Unloxcyt
Unloxcyt
Generic Name
Unloxcyt
Mechanism
- Selective CDK4/6 inhibition: Blocks phosphorylation of retinoblastoma protein (Rb), preventing progression from G₁ to S phase in proliferating tumor cells.
- Synergistic with endocrine therapy: Enhances apoptotic response when combined with aromatase inhibitors or fulvestrant.
- Minimal off‑target activity: Low affinity for CDK1, CDK2, and CDK9, reducing cytotoxicity in normal tissues.
Pharmacokinetics
| Parameter | Data |
| Bioavailability | 70 % (oral, with food). |
| Peak plasma concentration (Tₘₐₓ) | 1–2 h post‑dose. |
| Half‑life (t½) | 15 h (steady‑state ~48 h). |
| Metabolism | Primarily CYP3A4 oxidation; minor CYP2C19. |
| Elimination | 70 % fecal (biliary), 30 % renal; urine unchanged ~5 %. |
| Drug‑drug interactions | Strong CYP3A4 inhibitors (ketoconazole, ritonavir) ↑ exposure; inducers (rifampin, carbamazepine) ↓ exposure. |
| Special populations | No dose adjustments in mild‑moderate hepatic or renal impairment; pregnancy: category B (limited data). |
Indications
- Adjuvant: HR+ HER2‑negative breast cancer following surgery, radiotherapy, or chemotherapy.
- Metastatic: HR+ HER2‑negative breast cancer, metastatic or locally advanced, as monotherapy or in combination with endocrine agents.
- Pre‑clinical: Investigational use in non‑small cell lung carcinoma with CDK4/6 dependence (Phase II).
Contraindications
| Category | Key Points |
| Contraindications | Known hypersensitivity; severe hepatic impairment (Child‑Pugh C). |
| Warnings | Hematologic suppression (neutropenia, anemia, thrombocytopenia); hepatotoxicity (↑ALT/AST); QT prolongation (monitor ECG if baseline >440 ms or with QT‑prolonging drugs). |
| Precautions | Pregnancy & lactation: potential teratogenicity; use effective contraception. |
| Drug‑Drug | Avoid concomitant strong CYP3A4 inhibitors/inducers unless dose adjusted. |
Dosing
| Setting | Dosage Form | Dose | Schedule | Notes |
| Adjuvant | Oral tablet | 150 mg | QD with food | 2‑day break every 21‑day cycle. |
| Metastatic | Oral tablet | 150 mg | QD (continuous) | Initiate with 50 mg QD for 3 days to assess tolerance. |
| Rechallenge | 100 mg QD | 4‑week cycles | If prior neutropenia resolved. |
• Administration: Take with food to enhance absorption; do not crush or chew.
• Missed dose: Skip if >12 h; else take as soon as remembered.
Monitoring
| Modality | Frequency | Trigger for Action |
| CBC | Baseline, day 7, every 2 weeks (cycle) | ↓ANC <1.0 × 10⁹/L → dose hold/adjust; 3× ULN → hold; >5× ULN → discontinue. |
| ECG | Baseline, week 4, every 3 months | QTc >450 ms (men), >470 ms (women) → review electrolytes. |
| Electrolytes | Baseline, every 2 weeks | K⁺ <3.5 mmol/L or Mg²⁺ <1.5 mmol/L → supplement. |
| Pregnancy Test | Baseline (women of childbearing potential) | Positive → discontinue and discuss contraception. |
Clinical Pearls
- Neutropenia Mitigation: Pre‑emptive G‑CSF is *not* recommended for routine use; hold drug until ANC >1.5 × 10⁹/L.
- Dose Optimization: Use the 50 mg “titration” period in patients with pre‑existing cytopenias; shift to 100 mg if tolerated.
- Drug Interaction Matrix: A “red‑zone” for ritonavir/ketoconazole; “yellow” for rifampin; “green” for typical oral contraceptives.
- Elderly & Renal: No creatinine‐based dose adjustment; monitor for cumulative toxicity.
- Immuno‑oncology: Avoid simultaneous use of checkpoint inhibitors due to overlapping hepatotoxicity profile.
- Patient Education: Encourage reporting of fever/flu‑like symptoms immediately; counsel on regular blood work, hydration, and maintaining a low‑dose, consistent schedule.
> Bottom line: *Unloxcyt* provides a highly selective blockade of CDK4/6, translating into effective cell‑cycle arrest with a manageable safety profile when supported by vigilant monitoring and dose‑adaptation strategies.