Sulfadiazine interferes with bacterial growth by inhibiting the folic acid synthesis of bacteria through the competitive antagonism of PABA.

It is used to treat the following conditions:

• Treatment of chancroid,

• trachoma,

• inclusion conjunctivitis,

• nocardiosis,

• urinary tract infections,

• toxoplasmosis encephalitis,

• malaria,

• meningococcal meningitis,

• acute otitis media,

• meningitis (adjunctive);

• prophylaxis of rheumatic fever

Sulfadiazine dose in Adults

General dosing guidelines:

• An oral dose of 2 to 4 g once daily in 3 to 6 divided doses

Dose in the prophylaxis of Rheumatic fever (off-label dose):

• ≤27 kg:

  • 500 mg once a day

• >27 kg:

  • 1,000 mg once a day

Dose in the treatment of Toxoplasma gondii encephalitis:

• Treatment of acute infection (duration of therapy: ≥6 weeks):

  • 1,000 mg (<60 kg) or 1,500 mg (≥60 kg) every 6 hours in combination with pyrimethamine plus leucovorin calcium (preferred), alternatively 1,000 mg (<60 kg) or 1,500 mg (≥60 kg) may be given every 6 hours in combination with atovaquone.

• Chronic maintenance:

  • 2,000 to 4,000 mg once daily in 2 to 4 divided doses combined with pyrimethamine and leucovorin calcium (preferred), alternatively 2,000 to 4,000 mg/day in 2 to 4 divided doses in combination with atovaquone may be given.

• Manufacturer’s labeling:

  • Doses in the prescribing information may not show current clinical practice.
  • Initial dose 2,000 to 4,000 mg;
  • maintenance: 2,000 to 4,000 mg/day in 3 to 6 divided doses.

Sulfadiazine dose in Childrens

General dosing, susceptible infection:

• Infants ≥2 months, Children, and Adolescents:

  • Oral dose of 120 to 150 mg/kg/day in 4 to 6 divided doses;
  • maximum daily dose of 6 g/day.

• Manufacturer's labeling:

  • Oral: Initial: 75 mg/kg/dose or 2,000 mg/m /dose once followed by maintenance: 150 mg/kg/day or 4,000 mg/m /day divided every 4 to 6 hours;
  • maximum daily dose: 6 g/day

Dose in the treatment of Toxoplasmosis:

• Congenital:

  • Infants:
    • Oral: 50 mg/kg/dose every 12 hours for 12 months;
    • use in conjunction with pyrimethamine and supplemental leucovorin.

• Acquired:

  • Acute induction therapy: HIV-exposed/-positive or immunocompromised/competent with severe primary toxoplasmosis or reactivation:

    • Infants ≥2 months, Children, and Adolescents:
      • The oral dose of 25 to 50 mg/kg/dose every 6 hours;
      • The maximum dose of 1,500 mg/dose;
      • The maximum daily dose of 6 g/day;
      • conjunction use with pyrimethamine and supplemental leucovorin.
      • Continuation of acute induction therapy for at least 6 weeks, then follow up therapy with chronic suppressive therapy.

  • Chorioretinitis: Non-HIV-exposed/-positive:

    • Children and Adolescents:
      • The oral dose of 75 mg/kg once followed by 50 mg/kg/dose twice a day;
      • The maximum daily dose of 4,000 mg/day;
      • conjunction use with pyrimethamine and supplemental leucovorin;
      • 1 to 2 weeks treatment after the resolution of clinical manifestations is recommended (typically to a total of 4 to 6)

  • Suppressive therapy (HIV-exposed/-positive):

    • Infants ≥2 months and Children:
      • Oral: 42.5 to 60 mg/kg/dose twice a day, conjunction use with pyrimethamine and supplemental leucovorin;
      • A maximum daily dose of 4,000 mg/day

Dose in the treatment of Encephalitis; Toxoplasma gondii in HIV-exposed/-positive:

• Adolescents:

  • Acute therapy:

    • At least a 6 weeks therapy is recommended;
    • use in conjunction with pyrimethamine and supplemental leucovorin or with atovaquone.

