Evomela (Intra-arterial, Intravenous)

Melphalan injection is used to treat multiple myeloma (bone marrow cancer) before a stem cell transplant (conditioning treatment). Melphalan is part of a group of medicines called alkylating agents (cancer medicines). It works by disrupting the growth of cancer cells, which the body eventually destroys. Because melphalan can also affect the growth of normal cells, other unwanted effects may happen. Before starting treatment with melphalan, discuss the benefits and risks with your doctor.

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

It is very important for your doctor to check your progress at regular visits to ensure 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 can become pregnant, your doctor may perform tests to confirm you are not pregnant before receiving this medicine. Use an effective form of birth control while receiving this medicine and for at least 6 months after the last dose to avoid getting pregnant. Males receiving this medicine with female partners who can become pregnant must use effective birth control during treatment and for at least 3 months after the last dose. If you think you might be pregnant while receiving the medicine, inform your doctor immediately.

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

This medicine may cause bleeding problems. Contact your doctor immediately if you have bleeding gums, cough up blood, have difficulty breathing or swallowing, feel dizzy, have a headache, experience increased menstrual flow or vaginal bleeding, have nosebleeds, experience paralysis, have prolonged bleeding from cuts, or notice red or dark brown urine, or red or black, tarry stools.

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

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

• If possible, avoid people with infections. Contact your doctor immediately if you think you are getting an infection or if you develop a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Contact your doctor immediately if you notice any unusual bleeding or bruising, black or tarry stools, blood in your urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your doctor, dentist, or nurse may suggest other ways to clean your teeth and gums. Check with your 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 cautious when using sharp objects like safety razors or fingernail or toenail clippers to avoid cutting yourself.
• Avoid contact sports or other situations where bruising or injury could happen.

While you are being treated with melphalan, and after you finish treatment, do not receive 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 contract the infection the vaccine is intended to prevent. Additionally, you should not be around others in your household who receive live virus vaccines because they could potentially pass the virus to you. Some examples of live vaccines include measles, mumps, influenza (nasal flu vaccine), poliovirus (oral form), rotavirus, and rubella. Avoid close contact and do not stay in the same room with them for extended periods. 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 manage these symptoms.

Using this medicine may increase your risk of developing other types of cancer (eg, myeloproliferative syndrome, acute leukemia, and carcinoma). Discuss any concerns about this risk with your doctor.

Inform your doctor immediately if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellowing of your eyes or skin. These could indicate a serious liver problem.

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

In deciding to use a medicine, you and your doctor will need to weigh the risks of taking it against the benefits it may provide. For this medicine, please consider the following:

Allergies

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

Pediatric

Studies have not been done to determine how melphalan injection affects children. Safety and effectiveness have not been established.

Geriatric

Studies so far have not found specific problems in elderly patients that would limit the usefulness of melphalan injection in this age group. However, older patients are more likely to have liver, kidney, or heart issues due to aging, which may require caution when using this medicine.

Breast Feeding

There are no adequate studies in women to determine the risk to infants when using this medication while breastfeeding. Consider the potential benefits and risks before taking this medication during breastfeeding.

Interactions with Medicines

Some medicines should not be taken together at all, while in other cases, two different medicines may be used together even if there might be an interaction. If you are receiving this medicine, it is very important for your healthcare professional to know if you are taking any of the following medicines. The interactions listed below are based on their potential significance and are not 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 necessary in some cases. If both medicines are prescribed together, your doctor may adjust the dose or frequency of one or both 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 increase the risk of certain side effects, but taking both drugs may be the best option for you. If both medicines are prescribed together, your doctor may adjust the dose or frequency of one or both medicines.

• Buthionine Sulfoximine
• Nalidixic Acid

Interactions with Food/Tobacco/Alcohol

Some medicines should not be taken around the time of eating food or certain types of food due to possible interactions. Using alcohol or tobacco with certain medicines may also lead to interactions. Discuss with your healthcare professional about using your medicine with food, alcohol, or tobacco.

Other Medical Problems

Having other medical problems may affect the use of this medicine. Make sure to tell your doctor if you have any other medical issues, 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 (e.g., 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 these conditions.

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

• Infection—May reduce your ability to fight infections.

• Kidney disease—Use carefully. The effects may be increased because the body removes the medicine more slowly.

Along with its needed effects, a medicine may cause some unwanted effects. Not all of these side effects may occur, but if they do, 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. Your health care professional may also 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, 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.

In the U.S.

• Alkeran IV
• Evomela

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Alkylating Agent

Chemical Class: Nitrogen Mustard

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.