Dosing for relapsed or refractory multiple myeloma1-3

DOXIL®, in combination with bortezomib, is indicated for the treatment of patients with multiple myeloma who:

  • Have not previously received bortezomib1 and
  • Have received at least 1 prior therapy1
  • Do not substitute DOXIL® for doxorubicin HCl injection1
  • Do not administer as an undiluted suspension or as an intravenous bolus1

The recommended dose of DOXIL® is 30 mg/m2 intravenously over 60 minutes on Day 4 of each 21-day cycle for 8 cycles or until disease progression or unacceptable toxicity.1

  • Administer DOXIL® after bortezomib on Day 4 of each cycle1
    • Administration of the first dose of DOXIL® at an initial rate of 1 mg/min may help minimize the risk of infusion-related reactions1
    • If no infusion-related reactions are observed, increase the infusion rate to complete the administration over 1 hour. Do not rapidly flush the infusion line1

In the event of an infusion-related reaction, temporarily stop the drug until resolution, then resume at a reduced infusion rate. Discontinue DOXIL® infusion for serious or life-threatening infusion-related reactions. Medications/emergency equipment to treat such reactions should be available for immediate use.1 See Important Safety Information below.


Treatment schedule1-3

*Rapid flushing of the infusion line should be avoided.

An initial rate of 1 mg/min should be used with the first dose of DOXIL® to minimize the risk of infusion-related adverse reactions.


Dose modifications and management of adverse reactions1

  • Dose may be delayed, reduced, or discontinued to manage adverse reactions such as hand-foot syndrome (HFS), stomatitis, or hematologic toxicities1
  • DO NOT increase the dose of DOXIL® after a dose reduction for toxicity1

Hand-Foot Syndrome (HFS) and stomatitis1





Neutropenia or thrombocytopenia1





Recommended dose modifications of DOXIL® for toxicity when administered in combination with bortezomib1



For neuropathic pain or peripheral neuropathy, no dosage adjustments are required for DOXIL®. Refer to bortezomib manufacturer’s Prescribing Information.1



References

  1. DOXIL® (doxorubicin HCl liposome injection) Prescribing Information. Janssen Products, LP, Horsham, PA.

  2. Data on file. Janssen Products, LP, Horsham, PA.

  3. Velcade® (bortezomib) Prescribing Information. Millennium Pharmaceuticals, Inc.

IMPORTANT SAFETY INFORMATION

WARNING: CARDIOMYOPATHY and INFUSION-RELATED REACTIONS

DOXIL® (doxorubicin HCl liposome injection) can cause myocardial damage, including congestive heart failure, as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2. In a clinical study of 250 patients with advanced cancer who were treated with DOXIL®, the risk of cardiotoxicity was 11% when the cumulative anthracycline dose was between 450-550 mg/m2. Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dosage. The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation. See additional information on Cardiomyopathy in Warnings and Precautions below.

Acute infusion-related reactions consisting of, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension occurred in 11% of patients with solid tumors treated with DOXIL®. Serious, life-threatening and fatal infusion reactions have been reported. Medications/emergency equipment to treat such reactions should be available for immediate use. See additional information on Infusion-Related Reactions in Warnings and Precautions below.

Contraindications

DOXIL® is contraindicated in patients who have a history of severe hypersensitivity reactions, including anaphylaxis, to doxorubicin HCl.

Warnings and Precautions

Cardiomyopathy: Doxorubicin HCl can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy with doxorubicin HCl is generally proportional to the cumulative exposure. The relationship between cumulative DOXIL® dose and the risk of cardiac toxicity has not been determined. Assess left ventricular cardiac function (e.g. MUGA or echocardiogram) prior to initiation of DOXIL®, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Administer DOXIL® to patients with a history of cardiovascular disease only when the potential benefit of treatment outweighs the risk.

Infusion-Related Reactions: Serious and sometimes life-threatening infusion-related reactions characterized by one or more of the following symptoms can occur with DOXIL®: flushing, shortness of breath, facial swelling, headache, chills, chest pain, back pain, tightness in the chest and throat, fever, tachycardia, pruritus, rash, cyanosis, syncope, bronchospasm, asthma, apnea, and hypotension. The majority of infusion-related events occurred during the first infusion. Ensure that medications to treat infusion-related reactions and cardiopulmonary resuscitative equipment is available for immediate use prior to initiation of DOXIL®. Initiate DOXIL® infusions at a rate of 1 mg/min and increase rate as tolerated. In the event of an infusion-related reaction, temporarily stop the drug until resolution then resume at a reduced infusion rate. Discontinue DOXIL® infusion for serious or life-threatening infusion-related reactions.

Hand-foot syndrome (HFS): HFS may occur during therapy with DOXIL®. Based on HFS toxicity grade, dose reduction, delay in administration, or discontinuation of DOXIL® may be required.

  • HFS was generally observed after 2 to 3 cycles of treatment, but may occur earlier

  • Delay DOXIL® for the first episode of Grade 2 or greater HFS

  • Discontinue DOXIL® if HFS is severe and debilitating

Secondary Oral Neoplasms: Cases of secondary oral cancer have been reported in patients with more than one year's exposure to DOXIL®. Cases were diagnosed both during treatment and up to 6 years after the last dose. Patients should be examined at regular intervals for the presence of oral ulceration or any oral discomfort that may be indicative of secondary oral cancer.

