbation of colitis
Exacerbation of Crohn's disease
Exfoliative dermatitis
Eye changes
Fatigue
Fever
Flatulence
Fluid retention
Gastralgia
Gastritis
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastro-intestinal ulceration
Haematemesis
Haemolytic anaemia
Hallucinations
Headache
Heartburn
Hepatitis
Hypersensitivity reactions
Hypertension
Increase of liver transaminases
Induces asthma attacks
Insomnia
Interstitial nephritis
Jaundice
Malaise
Melaena
Mild confusion
Mood changes
Nausea
Neck stiffness
Nephrotic syndrome
Nephrotoxicity
Neutropenia
Non-specific allergic reactions
Oedema
Optic neuritis
Pancreatitis
Paraesthesia
Photosensitivity
Pruritus
Purpura
Rash
Renal failure
Rhinitis
Serum bilirubin increased
Shock
Somnolence
Stevens-Johnson syndrome
Stomatitis
Taste disturbances
Thrombocytopenia
Tinnitus
Ulcerative stomatitis
Urticaria
Vasodilatation
Vertigo
Visual disturbances
Vomiting
Weight gain

Presentation

Modified release formulations of ketoprofen.

Drugs List

Therapeutic Indications

Uses

Ankylosing spondylitis
Control of pain/inflammation after orthopaedic surgery
Dysmenorrhoea
Gout - acute
Musculo-skeletal conditions
Osteoarthritis
Rheumatoid arthritis

Dosage

Adults

Contraindications

Children under 18 years
Haemorrhagic diathesis
Breastfeeding
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History of gastrointestinal haemorrhage
History of gastrointestinal haemorrhage secondary to NSAID
History of gastrointestinal perforation
History of gastrointestinal ulceration
History of peptic ulcer
Peptic ulcer
Renal impairment - glomerular filtration rate below 10ml/minute
Severe cardiac failure
Severe hepatic impairment
Third trimester of pregnancy

Precautions and Warnings

Allergic disposition
Elderly
Females attempting to conceive
Risk factors for cardiovascular disorder
Asthma
Cardiac impairment
Cerebrovascular disorder
Coagulopathy
Connective tissue disorder
First trimester of pregnancy
History of asthma
History of cardiac failure
History of gastrointestinal disorder
Hypertension
Inflammatory bowel disease
Ischaemic heart disease
Mild hepatic impairment
Peripheral arterial circulatory disorder
Renal impairment - glomerular filtration rate 10 - 50ml/minute
Second trimester of pregnancy
Systemic lupus erythematosus

May mask symptoms or signs of infections
NSAIDs may provoke or exacerbate asthma
Advise ability to drive/operate machinery may be affected by side effects
Consider other first line treatment options in the elderly
Not all available brands are licensed for all indications
Preparation contains sucrose
Discontinue if signs of gastro-intestinal bleeding occur
Monitor closely any patient who develops new infection while on treatment
Monitor renal function in patients with cardiac impairment
Monitor renal function in patients with hepatic impairment
Discontinue if signs of gastro-intestinal ulceration occur
High dose/long term use may increase risk of arterial thrombotic events
NSAIDs may provoke bronchospasm/urticaria in susceptible patients
Risk of gastro-intestinal bleeding increased in the elderly
Severe gastro-intestinal side effects may occur without warning
Discontinue if any kind of visual disturbance occurs
Discontinue if hypersensitivity reactions occur
Discontinue if severe skin reaction occurs
Maintain treatment at the lowest effective dose
Start treatment at lowest recommended dose
May cause impaired fertility

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. Ketoprofen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Elderly patients 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 should be mointored for gastrointestinal bleeding throughout treatment during 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

Ketoprofen is contraindicated in the third trimester of pregnancy.

Use Ketoprofen 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.

Ketoprofen 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.

Ketoprofen 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 ketoprofen with caution in breastfeeding.

The manufacturer recommends avoiding the use of ketoprofen when breastfeeding.Although the level of excretion of ketoprofen in breast milk is unknown, some sources report adverse effects on breastfed infants such as gastrointestinal and renal effects.

Ibuprofen is considered a preferable choice in breastfeeding (Briggs 2015, Schaefer 2015).

Side Effects

Abdominal discomfort
Abdominal pain
Abnormal liver function
Aggravation of existing asthma
Agranulocytosis
Alopecia
Alterations in renal function tests
Anaemia
Anaphylaxis
Angioedema
Aplastic anaemia
Arterial thrombosis
Aseptic meningitis
Asthma
Blurred vision
Bone marrow aplasia
Bronchospasm
Bullous dermatoses
Cardiac failure
Confusion
Constipation
Convulsions
Depression
Diarrhoea
Disorientation
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Epidermal necrolysis
Erythema multiforme
Exacerbation of colitis
Exacerbation of Crohn's disease
Exfoliative dermatitis
Eye changes
Fatigue
Fever
Flatulence
Fluid retention
Gastralgia
Gastritis
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastro-intestinal ulceration
Haematemesis
Haemolytic anaemia
Hallucinations
Headache
Heartburn
Hepatitis
Hypersensitivity reactions
Hypertension
Increase of liver transaminases
Induces asthma attacks
Insomnia
Interstitial nephritis
Jaundice
Malaise
Melaena
Mild confusion
Mood changes
Nausea
Neck stiffness
Nephrotic syndrome
Nephrotoxicity
Neutropenia
Non-specific allergic reactions
Oedema
Optic neuritis
Pancreatitis
Paraesthesia
Photosensitivity
Pruritus
Purpura
Rash
Renal failure
Rhinitis
Serum bilirubin increased
Shock
Somnolence
Stevens-Johnson syndrome
Stomatitis
Taste disturbances
Thrombocytopenia
Tinnitus
Ulcerative stomatitis
Urticaria
Vasodilatation
Vertigo
Visual disturbances
Vomiting
Weight gain

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: Feburary 2021

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. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Oruvail 100mg capsules. Sanofi-Aventis. Revised November 2020.

Summary of Product Characteristics: Oruvail 200mg capsules. Sanofi-Aventis. Revised November 2020.

Summary of Product Characteristics: Larafen CR capsules 200mg. Ennogen Pharma Ltd. Revised June 2018.

The Renal Drug Handbook. Fifth Edition. (2019) ed. Ashley, C and Dunleavy, A. Radcliffe Publishing Ltd, London.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Ketoprofen. Last revised: 31 October 2018
Last accessed: 25 February 2021