  • If patient weight <60 kg:

    • The oral dose of 1,000 mg every 6 hours.

  • Patient weight ≥60 kg:

    • The oral dose of 1,500 mg every 6 hours.

  • Chronic maintenance therapy:

    • The oral dose of 2000 to 4000 mg/day in 2 to 4 divided doses used in conjunction with pyrimethamine and supplemental leucovorin or with atovaquone;
    • chronic maintenance therapy should begin after the completion of acute therapy.

Doses in the secondary prophylaxis of Rheumatic fever:

• Infants ≥2 months, Children, and Adolescents:

  • AHA Recommendations:

    • If patient weight ≤27 kg:

      • The oral dose of 500 mg once a day.

    • Patient weight >27 kg:

      • The oral dose of 1000 mg once a day.
  • Manufacturer's labeling:

    • ≤30 kg:

      • The oral dose of 500 mg once a day.

      • ≥30 kg:

        • The oral dose of 1000 mg once a day.

Sulfadiazine pregnancy Risk Factor: C

• The placenta is crossed by sulfadiazine
• Recent studies that evaluated maternal use of sulfonamides in pregnancy and the development birth defects have shown mixed results.
• Pregnant women should use sulfadiazine to prevent T gondii infection, for maternal treatment of Toxoplasmic encephalitis and as an alternate agent for secondary prevention of rheumatic disease.
• When clinically indicated for infections due to susceptible organisms, sulfonamides can be used in pregnancy to treat other infections. However, it is best to avoid using them during the first trimester.
• Patients with G6PD deficiency are advised to take alternative antibiotics.
• Manufacturers have advised against the use of sulfadiazine in the near-term due to the increased risk of hyperbilirubinemia or kernicterus.
• Neonatal health care providers should know if maternal sulfonamide treatment is administered near the time of birth.

Sulfadiazine use during breastfeeding:

• Breast milk contains sulfadiazine.
• According to the manufacturer, sulfadiazine should not be given to breastfeeding mothers as sulfonamides can cross into milk and cause kernicterus.
• The World Health Organization advises against breastfeeding if possible, particularly if the infant's age is less than one month.
• Breastfed infants must be closely monitored for side effects such as hemolysis, bloody diarrhea, jaundice, and hemolysis. Avoid breastfeeding if your infant is G6PD deficient.
• Breast milk antibiotics can cause non-dose-related changes in the bowel flora.

Sulfadiazine dose in kidney disease:

CrCl 25 - 50 mL/min:

• Increase the dosing interval to every 12 hours.

CrCl 10 to 25 mL/min:

• Increase the dosing interval to every 24 hours

CrCl < 10 mL/min and patients on dialysis:

• Avoid due to the high risk of crystalluria.

Sulfadiazine dose in Liver Disease:

No dosage adjustment has been recommended, however, liver function tests should be monitored.

Side effects of Sulfadiazine:

• Cardiovascular:

  • Allergic Myocarditis
  • Periarteritis Nodosa

• Central Nervous System:

  • Ataxia
  • Chills
  • Depression
  • Hallucination
  • Headache
  • Insomnia
  • Peripheral Neuritis
  • Seizure
  • Vertigo

• Dermatologic:

  • Erythema Multiforme
  • Exfoliative Dermatitis
  • Pruritus
  • Skin Photosensitivity
  • Skin Rash
  • Stevens-Johnson Syndrome
  • Toxic Epidermal Necrolysis
  • Urticaria

• Endocrine & Metabolic:

  • Hypoglycemia
  • Thyroid Dysfunction

• Gastrointestinal:

  • Abdominal Pain
  • Anorexia
  • Diarrhea
  • Nausea
  • Pancreatitis
  • Stomatitis
  • Vomiting

• Genitourinary:

  • Crystalluria
  • Diuresis
  • Toxic Nephrosis (With Anuria And Oliguria)

• Hematologic & Oncologic:

  • Agranulocytosis
  • Aplastic Anemia
  • Hemolytic Anemia
  • Hypoprothrombinemia
  • Leukopenia
  • Methemoglobinemia
  • Purpura
  • Thrombocytopenia

