Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
FOLOTYN vs AGRYLIN
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
FOLOTYN (pralatrexate) is a folate analogue metabolic inhibitor that competes for the reduced folate carrier and folylpolyglutamate synthetase, leading to intracellular accumulation of polyglutamated metabolites that inhibit dihydrofolate reductase (DHFR) and thymidylate synthase, thereby disrupting DNA synthesis and cell proliferation.
Agrylin (anagrelide) inhibits cyclic nucleotide phosphodiesterase III (PDE3) and reduces platelet production by interfering with megakaryocyte maturation and proliferation, likely via inhibition of cyclic AMP phosphodiesterase and modulation of intracellular calcium levels.
Relapsed or refractory peripheral T-cell lymphoma (PTCL)
Essential thrombocythemia (ET) to reduce elevated platelet counts and the risk of thrombotic complications
3.0 mg/m2 intravenously over 3-5 minutes on days 1, 8, and 15 of a 28-day cycle.
Adults: 0.5 mg orally once or twice daily, increased by 0.5 mg every 2 weeks to maintain platelet count <600,000/µL. Maximum dose: 10 mg/day.
Terminal elimination half-life is approximately 4–6 hours; clinical context: supports weekly dosing schedule.
Terminal elimination half-life: 1.3–1.5 days (31–36 hours) in patients with ET; allows twice-daily dosing.
Pralatrexate is primarily metabolized via hepatic metabolism; specific enzymes not fully characterized. It is not a significant substrate for CYP450 enzymes.
Primarily metabolized by CYP1A2 to the active metabolite 3-hydroxyanagrelide, and to a lesser extent by CYP2C19 and CYP2D6.
Primarily renal excretion (approximately 80% of the dose recovered in urine over 24 hours, with about 60% as unchanged drug); biliary/fecal elimination accounts for <1%.
Renal: 80% (primarily unchanged drug), Biliary/Fecal: 5%
Approximately 67% bound to human plasma proteins, primarily albumin.
82–88% bound to plasma proteins (primarily albumin).
Volume of distribution at steady state is approximately 0.5 L/kg (range 0.3–0.7 L/kg), indicating distribution into total body water with some tissue binding.
30–36 L (approximately 0.45–0.5 L/kg for a 70 kg adult); indicates extensive tissue distribution.
Only intravenous administration is approved; oral bioavailability has not been established (not for oral use).
Oral: 65–80% (median 73%)
No specific dose adjustment recommended; use caution in severe renal impairment (Cr Cl <30 m L/min) due to limited data.
No specific GFR-based recommendations; use with caution in renal impairment (Cr Cl <50 m L/min) and monitor closely.
Child-Pugh A: 2.0 mg/m2. Child-Pugh B: 1.5 mg/m2. Child-Pugh C: not recommended.
Child-Pugh A: No adjustment. Child-Pugh B or C: Reduce initial dose by 50% and titrate cautiously.
Not approved for pediatric use; safety and efficacy not established.
Children ≥7 years: 0.5 mg orally once or twice daily; adjust based on platelet response. Maximum: 10 mg/day. Not established for <7 years.
No specific dose adjustments; monitor for renal function and toxicity as elderly patients may have reduced organ function.
No specific adjustment; start at lower end of dosing range (0.5 mg twice daily) and monitor renal function and platelet counts closely.
WARNING: FOLOTYN may cause severe or fatal mucositis, thrombocytopenia, and other hematologic toxicities. Administer with close monitoring, and manage with dose modifications and supportive care as needed.
None
Mucositis, hematologic toxicity (including thrombocytopenia, neutropenia, anemia), dermatologic reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis), tumor lysis syndrome, hepatotoxicity, and renal toxicity. Monitor complete blood counts, liver function, renal function, and mucositis. Dose adjustments required for toxicity.
Cardiovascular risks: increased risk of ventricular tachycardia, QTc prolongation, and heart failure; use caution in patients with known cardiac disease.,Hematologic effects: monitor complete blood counts regularly due to risk of anemia, leukopenia, or thrombocytopenia.,Hepatic impairment: reduce dose in patients with moderate to severe hepatic impairment.,Renal impairment: use with caution in severe renal impairment.
Hypersensitivity to pralatrexate or any component of the formulation.
Severe hepatic impairment,Known hypersensitivity to anagrelide or any component of the formulation
Avoid grapefruit and grapefruit juice due to potential CYP3A4 interaction leading to increased toxicity. No other specific food restrictions.
Grapefruit and grapefruit juice should be avoided as they may increase anagrelide plasma concentrations. No other specific dietary restrictions; however, maintain adequate hydration to reduce risk of crystalluria.
FOLOTYN (pralatrexate) is a folate analog metabolic inhibitor; based on its mechanism of action and animal studies, it is expected to cause fetal harm when administered to a pregnant woman. In animal reproduction studies, pralatrexate caused embryo-fetal toxicity and malformations at doses below the recommended human dose. There are no adequate and well-controlled studies in pregnant women. Advise pregnant women of the potential risk to a fetus. During first trimester: high risk of teratogenicity (neural tube defects, cardiovascular malformations). Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and fetal death.
