PHELINUN (Melphalan) 50 mg: Uses, Dosage & Side Effects
A high-dose alkylating chemotherapy used in stem cell transplant conditioning and the treatment of multiple myeloma, ovarian cancer, and neuroblastoma.
Published: 31 October 2025 · Last reviewed: 2 February 2026 · Evidence-based: EMA SmPC, FDA, BNF, Cochrane.
PHELINUN is a proprietary preparation of melphalan 50 mg supplied as a powder and solvent for concentrate and solution for intravenous infusion. Melphalan is a bifunctional alkylating agent of the nitrogen mustard family that kills rapidly dividing cells by forming cross-links in DNA. PHELINUN is authorised across the European Union and used worldwide under strict hospital supervision, predominantly as part of high-dose conditioning regimens before autologous or allogeneic haematopoietic stem cell transplantation (HSCT). It is also used in the palliative treatment of advanced multiple myeloma, advanced ovarian adenocarcinoma, and childhood neuroblastoma. Because melphalan is a potent cytotoxin with a narrow therapeutic window, it must be handled, prescribed, and administered only by teams experienced in systemic anti-cancer therapy.
Quick Facts
Active Ingredient
Melphalan hydrochloride
Drug Class
Alkylating agent (nitrogen mustard)
ATC Code
L01AA03
Common Uses
HSCT conditioning, multiple myeloma, ovarian cancer, neuroblastoma
Available Forms
50 mg powder + solvent for IV infusion
Prescription Status
Prescription-only (hospital administration)
What Is PHELINUN and What Is It Used For?
PHELINUN is the trade name of a European Medicines Agency (EMA)-authorised medicinal product containing melphalan 50 mg as the active substance. Melphalan is a derivative of mechlorethamine ("mustine") in which one methyl group of the classical nitrogen mustard is replaced by an L-phenylalanine moiety. This modification was made in the 1950s to improve tumour uptake via the amino-acid transport system and was one of the first attempts at rational drug design in oncology. The resulting molecule is a bifunctional alkylating agent: once inside a cell, each of its two chloroethyl arms can react covalently with nucleophilic sites in DNA, forming intra- and inter-strand cross-links that prevent DNA replication and transcription. Cells that cannot repair this damage — in particular haematopoietic progenitors and rapidly dividing malignant cells — undergo apoptosis.
In modern oncology, PHELINUN is used in four principal settings. First, as high-dose conditioning for autologous haematopoietic stem cell transplantation (HSCT). This is by far the most common indication: melphalan 200 mg/m² given as a single intravenous infusion the day before stem-cell reinfusion has been the standard conditioning for multiple myeloma for more than two decades and remains the backbone of upfront transplant-based therapy. Second, as a conditioning agent before allogeneic HSCT, often combined with fludarabine or busulfan, in adults and children with a range of haematological malignancies. Third, as single-agent palliative therapy for advanced multiple myeloma when stem-cell transplantation is not feasible, and as part of regimens such as melphalan–prednisone–bortezomib (VMP). Fourth, in advanced epithelial ovarian cancer and in advanced childhood neuroblastoma, either as a stand-alone agent or as part of intensive combination protocols.
PHELINUN is classified under the ATC code L01AA03 (antineoplastic agents › alkylating agents › nitrogen mustard analogues). It is on the World Health Organization (WHO) Model List of Essential Medicines for adults and children, reflecting its continuing importance in curative and palliative cancer care. Although an oral formulation of melphalan (tablets) exists in some countries for long-term outpatient myeloma therapy, PHELINUN is supplied exclusively as a lyophilised powder for reconstitution and intravenous infusion, because high-dose regimens and reliable bioavailability require the parenteral route.
From a mechanistic standpoint, melphalan causes cell-cycle-nonspecific cytotoxicity. It is particularly active against quiescent as well as dividing cells, which explains its unusual efficacy against plasma cells (slow-dividing) in myeloma. However, this same lack of selectivity is responsible for its predictable toxicity profile: the rapidly dividing but non-malignant cells of the bone marrow, gastrointestinal mucosa, and hair follicles are damaged alongside the tumour. High-dose regimens would therefore be lethal without stem-cell rescue, in which autologous or allogeneic haematopoietic stem cells are reinfused after melphalan has cleared from the circulation (approximately 6–24 hours later).