• Hepatic:

  • Hepatitis

• Hypersensitivity:

  • Anaphylactoid Reaction

• Immunologic:

  • Serum Sickness-Like Reaction

• Neuromuscular & Skeletal:

  • Arthralgia
  • Lupus Erythematosus

• Ophthalmic:

  • Conjunctival Injection
  • Injected Sclera
  • Periorbital Edema

• Otic:

  • Tinnitus

• Renal:

  • Nephrolithiasis

• Miscellaneous:

  • Fever

Contraindication to Sulfadiazine Include:

• Hypersensitivity to any sulfa drug or any component of the formulation;
• infants less than 2 months of age unless indicated for the treatment of congenital toxoplasmosis;
• pregnancy (at term);
• breast-feeding

Warnings and Precautions

• Blood dyscrasias:

  • There have been fatalities due to severe reactions, including agranulocytosis and aplastic anemia.
  • If you notice a rash, or other signs of severe adverse reactions, stop using it.

• Dermatologic reactions

  • Fatalities associated with severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have occurred;
  • Stop using the product immediately you feel rashes.

• Hepatic necrosis

  • There have been fatalities due to hepatic necrosis.
  • Stop using it immediately you feel a rash.

• Allergy to sulfonamide ("sulfa")

  • Cross-reactivity concerns have been a concern for all compounds with the sulfonamide structural.
  • Nonantibiotic sulfonamides as well as antibiotics sulfonamides are unlikely to cause anaphylaxis (anaphylaxis).
  • Sulfasalazine is an antibiotic sulfonamide that has the arylamine structure. It may cross-react to antibiotic sulfonamides.
  • T-cell-mediated (type IV), reactions (eg maculopapular skin rash) are less well understood. It is difficult to exclude this possibility based on current knowledge.
  • Some clinicians opt to avoid these classes in cases of severe reactions (Stevens Johnson syndrome/TEN).

• Superinfection

  • After prolonged use, fungal or bacterial superinfections may occur. This includes pseudomembranous colitis and C. difficile-associated diarrhea.
  • CDAD was observed for >2 months after antibiotic treatment.

• Allergies/Asthma:

  • Patients with asthma or allergies should be cautious.

• Glucose 6-phosphate dehydrogenase (G6PD) deficiency:

  • Patients with G6PD deficiency should be cautious
  • It is possible to get hemolysis.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious.

• Renal impairment

  • Patients with impaired renal function should be cautious.
  • Modifications to dosage are required.
  • To prevent crystalluria, ensure that you have adequate water.

Sulfadiazine: Drug Interaction

Monitor:

• Prior to initiating therapy, perform culture and sensitivity testing;
• frequent CBC and urinalysis during therapy;
• signs of serious blood disorders (sore throat, fever, pallor, purpura, dark urine, jaundice);
• CD4+ count in HIV-exposed/-positive patients treated for toxoplasmosis

How to administer Sulfadiazine?

• Administer with at least 8 ounces of water and around-the-clock to promote less variation in peak and trough serum levels.
• To alkalize the urine of patients unable to maintain adequate fluid intake(in order to prevent crystalluria, azotemia, oliguria) oral sodium bicarbonate may be used.

Mechanism of action of Sulfadiazine:

It inhibits bacterial growth through the competitive antagonistic effect of PABA

AbsorptionIt is well absorbed

Distribution: In body tissues and fluids, including peritoneal and synovial fluids, as well as total body water. It is easily absorbed into CSF.

Protein binding: 38% to 48%

Metabolism: Via N-acetylation

Half-life elimination: 10 hours

Time to peak: Within 3-6 hours

Excretion: Excreted in urine (43% to 60% as unchanged drug and 15% to 40% as metabolites)

International Brands of Sulfadiazine:

• Adiazin
• Adiazine
• Labdiazina
• Sulfadiazin Streuli
• Sulfadiazin-Heyl
• Sulfadiazina
• Sulfadiazina Reig Jofre
• Sulfadiazine
• Sulfadiazine Suspensie FNA
• Sulzine

Sulfadiazine Brands in Pakistan: