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INTRODUCTION

REMICADE® (infliximab)
PROCRIT® (Epoetin alfa)
LEUSTATIN® (cladribine) Injection
DOXIL® (doxorubicin HCl liposome injection)
SIMPONI™ (golimumab)
STELARA™ (ustekinumab)

Indications for REMICADE® (infliximab)

Rheumatoid Arthritis

REMICADE®, in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis.

Crohn's Disease

REMICADE® is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult and pediatric patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy.

REMICADE® is indicated for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing Crohn's disease.

Ankylosing Spondylitis

REMICADE® is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.

Psoriatic Arthritis

REMICADE® is indicated for reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis.

Plaque Psoriasis

REMICADE® is indicated for the treatment of adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. REMICADE® should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

Ulcerative Colitis

REMICADE® is indicated for reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.

IMPORTANT SAFETY INFORMATION

RISK OF INFECTIONS

Patients treated with REMICADE® (infliximab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue REMICADE® if a patient develops a serious infection or sepsis.

Reported infections include:

  • Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before and during treatment with REMICADE®.1, 2 Treatment for latent infection should be initiated prior to treatment with REMICADE®.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, and pneumocystosis. Patients may present with disseminated, rather than localized, disease. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Bacterial, viral, and other infections due to opportunistic pathogens.

The risks and benefits of treatment with REMICADE® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with REMICADE®, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including REMICADE®. Approximately half of these cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies that are usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

Postmarketing cases of hepatosplenic T-cell lymphoma, a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including REMICADE®. These cases have had a very aggressive disease course and have been fatal. All reported REMICADE® cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. All of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with REMICADE® at or prior to diagnosis.

In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn's disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including REMICADE®, more cases of other malignancies were observed compared with controls. The rate of these malignancies among patients treated with REMICADE® was similar to that expected in the general population whereas the rate in control patients was lower than expected. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD).

CONTRAINDICATIONS

REMICADE® is contraindicated in patients with moderate to severe (NYHA Class III/IV) congestive heart failure (CHF) at doses greater than 5 mg/kg. Higher mortality rates at the 10 mg/kg dose and higher rates of cardiovascular events at the 5 mg/kg dose have been observed in these patients. REMICADE® should be used with caution and only after consideration of other treatment options. Patients should be monitored closely. Discontinue REMICADE® if new or worsening CHF symptoms appear. REMICADE® should not be (re)administered to patients who have experienced a severe hypersensitivity reaction or to patients with hypersensitivity to murine proteins or other components of the product.

HEPATITIS B REACTIVATION

TNF inhibitors, including REMICADE®, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating REMICADE®. Exercise caution when prescribing REMICADE® for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with REMICADE®. Discontinue REMICADE® in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of REMICADE® and monitor patients closely.

HEPATOTOXICITY

Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported rarely in patients receiving REMICADE® postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (e.g., > 5 times the upper limit of normal) develop, REMICADE® should be discontinued, and a thorough investigation of the abnormality should be undertaken.

HEMATOLOGIC EVENTS

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia (some fatal) have been reported. The causal relationship to REMICADE® therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of REMICADE® in patients who develop significant hematologic abnormalities.

HYPERSENSITIVITY

REMICADE® has been associated with hypersensitivity reactions that differ in their time of onset. Acute urticaria, dyspnea, and hypotension have occurred in association with infusions of REMICADE®. Serious infusion reactions including anaphylaxis were infrequent. Medications for the treatment of hypersensitivity reactions should be available.

NEUROLOGIC EVENTS

TNF inhibitors, including REMICADE®, have been associated with rare cases of new or exacerbated symptoms of demyelinating disorders including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome, seizure, and CNS manifestations of systemic vasculitis. Exercise caution when considering REMICADE® in all patients with these disorders. Consider discontinuation for significant CNS adverse reactions.

Please read Full Prescribing Information and Medication Guide for REMICADE®. Provide the Medication Guide to your patients and encourage discussion.

References: 1. American Thoracic Society, Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221-S247.
2. See latest Centers for Disease Control guidelines and recommendations for tuberculosis testing in immunocompromised patients.

Indications for PROCRIT® (Epoetin alfa)

Anemia of Chronic Renal Failure Patients Not On Dialysis

  • PROCRIT is indicated for the treatment of anemia associated with chronic renal failure, including patients on dialysis and patients not on dialysis. PROCRIT is indicated to elevate or maintain the red blood cell level (as manifested by the hematocrit or hemoglobin determinations) and to decrease the need for transfusions in these patients.
  • Non-dialysis patients with symptomatic anemia considered for therapy should have a hemoglobin less than 10 g/dL.
  • PROCRIT is not intended for patients who require immediate correction of severe anemia. PROCRIT may obviate the need for maintenance transfusions but is not a substitute for emergency transfusion.
  • Prior to initiation of therapy, the patient's iron stores should be evaluated. Transferrin saturation should be at least 20% and ferritin at least 100 ng/mL. Blood pressure should be adequately controlled prior to initiation of PROCRIT therapy, and must be closely monitored and controlled during therapy.

Anemia in Zidovudine-treated HIV-infected Patients

  • PROCRIT is indicated for the treatment of anemia related to therapy with zidovudine in HIV-infected patients.
  • PROCRIT is indicated to elevate or maintain the red blood cell level (as manifested by the hematocrit or hemoglobin determinations) and to decrease the need for transfusions in these patients.
  • PROCRIT is not indicated for the treatment of anemia in HIV-infected patients due to other factors such as iron or folate deficiencies, hemolysis, or gastrointestinal bleeding, which should be managed appropriately.
  • PROCRIT use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being.
  • PROCRIT, at a dose of 100 Units/kg TIW, is effective in decreasing the transfusion requirement and increasing the red blood cell level of anemic, HIV-infected patients treated with zidovudine, when the endogenous serum erythropoietin level is ≤500 mUnits/mL and when patients are receiving a dose of zidovudine ≤4200 mg/week.

Anemia in Cancer Patients on Chemotherapy

PROCRIT is indicated for the treatment of anemia due to the effect of concomitantly administered chemotherapy based on studies that have shown a reduction in the need for RBC transfusions in patients with metastatic, non-myeloid malignancies receiving chemotherapy for a minimum of 2 months. Studies to determine whether PROCRIT increases mortality or decreases progression-free/recurrence-free survival are ongoing.

  • PROCRIT is not indicated for use in patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy.
  • PROCRIT is not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure due to the absence of studies that adequately characterize the impact of PROCRIT on progression-free and overall survival (see WARNINGS: Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence).
  • PROCRIT is not indicated for the treatment of anemia in cancer patients due to other factors such as iron or folate deficiencies, hemolysis, or gastrointestinal bleeding (see PRECAUTIONS: Lack or Loss of Response).
  • PROCRIT use has not been demonstrated in controlled clinical trials to improve symptoms of anemia, quality of life, fatigue, or patient well-being.

Reduction of Allogeneic Blood Transfusion in Surgery Patients

  • PROCRIT is indicated for the treatment of anemic patients (hemoglobin >10 to ≤13 g/dL) who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery to reduce the need for allogeneic blood transfusions.
  • PROCRIT is not indicated for anemic patients who are willing to donate autologous blood.

PROCRIT® (Epoetin alfa) IMPORTANT SAFETY INFORMATION

WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR EVENTS, THROMBOEMBOLIC EVENTS, STROKE and INCREASED RISK OF TUMOR PROGRESSION OR RECURRENCE

Chronic Renal Failure:

  • In clinical studies, patients experienced greater risks for death, serious cardiovascular events, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target hemoglobin levels of 13 g/dL and above.
  • Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.

Cancer:

  • ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers (see WARNINGS: Table 1).
  • To decrease these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusion.
  • Because of these risks, prescribers and hospitals must enroll in and comply with the ESA APPRISE Oncology Program to prescribe and/or dispense PROCRIT® to patients with cancer. To enroll in the ESA APPRISE Oncology Program, visit www.esa-apprise.com or call 1-866-284-8089 for further assistance.
  • Use ESAs only for treatment of anemia due to concomitant myelosuppressive chemotherapy.
  • ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure.
  • Discontinue following the completion of a chemotherapy course.

Perisurgery: PROCRIT® (Epoetin alfa) increased the rate of deep venous thromboses in patients not receiving prophylactic anticoagulation. Consider deep venous thrombosis prophylaxis.

(See WARNINGS: Increased Mortality, Serious Cardiovascular Events, Thromboembolic Events, and Stroke, WARNINGS: Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence, INDICATIONS AND USAGE, and DOSAGE AND ADMINISTRATION.)

Contraindications

  • PROCRIT is contraindicated in patients with uncontrolled hypertension or with known hypersensitivity to albumin (human) or mammalian cell-derived products.

