Mircera

Mircera is an erythropoiesis-stimulating agent (ESA) indicated for the treatment of anemia associated with chronic kidney disease (CKD) in:

• •adult patients on dialysis and adult patients not on dialysis (
  1.1 Anemia Due to Chronic Kidney Disease

  Mircera is indicated for the treatment of anemia associated with chronic kidney disease (CKD) in:

  • •adult patients on dialysis and adult patients not on dialysis.
  • •pediatric patients 3 months to 17 years of age on dialysis or not on dialysis who are converting from another ESA after their hemoglobin level was stabilized with an ESA.

  Limitations of Use

  Mircera is not indicated and is not recommended:

  • •In the treatment of anemia due to cancer chemotherapy
    [see Warnings and Precautions ]
    .
  • •As a substitute for RBC transfusions in patients who require immediate correction of anemia
    [see Clinical Pharmacology ]
    .

  Mircera has not been shown to improve symptoms, physical functioning, or health-related quality of life.
  ).
• •pediatric patients 3 months to 17 years of age on dialysis or not on dialysis who are converting from another ESA after their hemoglobin level was stabilized with an ESA (
  1.1 Anemia Due to Chronic Kidney Disease

  Mircera is indicated for the treatment of anemia associated with chronic kidney disease (CKD) in:

  • •adult patients on dialysis and adult patients not on dialysis.
  • •pediatric patients 3 months to 17 years of age on dialysis or not on dialysis who are converting from another ESA after their hemoglobin level was stabilized with an ESA.

  Limitations of Use

  Mircera is not indicated and is not recommended:

  • •In the treatment of anemia due to cancer chemotherapy
    [see Warnings and Precautions ]
    .
  • •As a substitute for RBC transfusions in patients who require immediate correction of anemia
    [see Clinical Pharmacology ]
    .

  Mircera has not been shown to improve symptoms, physical functioning, or health-related quality of life.
  ).

Mircera is not indicated and is not recommended for use:

• •In the treatment of anemia due to cancer chemotherapy (
  5.2 Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence in Patients with Cancer

  Mircera is not indicated and is not recommended for use in the treatment of anemia due to cancer chemotherapy. A dose-ranging trial of Mircera in 153 patients who were undergoing chemotherapy for non-small cell lung cancer was terminated prematurely because more deaths occurred among patients receiving Mircera than another ESA.

  ESAs resulted in decreased locoregional control/progression-free survival and/or overall survival (see Table 5). These findings were observed in studies of patients with advanced head and neck cancer receiving radiation therapy (Studies 5 and 6), in patients receiving chemotherapy for metastatic breast cancer (Study 1) or lymphoid malignancy (Study 2), and in patients with non-small cell lung cancer or various malignancies who were not receiving chemotherapy or radiotherapy (Studies 7 and 8).

  Table 5: Randomized, Controlled Trials with Decreased Survival and/or Decreased Locoregional Control

  *Q1= 25th percentile; Q3= 75th percentile
  Study/Tumor (n)	Hemoglobin Target	Achieved Hemoglobin (Median Q1,Q3*)	Primary Endpoint	Adverse Outcome for ESA-containing Arm
  Chemotherapy
  Cancer Study 1 Metastatic breast cancer (n=939)	12 to 14 g/dL	12.9 g/dL 12.2, 13.3 g/dL	12-month overall survival	Decreased 12-month survival
  Cancer Study 2 Lymphoid malignancy (n=344)	13 to 15 g/dL (M) 13 to 14 g/dL (F)	11.0 g/dL 9.8, 12.1 g/dL	Proportion of patients achieving a hemoglobin response	Decreased overall survival
  Cancer Study 3 Early breast cancer (n=733)	12.5 to 13 g/dL	13.1 g/dL 12.5, 13.7 g/dL	Relapse-free and overall survival	Decreased 3-year relapse-free and overall survival
  Cancer Study 4 Cervical cancer (n=114)	12 to 14 g/dL	12.7 g/dL 12.1, 13.3 g/dL	Progression-free and overall survival and locoregional control	Decreased 3-year progression-free and overall survival and locoregional control
  Radiotherapy Alone
  Cancer Study 5 Head and neck cancer (n=351)	more than 15 g/dL (M) more than 14 g/dL (F)	Not available	Locoregional progression-free survival (LRPFS)	Decreased 5-year locoregional progression-free survival Decreased overall survival
  Cancer Study 6 Head and neck cancer (n=522)	14 to 15.5 g/dL	Not available	Locoregional disease control (LRC)	Decreased locoregional disease control
  No Chemotherapy or Radiotherapy
  Cancer Study 7 Non-small cell lung cancer (n=70)	12 to 14 g/dL	Not available	Quality of life	Decreased overall survival
  Cancer Study 8 Non-myeloid malignancy (n=989)	12 to 13 g/dL	10.6 g/dL 9.4, 11.8 g/dL	RBC transfusions	Decreased overall survival

