Drugs List

Therapeutic Indications

Uses

Crohn's disease : rectal complications
Ulcerative colitis

Contraindications

Children under 2 years
Acute porphyria

Precautions and Warnings

Allergic disposition
Soft contact lenses
Asthma
Breastfeeding
Folate deficiency
G6PD deficiency
Hepatic impairment
Pregnancy
Renal impairment - glomerular filtration rate below 50ml/minute
Slow acetylator status

Risk of blood disorders is substantially higher in patients treated for R.A
Ensure patient has adequate fluid intake
Monitor FBC prior, every two weeks for first 3 months & periodically after
Monitor liver function prior, every 2wks for first 3 months & periodically
Monitor renal function prior,monthly for first 3months & periodically after
Macrocytosis due to folate deficiency: give folic acid or folinic acid
Monitor for signs of blood dyscrasias eg fever, sore throat, malaise etc
Pregnancy: Monitor folate levels as supplements are recommended
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Pancytopenia due to folate deficiency: give folic acid or folinic acid
Discontinue immediately if suspicion of a blood dyscrasia
Male: May cause infertility
May discolour urine orange
May stain extended-wear soft contact lenses

Complete blood counts, including differential white cell count should be performed before starting sulfasalazine, and every two weeks during the first three months of therapy. During the second three months, the same tests should be done once monthly and thereafter once every three months, and as clinically indicated.

Generally about 75% of adverse drug reactions occur within 3 months of initiating therapy and over 90% by 6 months. Some undesirable effects are dose dependent and symptoms can often be alleviated by reduction of the dose.

Pregnancy and Lactation

Pregnancy

Sulfasalazine should be used with caution in pregnancy. Long term clinical use has not shown teratogenic effect.

Sulfasalazine and its metabolite, sulfapyridine, readily cross the placenta after oral administration and enter foetal circulation. At birth the resultant concentration of the drug and its metabolite in 11 infants was 4.6 and 18.2microgram/ml, respectively. As sulfonamides can cause jaundice in the newborn, Briggs (2011) suggests to use sulfasalazine with caution.

Sulfasalazine also has the affect of acting as a folate antagonist, inhibiting both the metabolism and absorption of folic acid and folate supplements are recommended for the mother to reduce the teratogenic risk, Briggs (2011).

The drug of choice in chronic inflammatory bowel disease remains mesalazine, Schaefer (2007).

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

The manufacturer advises that patients should avoid breastfeeding while taking this medicine.

Sulfasalazine is secreted in small amounts in breast milk. Since sulfasalazine may cause haemolytic anaemia there is a theoretical risk to G6PD deficient infants and premature neonates. There have been reports of bloody stools or diarrhoea in infants who are breastfeeding from mothers on sulfasalazine. In cases where the outcome was reported, bloody stools or diarrhoea resolved in the infant after discontinuation of sulfasalazine in the mother.

Schaefer, however, states that Sulfasalazine when administered at a maternal dosage of 2g daily, was found at a significantly lower concentration in expressed milk than when administered at increased doses of 3g daily. He found that this resulted in up to 10% weight-related portions of the drug reaching the baby (Schaefer 2007).

Schaefer concludes that sulfasalazine may be used but the drug of choice in chronic inflammatory bowel disease remains mesalazine (Schaefer 2007).

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 pancreatitis
Agranulocytosis
Alopecia
Anaphylaxis
Aplastic anaemia
Arthralgia
Aseptic meningitis
Ataxia
Autoantibody positive
Convulsions
Cough
Crystalluria
Cyanosis
Decreased appetite
Depression
Diarrhoea
Discolouration of urine
Dizziness
Drug fever
Dyspnoea
Elevation of liver enzymes
Encephalopathy
Eosinophilia
Epidermal necrolysis
Erythema
Exacerbation of colitis
Exanthema
Exfoliative dermatitis
Eye disorder
Facial oedema
Fibrosing alveolitis
Gastric upset
Haematuria
Haemolytic anaemia
Hallucinations
Headache
Heinz-body anaemia
Hepatitis
Hypoprothrombinaemia
Insomnia
Interstitial lung disease
Leucopenia
Lichen planus
Lupus erythematosus-like syndrome
Lymphadenopathy
Macrocytosis
Megaloblastic anaemia
Methaemoglobinaemia
Myocarditis
Nausea
Nephritis
Nephrotic syndrome
Neutropenia
Oligospermia (reversible)
Pancreatitis
Pancytopenia
Parotitis
Pericarditis
Periorbital oedema
Peripheral neuropathy
Photosensitivity
Polyarteritis nodosa
Possible staining of soft contact lenses
Proteinuria
Pruritus
Pseudomembranous colitis
Rash
Serum sickness
Smelling disturbances
Stevens-Johnson syndrome
Stomatitis
Taste disturbances
Thrombocytopenia
Tinnitus
Urticaria
Vasculitis
Vertigo
Vomiting

Presentation

Rectal formulations of sulfasalazine.

Drugs List

Therapeutic Indications

Uses

Crohn's disease : rectal complications
Ulcerative colitis

Dosage

The dose should be adjusted according to severity of the disease and the patient's tolerance to the drug.