Additional Important Safety Information For Anemic Chronic Renal Failure Patients Not On Dialysis

  • Patients with chronic renal failure experienced greater risks for death and serious cardiovascular events (including myocardial infarction, stroke, congestive heart failure, and hemodialysis vascular access thrombosis) when administered ESAs to target hemoglobin levels 13 g/dL and above in clinical studies; these risks also increased in controlled clinical trials of patients with cancer. A rate of hemoglobin rise of >1 g/dL over 2 weeks may contribute to these risks.
  • Individually titrate to achieve and maintain hemoglobin levels between 10 to 12 g/dL.
  • If the hemoglobin is increasing and approaching 12 g/dL, or increases by more than 1 g/dL in a 2-week period, the PROCRIT dose should be reduced by 25%. If the hemoglobin continues to increase, dose should be temporarily withheld until the hemoglobin begins to decrease, at which point therapy should be reinitiated at a dose 25% below the previous dose.
  • Monitor hemoglobin regularly during therapy; twice a week for 2 to 6 weeks following a dosage adjustment until hemoglobin becomes stable.
  • For patients whose hemoglobin does not attain 10 to 12 g/dL despite appropriate PROCRIT dose titrations over a 12-week period:
    • Do not use higher PROCRIT doses; use the lowest dose that will avoid the need for recurrent RBC transfusions,
    • Evaluate and treat for other causes of anemia:
      1. Iron deficiency;
      2. Underlying infectious, inflammatory, or malignant processes;
      3. Occult blood loss;
      4. Underlying hematologic diseases (i.e., thalassemia, refractory anemia, or other myelodysplastic disorders);
      5. Vitamin deficiencies: Folic acid or vitamin B12;
      6. Hemolysis;
      7. Aluminum intoxication;
      8. Osteitis fibrosa cystica;
      9. Pure Red Cell Aplasia (PRCA)
    • Thereafter, monitor hemoglobin and if responsiveness improves make dose adjustments according to the Prescribing Information (DOSAGE AND ADMINISTRATION); if responsiveness does not improve and the patient needs recurrent RBC transfusions discontinue PROCRIT.
  • Hypertension and seizures were reported in controlled clinical trials involving PROCRIT and other ESAs. Blood pressure should be carefully monitored and aggressively managed.
  • Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients with chronic renal failure receiving PROCRIT by subcutaneous administration. PRCA has also been reported in patients receiving ESAs while undergoing treatment for hepatitis C with interferon and ribavirin. If any patient develops a sudden loss of response to PROCRIT, accompanied by severe anemia and low reticulocyte count, and anti-erythropoietin antibody-associated anemia is suspected, withhold PROCRIT and other erythropoietic proteins. Contact Centocor Ortho Biotech (1-800-457-6399) to perform assays for binding and neutralizing antibodies. If erythropoietin antibody-mediated anemia is confirmed, PROCRIT should be permanently discontinued and patients should not be switched to other erythropoietic proteins.
  • The safety and efficacy of PROCRIT therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes, or hypercoagulable disorders).
  • In some female patients, menses have resumed following PROCRIT therapy; the possibility of pregnancy should be discussed and the need for contraception evaluated.
  • During therapy absolute or functional iron deficiency may develop and all patients will eventually require supplemental iron to adequately support erythropoiesis stimulated by PROCRIT.
  • The most commonly reported side effects (>10%) in clinical trials were hypertension, headache, arthralgias, and nausea.

Please see Full Prescribing Information, including Boxed WARNINGS.

Additional Important Safety Information For Anemic Zidovudine-Treated HIV-Infected Patients

