Drugs List

Therapeutic Indications

Uses

Acute migraine

Contraindications

Children under 18 years
Gastrointestinal haemorrhage
History of gastrointestinal haemorrhage
History of gastrointestinal haemorrhage secondary to NSAID
History of gastrointestinal perforation
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

Elderly
Females attempting to conceive
Risk factors for cardiovascular disorder
Asthma
Breastfeeding
Cardiac impairment
Cerebrovascular disorder
Coagulopathy
Congestive cardiac failure
Connective tissue disorder
Crohn's disease
First trimester of pregnancy
Hepatic impairment
History of asthma
History of cardiac failure
History of gastrointestinal disorder
History of gastrointestinal ulceration
Hypertension
Ischaemic heart disease
Occlusive peripheral arterial disease
Porphyria
Renal impairment - glomerular filtration rate 10-20ml/minute
Second trimester of pregnancy
Systemic lupus erythematosus
Ulcerative colitis
Uncontrolled hypertension

May precipitate bronchospasm in patients with asthma or allergy
NSAIDs may provoke or exacerbate asthma
Advise ability to drive/operate machinery may be affected by side effects
Consider the need for combination therapy with gastroprotective agents
Discontinue if signs of gastro-intestinal bleeding occur
Monitor renal function in patients with cardiac impairment
Monitor renal function in patients with hepatic impairment
Discontinue if signs of gastro-intestinal ulceration occur
Risk of gastro-intestinal bleeding increased in the elderly
Severe gastro-intestinal side effects may occur without warning
Discontinue if rash with systemic, allergic or mucosal symptoms occurs
Discontinue treatment if rash occurs
Maintain treatment at the lowest effective dose
Female: Reduced fertility (reversible) possible with long term use
Advise patients to report skin rash

NSAIDs may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Caution should be taken and renal function should be monitored in patients with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly.

Pregnancy and Lactation

Pregnancy

Tolfenamic acid is contraindicated in the third trimester of pregnancy due to the risk of closure of the ductus arteriosus.

The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child. Risk of possible persistent pulmonary hypertension in the newborn.

Tolfenamic acid should not be used during the first and second trimesters unless the potential benefit to the patient outweighs the potential risk to the foetus. If short term use of an NSAID is required then ibuprofen at the recommended therapeutic doses would be the preferred choice.

Schaefer (2007) recommends the use of more established NSAIDs, such as ibuprofen and diclofenac, during the first two trimesters. If NSAID therapy is absolutely necessary during the third trimester, foetal circulation should be monitored regularly (once or twice a week) with Doppler sonography, and medication should be stopped as soon as the first signs of ductal constriction appear. Oligohydramnios should be ruled out. If a drug, other than the more established drugs named above, of this group has been used in early pregnancy, there is no need for a termination of pregnancy or additional invasive diagnostic procedures.

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

Use tolfenamic acid with caution in breastfeeding.

The amount of tolfenamic acid present in breast milk is considered too small to be harmful, the use of tolfenamic acid should be avoided where possible in breast-feeding patients.

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 kidney function
Aggravation of existing asthma
Agranulocytosis
Alveolitis
Anaemia
Anaphylaxis
Angioedema
Aplastic anaemia
Arterial thrombosis
Aseptic meningitis
Asthma
Bronchospasm
Bullous dermatoses
Cardiac failure
Colitis
Confusion
Constipation
Depression
Diarrhoea
Discolouration of urine
Disorientation
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Dysuria
Electrolyte disturbances
Eosinophilia
Epidermal necrolysis
Erythema multiforme
Euphoria
Exacerbation of colitis or Crohn's proctocolitis
Exfoliative dermatitis
Eye changes
Fatigue
Fever
Flatulence
Fluid retention
Gastritis
Gastro-intestinal discomfort
Gastro-intestinal perforation
Gastro-intestinal ulceration
Gastrointestinal bleeding
Haematemesis
Haematuria
Haemolytic anaemia
Hallucinations
Headache
Hepatic damage
Hepatitis
Hypersensitivity reactions
Hypertension
Inhibition of platelet aggregation
Insomnia
Interstitial fibrosis
Interstitial nephritis
Jaundice
Malaise
Melaena
Myocardial infarction
Nausea
Neck stiffness
Nephritis
Nephropathy
Nephrotic syndrome
Nephrotoxicity
Nervousness
Neutropenia
Non-specific allergic reactions
Oedema
Optic neuritis
Pancreatitis
Papillary necrosis
Paraesthesia
Peptic ulceration with perforation and haemorrhage
Photosensitivity
Pruritus
Pulmonary eosinophilia
Pulmonary infiltration
Purpura
Rash
Renal failure
Stevens-Johnson syndrome
Stroke
Thrombocytopenia
Tinnitus
Tremor
Ulcerative stomatitis
Urticaria
Vertigo
Visual disturbances
Vomiting

Presentation

Tablets containing tolfenamic acid.