  Decreased Overall Survival

  Cancer Study 1 (the “BEST” study) was previously described [see

  Warnings and Precautions

  ]. Mortality at 4 months (8.7% vs. 3.4%) was significantly higher in the epoetin alfa arm. The most common investigator-attributed cause of death within the first 4 months was disease progression; 28 of 41 deaths in the epoetin alfa arm and 13 of 16 deaths in the placebo arm were attributed to disease progression. Investigator assessed time to tumor progression was not different between the two groups. Survival at 12 months was significantly lower in the epoetin alfa arm (70% vs. 76%, HR 1.37, 95% CI: 1.07, 1.75; p=0.012).

  Cancer Study 2 was a Phase 3, double-blind, randomized (darbepoetin alfa vs. placebo) study conducted in 344 anemic patients with lymphoid malignancy receiving chemotherapy. With a median follow-up of 29 months, overall mortality rates were significantly higher among patients randomized to darbepoetin alfa as compared to placebo (HR 1.36, 95% CI: 1.02, 1.82).

  Cancer Study 7 was a Phase 3, multicenter, randomized (epoetin alfa vs. placebo), double-blind study, in which patients with advanced non-small cell lung cancer receiving only palliative radiotherapy or no active therapy were treated with epoetin alfa to achieve and maintain hemoglobin levels between 12 and 14 g/dL. Following an interim analysis of 70 of 300 patients planned, a significant difference in survival in favor of the patients on the placebo arm of the trial was observed (median survival 63 vs. 129 days; HR 1.84; p=0.04).

  Cancer Study 8 was a Phase 3, double-blind, randomized (darbepoetin alfa vs. placebo), 16-week study in 989 anemic patients with active malignant disease, neither receiving nor planning to receive chemotherapy or radiation therapy. There was no evidence of a statistically significant reduction in proportion of patients receiving RBC transfusions. The median survival was shorter in the darbepoetin alfa treatment group (8 months) compared with the placebo group (10.8 months); HR 1.30, 95% CI: 1.07, 1.57.

  Decreased Progression-Free Survival and Overall Survival

  Cancer Study 3 (the “PREPARE” study) was a randomized controlled study in which darbepoetin alfa was administered to prevent anemia conducted in 733 women receiving neo-adjuvant breast cancer treatment. A final analysis was performed after a median follow-up of approximately 3 years at which time the survival rate was lower (86% vs. 90%, HR 1.42, 95% CI: 0.93, 2.18) and relapse-free survival rate was lower (72% vs. 78%, HR 1.33, 95% CI: 0.99, 1.79) in the darbepoetin alfa-treated arm compared to the control arm.

  Cancer Study 4 (protocol GOG 191) was a randomized controlled study that enrolled 114 of a planned 460 cervical cancer patients receiving chemotherapy and radiotherapy. Patients were randomized to receive epoetin alfa to maintain hemoglobin between 12 and 14 g/dL or to transfusion support as needed. The study was terminated prematurely due to an increase in thromboembolic events in epoetin alfa-treated patients compared to control (19% vs. 9%). Both local recurrence (21% vs. 20%) and distant recurrence (12% vs. 7%) were more frequent in epoetin alfa-treated patients compared to control. Progression-free survival at 3 years was lower in the epoetin alfa-treated group compared to control (59% vs. 62%, HR 1.06, 95% CI: 0.58, 1.91). Overall survival at 3 years was lower in the epoetin alfa-treated group compared to control (61% vs. 71%, HR 1.28, 95% CI: 0.68, 2.42).

