Clozapine
Severe
Database
Additive marrow toxicity
Avoid combination
Source: Kimi deep-research + Cla
Drug reference
melflufen
Peptide-drug conjugate alkylating agent (antineoplastic)
START
40 mg IV over 30 min, day 1 of 28-day cycle (+ dexamethasone)
TYPICAL MAX
40 mg every 28 days
STOP IF
Severe cytopenias/bleeding or serious infection
WATCH
CBC (platelets/ANC) before each cycle, infection, bleeding
CDSCO approvedATC L01XL04
KDIGO 2024 + manufacturer label
- ONSET
- 6min · infusion start
- PEAK
- 30min · end infusion
- t½
- 2min · parent ~2 min
- DURATION
- 4w · q28d cycle
EXCRETION
Via melphalan hydrolysis/renal elimination
route + CYP
INTERACTIONS
3 major
SEVERE in our sources
PREGNANCY
Can cause fetal harm — contraindicated; effective contraception required.
FDA category + note
Top interactionssee all 5 →
- ClozapineSevereDatabaseKimi deep-research + Cla
- Live VaccinesSevereDatabaseKimi deep-research + Cla
- Other Myelosuppressive ChemoSevereDatabaseKimi deep-research + Cla
Mechanism
Lipophilic peptide-conjugated alkylator (melphalan flufenamide) that is rapidly taken up by tumour cells and cleaved by aminopeptidases (enriched in myeloma cells) to release alkylating melphalan, causing DNA crosslinking and apoptosis.
Indications
Relapsed/refractory multiple myeloma (with dexamethasone; restricted/withdrawn in some regions — specialist use)
Dosing
- Adult
- 40 mg IV over 30 min on day 1 of each 28-day cycle, with dexamethasone; adjust for cytopenias.
- Pediatric
- Not established.
- Renal adjustment
- eGFR ≥45: no adjustment; <45 not recommended/limited data.
- Hepatic adjustment
- Caution; not studied in moderate–severe.
- Geriatric
- Increased toxicity risk; monitor closely.
- Max dose
- 40 mg IV every 28 days
Pharmacokinetics
Onset
Cytoreduction over cycles
Peak effect
End of infusion (rapid intracellular cleavage)
Duration
28-day cycle
Half-life
Very short parent (~2 min); released melphalan longer
Bioavailability
IV 100%
Protein binding
High (lipophilic)
Metabolism
Aminopeptidase cleavage to melphalan
Excretion
Via melphalan elimination (hydrolysis/renal)
Contraindications
- Severe hypersensitivity
- Pregnancy
- Caution: significant cytopenias, infection
Side effects
Common
ThrombocytopeniaNeutropeniaAnaemiaNauseaFatigueDiarrhoea
Serious
- Severe myelosuppression/bleeding
- Serious infections
- Secondary malignancies
- Possible decreased survival in some subgroups (OCEAN — restricted use)
Pregnancy & lactation
Pregnancy
Can cause fetal harm — contraindicated; effective contraception required.
Lactation
Contraindicated during therapy.
Drug interactions
Live Vaccines
Severe
Database
Severe immunosuppression
Avoid live vaccines
Source: Kimi deep-research + Cla
Other Myelosuppressive Chemo
Severe
Database
Additive marrow suppression
Per protocol; supportive care
Source: Kimi deep-research + Cla
Anticoagulants
Moderate
Database
Thrombocytopenia + bleeding
Monitor platelets/bleeding
Source: Kimi deep-research + Cla
Nephrotoxic Drugs
Moderate
Database
Altered melphalan clearance
Monitor renal function
Source: Kimi deep-research + Cla
Related guidelines
Ask House about melflufen
Continue into a citation-backed clinical answer with the drug context already attached.
Sources: Harrison 22e·Verified: 2026-05-20 · House clinical team·Cockpit curated: 2026-05-20