Pronunciation:

MEL-fa-lan

Brand Names:

• Alkeran IV
• Evomela

Dosage Forms:

• Powder for Solution

Warnings:

Alkeran(R): Melphalan should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Severe bone marrow suppression with resulting infection or bleeding may occur. Controlled trials comparing intravenous (IV) to oral melphalan have shown more myelosuppression with the IV formulation. Hypersensitivity reactions, including anaphylaxis, have occurred in approximately 2% of patients who received the IV formulation. Melphalan is leukemogenic in humans. Melphalan produces chromosomal aberrations in vitro and in vivo and, therefore, should be considered potentially mutagenic in humans

Evomela(TM): Severe bone marrow suppression with resulting infection or bleeding may occur. Controlled trials have shown more myelosuppression with the IV formulation than the oral formulation. Monitor hematologic laboratory parameters. Hypersensitivity reactions, including anaphylaxis, have occurred in patients who received the IV formulation of melphalan hydrochloride. Discontinue treatment with melphalan hydrochloride for serious hypersensitivity reactions. Melphalan produces chromosomal aberrations in vitro and in vivo. Melphalan hydrochloride should be considered potentially leukemogenic in humans .

Warning: Peri-Procedural Complications, MyelosuppressionSevere peri-procedural complications including hemorrhage, hepatocellular injury, and thromboembolic events may occur via hepatic intra-arterial administration of melphalan. Assess patients for these adverse reaction during and for at least 72 hours following administration of melphalan.Melphalan is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the HEPZATO KIT REMS.Myelosuppression with resulting severe infection, bleeding, or symptomatic anemia may occur with melphalan. Monitor hematologic laboratory parameters and delay additional cycles of melphalan therapy until blood counts have improved .

Classifications:

Therapeutic—

Antineoplastic Agent

Pharmacologic—

Alkylating Agent

Chemical—

Nitrogen Mustard

Uses of This Medicine:

Melphalan injection is used to treat multiple myeloma (bone marrow cancer) before receiving a stem cell transplant (conditioning treatment). Melphalan belongs to the group of medicines called alkylating agents (cancer medicines). It works by interfering with the growth of cancer cells, which are eventually destroyed by the body. Since the growth of normal cells may also be affected by melphalan, other unwanted effects will also occur. Before you begin treatment with melphalan, talk to your doctor about the benefits as well as the risks of using it.

Melphalan injection is also used to treat uveal melanoma (eye cancer) that has spread to the liver and cannot be removed by surgery (unresectable liver metastases).

Evomela®, Alkeran®, and Melphalan injection are to be given only by or under the direct supervision of your doctor. Hepzato® injection is available only under a restricted distribution program called Hepzato® Kit REMS (Risk Evaluation and Mitigation Strategy) Program.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of melphalan injection in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of melphalan injection in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution in patients receiving this medicine.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Measles Virus Vaccine, Live
• Mumps Virus Vaccine, Live
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Varicella Virus Vaccine, Live
• Zoster Vaccine, Live

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Aceclofenac
• Acemetacin
• Adenovirus Vaccine
• Alfuzosin
• Amlodipine
• Amtolmetin Guacil
• Anagrelide
• Apixaban
• Aranidipine
• Aspirin
• Bacillus of Calmette and Guerin Vaccine, Live
• Benazepril
• Bepridil
• Bromfenac
• Bufexamac
• Bunazosin
• Captopril
• Celecoxib
• Cholera Vaccine, Live
• Choline Salicylate
• Cilnidipine
• Cilostazol
• Clevidipine
• Clonixin
• Clopidogrel
• Dabigatran Etexilate
• Dapiprazole
• Dengue Tetravalent Vaccine, Live
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Diltiazem
• Dipyridamole
• Dipyrone
• Doxazosin
• Droxicam
• Edoxaban
• Enalapril
• Enalaprilat
• Eptifibatide
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Felodipine
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Fosinopril
• Ibuprofen
• Indomethacin
• Influenza Virus Vaccine, Live
• Isradipine
• Ketoprofen
• Ketorolac
• Lercanidipine
• Lisinopril
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Manidipine
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Moexipril
• Morniflumate
• Moxisylyte
• Nabumetone
• Naproxen
• Nepafenac
• Nicardipine
• Nifedipine
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nimodipine
• Nisoldipine
• Nitrendipine
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Perindopril
• Phenoxybenzamine
• Phentolamine
• Phenylbutazone
• Piketoprofen
• Piroxicam
• Poliovirus Vaccine, Live
• Pranoprofen
• Prasugrel
• Prazosin
• Proglumetacin
• Propyphenazone
• Proquazone
• Quinapril
• Ramipril
• Rivaroxaban
• Rofecoxib
• Salicylic Acid
• Salsalate
• Silodosin
• Smallpox Vaccine
• Sodium Salicylate
• Sulfinpyrazone
• Sulindac
• Tamsulosin
• Tenoxicam
• Terazosin
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Trandolapril
• Treprostinil
• Trimazosin
• Typhoid Vaccine, Live
• Urapidil
• Valdecoxib
• Verapamil
• Vorapaxar
• Warfarin
• Yellow Fever Vaccine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Buthionine Sulfoximine
• Nalidixic Acid

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to heparin, history of or
• Allergy to iodinated contrast agents not controlled by allergy medicine or steroids, history of or
• Allergy to latex, history of or
• Angina (chest pain) or
• Bleeding problems or
• Blood clotting problems (eg, uncorrectable coagulopathy) or
• Brain cancer, active or
• Heart attack or
• Heart disease or
• Heart failure, new or worsening or
• Heart rhythm problems or
• Liver failure or
• Liver treatment or surgery within the past 4 weeks or
• Portal hypertension (high blood pressure in the liver portal vein) or
• Thrombocytopenia (low number of platelets), heparin-induced—Should not be used in patients with these conditions.