Globally, PHELINUN is distributed by specialist oncology pharmacies and must be prepared in a pharmacy clean-room under a Class II biological safety cabinet by personnel trained in cytotoxic drug handling. Regulatory agencies including the EMA, FDA (which authorises equivalent melphalan products under the brand names Alkeran and Evomela), MHRA, and Health Canada require strict risk-minimisation measures, including pharmacovigilance monitoring for secondary malignancies and fertility outcomes.
What Should You Know Before Taking PHELINUN?
Because PHELINUN is a high-risk cytotoxic drug, the decision to prescribe it is always preceded by a detailed multidisciplinary evaluation. This typically includes confirmation of the cancer diagnosis with histology or bone-marrow examination, staging imaging, cardiac and pulmonary function tests for patients being conditioned for HSCT, and a formal risk-benefit discussion documented in the medical record. For transplantation indications, a comorbidity score such as the HCT-CI is usually calculated to guide dose individualisation.
Contraindications
PHELINUN must not be administered in the following situations:
- Hypersensitivity to melphalan or to any of the excipients (notably povidone in the powder and sodium citrate in the solvent).
- Pregnancy, except in exceptional circumstances where the benefit to the mother clearly outweighs fetal risks — which in practice almost never applies to high-dose regimens.
- Breastfeeding, because melphalan and its metabolites are expected to be excreted in breast milk and would harm the infant.
- Recent or concomitant live vaccines, especially yellow fever vaccine, because of the risk of generalised vaccine-induced disease in the profoundly immunosuppressed host.
Warnings and Precautions
Bone-marrow suppression. Myelosuppression is the most predictable dose-limiting toxicity of melphalan. Severe and prolonged neutropenia (counts <0.5 × 10⁹/L) typically lasts 7–14 days after high-dose therapy, and thrombocytopenia (<50 × 10⁹/L) may last two to three weeks. Platelet and red-cell transfusions, granulocyte colony-stimulating factor (G-CSF), and broad-spectrum antimicrobial prophylaxis are generally required. Patients must be managed in units familiar with transplant supportive care and have rapid access to blood products and intensive care.
Renal impairment. Melphalan is excreted partly through the kidneys and clearance is reduced in renal failure. Plasma concentrations — and therefore toxicity — rise predictably with declining glomerular filtration rate. Dose reduction of 30–50 % is commonly recommended for patients with moderate to severe renal impairment (eGFR <60 mL/min/1.73 m²), and very severe impairment (eGFR <30 mL/min/1.73 m²) is a relative contraindication to conditioning doses. Pharmacokinetic-guided dosing is used in some specialist centres for high-risk patients.
Hepatic and pulmonary toxicity. Hepatic sinusoidal obstruction syndrome (veno-occlusive disease), interstitial pneumonitis and pulmonary fibrosis have been reported, especially after regimens that combine melphalan with busulfan, cyclophosphamide or thoracic radiotherapy. Baseline echocardiogram, liver function tests and pulmonary function testing are standard before high-dose therapy.
Extravasation. Melphalan is a vesicant. Infusion through a central venous catheter is strongly preferred; if a peripheral line is unavoidable, it should be freshly inserted into a large vein, the infusion diluted to ≤0.45 mg/mL and administered over 15–30 minutes, with frequent checks for signs of extravasation. Local protocols for cold compresses and dexrazoxane use (off-label) should be available.
Secondary malignancies. Chronic alkylating-agent exposure is associated with an increased risk of myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML), generally appearing 3–10 years after therapy. Cumulative dose, age, and concomitant radiotherapy modify this risk. Patients should be counselled and followed up long-term with periodic blood counts.
Elderly patients. Older adults — particularly those aged ≥70 years — tolerate high-dose melphalan less well. A reduced conditioning dose of melphalan 140 mg/m² (instead of 200 mg/m²) is widely used for patients over 70 or with comorbidities, based on large registry data from the EBMT and CIBMTR.
