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Melphalan is an orally and parenterally administered nitrogen mustard-like alkylating agent used in the therapy of multiple myeloma and ovarian cancer. Melphalan therapy has been associated with low rates of serum enzyme elevations during therapy, but when used in high doses as myeloablative therapy in preparation for hematopoietic cell transplantation, it is associated with high rates of enzyme elevations and acute liver injury due to sinusoidal obstruction syndrome.
Melphalan is a phenylalanine derivative of nitrogen mustard with antineoplastic activity. Melphalan alkylates DNA at the N7 position of guanine and induces DNA inter-strand cross-linkages, resulting in the inhibition of DNA and RNA synthesis and cytotoxicity against both dividing and non-dividing tumor cells.
Melphalan Hydrochloride is a bifunctional alkylating agent and phenylalanine derivative of nitrogen mustard. Melphalan hydrochloride is converted into highly reactive ethylenimmonium intermediates that induce covalent guanine N7-N7 intra- and inter-crosslinks and alkylation of adenine N3 of DNA. This agent also alkylates RNA and protein structures. As a result RNA transcription and protein synthesis are inhibited, ultimately leading to cell growth arrest and/or death.
Melphalan Flufenamide is a peptide-drug conjugate composed of a peptide conjugated, via an aminopeptidase-targeting linkage, to the alkylating agent melphalan, with potential antineoplastic and anti-angiogenic activities. Upon administration, the highly lipophilic melphalan sulfenamide penetrates cell membranes and enters cells. In aminopeptidase-positive tumor cells, melphalan flufenamide is hydrolyzed by peptidases to release the hydrophilic alkylating agent melphalan. This results in the specific release and accumulation of melphalan in aminopeptidase-positive tumor cells. Melphalan alkylates DNA at the N7 position of guanine residues and induces DNA intra- and inter-strand cross-linkages. This results in the inhibition of DNA and RNA synthesis and the induction of apoptosis, thereby inhibiting tumor cell proliferation. Peptidases are overexpressed by certain cancer cells. The administration of melphalan flufenamide allows for enhanced efficacy and reduced toxicity compared to melphalan.
Melphalan flufenamide, also known as melflufen or J1, is a prodrug of [melphalan]. Melphalan flufenamide is more readily uptaken by cells than melphalan and is cleaved to the active metabolite by aminopeptidases. In vitro models show that melphalan is 10 to hundreds of times more potent than melphalan. The increased potency makes melphalan flufenamide a treatment option for patients with relapsed or refractory multiple myeloma who have attempted at least 4 lines of therapy already. Melphalan flufenamide was granted FDA approval on 26 February 2021.. It has since been withdrawn from the market in the wake of the phase 3 OCEAN trial which showed a decrease in overall survival in comparison to standard treatment with [pomalidomide] and [dexamethasone] despite superior progression-free survival.
Mechanism of Action
Melphalan attaches alkyl groups to the N-7 position of guanine and the N-3 position of adenine, leading to the formation of mono adducts, and DNA fragmenting when repair enzymes attempt to correct the error. It can also cause DNA cross-linking from the N-7 position of one guanine to the N-7 position of another, preventing DNA strands from separating for synthesis or transcription. Finally, melphalan can induce a number of different mutations.
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Melphalan flufenamide is a more lipophilic prodrug of melphalan, which allows it to be more readily uptaken by cells. It is likely taken up into malignant cells by passive diffusion, where it is hydrolyzed by aminopeptidase N. The expression of aminopeptidases, along with other hydrolytic enzymes, is upregulated in many malignant cells, making the hydrolysis reaction to melphalan more favorable in a malignant cell. Increased concentrations of free melphalan in malignant cells lead to rapid irreversible DNA damage and apoptosis, reducing the potential for the development of resistance. Free melphalan is a nitrogen mustard derivative alkylating agent. Melphalan attaches alkyl groups to the N-7 position of guanine and the N-3 position of adenine, leading to the formation of mono adducts, and DNA fragmenting when repair enzymes attempt to correct the error. It can also cause DNA cross-linking from the N-7 position of one guanine to the N-7 position of another, preventing DNA strands from separating for synthesis or transcription. Finally, melphalan can induce a number of different mutations. While melphalan induces phosphorylation of the DNA damage marker γ-H2AX in melphalan-sensitive cells at 6 hours, melphalan flufenamide induces γ-H2AX at 2 hours. Melphalan flufenamide is also able to induce γ-H2AX in melphalan-resistant cells.
Indication
- For the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary. Has also been used alone or as part of various chemotherapeutic regimens as an adjunct to surgery in the treatment of breast cancer, alone or in combination regimens for palliative treatment of locally recurrent or unresectable in-transit metastatic melanoma of the extremities, as well as for the treatment of amyloidosis with prednisone.
- High-dose of Phelinun used alone or in combination with other cytotoxic medicinal products and/or total body irradiation is indicated in the treatment of: multiple myeloma, malignant lymphoma (Hodgkin, non-Hodgkin lymphoma), acute lymphoblastic, and myeloblastic leukemia, childhood neuroblastoma, ovarian cancer, mammary adenocarcinoma.
- Phelinun in combination with other cytotoxic medicinal products is indicated as reduced intensity conditioning (RIC) treatment prior to allogeneic hematopoietic stem cell transplantation (also HSCT) in malignant hematological diseases in adults.
- Phelinun in combination with other cytotoxic medicinal products is indicated as a conditioning regimen prior to allogeneic hematopoietic stem cell transplantation in hematological diseases in the pediatric population as Myeloablative conditioning (MAC) treatment in case of malignant hematological diseases RIC treatment in case of non-malignant hematological diseases.
- Melphalan flufenamide is indicated in combination with [dexamethasone] to treat adults with relapsed or refractory multiple myeloma who have received ≥4 therapies and are refractory to at least one proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody. The FDA has withdrawn the drug from the market for this indication following phase 3 trial data showing decreased overall survival.
- Pepaxti is indicated, in combination with dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least three prior lines of therapies, whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapy. For patients with a prior autologous stem cell transplantation, the time to progression should be at least 3 years from transplantation
- Multiple Myeloma (MM)
- Unresectable Ovarian Cancer (Epithelial)
- Conditioning regimens for allogeneic stem cell transplantation therapy
Use in Cancer
Melphalan hydrochloride is approved to treat:
- Multiple myeloma.
- It is used for palliative treatment in patients who cannot take melphalan by mouth. This use is approved for the Alkeran and Evomela brands.
- It is used as a conditioning treatment to prepare patients for a stem cell transplant. This use is approved for the Evomela brand.
Melphalan hydrochloride is also being studied in the treatment of other types of cancer.
Melphalan is also available in a tablet form. For more information, see the Drug Information Summary for Melphalan.
