Anagrelide

Anagrelide is used to reduce abnormally high platelet counts in people whose bone marrow is overproducing platelets due to a myeloproliferative neoplasm (a type of bone marrow disorder).

• Agrylin capsules are indicated for thrombocythemia secondary to myeloproliferative neoplasms — to lower the elevated platelet count, reduce the risk of thrombosis (dangerous blood clots), and relieve associated symptoms including thrombo-hemorrhagic events (episodes of abnormal clotting or bleeding)
• Anagrelide capsules (generic) are indicated for the same condition: thrombocythemia secondary to myeloproliferative neoplasms, with the same goals of lowering platelet counts and reducing clot risk

Anagrelide targets the bone marrow cells called megakaryocytes — the cells responsible for making platelets. It blocks key proteins (transcription factors GATA-1 and FOG-1) that these cells need to fully develop, disrupting their maturation process and reducing their size. The end result: fewer platelets are released into your bloodstream. The exact mechanism isn't fully pinned down, but the platelet-lowering effect is clear and dose-related.

Anagrelide also inhibits an enzyme called PDE3 (phosphodiesterase 3). This PDE3 inhibition doesn't directly reduce platelet production, but it can affect platelet clumping (aggregation) at higher doses and has cardiovascular effects — including widening blood vessels and speeding up the heart rate — which is why heart monitoring is so important during treatment.

Anagrelide capsules are taken by mouth. Adults typically start at a low dose taken several times per day; the dose is then gradually increased over weeks until platelet counts reach a target range. Pediatric patients (age 7 and older) start at a lower daily dose. Dose increases are made slowly — no more than a small step-up per week — and your prescriber will monitor your platelet counts frequently during this adjustment phase.

• Can be taken with or without food — food modestly slows absorption but does not significantly reduce the overall amount absorbed
• Regular blood tests are required, especially during the first weeks, to guide dose adjustments
• If you miss doses or stop taking anagrelide, platelet counts can rise back within days — do not stop without talking to your prescriber
• People with moderate liver impairment need a lower starting dose and extra heart monitoring; anagrelide should be avoided entirely in severe liver impairment

The most common side effects reported in clinical trials include:

More serious reactions — including heart failure, heart attack, serious arrhythmias (abnormal heart rhythms), pulmonary hypertension, significant bleeding, and lung inflammation — have been reported and require immediate medical attention. Tell your doctor right away if you develop chest pain, fainting, worsening shortness of breath, or unusual bleeding.

• Heart rhythm risks (most important): Anagrelide can prolong the QT interval on an ECG and increase heart rate, raising the risk of serious arrhythmias including torsades de pointes and ventricular tachycardia. A heart exam and ECG are required before starting. People with known QT prolongation, congenital long QT syndrome, low potassium levels, or who take QT-prolonging medications should not use anagrelide.
• Heart failure and cardiovascular effects: Because anagrelide inhibits PDE3, it can cause vasodilation (blood vessel widening), palpitations, and may worsen heart failure. Similar drugs in this class have been associated with reduced survival in patients with severe heart failure. Use only when the benefits outweigh the risks in patients with existing heart disease.
• Bleeding risk: Anagrelide increases bleeding risk, especially when combined with aspirin or other blood thinners. Major bleeding events have been reported, most often in people also taking aspirin.
• Pulmonary hypertension: High blood pressure in the arteries of the lungs has been reported. Your doctor should check for signs of this before and during treatment.
• Lung inflammation: Serious lung conditions including interstitial pneumonitis and eosinophilic pneumonia have been reported, sometimes starting weeks to years after beginning treatment. Report new or worsening breathing symptoms promptly.
• Liver impairment: The liver breaks down anagrelide. In moderate liver impairment, drug exposure is much higher than normal — a lower starting dose and close monitoring are required. Anagrelide should be avoided entirely in severe liver impairment.