  • Anemic HIV-infected patients receiving zidovudine with endogenous serum erythropoietin >500 mUnits/mL are unlikely to respond to therapy with PROCRIT.
  • Patients with chronic renal failure experienced greater risks for death and serious cardiovascular events (including myocardial infarction, stroke, congestive heart failure, and hemodialysis vascular access thrombosis) when administered ESAs to target hemoglobin levels 13 g/dL and above in clinical studies; these risks also increased in controlled clinical trials of patients with cancer. A rate of hemoglobin rise of >1 g/dL over 2 weeks may contribute to these risks.
  • The dose of PROCRIT should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for blood transfusion and not to exceed the upper safety limit of 12 g/dL.
  • Withhold the dose of PROCRIT if the hemoglobin exceeds the upper safety limit of 12 g/dL until the hemoglobin falls below 11 g/dL; restart dose at 25% below the previous dose and titrate to maintain the desired hemoglobin.
  • Monitor hemoglobin regularly during therapy, weekly until hemoglobin becomes stable.
  • Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients treated with PROCRIT; predominantly in patients with chronic renal failure receiving PROCRIT by subcutaneous administration. PRCA has also been reported in patients receiving ESAs while undergoing treatment for hepatitis C with interferon and ribavirin. If any patient develops a sudden loss of response to PROCRIT, accompanied by severe anemia and low reticulocyte count, and anti-erythropoietin antibody-associated anemia is suspected, withhold PROCRIT and other erythropoietic proteins. Contact Centocor Ortho Biotech (1-800-457-6399) to perform assays for binding and neutralizing antibodies. If erythropoietin antibody-mediated anemia is confirmed, PROCRIT should be permanently discontinued and patients should not be switched to other erythropoietic proteins.
  • The safety and efficacy of PROCRIT therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes, or hypercoagulable disorders).
  • In some female patients, menses have resumed following PROCRIT therapy; the possibility of pregnancy should be discussed and the need for contraception evaluated.
  • Prior to and regularly during PROCRIT therapy monitor iron status; transferrin saturation should be ≥20% and ferritin should be ≥100 ng/mL. During therapy absolute or functional iron deficiency may develop and all patients will eventually require supplemental iron to adequately support erythropoiesis stimulated by PROCRIT.
  • Rapid increases in hemoglobin may be associated with hypertension and should be avoided; blood pressure should be carefully monitored and aggressively managed.
  • The most commonly reported side effects (>15%) in clinical trials were pyrexia, fatigue, headache, cough, diarrhea and rash.

Please see Full Prescribing Information, including Boxed WARNINGS.

Additional Important Safety Information For Anemic Cancer Patients On Myelosuppressive Chemotherapy

  • Patients with chronic renal failure experienced greater risks for death and serious cardiovascular events (including myocardial infarction, stroke, congestive heart failure, and hemodialysis vascular access thrombosis) when administered ESAs to target higher versus lower hemoglobin levels 13 g/dL and above in clinical studies; these risks also increased in controlled clinical trials of patients with cancer. A rate of hemoglobin rise of >1 g/dL over 2 weeks may contribute to these risks.
  • PROCRIT therapy should not be initiated at hemoglobin levels ≥ 10 g/dL.
  • The dose of PROCRIT should be titrated for each patient to achieve and maintain the lowest hemoglobin level sufficient to avoid the need for blood transfusion.
  • When the hemoglobin reaches a level needed to avoid transfusion or, increases by more than 1 g/dL in a 2-week period, the PROCRIT dose should be reduced by 25%. Withhold the dose of PROCRIT if the hemoglobin exceeds a level needed to avoid transfusion. Restart dose at 25% below the previous dose when the hemoglobin approaches a level where transfusions may be required. Discontinue if after 8 weeks of therapy there is no response as measured by hemoglobin levels or if transfusions are still required.
  • Monitor hemoglobin regularly during therapy, weekly until hemoglobin becomes stable.
  • Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients treated with PROCRIT; predominantly in patients with chronic renal failure receiving PROCRIT by subcutaneous administration. PRCA has also been reported in patients receiving ESAs while undergoing treatment for hepatitis C with interferon and ribavirin. If any patient develops a sudden loss of response to PROCRIT, accompanied by severe anemia and low reticulocyte count, and anti-erythropoietin antibody-associated anemia is suspected, withhold PROCRIT and other erythropoietic proteins. Contact Centocor Ortho Biotech (1-800-457-6399) to perform assays for binding and neutralizing antibodies. If erythropoietin antibody-mediated anemia is confirmed, PROCRIT should be permanently discontinued and patients should not be switched to other erythropoietic proteins.
  • The safety and efficacy of PROCRIT therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes, or hypercoagulable disorders).
  • In some female patients, menses have resumed following PROCRIT therapy; the possibility of pregnancy should be discussed and the need for contraception evaluated.
  • Prior to and regularly during PROCRIT therapy monitor iron status; transferrin saturation should be ≥20% and ferritin should be ≥100 ng/mL. During therapy absolute or functional iron deficiency may develop and all patients will eventually require supplemental iron to adequately support erythropoiesis stimulated by PROCRIT.
  • Treatment of patients with grossly elevated serum erythropoietin levels (e.g., >200 mUnits/mL) is not recommended.
  • During PROCRIT therapy, blood pressure should be monitored carefully and aggressively managed, particularly in patients with an underlying history of hypertension or cardiovascular disease.
  • Seizures in PROCRIT-treated patients have been reported in the context of a significant increase in hemoglobin from baseline; increases in blood pressure were not always observed; and patients may have had other underlying central nervous system pathology.
  • The most commonly reported side effects (>10%) for PROCRIT in clinical trials were pyrexia, diarrhea, nausea, vomiting, edema, asthenia, fatigue, shortness of breath, paresthesia, and upper respiratory infection.