Contraindication
- a bad infection
- a type of blood disorder where the red blood cells burst called hemolytic anemia
- decreased function of bone marrow
- anemia
- decreased blood platelets
- low levels of white blood cells
- low levels of granulocytes, a type of white blood cell
- inflammation of the blood vessels
- hepatic veno-occlusive disease, a type of liver disease
- bleeding
- a type of inflammation of the lung called interstitial pneumonitis
- a condition where there is formation of fibrous tissue in the lung called pulmonary fibrosis
- damage to the liver and inflammation
- decreased kidney function
- abnormal liver function tests
- pregnancy
- a patient who is producing milk and breastfeeding
Dosage
Strengths: 2 mg; 50 mg
Multiple Myeloma
ORAL:
A typical oral dosage regimen is:
- 6 mg orally once daily; after 2 to 3 weeks therapy should be discontinued for up to 4 weeks and the blood count followed; when white blood cell and platelet counts are rising, a maintenance dose of 2 mg daily may be instituted
Alternate Oral Regimens:
- Osserman and Takatsuki have used an initial course of 10 mg/day for 7 to 10 days. They report that maximal suppression of the leukocyte and platelet counts occurs within 3 to 5 weeks and recovery within 4 to 8 weeks. Continuous orally maintenance therapy with 2 mg/day is instituted when the white blood cell count is greater than 4000 cells/mcL and the platelet count is greater than 100,000 cells/mcL. The dosage is adjusted to between 1 and 3 mg/day depending on the hematological response. It is desirable to try to maintain a significant degree of bone marrow depression to keep the leukocyte count in the range of 3000 to 3500 cells/mcL.
- Hoogstraten et al have started therapy with 0.15 mg/kg/day for 7 days followed by a rest period of at least 14 days, but it may be up to 5 to 6 weeks. Maintenance therapy is started when the white blood cell and platelet counts are rising. The maintenance dose is 0.05 mg/kg/day or less and is adjusted according to the blood count.
- One study by Alexanian et al has shown that using this drug in combination with prednisone significantly improves the percentage of patients with multiple myeloma who achieve palliation. One regimen has been to administer courses of this drug at 0.25 mg/kg/day for 4 consecutive days (or, 0.2 mg/kg/day for 5 consecutive days) for a total dose of 1 mg/kg/course. These 4- to 5-day courses are then repeated every 4 to 6 weeks if the granulocyte and platelet count have returned to normal levels.
- The entire oral dose may be given at one time.
- Numerous oral regimes have been used. Scientific literature and/or institutional protocol should be consulted for further information.
- Oral administration of this drug results in variable absorption; dosage may need to be cautiously increased until myelosuppression is seen to ensure that therapeutic levels have been reached.
- The administration of this drug with prednisone is more effective than this drug as monotherapy. The combination is usually given on an intermittent basis, although the superiority of this technique over continuous therapy has not been established.
- Evidence suggests that one-third to one-half of the patients with multiple myeloma show a favorable response to administration of this drug.
- Experience with oral administration suggests that repeated courses should be given since improvement may continue slowly over many months, and the maximum benefit may be missed if therapy is abandoned prematurely.
- There is no general agreement that all the procedures recommended in the guidelines are necessary or appropriate.
IV (when oral therapy is not appropriate):
- 16 mg/m2 as a single IV infusion over 15 to 20 minutes every 2 weeks for 4 doses; then, after adequate recovery from toxicity, at 4-week intervals
- Evidence suggests that one-third to one-half of the patients with multiple myeloma show a favorable response to administration of this drug.
- Dose adjustment based on blood cell counts at the nadir and day of therapy should be considered.
- There is no general agreement that all the procedures recommended in the guidelines are necessary or appropriate.
- Consult local institutional guidelines for alternate dosing options.
- Oral: For the palliative treatment of multiple myeloma.
- IV: For the palliative treatment of multiple myeloma when oral therapy is not appropriate.
Ovarian Cancer
- Common regimen: 0.2 mg/kg orally daily for 5 days as a single course; courses are repeated every 4 to 5 weeks depending upon hematologic tolerance
- There is no general agreement that all the procedures recommended in the guidelines are necessary or appropriate.
- Consult local institutional guidelines for alternate dosing options.
- For the palliation of nonresectable epithelial carcinoma of the ovary.
Renal Dose Adjustments
- In patients with moderate to severe renal impairment, currently available pharmacokinetic data do not justify an absolute recommendation on dosage reduction to those patients, but it may be prudent to use a reduced dose initially.
- Patients with azotemia should be closely observed to make dosage reductions, if required, as soon as possible.
IV:
A reduction of up to 50% should be considered in patients with renal insufficiency (BUN greater than or equal to 30 mg/dL).
ORAL:
A recommendation as to whether dosage reduction should be made routinely in patients with renal insufficiency cannot be made because:
- There is considerable inherent patient-to-patient variability in the systemic availability of this drug in patients with normal renal function.
- Only a small amount of the administered dose appears as parent drug in the urine of patients with normal renal function.
or
Dosage Intra-arterial
Malignant melanoma, Soft tissue sarcoma
Malignant melanoma, Soft tissue sarcoma
- Adult: As melphalan hydrochloride: Upper extremity perfusions: 0.6-1 mg/kg. Lower extremity perfusions: 0.8-1.5 mg/kg (in melanoma) or 1-1.4 mg/kg (in sarcoma).
- Elderly: Initiate treatment at the lower end of the dosing range.
Intravenous
Multiple myeloma
Multiple myeloma
- Adult: As melphalan hydrochloride: 0.4 mg/kg (16 mg/m2) repeated at appropriate intervals (e.g. once every 4 weeks) provided there has been a recovery of the peripheral blood count during this period. A high-dose regimen: 100-200 mg/m2, to be followed by hematopoietic stem cell rescue if doses are >140 mg/m2. As melphalan flufenamide: In patients with relapsed or refractory multiple myeloma who have received ≥4 prior lines of therapy and whose disease is refractory to ≥1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-directed monoclonal antibody: 40 mg over 30 minutes on Day 1 of each 28-day treatment cycle, in combination with dexamethasone. Continue until disease progression or unacceptable toxicity. Dose reduction or modifications may be required according to individual safety or tolerability (refer to detailed product guidelines).
- Elderly: Initiate treatment at the lower end of the dosing range.
Intravenous
Ovarian adenocarcinoma
Ovarian adenocarcinoma
- Adult: As melphalan hydrochloride: Monotherapy: 1 mg/kg (approx 40 mg/m2) given at intervals of 4 weeks. In combination with other cytotoxic drugs: 0.3-0.4 mg/kg (12-16 mg/m2) at intervals of 4-6 weeks
- Elderly: Initiate treatment at the lower end of the dosing range.
Intravenous
Advanced neuroblastoma
Advanced neuroblastoma
- Child: As melphalan hydrochloride: High-dose regimen: 100-240 mg/m2 (may be divided equally over 3 consecutive days) followed by hematopoietic stem cell rescue if doses are >140 mg/m2.
Oral
Ovarian adenocarcinoma
Ovarian adenocarcinoma
- Adult: 0.2 mg/kg daily for 5 days, repeated every 4-8 weeks, or as soon as the bone marrow has recovered.
- Elderly: Initiate treatment at the lower end of the dosing range.
Oral
Breast cancer
Breast cancer
- Adult: 0.15 mg/kg or 6 mg/m2 daily for 5 days, repeated every 6 weeks. Dose reduction may be needed if bone marrow toxicity was observed.
- Elderly: Initiate treatment at the lower end of the dosing range.
