Dabigatran (Pradaxa) IPad App

There is an IPad App available to provide advice about the anticoagulation dabigatran. This was developed by Dr Paul Harper MD, FRCP, FRACP. This app is provides extremely important information, as there is no antidote should you need emergency treatment. I would be interested in anyone who would like to use this app or are already using it?

[warfarin1]

Interested, where can I see this app before buying?

[Hidden in reply to warfarin1]

This is a free Ipad App - goto App Store and search for Dabigatran. I know it is recommended for clinicians but there is a lot of interesting information. There is no reason why the layperson can't use it but you will need to obtain medical information to enter into the data. I have a Dr friend who could help us to enter the technical data if you are interested.

[warfarin1]

I googled it and found it. Although it contains good information this App is for clinicians

itunes.apple.com/ph/app/man...

[Hidden in reply to warfarin1]

Yes, I agree but there is no reason why the layperson can't use it but you will need to obtain medical information to enter into the data. I have a Dr friend who could help us to enter the technical data if you are interested.

[Hidden in reply to Hidden]

Anyone interested in looking after their own well-being on anticoaguation maybe interested in the following excellent web site, it's free to join. I have emailed Dr Paul Harper to see if he will add Pulmonary Embolism to the Dose/Indication in his next upgrade.

healthobs.com - Warfarin Community

[Hidden in reply to Hidden]

Very Interesting point of view.

If you are considering moving to Dibagitran then you might be interested in this article found on healthobs.com.

Why I would not use Dibagitran

Dabigatran Demystified: What Warfarin Patients Should Know About this New Anticoagulant

May, 2011

Marie B. Walker, Henry I. Bussey, Pharm.D., and Edith Nutescu, Pharm.D.

Late last year the FDA approved a new anticoagulant drug called dabigatran (brand name Pradaxa) for the prevention of stroke in patients with an irregular heart beat called atrial fibrillation (AF). This medication is the first orally-administered alternative to warfarin (brand name Coumadin) to be approved by the FDA in the more than 60 years since warfarin became available. The attention that dabigatran has drawn is, in large part, due to the fact that frequent blood tests and dosage adjustments are not required for this medication as is the case with warfarin.

Much has been written about this new drug in both the news media and medical literature. Most of the published information, however, has been directed at health care professionals or those with an interest in health care costs and pharmaceutical marketing. Little has been done to communicate to patients on warfarin (brand name Coumadin) what they should know about this new medication. This article will attempt to cover the key points that a patient taking warfarin should know about dabigatran.

What are some major differences between taking dabigatran and taking warfarin?

If you are currently taking warfarin, then you probably know that the correct dose of warfarin has to be determined for each individual and may change from time-to-time. Factors that may require a change in warfarin dose include such things as changes in diet, use of dietary supplements, physical activity, illness, alcohol use, smoking practices, and other issues. When taking warfarin, you should have a blood test called the INR checked at least once every four weeks, and your clinician will adjust your warfarin dose as necessary to keep your INR in the target range, which is usually 2.0-3.0.

Dabigatran is a new medication that works differently than warfarin. Your body produces a chemical called thrombin that is needed in order to form a blood clot. Dabigatran helps to prevent blood clots by blocking the effect of thrombin.

Dabigatran comes as two standard doses in the U.S. Most patients on dabigatran take 150 mg two times a day. Some patients require a lower dose, however. In patients whose kidneys do not work as well as they should, dabigatran may build up in the blood stream since the kidneys cannot eliminate the drug from the body as fast as they should. Patients whose kidneys do not work well take 75 mg of dabigatran twice a day. In Canada and other countries, a 110 mg capsule is available, but this size was not approved by the U.S. FDA.

Regardless of the dose, with dabigatran, you take a capsule twice a day, and there is no blood test to measure the effect of the drug. The capsule formulation, however, presents some rather unique considerations. When taken as prescribed, less than 10% of the dose is absorbed into the blood stream. The capsule should NOT be opened before taking the dose (such as sprinkling the contents of the capsule on food) because the amount of drug absorbed is substantially increased. Absorbing a larger amount of the drug would be expected to result in an elevated drug concentration and an increased risk of bleeding. The medication also is subject to being degraded by moisture and, therefore, must be stored in the original bottle, which should be kept tightly closed. Once the original bottle is opened, the initial FDA approval called for the capsules to be used within 30 days or discarded. More recently, the FDA has been considering extending that time frame to 60 days. This susceptibility to moisture also means that the capsules cannot be stored in another container such as a typical prescription vial or a “weekly pill box,” as is often used by warfarin patients to enhance adherence to the dosing schedule. This issue has led some to suggest that it may be preferable to use dabigatran that is “strip packaged” where each capsule is sealed separately. This type of packaging would seem a reasonable option as long as the integrity of the strip packaging is maintained to be moisture proof.

