Dispensing Oral Blood Thinners

Full update December 2018

Blood thinners, or antithrombotics, are used to help prevent blood clots that can lead to problems such as heart attacks and strokes. Blood clots can be fatal or cause permanent harm because they block blood flow to the rest of the body. Without blood flow, tissue starts to die. Blood thinners are divided into two classes, anticoagulants and antiplatelets. Both groups prevent blood clots, they just do it in different ways. Some examples of oral anticoagulants are warfarin (Coumadin, Jantoven [U.S.], etc), apixaban (Eliquis), dabigatran (Pradaxa), edoxaban (Savaysa [U.S.], Lixiana [Canada]), and rivaroxaban (Xarelto). Examples of more commonly used oral antiplatelets include aspirin, clopidogrel (Plavix), prasugrel (Effient), and ticagrelor (Brilinta).

Getting too much or too little of a blood thinner can lead to big problems. Too much of a blood thinner can cause bleeding which can be life threatening. Too little of a blood thinner can increase the risk for blood clots which can cause heart attack, stroke, or pulmonary embolism (when a blood clot causes blockage of an artery within the lungs). Anticoagulants are more likely than antiplatelets to cause bleeding. In fact, anticoagulant blood thinners are actually considered high-alert medications, meaning errors with these meds are especially likely to lead to serious patient harm. You play an important role in making sure prescriptions for blood thinners are dispensed correctly.

Xarelto

Mr. Murray is a 55-year-old male who comes into the pharmacy to drop off a new prescription for Xarelto 20 mg tablets. The directions on the prescription are to take 1 tablet by mouth every evening.

Why do some patients need to take a blood thinner?

Patients may need to take an anticoagulant if they have atrial fibrillation, which is an irregular heartbeat, or a history of blood clot formation in their legs (known as deep vein thrombosis, or “DVT”) or lungs (pulmonary embolism). Patients who are at especially high risk for blood clots, such as those with an artificial heart valve or recent surgery, may also need to take an anticoagulant.

Antiplatelets are usually used in patients who have had a heart attack or a stroke, to help prevent these events from occurring again. They may also be used to help prevent a first heart attack or stroke in certain patients who are at high risk, such as those with peripheral artery disease (poor circulation to the limbs), coronary artery disease, or after certain heart procedures, such as stent placement.

Mr. Murray tells you that he needs to start taking this medication because he has atrial fibrillation. You recall that this is a condition where the heart beats abnormally and that people with this condition are at a higher risk for blood clots that can cause stroke.

What is the difference between how anticoagulants and antiplatelets work?

Anticoagulants are used to prevent clots that can form in the veins. They can also be used to prevent existing clots from growing larger. They do this by working on certain parts of the “clotting cascade.” The “clotting cascade” is the stepwise process which occurs naturally in the body to initiate blood clot formation. By interrupting steps in this process, anticoagulants can help delay blood clotting. For example, warfarin blocks the action of vitamin K in the blood’s clotting cascade. Vitamin K is needed to help blood clot, so by blocking vitamin K’s action, warfarin makes it harder for the body to form clots.

Antiplatelets prevent clots that form in the arteries. These clots are often caused by platelets, a type of blood cell that can clump together to form blood clots in the arteries that affect the heart. Antiplatelets prevent platelets from sticking together.

Which oral anticoagulant blood thinners should I be familiar with?

Warfarin is the most commonly known and oldest oral anticoagulant still used today. In order to make sure a patient is getting the right amount of warfarin, an International Normalized Ratio (INR) blood test will be performed. Test results indicate the clotting ability of the blood and give an idea whether the patient is getting too much or too little warfarin. Too much warfarin can cause bleeding. Too little warfarin won’t be effective in preventing blood clots. When a person starts warfarin, INR testing will be done every few days or weekly at a lab or prescriber’s office. But once the dose is stabilized, INR testing will usually be done monthly.

Since warfarin prevents clotting, bleeding and bruising are big issues. In some cases, it may be very difficult to stop bleeding from an injury or surgery. Since warfarin interferes with vitamin K, it’s important for patients to watch their diet for sources of vitamin K. Green leafy vegetables such as kale, spinach, and cabbage, and other foods high in vitamin K such as avocados can interfere with warfarin’s action. Patients taking warfarin need to maintain a consistent diet of vitamin K-containing foods so that proper warfarin dosing can be established. In addition to dietary concerns, warfarin has a long list of drug interactions. Patients on warfarin should be extra careful in taking other medications that can thin the blood like clopidogrel, aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen. The blood could become too thin and a patient could have fatal blood loss, or “bleed out” if an injury was to occur.