Oral
Polycythemia vera
Polycythemia vera
- Adult: Remission induction: 6-10 mg daily for 5-7 days, then 2-4 mg daily until satisfactory disease control is achieved. Maintenance: 2-6 mg once weekly, with careful hematological control and dosage adjustment based on blood counts.
- Elderly: Initiate treatment at the lower end of the dosing range.
Oral
Multiple myeloma
- Adult: Usual dosage regimens: Regimen 1: 0.15 mg/kg daily in divided doses for 4 days, repeated at 6-week intervals, usually in combination with a corticosteroid. Regimen 2: 6 mg once daily for 2-3 weeks, followed by up to 4 weeks rest with careful monitoring of blood counts. A maintenance dose of 2 mg daily may be given if WBC and platelet counts are rising. Several regimens have been used; refer to detailed product-specific guidelines. Delay or adjust dose if necessary. Dosage may need to be cautiously increased until myelosuppression is observed, to ensure that potentially therapeutic levels have been reached.
- Elderly: Initiate treatment at the lower end of the dosing range.
Side Effects
The Most Common
- nausea
- vomiting
- loss of appetite or weight
- sores in the mouth and throat
- missed menstrual periods (in girls and women)
- joint, muscle, or back pain
- rash
- hives
- itching
- difficulty breathing or swallowing
- pale skin
- excessive tiredness
- fainting
- fast, irregular, or pounding heartbeat
- yellowing of the skin or eyes
- pain in the upper right part of the stomach
- dark colored urine
- unusual lumps or masses
More Common
- low white blood cell counts–fever, chills, cough, pain or burning when you urinate.
- low red blood cells (anemia)–pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet;
- easy bruising, unusual bleeding, purple or red spots under your skin;
- sores or white patches in or around your mouth, trouble swallowing or talking, dry mouth, bad breath, altered sense of taste;
- severe ongoing nausea, vomiting, or diarrhea;
- new or worsening cough, fever, trouble breathing;
- unusual lumps or masses;
- missed menstrual periods;
- inflammation of your blood vessels–warmth or tingling, skin rash, fever, headache, body aches, night sweats, weight loss, feeling or weak or tired;
- liver problems–loss of appetite, stomach pain (upper right side), dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or
- low potassium level–leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.
- low blood cell counts;
- mouth sores;
- tiredness;
- low potassium levels; or
- hair loss.
Rare
- Nausea
- Bone marrow suppression, including
- Decreased white blood cell count causing the increased risk of infection
- Decreased platelet count causing an increased risk of bleeding
- Severe allergic reactions
- Pulmonary fibrosis (scarring of lung tissue) including fatal outcomes (usually only with prolonged use)
- Hair loss
- Interstitial pneumonitis
- Rash
- Itching
- Irreversible bone marrow failure due to melphalan not being withdrawn early enough
- Cardiac arrest
Drug Interaction
| DRUG | INTERACTION |
|---|---|
| Abatacept | The risk or severity of adverse effects can be increased when Melphalan is combined with Abatacept. |
| Abciximab | The risk or severity of bleeding can be increased when Abciximab is combined with Melphalan. |
| Acenocoumarol | The risk or severity of bleeding can be increased when Acenocoumarol is combined with Melphalan. |
| Acetylsalicylic acid | The risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Melphalan. |
| Adalimumab | The risk or severity of adverse effects can be increased when Adalimumab is combined with Melphalan. |
| Adenovirus type | The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Melphalan. |
| Aldesleukin | The risk or severity of adverse effects can be increased when Aldesleukin is combined with Melphalan. |
| Alefacept | The risk or severity of adverse effects can be increased when Alefacept is combined with Melphalan. |
| Alemtuzumab | The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Melphalan. |
| Allogeneic | The therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Melphalan. |
| Allopurinol | The risk or severity of adverse effects can be increased when Allopurinol is combined with Melphalan. |
| Alteplase | The risk or severity of bleeding can be increased when Alteplase is combined with Melphalan. |
| Altretamine | The risk or severity of adverse effects can be increased when Altretamine is combined with Melphalan. |
| Amsacrine | The risk or severity of adverse effects can be increased when Amsacrine is combined with Melphalan. |
| Anagrelide | The risk or severity of bleeding can be increased when Anagrelide is combined with Melphalan. |
| Anakinra | The risk or severity of adverse effects can be increased when Anakinra is combined with Melphalan. |
| Ancrod | The risk or severity of bleeding can be increased when Ancrod is combined with Melphalan. |
| Anifrolumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Anifrolumab. |
| Anistreplase | The risk or severity of bleeding can be increased when Anistreplase is combined with Melphalan. |
| Anthrax immune globulin human | The therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Melphalan. |
| Anthrax vaccine | The risk or severity of infection can be increased when Anthrax vaccine is combined with Melphalan. |
| Antilymphocyte ) | The risk or severity of adverse effects can be increased when Melphalan is combined with Antilymphocyte immunoglobulin (horse). |
| Antithrombin Alfa | The risk or severity of bleeding can be increased when Antithrombin Alfa is combined with Melphalan. |
| Antithrombin III human | The risk or severity of bleeding can be increased when Antithrombin III human is combined with Melphalan. |
| Antithymocyte | The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Melphalan. |
| Apixaban | The risk or severity of bleeding can be increased when Apixaban is combined with Melphalan. |
| Apremilast | The risk or severity of adverse effects can be increased when Melphalan is combined with Apremilast. |
| Ardeparin | The risk or severity of bleeding can be increased when Ardeparin is combined with Melphalan. |
| Argatroban | The risk or severity of bleeding can be increased when Argatroban is combined with Melphalan. |
| Arsenic trioxide | The risk or severity of adverse effects can be increased when Melphalan is combined with Arsenic trioxide. |
| Articaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Articaine. |
| COVID-19 Vaccine | The therapeutic efficacy of AstraZeneca COVID-19 Vaccine can be decreased when used in combination with Melphalan. |
| Azacitidine | The risk or severity of adverse effects can be increased when Azacitidine is combined with Melphalan. |
| Azathioprine | The risk or severity of adverse effects can be increased when Azathioprine is combined with Melphalan. |
| Bacillus calmette | The risk or severity of infection can be increased when Bacillus calmette-guerin substrain connaught live antigen is combined with Melphalan. |
| substrain russian BCG | The therapeutic efficacy of Bacillus calmette-guerin substrain russian BCG-I live antigen can be decreased when used in combination with Melphalan. |
| Bacillus calmette | The risk or severity of infection can be increased when Bacillus calmette-guerin substrain tice live antigen is combined with Melphalan. |
| Baricitinib | The risk or severity of adverse effects can be increased when Melphalan is combined with Baricitinib. |
| Basiliximab | The risk or severity of adverse effects can be increased when Basiliximab is combined with Melphalan. |
| BCG vaccine | The risk or severity of infection can be increased when BCG vaccine is combined with Melphalan. |
| Beclomethasone | The risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Melphalan. |
| Belatacept | The risk or severity of adverse effects can be increased when Melphalan is combined with Belatacept. |
| Belimumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Belimumab. |
| Belinostat | The risk or severity of adverse effects can be increased when Melphalan is combined with Belinostat. |
| Belumosudil | The risk or severity of adverse effects can be increased when Melphalan is combined with Belumosudil. |