Except for the special storage and handling issues addressed above, taking dabigatran is simple and not having a blood test every few weeks may sound appealing. On the other hand, fingerstick devices are readily available such that if you are taking warfarin, your INR can be checked with a quick stick of your finger rather than a traditional blood draw. Additionally, there is no way to monitor the effect of dabigatran, and there is no easy way to reverse the effect of dabigatran if bleeding should occur. If you take too much warfarin and bleeding occurs, the effects of warfarin can be reversed by administering vitamin K or, if more urgent reversal is needed, by administering clotting factors.

What are some potential side effects of taking dabigatran?

In the study mentioned above, more patients stopped taking dabigatran than stopped taking warfarin, and a significant reason for discontinuation was a higher rate of “dyspepsia” (or upset stomach). If an upset stomach occurs, patients should contact their prescribing clinician and should NOT stop the medication on their own. If you stop taking dabigatran, you increase your risk of having a stroke or other blood clot related event.

Dabigatran requires an acid environment in order to be absorbed in the body. As such, many experts believe that the upset stomach is due to the acid that is combined with the drug in the capsule. Another possibility is that the upset stomach is due to the fact that more than 90% of the drug is not absorbed and remains in the stomach and intestines (the gastro-intestinal or “GI” tract). The large amount of drug that stays in the GI tract also may explain a higher risk of GI bleeding seen with dabigatran. Patients who experience any bleeding, of course, should contact their prescribing clinician immediately.

What drugs are known to interact with dabigatran?

Although dabigatran is thought to have fewer and less clinically-significant drug interactions than what has been seen with warfarin, a few significant interactions have been identified. It also is worth noting that the lack of a blood test to monitor dabigatran makes it difficult to determine if a given patient is experiencing a drug interaction. Specific drug interactions that have been identified were reviewed recently in an article by Nutescu, et. Al. and are summarized below. Most of the potentially significant drug interactions with dabigatran appear to be related to the way the interacting drug affects the activity of something in the body called a P-glycoprotein. The P-glycoprotein is basically a pump that works to pump dabigatran back into the intestines. Some drugs prevent the P-glycoprotein from pumping dabigatran back into the intestines, so more dabigatran stays in the blood, which may increase the risk of bleeding. Alternatively, some drugs cause the P-glycoprotein to pump more dabigatran back into the intestines, so less dabigatran remains in the blood. With less dabigatran in the blood, the risk of stroke may increase. Exactly how much of a change in dabigatran blood levels is acceptable is not known. Since worsening kidney function can also lead to an increase in dabigatran blood concentration, it would seem logical to use the data on drug interactions together with how well the patient’s kidneys are working in trying to determine how significant various drug interactions may be.

Antacids and drugs to reduce acid secretion (for example: Pepcid): Dabigatran requires an acid environment in order for it to be absorbed into the blood stream. Medicines such as Pepcid that neutralize or suppress stomach acid have been shown to reduce absorprtion of dabigatran by approximately 11% to 35%. This degree of reduction in drug absorption is not thought to be clinically important.

Verapamil has been reported to more than double the blood concentration of dabigatran if the verapamil is given right before the dabigatran. However, there appears to be no interaction if the verapamil is taken at least 2 hours after the dabigatran dose. Use of a sustained release formulation of verapamil also may avoid this drug interaction.

Amiodarone and/or Dronedarone: Amiodarone and dronedarone are listed together because they are closely related chemically and both are used to treat atrial fibrillation. Amiodarone has been reported to increase dabigatran blood levels by approximately 65%. Additionally, data on file with Sanofi-Aventis suggest that dronedarone may cause a doubling of dabigatran blood levels. Amiodarone, however, also causes the kidneys to eliminate dabigatran from the body at a faster rate. As such, the initial increase in dabigatran blood levels may be offset by an increase in kidney elimination of the drug. Whether dronedarone has a similar effect on kidney elimination of dabigatran is not known at this time.

Other drugs that may increase dabigatran blood levels by preventing the P-glycoprotein from pumping dabigatran back into the intestines include Ketaconazole (150% increase), Quinidine (53% increase), Clarithromycin (19% increase), and Clopidogrel (30% increase).

Rifampin is thought to cause the P-glycoprotein to pump more dabigatran back into the intestines, which causes a lowering of dabigatran blood levels. The data suggest that rifampin may cause a two-thirds reduction in dabigatran blood levels. A two-thirds reduction in dabigatran blood levels would be expected to cause a loss of anticoagulant effect, which would increase the patient’s risk of stroke.

The drugs mentioned above that cause the P-glycoprotein to increase or decrease its pumping rate should be considered a partial list. Whether other medications may produce interactions with dabigatran in this same way remains to be determined.

