Eltrombopag, a novel Thrombopoietin (TPO) Receptor Agonist: An overview

T. Noorul Sahin

Clinical pharmacist Kauvery Hospital, Thennur, Trichy.

Drug Information

  1. Tab. Eltrombopag
  2. Molecule name: Eltrombopag
  3. Chemical Class-Biphenyls Derivatives
  4. Habit Forming: No
  5. Pharmacological class: Thrombopoietin (TPO) receptor agonist
  6. Therapeutic class: Anticoagulant
  7. Rebopag Tablet 50mg. Available at 12.5, 25, 50, 75 mg tablets.

Background

  1. It is an anticoagulant drug belonging to the thrombopoietin (TPO) receptor agonist category, containing the active ingredient Eltrombopag.
  2. It is used in the treatment of low platelet counts caused by primary immune thrombocytopenia (ITP) or hepatitis C (HCV) infection.
  3. ITP refers to an autoimmune disorder in which the immune system destroys platelets.
Monitoring-Parameters-1

Indications

  1. Chronic Immune Thrombocytopenia (ITP).
  2. Chronic Hepatitis C-associated Thrombocytopenia.
  3. Severe Aplastic Anemia
Monitoring-Parameters-2

Mechanism of Action

Eltrombopag selectively binds to the trans-membrane domain of the receptor. It stimulates megakaryocytopoiesis through the Janus Kinase / Signal Transducer and Activator of the Transcription (JAK/STAT) signalling pathway.

Cautions

  1. Not indicated for the treatment of patients with myelodysplastic syndromes (MDS)
  2. Thrombotic/thromboembolic complications
  3. Portal vein thrombosis
  4. Risk of thrombocytopenia and haemorrhage after discontinuation
  5. May develop or worsen cataracts
  6. Hepatotoxicity.

Monitoring Parameters

Measure ALT, AST, and bilirubin prior to initiation of therapy, then every 2 weeks during treatment.

Monitoring-Parameters-3

Drug-Drug Interactions

  1. Anti-cancer drugs (methotrexate, topotecan),
  2. Rheumatoid Arthritis (cyclosporine, azathioprine),
  3. HIV/AIDS drugs (lopinavir, ritonavir),
  4. Corticosteroids and steroid hormones (danazol),

Side Effects

  1. Nausea
  2. Diarrhoea
  3. Upper respiratory tract infection
  4. Vomiting
  5. Increased liver enzymes
  6. Muscle pain
  7. Urinary tract infection.

Drug-Food Interaction

Take Rebopag 50 mg at least 2 h before or four hours after consuming dairy products, calcium-enriched foods, and fortified juices since they interfere with the absorption of Rebopag 50 mg.

Drug-Disease Interaction

People with blood clots, clotting disorders (Factor V Leiden), and blood disorders like blood cancer, myelodysplastic syndrome, cataracts, and liver or kidney diseases should consult the doctor before taking Rebopag 50 mg.

Case Presentation

Case 1

A 72-year-old male with Parkinsonism on medications was evaluated for tiredness and found to have pancytopenia.

Diagnosis

  1. Severe Aplastic Anemia
  2. PNH Clone-Present.
  3. On Antithymocyte Globulin Therapy Since 02.09.2023
  4. Febrile Neutropenia
  5. Parkinsonism on treatment.

Course

  • Physical examination revealed features of Parkinsonism and pallor but no lymphadenopathy or organomegaly. Lab evaluation revealed pancytopenia with macrocytic blood picture and lymphocyte predominant differential count. Reticulocyte count was inappropriately low, LDH was within normal limits and hepatorenal functions were normal.
  • Peripheral smear revealed no atypical cells. Bone marrow biopsy and aspirate were consistent with that of aplastic anemia. PNH clone for immunophenotyping was positive.
  • He was advised ATG therapy with Cyclosporine and Eltrombopag
  • After informed consent, he was administered Anti Thymocyte Globulin 1750 mg IV/day as an infusion for 4 days from 02.09.2023 to 05.09.2023. Infusions were uneventful. Febrile, neutropenia during ward stay was managed with broad-spectrum IV antibiotics after drawing blood cultures. Blood cultures were sterile at the end of 72 hrs.
  • He received 6 units of platelets and 1 unit of packed red cells during his ward stay. Steroids were given as prophylaxis against serum sickness
  • Tab. Eltrombopag 100 mg/day was given from 06.09.2023. He was discharged and advised to review in OPD for continuing further therapy.
  • Still patient is on treatment, in OPD basis.