Another group of oral anticoagulants newer to the market are direct factor Xa and direct thrombin inhibitors, commonly referred to as Direct Oral AntiCoagulants or DOACs. Direct factor Xa anticoagulants include apixaban, betrixaban (Bevyxxa [U.S.]), edoxaban, and rivaroxaban. For help with identifying direct factor Xa inhibitors, look at their generic drug names. They end in “–xaban,” such as rivaroxaban and edoxaban. An example of an oral direct thrombin inhibitor is dabigatran. Unlike warfarin, DOACs don’t need monthly blood monitoring or clinic visits, but they can still cause problems if used incorrectly. Skipping even one or two doses can put patients at risk for a blood clot.

You can get more details on these oral anticoagulants, such as drug interactions, dosing, and more, by reviewing our chart, Comparison of Oral Anticoagulants.

Which oral antiplatelet blood thinners should I be familiar with?

Aspirin is used frequently because it’s inexpensive and available over-the-counter (OTC). For most patients, the low dose of 81 mg per day works well for preventing clots. But aspirin can cause stomach irritation and possible ulceration of the stomach lining. So patients should be advised to take their aspirin with food or milk to help this side effect. Some patients prefer enteric-coated or extended-release versions (U.S.) to lessen the stomach irritation. Like the anticoagulants, aspirin should be used cautiously with other medications that thin the blood. Aspirin is also used as a pain reliever and a fever reducer. So stay on the lookout for patients taking two doses of aspirin. One for clot prevention, and another from cough/cold preps, or from taking Pepto-Bismol, or pain medications like Percodan (oxycodone/aspirin [U.S.]) or Fiorinal (butalbital/aspirin/caffeine). Just like acetaminophen, patients can accidentally overdose on aspirin. Patients can also be allergic to aspirin. This is called a salicylate allergy. Anyone who develops a rash after taking aspirin should not take other salicylates or NSAIDs. Make sure patient allergy profiles are kept up to date.

Another common antiplatelet is clopidogrel. Clopidogrel is usually well tolerated by patients but since it also prevents blood clots, the biggest complaints are bleeding and bruising. Drug interactions can occur with clopidogrel since it’s metabolized by the liver. For example, antifungals such as ketoconazole, can decrease the metabolism of clopidogrel to its active form, making it less effective. Like anticoagulants, clopidogrel should be used very cautiously with other drugs that thin the blood (aspirin, warfarin, NSAIDs, etc).

Ticagrelor, and prasugrel, are similar to clopidogrel. Ticagrelor works quicker than prasugrel or clopidogrel, but wears off faster. This could be advantageous if the patient begins bleeding or needs surgery. Patients will take ticagrelor twice a day, instead of once daily like clopidogrel or prasugrel.

Vorapaxar (Zontivity [U.S.]) is another antiplatelet used for preventing clots. It’ll be saved for patients at very high risk of a heart attack, but low risk of bleeding. Vorapaxar’s risk of causing a serious bleed seems to outweigh its heart benefits in some patients.

Other oral antiplatelets you may see less commonly include ticlopidine, dipyridamole extended-release/aspirin (Aggrenox), dipyridamole (Persantine), or cilostazol (Pletal [U.S.]). You can find out more about these antiplatelets by reviewing our chart, Comparison of Oral Antiplatelets.

What information should you ask for when a patient drops off an Rx for a blood thinner?

Some information, such as allergies, date of birth, and address, are commonly requested when patients drop off any prescription. Additional details can be helpful for patients taking blood thinners to identify those that may be at risk for bleeding or other problems.

Always ask patients about other drugs they may be taking so that pharmacists can check for drug interactions. For example, many common medications, including antibiotics, thyroid hormones, medications for heartburn, and cholesterol medications, can interact with warfarin. Some of these medications make patients taking warfarin more likely to bleed. Others decrease warfarin’s effectiveness, making patients more likely to have a clot. Drug-drug interactions can also occur with DOACs. For example, apixaban and dabigatran doses must be reduced if a patient is taking ketoconazole, which can drastically increase their blood levels. And rivaroxaban shouldn’t be used with ketoconazole at all.

Prescription and OTC NSAIDs, such as aspirin and ibuprofen, can increase the risk of bleeding with blood thinning meds. However, sometimes patients with certain conditions will actually take two antiplatelet drugs at the same time (dual antiplatelet therapy), such as aspirin plus clopidogrel, to get better effects. Supplements can also interact with blood thinners. For example, garlic might increase the risk of bleeding, especially when used with blood thinners.

