Anagrelide (Oral)

Anagrelide, an antiplatelet agent, is designed to reduce the risk of blood clots in patients with thrombocythemia, a disorder which causes excessive production of blood platelets.

Overview

Anagrelide is an antiplatelet agent prescribed to patients with thrombocythemia to reduce the risk of blood clots. Thrombocythemia is a condition in which the body produces too many platelets within the blood, which can lead to abnormal bleeding and blood clotting. Blood clots can cause a wide variety of health complications, including stroke, heart attack, and deep vein thrombosis. Anagrelide works by reducing platelet production to reduce the risk of clotting.

Sometimes anagrelide is prescribed to children for the treatment of chronic myelogenous leukemia. This is a type of cancer which affects white blood cells and can interfere with normal platelet production.

Anagrelide is only available with a doctor's prescription and cannot be purchased over the counter. It is available both in its generic form and under US brand name Agrylin. It's an oral medicine administered in capsule form.

Condition treated

  • Thrombocythemia

Type of medicine

  • Antiplatelet agent

Side Effects

Anagrelide poses a wide variety of side effects, most of which are uncommon or rare. Some are minor and do not require medical attention unless they become very persistent and bothersome, but others are serious and should be reported to your doctor. Familiarize yourself with all potential side effects so that you can recognize the serious ones and seek medical care as soon as possible where necessary.

Serious side effects

The following are more common side effects which require medical attention:

  • Bloating or swelling of face, arms, hands, legs or feet
  • Aches and pains throughout body
  • Pounding, irregular or racing heartbeat
  • Chest pain
  • Tightness in chest
  • Labored breathing
  • Difficulty swallowing
  • Cough or dry or sore throat
  • Hoarseness
  • Changes in voice
  • Fever
  • Swollen or tender glands in neck
  • Burning, itching, numb, prickling, crawling or tingling sensations
  • Rapid weight gain

The following are less common side effects which require medical attention:

  • Blurred vision
  • Anxiety
  • Confusion
  • Dizziness, lightheadedness or faintness when standing from lying down or sitting
  • Extreme fatigue
  • Feeling unusually weak or tired
  • General feeling of being unwell or uncomfortable
  • Headache
  • Burning sensation during urination
  • Decreased urination
  • Difficult or painful urination
  • Dehydration
  • Chills
  • Cold sweats
  • Dilated veins in neck
  • Irregular breathing
  • Noisy breathing or wheezing
  • Difficult breathing when exerted (such as after exercise)
  • Joint pain
  • Muscular aches and pains
  • Pale skin
  • Redness in face, neck arms or upper chest
  • Pain or pressure in jaw, neck back or arms
  • Flat, blue-purple patches on skin
  • Unusual bruising or bleeding
  • Swelling or inflammation of mouth
  • Low appetite
  • Nausea or vomiting
  • Vomiting substance which looks like coffee grounds

The following side effects are possible, but the rate at which they occur is unknown. All require urgent medical care:

  • Clay-colored stools
  • Dark urine
  • Pain in stomach or abdomen
  • Dry cough
  • Skin itching or rash
  • Yellow skin or eyes

Minor side effects

Some side effects don't require urgent medical attention. Often, they dissipate after a few days after your body adjusts to the medicine. You might notice them only when your dose of anagrelide is increased during the first few weeks of anagrelide therapy and until you reach your maintenance dose. If any of these side effects persist or you find them particularly difficult to cope with, you may want to report them to your doctor. There may be lifestyle changes you could make to relieve or reduce them.

Some of the more common minor side effects of anagrelide are:

  • Sour or acidic stomach
  • Uncomfortable, upset or painful stomach
  • Belching
  • Excess gas
  • Bloating or feeling full
  • Indigestion
  • Diarrhea
  • Back pain
  • Lack of strength
  • Hives or welts
  • Headache

Less common minor side effects include:

  • Burning sensation in stomach or chest
  • Vision changes
  • Double vision
  • Ringing or buzzing sounds in ears
  • Hearing loss
  • Constipation
  • Depression
  • Sleepiness or drowsiness
  • Memory problems
  • Difficulty moving
  • Leg cramps
  • Swollen joints
  • Pain or stiffness in muscles
  • Hair loss or thinning
  • Increased sensitivity to sunlight, such as skin rash, redness or severe sunburn
  • Redness or discoloration of skin
  • Nasal congestion
  • Runny nose

Dosage

For both adults and children with either thrombocythemia or myelogenous leukemia, the recommended dose of anagrelide is either 0.5 mg four times each day, or 1 mg twice each day, for at least 7 days. Then, if necessary, this is increased by up to 0.5 mg day until platelet counts reach normal levels. Once normal platelet levels are reached, patients continue at the same “maintenance” dosage to prevent thrombocythemia. Dosage should never exceed 10 mg in one day or 2.5mg in a single dose.

In patients with renal impairment, dosages may be lower or administered less regularly to account for slower processing of the drug in the liver.