Lastly, it should be noted that non-steroidal anti-inflammatory drugs (NSAIDS) - such as ibuprofen and similar agents - as well as other antiplatelet agents (such as clopidogrel) and other anticoagulants can increase the bleeding risk with dabigatran without changing the blood level of the drug.

Can any warfarin patient switch to dabigatran?

No. When the FDA approves a drug, it approves it only for specific conditions. Currently dabigatran is approved only for patients with atrial fibrillation. FDA approval was based largely on a single study that involved more than 18,000 patients who received either warfarin or one of two doses of dabigatran (110 mg twice daily or 150 mg twice daily). In the future, dabigatran may be approved for other indications in which blood clots may be a problem; but in order for such approval to be granted by the FDA, the manufacturer will have to conduct clinical trials and show benefit for the medication in patients who have the specific indication in question for anticoagulation.

Is dabigatran better than warfarin?

In order to get approval from the FDA, dabigatran had to go through “non-inferiority” trials. The purpose of a non-inferiority trial is to show that the investigational drug (in this case, dabigatran) is at least as safe and effective as the comparator drug (in this case, warfarin). The trials do not have to show that the new drug is better than the old drug. In the trial mentioned above, dabigatran 110 mg twice daily was “non-inferior” to warfarin in preventing strokes and had less bleeding than warfarin. The dose of 150 mg twice daily was actually found to be superior to warfarin in preventing strokes but with a similar rate of bleeding complications.

It also is important to understand that the studies look at group data. In other words, they have to show that the group on dabigatran does at least as well as the group taking warfarin. When one looks at individual data, however, the results sometimes look different. For example, 50% of warfarin-treated patients in the study mentioned above had their INRs in range 67% of the time or more. In such patients, the data suggest that warfarin is more effective and safer than dabigatran. On the other hand, when one compares data from the 25% of warfarin-treated patients with the poorest INR control (INRs in range less than 53% of the time), then dabigatran appears to be considerably safer and more effective.

Should I switch to dabigatran?

So, what’s the bottom line; should you make the switch? Patients with severe reduction in kidney function and those with significant liver disease should not take dabigatran because of a potential increased risk of bleeding. Otherwise, the answer as to whether you should switch is…it depends. Well-managed warfarin appears to be safer and more effective than dabigatran. So, if you are taking warfarin and have a good clinician management system in place such that your INR is usually in range and stable, then warfarin is probably safer and more effective for you than dabigatran would be. If, however, your INR is often out of control and measures to improve INR stability have not worked, then dabigatran may be a better option for you.

References

[warfarin1]

Quick points on this article.

Firstly all of this refers to the USA.

In UK Dabigatran comes in blister packs not bottles.

In UK it is licenced for use to prevent blood clots after hip and knee surgery and for stroke prevention in non-valvular atrial fibrillation. Th words non-valvular are important as anyone who develops AF after receiving treatment for their heart valve is not suitable to take Dabigatran or any other new oral anticoagulant.

[Hidden in reply to warfarin1]

Excellent points but understand that NICE have approved it for PE's as well! NICE has only recently approved two new anticoagulation drugs so we lack long term data about the side effects! I am researching the advantageous and disadvantageous and don't mind where the information comes from.

I would like to see more ACE members contributing to this debate.

[Hidden in reply to Hidden]

I would like to update my blog on Dabigatran and Rivaroxaban following advice from the Department of Haematology at Addenbrooke's Hospital August 2012.

Dabigatran is not currently licensed for treatment of patients with venous thromboembolism. However, Rivaroxaban is licensed and the dose is 20mg once daily orally. However, please be advised that the cost of Rivaroxaban is considerable more expensive than warfarin and some PCT may not prescribe it due to cost unless there are exceptional circumstances.

[Lf981400Q in reply to Hidden]

Hi Firemansam, I see that you quote that NICE have approved Dabigatran for PE's. Does this also apply to DVT, so that there is no re-occurance of DVT's??? Many thanks for your interesting Inputs. Lf981400Q

[Hidden in reply to Lf981400Q]

Thank you for your kind remarks which are greatly appreciated.

I think that Warfarin maybe better placed to answer this question as there are a number of research trials going on and ACE will have the most up to date information on Dabigatran.

[Lf981400Q in reply to warfarin1]

Hi warfarin. I wrote to Firemansam and wondered if Dabigatran was approved for DVT's if it is approved for PE's. I wonder if Warfarin is better at thinning the blood, rather than Dabigatran. Looking forward to a favourable reply and hope that you are keeping well. Kind regards. Lf981400Q

[Lf981400Q]

Hi Warfarin, I wrote to Firemansam and wondered if Dabigatran was approved for EVT;s if it is approved for PE's. I wonder if Warfarin is better at thinning the blood, rather than Dabigatranb. Looking forward to a favourable reply and hope that you are keeping well. Kind Regards. Lf981400Q