| Bemiparin | The risk or severity of bleeding can be increased when Bemiparin is combined with Melphalan. |
| Bendamustine | The risk or severity of adverse effects can be increased when Melphalan is combined with Bendamustine. |
| Bendroflumethiazide | The risk or severity of neutropenia and thrombocytopenia can be increased when Bendroflumethiazide is combined with Melphalan. |
| Benzocaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Benzocaine. |
| Benzthiazide | The risk or severity of neutropenia and thrombocytopenia can be increased when Benzthiazide is combined with Melphalan. |
| Benzyl alcohol | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Benzyl alcohol. |
| Betamethasone | The risk or severity of adverse effects can be increased when Betamethasone is combined with Melphalan. |
| Betrixaban | The risk or severity of bleeding can be increased when Betrixaban is combined with Melphalan. |
| Bexarotene | The risk or severity of adverse effects can be increased when Bexarotene is combined with Melphalan. |
| Bimekizumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Bimekizumab. |
| Bivalirudin | The risk or severity of bleeding can be increased when Bivalirudin is combined with Melphalan. |
| Bleomycin | The risk or severity of adverse effects can be increased when Bleomycin is combined with Melphalan. |
| Blinatumomab | The risk or severity of adverse effects can be increased when Melphalan is combined with Blinatumomab. |
| Bordetella pertussis | The therapeutic efficacy of Bordetella pertussis toxoid antigen (formaldehyde, glutaraldehyde inactivated) can be decreased when used in combination with Melphalan. |
| Bortezomib | The risk or severity of adverse effects can be increased when Bortezomib is combined with Melphalan. |
| Bosutinib | The risk or severity of adverse effects can be increased when Melphalan is combined with Bosutinib. |
| Brentuximab vedotin | The risk or severity of adverse effects can be increased when Melphalan is combined with Brentuximab vedotin. |
| Brodalumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Brodalumab. |
| Budesonide | The risk or severity of adverse effects can be increased when Melphalan is combined with Budesonide. |
| Bupivacaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Bupivacaine. |
| Busulfan | The risk or severity of adverse effects can be increased when Busulfan is combined with Melphalan. |
| Butacaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Butacaine. |
| Butamben | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Butamben. |
| Cabazitaxel | The risk or severity of adverse effects can be increased when Melphalan is combined with Cabazitaxel. |
| Canakinumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Canakinumab. |
| Cangrelor | The risk or severity of bleeding can be increased when Cangrelor is combined with Melphalan. |
| Capecitabine | The risk or severity of adverse effects can be increased when Melphalan is combined with Capecitabine. |
| Caplacizumab | The risk or severity of bleeding can be increased when Caplacizumab is combined with Melphalan. |
| Capsaicin | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Capsaicin. |
| Carbamazepine | The risk or severity of adverse effects can be increased when Carbamazepine is combined with Melphalan. |
| Carboplatin | The risk or severity of adverse effects can be increased when Carboplatin is combined with Melphalan. |
| Carfilzomib | The risk or severity of adverse effects can be increased when Melphalan is combined with Carfilzomib. |
| Carmustine | The risk or severity of pulmonary toxicity can be increased when Melphalan is combined with Carmustine. |
| Certolizumab pegol | The risk or severity of adverse effects can be increased when Melphalan is combined with Certolizumab pegol. |
| Chlorambucil | The risk or severity of adverse effects can be increased when Chlorambucil is combined with Melphalan. |
| Chloramphenicol | The risk or severity of adverse effects can be increased when Chloramphenicol is combined with Melphalan. |
| Chloroprocaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Chloroprocaine. |
| Chlorothiazide | The risk or severity of neutropenia and thrombocytopenia can be increased when Chlorothiazide is combined with Melphalan. |
| Ciclesonide | The risk or severity of adverse effects can be increased when Melphalan is combined with Ciclesonide. |
| Cilostazol | The risk or severity of bleeding can be increased when Cilostazol is combined with Melphalan. |
| Cinchocaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Cinchocaine. |
| Cisplatin | The risk or severity of adverse effects can be increased when Cisplatin is combined with Melphalan. |
| Cladribine | The risk or severity of adverse effects can be increased when Cladribine is combined with Melphalan. |
| Clobetasol propionate | The risk or severity of adverse effects can be increased when Clobetasol propionate is combined with Melphalan. |
| Clofarabine | The risk or severity of adverse effects can be increased when Clofarabine is combined with Melphalan. |
| Clopidogrel | The risk or severity of bleeding can be increased when Clopidogrel is combined with Melphalan. |
| Clostridium tetani | The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Melphalan. |
| Clozapine | The risk or severity of neutropenia can be increased when Melphalan is combined with Clozapine. |
| Cocaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Cocaine. |
| Corticotropin | The risk or severity of adverse effects can be increased when Melphalan is combined with Corticotropin. |
| Cortisone acetate | The risk or severity of adverse effects can be increased when Melphalan is combined with Cortisone acetate. |
| Corynebacterium | The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Melphalan. |
| Cyanocobalamin | The therapeutic efficacy of Cyanocobalamin can be decreased when used in combination with Melphalan. |
| Cyclopenthiazide | The risk or severity of neutropenia and thrombocytopenia can be increased when Cyclopenthiazide is combined with Melphalan. |
| Cyclophosphamide | The risk or severity of adverse effects can be increased when Cyclophosphamide is combined with Melphalan. |
| Cyclosporine | Melphalan may increase the nephrotoxic activities of Cyclosporine. |
| Cyclothiazide | The risk or severity of neutropenia and thrombocytopenia can be increased when Cyclothiazide is combined with Melphalan. |
| Cytarabine | The risk or severity of adverse effects can be increased when Cytarabine is combined with Melphalan. |
| Dabigatran | The risk or severity of bleeding can be increased when Dabigatran is combined with Melphalan. |
| Dabigatran etexilate | The risk or severity of bleeding can be increased when Dabigatran etexilate is combined with Melphalan. |
| Dacarbazine | The risk or severity of adverse effects can be increased when Dacarbazine is combined with Melphalan. |
| Dactinomycin | The risk or severity of adverse effects can be increased when Dactinomycin is combined with Melphalan. |
| Dalteparin | The risk or severity of bleeding can be increased when Dalteparin is combined with Melphalan. |
| Danaparoid | The risk or severity of bleeding can be increased when Danaparoid is combined with Melphalan. |
| Darbepoetin alfa | The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Melphalan. |
| Dasatinib | The risk or severity of adverse effects can be increased when Melphalan is combined with Dasatinib. |
| Daunorubicin | The risk or severity of adverse effects can be increased when Daunorubicin is combined with Melphalan. |
| Decitabine | The risk or severity of adverse effects can be increased when Melphalan is combined with Decitabine. |
| Defibrotide | The risk or severity of bleeding can be increased when Defibrotide is combined with Melphalan. |
| Deflazacort | The risk or severity of adverse effects can be increased when Melphalan is combined with Deflazacort. |
| Denosumab | The risk or severity of adverse effects can be increased when Denosumab is combined with Melphalan. |
| Desirudin | The risk or severity of bleeding can be increased when Desirudin is combined with Melphalan. |