Anagrelide has several important drug interactions that can raise the risk of serious side effects:

• QT-prolonging drugs (chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, amiodarone, disopyramide, procainamide, pimozide): avoid combining — the risk of dangerous heart rhythm problems is increased
• Other PDE3 inhibitors (cilostazol, milrinone): avoid — can amplify cardiovascular side effects
• Aspirin: combined use increases platelet-inhibiting effects and major bleeding risk — weigh carefully, especially in high-risk patients
• Anticoagulants, NSAIDs, antiplatelet agents, SSRIs: all increase bleeding risk when used alongside anagrelide
• CYP1A2 inhibitors (fluvoxamine, ciprofloxacin): can raise anagrelide blood levels, increasing side effects — monitor closely and adjust dose if needed
• CYP1A2 inducers (omeprazole): can lower anagrelide blood levels, potentially reducing effectiveness — dose adjustment may be needed
• CYP1A2 substrates (theophylline, ondansetron): anagrelide may alter how these drugs behave — monitor for changes in their effects

Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.

• Heart conditions: Tell your doctor if you have heart failure, a slow heart rate, a known or suspected QT interval problem, or any other heart condition — extra monitoring or avoidance may be needed
• Liver disease: Dose adjustments are required for moderate liver impairment; anagrelide must be avoided in severe liver impairment because drug exposure rises dramatically
• Kidney disease: Inform your prescriber — kidney function should be assessed before and during treatment
• Low potassium or electrolyte abnormalities: These increase the risk of dangerous heart rhythms with anagrelide
• Pregnancy: Animal studies showed developmental delays at high doses. Discuss the risks and benefits with your doctor — untreated thrombocythemia also carries pregnancy risks (miscarriage, blood clots, preeclampsia)
• Breastfeeding: Do not breastfeed while taking anagrelide or for one week after your last dose — the drug or its byproducts may pass into breast milk and could harm the infant
• Women who may become pregnant: Anagrelide may impair female fertility based on animal studies — discuss this with your prescriber
• Children under 7: Safety and effectiveness have not been established for children younger than 7 years old
• Older adults: Drug levels can be higher in elderly patients — your prescriber should monitor you carefully, though no overall difference in safety or effectiveness has been found in clinical trials

Taking more anagrelide than prescribed can cause low blood pressure, a fast heart rate (sinus tachycardia), and vomiting. More critically, too much anagrelide can drop your platelet count too low (thrombocytopenia), which increases the risk of serious bleeding.

If an overdose is suspected, stop taking anagrelide and seek medical care immediately. Doctors will monitor platelet counts closely and watch for bleeding complications. Anagrelide dosing can be considered once platelet counts return to a safe range.

Anagrelide disrupts the late stages of megakaryocyte (platelet-producing cell) development, reducing both the size of these cells and the number of platelets they release. At therapeutic doses, it does not significantly affect white blood cell counts or clotting factors, and has only a minor effect on red blood cell measures. At doses higher than those typically used to lower platelet counts, anagrelide's PDE3-inhibiting activity can also reduce platelet clumping (aggregation). As a PDE3 inhibitor, it has cardiovascular effects including widening of blood vessels, increased heart rate, and increased force of heart contractions — effects that require monitoring, especially in people with existing heart disease.

After swallowing an anagrelide capsule, at least 70% is absorbed from the gut, with peak blood levels reached in about 1 hour on an empty stomach. Food slows absorption slightly but doesn't substantially change the total amount absorbed. Anagrelide is broken down mainly by a liver enzyme called CYP1A2 into an active metabolite (3-hydroxy anagrelide), which is then converted to an inactive form. The parent drug and its active metabolite clear the body fairly quickly — with half-lives of roughly 1.5 and 2.5 hours, respectively — so they don't build up with regular dosing. Drug levels can be meaningfully higher in older adults, in children (on a dose-adjusted basis), and especially in people with moderate liver impairment, all of which affects how the dose is managed.

Store at 20°C to 25°C (68°F to 77°F). Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.