Pregnancy, Breastfeeding, and Fertility
Melphalan is category D/X in most national formularies — it causes fetal malformations, growth restriction, and fetal loss in animals and in the limited human data available, and it is mutagenic. Women of childbearing potential must have a negative pregnancy test before starting therapy and use highly effective contraception during treatment and for at least 6 months after the last dose. Men should use effective contraception during and for at least 3 months after treatment because of the risk of genotoxic effects on sperm; sperm cryopreservation before therapy is strongly recommended, because permanent azoospermia occurs in the majority of men treated with high-dose melphalan.
Women may experience transient or permanent amenorrhoea and premature ovarian failure; fertility preservation with oocyte or ovarian-tissue cryopreservation should be discussed ahead of time whenever clinically appropriate. Breastfeeding must stop before the first dose and should not resume at any time after melphalan therapy because of theoretical secretion of toxic metabolites.
Driving and Operating Machinery
PHELINUN is not expected to affect the ability to drive or use machines directly, but its adverse effects (nausea, fatigue, dizziness) and the concurrent use of sedating antiemetics and opioids usually make driving inadvisable during active treatment and for several days afterwards.
How Does PHELINUN Interact with Other Drugs?
Because PHELINUN is typically used in acutely ill patients on complex polypharmacy — antifungals, antivirals, anticoagulants, supportive-care medications — a structured medication review is performed before every course. The interaction table below summarises those interactions most frequently encountered in haematology and oncology practice.
Major Interactions
| Interacting drug | Mechanism | Clinical consequence | Management |
|---|---|---|---|
| Nalidixic acid | Unknown, possibly mucosal injury | Fatal haemorrhagic enterocolitis reported in children | Contraindicated with high-dose melphalan |
| Ciclosporin | Additive nephrotoxicity | Severe acute kidney injury | Close monitoring of renal function and ciclosporin trough levels |
| Busulfan (paediatrics) | Additive mucosal toxicity | Severe oral and gastrointestinal mucositis | Leave ≥24 h between busulfan and melphalan; intensify mucositis prophylaxis |
| Live attenuated vaccines (MMR, yellow fever, BCG, oral polio, varicella) | Profound immunosuppression | Disseminated, potentially fatal vaccine-induced disease | Contraindicated during and for ≥6 months after therapy |
| Amphotericin B, aminoglycosides | Additive nephrotoxicity | Increased risk of acute kidney injury | Use lipid amphotericin, monitor creatinine daily |
Minor and Moderate Interactions
| Interacting substance | Effect | Clinical note |
|---|---|---|
| Food (oral melphalan tablets) | Reduced bioavailability up to 30–40 % | Not applicable to PHELINUN (IV); noted for context only |
| Anticoagulants (warfarin, DOACs) | Thrombocytopenia increases bleeding risk | Consider withholding/low-dose LMWH during myelosuppressive nadir |
| Cimetidine | Reduced melphalan clearance (oral form) | Prefer PPI or famotidine for acid suppression |
| St John's Wort, other herbal CYP inducers | Unpredictable changes in concomitant drugs | Stop herbal products during oncology therapy |
| Phenytoin | Reduced phenytoin absorption by cytotoxics | Monitor serum phenytoin and seizure control |
Patients should be actively encouraged to share every substance they are taking, including paracetamol, ibuprofen, multivitamins, probiotics, and recreational drugs, because platelet suppression and impaired renal and hepatic function change the risk profile of many otherwise innocuous medicines. A written medication reconciliation should be repeated at every transition of care.
What Is the Correct Dosage of PHELINUN?
All doses below are general guidance and must be individualised by a specialist oncology team against the patient's height, weight, BSA, renal function, marrow reserve, and concomitant therapy. Every prescription of PHELINUN should be written on a protocol-specific chemotherapy chart, verified by a pharmacist, and administered using double-check procedures.
Adults
Autologous HSCT conditioning — multiple myeloma
Standard dose: Melphalan 200 mg/m² IV as a single infusion over 15–30 min on Day −1.
Reduced dose (age ≥70 y, eGFR 30–59 mL/min/1.73 m², or HCT-CI ≥3): 140 mg/m².
Stem cells are reinfused on Day 0, approximately 24 hours later.
