Direct Oral Anticoagulants (DOAC) in Atrial Fibrillation

Newer drugs called direct oral anticoagulants which include edoxaban, apixaban, rivaroxaban and dabigatran have been approved by the US Food and Drug Administration (USFDA) for the treatment of non-valvular atrial fibrillation. A review on the use of the drugs for the purpose was published in the US Pharmacist. Atrial fibrillation is a condition where the upper chambers of the heart flutter at a very fast pace. It results in stagnation of blood and formation of clots in the heart. A clot within the circulation can travel to different parts of the body and obstruct the blood supply to that part. This could have serious consequences including a stroke.

Therefore, along with the other medications that are used for atrial fibrillation, anticoagulants form an important part of the treatment of atrial fibrillation.

Warfarin has been the only oral anticoagulant available for a very long time.

• It requires frequent monitoring of its effect through the measurement of the International Normalized Ratio (INR)
• It interacts with other medications
• It can cause fetal malformation when used in pregnancy

Newer oral anticoagulants have been approved by the USFDA for the treatment of non-valvular atrial fibrillation, that is, atrial fibrillation that occurs in the absence of heart valve disease. The heart valves allow the passage of blood through the chambers of the heart in a single direction.

The DOACs can be used in those patients in whom the INR cannot be maintained within the desired range. They do not require monitoring of INR and can be administered as a fixed dose. However, kidney function should be regularly monitored in patients taking these medications. It is also important to note that specific antagonists to these drugs are not yet available. Prothrombin complex concentrate has sometimes been used to reverse the anticoagulation caused by the medications. Idarucizumab has recently been approved for the treatment of serious bleeding following the use of dabigatran.

A summary of the important information derived from the article published in the US Pharmacist by Hoie EB and colleagues is presented below:

Edoxaban

• Edoxaban is available as a tablet to be taken in a dosage of 60 mg per day for a patient with non-valvular atrial fibrillation
• Since most of it is excreted from the body through the urine, the dosage has to be reduced in those with reduced kidney function. It should not be used by patients with severe kidney disease and mild-to-moderate liver disease. It belongs to pregnancy Category C and should not be used during breastfeeding
• The use of drugs like rifampin, other anticoagulants and antiplatelet drugs which could alter the effect of edoxaban should be avoided in a patient taking edoxaban
• As expected, side effects are bleeding and anemia

Apixaban

• Apixaban is used in a dosage of 5 mg twice a day. The dosage should be reduced in individuals with severe kidney disease, over 80 years of age, and in patients with body weight of less than 60 kg
• It can be used during pregnancy (Pregnancy category B), but can increase the risk of bleeding. It should not be used by nursing mothers or those with severe liver disease
• It should not be used with drugs that may alter its metabolism or its blood levels

Rivaroxaban

• Rivaroxaban is used in a dose of 20 mg a day with the evening meal. Dosage should be reduced in patients with kidney disease, and should be avoided in patient with severe kidney disease.
• It belongs to Pregnancy Category C and should not be used in nursing mothers
• It should not be used in patients with moderate-to-severe liver disease
• It should not be used with drugs that may alter its metabolism or its blood levels

Dabigatran

• Dabigatran is used in a dose of 150 mg twice daily, which should be reduced in patients with kidney disease
• It belongs to Pregnancy Category C and should not be used by nursing women
• It commonly causes gastritis-like adverse events

While dispensing the medication, the pharmacist should also advise and educate the patient on the necessity in taking the medication regularly, to inform the physician in case any other medications need to be taken and the symptoms of side effects, which may appear during the treatment.

Advertisement

Reference:

1. Hoie EB, O’Brien KK, Neighbors K, Castillo SL, Begley KJ. Direct Oral Anticoagulants for the Prevention of Stroke in Nonvalvular Atrial Fibrillation. US Pharm. (2017);42(2):32-35.

Source-Medindia