Generic Name

Promacta

Mechanism

• Binding: Eltrombopag is a non‑peptide small molecule that binds to the intracellular domain of the thrombopoietin receptor (cMpl) on megakaryocytes and precursor cells.
• Signal Transduction: Receptor activation triggers the JAK/STAT, PI3K/AKT, and MAPK pathways, promoting survival, proliferation, and differentiation of megakaryocyte progenitors.
• Outcome: Increases platelet production, elevating platelet counts in patients with chronic immune thrombocytopenia (ITP) or other platelet disorders.

Pharmacokinetics

• Absorption: Oral bioavailability is low (~13 %) due to extensive first‑pass metabolism; food reduces absorption, so it should be taken on an empty stomach (no food ± 1 h).
• Distribution: Highly protein‑bound (~95 %); volume of distribution ~400 mL/kg.
• Metabolism: Primarily hepatic via CYP1A2, CYP2C9, CYP3A4; active metabolites are excreted in bile.
• Elimination: Half‑life ≈ 27 hrs; steady state achieved by day 5–7.
• Drug Interactions: Inhibits absorption when taken with divalent cations (magnesium, calcium, iron, antacids); concomitant use of doxycycline or fluoroquinolones may reduce efficacy.

Indications

• Chronic ITP in adults: refractory to corticosteroid, splenectomy, or other therapies.
• ITP in adults and children 12 yrs or older: failing standard therapy.
• Hepatitis C–related thrombocytopenia: to enable antiviral therapy, in adults & children ≥ 12 yrs.
• Platelet depletion in HIV‑infected patients receiving ritonavir‑boosted protease inhibitors.

Contraindications

• Contraindications:
• Known hypersensitivity to eltrombopag or excipients.
• Active significant liver disease or hepatic failure (ALT/AST > 5× ULN).
• Warnings:
• Thrombosis: Increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE).
• Retained high platelet counts: Must avoid platelet counts > 450 × 10⁹/L to reduce thrombotic risk.
• Pregnancy: Category B; avoid use if possible during pregnancy or lactation unless the benefit outweighs risk.
• Precautions:
• Monitor LFTs and platelet counts closely.
• Avoid alcohol and hepatotoxic drugs.
• Check iron status—iron deficiency can blunt response.

Dosing

• Administration: orally, empty stomach. Avoid taking with multivitamins containing multivalent cations; a 12‑hr separation is recommended.
• Dose adjustments: Reduce by 25 % in mild hepatic impairment, discontinue in moderate–severe hepatic dysfunction.

Adverse Effects

• Common (≥10 %): headache, nausea, constipation, arthralgia, fatigue, rash, dysgeusia.
• Serious:
• Elevated liver enzymes (ALT/AST > 5× ULN).
• Thrombosis (DVT, PE, arterial thrombotic events).
• Secondary popliteal lymphedema (rare).
• Iron overload: due to increased iron uptake.
• Other: hypersensitivity reactions, dizziness, anemia.

Monitoring

• Platelet count: every 3–4 days during titration; then weekly until stable; adjust dose to keep within 50–200 × 10⁹/L.
• Liver function tests (ALT/AST, bilirubin): baseline, every 2 weeks for first 3 months, then monthly.
• Ferritin & iron studies: at baseline, especially in patients receiving multiple transfusions.
• Serum creatinine: baseline and periodically for renal safety.
• Signs of thrombosis: assess for swelling, pain, shortness of breath; if suspected, obtain Doppler US or imaging.

Clinical Pearls

• Avoid concomitant iron or multivalent‑cation supplements (including antacids) on the same day; separate by ≥ 2 hrs to preserve absorption.
• Use the lowest effective dose for the shortest time to reduce thrombotic risk; stop treatment when platelet counts normalize.
• Check ferritin first: patients with iron deficiency ( 5× ULN warrant immediate drug discontinuation and referral for liver support.
• For patients on ritonavir‑boosted HAART, start eltrombopag at 25 mg to minimize drug–drug interactions; titrate cautiously.
• Pregnancy & lactation: limited data—consult obstetrician and review risk/benefit before use.

Keywords: eltrombopag, Promacta, thrombopoietin receptor agonist, ITP treatment, platelet production, liver toxicity, thrombosis risk.