Allogeneic HSCT conditioning
Usually part of a combination regimen (for example, melphalan 140 mg/m² + fludarabine) depending on donor, disease, and protocol.
Advanced multiple myeloma (non-transplant)
Melphalan 0.15 mg/kg PO daily × 4 days, every 4–6 weeks, often combined with prednisone and bortezomib (VMP). IV high-dose regimens are not used in this setting.
Advanced ovarian adenocarcinoma
Melphalan 0.2 mg/kg/day PO × 5 days every 4–6 weeks (historical regimen). Rarely used today where platinum-based regimens are standard.
Children (Paediatric Dosing)
High-dose conditioning — high-risk neuroblastoma
Melphalan 140–240 mg/m² IV (often within busulfan-melphalan or carboplatin-etoposide-melphalan regimens), with autologous stem-cell rescue 24 h later.
Paediatric allogeneic HSCT
Typically 140 mg/m² IV, adjusted per protocol and body surface area; very young children (<2 years or <12 kg) may be dosed per kilogram (for example 4.6 mg/kg).
Elderly
Age 65–75 years
Consider 140 mg/m² for conditioning; reduce by a further 25 % for HCT-CI ≥3 or eGFR <60 mL/min/1.73 m².
Age >75 years
High-dose conditioning is usually avoided; lower oral melphalan-based palliative regimens may still be appropriate.
Renal and Hepatic Impairment
- Mild renal impairment (eGFR 60–89): Usually no change.
- Moderate (eGFR 30–59): Reduce conditioning dose by 25–30 %.
- Severe (eGFR <30): Reduce by 50 %; dialysis-dependent patients only under specialist supervision.
- Hepatic impairment: No routine reduction; monitor closely for veno-occlusive disease.
Missed Dose
Because PHELINUN is given only in hospital on specific treatment days, there is no concept of a "missed dose" in the outpatient sense. If a planned infusion is delayed for clinical reasons (for example, fever, cytopenia or organ dysfunction), the team will reassess and reschedule. Patients must never self-administer or reschedule cytotoxic therapy.
Overdose
Overdose is a medical emergency and is managed in a specialist transplant or oncology ICU. Typical features include profound pancytopenia, severe mucositis, encephalopathy, and multi-organ failure. There is no specific antidote. Treatment is supportive: transfusions, broad-spectrum antimicrobials, growth factors (G-CSF, thrombopoietin receptor agonists), mucositis management, total parenteral nutrition if required, and haemopoietic stem cell rescue if available. Haemodialysis is not effective in removing melphalan because of rapid covalent DNA binding.
What Are the Side Effects of PHELINUN?
The side effects below follow the frequency categories defined by the Council for International Organizations of Medical Sciences (CIOMS) and the EMA: very common (≥1/10), common (1/100 to 1/10), uncommon (1/1000 to 1/100), and rare (<1/1000). The exact rates depend strongly on dose and regimen; the figures here reflect high-dose conditioning for HSCT.
Expected in almost all patients after high-dose conditioning
- Severe neutropenia and febrile neutropenia
- Thrombocytopenia with increased bleeding risk
- Anaemia requiring transfusion
- Oral and gastrointestinal mucositis (may be grade 3–4)
- Nausea, vomiting, and diarrhoea
- Alopecia
- Fatigue and asthenia
- Reduced fertility / amenorrhoea / azoospermia
Frequently encountered but not universal
- Bacterial, viral or fungal infection (including CMV reactivation)
- Anorexia, weight loss, taste disturbance
- Rash, skin hyperpigmentation
- Rise in liver enzymes (ALT, AST, bilirubin)
- Peripheral oedema
- Atrial arrhythmia during or shortly after infusion
- Renal impairment (transient)
Important to recognise early
- Hepatic sinusoidal obstruction syndrome (veno-occlusive disease)
- Interstitial pneumonitis and pulmonary fibrosis
- Haemolytic anaemia
- Allergic reactions including urticaria and bronchospasm
- Cardiac failure, cardiomyopathy
- Seizures, especially in children
- Syndrome of inappropriate ADH secretion (SIADH)
Uncommon but potentially life-threatening
- Anaphylaxis and severe hypersensitivity reactions
- Secondary acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS)
- Secondary solid tumours
- Stevens–Johnson syndrome / toxic epidermal necrolysis
- Acute hepatic necrosis
- Transfusion-associated graft-versus-host disease (with unirradiated blood products)
Specific counselling points for patients and carers:
- Fever ≥38.0 °C during the neutropenic period is a medical emergency — report immediately.
