Romiplostim

Romiplostim is a subcutaneous thrombopoietin receptor agonist, an Fc-peptide fusion protein, used for chronic immune thrombocytopenia in adults and children 1 year and over who have not responded to corticosteroids, immunoglobulin or splenectomy.

Classification. Thrombopoietin receptor agonist.

Mechanism. Binds and activates the thrombopoietin receptor, increasing megakaryocyte proliferation and platelet production. It has no sequence homology with endogenous thrombopoietin.

Pharmacokinetics. Absorbed subcutaneously, with peak levels at 7 to 50 hours. Clearance is by the receptor on platelets and megakaryocytes. The half-life is 1 to 34 days (median about 3.5 days).

Chronic immune thrombocytopenia.

• Dose: 1 µg/kg subcutaneously once weekly, based on actual body weight.
• Titration: increase by 1 µg/kg each week until platelets reach 50 × 10⁹/L or more. Reduce by 1 µg/kg if platelets exceed 200 × 10⁹/L for two weeks; hold if above 400 × 10⁹/L and restart at 1 µg/kg lower when under 200 × 10⁹/L.
• Maximum: 10 µg/kg weekly. If there is no response after 4 weeks at the maximum dose, stop. Loading dose: none. Maintenance: the lowest weekly dose that keeps platelets at 50 × 10⁹/L or more.
• Children aged 1 year and over: the same schedule.

Adjustments. Kidney and liver: no adjustment; use caution in hepatic impairment because of thrombosis risk. Age: no adjustment.

Contraindications. Hypersensitivity. Not used for myelodysplastic syndromes outside specialist care.

Warnings. Thromboembolic events, bone marrow reticulin deposition, rebound thrombocytopenia after stopping, progression of myelodysplastic syndrome, and rare neutralising antibodies.

Adverse effects. Headache, arthralgia, fatigue, nasopharyngitis, injection-site reaction.

Interactions. None important. Dose reduction is not needed with corticosteroids or immunoglobulin.

Pregnancy and breastfeeding. Avoid unless the benefit outweighs the risk; breastfeeding data are limited.

Common errors. Dosing on ideal rather than actual weight; stopping suddenly; using for thrombocytopenia of other causes.

Administration. Reconstitute with sterile water for injection; subcutaneous injection once weekly. Store at 2 to 8°C, protected from light.

Baseline. Full blood count, blood film, bone marrow if indicated.

Monitoring. Platelets weekly until stable for 4 weeks, then monthly. After stopping, weekly for 2 to 4 weeks.

Referral and escalation. Refer for thrombosis, lack of response at maximum dose, new cytopenias or blast cells on the film.