Drugs List

Therapeutic Indications

Uses

Osteoarthritis
Rheumatoid arthritis

Contraindications

Children under 18 years
Galactosaemia
History of gastrointestinal haemorrhage secondary to NSAID
History of peptic ulcer
Peptic ulcer
Severe cardiac failure
Severe hepatic impairment
Severe renal impairment
Third trimester of pregnancy

Precautions and Warnings

Elderly
Females attempting to conceive
Fluid retention
Asthma
Breastfeeding
Cardiac failure
Cardiac impairment
Cerebrovascular disorder
Connective tissue disorder
Crohn's disease
First trimester of pregnancy
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of asthma
Hypertension
Ischaemic heart disease
Lactose intolerance
Renal impairment
Second trimester of pregnancy
Severe peripheral arterial disease
Systemic lupus erythematosus
Ulcerative colitis

Advise ability to drive/operate machinery may be affected by side effects
Contains lactose
Discontinue if signs of gastro-intestinal bleeding occur
May affect platelet function
Monitor liver function on prolonged therapy
Monitor renal function in patients with cardiac impairment
Monitor renal function in patients with hepatic impairment
Patients on long-term therapy should be regularly reviewed
Perform blood counts on prolonged use of this treatment
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
May affect results of some laboratory tests
Discontinue if symptoms of peptic ulcer occur
Discontinue treatment if skin rash or other allergic reaction occurs
Maintain treatment at the lowest effective dose
May cause impaired fertility

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with etodolac after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking). Fluid retention and oedema have been reported with NSAID treatment.

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 in the majority of cases within the first month of treatment. Treatment should be discontinued at the first appearance of skin rash, mucosal lesions, or any other signs of hypersensitivity.

In patients with renal impairment, cardiac impairment or hepatic impairment especially those taking diuretics, caution is required since the use of NSAIDs may result in deterioration of renal function. The dose should be kept as low as possible and renal function should be monitored.

The risk of bleeding, ulceration or perforation is higher with increasing NSAID doses in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly. These patients should commence treatment on the lowest effective dose. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin or other drugs likely to increase gastrointestinal risk.

In patients with systemic lupus erythematous and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.

Pregnancy and Lactation

Pregnancy

Drugs which inhibit prostaglandin biosynthesis may cause dystocia and delayed parturition as evidenced by studies in pregnant animals. Some inhibitors of prostaglandin biosynthesis have been shown to interfere with the closure of the ductus arteriosus. Safety in human pregnancy has not been established and etodolac should not be used during 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 14-17 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

No reports describing the use of etodolac during lactation have been located. The low molecular weight (287), the excretion of etodolac into breast milk should be expected. Moreover, because of its long termination adult plasma half-life (7.3 hours), other agents e.g. ibuprofen may be preferred during lactation (Briggs, 2011).

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
Abnormal vision
Agranulocytosis
Anaemia
Anaphylactoid reaction
Angioedema
Aseptic meningitis
Bilirubinuria
Bronchospasm
Cardiac failure
Colitis
Confusion
Constipation
Depression
Diarrhoea
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Dysuria
Epigastric pain
Exacerbation of colitis
Exacerbation of Crohn's disease
Eye changes
Fatigue
Flatulence
Fluid retention
Gastritis
Gastro-intestinal haemorrhage
Gastro-intestinal ulceration
Haematemesis
Haematuria
Headache
Heartburn
Hepatic damage
Hypersensitivity reactions
Hypertension
Indigestion
Insomnia
Interstitial nephritis
Jaundice
Liver function disturbances
Malaise
Melaena
Nausea
Nephritis
Nephrotic syndrome
Nephrotoxicity
Neutropenia
Oedema
Palpitations
Pancreatitis
Papillary necrosis
Paraesthesia
Peptic ulceration
Peptic ulceration with perforation and haemorrhage
Photosensitivity
Pruritus
Pyrexia
Rash
Rectal bleeding
Renal failure
Stevens-Johnson syndrome
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Tremor
Ulcerative stomatitis
Urinary frequency
Urticaria
Vasculitis
Vertigo
Vomiting
Weakness

Presentation

Modified release formulations of etodolac.

Drugs List

Therapeutic Indications

Uses

Osteoarthritis
Rheumatoid arthritis

Dosage

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.

