Drugs List

Therapeutic Indications

Uses

Antibiotic sensitive infections
Prevention of rheumatic fever recurrence

Prevention of recurrence of rheumatic fever.

Treatment of infection caused by susceptible organisms, for example:
Gram positive bacteria such as group A Streptococci and some strains of Streptococcus pneumoniae, Bacillus anthracis, Nocardia (especially N. asteroides), Actinomyces spp., Staphylococci and Clostridium perfringens.

Gram negative bacteria such as Haemophilus influenzae, H. ducreyi, Escherichia coli, Klebsiella, Proteus, Salmonella, Serratia, Vibrio cholerae, Brucella, Legionella, Yersinia pestis, Chlamydia, Pseudomonas pseudomallei.

Note that sensitivity to sulfadiazine varies widely in the Enterobacteriaceae.

Sulfadiazine should not be used for the initial treatment of meningococcal meningitis although may be used instead of parenteral penicillin once susceptibility to sulfadiazine is established.

Unlicensed Uses

Congenital toxoplasmosis in combination with other drugs
Foetal toxoplasmosis in pregnancy in combination with other drugs
Ocular toxoplasmosis in combination with other drugs
Toxoplasmosis in the immunocompromised in combination with other drugs

Foetal toxoplasmosis in pregnancy in combination with pyrimethamine and folinic acid
Congenital toxoplasmosis in combination with pyrimethamine and folinic acid
Toxoplasmosis in the immunocompromised in combination with other drugs
Ocular toxoplasmosis in combination with other drugs

Contraindications

Haematological disorder
Jaundice
Porphyria
Severe hepatic impairment
Severe renal impairment

Precautions and Warnings

Allergic disposition
Elderly
Neonates
Predisposition to folate deficiency
Asthma
Breastfeeding
G6PD deficiency
Immunodeficiency syndromes
Mild hepatic impairment
Mild renal impairment
Pregnancy
Systemic lupus erythematosus

Consult national/regional policy on the use of anti-infectives
Folate supplementation may be necessary in some patients
Ensure patient has adequate fluid intake
Maintain hydration and urinary output
Monitor for signs of bone marrow depression
Monitor plasma levels and adapt dose in patients with renal impairment
Perform blood counts on prolonged use of this treatment
Discontinue immediately if blood disorders or rashes develop
Advise patients to report skin rash

Use with caution in patients with severe allergy or bronchial asthma. Sulfonamides may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible individuals.

Advise patients to report incidence of rash. Discontinue treatment at first appearance of skin rash. Severe reactions and fatalities have been reported in sulfonamide use including Stevens-Johnson syndrome, Lyell syndrome (toxic epidermal necrolysis), fulminant hepatic necrosis, agranulocytosis, aplastic anaemia, other blood dyscrasias and hypersensitivity of the respiratory tract. If patients develop Stevens-Johnson syndrome or toxic epidermal necrolysis, sulfadiazine treatment must not be re-started.

Advise patients to consume 5 to 6 pints of fluid every 24 hours. It is essential to maintain an adequate fluid intake and urinary output. If necessary, the urine may be rendered alkaline to prevent crystallisation of acetyl sulfadiazine. The low solubility of sulfadiazine and its acetyl derivative means that crystalluria is more likely with sulfadiazine than sulfamethoxazole.

Haemolysis may occur in patients with glucose-6-phosphate dehydrogenase deficiency.

Monitor blood counts monthly in patients on long-term treatment as asymptomatic changes may occur due to the lack of available folate. Blood counts should also be taken in patients who are predisposed to folate deficiency (such as the elderly, chronic alcoholics and patients with rheumatoid arthritis), patients with malabsorption syndromes or malnutrition, and patients receiving concurrent anticonvulsant medication.

Pregnancy and Lactation

Pregnancy

Use sulfadiazine with caution in pregnancy.

Briggs suggests because of the potential toxicity to the newborn, sulfonamides should be avoided near term. The manufacturer suggests the risks and benefits of therapy should be considered before sulfadiazine is used in pregnancy. It is generally recommended that sulfadiazine is not administered late in pregnancy due to the risk of haemolytic anaemia in the newborn.

There is epidemiological evidence of the safety of sulfadiazine during therapy, however animal studies with high doses have shown evidence embryotoxicity and teratogenicity, especially during the first trimester.

For treatment of toxoplasmosis in pregnancy, seek specialist advice; the regimen should include folinic acid.