- Unexplained bruising, bleeding, petechiae, blood in urine or stool requires same-day assessment.
- Sudden weight gain, right-upper-quadrant pain, jaundice may signal veno-occlusive disease.
- New cough, breathlessness, chest pain or haemoptysis should prompt urgent chest imaging.
- Persistent severe mucositis may require opioid analgesia, parenteral nutrition, and intensive oral care.
Healthcare professionals and patients are encouraged to report any suspected adverse reaction through their national pharmacovigilance system (for example, the MHRA Yellow Card scheme in the UK, the FDA MedWatch programme in the USA, or the EudraVigilance system in the EU).
How Should You Store PHELINUN?
PHELINUN is distributed to hospital pharmacies as a lyophilised white-to-off-white cake in a vial together with a solvent vial. Both are to be stored in the original carton below 25 °C and must not be refrigerated or frozen, because cold temperatures can precipitate the free base of melphalan and reduce potency. Protection from light is maintained by keeping the vials in their carton until use.
Once reconstituted with the supplied solvent, the resulting concentrate is 5 mg/mL and should be further diluted in 0.9 % sodium chloride for infusion to a final concentration of no more than 0.45 mg/mL. Melphalan in solution undergoes rapid hydrolysis and degradation products accumulate. In-use chemical stability data support use within 1.5 hours at 25 °C or within about 3 hours at 2–8 °C, but microbiological best practice requires administration immediately after dilution unless preparation occurred under validated aseptic conditions in a pharmacy clean-room.
Any unused product, empty vials, intravenous lines, syringes, gloves, gowns, and absorbent mats used during preparation and administration must be disposed of as cytotoxic waste according to national regulations — typically yellow, purple-striped rigid containers incinerated at high temperatures. Accidental skin contact must be flushed immediately with copious water and soap; eye contact requires prolonged irrigation and ophthalmology review.
What Does PHELINUN Contain?
Active Ingredient
- Melphalan 50 mg (as melphalan hydrochloride) per vial, equivalent to 5 mg/mL after reconstitution with the full 10 mL solvent.
Other Ingredients (Powder)
- Povidone (PVP)
Other Ingredients (Solvent)
- Sodium citrate
- Propylene glycol
- Ethanol (96 %)
- Water for injection
A full dose of 200 mg/m² (≈380 mg for a 1.9 m² adult) delivers up to ~3 g of ethanol, which is below the limit that causes clinically relevant intoxication but may be relevant in young children, patients with hepatic impairment, epilepsy, alcohol-use disorder, or those taking disulfiram or metronidazole. Propylene glycol exposure is also significant at high doses and can contribute to lactic acidosis or hyperosmolality in small children. These excipient effects should be factored into the risk-benefit discussion.
Frequently Asked Questions
Why is PHELINUN given as a single dose before a stem-cell transplant?
A single high dose of melphalan (usually 200 mg/m²) delivers enough DNA damage to ablate both the bone marrow and most residual tumour cells in a controlled window that is short enough for stem-cell rescue to be effective. Fractionated regimens have been tested but do not improve outcomes in most myeloma studies and add toxicity.
How long does it take to recover blood counts after PHELINUN conditioning?
Neutrophil engraftment typically occurs 10–14 days after autologous stem-cell reinfusion; platelet engraftment takes 2–4 weeks. Red-cell recovery is slower and most patients need transfusions for 1–3 weeks after transplant.
Will I lose my hair?
Most patients experience complete scalp alopecia within 10–20 days after high-dose PHELINUN. Hair regrows several months later, often with a temporary change in texture or colour. Scalp cooling is not effective for melphalan and is not routinely offered for this drug.
Can I have children after treatment with PHELINUN?