Adults

Elderly

Contraindications

Children under 18 years
Galactosaemia
History of gastrointestinal haemorrhage secondary to NSAID
History of peptic ulcer
Peptic ulcer
Severe cardiac failure
Severe hepatic impairment
Severe renal impairment
Third trimester of pregnancy

Precautions and Warnings

Elderly
Females attempting to conceive
Fluid retention
Asthma
Breastfeeding
Cardiac failure
Cardiac impairment
Cerebrovascular disorder
Connective tissue disorder
Crohn's disease
First trimester of pregnancy
Glucose-galactose malabsorption syndrome
Hepatic impairment
History of asthma
Hypertension
Ischaemic heart disease
Lactose intolerance
Renal impairment
Second trimester of pregnancy
Severe peripheral arterial disease
Systemic lupus erythematosus
Ulcerative colitis

Advise ability to drive/operate machinery may be affected by side effects
Contains lactose
Discontinue if signs of gastro-intestinal bleeding occur
May affect platelet function
Monitor liver function on prolonged therapy
Monitor renal function in patients with cardiac impairment
Monitor renal function in patients with hepatic impairment
Patients on long-term therapy should be regularly reviewed
Perform blood counts on prolonged use of this treatment
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
May affect results of some laboratory tests
Discontinue if symptoms of peptic ulcer occur
Discontinue treatment if skin rash or other allergic reaction occurs
Maintain treatment at the lowest effective dose
May cause impaired fertility

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with etodolac after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking). Fluid retention and oedema have been reported with NSAID treatment.

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 in the majority of cases within the first month of treatment. Treatment should be discontinued at the first appearance of skin rash, mucosal lesions, or any other signs of hypersensitivity.

In patients with renal impairment, cardiac impairment or hepatic impairment especially those taking diuretics, caution is required since the use of NSAIDs may result in deterioration of renal function. The dose should be kept as low as possible and renal function should be monitored.

The risk of bleeding, ulceration or perforation is higher with increasing NSAID doses in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly. These patients should commence treatment on the lowest effective dose. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin or other drugs likely to increase gastrointestinal risk.

In patients with systemic lupus erythematous and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.

Pregnancy and Lactation

Pregnancy

Drugs which inhibit prostaglandin biosynthesis may cause dystocia and delayed parturition as evidenced by studies in pregnant animals. Some inhibitors of prostaglandin biosynthesis have been shown to interfere with the closure of the ductus arteriosus. Safety in human pregnancy has not been established and etodolac should not be used during 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 14-17 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

No reports describing the use of etodolac during lactation have been located. The low molecular weight (287), the excretion of etodolac into breast milk should be expected. Moreover, because of its long termination adult plasma half-life (7.3 hours), other agents e.g. ibuprofen may be preferred during lactation (Briggs, 2011).

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

Effects on Ability to Drive and Operate Machinery

The ability to drive or operate machinery may be affected by side effects such as dizziness, drowsiness or abnormal vision.

Side Effects

Abdominal pain
Abnormal vision
Agranulocytosis
Anaemia
Anaphylactoid reaction
Angioedema
Aseptic meningitis
Bilirubinuria
Bronchospasm
Cardiac failure
Colitis
Confusion
Constipation
Depression
Diarrhoea
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Dysuria
Epigastric pain
Exacerbation of colitis
Exacerbation of Crohn's disease
Eye changes
Fatigue
Flatulence
Fluid retention
Gastritis
Gastro-intestinal haemorrhage
Gastro-intestinal ulceration
Haematemesis
Haematuria
Headache
Heartburn
Hepatic damage
Hypersensitivity reactions
Hypertension
Indigestion
Insomnia
Interstitial nephritis
Jaundice
Liver function disturbances
Malaise
Melaena
Nausea
Nephritis
Nephrotic syndrome
Nephrotoxicity
Neutropenia
Oedema
Palpitations
Pancreatitis
Papillary necrosis
Paraesthesia
Peptic ulceration
Peptic ulceration with perforation and haemorrhage
Photosensitivity
Pruritus
Pyrexia
Rash
Rectal bleeding
Renal failure
Stevens-Johnson syndrome
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Tremor
Ulcerative stomatitis
Urinary frequency
Urticaria
Vasculitis
Vertigo
Vomiting
Weakness

Effects on Laboratory Tests

The presence of phenolic metabolites of etodolac in the urine may give a false positive bilirubin test result.

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: February 2013

Reference Sources

British National Formulary, 64th Edition (2012) Pharmaceutical Press, 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.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Etolyn 600 mg prolongd release tablets. Abdi Farma, Unipessoal Lda. Revised February 2015.
Summary of Product Characteristics: Etopan XL. Taro Pharmaceuticals (UK) Ltd. Revised May 2006
Summary of Product Characteristics: Lodine SR. Almirall Ltd. Revised October 2018.

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
Etodolac Last revised: April 3, 2012
Last accessed: February 12, 2013