What are the side effects and drug interactions of anticoagulants?
There are numerous drug interactions and side effects related to all forms of anticoagulants.
Warfarin side effects and drug interactions
In the case of warfarin, cranberry juice can increase the INR. In the event of the INR not being kept in the desired range (2-3), it can result in bleeding if lower, or clotting if higher. In the event that the patient overdoses on it, then they can be given IV vit K, or fresh frozen plasma, both of which will reverse the effects of the warfarin. Also, allopurinol, omeprazole, and amiodarone can increase the effect of warfarin. Drugs which can lower the effect of warfarin include carbamazepine, rifampicin, and also phenytoin. In terms of side effects, they include haemorrhage, fever, jaundice, rash, hepatic dysfunction and also diarrhoea and nausea.
Heparin side effects and drug interactions
With regard to heparin, the drug interactions include cephalosporin which affect coagulation and further increase the anticoagulant activity of the heparin. Also, when given with ACEI, it can result in hyperkalaemia. Nicotine may result in a partially antagonism of the heparin and therefore those that smoke are required to be given a higher dose of heparin. Also, when given with other anticoagulants, it can further increase this effect therefore increasing the risk of bleeding. Side effects of heparin include alopecia and osteoporosis when on long term therapy. The patient may also suffer from thrombocytopenia, in which case therapy should be immediately removed. It can also cause hypoaldosteronism which may in turn cause in an increase in potassium (in the absence of ACEI). There may also be hypersensitivity reactions such as asthma, cyanosis, fever, chills and also conjunctivitis, although these are rare.
Dabigatran side effects and drug interactions
Dabigatran also has various drug interactions. These include low molecular weight heparin, Clopidogrel, and also vitamin K antagonists. Also, when using Dabigatran, NSAID’s should be used with caution since they can increase the risk of bleeding. Moreover, it has been found that when taken with rifampicin, that the peak and total exposure of Dabigatran was increased by 66.5 and 67% respectively, effectively increasing the anticoagulant effect more than is required. After 7 days of stopping rifampicin, the Dabigatran levels return to normal. Also, when on PPI’s such as pantoprazole, it will cause a 30% reduction in AUC of Dabigatran. With regard to side effects, it can cause a reduction in haemoglobin, anaemia, epitaxis, nausea and diarrhoea and also GI bleeding. Less common side effects include vomiting, GORD, haematuria, abnormal LFT elevation and also thrombocytopenia.
In the case of Ximelagatran, this was removed from the market by the manufacturer. This was due to the fact that there were concerns raised with it causing liver damage, since there was an increase of LFTs at day 60, and a return to normal reference ranges by day 120.