Dietary factors can affect warfarin. High protein diets (e.g., Atkins, South Beach) and foods high in vitamin K (dark green vegetables) can decrease warfarin’s effectiveness. Vitamin K may also be found in multivitamins, green tea, and soy products. Alcohol may also increase warfarin’s effects.

Ask patients presenting with a new or refill Rx for blood thinners if they take any supplements or OTC medications, follow any special diet, or take any Rx medications other than the ones they get at your pharmacy (e.g., samples from the prescriber or mail-order prescriptions). Update patient profiles and provide this information to the pharmacist so he or she can appropriately counsel the patient.

Also update patient profiles with medical conditions to help the pharmacist ensure the patient is getting the right blood thinner at the right dose. For example, rivaroxaban is dosed 20 mg once daily to reduce the risk of stroke and blood clots in patients with atrial fibrillation, versus 15 mg twice daily for the initial treatment of blood clots. And if the patient’s kidneys aren’t functioning normally, some anticoagulant doses will need to be adjusted or the medication switched.

You update Mr. Murray’s profile to include atrial fibrillation in the medical conditions section. You ask him if he is taking any prescription meds that he gets from somewhere else and he tells you that he gets all his medications from your pharmacy. You ask him if he is taking any OTC meds or supplements. He says that the only thing he takes is ibuprofen every once in a while for a headache and he recently started taking aspirin because he heard from a friend that it can protect the heart.

What should be considered when entering a prescription for a blood thinner into the computer?

Look-alike, sound-alike errors. Warfarin is available in nine different strengths, ranging from 1 mg to 10 mg. Some strengths can be easily confused with other medications, such as Coumadin and Cardura or Coumadin and Avandia. Clarify if you are unsure if a prescription is written for warfarin or a medication with a similar name. Asking the patient why he or she is taking the medicine can help. Using warfarin in a patient that does not need to take it can lead to toxicity or a fatal bleeding reaction. Consider look-alike, sound-alike drug names with other blood thinners, such as Pradaxa/Plavix and Plavix/Paxil.

Dosing and instructions. Watch out for decimal points and trailing zeros with warfarin prescriptions. A dose written for “1.0 mg” could easily be mistaken for “10 mg” and lead to a ten-fold overdose. In fact, it’s always a good idea to carefully examine any warfarin prescription written for more than 9 mg. Doses higher than 9 mg of warfarin are unusual and may result in serious bleeding if taken in error.

As mentioned, warfarin doses are often individualized and may change frequently so that prescribers can achieve a specific goal INR level to make sure it is working correctly. Warfarin Rxs may have complex instructions such as “Take 1 tablet on Monday, Wednesday, and Friday. Take ½ tablet on Tuesday, Thursday, Saturday, and Sunday.” These specific instructions allow prescribers to make dose changes in small increments without requiring the patient to get a new strength of the medication from the pharmacy.

Pay special attention when entering dosing instructions for blood thinner prescriptions into the computer. Make sure the prescription label reads exactly as it is written on the prescription. Additional label space may be required for more detailed instructions, such as those that may be seen with warfarin.

Days’ supply. Having detailed instructions will allow you to estimate an accurate days’ supply for insurance purposes. Work with the pharmacist to clarify prescription instructions that say “Take (or use) as directed.” This practice may not be allowed by some insurers and is generally frowned upon.

Some DOACs are indicated to prevent clots after hip or knee replacements. These DOACs include apixaban, dabigatran (off-label in the U.S. for knee replacement), and rivaroxaban. Patients might only get short courses of these drugs with no refills, such as 35 days’ worth of rivaroxaban for a hip replacement or 12 (U.S.) to 14 (Canada) days’ worth of rivaroxaban for a knee replacement.

Betrixaban (U.S.) is only approved to prevent blood clots in the leg or lungs in certain hospitalized patients with multiple risk factors (e.g., reduced mobility plus older age and heart failure). It should not be used for more than six weeks because longer use may increase the risk of side effects, such as bleeding. Be sure to check days’ supply and refills if you get prescriptions for betrixaban.

Duplicate therapies. Patients may switch from warfarin to one of the DOACs, or vice versa. Two of these anticoagulants should generally not be taken at the same time because this duplication could increase the risk of bleeding. The exception may be when a patient is switched from a DOAC to warfarin. The DOAC may be temporarily continued until the warfarin start working. Let the pharmacist know if you see two anticoagulants being given together or if you’re not clear on which drug a patient should be taking.

As mentioned, some patients will take two antiplatelets at the same time, or you may occasionally see an anticoagulant given with an antiplatelet (e.g., rivaroxaban in combination with aspirin to decrease the risk of heart attack, stroke, and cardiovascular events in certain patients with heart disease). The most common antiplatelet combination is aspirin plus clopidogrel. Additionally, prasugrel and ticagrelor are actually indicated to be given in combination with aspirin. If you’re not sure, double check with the pharmacist to find out whether duplicate therapies with blood thinners are appropriate.