The initial effects of anagrelide usually occur within 7 to 14 days, but it can take anywhere between 4 and 12 weeks for the drug to reach its full effects. If a patient stops taking the medicine, platelet count will begin to rise again within 4 days.

During the first week of anagrelide therapy, patients can expect their platelet count to be monitored every two days. After that, platelet counts will usually be monitored at least once a week until the maintenance dosage is established. Blood counts, liver function, and renal function are also usually carefully monitored during the first two weeks of anagrelide treatment.

How to take anagrelide

Anagrelide can be taken either with or without food, but doctors usually recommend that patients take doses at the same times each day and coordinating them with mealtimes may help you to remember to take the medicine.

If you do miss a dose of anagrelide, take it as soon as you remember. If it's almost time for the next dose when you realize you've missed a dose, simply skip the missed dose. Do not take double doses to make up for missed ones.

In the event that you take too much anagrelide, seek emergency medical care. Overdoses of any drug, including anagrelide, can be harmful and it's important to seek advice from a medical professional even if you feel well.

Interactions

Risk of heart rhythm irregularities

Some QTc-prolonging drugs, when combined with anagrelide, pose a risk of heart rhythm irregularities which could be incredibly dangerous. Some should never be used with anagrelide, while others may be used with careful monitoring of the patient and dosage adjustment where necessary.

QTc-prolonging agents which should never be used with anagrelide include:

  • Amifampridine (Firdapse)
  • Hydroxychloroquine (Plaquenil, Quineprox)
  • Mifepristone (Korlym)
  • Mizolastine (Mizollen)
  • Promazine (Sparine)
  • Vinflunine (Javlor)

QTc-prolonging agents which may be combined with anagrelide with careful monitoring and/or dosage adjustments include:

  • Buprenorphine (Probuphine)
  • Indapamide (Lozol)
  • Teneligliptin (Fareston)
  • Xipamide (Diurexan)

Risk of low platelet counts and enhanced anticoagulant effects

Some drugs with antiplatelet properties or anticoagulant properties could enhance the effects of anagrelide. This might result in platelet count becoming too low or increase the risk of in abnormal bleeding. If taking these drugs concurrently, patients may require additional monitoring and dosages of anagrelide may be lower than average. Examples of such drugs include:

  • Aspirin and other NSAIDs (types of painkillers)
  • Dabigatran (Pradaxa)
  • Glucosamine (Genicin, Optiflex-G)
  • Pentoxifylline (Trental)
  • Prostacyclin analogues
  • P2Y12 inhibitors such as:
  • clopidogrel (Plavix)
  • prasugrel (Effient)
  • ticlopidine (Ticlid)
  • Rivaroxaban (Xarelto)
  • Some SSRIs (used to treat depression
  • Tipranavir (aptivus)
  • Urokinase (Kinlytic, Abbokinase, Annokinase Open-Cath)

Risk of enhanced toxic effects

Some drugs interact with anagrelide and pose the risk of adverse or toxic effects. Examples of such drugs include:

  • Apixaban (Eliquis)
  • Cephalothin (Keflin)
  • Cilostazol (Pletal)
  • Collegenase (Santyl)
  • Deoxycholic acid (Kybella)
  • Edoxaban (Savaysa)
  • Enoximone (Perfan)
  • Ibritumomab (Zevalin)
  • Ibrutinib (Imbruvica)
  • Milrinone (Primacor)
  • Obinutuzumab (Gazya)
  • Pentosan polysulfate sodium (Elmiron)
  • Salicylates
  • Tositumomab and Iodine I 131 Tositumomab (Bexxar)

Riociguat, also known as Adempas, is a treatment for pulmonary hypertension. Anagrelide may enhance the hypotensive (blood pressure reducing) effects of this drug.

Interactions with supplements and vitamins

Certain herbs which have anticoagulant or antiplatelet properties could enhance the toxic effects or side effects of anagrelide. Although in small quantities these herbs usually will pose little risk, if they are taken in food supplements on a regular basis they could pose some risk. Examples of such herbs include:

  • Alfalfa
  • Anise
  • Bilberry
  • Garlic
  • Ginseng
  • St. John's Wort

Certain multivitamins, particularly those which contain ADE, ADEK, folate or iron, might enhance antiplatelet effects when used with anagrelide. Omega-3 fatty acids and vitamin E can have similar effects, so consult your doctor if you plan to take supplements of this nature. Ensure your doctor knows all the multivitamins you are taking to ensure there are no harmful interactions between their ingredients and anagrelide.

Warnings

Anagrelide may make certain medical conditions worse. Whether the drug is prescribed or not to people with these conditions is the discretion of the prescribing doctor. Dosages may be adjusted to account for increased health risks, or the patient may be monitored more closely than usual.