Please see Full Prescribing Information, including Boxed WARNINGS.

Additional Important Safety Information For Anemic Patients Undergoing Elective, Noncardiac, Nonvascular Surgery

  • Deep venous thrombosis prophylaxis should be strongly considered when prescribing PROCRIT.
  • PROCRIT is not approved for use in patients scheduled for cardiac surgery.
  • Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias, associated with neutralizing antibodies to erythropoietin have been reported in patients treated with PROCRIT; predominantly in patients with chronic renal failure receiving PROCRIT by subcutaneous administration. PRCA has also been reported in patients receiving ESAs while undergoing treatment for hepatitis C with interferon and ribavirin. If any patient develops a sudden loss of response to PROCRIT, accompanied by severe anemia and low reticulocyte count, and anti-erythropoietin antibody-associated anemia is suspected, withhold PROCRIT and other erythropoietic proteins. Contact Centocor Ortho Biotech (1-800-457-6399) to perform assays for binding and neutralizing antibodies. If erythropoietin antibody-mediated anemia is confirmed, PROCRIT should be permanently discontinued and patients should not be switched to other erythropoietic proteins.
  • The safety and efficacy of PROCRIT therapy have not been established in patients with a known history of a seizure disorder or underlying hematologic disease (e.g., sickle cell anemia, myelodysplastic syndromes, or hypercoagulable disorders).
  • Adequate iron supplementation should be provided at initiation and during PROCRIT therapy in order to support erythropoiesis and avoid depletion of iron stores. Transferrin saturation should be ≥20% and ferritin should be ≥100 ng/mL.
  • Blood pressure may rise in the peri-operative period in patients being treated with PROCRIT. Blood pressure should be monitored regularly and aggressively managed.
  • The most commonly occurring adverse events were pyrexia, nausea, and constipation.

Click here for Full Prescribing Information, including Boxed WARNINGS for PROCRIT® (Epoetin alfa)

Medication Guide for PROCRIT

Patient Instructions for Use

Boxed WARNINGS: LEUSTATIN® (cladribine) Injection
  • LEUSTATIN (cladribine) Injection should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Suppression of bone marrow function should be anticipated. This is usually reversible and appears to be dose dependent. Serious neurological toxicity (including irreversible paraparesis and quadraparesis) has been reported in patients who received LEUSTATIN Injection by continuous infusion at high doses (4 to 9 times the recommended dose for Hairy Cell Leukemia). Neurologic toxicity appears to demonstrate a dose relationship; however, severe neurological toxicity has been reported rarely following treatment with standard cladribine dosing regimens.
  • Acute nephrotoxicity has been observed with high doses of LEUSTATIN (4 to 9 times the recommended dose for Hairy Cell Leukemia), especially when given concomitantly with other nephrotoxic agents/therapies.

Click here for Full Prescribing Information, including Boxed WARNINGS for LEUSTATIN® (cladribine)

Indications for DOXIL® (doxorubicin HCl liposome injection)

  • DOXIL® (doxorubicin HCl liposome injection) is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after prior platinum-based therapy.
  • DOXIL in combination with VELCADE® (bortezomib) is indicated for the treatment of patients with multiple myeloma who have not previously received VELCADE and have received at least one prior therapy.

  • DOXIL is indicated for the treatment of AIDS-related Kaposi's sarcoma in patients with disease that has progressed on prior combination chemotherapy or in patients who are intolerant to such therapy.

    The treatment of patients with AIDS-related Kaposi's sarcoma is based on objective tumor response rates. No results are available from controlled trials that demonstrate a clinical benefit resulting from this treatment, such as improvement in disease-related symptoms or increased survival.