Case-2

A 72-year-old male with severe aplastic anaemia and post antithymocyteglobulin therapy patient was admitted for blood transfusion.

Past Medical History

H/o giddiness

Diagnosis

Severe Aplastic Anemia

Paroxysmal Nocturnal Hemoglobinuria Clone-Present

Antithymocyteglobulin Therapy on 27.09.2022

Ischemic stroke

Hypertensive Heart Disease

Cyclosporine-induced Acute Kidney Injury-resolved

Sirolimus Induced nephrotoxicity

Asteatotic Eczema

Admitted for Blood Transfusion.

Course

  • A case of severe aplastic anaemia and post antithymocyteglobulin therapy patient was admitted for blood transfusion. He received 2 units of platelets and 4 units packed red cells uneventfully. In view of, Cyclosporine and Sirolimus induced nephrotoxicity both agents were not rechallenged.
  • Peripheral smear revealed no atypical cells. Bone marrow biopsy and aspirate were consistent with that of aplastic anemia. PNH clone for immunophenotyping is positive.
  • He was advised ATG therapy with Cyclosporine and Eltrombopag.
  • As bi-cytopenia persisted after one year of ATG therapy, a repeat bone marrow examination, cytogenetics and NGS for myeloid mutations were sent and reports are awaited. He had leg pain during his ward day, orthopaedical opinion was sought and they found no obvious abnormalities. Danazol-induced muscle pain was considered. He was discharged and advised to review in OPD after 2 weeks with pending reports.
  • Still patient on treatment in OPD basis

Case-3

A 23-year-old female with immune thrombocytopenia with a recent intracerebral bleed (01.10.2023) was treated initially with IVG therapy, steroids and Eltrombopag. She responded and she was discharged on 05.10.2023 without any neuro deficits. However, within 48 hours of discharge, she came back to the hospital on 07.10.2023 with a severe headache. CT brain done outside showed previous left parietal bleed and CVT. She had no neuro deficits

Diagnosis

Immune Thrombocytopenia

Intracerebral Bleed (Left Anterior Parietal Region)

Hemorrhagic Ovarian Cyst

IVIg Therapy on 01.10.2023

Iron Deficiency Anaemia.

Course

  • She was readmitted with the above-mentioned complaints. Physical examination was unremarkable. She had no neurological deficits. Platelet count was 124000/cu.mm and haemoglobin was 10.5 g%. Hepatorenal functions were normal. CVT was suspected and then an urgent MRI brain revealed multi-focal intracerebral bleeds in left high parietal and bilateral frontal regions and a thin subdural haemorrhage involving both front parietal regions, straight and right transverse sigmoid sinuses were hypoplastic.
  • She was managed with steroids, Eltromobopag and analgesics. Neurologist opinion was sought and conservative management was advised. She symptomatically became better with the above management and hydration. She is discharged and advised to review in OPD on 22.10.2023.
  • Still patient on treatment in OPD basis.

 

References

  1. Eltrombopag. https://reference.medscape.com/drug/promacta-eltrombopag-342178
  2. Gregory Cheng , Eltrombopag, a thrombopoietin- receptor agonist in the treatment of adult chronic immune thrombocytopenia: a review of the efficacy and safety profile, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573439/
  3. Thrombopoietin and thrombopoietin receptor agonists, https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/eltrombopag
T.-Noorul-Sahin

T. Noorul Sahin

Clinical Pharmacist

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