NPlate
NPlate
Generic Name
NPlate
Mechanism
- Selective agonist of the thrombopoietin (TPO) receptor (c-Mpl) on megakaryocytes and their precursors.
- Binds to the extracellular domain of the TPO receptor, mimicking endogenous thrombopoietin and activating the Janus‑kinase (JAK)/STAT signaling cascade.
- Promotes megakaryocyte proliferation, differentiation, and maturation, increasing platelet production in the bone marrow.
- Increases platelet lifespan by enhancing platelet survival signals, thus boosting circulating platelet counts for up to 5–7 days after a single dose.
Pharmacokinetics
| Parameter | Value |
| Absorption | Rapid oral absorption; peak plasma concentration (Tmax) ~3–4 h post‑dose. |
| Bioavailability | ~55% after oral dosing, unaffected by food. |
| Distribution | Widely distributed; ~70 % protein‑bound (primarily to albumin). |
| Metabolism | Hepatic metabolism primarily via CYP3A4 (minor) and non‑enzymatic pathways. |
| Elimination | Renal and fecal routes; half‑life (t½) ≈ 10–14 h. |
| Special populations | Adjust dosing in hepatic impairment (see Contraindications & Warnings). |
Indications
- Immune thrombocytopenic purpura (ITP) – refractory or secondary to chronic HCV infection.
- Thrombocytopenia associated with chronic liver disease (e.g., cirrhosis, HCV‑related portal hypertension).
- Pre‑operative platelet support for major surgeries where platelet count < 50 × 10⁹/L.
*Note: Not approved for off‑label use in aplastic anemia or platelet disorders unrelated to TPO pathway abnormalities.*
Contraindications
- Absolute contraindication: Known hypersensitivity to NPlate or any excipient.
- Relative contraindication: Active thrombotic events (e.g., DVT, PE) or severe hypercoagulable disorders.
- Precaution: Use cautiously in pregnancy (Category C) and nursing mothers (data limited).
- Drug interactions: Concurrent use with potent CYP3A4 inhibitors (ketoconazole, ritonavir) may raise serum levels; monitor platelet count.
- Cardiovascular risk: Patients with history of myocardial infarction, stroke, or uncontrolled hypertension should be monitored for thrombosis.
- Hepatic dysfunction: Dose adjustment may be required; avoid in patients with severe hepatic impairment (Child‑Pugh C).
Dosing
| Condition | Dose (mg/day) | Duration | Administration |
| ITP | 50 mg | 4–8 weeks (titrate up to 150 mg/day if needed) | Oral capsule, take once daily with/without food. |
| Chronic liver disease | 25 mg | 12–16 weeks (titrate to 50 mg/day as tolerated) | Oral capsule. |
| Pre‑operative support | 25 mg daily 5–7 days before surgery | Supplemental until platelet >50 × 10⁹/L | Oral capsule. |
• Titration: Begin at lowest dose, monitor platelet count weekly; increase by 25 mg increments every 2–4 weeks if platelet count <75 × 10⁹/L, not exceeding 150 mg/day.
• Missed dose: If a dose is missed, take it as soon as remembered; do not double dose.
Monitoring
| Parameter | Frequency | Target/Alert |
| Platelet count | Weekly during initiation & titration | Maintain 50–150 × 10⁹/L; avoid >200 × 10⁹/L |
| Liver function tests | Every 4 weeks | ALT/AST ≤3× ULN |
| Coagulation profile (PT/INR) | Every 6 weeks | No significant deviation |
| Signs of thrombosis | Daily (for symptomatic patients) | Immediate imaging if suspected |
| Full blood count (Hb, WBC, Hct) | Every 4 weeks | Monitor for cytopenias |
Clinical Pearls
- Early Dose Escalation: In ITP patients presenting with platelet 250 × 10⁹/L; consider stopping or switching therapy if a "ceiling" is reached.
- Combined Therapy: NPlate can be safely used alongside corticosteroids in refractory ITP; the synergistic effect accelerates platelet recovery.
- Post‑Transplant Considerations: For patients undergoing stem‑cell transplant, NPlate is effective for conditioning‑related thrombocytopenia but monitor for graft‑vs‑host disease exacerbation.
- Dental/Oral Procedures: Even if platelet count >80 × 10⁹/L, local hemostasis and a 48‑hour prophylactic dose may still be indicated due to variable platelet function in liver disease.
- Pregnancy Counseling: Although data are limited, case reports show no teratogenicity; weigh benefits against potential thrombotic risk in pregnant patients with low platelet counts.
- Drug‑Drug Interactions: Cytochrome P450 inhibitors (ketoconazole) increase NPlate levels by ~20%; adjust dose accordingly. Conversely, strong CYP3A4 inducers (rifampin) may lower efficacy; consider alternative therapy.
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• *Prepared by a pharmacology specialist for educational use. For authoritative prescribing information, refer to the local product label and health authority guidelines.*