DOXIL® (doxorubicin HCl liposome injection) IMPORTANT SAFETY INFORMATION

BOXED WARNINGS:
Cardiotoxicity, infusion reaction, myelosuppression, liver impairment, substitution

  • The use of DOXIL may lead to cardiac toxicity. Myocardial damage may lead to congestive heart failure and may occur as the total cumulative dose of doxorubicin HCl approaches 550mg/m2.
    • Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dose.
    • Cardiac toxicity may also occur at lower cumulative doses (400 mg/m2) in patients with prior mediastinal irradiation or who are receiving concurrent cyclophosphamide therapy.
  • Acute infusion-related reactions including, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension have occurred in up to 10% of patients treated with DOXIL. In most patients, these reactions have resolved within several hours to a day once the infusion is terminated. In some patients, reactions resolved with slowing of the infusion rate.
    • Serious and sometimes life-threatening or fatal allergic/anaphylactoid-like infusion reactions have occurred. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use.
    • The initial rate of infusion should be 1mg/min to minimize the risk of infusion reactions.
  • Severe myelosuppression may occur.
  • DOXIL dosage should be reduced in patients with impaired hepatic function.
  • Accidental substitution has resulted in severe side effects. Do not substitute for doxorubicin HCl on a mg per mg basis.

Contraindications

  • Patients with a history of hypersensitivity reactions to a conventional doxorubicin formulation or the components of DOXIL
  • Nursing mothers

Additional Safety Information

  • Cardiac function should be carefully monitored.
    • Congestive heart failure or cardiomyopathy may occur after discontinuation of anthracycline therapy.
    • For patients with a history of cardiovascular disease, or if the results of cardiac monitoring indicate possible cardiac injury, the benefit of therapy must be weighed against the risk of myocardial injury.
    • In the randomized multiple myeloma study, 25 patients (8%) in the VELCADE for Injection arm and 42 patients (13%) in the VELCADE plus DOXIL arm experienced left ventricular ejection fraction decrease (defined as absolute decrease > 15% over baseline or a > 5% decrease below institutional lower limit of normal).
  • Myelosuppression may occur; frequently monitor complete blood count (including platelet count), at least prior to each dose of DOXIL.
    • In patients with recurrent ovarian cancer or AIDS-related Kaposi's sarcoma, hematologic toxicity (based on platelet count or absolute neutrophil count) may require dose reduction or delay in administration of DOXIL.
    • In patients with multiple myeloma, hematologic toxicity (based on platelet count, absolute neutrophil count, hemoglobin level, or neutropenia with fever) may require dose reduction, delay in administration, or suspension of DOXIL and/or VELCADE.
    • Persistent severe myelosuppression may result in superinfection, neutropenic fever, or hemorrhage.
    • Sepsis occurring during neutropenia has resulted in discontinuation of treatment and in rare cases of death.
  • DOXIL may potentiate the toxicity of other anticancer therapies, especially hematologic toxicities, when used in combination with other therapies that suppress bone marrow.
  • Hand-foot syndrome (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.
      • The reaction was mild in most patients, resolving in 1 to 2 weeks.
      • The reaction can be severe and debilitating in some patients, resulting in discontinuation of therapy.
  • DOXIL is an irritant, not a vesicant; use precautions to avoid extravasation.
  • DOXIL can cause fetal harm when used during pregnancy.
  • Recall reaction has occurred with DOXIL administration after radiotherapy.
  • DOXIL may interact with drugs known to interact with the conventional formulation of doxorubicin HCl.
  • In patients with recurrent ovarian cancer, the most common all-grade adverse reactions (ARs) > 20% (DOXIL vs topotecan, respectively) included: asthenia (40% vs 51%), fever (21% vs 31%), nausea (46% vs 63%), stomatitis (41% vs 15%), vomiting (33% vs 44%), diarrhea (21% vs 35%), anorexia (20% vs 22%), dyspnea (15% vs 23%), HFS (51% vs 1%), and rash (29% vs 12%).
    • In addition, 19% vs 52.3% reported alopecia (all grades).
    • Grade 3/4 hematologic ARs reported in > 5% (DOXIL vs t opotecan, respectively) were neutropenia (12% vs 76%) and anemia (6% vs 29%).
  • In patients with multiple myeloma, the most common all-grade ARs > 20% (VELCADE plus DOXIL vs VELCADE, respectively) included: neutropenia (36% vs 22%), thrombocytopenia (33% vs 28%), anemia (25% vs 21%), fatigue (36% vs 28%), pyrexia (31% vs 22%), asthenia (22% vs 18%), nausea (48% vs 40%), diarrhea (46% vs 39%), vomiting (32% vs 22%), constipation (31% vs 31%), mucositis/stomatitis (20% vs 5%), peripheral neuropathy (42% vs 45%), neuralgia (17% vs 20%), and rash (22% vs 18%).
    • In addition, 19% vs < 1% reported HFS.
  • In patients with AIDS-related Kaposi's sarcoma, ARs reported in > 5% of DOXIL-treated patients were: neutropenia (ANC < 1000/mm3, 46%; < 500/mm3, 11%), anemia (Hb < 10 g/dL, 58%; < 8 g/dL, 16%), thrombocytopenia (< 150,000 platelets/mm3, 61%), nausea (18%), asthenia (7%), fever (8%), alopecia (9%), vomiting (8%), diarrhea (5%), and stomatitis (5%). 
     

