Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
TRABECTEDIN vs AGRYLIN
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Trabectedin binds to the minor groove of DNA, forming adducts that lead to DNA strand breaks and inhibition of transcription. It also affects the tumor microenvironment by modulating cytokine production and inhibiting activated macrophages.
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.
Unresectable or metastatic liposarcoma or leiomyosarcoma after prior anthracycline-containing therapy,Metastatic soft tissue sarcoma (EU)
Essential thrombocythemia (ET) to reduce elevated platelet counts and the risk of thrombotic complications
1.5 mg/m² intravenously over 24 hours every 3 weeks.
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 ranges from 26 to 40 hours (mean ~33 hours) in patients with normal hepatic function, allowing for a 3-weekly dosing interval.
Terminal elimination half-life: 1.3–1.5 days (31–36 hours) in patients with ET; allows twice-daily dosing.
Primarily hepatic via CYP3A4; also a substrate of P-glycoprotein.
Primarily metabolized by CYP1A2 to the active metabolite 3-hydroxyanagrelide, and to a lesser extent by CYP2C19 and CYP2D6.
Primarily fecal (approximately 58% of administered dose) with minor renal excretion (about 21% as unchanged drug and metabolites). Biliary excretion accounts for a significant portion of elimination via feces.
Renal: 80% (primarily unchanged drug), Biliary/Fecal: 5%
Approximately 97-98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
82–88% bound to plasma proteins (primarily albumin).
Volume of distribution at steady state is approximately 1000 L (>10 L/kg), indicating extensive tissue distribution and binding.
30–36 L (approximately 0.45–0.5 L/kg for a 70 kg adult); indicates extensive tissue distribution.
Not applicable; administered intravenously. Oral bioavailability is negligible due to extensive first-pass metabolism.
Oral: 65–80% (median 73%)
No dose adjustment required for mild to moderate renal impairment (Cr Cl ≥30 m L/min). Not recommended in severe renal impairment (Cr Cl <30 m L/min) due to lack of data.
No specific GFR-based recommendations; use with caution in renal impairment (Cr Cl <50 m L/min) and monitor closely.
Contraindicated in patients with severe hepatic impairment (Child-Pugh C). For moderate hepatic impairment (Child-Pugh B), reduce starting dose to 0.9 mg/m². For mild hepatic impairment (Child-Pugh A), no dose adjustment but monitor closely.
Child-Pugh A: No adjustment. Child-Pugh B or C: Reduce initial dose by 50% and titrate cautiously.
Safety and efficacy not established in pediatric patients.
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 adjustment recommended based on age alone; monitor renal and hepatic function due to potential age-related decline.
No specific adjustment; start at lower end of dosing range (0.5 mg twice daily) and monitor renal function and platelet counts closely.
Trabectedin is associated with severe and fatal neutropenic sepsis, rhabdomyolysis with renal failure, cardiotoxicity (cardiomyopathy, heart failure), hepatotoxicity, and extravasation leading to tissue necrosis. It should only be administered under the supervision of a qualified healthcare provider experienced in the use of antineoplastic agents.
None
Myelosuppression (neutropenia, thrombocytopenia, anemia), hepatotoxicity (elevated liver enzymes, bilirubin, hepatic failure), cardiotoxicity (LVEF decline, heart failure), rhabdomyolysis, extravasation injury, hypersensitivity reactions, and embryo-fetal 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 trabectedin or any of its excipients, concomitant use with yellow fever vaccine, severe hepatic impairment.
Severe hepatic impairment,Known hypersensitivity to anagrelide or any component of the formulation
Grapefruit and grapefruit juice should be avoided as they may increase trabectedin levels. There are no other specific dietary 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.
Trabectedin is teratogenic based on animal studies. It is contraindicated in pregnancy. First trimester exposure carries high risk of major malformations and pregnancy loss. Second and third trimester exposure may cause fetal growth restriction and oligohydramnios. Effective contraception is required during treatment and for at least 3 months after the last dose.
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.
Unknown if trabectedin is excreted in human milk; however, due to potential serious adverse reactions in breastfeeding infants, women should discontinue breastfeeding during treatment and for at least 3 weeks after the last dose. M/P ratio is not available.
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.
No clinical data are available for dose adjustments during pregnancy. Trabec... is contraindicated in pregnancy; therefore, no dose adjustment is recommended. If inadvertent exposure occurs, immediate discontinuation and supportive care are advised.
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.
Trabectedin is a marine-derived alkylating agent indicated for advanced soft tissue sarcoma (STS) and relapsed platinum-sensitive ovarian cancer. It requires dexamethasone premedication to reduce hepatotoxicity. Monitor liver function tests (LFTs) closely; dose reduction or interruption is needed for transaminase elevation. Administer via central line due to vesicant properties. Consider cardiac monitoring as QT prolongation can occur. Use with caution in patients with hepatic impairment.
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 medication is given intravenously over 24 hours through a central line.,You will receive dexamethasone before each infusion to help prevent liver side effects.,Report any signs of liver problems: yellowing of skin/eyes, dark urine, severe fatigue.,Avoid grapefruit and grapefruit juice during treatment.,Use effective contraception during treatment and for at least 3 months after the last dose.,Do not breastfeed during treatment and for 3 months after the last dose.
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.
"Trabectedin, a potent anticancer agent, inhibits the cytochrome P450 (CYP) enzyme CYP3A4, which is primarily responsible for the metabolism of cyclosporine. When co-administered, trabectedin decreases the clearance of cyclosporine, leading to significantly elevated cyclosporine blood concentrations. This increased exposure raises the risk of cyclosporine-related toxicities, particularly nephrotoxicity, hepatotoxicity, and immunosuppression-related complications, potentially requiring dose adjustments and close monitoring."
"Nilotinib is primarily metabolized by CYP3A4, and trabectedin is a moderate inhibitor of CYP3A4. Concomitant use may increase nilotinib exposure, leading to elevated plasma concentrations and a higher risk of QT prolongation, torsade de pointes, and sudden cardiac death. This interaction requires cautious monitoring and potential dose adjustment."
"Trabectedin, an alkylating agent used for soft tissue sarcoma, is metabolized primarily by CYP3A4. Posaconazole, a potent CYP3A4 inhibitor, can significantly increase trabectedin exposure by reducing its clearance. This elevated concentration may enhance trabectedin-induced hepatotoxicity and myelosuppression, increasing the risk of severe adverse effects such as elevated liver enzymes and febrile neutropenia."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about TRABECTEDIN vs AGRYLIN, answered by our medical review team.
TRABECTEDIN is a Antineoplastic Agent that works by Trabectedin binds to the minor groove of DNA, forming adducts that lead to DNA strand breaks and inhibition of transcription. It also affects the tumor microenvironment by modulating cytokine production and inhibiting activated macrophages.. 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 TRABECTEDIN 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 TRABECTEDIN is: 1.5 mg/m² intravenously over 24 hours every 3 weeks.. 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 TRABECTEDIN 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. TRABECTEDIN is classified as Category C. Trabectedin is teratogenic based on animal studies. It is contraindicated in pregnancy. First trimester exposure carries high risk of major malformations and pregnancy loss. Second. 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.