Generic substitution. There has been some controversy in the past about the use of generic forms of warfarin instead of the brand product. This stems from potential toxicities with warfarin and the concern that subtle product differences between brand and generic forms might mean big changes in effect or adverse events. However, this concern is unique to warfarin and isn’t an issue with DOACs or antiplatelet meds. Generic warfarin is now commonly used in place of brand products. However, some prescribers may still prefer patients to start or remain on a brand warfarin product. Keep a close eye out for warfarin prescriptions marked as “Brand only,” “Do not substitute,” or “Dispense as written.” In these cases, the prescriber is indicating that the patient should receive a specific brand of warfarin. The specific product should be selected in the inventory list when entering the prescription into the computer and the appropriate DAW code will need to be submitted to the insurance. DAW codes are a nationally recognized code set in the U.S. that is transmitted with the pharmacy claim to the insurance provider.

Drug interaction alerts. It’s important to alert the pharmacist to any drug interaction warnings that come up for patients taking blood thinners. Computer generated drug interaction alerts are particularly common when entering warfarin prescriptions because of the high number of potential drug interactions. You may encounter an alert when you are entering a prescription for a blood thinner OR entering another medication for a patient who is also taking a blood thinner. This is especially important if the interacting drugs are prescribed by two different prescribers, since a prescriber may not be aware of medications a patient is taking from another prescriber. The pharmacist may need to discuss any potential interaction with the patient or contact the appropriate prescriber.

When you hear Mr. Murray tell you that he sometimes takes ibuprofen and recently started taking aspirin, you get the pharmacist involved. You know that all of these medications can cause blood thinning which can increase Mr. Murray’s risk for bleeding with Xarelto.

What should be considered when selecting a blood thinner from the shelf?

Warfarin products are especially prone to mix-ups since there are so many different strengths. These are usually stored close to each other on pharmacy shelves, with at least one bottle of each of the nine strengths in both a brand and generic form kept in stock. Some doses are easily confused, for example, 1 mg and 10 mg or 2 mg and 2.5 mg. The bottles of different strengths also look similar.

Also watch for mix-ups with rivaroxaban, which is available in four different strengths: 2.5 mg, 10 mg, 15 mg, and 20 mg. In addition, it’s available as a 30-day starter pack (U.S.) for the treatment of blood clots in the legs or lungs. Patients prescribed this starter pack must initially take 15 mg twice a day for the first three weeks, then 20 mg once daily for the continued treatment and prevention of blood clots.

To avoid a mix-up, make sure to pay close attention when you are pulling a product from the shelf to fill an Rx. Do not store the warfarin 1 mg and 10 mg strengths right next to each other. Instead store products in the order of increasing or decreasing strength to space 1 mg and 10 mg strengths as far apart as possible. Make a habit of checking the strength indicated on the Rx against the stock bottle. Verify the NDC number or DIN on the Rx label against the stock bottle as another double check.

What additional labeling should be included when dispensing prescriptions for blood thinners?

Check with your pharmacist about manually adding a sticker to prescriptions for blood thinners stating, “Do not take aspirin without the consent of your physician,” or a similar message if this does not automatically print on the prescription label. Although aspirin may occasionally be used with other blood thinners, it can also increase the risk of serious bleeding in some patients.

Apply a “take with food” label to rivaroxaban 15 mg and 20 mg strengths, since food helps improve absorption of the drug. The lower rivaroxaban strengths (2.5 mg, 10 mg) can be taken without regard to meals since its absorption is not affected by food. Also apply a “take with food” label to prescriptions for betrixaban, since taking it with a meal helps to keep absorption consistent.

In the U.S., remember to dispense a MedGuide with the following blood thinners: all DOACs, warfarin, clopidogrel, prasugrel, and ticagrelor. MedGuides can help warn patients about bleeding risks and signs that their blood may be too thin (e.g., bloody gums or nose bleeds).

Keep in mind that dabigatran and prasugrel must be dispensed and kept in their original containers to protect the drugs from moisture. The tablets shouldn’t be put in other containers such as pillboxes. In the U.S., apply an auxiliary label to prescription bottles of dabigatran to let patients know to discard any remaining drug four months after opening the bottle. In Canada, dabigatran is currently only available in blister packs.

When should you alert the pharmacist to a potential problem with a blood thinner Rx?

