Usage
Sulfadiazine is a sulfonamide antibiotic prescribed for treating and preventing various infections caused by susceptible bacteria. It is commonly used in combination with pyrimethamine and leucovorin for treating toxoplasmosis, particularly in individuals with compromised immune systems (such as those with HIV). It’s also used for prophylaxis against rheumatic fever in penicillin-allergic patients.
Pharmacological Classification: Sulfonamide Antibiotic
Mechanism of Action: Sulfadiazine inhibits bacterial growth by competitively antagonizing para-aminobenzoic acid (PABA), a crucial component in folic acid synthesis. By interfering with folic acid production, Sulfadiazine disrupts bacterial DNA synthesis and cellular replication. Microorganisms reliant on exogenous folic acid sources are unaffected.
Alternate Names
No widely recognized alternate names exist for Sulfadiazine. Several brand names are available, including Microsulfon and generic formulations.
How It Works
Pharmacodynamics: Sulfadiazine exhibits bacteriostatic activity against a wide range of Gram-positive and Gram-negative bacteria and some protozoa. Its therapeutic effect is achieved through interference with folic acid synthesis, essential for bacterial growth.
Pharmacokinetics:
- Absorption: Well-absorbed orally.
- Distribution: Distributes widely into body tissues and crosses cell membranes readily. Approximately 32-56% protein-bound.
- Metabolism: Primarily hepatic metabolism.
- Elimination: Primarily renal excretion. Urinary concentrations are typically significantly higher than serum levels.
Mode of Action: Sulfadiazine acts as a competitive inhibitor of dihydropteroate synthase, a bacterial enzyme crucial for folic acid synthesis. This competitive antagonism disrupts the production of tetrahydrofolic acid, a vital cofactor in DNA synthesis, thereby inhibiting bacterial growth and proliferation.
Elimination Pathways: Predominantly renal excretion, with minor hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Infections: 2-4 g per day divided into 3-6 doses.
- Rheumatic Fever Prophylaxis: 1 g once daily for patients >30 kg; 500 mg once daily for patients <30 kg.
Children:
- Infections: 75-150 mg/kg/day divided into 4-6 doses (maximum 6 g daily).
- Toxoplasmosis (congenital, in combination with pyrimethamine and leucovorin): <2 months: 50 mg/kg twice daily for 12 months. Dosage adjustments required based on weight and age for older children.
- Rheumatic Fever Prophylaxis: 1 g once daily for patients >30 kg; 500 mg once daily for patients <30 kg.
Special Cases:
- Elderly Patients: Caution advised; dose adjustment may be necessary due to age-related decline in renal function.
- Patients with Renal Impairment: Dosage adjustments are needed based on creatinine clearance. Close monitoring is essential.
- Patients with Hepatic Dysfunction: Use with caution, dose adjustment may be needed.
- Patients with Comorbid Conditions: Individualized dosing may be required based on co-existing conditions.
Clinical Use Cases
Dosage guidelines for Sulfadiazine in specialized medical settings are not explicitly defined, but are based on treating specific infection types and not the setting where the drug is administered.
Dosage Adjustments
Dose modifications are necessary for patients with renal or hepatic impairment, and should be determined based on creatinine clearance and liver function tests, respectively. For patients with other metabolic disorders or genetic polymorphisms, individualize dosage based on drug levels and clinical response.
Side Effects
Common Side Effects
Nausea, vomiting, diarrhea, headache, rash, anorexia.
Rare but Serious Side Effects
Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, aplastic anemia, hepatitis, crystalluria, renal failure.
Long-Term Effects
Chronic kidney disease (with prolonged use), blood disorders.
Adverse Drug Reactions (ADR)
Severe skin reactions, blood dyscrasias, hepatic injury, acute renal failure.
Contraindications
Hypersensitivity to sulfonamides, severe renal or hepatic failure, acute porphyria, jaundice, blood disorders, neonates.
Drug Interactions
Sulfadiazine interacts with several drugs, including warfarin, phenytoin, methotrexate, cyclosporine, and oral hypoglycemic agents. It can potentiate the effects of these medications. Sulfadiazine may also interact with other antibiotics, and caution is advised when used concurrently with methenamine, due to increased risk of crystalluria. Consult comprehensive drug interaction resources for detailed information.
Pregnancy and Breastfeeding
Pregnancy Category: C (first trimester) and D (later trimesters). Sulfadiazine crosses the placenta and should be avoided during the last trimester due to the risk of kernicterus in the newborn. It is present in breast milk, hence breastfeeding is not recommended.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial folic acid synthesis.
- Side Effects: Nausea, vomiting, diarrhea, rash, severe skin reactions, blood dyscrasias, renal/hepatic dysfunction.
- Contraindications: Sulfonamide hypersensitivity, severe renal/hepatic impairment, pregnancy (late term).
- Drug Interactions: Warfarin, phenytoin, methotrexate, cyclosporine.
- Pregnancy & Breastfeeding: Avoid during late pregnancy and breastfeeding.
- Dosage: Varies by indication and patient specifics.
- Monitoring Parameters: Renal function, liver function tests, complete blood counts.
Popular Combinations
Sulfadiazine is frequently combined with pyrimethamine and leucovorin for toxoplasmosis treatment.
Precautions
Ensure adequate hydration to prevent crystalluria. Monitor renal and hepatic function regularly. Baseline blood counts should be obtained and monitored throughout therapy. Assess for G6PD deficiency before initiating treatment. Caution advised for patients with pre-existing renal or hepatic conditions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sulfadiazine?
A: The dosage varies depending on the infection being treated, the patient’s age and weight, and renal function. Please refer to the detailed dosage section above.
Q2: What are the common side effects of Sulfadiazine?
A: Common side effects include nausea, vomiting, diarrhea, headache, and rash.
Q3: What are the serious adverse reactions associated with Sulfadiazine?
A: Serious side effects include severe skin reactions like Stevens-Johnson syndrome and toxic epidermal necrolysis, blood disorders, and liver or kidney damage.
Q4: Can Sulfadiazine be used during pregnancy?
A: Sulfadiazine should be avoided during the last trimester of pregnancy due to the risk of kernicterus in newborns. Use during earlier stages of pregnancy should be carefully weighed against potential risks.
Q5: Is Sulfadiazine safe for breastfeeding mothers?
A: Sulfadiazine is present in breast milk and can cause adverse effects in newborns. Breastfeeding is generally not recommended while taking this medication.
Q6: How does Sulfadiazine interact with other medications?
A: Sulfadiazine can interact with various drugs, including warfarin, phenytoin, methotrexate, and others. Consult a drug interaction resource or pharmacist before co-administering.
Q7: What are the contraindications for using Sulfadiazine?
A: Contraindications include hypersensitivity to sulfonamides, severe kidney or liver disease, and certain blood disorders.
Q8: What precautions should be taken while administering Sulfadiazine?
A: Patients should maintain adequate hydration to prevent crystalluria. Monitor renal and hepatic function, as well as blood counts, especially during long-term use.
Q9: What is the role of leucovorin when Sulfadiazine is used for toxoplasmosis?
A: Leucovorin is administered concurrently with Sulfadiazine and pyrimethamine to mitigate the risk of bone marrow suppression caused by pyrimethamine. It helps by providing a reduced form of folic acid that does not require the enzymatic step inhibited by the drug combination.