People with the following conditions, or a history of them, should use anagrelide with caution as the drug could worsen their symptoms:

  • Bleeding problems
  • Congestive heart failure
  • Heart disease
  • Heart rhythm problems
  • Hypotension (low blood pressure)
  • Kidney disease
  • Lung disease

People with the following conditions should not take anagrelide in any circumstances, as doing so could cause very serious and harmful health complications:

  • Congenital Long QT syndrome
  • QT prolongation
  • Hypokalemia
  • Severe liver disease

Hepatic and renal impairment

Individuals with decreased liver or kidney function may find that the effects of anagrelide are increased. This is because the medicine will be removed from the body at a slower rate than normal. Since it will remain in the body for longer, it's platelet-reducing effects will be heightened. Plus, the risk of side effects might be worsened. Doctors may reduce the dosage of anagrelide to account for hepatic or renal impairment or reduce the frequency at which doses are taken. Patients may also require additional monitoring of blood counts.

Elderly patients often have decreased renal impairment due to their age. For this reason, elderly patients are more likely to be administered the lowest dosages of anagrelide. They may also be monitored more closely or more frequently than younger patients.

Pregnancy and breastfeeding

Anagrelide is a pregnancy category 3 drug, which means it should be used with great caution during pregnancy. Adverse reactions were observed during animal reproduction studies involving the drug, but there have been limited studies conducted on the effects of the drug during human pregnancy. The risks of the drug to the fetus are therefore unknown. Consequently, women should only use anagrelide if other treatments are not suitable and if the benefits to the health of the mother far outweigh the potential risk to the fetus.

Similar warnings are given for the use of anagrelide during breastfeeding. There have not been enough studies performed to understand whether the drug is excreted in human milk and, if so, what risk it might pose to a nursing infant. For this reason, women are advised to avoid breastfeeding while taking anagrelide.

Use of aspirin while taking anagrelide

Aspirin, a common painkiller, is an antiplatelet agent and can therefore enhance the effects of anagrelide in reducing platelet count and thinning the blood. It therefore poses the risk of abnormal bleeding if taken with anagrelide. Avoid aspirin unless your doctor has advised that you can take it, and in these instances, take only the amount your doctor has recommended.

You should also take care to avoid over-the-counter (OTC) medications which contain aspirin. Pain, cold and flu, allergy-relief and sleep medications can all contain aspirin. Read the ingredients carefully; sometimes aspirin is referred to as ASA. If you're in doubt, ask a doctor or pharmacist for an OTC remedy which doesn't contain aspirin and is safe to take with anagrelide.

Storage

Anagrelide should be stored in a closed container in a room temperature environment. It should not be exposed to direct light, heat or moisture. The bathroom is therefore not the ideal environment in which to keep the medicine.

Always keep anagrelide away from children and pets by storing it up and away from the ground so that it is not within easy reach. If possible, use containers which have childproof safety caps.

Do not share anagrelide with other people. The drug is available only with a prescription from a doctor, and could be harmful to those who are not prescribed it.

Do not simply throw anagrelide in the trash without first checking with your healthcare provider about how to safely dispose of unused medicines. Avoid flushing it down the toilet or pouring it down the train, too. Don't hold on to unused or expired medicine, and never consume anagrelide capsules which are beyond their expiry date.

Summary

Anagrelide is an antiplatelet agent which works to reduced blood platelets. It is usually prescribed to individuals with thrombocythemia, in which the body produces excessive levels of some blood platelets. The condition poses risks of abnormal bleeding and blood clots. Anagrelide is sometimes prescribed to children with chronic myelogenous leukemia which can also cause abnormal platelet production.

The major risks associated with anagrelide are related to the cardiovascular system and bleeding. Chest pain or discomfort, labored breathing, wheezing, pounding or irregular heartbeat should always be referred to a doctor as a matter of urgency. You should also look out for abnormal bruising or bleeding or flat, purple patches underneath the skin.

It is vital to avoid aspirin while taking anagrelide, unless a doctor recommends it. Aspirin had antiplatelet properties and can enhance the platelet-reducing effects of anagrelide. Do not use any painkillers that contain aspirin, and look out for aspirin on cold and flu, allergy relief and sleep medications. Sometimes aspirin is referred to as ASA on medicine packaging. If in doubt about the contents of medicine, ask a pharmacist or a doctor.

NSAIDs, SSRIs and a range of other drugs which are antiplatelet agents can also interact with anagrelide and lead to an increased risk of abnormal bleeding or other side effects. Make sure your doctor is aware of all the medicines you are currently taking before you begin anagrelide therapy.

Anagrelide therapy is usually started at 0.5 mg doses, four times each day, or 1 mg doses twice each day, for 7 days. During this time, platelet levels are monitored every two days. Then, the dosage is increased in increments of no more than 0.5mg increments each day, with platelet counts monitored once a week, until platelets are reduced to normal levels. The dosage then remains at this higher level permanently; this is known as the maintenance dosage. If the patient then stops taking anagrelide, their platelet count will begin to rise again within four days.

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Last Reviewed:
December 24, 2017
Last Updated:
April 04, 2018