| Desoximetasone | The risk or severity of adverse effects can be increased when Desoximetasone is combined with Melphalan. |
| Deucravacitinib | The risk or severity of adverse effects can be increased when Melphalan is combined with Deucravacitinib. |
| Dexamethasone | The risk or severity of adverse effects can be increased when Melphalan is combined with Dexamethasone. |
| Dexrazoxane | The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Melphalan. |
| Dextran | The risk or severity of bleeding can be increased when Dextran is combined with Melphalan. |
| Dicoumarol | The risk or severity of bleeding can be increased when Dicoumarol is combined with Melphalan. |
| Difluocortolone | The risk or severity of adverse effects can be increased when Melphalan is combined with Difluocortolone. |
| Dimethyl fumarate | The risk or severity of adverse effects can be increased when Melphalan is combined with Dimethyl fumarate. |
| Dinutuximab | The risk or severity of adverse effects can be increased when Melphalan is combined with Dinutuximab. |
| Diphenhydramine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Diphenhydramine. |
| Dipyridamole | The risk or severity of bleeding can be increased when Dipyridamole is combined with Melphalan. |
| Diroximel fumarate | The risk or severity of adverse effects can be increased when Melphalan is combined with Diroximel fumarate. |
| Docetaxel | The risk or severity of adverse effects can be increased when Melphalan is combined with Docetaxel. |
| Doxorubicin | The risk or severity of adverse effects can be increased when Doxorubicin is combined with Melphalan. |
| Drotrecogin alfa | The risk or severity of bleeding can be increased when Drotrecogin alfa is combined with Melphalan. |
| Dyclonine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Dyclonine. |
| Ebola Zaire vaccine | The therapeutic efficacy of Ebola Zaire vaccine (live, attenuated) can be decreased when used in combination with Melphalan. |
| Eculizumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Eculizumab. |
| Edetic acid | The risk or severity of bleeding can be increased when Edetic acid is combined with Melphalan. |
| Edoxaban | The risk or severity of bleeding can be increased when Edoxaban is combined with Melphalan. |
| Efalizumab | The risk or severity of adverse effects can be increased when Efalizumab is combined with Melphalan. |
| Emapalumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Emapalumab. |
| Enoxaparin | The risk or severity of bleeding can be increased when Enoxaparin is combined with Melphalan. |
| Epirubicin | The risk or severity of adverse effects can be increased when Epirubicin is combined with Melphalan. |
| Epoprostenol | The risk or severity of bleeding can be increased when Epoprostenol is combined with Melphalan. |
| Eptifibatide | The risk or severity of bleeding can be increased when Eptifibatide is combined with Melphalan. |
| Eribulin | The risk or severity of adverse effects can be increased when Melphalan is combined with Eribulin. |
| Erythropoietin | The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Melphalan. |
| Estramustine | The risk or severity of adverse effects can be increased when Melphalan is combined with Estramustine. |
| Etanercept | The risk or severity of adverse effects can be increased when Etanercept is combined with Melphalan. |
| Ethyl chloride | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Ethyl chloride. |
| Etidocaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Etidocaine. |
| Etoposide | The risk or severity of adverse effects can be increased when Etoposide is combined with Melphalan. |
| Everolimus | The risk or severity of adverse effects can be increased when Melphalan is combined with Everolimus. |
| Famtozinameran | The therapeutic efficacy of Famtozinameran can be decreased when used in combination with Melphalan. |
| Filgotinib | The risk or severity of adverse effects can be increased when Melphalan is combined with Filgotinib. |
| Fingolimod | Melphalan may increase the immunosuppressive activities of Fingolimod. |
| Floxuridine | The risk or severity of adverse effects can be increased when Floxuridine is combined with Melphalan. |
| Flucytosine | The risk or severity of adverse effects can be increased when Melphalan is combined with Flucytosine. |
| Fludarabine | The risk or severity of adverse effects can be increased when Melphalan is combined with Fludarabine. |
| Fludrocortisone | The risk or severity of adverse effects can be increased when Fludrocortisone is combined with Melphalan. |
| Fluindione | The risk or severity of bleeding can be increased when Fluindione is combined with Melphalan. |
| Flunisolide | The risk or severity of adverse effects can be increased when Flunisolide is combined with Melphalan. |
| Fluocinolone acetonide | The risk or severity of adverse effects can be increased when Fluocinolone acetonide is combined with Melphalan. |
| Fluocinonide | The risk or severity of adverse effects can be increased when Melphalan is combined with Fluocinonide. |
| Fluocortolone | The risk or severity of adverse effects can be increased when Melphalan is combined with Fluocortolone. |
| Fluorometholone | The risk or severity of adverse effects can be increased when Fluorometholone is combined with Melphalan. |
| Fluorouracil | The risk or severity of adverse effects can be increased when Fluorouracil is combined with Melphalan. |
| Flupentixol | The risk or severity of myelosuppression can be increased when Flupentixol is combined with Melphalan. |
| Fluprednisolone | The risk or severity of adverse effects can be increased when Melphalan is combined with Fluprednisolone. |
| Fluticasone | The risk or severity of adverse effects can be increased when Melphalan is combined with Fluticasone. |
| Fluticasone furoate | The risk or severity of adverse effects can be increased when Melphalan is combined with Fluticasone furoate. |
| Fluticasone propionate | The risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Melphalan. |
| Fondaparinux | The risk or severity of bleeding can be increased when Fondaparinux is combined with Melphalan. |
| Gallium nitrate | The risk or severity of adverse effects can be increased when Melphalan is combined with Gallium nitrate. |
| Gemcitabine | The risk or severity of adverse effects can be increased when Gemcitabine is combined with Melphalan. |
| Gemtuzumab ozogamicin | The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Melphalan. |
| Glatiramer | The risk or severity of adverse effects can be increased when Melphalan is combined with Glatiramer. |
| Golimumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Golimumab. |
| Guselkumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Guselkumab. |
| Haemophilus | The therapeutic efficacy of Haemophilus influenzae type B strain 20752 capsular polysaccharide tetanus toxoid conjugate antigen can be decreased when used in combination with Melphalan. |
| Heparin | The risk or severity of bleeding can be increased when Heparin is combined with Melphalan. |
| Hepatitis A Vaccine | The therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Melphalan. |
| Hepatitis B Vaccine (Recombinant) | The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Melphalan. |
| Human adenovirus | The risk or severity of infection can be increased when Human adenovirus e serotype 4 strain cl-68578 antigen is combined with Melphalan. |
| Hydrochlorothiazide | The risk or severity of neutropenia and thrombocytopenia can be increased when Hydrochlorothiazide is combined with Melphalan. |
| Hydrocortisone acetate | The risk or severity of adverse effects can be increased when Melphalan is combined with Hydrocortisone acetate. |
| Hydrocortisone butyrate | The risk or severity of adverse effects can be increased when Melphalan is combined with Hydrocortisone butyrate. |
| Hydrocortisone succinate | The risk or severity of adverse effects can be increased when Melphalan is combined with Hydrocortisone succinate. |
| Hydroflumethiazide | The risk or severity of neutropenia and thrombocytopenia can be increased when Hydroflumethiazide is combined with Melphalan. |