  Cancer Study 5 (the “ENHANCE” study) was a randomized controlled study in 351 head and neck cancer patients where epoetin beta or placebo was administered to achieve target hemoglobins of 14 and 15 g/dL for women and men, respectively. Locoregional progression-free survival was significantly shorter in patients receiving epoetin beta (HR 1.62, 95% CI: 1.22, 2.14, p=0.0008) with a median of 406 days epoetin beta vs. 745 days placebo. Overall survival was significantly shorter in patients receiving epoetin beta (HR 1.39, 95% CI: 1.05, 1.84; p=0.02).

  Decreased Locoregional Control

  Cancer Study 6 (DAHANCA 10) was conducted in 522 patients with primary squamous cell carcinoma of the head and neck receiving radiation therapy randomized to darbepoetin alfa with radiotherapy or radiotherapy alone. An interim analysis on 484 patients demonstrated that locoregional control at 5 years was significantly shorter in patients receiving darbepoetin alfa (RR 1.44, 95% CI: 1.06, 1.96; p=0.02). Overall survival was shorter in patients receiving darbepoetin alfa (RR 1.28, 95% CI: 0.98, 1.68; p=0.08).
  ).
• •As a substitute for RBC transfusions in patients who require immediate correction of anemia (
  12.2 Pharmacodynamics

  Following a single-dose of Mircera in adult patients with CKD, the onset of hemoglobin increase (defined as an increase more than 0.4 g/dL from baseline) was observed 7 to 15 days following initial dose administration

  [see Dosage and Administration ]

  .
  ).

Mircera has not been shown to improve quality of life, fatigue, or patient well-being.

Mircera is administered by subcutaneous or intravenous injection (

• •Initial Treatment: (patients not currently treated with an ESA):
  • •CKD patients on dialysis: 0.6 mcg/kg body weight administered once every two weeks (
    2.2 For Adult Patients with CKD

    Prefilled syringes are not designed for administration of partial doses. Round doses to the closest dose achievable with the prefilled syringes.

    When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. A single hemoglobin excursion may not require a dosing change.

    • •Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments.
    • •If the hemoglobin rises rapidly (e.g., more than 1 g/dL in any 2-week period), reduce the dose of Mircera by approximately 25% to the closest dose achievable with the prefilled syringes to reduce rapid responses.
    • •If the hemoglobin continues to rise following a dose reduction, discontinue Mircera until the hemoglobin level begins to decrease, at which point therapy should be restarted with a dose that is approximately 25% below the previously administered dose.
    • •For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by approximately 25% to the closest dose achievable with the prefilled syringes.
    • •For patients who do not respond adequately over a 12-week escalation period, increasing the Mircera dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue Mircera if responsiveness does not improve.

    Administer Mircera either intravenously or subcutaneously. When administered subcutaneously, Mircera should be injected in the abdomen, arm or thigh.

    For Adult Patients with CKD

    on dialysis

    :

    • •Initiate Mircera treatment when the hemoglobin level is less than 10 g/dL.
    • •If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of Mircera.
    • •The recommended starting dose of Mircera for the treatment of anemia in
      adult
      CKD patients who are not currently treated with an ESA is 0.6 mcg/kg body weight administered once every two weeks as a single intravenous or subcutaneous injection. The intravenous route is recommended for patients receiving hemodialysis because the intravenous route may be less immunogenic
      [see Adverse Reactions ]
      .
    • •Once the hemoglobin has been stabilized, Mircera may be administered once monthly using a dose that is twice that of the every-two-week dose and subsequently titrated as necessary.

    For Adult Patients with CKD

    not on dialysis

    :

    • •Consider initiating Mircera treatment only when the hemoglobin level is less than 10 g/dL
      and
      the following considerations apply:
      • oThe rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion
        and
        ,
      • oReducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal.
    • •If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of Mircera, and use the lowest dose of Mircera sufficient to reduce the need for RBC transfusions.
    • •The recommended starting dose of Mircera for the treatment of anemia in
      adult
      CKD patients who are not currently treated with an ESA is 1.2 mcg/kg body weight administered once every month as a single subcutaneous injection. Alternatively, a starting dose of 0.6 mcg/kg body weight may be administered once every two weeks as a single intravenous or subcutaneous injection.
    • •Once the hemoglobin has been stabilized, Mircera may be administered once monthly using a dose that is twice that of the every-two-week dose and subsequently titrated as necessary.

