Alkeran Injection

Multiple Myeloma-Conditioning Treatment

Alkeran Injection is indicated for use as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma.

Multiple Myeloma-Palliative Treatment

Alkeran Injection is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.

Alkeran Injection belongs to the group of medicines called alkylating agents. It is used to treat cancer of the ovaries and a certain type of cancer in the bone marrow.

Alkeran Injection interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by Alkeran Injection, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used.

Before you begin treatment with Alkeran Injection, you and your doctor should talk about the good Alkeran Injection will do as well as the risks of using it.

Alkeran Injection is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Alkeran Injection is used in certain patients with the following conditions:

• Cancer of the breast
• Waldenström's macroglobulinemia (type of cancer of the blood)
• Cancer of the blood and lymph system
• Cancer of the endometrium
• Malignant melanoma (type of skin cancer that has spread to other parts of the body)

Recommended Dosage For Conditioning Treatment

The recommended dose of Alkeran Injection for conditioning treatment is 100 mg/m²/day administered over 30 minutes by intravenous infusion for 2 consecutive days (Day -3 and Day -2) prior to autologous stem cell transplantation (ASCT, Day 0). For patients who weigh more than 130% of their ideal body weight, body surface area should be calculated based on adjusted ideal body weight.

Administer prophylactic antiemetics.

Recommended Dosage For Palliative Treatment

The recommended dose of Alkeran Injection for palliative treatment is 16 mg/m² administered as a single intravenous infusion over 15-20 minutes at 2-week intervals for 4 doses, then, after adequate recovery from toxicity, at 4-week intervals.

Administer prophylactic anti-emetics.

Dose Modification For Renal Impairment

For Conditioning Treatment

No dose adjustment is necessary.

For Palliative Treatment

Dosage reduction of up to 50% should be considered in patients with renal impairment (BUN ≥ 30 mg/dL).

Preparation And Administration

Alkeran Injection is a cytotoxic drug. Follow applicable special handling and disposal procedures.

Alkeran Injection is light sensitive. Retain in original carton until use.

Do not mix Alkeran Injection with other Alkeran Injection hydrochloride for injection drug products.

Reconstitution and Infusion Instructions

1. Use normal saline solution (0.9% Sodium Chloride Injection, USP) (8.6 mL as directed) to reconstitute Alkeran Injection and make a 50 mg/10 mL (5 mg/ mL) nominal concentration of Alkeran Injection. The normal saline used to reconstitute each vial should appear to be assisted or pulled into the vial by the negative pressure (partial vacuum) present in the vial. Discard any vial (and replace with another vial) if there is no vacuum present when reconstituting the vial with normal saline.

The reconstituted Alkeran Injection drug product is stable for 24 hours at refrigerated temperature (5oC) without any precipitation due to the high solubility.

The reconstituted Alkeran Injection drug product is stable for 1 hour at room temperature.

2. Calculate the required volume of Alkeran Injection needed for a patient's dose and withdraw that volume from the vial(s).

3. Add the required volume of Alkeran Injection to the appropriate volume of 0.9% Sodium Chloride Injection, USP to a final concentration of 0.45 mg/mL.

The Alkeran Injection admixture solution is stable for 4 hours at room temperature in addition to the 1 hour following reconstitution.

4. Infuse over 30 minutes via an injection port or central venous catheter.

Alkeran Injection may cause local tissue damage should extravasation occur. Do not administer by direct injection into a peripheral vein. Administer Alkeran Injection by injecting slowly into a fast-running IV infusion via a central venous access line.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

How supplied

Dosage Forms And Strengths

For injection: 50 mg, white to off-white lyophilized powder in single-dose vial for reconstitution (after reconstitution the solution is clear and colorless to light yellow). Each vial contains 50 mg Alkeran Injection free base equivalent to 56 mg Alkeran Injection hydrochloride.

Alkeran Injection is supplied in a single carton containing one (1) vial. Each 50 mg vial contains a white to off-white lyophilized powder in single-dose vial for reconstitution (after reconstitution the solution is clear and colorless to light yellow). Each vial contains 50 mg Alkeran Injection free base equivalent to 56 mg Alkeran Injection hydrochloride.

NDC 68152-109-00: Individual carton of Alkeran Injection 20 mL single-dose vial containing 50 mg Alkeran Injection free base.

Storage And Handling

Store Alkeran Injection at room temperature 25°C (77°F). Temperature excursions are permitted between 15-30°C (59- 86°F).

Alkeran Injection is light sensitive. Retain in original carton until use.

Alkeran Injection is a cytotoxic drug. Follow special handling and disposal procedures.

REFERENCES

1 OSHA Hazardous Drugs. OSHA. [Accessed on 9 December 2014, from http://www.osha.gov/SLTC/hazardousdrugs/index.html].

Manufactured for: Spectrum Pharmaceuticals, In cc. Irvine, CA 92618. Revised: March 2016

See also:
What is the most important information I should know about Alkeran Injection?

Do not use this medication if you are pregnant. It could cause harm to the unborn baby. Use an effective form of birth control, and tell your doctor if you become pregnant during treatment.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Alkeran Injection can cause serious side effects, including: decreased bone marrow function and blood problems (easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms, bloody or black stools, pale or yellowed skin, confusion or weakness); breathing problems; or liver damage (nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice [yellowing of the skin or eyes]). Call your doctor at once if you have any of these side effects.