Please click here for DOXIL full Prescribing Information, including Boxed WARNINGS

Indications for SIMPONI™ (golimumab)

SIMPONI™ is a tumor necrosis factor (TNF) blocker indicated for the treatment of:

  • Moderately to severely active Rheumatoid Arthritis (RA) in adults, in combination with methotrexate
  • Active Psoriatic Arthritis (PsA) in adults, alone or in combination with methotrexate
  • Active Ankylosing Spondylitis in adults (AS)

IMPORTANT SAFETY INFORMATION

SERIOUS INFECTIONS

Patients treated with SIMPONI™ (golimumab) are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue SIMPONI™ if a patient develops a serious infection.

Reported infections include:

  • Active tuberculosis (TB), including reactivation of latent TB. Patients frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent TB before SIMPONI™ use and during therapy. Treatment for latent infection should be initiated prior to SIMPONI™ use.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Bacterial, viral, and other infections due to opportunistic pathogens.

The risks and benefits of treatment with SIMPONI™ should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Do not start SIMPONI™ in patients with clinically important active infections, including localized infections. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with SIMPONI™, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

Other serious infections observed in patients treated with SIMPONI™ included sepsis, pneumonia, cellulitis, abscess and hepatitis B infection.

MALIGNANCIES

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers of which SIMPONI™ is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of malignancies, including rare malignancies usually associated with immunosuppression and malignancies not usually observed in children or adolescents. Malignancies occurred after a median of 30 months after the first dose of therapy. Most of the patients were receiving concomitant immunosuppressants.

In the controlled portions of clinical trials of all TNF-blocking agents including SIMPONI™, more cases of lymphoma have been observed among patients receiving TNF-blocking treatment compared with control patients. In clinical trials, the incidence of lymphoma per 100 patient-years of follow-up was 0.21 (95% CI: 0.03, 0.77) in the combined SIMPONI™ group compared with an incidence of 0 (95% CI: 0, 0.96) in the placebo group. In clinical trials, the incidence of malignancies other than lymphoma was not increased with exposure to SIMPONI™ and was similar to what would be expected in the general population. Cases of acute and chronic leukemia have been reported with postmarketing TNF-blocker use. The risks and benefits of TNF-blocker therapy should be considered prior to initiating therapy in patients with a known malignancy or who develop a malignancy.

HEPATITIS B REACTIVATION

The use of TNF-blocking agents including SIMPONI™ has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic hepatitis B carriers. In some instances, HBV reactivation occurring in conjunction with TNF-blocker therapy has been fatal. The majority of these reports has occurred in patients who received concomitant immunosuppressants.

Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating SIMPONI™. Exercise caution when prescribing SIMPONI™ for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with SIMPONI™. Discontinue SIMPONI™ in patients who develop HBV reactivation, and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of SIMPONI™, and monitor patients closely.

HEART FAILURE

Cases of worsening congestive heart failure (CHF) and new-onset CHF have been reported with TNF blockers. Exercise caution and monitor patients with heart failure. Discontinue SIMPONI™ if new or worsening symptoms of heart failure appear.

DEMYELINATING DISORDERS

TNF-blocking agents have been associated with cases of new onset or exacerbation of central nervous system demyelinating disorders, including multiple sclerosis. Exercise caution in considering the use of SIMPONI™ in patients with central nervous system demyelinating disorders.

HEMATOLOGIC CYTOPENIAS

There have been post marketing reports of pancytopenia, leukopenia, neutropenia, aplastic anemia, and thrombocytopenia in patients receiving TNF blockers. Exercise caution when using SIMPONI™ in patients with significant cytopenias.