Drugs List

Therapeutic Indications

Uses

Acute migraine

Dosage

Adults

Elderly

Contraindications

Children under 18 years
Gastrointestinal haemorrhage
History of gastrointestinal haemorrhage
History of gastrointestinal haemorrhage secondary to NSAID
History of gastrointestinal perforation
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

Elderly
Females attempting to conceive
Risk factors for cardiovascular disorder
Asthma
Breastfeeding
Cardiac impairment
Cerebrovascular disorder
Coagulopathy
Congestive cardiac failure
Connective tissue disorder
Crohn's disease
First trimester of pregnancy
Hepatic impairment
History of asthma
History of cardiac failure
History of gastrointestinal disorder
History of gastrointestinal ulceration
Hypertension
Ischaemic heart disease
Occlusive peripheral arterial disease
Porphyria
Renal impairment - glomerular filtration rate 10-20ml/minute
Second trimester of pregnancy
Systemic lupus erythematosus
Ulcerative colitis
Uncontrolled hypertension

May precipitate bronchospasm in patients with asthma or allergy
NSAIDs may provoke or exacerbate asthma
Advise ability to drive/operate machinery may be affected by side effects
Consider the need for combination therapy with gastroprotective agents
Discontinue if signs of gastro-intestinal bleeding occur
Monitor renal function in patients with cardiac impairment
Monitor renal function in patients with hepatic impairment
Discontinue if signs of gastro-intestinal ulceration occur
Risk of gastro-intestinal bleeding increased in the elderly
Severe gastro-intestinal side effects may occur without warning
Discontinue if rash with systemic, allergic or mucosal symptoms occurs
Discontinue treatment if rash occurs
Maintain treatment at the lowest effective dose
Female: Reduced fertility (reversible) possible with long term use
Advise patients to report skin rash

NSAIDs may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Caution should be taken and renal function should be monitored in patients with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly.

Pregnancy and Lactation

Pregnancy

Tolfenamic acid is contraindicated in the third trimester of pregnancy due to the risk of closure of the ductus arteriosus.

The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child. Risk of possible persistent pulmonary hypertension in the newborn.

Tolfenamic acid should not be used during the first and second trimesters unless the potential benefit to the patient outweighs the potential risk to the foetus. If short term use of an NSAID is required then ibuprofen at the recommended therapeutic doses would be the preferred choice.

Schaefer (2007) recommends the use of more established NSAIDs, such as ibuprofen and diclofenac, during the first two trimesters. If NSAID therapy is absolutely necessary during the third trimester, foetal circulation should be monitored regularly (once or twice a week) with Doppler sonography, and medication should be stopped as soon as the first signs of ductal constriction appear. Oligohydramnios should be ruled out. If a drug, other than the more established drugs named above, of this group has been used in early pregnancy, there is no need for a termination of pregnancy or additional invasive diagnostic procedures.

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

Use tolfenamic acid with caution in breastfeeding.

The amount of tolfenamic acid present in breast milk is considered too small to be harmful, the use of tolfenamic acid should be avoided where possible in breast-feeding patients.

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 kidney function
Aggravation of existing asthma
Agranulocytosis
Alveolitis
Anaemia
Anaphylaxis
Angioedema
Aplastic anaemia
Arterial thrombosis
Aseptic meningitis
Asthma
Bronchospasm
Bullous dermatoses
Cardiac failure
Colitis
Confusion
Constipation
Depression
Diarrhoea
Discolouration of urine
Disorientation
Dizziness
Drowsiness
Dyspepsia
Dyspnoea
Dysuria
Electrolyte disturbances
Eosinophilia
Epidermal necrolysis
Erythema multiforme
Euphoria
Exacerbation of colitis or Crohn's proctocolitis
Exfoliative dermatitis
Eye changes
Fatigue
Fever
Flatulence
Fluid retention
Gastritis
Gastro-intestinal discomfort
Gastro-intestinal perforation
Gastro-intestinal ulceration
Gastrointestinal bleeding
Haematemesis
Haematuria
Haemolytic anaemia
Hallucinations
Headache
Hepatic damage
Hepatitis
Hypersensitivity reactions
Hypertension
Inhibition of platelet aggregation
Insomnia
Interstitial fibrosis
Interstitial nephritis
Jaundice
Malaise
Melaena
Myocardial infarction
Nausea
Neck stiffness
Nephritis
Nephropathy
Nephrotic syndrome
Nephrotoxicity
Nervousness
Neutropenia
Non-specific allergic reactions
Oedema
Optic neuritis
Pancreatitis
Papillary necrosis
Paraesthesia
Peptic ulceration with perforation and haemorrhage
Photosensitivity
Pruritus
Pulmonary eosinophilia
Pulmonary infiltration
Purpura
Rash
Renal failure
Stevens-Johnson syndrome
Stroke
Thrombocytopenia
Tinnitus
Tremor
Ulcerative stomatitis
Urticaria
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 2014

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.

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com Accessed on July 18, 2014.

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

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications https://www.medicinescomplete.com Accessed on July 18, 2014.

Summary of Product Characteristics: Clotam Rapid. Galen Ltd. Revised October 2011.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

The Norwegian Porphyria Centre (NAPOS).
Available at: https://www.drugs-porphyria.com/languages/UnitedKingdom/s1.php?l=gbr
Last revised: October 1, 2004
Last accessed: July 18, 2014