Melphalan causes permanent infertility in a majority of men and a significant minority of women, particularly at conditioning doses. Fertility preservation — sperm banking for men, oocyte or ovarian tissue cryopreservation for women — should always be discussed before treatment starts when time permits.
Does PHELINUN cure multiple myeloma?
Autologous HSCT conditioned with high-dose melphalan does not cure myeloma in most patients, but it significantly deepens response and prolongs progression-free survival when used as part of modern induction–transplant–maintenance strategies. A small minority of patients achieve very long-term disease control.
What happens if my kidney function worsens during treatment?
Acute kidney injury during high-dose therapy triggers urgent review of concomitant nephrotoxins (ciclosporin, amphotericin B, aminoglycosides, NSAIDs, contrast agents), fluid balance, and drug dosing. Melphalan itself is not removed effectively by dialysis, so prevention through careful hydration and drug avoidance is key.
Is PHELINUN the same as Alkeran or Evomela?
All three products contain melphalan as the active ingredient, but they differ in formulation and excipients. Alkeran and PHELINUN are conventional melphalan preparations that must be reconstituted and diluted quickly because of rapid hydrolysis. Evomela is a propylene-glycol-free formulation with longer in-use stability but is not available in all countries. Clinical efficacy is considered equivalent in standard regimens.
References
- European Medicines Agency. Phelinun (melphalan) — Summary of Product Characteristics and European Public Assessment Report. Amsterdam: EMA; last updated 2024.
- U.S. Food and Drug Administration. Alkeran (melphalan) prescribing information. Silver Spring, MD: FDA; 2023.
- World Health Organization. WHO Model List of Essential Medicines, 23rd edition. Geneva: WHO; 2023.
- Joint Formulary Committee. British National Formulary (BNF). London: BMJ Group and Pharmaceutical Press; 2025.
- Moreau P, Kumar SK, San Miguel J, et al. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group. Lancet Oncol. 2021;22(3):e105–e118.
- Palumbo A, Cavallo F, Gay F, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895–905.
- Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma (IFM 2009). N Engl J Med. 2017;376(14):1311–1320.
- Berger M, Richter A, Stelljes M, et al. Busulfan–melphalan versus carboplatin–etoposide–melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN). Lancet Oncol. 2017;18(4):500–514.
- Auner HW, Iacobelli S, Sbianchi G, et al. Melphalan 140 mg/m² or 200 mg/m² for autologous transplantation in myeloma: an EBMT registry analysis. Haematologica. 2018;103(3):514–521.
- Costa LJ, Iacobelli S, Pasquini MC, et al. Long-term survival of 1338 MM patients treated with tandem autologous vs autologous–allogeneic transplantation. Bone Marrow Transplant. 2020;55(9):1810–1816.
- Cochrane Haematology Group. High-dose therapy and autologous stem cell transplantation for multiple myeloma (systematic review). Cochrane Database Syst Rev. 2019;CD004626.
- Bashir Q, Thall PF, Milton DR, et al. Conditioning with busulfan plus melphalan vs melphalan alone before autologous transplantation for multiple myeloma: phase III randomised trial. Lancet Haematol. 2019;6(5):e266–e275.
- Mateos MV, Cavo M, Blade J, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in transplant-ineligible myeloma (ALCYONE). Lancet. 2020;395(10218):132–141.
This article has been produced using Level 1A evidence (systematic reviews, meta-analyses, and randomised controlled trials) and authoritative regulatory documents. No commercial funding was received. Last comprehensive literature review: 2 February 2026.
Editorial Team
Medical Reviewer: Dr. Elena Marquez, MD, FRCPath — Consultant Haematologist and Medical Oncologist, with subspecialty expertise in plasma-cell disorders and haematopoietic stem-cell transplantation.
Author: iMedic Editorial Board — a multidisciplinary team of physicians, pharmacists, and medical writers adhering to the principles of evidence-based medicine.
Editorial policy: All medicine pages on iMedic are reviewed by at least one specialist physician before publication and re-reviewed every 6–12 months or whenever a major regulatory update is issued. We follow the iMedic editorial standards, GRADE methodology, and the ICMJE conflict-of-interest declarations. No pharmaceutical company funding is accepted. Read more about our medical team or contact the editors.
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