| Subclass | Drug (Generic → Brand) | Mechanism of Action | Adult Dosing (common regimens) | Pediatric Dosing | Renal/Hepatic Adjustment | Major Toxicities | Monitoring |
|---|---|---|---|---|---|---|---|
| Folate Antagonists | Methotrexate (MTX) → Trexall®, Rheumatrex® | Inhibits dihydrofolate reductase (DHFR) → ↓ thymidylate/purine synthesis | Low dose (15–30 mg PO weekly in ALL maintenance); High dose (1–12 g/m² IV over 4–36h with leucovorin rescue) | 20–40 mg/m² IV weekly or protocol-based | Reduce if CrCl <60 mL/min; hold if bilirubin >5 mg/dL | Myelosuppression, mucositis, hepatotoxicity, renal precipitation, neurotoxicity (HDMTX) | CBC, LFTs, renal function, MTX levels (HDMTX), urine alkalinization |
| Pemetrexed → Alimta® | Multi-targeted antifolate (DHFR, TS, GARFT) | 500 mg/m² IV q21d (NSCLC, mesothelioma) + folic acid & B12 supplementation | Limited pediatric use (investigational) | Avoid if CrCl <45 mL/min | Myelosuppression, rash, mucositis, fatigue | CBC, renal, hepatic function | |
| Pralatrexate → Folotyn® | Antifolate; inhibits DHFR & polyglutamated for retention | 30 mg/m² IV weekly x6 in 7-week cycle (PTCL) | Limited pediatric use | Avoid in severe renal impairment; adjust for hepatic | Mucositis, myelosuppression, fatigue | CBC, mucositis checks, renal/hepatic | |
| Pyrimidine Analogs | 5-Fluorouracil (5-FU) → Adrucil® | Converted to FdUMP → inhibits thymidylate synthase & incorporates into RNA/DNA | Bolus: 400–600 mg/m² IV; Continuous infusion: 2400–3000 mg/m² over 46h | Pediatric dosing less common; protocol-based | Caution in hepatic impairment | Bolus: myelosuppression; Infusion: diarrhea, mucositis, hand-foot syndrome | CBC, mucositis, skin, DPD deficiency risk |
| Capecitabine → Xeloda® | Oral prodrug of 5-FU (tumor-selective activation) | 1250 mg/m² PO BID x14d q21d | Limited pediatric use | Reduce if CrCl <50; contraindicated <30 | Diarrhea, HFS, mucositis, myelosuppression | CBC, renal, hepatic | |
| Cytarabine (Ara-C) → Cytosar-U® | Pyrimidine analog → inhibits DNA polymerase & chain termination | Standard dose: 100–200 mg/m²/day IV; High dose: 1–3 g/m² IV q12h x2–6d | 100–200 mg/m²/day IV (protocol-based) | No renal adj (except HiDAC >3 g/m²); caution hepatic impairment | Myelosuppression, cerebellar toxicity, conjunctivitis, mucositis | CBC, neuro exam, eye exam, LFTs | |
| Gemcitabine → Gemzar® | Pyrimidine analog → inhibits ribonucleotide reductase & DNA polymerase | 1000 mg/m² IV weekly x3 q28d | Limited pediatric use | Caution in hepatic impairment | Myelosuppression, flu-like symptoms, pulmonary toxicity, HFS | CBC, pulmonary function | |
| Azacitidine → Vidaza® | Hypomethylating agent; incorporates into DNA/RNA → epigenetic reactivation of silenced genes | 75 mg/m² SC or IV x7d q28d (MDS, AML) | Pediatric dosing limited | Caution hepatic impairment | Myelosuppression, GI toxicity, injection site rxn | CBC, renal, hepatic | |
| Decitabine → Dacogen® | DNA hypomethylating agent | 20 mg/m² IV daily x5d q28d | Investigational pediatric dosing | Caution hepatic impairment | Myelosuppression, fatigue, infections | CBC, hepatic | |
| Purine Analogs | 6-Mercaptopurine (6-MP) → Purinethol® | Inhibits purine synthesis; incorporates into DNA/RNA | 50–100 mg/m² PO daily (ALL maintenance) | 50 mg/m² PO daily (ALL) | Reduce in TPMT/NUDT15 deficiency; ↓ dose 50–75% if given with allopurinol | Myelosuppression, hepatotoxicity, GI | CBC, LFTs, TPMT/NUDT15 genotype |
| 6-Thioguanine (6-TG) | Similar to 6-MP; purine analog | 2 mg/kg/day PO | Pediatric ALL (protocol-based) | Hepatic dose adjustment | Myelosuppression, hepatotoxicity (veno-occlusive disease) | CBC, LFTs | |
| Fludarabine → Fludara® | Inhibits DNA polymerase & ribonucleotide reductase | 25 mg/m² IV daily x5d q28d | Pediatric dosing limited | Caution renal impairment | Profound immunosuppression, myelosuppression, neurotoxicity | CBC, CD4 counts, infection monitoring | |
| Cladribine → Leustatin® | Purine analog → inhibits DNA synthesis | 0.09 mg/kg IV daily x7d (hairy cell leukemia) | Used in pediatric protocols (e.g., LCH) | Caution renal/hepatic impairment | Myelosuppression, immunosuppression, fever | CBC, infection signs | |
| Clofarabine → Clolar® | Purine nucleoside analog | 52 mg/m² IV daily x5d q28d (ALL pediatric ≥1 yr) | Approved pediatric ALL | Adjust renal/hepatic | Myelosuppression, hepatotoxicity, capillary leak syndrome | CBC, LFTs, fluids, BP |
Key Pharmacist Pearls
- Folate antagonists (MTX, Pemetrexed, Pralatrexate): require rescue/supportive supplementation (Leucovorin for MTX, folic acid + B12 for Pemetrexed/Pralatrexate).
- Pyrimidine analogs:
- 5-FU: bolus → myelosuppression, infusion → HFS, diarrhea.
- Cytarabine HiDAC → cerebellar toxicity + conjunctivitis (prophylactic steroid eye drops).
- Purine analogs:
- 6-MP: major DDI with allopurinol/febuxostat.
- Fludarabine: T-cell depletion → opportunistic infections (needs PJP prophylaxis).