What is the effect of Augmentin (amoxicillin-clavulanate) on coagulation?

From the Guidelines

Augmentin (amoxicillin-clavulanate) can increase the risk of bleeding in patients on warfarin due to its effect on the gut microbiome and potential to alter vitamin K levels, and therefore, close monitoring of INRs is recommended when initiating Augmentin in patients on chronic warfarin therapy. In a prospective study of 120 patients who received a combination of amoxicillin/clavulanate, patients who received the higher maintenance dose (10–12 g/day) versus the usual dose (3.6 g/day) developed a higher proportion of INR values ≥ 4 1. This suggests that the dose of Augmentin may contribute to the severity of the interaction with warfarin. The mechanism of this interaction is thought to be related to the alteration of the gut microbiome, which is a rich source of vitamin K, and thereby potentiates the anticoagulant effects of warfarin 1. It is essential to monitor INRs closely whenever antibiotics, including Augmentin, are initiated in the setting of chronic warfarin use 1. Key points to consider when using Augmentin in patients on anticoagulant therapy include:

• Close monitoring of INRs to prevent adverse bleeding events
• Potential dose adjustments of warfarin may be necessary to maintain a therapeutic INR
• The underlying infection being treated with Augmentin may affect coagulation parameters in some cases, as severe infections can sometimes lead to coagulation abnormalities through inflammatory pathways
• Patients with severe hepatic impairment should be monitored more closely as the liver plays a key role in both drug metabolism and production of coagulation factors.

From the FDA Drug Label

1. 2 Oral Anticoagulants Abnormal prolongation of prothrombin time (increased international normalized ratio [INR]) has been reported in patients receiving amoxicillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently with amoxicillin and clavulanate potassium Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation. The effect of Augmentin (amoxicillin-clavulanate) on coagulation is an increased risk of abnormal prolongation of prothrombin time and increased international normalized ratio (INR) when used concurrently with oral anticoagulants.

• Key points to consider:
  • Monitoring is necessary when coadministering Augmentin with oral anticoagulants
  • Adjustments in the dose of oral anticoagulants may be required to maintain the desired level of anticoagulation 2

From the Research

Effect of Augmentin on Coagulation

• The effect of Augmentin (amoxicillin-clavulanate) on coagulation is primarily related to its impact on vitamin K-producing gut flora, which can lead to a decrease in vitamin K levels and subsequently affect coagulation homeostasis 3.
• A case report describes a patient who developed an elevated international normalized ratio (INR) and microscopic hematuria as a result of a drug-drug interaction between warfarin and amoxicillin/clavulanate potassium (AM/CL), suggesting that Augmentin can interact with warfarin and increase the risk of bleeding complications 3.
• The mechanism of this interaction is not fully known, but it is suspected that a decrease in vitamin K-producing gut flora with resulting vitamin K deficiency is the most likely contributing factor 3.
• Another study highlights the importance of monitoring coagulation parameters in patients receiving broad-spectrum antibiotic therapy, especially those with underlying malnutritive or malabsorptive conditions, as they may be at risk of developing coagulation disorders due to altered vitamin K metabolism 4.
• However, it is essential to note that the direct effect of Augmentin on coagulation is not as well-studied as its interaction with warfarin, and more research is needed to fully understand its impact on coagulation homeostasis.

Relevance to Coagulation Disorders

• Vitamin K deficiency is a known cause of coagulation disorders, and broad-spectrum antibiotic therapy, including Augmentin, can contribute to this deficiency by disrupting the gut flora that produces vitamin K 4, 5.
• Patients with underlying medical conditions, such as malnutrition or malabsorption, may be more susceptible to coagulation disorders when taking Augmentin or other broad-spectrum antibiotics 4, 5.
• Monitoring coagulation parameters and being aware of the potential interaction between Augmentin and warfarin can help prevent bleeding complications and ensure timely intervention if necessary 3, 6.