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 sulfadiazine with caution in breastfeeding.

Briggs suggests sulfonamide excretion into breast milk does not pose a significant risk to a healthy, full-term neonate. However exposure to sulfonamides via breast milk should be avoided in ill, stressed or premature infants and in infants with hyperbilirubinemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency. The manufacturer suggests a decision to continue/discontinue breastfeeding or to continue/discontinue therapy with sulfadiazine should be made following assessment of the risks and benefits of therapy.

Sulfonamides are excreted in breast milk in small amounts. There is a risk of kernicterus in the neonate and a risk of haemolysis in breastfed G6PD deficient neonates.

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

Agranulocytosis
Anaphylaxis
Anorexia
Antibiotic-associated colitis
Anuria
Aplastic anaemia
Aseptic meningitis
Ataxia
Back pain
Benign intracranial hypertension
Blood disorders
Contact dermatitis
Convulsions
Crystalluria
Cyanosis
Depression
Diarrhoea
Dizziness
Drowsiness
Eosinophilia
Erythema nodosum
Exfoliative dermatitis
Fatigue
Fever
Fibrosing alveolitis
Haematuria
Haemolytic anaemia
Headache
Hepatic necrosis
Hepatomegaly
Hypersensitivity reactions
Hypoglycaemia
Hypoprothrombinaemia
Hypothyroidism
Insomnia
Interstitial nephritis
Jaundice
Leucopenia
Methaemoglobinaemia
Myocarditis
Nausea
Nephrotoxicity
Neurological effects
Oliguria
Optic neuropathy
Pancreatitis
Peripheral neuropathy
Photosensitivity
Pseudomembranous colitis
Psychosis
Pulmonary eosinophilia
Rash
Renal failure
Renal tubular necrosis
Serum sickness-like reactions
Stevens-Johnson syndrome
Systemic lupus erythematosus
Thrombocytopenia
Toxic epidermal necrolysis
Vasculitis
Vertigo
Vomiting

Presentation

Tablets containing sulfadiazine

Drugs List

Therapeutic Indications

Uses

Antibiotic sensitive infections
Prevention of rheumatic fever recurrence

Prevention of recurrence of rheumatic fever.

Treatment of infection caused by susceptible organisms, for example:
Gram positive bacteria such as group A Streptococci and some strains of Streptococcus pneumoniae, Bacillus anthracis, Nocardia (especially N. asteroides), Actinomyces spp., Staphylococci and Clostridium perfringens.

Gram negative bacteria such as Haemophilus influenzae, H. ducreyi, Escherichia coli, Klebsiella, Proteus, Salmonella, Serratia, Vibrio cholerae, Brucella, Legionella, Yersinia pestis, Chlamydia, Pseudomonas pseudomallei.

Note that sensitivity to sulfadiazine varies widely in the Enterobacteriaceae.

Sulfadiazine should not be used for the initial treatment of meningococcal meningitis although may be used instead of parenteral penicillin once susceptibility to sulfadiazine is established.

Unlicensed Uses

Congenital toxoplasmosis in combination with other drugs
Foetal toxoplasmosis in pregnancy in combination with other drugs
Ocular toxoplasmosis in combination with other drugs
Toxoplasmosis in the immunocompromised in combination with other drugs

Foetal toxoplasmosis in pregnancy in combination with pyrimethamine and folinic acid
Congenital toxoplasmosis in combination with pyrimethamine and folinic acid
Toxoplasmosis in the immunocompromised in combination with other drugs
Ocular toxoplasmosis in combination with other drugs

Dosage

Adults

Children

Neonates

Patients with Renal Impairment

Contraindications

Haematological disorder
Jaundice
Porphyria
Severe hepatic impairment
Severe renal impairment

Precautions and Warnings

Allergic disposition
Elderly
Neonates
Predisposition to folate deficiency
Asthma
Breastfeeding
G6PD deficiency
Immunodeficiency syndromes
Mild hepatic impairment
Mild renal impairment
Pregnancy
Systemic lupus erythematosus

Consult national/regional policy on the use of anti-infectives
Folate supplementation may be necessary in some patients
Ensure patient has adequate fluid intake
Maintain hydration and urinary output
Monitor for signs of bone marrow depression
Monitor plasma levels and adapt dose in patients with renal impairment
Perform blood counts on prolonged use of this treatment
Discontinue immediately if blood disorders or rashes develop
Advise patients to report skin rash

Use with caution in patients with severe allergy or bronchial asthma. Sulfonamides may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible individuals.