| Hydroxychloroquine | The risk or severity of adverse effects can be increased when Melphalan is combined with Hydroxychloroquine. |
| Hydroxyurea | The risk or severity of adverse effects can be increased when Hydroxyurea is combined with Melphalan. |
| Ibritumomab tiuxetan | The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Melphalan. |
| Ibrutinib | The risk or severity of adverse effects can be increased when Melphalan is combined with Ibrutinib. |
| Icosapent ethyl | The risk or severity of bleeding can be increased when Icosapent ethyl is combined with Melphalan. |
| Idarubicin | The risk or severity of adverse effects can be increased when Melphalan is combined with Idarubicin. |
| Idelalisib | The risk or severity of adverse effects can be increased when Melphalan is combined with Idelalisib. |
| Ifosfamide | The risk or severity of adverse effects can be increased when Melphalan is combined with Ifosfamide. |
| Iloprost | The risk or severity of bleeding can be increased when Iloprost is combined with Melphalan. |
| Imatinib | The risk or severity of adverse effects can be increased when Imatinib is combined with Melphalan. |
| Indomethacin | The risk or severity of adverse effects can be increased when Indomethacin is combined with Melphalan. |
| Inebilizumab | The risk or severity of infection can be increased when Melphalan is combined with Inebilizumab. |
| Infliximab | The risk or severity of adverse effects can be increased when Infliximab is combined with Melphalan. |
| Leflunomide | The risk or severity of adverse effects can be increased when Melphalan is combined with Leflunomide. |
| Lenalidomide | The risk or severity of adverse effects can be increased when Lenalidomide is combined with Melphalan. |
| Lepirudin | The risk or severity of bleeding can be increased when Lepirudin is combined with Melphalan. |
| Levobupivacaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Levobupivacaine. |
| Lidocaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Lidocaine. |
| Linezolid | The risk or severity of adverse effects can be increased when Linezolid is combined with Melphalan. |
| Lipegfilgrastim | Melphalan may increase the myelosuppressive activities of Lipegfilgrastim. |
| Lomustine | The risk or severity of adverse effects can be increased when Melphalan is combined with Lomustine. |
| Lopinavir | The serum concentration of Melphalan can be increased when it is combined with Lopinavir. |
| Magnesium | The serum concentration of Magnesium can be decreased when it is combined with Melphalan. |
| Measles virus vaccine live attenuated | The therapeutic efficacy of Measles virus vaccine live attenuated can be decreased when used in combination with Melphalan. |
| Mechlorethamine | The risk or severity of adverse effects can be increased when Mechlorethamine is combined with Melphalan. |
| Meloxicam | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Meloxicam. |
| Meningococcal | The therapeutic efficacy of Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine can be decreased when used in combination with Melphalan. |
| Mepivacaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Mepivacaine. |
| Mepolizumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Mepolizumab. |
| Meprednisone | The risk or severity of adverse effects can be increased when Melphalan is combined with Meprednisone. |
| Mercaptopurine | The risk or severity of adverse effects can be increased when Mercaptopurine is combined with Melphalan. |
| Metamizole | The risk or severity of myelosuppression can be increased when Metamizole is combined with Melphalan. |
| Methimazole | The risk or severity of adverse effects can be increased when Methimazole is combined with Melphalan. |
| Methotrexate | The risk or severity of adverse effects can be increased when Methotrexate is combined with Melphalan. |
| Methoxy polyethylene | The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Melphalan. |
| Methylprednisolone | The risk or severity of adverse effects can be increased when Methylprednisolone is combined with Melphalan. |
| Mitomycin | The risk or severity of adverse effects can be increased when Mitomycin is combined with Melphalan. |
| Mitoxantrone | The risk or severity of adverse effects can be increased when Melphalan is combined with Mitoxantrone. |
| COVID-19 Vaccine | The therapeutic efficacy of Moderna COVID-19 Vaccine can be decreased when used in combination with Melphalan. |
| Modified vaccinia ankara | The therapeutic efficacy of Modified vaccinia ankara can be decreased when used in combination with Melphalan. |
| Mometasone furoate | The risk or severity of adverse effects can be increased when Melphalan is combined with Mometasone furoate. |
| Monomethyl fumarate | The risk or severity of adverse effects can be increased when Melphalan is combined with Monomethyl fumarate. |
| Mosunetuzumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Mosunetuzumab. |
| Mumps virus strain | The therapeutic efficacy of Mumps virus strain B level jeryl lynn live antigen can be decreased when used in combination with Melphalan. |
| Muromonab | The risk or severity of adverse effects can be increased when Muromonab is combined with Melphalan. |
| Mycophenolate mofetil | The risk or severity of adverse effects can be increased when Mycophenolate mofetil is combined with Melphalan. |
| Mycophenolic acid | The risk or severity of adverse effects can be increased when Mycophenolic acid is combined with Melphalan. |
| Nadroparin | The risk or severity of bleeding can be increased when Nadroparin is combined with Melphalan. |
| Nalidixic acid | The risk or severity of gastrointestinal bleeding can be increased when Nalidixic acid is combined with Melphalan. |
| Natalizumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Natalizumab. |
| Nelarabine | The risk or severity of adverse effects can be increased when Melphalan is combined with Nelarabine. |
| Nilotinib | The risk or severity of adverse effects can be increased when Melphalan is combined with Nilotinib. |
| Nimesulide | The risk or severity of bleeding can be increased when Nimesulide is combined with Melphalan. |
| Nuvaxovid | The therapeutic efficacy of Nuvaxovid can be decreased when used in combination with Melphalan. |
| Obinutuzumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Obinutuzumab. |
| Ocrelizumab | Ocrelizumab may increase the immunosuppressive activities of Melphalan. |
| Ofatumumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Ofatumumab. |
| Olaparib | The risk or severity of adverse effects can be increased when Melphalan is combined with Olaparib. |
| Oxaliplatin | The risk or severity of adverse effects can be increased when Oxaliplatin is combined with Melphalan. |
| Oxetacaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Oxetacaine. |
| Oxybuprocaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Oxybuprocaine. |
| Ozanimod | The risk or severity of adverse effects can be increased when Melphalan is combined with Ozanimod. |
| Paclitaxel | The risk or severity of adverse effects can be increased when Melphalan is combined with Paclitaxel. |
| Palbociclib | The risk or severity of adverse effects can be increased when Melphalan is combined with Palbociclib. |
| Palifermin | The therapeutic efficacy of Palifermin can be decreased when used in combination with Melphalan. |
| Panobinostat | The risk or severity of adverse effects can be increased when Melphalan is combined with Panobinostat. |
| Parnaparin | The risk or severity of bleeding can be increased when Parnaparin is combined with Melphalan. |
| Pazopanib | The risk or severity of adverse effects can be increased when Melphalan is combined with Pazopanib. |
| Pegaspargase | The risk or severity of adverse effects can be increased when Pegaspargase is combined with Melphalan. |
| Pegcetacoplan | The risk or severity of adverse effects can be increased when Melphalan is combined with Pegcetacoplan. |
| Peginesatide | The risk or severity of Thrombosis can be increased when Peginesatide is combined with Melphalan. |
