SULTIME INJECTION

Indications

• Bacterial infections
• Toxoplasmosis in pregnancy (in combination with pyrimethamine and folinic acid)
• Congenital toxoplasmosis (in combination with pyrimethamine and folinic acid)

Dosage

Children: For children aged 12–17 years, the recommended dose is 1 g three times a day until delivery for toxoplasmosis in pregnancy. For other specific conditions, refer to the BNF for Children for detailed dosing guidelines.

Adults: For adults, the typical dosing for bacterial infections can vary, and it is essential to refer to the BNF for specific recommendations based on the condition being treated. Generally, dosage adjustments may be necessary in renal impairment.

Mechanism of action

Sulfadiazine acts as a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase, blocking the conversion of para-aminobenzoic acid (PABA) to folic acid. This inhibition is crucial for bacterial growth and reproduction, as folic acid is vital for nucleic acid synthesis.

Pharmacodynamics

Sulfadiazine is a synthetic bacteriostatic antibiotic effective against many gram-positive and some gram-negative organisms. It inhibits bacterial multiplication by interfering with folic acid metabolism. Resistance to sulfadiazine usually implies resistance to all sulfonamides, as they share similar mechanisms of action.

Pharmacokinetics

Sulfadiazine is well absorbed when administered orally, with high tissue distribution. It achieves significant concentrations in various bodily fluids, including pleural and synovial fluids. While it is effective, its absorption can be affected by the presence of pus, which can inhibit its antibacterial action. Renal function can influence its clearance, necessitating dose adjustments in cases of impaired renal function.

Contra-indications

• Acute porphyrias

Adverse effects

• Agranulocytosis
• Aplastic anaemia
• Haemolytic anaemia
• Decreased appetite
• Ataxia
• Back pain
• Blood disorders
• Cough
• Crystaluria
• Cyanosis
• Depression
• Diarrhoea
• Dizziness
• Drowsiness
• Dyspnoea
• Eosinophilia
• Erythema nodosum
• Fatigue
• Fever
• Haematuria
• Hallucination
• Headache
• Hepatic disorders
• Hypoglycaemia
• Neutropenia
• Oral disorders
• Pancreatitis
• Photosensitivity reaction
• Skin reactions
• Thrombocytopenia
• Tinnitus
• Vertigo
• Vomiting

Interactions

• Sulfadiazine + antiepileptics: Moderate (increases concentration)
• Sulfadiazine + fosphenytoin: Moderate (increases concentration)
• Sulfadiazine + phenytoin: Moderate (increases concentration)

Precautions

• Caution in asthma
• Caution in blood disorders
• Caution in elderly patients
• Monitor blood counts on prolonged treatment
• Plasma concentration monitoring may be required in moderate to severe renal impairment

Pregnancy

Risk of neonatal haemolysis and methaemoglobinaemia in the third trimester; fear of increased risk of kernicterus in neonates appears to be unfounded.

Breast-feeding

Small risk of kernicterus in jaundiced infants and of haemolysis in G6PD-deficient infants.

Storage

Store in a cool, dry place away from light.

Formulations

• Solution for infusion
• Oral suspension

Indications

• Urinary tract infections
• Acute exacerbations of chronic bronchitis
• Pneumocystis pneumonia
• Gastrointestinal infections caused by susceptible organisms

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Trimethoprim selectively inhibits dihydrofolate reductase, leading to a decrease in the production of tetrahydrofolate, which is vital for the synthesis of DNA, RNA, and proteins in bacteria. This inhibition ultimately results in the suppression of bacterial growth and replication.

Pharmacodynamics

Trimethoprim exhibits bactericidal activity, particularly against actively dividing bacteria. Its effectiveness is influenced by the concentration of the drug at the site of infection, with higher concentrations leading to increased antibacterial activity. The drug's action is more potent against susceptible organisms and is characterized by a concentration-dependent effect.

Pharmacokinetics

Trimethoprim is well absorbed after oral administration, with peak plasma concentrations occurring within 1 to 4 hours. It has a volume of distribution that indicates extensive tissue penetration, including into the lungs and kidneys. The drug is approximately 60-70% excreted unchanged in the urine, with a half-life of about 8 to 10 hours. Renal impairment can significantly affect its clearance, necessitating dose adjustments in patients with compromised renal function.

Contra-indications

• Hypersensitivity to trimethoprim or any of its components
• Severe renal impairment
• Pregnant women at term

Adverse effects

• Nausea
• Vomiting
• Rash
• Itching
• Anorexia
• Megaloblastic anemia
• Hyperkalemia
• Elevated liver enzymes

Interactions

• Increased effect of anticoagulants such as warfarin
• Potential interaction with methotrexate leading to increased toxicity
• May enhance the effects of other nephrotoxic agents

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of blood dyscrasias
• Consider alternative therapy in patients with a history of folate deficiency

Pregnancy

Trimethoprim is not recommended during the first trimester and should be avoided during the third trimester due to the risk of fetal harm.

Breast-feeding

Trimethoprim is excreted in breast milk. Caution is advised if administered to nursing mothers, as it may affect the infant's hematopoietic system.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Oral tablets
• Oral suspension
• Injectable solution

Mechanism of action

Sulfadiazine is a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase. This enzyme is needed for the proper processing of para-aminobenzoic acid (PABA) which is essential for folic acid synthesis. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.

Pharmacodynamics

Sulfadiazine is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of <i>p</i>-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.