Advise patients to report incidence of rash. Discontinue treatment at first appearance of skin rash. Severe reactions and fatalities have been reported in sulfonamide use including Stevens-Johnson syndrome, Lyell syndrome (toxic epidermal necrolysis), fulminant hepatic necrosis, agranulocytosis, aplastic anaemia, other blood dyscrasias and hypersensitivity of the respiratory tract. If patients develop Stevens-Johnson syndrome or toxic epidermal necrolysis, sulfadiazine treatment must not be re-started.

Advise patients to consume 5 to 6 pints of fluid every 24 hours. It is essential to maintain an adequate fluid intake and urinary output. If necessary, the urine may be rendered alkaline to prevent crystallisation of acetyl sulfadiazine. The low solubility of sulfadiazine and its acetyl derivative means that crystalluria is more likely with sulfadiazine than sulfamethoxazole.

Haemolysis may occur in patients with glucose-6-phosphate dehydrogenase deficiency.

Monitor blood counts monthly in patients on long-term treatment as asymptomatic changes may occur due to the lack of available folate. Blood counts should also be taken in patients who are predisposed to folate deficiency (such as the elderly, chronic alcoholics and patients with rheumatoid arthritis), patients with malabsorption syndromes or malnutrition, and patients receiving concurrent anticonvulsant medication.

Pregnancy and Lactation

Pregnancy

Use sulfadiazine with caution in pregnancy.

Briggs suggests because of the potential toxicity to the newborn, sulfonamides should be avoided near term. The manufacturer suggests the risks and benefits of therapy should be considered before sulfadiazine is used in pregnancy. It is generally recommended that sulfadiazine is not administered late in pregnancy due to the risk of haemolytic anaemia in the newborn.

There is epidemiological evidence of the safety of sulfadiazine during therapy, however animal studies with high doses have shown evidence embryotoxicity and teratogenicity, especially during the first trimester.

For treatment of toxoplasmosis in pregnancy, seek specialist advice; the regimen should include folinic acid.

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 sulfadiazine with caution in breastfeeding.

Briggs suggests sulfonamide excretion into breast milk does not pose a significant risk to a healthy, full-term neonate. However exposure to sulfonamides via breast milk should be avoided in ill, stressed or premature infants and in infants with hyperbilirubinemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency. The manufacturer suggests a decision to continue/discontinue breastfeeding or to continue/discontinue therapy with sulfadiazine should be made following assessment of the risks and benefits of therapy.

Sulfonamides are excreted in breast milk in small amounts. There is a risk of kernicterus in the neonate and a risk of haemolysis in breastfed G6PD deficient neonates.

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

Counselling

Advise the patient to consume 5 to 6 pints of water every 24 hours to maintain a high urine output.

Advise patients to report incidence of rash.

Side Effects

Agranulocytosis
Anaphylaxis
Anorexia
Antibiotic-associated colitis
Anuria
Aplastic anaemia
Aseptic meningitis
Ataxia
Back pain
Benign intracranial hypertension
Blood disorders
Contact dermatitis
Convulsions
Crystalluria
Cyanosis
Depression
Diarrhoea
Dizziness
Drowsiness
Eosinophilia
Erythema nodosum
Exfoliative dermatitis
Fatigue
Fever
Fibrosing alveolitis
Haematuria
Haemolytic anaemia
Headache
Hepatic necrosis
Hepatomegaly
Hypersensitivity reactions
Hypoglycaemia
Hypoprothrombinaemia
Hypothyroidism
Insomnia
Interstitial nephritis
Jaundice
Leucopenia
Methaemoglobinaemia
Myocarditis
Nausea
Nephrotoxicity
Neurological effects
Oliguria
Optic neuropathy
Pancreatitis
Peripheral neuropathy
Photosensitivity
Pseudomembranous colitis
Psychosis
Pulmonary eosinophilia
Rash
Renal failure
Renal tubular necrosis
Serum sickness-like reactions
Stevens-Johnson syndrome
Systemic lupus erythematosus
Thrombocytopenia
Toxic epidermal necrolysis
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: July 2014

Reference Sources

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

Summary of Product Characteristics: Sulfadiazine 500 mg tablets. Wockhardt UK Ltd. Revised May 2014.

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

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 04 September 2017