BISPIRAZOLE

Indications

• Bacterial infections
• Toxoplasmosis
• Infections in penicillin-allergic patients

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to the BNF for specific adult dosing guidelines, as these may vary based on the indication and severity of the infection.

Mechanism of action

Spiramycin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, which impedes the translocation process during protein synthesis. This binding prevents the dissociation of peptidyl-tRNA from the ribosome, effectively stopping bacterial growth.

Pharmacodynamics

The absolute bioavailability of oral spiramycin is typically between 30% to 40%. Following a dose of 1 g, peak serum concentrations range from 0.4 to 1.4 mg/L. Spiramycin's pharmacodynamic profile allows it to exert a bacteriostatic effect at therapeutic concentrations, making it effective in the treatment of susceptible infections.

Pharmacokinetics

Spiramycin is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within a few hours after administration. It is distributed widely in body tissues, including the lungs and liver, and has a long half-life, allowing for once or twice daily dosing. The drug is primarily excreted in the bile and feces, with minimal renal excretion.

Contra-indications

• Hypersensitivity to spiramycin or other macrolide antibiotics
• Severe hepatic impairment

Adverse effects

• Nausea
• Vomiting
• Diarrhoea
• Rash
• Headache
• Flushing
• Dysphonia
• QT interval prolongation
• Arrhythmias
• Convulsions (in overdose)

Interactions

• May interact with other drugs that prolong the QT interval
• Caution with other macrolides due to potential for cross-sensitivity
• May affect the metabolism of drugs processed by hepatic enzymes

Precautions

• Use with caution in patients with a history of arrhythmias or cardiac disease
• Monitor for potential hepatotoxicity in patients with liver impairment
• Evaluate for signs of hemolytic uremic syndrome

Pregnancy

High doses are teratogenic in the first trimester; however, in cases of malaria, the benefits of treatment may outweigh the risks.

Breast-feeding

Present in breast milk but not known to be harmful.

Storage

Store in a cool, dry place, protected from light.

Formulations

• Spiramycin 1.5 million unit tablets
• Spiramycin 3 million unit tablets

Mechanism of action

The mechanism of action of macrolides has been a matter of controversy for some time. Spiramycin, a 16-membered macrolide, inhibits translocation by binding to bacterial 50S ribosomal subunits with an apparent 1 : 1 stoichiometry. This antibiotic is a potent inhibitor of the binding to the ribosome of both donor and acceptor substrates. The primary mechanism of action is done by stimulation of dissociation of peptidyl-tRNA from ribosomes during translocation.I

Pharmacodynamics

The absolute bioavailability of oral spiramycin is generally within the range of 30 to 40%. After a 1 g oral dose, the maximum serum drug concentration was found to be within the range 0.4 to 1.4 mg/L.