Because of the potential for serious bleeding with blood thinners, pharmacists should be notified of any computer alerts such as therapy duplications, dosing issues, and drug-drug or drug-disease interactions. In addition, let pharmacists know about any patient reports of changes in diet, OTC medications, supplements, etc, and add this information to the patient profile.

Let the pharmacist know if you see a patient is getting late refills of any blood thinner. Late refills could signal a problem with adherence. Adherence to blood thinner regimens is very important, but patients must stick especially closely with their DOAC regimens. Skipping even a dose or two of these drugs can increase the risk for a blood clot in some patients. Manufacturers of these drugs will provide phone or email reminders to help patients stay on track. They may also provide assistance programs for patients who skip doses because they have trouble affording these meds.

Also get the pharmacist involved if you hear patients complaining about excessive bruising, bloody gums, frequent bloody noses, or other unusual bleeding. These are signs that a patient’s blood may be too thin.

You hear the pharmacist counsel Mr. Murray that he should be careful with using ibuprofen while taking Xarelto because it can increase his risk for bleeding. The pharmacist recommends he take acetaminophen instead when he has a headache. The pharmacist also advises that Mr. Murray stop taking the aspirin until he can talk to his prescriber about it, since aspirin can also increase the risk of bleeding. The pharmacist counsels Mr. Murray that he will need to take Xarelto with his evening meal, to help improve absorption. You make sure to include a “take with food” auxiliary label on the prescription bottle and prepare a MedGuide to be given to Mr. Murray.

Project Leader in preparation of this technician tutorial (341280): Flora Harp, PharmD/Assistant Editor

Cite this document as follows: Technician Tutorial, Dispensing Oral Blood Thinners. Pharmacist’s Letter/Pharmacy Technician’s Letter. December 2018.

—Continue to the next page for a “cheat sheet” about blood thinners—


“Cheat Sheet” for Dispensing Oral Blood Thinners

What are blood thinners and why do some people need to take them?

Blood thinners are used to help prevent blood clots that can lead to problems such as heart attacks and strokes. There are two types of blood thinners: anticoagulants (warfarin, dabigatran, rivaroxaban, etc) and antiplatelets (aspirin, clopidogrel, prasugrel, etc). People may need to take an anticoagulant if they have atrial fibrillation (irregular heartbeat), need to treat a blood clot, or are at high risk for having a blood clot. People may need to take an antiplatelet to prevent heart attack or stroke if they’ve had one in the past or if they are at high risk for having one in the future.

Which oral blood thinners should I be familiar with?

  • Anticoagulants
    • Warfarin (Coumadin, Jantoven [U.S.], etc) – requires INR blood test monitoring
    • Direct Oral AntiCoagulants (DOACs) – do NOT require blood test monitoring
      • Apixaban (Eliquis)
      • Betrixaban (Bevyxxa [U.S.])
      • Dabigatran (Pradaxa)
      • Edoxaban (Savaysa [U.S.], Lixiana [Canada])
      • Rivaroxaban (Xarelto)
  • Antiplatelets (most commonly used)
    • Aspirin – available OTC; dose of 81 mg used for clot prevention
    • Clopidogrel (Plavix)
    • Prasugrel (Effient)
    • Ticagrelor (Brilinta)

What should be done when processing prescriptions for blood thinners?

  • Update patient profiles with:
    • Other Rx meds, OTCs, and herbals/supplements patient is taking
    • Special diets (especially with warfarin, since vitamin K in diet can impact efficacy)
    • Medical conditions
  • Watch for look-alike, sound-alike errors (e.g., Coumadin/Cardura, Coumadin/Avandia, Pradaxa/Plavix)
  • Pay attention to dosing and instructions – watch for decimal points and trailing zeros with warfarin Rxs; ensure directions are clear and complete
  • Enter the correct days’ supply – clarify Rxs that just say “Take (or use) as directed”
  • Alert the pharmacist any time there are computer alerts warning of duplicate therapy, drug-drug interactions, drug-disease interactions, and dose too high or too low
  • Watch for warfarin Rxs marked as “Brand only,” “Do not substitute,” or “Dispense as written” – in these cases you cannot perform generic substitution


What should be done when filling prescriptions for blood thinners?

  • Make sure to select the right product from the shelf by checking the NDC number or DIN and strength on the stock bottle against the prescription label
  • Dispense dabigatran and prasugrel in the original container
  • Add appropriate auxiliary labels: “Do not take with aspirin,” “Take with food” for rivaroxaban 15 and 20 mg and betrixaban, “Discard after ____” for dabigatran
  • Provide MedGuides (U.S.)
  • Get the pharmacist involved if there are late/erratic refills or complaints of unusual bleeding


[December 2018; 341280]