| Peginterferon alfa-2a | The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Melphalan. |
| Peginterferon alfa-2b | The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Melphalan. |
| Peginterferon beta-1a | The risk or severity of adverse effects can be increased when Melphalan is combined with Peginterferon beta-1a. |
| Pemetrexed | The risk or severity of adverse effects can be increased when Pemetrexed is combined with Melphalan. |
| Penicillamine | The risk or severity of adverse effects can be increased when Penicillamine is combined with Melphalan. |
| Pentosan polysulfate | The risk or severity of bleeding can be increased when Pentosan polysulfate is combined with Melphalan. |
| Pentostatin | The risk or severity of adverse effects can be increased when Pentostatin is combined with Melphalan. |
| Pentoxifylline | The risk or severity of bleeding can be increased when Pentoxifylline is combined with Melphalan. |
| Pertussis vaccine | The therapeutic efficacy of Pertussis vaccine can be decreased when used in combination with Melphalan. |
| Phenindione | The risk or severity of bleeding can be increased when Phenindione is combined with Melphalan. |
| Phenol | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Phenol. |
| Phenprocoumon | The risk or severity of bleeding can be increased when Phenprocoumon is combined with Melphalan. |
| Phenylalanine | The risk or severity of adverse effects can be increased when Phenylalanine is combined with Melphalan. |
| Pimecrolimus | The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Melphalan. |
| Pirfenidone | The risk or severity of adverse effects can be increased when Melphalan is combined with Pirfenidone. |
| Polythiazide | The risk or severity of neutropenia and thrombocytopenia can be increased when Polythiazide is combined with Melphalan. |
| Pomalidomide | The risk or severity of adverse effects can be increased when Melphalan is combined with Pomalidomide. |
| Ponatinib | The risk or severity of adverse effects can be increased when Melphalan is combined with Ponatinib. |
| Ponesimod | The risk or severity of adverse effects can be increased when Melphalan is combined with Ponesimod. |
| Pralatrexate | The risk or severity of adverse effects can be increased when Melphalan is combined with Pralatrexate. |
| Pramocaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Pramocaine. |
| Prasugrel | The risk or severity of bleeding can be increased when Prasugrel is combined with Melphalan. |
| Prednisolone | The risk or severity of adverse effects can be increased when Prednisolone is combined with Melphalan. |
| Prednisone | The risk or severity of adverse effects can be increased when Prednisone is combined with Melphalan. |
| Prilocaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Prilocaine. |
| Procaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Procaine. |
| Procarbazine | The risk or severity of adverse effects can be increased when Melphalan is combined with Procarbazine. |
| Proparacaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Proparacaine. |
| Propoxycaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Propoxycaine. |
| Propylthiouracil | The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Melphalan. |
| Protein C | The risk or severity of bleeding can be increased when Protein C is combined with Melphalan. |
| Protein S human | The risk or severity of bleeding can be increased when Protein S human is combined with Melphalan. |
| Rabies immune globulin | The therapeutic efficacy of Rabies immune globulin, human can be decreased when used in combination with Melphalan. |
| Rabies antigen, A | The therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Melphalan. |
| Rabies virus | The therapeutic efficacy of Rabies virus inactivated antigen, B can be decreased when used in combination with Melphalan. |
| Raltitrexed | The risk or severity of adverse effects can be increased when Raltitrexed is combined with Melphalan. |
| Ravulizumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Ravulizumab. |
| Reteplase | The risk or severity of bleeding can be increased when Reteplase is combined with Melphalan. |
| Reviparin | The risk or severity of bleeding can be increased when Reviparin is combined with Melphalan. |
| Rilonacept | The risk or severity of adverse effects can be increased when Melphalan is combined with Rilonacept. |
| Risankizumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Risankizumab. |
| Rituximab | The risk or severity of adverse effects can be increased when Rituximab is combined with Melphalan. |
| Rivaroxaban | The risk or severity of bleeding can be increased when Rivaroxaban is combined with Melphalan. |
| Roflumilast | Roflumilast may increase the immunosuppressive activities of Melphalan. |
| Ropeginterferon alfa-2b | The risk or severity of adverse effects can be increased when Melphalan is combined with Ropeginterferon alfa-2b. |
| Ropivacaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Ropivacaine. |
| Rotavirus vaccine | The therapeutic efficacy of Rotavirus vaccine can be decreased when used in combination with Melphalan. |
| Rubella virus vaccine | The risk or severity of infection can be increased when Rubella virus vaccine is combined with Melphalan. |
| Ruxolitinib | The risk or severity of adverse effects can be increased when Melphalan is combined with Ruxolitinib. |
| Sarilumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Sarilumab. |
| Satralizumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Satralizumab. |
| Secukinumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Secukinumab. |
| Siltuximab | The risk or severity of adverse effects can be increased when Melphalan is combined with Siltuximab. |
| Siponimod | The risk or severity of adverse effects can be increased when Melphalan is combined with Siponimod. |
| Sipuleucel-T | The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Melphalan. |
| Sirolimus | The risk or severity of adverse effects can be increased when Sirolimus is combined with Melphalan. |
| Smallpox (Vaccinia) | The therapeutic efficacy of Smallpox (Vaccinia) Vaccine, Live can be decreased when used in combination with Melphalan. |
| Sodium citrate | The risk or severity of bleeding can be increased when Sodium citrate is combined with Melphalan. |
| Sorafenib | The risk or severity of adverse effects can be increased when Sorafenib is combined with Melphalan. |
| Spesolimab | The risk or severity of adverse effects can be increased when Melphalan is combined with Spesolimab. |
| Streptokinase | The risk or severity of bleeding can be increased when Streptokinase is combined with Melphalan. |
| Streptozocin | The risk or severity of adverse effects can be increased when Streptozocin is combined with Melphalan. |
| Sulfamethoxazole | The risk or severity of myelosuppression can be increased when Sulfamethoxazole is combined with Melphalan. |
| Sulfasalazine | The risk or severity of adverse effects can be increased when Sulfasalazine is combined with Melphalan. |
| Sulfinpyrazone | The risk or severity of bleeding can be increased when Sulfinpyrazone is combined with Melphalan. |
| Sulodexide | The risk or severity of bleeding can be increased when Sulodexide is combined with Melphalan. |
| Sunitinib | The risk or severity of adverse effects can be increased when Melphalan is combined with Sunitinib. |
| Tacrolimus | Tacrolimus may increase the immunosuppressive activities of Melphalan. |
| Tedizolid phosphate | The risk or severity of myelosuppression can be increased when Melphalan is combined with Tedizolid phosphate. |
| Temozolomide | The risk or severity of adverse effects can be increased when Temozolomide is combined with Melphalan. |
| Temsirolimus | The risk or severity of adverse effects can be increased when Melphalan is combined with Temsirolimus. |
| Tenecteplase | The risk or severity of bleeding can be increased when Tenecteplase is combined with Melphalan. |
| Teniposide | The risk or severity of adverse effects can be increased when Teniposide is combined with Melphalan. |
| Teprotumumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Teprotumumab. |