Pregnancy Category C. Anagrelide is not recommended in pregnancy. Animal studies have shown embryotoxicity and teratogenicity (e.g., increased fetal resorptions, skeletal anomalies) at doses less than the human therapeutic dose. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefit justifies potential risk to fetus. First trimester: Avoid due to organogenesis risk. Second and third trimesters: Unknown risks; consider alternative therapy.
No data are available regarding the presence of pralatrexate in human milk, effects on the breastfed infant, or effects on milk production. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with FOLOTYN and for at least 1 week after the last dose. M/P ratio: unknown.
It is not known whether anagrelide is excreted in human milk. No M/P ratio is available. Due to potential for serious adverse reactions in breastfed infants (e.g., thrombocytopenia, cardiovascular effects), advise women not to breastfeed during treatment and for at least 7 days after last dose.
Physiologic changes in pregnancy can alter drug pharmacokinetics, but there are no established dosing guidelines for FOLOTYN during pregnancy. Dose adjustments should be based on toxicity monitoring (e.g., mucositis, myelosuppression). Due to potential for teratogenicity, avoid use in pregnancy unless benefit outweighs risk. No specific dose adjustments recommended for pregnancy alone.
No specific pharmacokinetic studies in pregnancy. Pregnancy-induced plasma volume expansion may lower drug concentrations, potentially requiring dose adjustment to maintain therapeutic effect. However, due to teratogenicity risks, avoid use in pregnancy. If necessary, start at lowest effective dose (0.5 mg/day) and titrate based on platelet count monitoring, not to exceed 10 mg/day.
Administer intramuscularly; rotate injection sites. Premedicate with corticosteroid, antihistamine, and antipyretic to reduce infusion reactions. Monitor for tumor lysis syndrome, hepatotoxicity, and myelosuppression. Dose adjustment required for renal impairment (Cr Cl <50 m L/min). Contraindicated in pregnancy.
Agrylin (anagrelide) is a phosphodiesterase III inhibitor used to reduce platelet counts in essential thrombocythemia. Monitor platelet count weekly during titration; target <600,000/µL. Avoid in patients with severe hepatic impairment (Child-Pugh C). Use with caution in cardiac disease due to risk of QT prolongation and arrhythmias. Anagrelide may increase bleeding risk, especially when combined with anticoagulants or NSAIDs. Discontinue 4-5 days before elective surgery.
This medicine is given as an injection into a muscle, usually once weekly.,You may receive medications before your dose to prevent allergic reactions.,Report any signs of infection, unusual bleeding, or bruising promptly.,Avoid pregnancy during treatment; use effective contraception.,Limit alcohol intake to reduce liver strain.,Avoid grapefruit and grapefruit juice as they may increase side effects.
Take exactly as prescribed; do not skip doses or double up.,Report any signs of bleeding (easy bruising, nosebleeds, black/tarry stools) or palpitations immediately.,Avoid NSAIDs like ibuprofen and aspirin unless directed by your doctor.,Do not consume grapefruit or grapefruit juice while taking this medication.,Inform all healthcare providers (including dentists) that you are on anagrelide.,Store at room temperature away from moisture and heat.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about FOLOTYN vs AGRYLIN, answered by our medical review team.
FOLOTYN is a Antineoplastic Agent that works by FOLOTYN (pralatrexate) is a folate analogue metabolic inhibitor that competes for the reduced folate carrier and folylpolyglutamate synthetase, leading to intracellular accumulation of polyglutamated metabolites that inhibit dihydrofolate reductase (DHFR) and thymidylate synthase, thereby disrupting DNA synthesis and cell proliferation.. AGRYLIN is a Antineoplastic Agent that works by Agrylin (anagrelide) inhibits cyclic nucleotide phosphodiesterase III (PDE3) and reduces platelet production by interfering with megakaryocyte maturation and proliferation, likely via inhibition of cyclic AMP phosphodiesterase and modulation of intracellular calcium levels.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between FOLOTYN and AGRYLIN depend on the specific clinical indication. These are both Antineoplastic Agent agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of FOLOTYN is: 3.0 mg/m2 intravenously over 3-5 minutes on days 1, 8, and 15 of a 28-day cycle.. The standard adult dose of AGRYLIN is: Adults: 0.5 mg orally once or twice daily, increased by 0.5 mg every 2 weeks to maintain platelet count <600,000/µL. Maximum dose: 10 mg/day.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between FOLOTYN and AGRYLIN in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. FOLOTYN is classified as Category C. FOLOTYN (pralatrexate) is a folate analog metabolic inhibitor; based on its mechanism of action and animal studies, it is expected to cause fetal harm when administered to a pregna. AGRYLIN is classified as Category C. Pregnancy Category C. Anagrelide is not recommended in pregnancy. Animal studies have shown embryotoxicity and teratogenicity (e.g., increased fetal resorptions, skeletal anomalies. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.