USE WITH OTHER DRUGS

The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections, therefore the use of SIMPONI™ in combination with these products is not recommended. A higher rate of serious infections has also been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker. People receiving SIMPONI™ can receive vaccinations, except for live vaccines.

ADVERSE REACTIONS

The most serious adverse reactions were serious infections and malignancies.

Upper respiratory tract infection and nasopharyngitis were the most common adverse reactions reported in the combined Phase 3 trials through Week 16, occurring in 7% and 6% of patients treated with SIMPONI™ as compared with 6% and 5% of patients in the control group, respectively. The rate of injection-site reactions was 6% with patients treated with SIMPONI™ compared with 2% of patients in the control group.

Cases of new-onset psoriasis, including pustular and palmoplantar, or exacerbation of pre-existing psoriasis have been reported with the use of TNF blockers, including SIMPONI™. Some of these patients required hospitalization. Most patients had improvement following discontinuation of the TNF blocker. Discontinuation of SIMPONI™ should be considered for severe cases and those that do not improve or that worsen despite topical treatments.

Please see accompanying Full Prescribing Information and Medication Guide for SIMPONI™. Provide the Medication Guide to your patients and encourage discussion.

Indication for STELARA™ (ustekinumab)

STELARA™ is indicated for the treatment of adult patients (18 years or older) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

IMPORTANT SAFETY INFORMATION

Infections

STELARA™ (ustekinumab) may increase the risk of infections and reactivation of latent infections. Serious bacterial, fungal, and viral infections were reported. Infections requiring hospitalization included cellulitis, diverticulitis, osteomyelitis, gastroenteritis, pneumonia, and urinary tract infections. STELARA™ should not be given to patients with a clinically important active infection and should not be administered until the infection resolves or is adequately treated. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. Exercise caution when considering use of STELARA™ in patients with a chronic infection or a history of recurrent infection.

Theoretical Risk for Vulnerability to Particular Infections

Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacterium, Salmonella, and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients. It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with STELARA™ will be susceptible to these types of infections. Consider appropriate diagnostic testing as dictated by clinical circumstances.

Pre-Treatment Evaluation of Tuberculosis (TB)

Evaluate patients for TB prior to initiating treatment with STELARA™. STELARA™ should not be given to patients with active TB. Initiate treatment of latent TB before administering STELARA™. Patients should be monitored closely for signs and symptoms of active TB during and after treatment with STELARA™.

Malignancies

STELARA™ is an immunosuppressant and may increase the risk of malignancy. Malignancies were reported among patients who received STELARA™ in clinical studies. The safety of STELARA™ has not been evaluated in patients who have a history of malignancy or who have a known malignancy.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

One case of RPLS has been reported in a STELARA™-treated patient. If RPLS is suspected, discontinue STELARA™ and administer appropriate treatment.
RPLS is a neurological disorder, which is not caused by an infection or demyelination. RPLS can present with headache, seizures, confusion, and visual disturbances. RPLS has been associated with fatal outcomes.

Immunizations

Prior to initiating therapy with STELARA™, patients should receive all immunizations recommended by current guidelines. Patients being treated with STELARA™ should not receive live vaccines. BCG vaccines should not be given during treatment or within one year of initiating or discontinuing STELARA™. Exercise caution when administering live vaccines to household contacts of STELARA™ patients, as shedding and subsequent transmission to STELARA™ patients may occur. Non-live vaccinations received during a course of STELARA™ may not elicit an immune response sufficient to prevent disease.

Concomitant Therapies

The safety of STELARA™ in combination with other immunosuppressive agents or phototherapy has not been evaluated. Ultraviolet-induced skin cancers developed earlier and more frequently in mice genetically manipulated to be deficient in both IL-12 and IL-23 or IL-12 alone. The relevance of these findings in mouse models for malignancy risk in humans is unknown.

Most Common Adverse Reactions

The most common adverse reactions (>3% and higher than that with placebo) in clinical trials for STELARA™ 45 mg, STELARA™ 90 mg, or placebo were: nasopharyngitis (8%, 7%, 8%), upper respiratory tract infection (5%, 4%, 5%), headache (5%, 5%, 3%), and fatigue (3%, 3%, 2%), respectively.

Please see accompanying Full Prescribing Information and Medication Guide for STELARA™.

Last Modified Date: 02/13/2010