Adults

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Contraindications

Children under 2 years
Acute porphyria

Precautions and Warnings

Allergic disposition
Soft contact lenses
Asthma
Breastfeeding
Folate deficiency
G6PD deficiency
Hepatic impairment
Pregnancy
Renal impairment - glomerular filtration rate below 50ml/minute
Slow acetylator status

Risk of blood disorders is substantially higher in patients treated for R.A
Ensure patient has adequate fluid intake
Monitor FBC prior, every two weeks for first 3 months & periodically after
Monitor liver function prior, every 2wks for first 3 months & periodically
Monitor renal function prior,monthly for first 3months & periodically after
Macrocytosis due to folate deficiency: give folic acid or folinic acid
Monitor for signs of blood dyscrasias eg fever, sore throat, malaise etc
Pregnancy: Monitor folate levels as supplements are recommended
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Pancytopenia due to folate deficiency: give folic acid or folinic acid
Discontinue immediately if suspicion of a blood dyscrasia
Male: May cause infertility
May discolour urine orange
May stain extended-wear soft contact lenses

Complete blood counts, including differential white cell count should be performed before starting sulfasalazine, and every two weeks during the first three months of therapy. During the second three months, the same tests should be done once monthly and thereafter once every three months, and as clinically indicated.

Generally about 75% of adverse drug reactions occur within 3 months of initiating therapy and over 90% by 6 months. Some undesirable effects are dose dependent and symptoms can often be alleviated by reduction of the dose.

Pregnancy and Lactation

Pregnancy

Sulfasalazine should be used with caution in pregnancy. Long term clinical use has not shown teratogenic effect.

Sulfasalazine and its metabolite, sulfapyridine, readily cross the placenta after oral administration and enter foetal circulation. At birth the resultant concentration of the drug and its metabolite in 11 infants was 4.6 and 18.2microgram/ml, respectively. As sulfonamides can cause jaundice in the newborn, Briggs (2011) suggests to use sulfasalazine with caution.

Sulfasalazine also has the affect of acting as a folate antagonist, inhibiting both the metabolism and absorption of folic acid and folate supplements are recommended for the mother to reduce the teratogenic risk, Briggs (2011).

The drug of choice in chronic inflammatory bowel disease remains mesalazine, Schaefer (2007).

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

The manufacturer advises that patients should avoid breastfeeding while taking this medicine.

Sulfasalazine is secreted in small amounts in breast milk. Since sulfasalazine may cause haemolytic anaemia there is a theoretical risk to G6PD deficient infants and premature neonates. There have been reports of bloody stools or diarrhoea in infants who are breastfeeding from mothers on sulfasalazine. In cases where the outcome was reported, bloody stools or diarrhoea resolved in the infant after discontinuation of sulfasalazine in the mother.

Schaefer, however, states that Sulfasalazine when administered at a maternal dosage of 2g daily, was found at a significantly lower concentration in expressed milk than when administered at increased doses of 3g daily. He found that this resulted in up to 10% weight-related portions of the drug reaching the baby (Schaefer 2007).

Schaefer concludes that sulfasalazine may be used but the drug of choice in chronic inflammatory bowel disease remains mesalazine (Schaefer 2007).

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 pancreatitis
Agranulocytosis
Alopecia
Anaphylaxis
Aplastic anaemia
Arthralgia
Aseptic meningitis
Ataxia
Autoantibody positive
Convulsions
Cough
Crystalluria
Cyanosis
Decreased appetite
Depression
Diarrhoea
Discolouration of urine
Dizziness
Drug fever
Dyspnoea
Elevation of liver enzymes
Encephalopathy
Eosinophilia
Epidermal necrolysis
Erythema
Exacerbation of colitis
Exanthema
Exfoliative dermatitis
Eye disorder
Facial oedema
Fibrosing alveolitis
Gastric upset
Haematuria
Haemolytic anaemia
Hallucinations
Headache
Heinz-body anaemia
Hepatitis
Hypoprothrombinaemia
Insomnia
Interstitial lung disease
Leucopenia
Lichen planus
Lupus erythematosus-like syndrome
Lymphadenopathy
Macrocytosis
Megaloblastic anaemia
Methaemoglobinaemia
Myocarditis
Nausea
Nephritis
Nephrotic syndrome
Neutropenia
Oligospermia (reversible)
Pancreatitis
Pancytopenia
Parotitis
Pericarditis
Periorbital oedema
Peripheral neuropathy
Photosensitivity
Polyarteritis nodosa
Possible staining of soft contact lenses
Proteinuria
Pruritus
Pseudomembranous colitis
Rash
Serum sickness
Smelling disturbances
Stevens-Johnson syndrome
Stomatitis
Taste disturbances
Thrombocytopenia
Tinnitus
Urticaria
Vasculitis
Vertigo
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: May 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.

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: Salazopyrin Suppositories. Pfizer Limited. Revised February 2014.

Therapeutics in Pregnancy and Lactation (2000) Lee, A., Inch, S. and Finnigan, D. Radcliffe Medical Press, Abingdon.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 24 August 2017

The Norwegian Porphyria Centre (NAPOS) Drug Database for Acute Porphyria (2007)
Last revised: 17/03/10
Available at https://www.drugs-porphyria.org/languages/UnitedKingdom/index.php?l=gbr
Accessed 30/04/10