| Teriflunomide | The risk or severity of adverse effects can be increased when Melphalan is combined with Teriflunomide. |
| Tetracaine | The risk or severity of methemoglobinemia can be increased when Melphalan is combined with Tetracaine. |
| Thalidomide | The risk or severity of adverse effects can be increased when Thalidomide is combined with Melphalan. |
| Thiotepa | The risk or severity of adverse effects can be increased when Melphalan is combined with Thiotepa. |
| Ticagrelor | The risk or severity of bleeding can be increased when Ticagrelor is combined with Melphalan. |
| Tick-borne encephalitis | The therapeutic efficacy of Tick-borne encephalitis vaccine (whole virus, inactivated) can be decreased when used in combination with Melphalan. |
| Ticlopidine | The risk or severity of bleeding can be increased when Ticlopidine is combined with Melphalan. |
| Tinzaparin | The risk or severity of bleeding can be increased when Tinzaparin is combined with Melphalan. |
| Tioguanine | The risk or severity of adverse effects can be increased when Tioguanine is combined with Melphalan. |
| Tirofiban | The risk or severity of bleeding can be increased when Tirofiban is combined with Melphalan. |
| Tixocortol | The risk or severity of adverse effects can be increased when Melphalan is combined with Tixocortol. |
| Tocilizumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Tocilizumab. |
| Tofacitinib | Melphalan may increase the immunosuppressive activities of Tofacitinib. |
| Topotecan | The risk or severity of adverse effects can be increased when Topotecan is combined with Melphalan. |
| Tositumomab | The risk or severity of adverse effects can be increased when Tositumomab is combined with Melphalan. |
| Trabectedin | The risk or severity of adverse effects can be increased when Melphalan is combined with Trabectedin. |
| Trastuzumab | Trastuzumab may increase the neutropenic activities of Melphalan. |
| Trastuzumab emtansine | The risk or severity of adverse effects can be increased when Melphalan is combined with Trastuzumab emtansine. |
| Tretinoin | The risk or severity of adverse effects can be increased when Tretinoin is combined with Melphalan. |
| Triamcinolone | The risk or severity of adverse effects can be increased when Triamcinolone is combined with Melphalan. |
| Trichlormethiazide | The risk or severity of neutropenia and thrombocytopenia can be increased when Trichlormethiazide is combined with Melphalan. |
| Trifluridine | The risk or severity of adverse effects can be increased when Trifluridine is combined with Melphalan. |
| Triflusal | The risk or severity of bleeding can be increased when Triflusal is combined with Melphalan. |
| Trilostane | The risk or severity of adverse effects can be increased when Melphalan is combined with Trilostane. |
| Typhoid vaccine | The therapeutic efficacy of Typhoid vaccine can be decreased when used in combination with Melphalan. |
| Typhoid Vaccine Live | The risk or severity of infection can be increased when Typhoid Vaccine Live is combined with Melphalan. |
| Typhoid Vi polysaccharide | The therapeutic efficacy of Typhoid Vi polysaccharide vaccine can be decreased when used in combination with Melphalan. |
| Upadacitinib | The risk or severity of adverse effects can be increased when Melphalan is combined with Upadacitinib. |
| Urokinase | The risk or severity of bleeding can be increased when Urokinase is combined with Melphalan. |
| Varicella zoster vaccine | The risk or severity of infection can be increased when Varicella zoster vaccine (live/attenuated) is combined with Melphalan. |
| Varicella zoster vaccine | The therapeutic efficacy of Varicella zoster vaccine (recombinant) can be decreased when used in combination with Melphalan. |
| Vedolizumab | The risk or severity of adverse effects can be increased when Melphalan is combined with Vedolizumab. |
| CVD 103-HgR strain live antigen | The therapeutic efficacy of Vibrio cholerae CVD 103-HgR strain live antigen can be decreased when used in combination with Melphalan. |
| Vilanterol | The risk or severity of adverse effects can be increased when Melphalan is combined with Vilanterol. |
| Vinblastine | The risk or severity of adverse effects can be increased when Vinblastine is combined with Melphalan. |
| Vincristine | The risk or severity of adverse effects can be increased when Vincristine is combined with Melphalan. |
| Vindesine | The risk or severity of adverse effects can be increased when Vindesine is combined with Melphalan. |
| Vinorelbine | The risk or severity of adverse effects can be increased when Vinorelbine is combined with Melphalan. |
| Voclosporin | The risk or severity of adverse effects can be increased when Melphalan is combined with Voclosporin. |
| Vorapaxar | The risk or severity of bleeding can be increased when Vorapaxar is combined with Melphalan. |
| Vorinostat | The risk or severity of adverse effects can be increased when Melphalan is combined with Vorinostat. |
| Warfarin | The risk or severity of bleeding can be increased when Warfarin is combined with Melphalan. |
| Ximelagatran | The risk or severity of bleeding can be increased when Ximelagatran is combined with Melphalan. |
Pregnancy and Lactation
US FDA pregnancy category: Not Assigned
Pregnancy
There are no animal studies to evaluate the risk of exposure to the mother or the unborn child. This drug is genotoxic and has shown to be toxic to actively dividing animal cells. This drug has the potential to be teratogenic and cause embryo-fetal lethality. Based on animal toxicology studies, this drug may impair fertility in males and cause irreversible testicular suppression. There are no controlled data in human pregnancy.
Lactation
This drug should not be used during breastfeeding and for at least 1 week following the last dose. The effects on the nursing infant and milk production are unknown.
How should this medicine be used?
Melphalan comes as a tablet to take by mouth. It is usually taken on an empty stomach once a day. The length of treatment depends on the types of drugs you are taking, how well your body responds to them, and the type of cancer you have. Take melphalan at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take melphalan exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Your doctor may need to delay your treatment or adjust your dose of melphalan depending on your response to treatment and any side effects that you experience. Talk to your doctor about how you are feeling during your treatment. Do not stop taking melphalan without talking to your doctor.
Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient.
What special precautions should I follow?
Before taking melphalan,
- tell your doctor and pharmacist if you are allergic to melphalan, any other medications, or any of the ingredients in melphalan tablets. Ask your pharmacist for a list of the ingredients.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: carmustine (BICNU, BCNU), cimetidine (Tagamet), cisplatin (Platinol AQ), cyclosporine (Sandimmune, Gengraf, Neoral), or interferon alfa (Intron A, Infergen, Alferon N).
- tell your doctor if you have taken melphalan before, but your cancer did not respond to the medication. Your doctor will probably tell you not to take melphalan.
- tell your doctor if you have received radiation therapy or other chemotherapy recently or if you have or have ever had kidney disease.
- you should know that melphalan may interfere with the normal menstrual cycle (period) in women and may temporarily or permanently stop sperm production in men. Melphalan may cause infertility (difficulty becoming pregnant); however, you should not assume that you cannot get pregnant or that you cannot get someone else pregnant. Women who are pregnant or breast-feeding should tell their doctors before they begin taking this drug. You should not plan to have children while receiving chemotherapy or for a while after treatments. (Talk to your doctor for further details.) Use a reliable method of birth control to prevent pregnancy. Melphalan may harm the fetus.
- do not have any vaccinations without talking to your doctor.
References