Embryofetal Toxicity: Based on animal data, DOXIL® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during and for 6 months after treatment with DOXIL®.

Adverse Reactions

Most common adverse reactions observed with DOXIL® (>20%) are asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand-foot syndrome, rash, neutropenia, thrombocytopenia, and anemia.

Use in Specific Populations

Lactation: Because of the potential for serious adverse reactions in nursing infants, discontinue nursing during treatment with DOXIL®.

INDICATIONS

DOXIL® is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.

DOXIL® is indicated for the treatment of AIDS-related Kaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.

DOXIL® in combination with bortezomib is indicated for the treatment of patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

Click here to see the full Prescribing Information, including BOXED WARNINGS.

020669-150414

IMPORTANT SAFETY INFORMATION

WARNING: CARDIOMYOPATHY and INFUSION-RELATED REACTIONS

DOXIL® (doxorubicin HCl liposome injection) can cause myocardial damage, including congestive heart failure, as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2. In a clinical study of 250 patients with advanced cancer who were treated with DOXIL®, the risk of cardiotoxicity was 11% when the cumulative anthracycline dose was between 450-550 mg/m2. Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dosage. The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation. See additional information on Cardiomyopathy in Warnings and Precautions below.

Acute infusion-related reactions consisting of, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension occurred in 11% of patients with solid tumors treated with DOXIL®. Serious, life-threatening and fatal infusion reactions have been reported. Medications/emergency equipment to treat such reactions should be available for immediate use. See additional information on Infusion-Related Reactions in Warnings and Precautions below.

Contraindications

DOXIL® is contraindicated in patients who have a history of severe hypersensitivity reactions, including anaphylaxis, to doxorubicin HCl.

Warnings and Precautions

Cardiomyopathy: Doxorubicin HCl can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy with doxorubicin HCl is generally proportional to the cumulative exposure. The relationship between cumulative DOXIL® dose and the risk of cardiac toxicity has not been determined. Assess left ventricular cardiac function (e.g. MUGA or echocardiogram) prior to initiation of DOXIL®, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Administer DOXIL® to patients with a history of cardiovascular disease only when the potential benefit of treatment outweighs the risk.

Infusion-Related Reactions: Serious and sometimes life-threatening infusion-related reactions characterized by one or more of the following symptoms can occur with DOXIL®: flushing, shortness of breath, facial swelling, headache, chills, chest pain, back pain, tightness in the chest and throat, fever, tachycardia, pruritus, rash, cyanosis, syncope, bronchospasm, asthma, apnea, and hypotension. The majority of infusion-related events occurred during the first infusion. Ensure that medications to treat infusion-related reactions and cardiopulmonary resuscitative equipment is available for immediate use prior to initiation of DOXIL®. Initiate DOXIL® infusions at a rate of 1 mg/min and increase rate as tolerated. In the event of an infusion-related reaction, temporarily stop the drug until resolution then resume at a reduced infusion rate. Discontinue DOXIL® infusion for serious or life-threatening infusion-related reactions.

Hand-foot syndrome (HFS): HFS may occur during therapy with DOXIL®. Based on HFS toxicity grade, dose reduction, delay in administration, or discontinuation of DOXIL® may be required.

  • HFS was generally observed after 2 to 3 cycles of treatment, but may occur earlier

  • Delay DOXIL® for the first episode of Grade 2 or greater HFS

  • Discontinue DOXIL® if HFS is severe and debilitating

Secondary Oral Neoplasms: Cases of secondary oral cancer have been reported in patients with more than one year's exposure to DOXIL®. Cases were diagnosed both during treatment and up to 6 years after the last dose. Patients should be examined at regular intervals for the presence of oral ulceration or any oral discomfort that may be indicative of secondary oral cancer.

Embryofetal Toxicity: Based on animal data, DOXIL® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during and for 6 months after treatment with DOXIL®.

Adverse Reactions

Most common adverse reactions observed with DOXIL® (>20%) are asthenia, fatigue, fever, anorexia, nausea, vomiting, stomatitis, diarrhea, constipation, hand-foot syndrome, rash, neutropenia, thrombocytopenia, and anemia.

Use in Specific Populations

Lactation: Because of the potential for serious adverse reactions in nursing infants, discontinue nursing during treatment with DOXIL®.

INDICATIONS

DOXIL® is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.

DOXIL® is indicated for the treatment of AIDS-related Kaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.

DOXIL® in combination with bortezomib is indicated for the treatment of patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

Click here to see the full Prescribing Information, including BOXED WARNINGS.

020669-150414

INDICATIONS

DOXIL® is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.

DOXIL® is indicated for the treatment of AIDS-related Kaposi’s sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.

DOXIL® in combination with bortezomib is indicated for the treatment of patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

Please see full Prescribing Information, including BOXED WARNINGS, for DOXIL® at www.DOXIL.com.

020669-150414