• Anemia or
• Bone marrow suppression or
• Leukopenia (low white blood cells) or
• Liver disease or
• Thrombocytopenia (low platelets in the blood)—Use with caution. May make these conditions worse.

• Infection—May decrease your ability to fight an infection.

• Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of This Medicine:

Evomela® and Alkeran®: A nurse or other trained health professional will give you this medicine in a hospital or cancer treatment center. It is given through a needle placed into one of your veins. This medicine must be given slowly, so the IV tube will need to stay in place for at least 30 minutes. It is usually given for 2 days before receiving a stem cell transplant.

Melphalan injection: A nurse or other trained health professional will give you this medicine in a hospital or cancer treatment center. It is given through a needle placed into one of your veins. This medicine must be given slowly, so the IV tube will need to stay in place for at least 15 to 20 minutes.

Hepzato®: A doctor or other trained health professional will give you this medicine in a hospital. It is given through a needle placed into an artery of the liver every 6 to 8 weeks.

This medicine should come with a patient information leaflet. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Receiving this medicine while you are pregnant can harm your unborn baby. If you are a woman who can get pregnant, your doctor may do tests to make sure you are not pregnant before receiving this medicine. Use an effective form of birth control while you are receiving this medicine and for at least 6 months after the last dose to keep from getting pregnant. Males who are receiving this medicine, with female partners who can become pregnant, must use effective birth control during and for at least 3 months after the last dose of this medicine. If you think you have become pregnant while receiving the medicine, tell your doctor right away.

This medicine may cause serious allergic reactions, including anaphylaxis, which can be life-threatening and require immediate medical attention. Tell your doctor right away if you have a rash, itching, hives, hoarseness, lightheadedness or fainting, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are receiving this medicine.

This medicine may cause bleeding problems. Check with your doctor right away if you have bleeding gums, coughing up blood, difficulty in breathing or swallowing, dizziness, headache, increased menstrual flow or vaginal bleeding, nosebleeds, paralysis, prolonged bleeding from cuts, red or dark brown urine, or red or black, tarry stools.

Check with your doctor right away if you have pain in the chest, groin, or legs, especially the calves, severe headache, slurred speech, sudden, unexplained trouble breathing, sudden loss of coordination, sudden, severe weakness or numbness in the arm or leg, or vision changes. These may be symptoms of blood clots (eg, thromboembolism).

Melphalan can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

While you are being treated with melphalan, and after you stop treatment with it, do not have any immunizations (vaccines) without your doctor's approval. Melphalan may lower your body's resistance and the vaccine may not work as well or you might get the infection the vaccine is meant to prevent. In addition, you should not be around other persons living in your household who receive live virus vaccines because there is a chance they could pass the virus on to you. Some examples of live vaccines include measles, mumps, influenza (nasal flu vaccine), poliovirus (oral form), rotavirus, and rubella. Do not get close to them and do not stay in the same room with them for very long. If you have questions about this, talk to your doctor.

Melphalan can cause diarrhea, nausea or vomiting, or sores or ulcers in the mouth, sometimes even after you receive medicine to prevent these effects. Ask your doctor or nurse about ways to control these symptoms.

Using this medicine may increase your risk of getting other types of cancer (eg, myeloproliferative syndrome, acute leukemia, and carcinoma). Talk to your doctor if you have concerns about this risk.

Tell your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Some men and women using this medicine have become infertile (unable to have children). This medicine might make a woman stop having menstrual periods temporarily. Talk with your doctor if this is a concern.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

More common

Bleeding gums

blurred vision

chest pain

chills

confusion

cough or hoarseness

coughing up blood

difficulty in swallowing

dizziness

dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position

fever

headache

increased menstrual flow or vaginal bleeding

lower back or side pain

nosebleeds

painful or difficult urination

paralysis

pinpoint red spots on skin

prolonged bleeding from cuts

red or dark brown urine

red or black, tarry stools

sores, ulcers, or white spots on the lips or in the mouth

sweating

swollen glands

trouble breathing

unusual bleeding or bruising

unusual tiredness or weakness

Less common

Blue lips and fingernails

coughing that sometimes produces a pink frothy sputum

dark-colored urine

fast heartbeat

increased sweating

light-colored stools

no blood pressure or pulse

pain, redness, or swelling in the arm or leg

pale skin

stomach pain

stopping of the heart

swelling in the legs and ankles

unconsciousness

vomiting

yellow eyes or skin

Incidence not known

Absent, missed, or irregular menstrual periods

back or leg pains

bloated stomach

chest tightness

clay-colored stools

confusion

fast, pounding, or irregular heartbeat or pulse

general body swelling

hives, itching, rash

indigestion

light-colored stools

loss of appetite

nausea

noisy breathing

pain and fullness in the right upper abdomen or stomach

puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue

reddening of the skin, especially around the ears

sore throat

swelling of the eyes, face, hands, ankles, feet, or lower legs

unpleasant breath odor

unusual lumps or masses

vomiting of blood

weight gain or loss

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

Indigestion

passing of gas

stomach fullness

Incidence not known

Blue-green to black skin discoloration

hair loss or thinning of the hair

pain, redness, soreness, or sloughing of the skin at the injection site

sores, welting, or blisters

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.