Information regarding infusion-related reactions1

Keep medications to treat serious, life-threatening, and fatal infusion reactions and emergency equipment to treat such reactions available for immediate use during infusions.

  • Ensure that medications to treat infusion-related reactions and cardiopulmonary resuscitative equipment are available for immediate use prior to initiation of DOXIL®


Rapid infusion may increase the risk of infusion-related reactions; in some patients, the reaction resolved when rate of infusion was slowed.



The majority of infusion-related events occurred during the first infusion of DOXIL®.



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.


In clinical trials, 11% of patients with solid tumors treated with DOXIL® experienced 1 or more acute infusion-related reactions such as:

  • Flushing
  • Shortness of breath
  • Facial swelling
  • Headache
  • Chills
  • Chest pain
  • Back pain
  • Tightness in the chest or throat
  • Fever
  • Tachycardia
  • Pruritus
  • Rash
  • Cyanosis
  • Syncope
  • Bronchospasm
  • Asthma
  • Apnea
  • Hypotension

Serious, life-threatening, and fatal infusion reactions have been reported.



How to manage extravasation1

Discontinue DOXIL® for burning or stinging sensation or other evidence indicating perivenous infiltration or extravasation.

Manage confirmed or suspected extravasation as follows:

  • Do not remove the needle until attempts are made to aspirate extravasated fluid
  • Do not flush the line
  • Avoid applying pressure to the site
  • Apply ice to the site intermittently for 15 minutes, 4 times a day for 3 days
  • If the extravasation is in an extremity, elevate the extremity

Instruct patients to alert you and your team of healthcare professionals if they:

  • Develop any symptoms of heart failure (cardiomyopathy)
  • Experience discoloration (reddish-orange color) of urine and other body fluids
  • Experience a burning or stinging sensation or other evidence indicating perivenous infiltration or extravasation
  • Develop a fever or symptoms of infection (myelosuppression)
  • Experience tingling or burning, redness, flaking, bothersome swelling, small blisters, or small sores on the palms of their hands or soles of their feet (hand-foot syndrome)
  • Develop painful redness, swelling, or sores in the mouth (stomatitis)
  • Suspect that they may be pregnant, or may become pregnant during treatment with DOXIL®
    • Advise patients not to breastfeed during treatment with DOXIL®
    • Advise females and males of reproductive potential to use effective contraception during and for 6 months following treatment with DOXIL®, and that treatment with DOXIL® may cause temporary or permanent infertility

Advise patients about the symptoms of infusion-related reactions and to seek immediate medical attention if they develop any of these symptoms.


References

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

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