In some cases, second cancers have been reported to occur during and after treatment with Alkeran Injection. Talk to your doctor about your individual risk and benefit of this medication.

Use Alkeran Injection as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Alkeran Injection is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Alkeran Injection at home, a health care provider will teach you how to use it. Be sure you understand how to use Alkeran Injection. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Do not use Alkeran Injection if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• If you spill Alkeran Injection on your skin, wash it off right away with soap and water. Clean any areas (tables, counters) where Alkeran Injection may have spilled or sprayed.
• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Alkeran Injection, contact your doctor immediately.

Ask your health care provider any questions you may have about how to use Alkeran Injection.

Use: Labeled Indications

Multiple myeloma: Palliative treatment of multiple myeloma (injection [Alkeran Injection and Alkeran Injection] and tablets); high-dose conditioning treatment prior to hematopoietic stem cell transplantation (HSCT) (Alkeran Injection only).

Ovarian cancer: Palliative treatment of nonresectable epithelial ovarian carcinoma (tablets)

Off Label Uses

Amyloidosis, light chain

Data from a randomized study support the use of oral Alkeran Injection at a standard dose (in combination with high-dose dexamethasone) for the treatment of light chain amyloidosis.

See also:
What other drugs will affect Alkeran Injection?

The development of severe renal failure has been reported in patients treated with a single dose of IV Alkeran Injection followed by standard oral doses of cyclosporine. Cisplatin may affect Alkeran Injection kinetics by inducing renal dysfunction and subsequently altering Alkeran Injection clearance. IV Alkeran Injection may also reduce the threshold for BCNU lung toxicity. When nalidixic acid and IV Alkeran Injection are given simultaneously, the incidence of severe hemorrhagic necrotic enterocolitis has been reported to increase in pediatric patients.

See also:
What are the possible side effects of Alkeran Injection?

The following serious adverse reactions are described in more detail in other sections of the prescribing information.

• Bone Marrow Suppression
• Gastrointestinal Toxicity
• Hepatotoxicity
• Hypersensitivity
• Secondary Malignancies

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of Alkeran Injection may not reflect the rates observed in practice.

The most common adverse reactions observed in at least 50% of patients with multiple myeloma treated with Alkeran Injection were neutrophil count decreased, white blood cell count decreased, lymphocyte count decreased, platelet count decreased, diarrhea, nausea, fatigue, hypokalemia, anemia, and vomiting.

Myeloablative Conditioning In Multiple Myeloma Patients Undergoing ASCT

The safety of Alkeran Injection was evaluated in 61 patients with multiple myeloma in a single arm clinical trial in which patients were administered Alkeran Injection at a dosage of 100 mg/m /day administered over ~30 minutes (range: 24-48 minutes) by intravenous (IV) infusion for 2 consecutive days (Day -3 and Day -2) prior to autologous stem cell transplant (ASCT, Day 0).

Table 1 summarizes the adverse reactions from the single-arm trial in patients with multiple myeloma. Severe myelosuppression is expected and these adverse reactions are not listed below.

Table 1: Non-hematologic Adverse Reactions in > 25% of Patients with Multiple Myeloma Who Received Alkeran Injection Conditioning for ASCT

Serious Adverse Reactions

Twelve (20%) patients experienced a treatment emergent serious adverse reaction while on study. The most common serious adverse reactions ( > 1 patient, 1.6%) were pyrexia, hematochezia, febrile neutropenia, and renal failure. Treatment-related serious adverse reactions reported in > 1 patient were pyrexia (n=2, 3%), febrile neutropenia (n=2, 3%), and hematochezia (n=2, 3%).

Palliative Treatment Of Patients With Multiple Myeloma

The safety of Alkeran Injection was evaluated in 295 patients with multiple myeloma in the randomized clinical trial. One hundred and ninety-five patients were administered IV Alkeran Injection at a dosage of 16 mg/m q 2 weeks x 4 (over 6 weeks) followed by the same dose every 4 weeks. One hundred patients were administered oral Alkeran Injection at a dosage of 0.15 mg/kg/day x 7 followed by 0.05 mg/kg/day when WBC counts began to rise.

Severe myelotoxicity (WBC ≤ 1,000 and/or platelets ≤ 25,000) was more common in the IV Alkeran Injection arm (28%) than in the oral Alkeran Injection arm (11%).

An association was noted between poor renal function and myelosuppression; consequently, an amendment to the protocol required a 50% reduction in IV Alkeran Injection dose if the BUN was ≥ 30 mg/dL. The rate of severe leukopenia in the IV arm in the patients with BUN over 30 mg/dL decreased from 50% (8/16) before protocol amendment to 11% (3/28) after the amendment.

Before the dosing amendment, there was a 10% (8/77) incidence of drug-related death in the IV arm. After the dosing amendment, this incidence was 3% (3/108). This compares to an overall 1% (1/100) incidence of drugrelated death in the oral Alkeran Injection arm.

An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - Alkeran Injection, the racemic mixture - merphalan, and the dextro isomer - medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [PubChem]