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

Dosage

Children: Refer to specific drug information for detailed dosage recommendations.

Adults: Refer to specific drug information for detailed dosage recommendations.

Mechanism of action

The mechanism of action varies depending on the specific drug that 'contains' certain active ingredients. Each compound will have its own unique pharmacological pathway and target within the body, which can include receptor modulation, enzyme inhibition, or other biochemical interactions.

Pharmacodynamics

Pharmacodynamics will depend on the active ingredients in the formulation. It generally encompasses the biochemical and physiological effects of the drug and its mechanisms of action, including the relationship between drug concentration and effect.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion of the specific active ingredients within the formulation. This can vary significantly based on the drug's chemical properties, route of administration, and individual patient factors.

Pregnancy

Consult with a healthcare provider before use, as safety during pregnancy has not been established.

Breast-feeding

Consult with a healthcare provider before use, as it is not known if this drug is excreted in human milk.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Urinary tract infections
• Acute exacerbations of chronic bronchitis
• Pneumocystis pneumonia
• Travelers' diarrhea caused by susceptible organisms

Dosage

Children: Refer to the BNF for Children for appropriate dosing information based on age and weight.

Adults: Refer to the BNF for specific dosing guidelines based on the type of infection and patient condition.

Mechanism of action

Trimethoprim selectively inhibits dihydrofolate reductase in bacteria, blocking the conversion of dihydrofolate to tetrahydrofolate. This interruption in folate synthesis leads to a decrease in nucleic acid synthesis, ultimately inhibiting bacterial growth.

Pharmacodynamics

Trimethoprim exhibits bactericidal properties against a variety of Gram-positive and Gram-negative bacteria. The drug's effectiveness is influenced by its ability to penetrate bacterial cells and its affinity for bacterial dihydrofolate reductase compared to the mammalian enzyme, resulting in a low toxicity profile for human cells.

Pharmacokinetics

After oral administration, trimethoprim is rapidly absorbed, with peak plasma concentrations occurring within 1-4 hours. It has a bioavailability of approximately 90%. The drug is extensively distributed throughout bodily tissues and fluids, including the prostate and lungs. Trimethoprim is primarily excreted through the kidneys, with about 50-70% of an administered dose appearing in urine as unchanged drug. Its half-life is approximately 8-10 hours in healthy individuals.

Contra-indications

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

Adverse effects

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

Interactions

• Increased effect of anticoagulants (e.g., warfarin)
• Increased risk of nephrotoxicity with other nephrotoxic drugs
• Reduced efficacy of certain anticonvulsants
• Potentiation of the effects of diuretics, leading to increased potassium levels

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of blood dyscrasias
• Assess potassium levels in patients at risk for hyperkalemia
• Caution in patients with a history of drug allergies

Pregnancy

Trimethoprim is contraindicated during pregnancy, particularly in the first trimester due to potential teratogenic effects.

Breast-feeding

Trimethoprim is excreted in breast milk; caution is advised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and direct light.

Formulations

• Oral tablet
• Oral suspension

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.