SCIENTIFIC 0.05G/KG READY TO USE

Indications

• Rodent control in agricultural settings
• Urban rodent control

Dosage

Children: For pediatric exposure, especially in cases of accidental ingestion, consult the BNF for Children for guidance on management and potential treatment.

Adults: For the control of rodent populations, follow specific product guidelines as per local regulations and product labeling. Refer to BNF for detailed dosing recommendations.

Mechanism of action

Bromadiolone functions as an anticoagulant by inhibiting vitamin K(1)-2,3-epoxide reductase. This inhibition disrupts the vitamin K cycle, leading to decreased synthesis of clotting factors II, VII, IX, and X. The potency and long duration of action of bromadiolone are due to its high affinity for the target enzyme, its ability to interrupt the vitamin K cycle at multiple points, accumulation in the liver, and its prolonged biological half-life resulting from high lipid solubility and enterohepatic circulation.

Pharmacodynamics

As an anticoagulant, bromadiolone reduces the ability of blood to clot by interfering with the synthesis of vitamin K-dependent clotting factors. This action results in increased bleeding risk and prolonged coagulation times. The effects are dose-dependent, with lower doses typically resulting in mild anticoagulant effects and higher doses leading to significant anticoagulation, which may necessitate medical intervention.

Pharmacokinetics

Bromadiolone is well-absorbed from the gastrointestinal tract and is highly lipophilic, which contributes to its prolonged action. It undergoes hepatic metabolism and has a long half-life due to enterohepatic recirculation. The elimination of bromadiolone can vary based on individual metabolic rates and factors such as liver function, which can affect the duration of anticoagulation following exposure.

Adverse effects

• Hemorrhage
• Gastrointestinal bleeding
• Ecchymosis
• Hematuria
• Intracranial bleeding
• Liver dysfunction

Interactions

• Other anticoagulants
• Antiplatelet agents
• NSAIDs
• Corticosteroids
• Certain antibiotics (e.g., cephalosporins)

Precautions

• Use with caution in patients with liver disease
• Monitor coagulation parameters regularly
• Avoid use in individuals with known hypersensitivity to bromadiolone

Pregnancy

Bromadiolone is classified as a category C drug. Its effects during pregnancy are not well studied, and it should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown whether bromadiolone is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Bromadiolone bait formulations (e.g., pellets, blocks)

Mechanism of action

An anticoagulant inhibiting the formation of prothrombin. Anticoagulant pesticides are used widely in agricultural and urban rodent control. The emergence of warfarin-resistant strains of rats led to the introduction of a new group of anticoagulant rodenticides variously referred to as 'superwarfarins', 'single dose' or 'long-acting'. This group includes the second generation 4-hydroxycoumarins brodifacoum, bromadiolone, difenacoum, flocoumafen and the indanedione derivatives chlorophacinone and diphacinone. Most cases of anticoagulant rodenticide exposure involve young children and, as a consequence, the amounts ingested are almost invariably small. In contrast, intentional ingestion of large quantities of long-acting anticoagulant rodenticides may cause anticoagulation for several weeks or months. Occupational exposure has also been reported. Anticoagulant rodenticides inhibit vitamin K(1)-2,3 epoxide reductase and thus the synthesis of vitamin K and subsequently clotting factors II, VII, IX and X. The greater potency and duration of action of long-acting anticoagulant rodenticides is attributed to their: (i) greater affinity for vitamin K(1)-2,3-epoxide reductase; (ii) ability to disrupt the vitamin K(1)-epoxide cycle at more than one point; (iii) hepatic accumulation; and (iv) unusually long biological half-lives due to high lipid solubility and enterohepatic circulation... The effects of coumarins and indandiones on prothrombin synthesis and conversion of vitamin k1 2,3-epoxide to vitamin k1 were measured. Results provided evidence for the proposed mechanism of action by preventing regeneration of vitamin k1 from its metabolite. /Coumarins and indandiones/ Both 4-hydroxycoumarin derivatives and indandiones (also known as oral anticoagulants) are antagonists of vitamin K. Their use as rodenticides is based on the inhibition of the vitamin K-dependent step in the synthesis of a number of blood coagulation factors. The vitamin K-dependent proteins ...in the coagulation cascade... are the procoagulant factors II (prothrombin), VII (proconvertin), IX (Christmas factor) and X (Stuart-Prower factor), and the coagulation-inhibiting proteins C and S. All these proteins are synthesized in the liver. Before they are released into the circulation the various precursor proteins undergo substantial (intracellular) post-translational modification. Vitamin K functions as a co-enzyme in one of these modifications, namely the carboxylation at well-defined positions of 10-12 glutamate residues into gamma-carboxyglutamate (Gla). The presence of these Gla residues is essential for the procoagulant activity of the various coagulations factors. Vitamin K hydroquinone (KH2) is the active co-enzyme, and its oxidation to vitamin K 2,3-epoxide (KO) provides the energy required for the carboxylation reaction. The epoxide is than recycled in two reduction steps mediated by the enzyme KO reductase... . The latter enzyme is the target enzyme for coumarin anticoagulants. Their blocking of the KO reductase leads to a rapid exhaustion of the supply of KH2, and thus to an effective prevention of the formation of Gla residues. This leads to an accumulation of non-carboxylated coagulation factor precursors in the liver. In some cases these precursors are processed further without being carboxylated, and (depending on the species) may appear in the circulation. At that stage the under-carboxylated proteins are designated as descarboxy coagulation factors. Normal coagulation factors circulate in the form of zymogens, which can only participate in the coagulation cascade after being activated by limited proteolytic degradation. Descarboxy coagulation factors have no procoagulant activity (i.e. they cannot be activated) and neither they can be converted into the active zymogens by vitamin K action. Whereas in anticoagulated humans high levels of circulating descarboxy coagulation factors are detectable, these levels are negligible in warfarin-treated rats and mi