    Refer patients who self-administer Mircera to the Instructions for Use

    [see Patient Counseling Information ]

    .

    Conversion from Epoetin alfa or Darbepoetin alfa to Mircera in Adult Patients with CKD

    Mircera can be administered once every two weeks or once monthly to patients whose hemoglobin has been stabilized by treatment with an ESA (see Table 1). The dose of Mircera, given as a single intravenous or subcutaneous injection, should be based on the total weekly ESA dose at the time of conversion.

    Table1: Mircera Starting Doses for Adult Patients Currently Receiving an ESA

    Previous Weekly Epoetin alfa Dose (units/week)	Previous Weekly Darbepoetin alfa Dose (mcg/week)	Mircera Dose
    		Once Monthly (mcg/month)	Once Every Two Weeks (mcg/every two weeks)
    Less than 8000 units	Less than 40 mcg	120 mcg	60 mcg
    8000 units to 16000 units	40 mcg to 80 mcg	200 mcg	100 mcg
    More than 16000 units	More than 80 mcg	360 mcg	180 mcg
    ).
  • •CKD patients not on dialysis: 1.2 mcg/kg body weight administered once every month as a single subcutaneous injection. Alternatively, a starting dose of 0.6 mcg/kg body weight may be administered once every two weeks as a single intravenous or subcutaneous injection (
    2.2 For Adult Patients with CKD

    Prefilled syringes are not designed for administration of partial doses. Round doses to the closest dose achievable with the prefilled syringes.

    When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. A single hemoglobin excursion may not require a dosing change.

    • •Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments.
    • •If the hemoglobin rises rapidly (e.g., more than 1 g/dL in any 2-week period), reduce the dose of Mircera by approximately 25% to the closest dose achievable with the prefilled syringes to reduce rapid responses.
    • •If the hemoglobin continues to rise following a dose reduction, discontinue Mircera until the hemoglobin level begins to decrease, at which point therapy should be restarted with a dose that is approximately 25% below the previously administered dose.
    • •For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by approximately 25% to the closest dose achievable with the prefilled syringes.
    • •For patients who do not respond adequately over a 12-week escalation period, increasing the Mircera dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue Mircera if responsiveness does not improve.

    Administer Mircera either intravenously or subcutaneously. When administered subcutaneously, Mircera should be injected in the abdomen, arm or thigh.

    For Adult Patients with CKD

    on dialysis

    :

    • •Initiate Mircera treatment when the hemoglobin level is less than 10 g/dL.
    • •If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of Mircera.
    • •The recommended starting dose of Mircera for the treatment of anemia in
      adult
      CKD patients who are not currently treated with an ESA is 0.6 mcg/kg body weight administered once every two weeks as a single intravenous or subcutaneous injection. The intravenous route is recommended for patients receiving hemodialysis because the intravenous route may be less immunogenic
      [see Adverse Reactions ]
      .
    • •Once the hemoglobin has been stabilized, Mircera may be administered once monthly using a dose that is twice that of the every-two-week dose and subsequently titrated as necessary.

    For Adult Patients with CKD

    not on dialysis

    :

    • •Consider initiating Mircera treatment only when the hemoglobin level is less than 10 g/dL
      and
      the following considerations apply:
      • oThe rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion
        and
        ,
      • oReducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal.
    • •If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of Mircera, and use the lowest dose of Mircera sufficient to reduce the need for RBC transfusions.
    • •The recommended starting dose of Mircera for the treatment of anemia in
      adult
      CKD patients who are not currently treated with an ESA is 1.2 mcg/kg body weight administered once every month as a single subcutaneous injection. Alternatively, a starting dose of 0.6 mcg/kg body weight may be administered once every two weeks as a single intravenous or subcutaneous injection.
    • •Once the hemoglobin has been stabilized, Mircera may be administered once monthly using a dose that is twice that of the every-two-week dose and subsequently titrated as necessary.

    Refer patients who self-administer Mircera to the Instructions for Use

    [see Patient Counseling Information ]

    .

    Conversion from Epoetin alfa or Darbepoetin alfa to Mircera in Adult Patients with CKD

    Mircera can be administered once every two weeks or once monthly to patients whose hemoglobin has been stabilized by treatment with an ESA (see Table 1). The dose of Mircera, given as a single intravenous or subcutaneous injection, should be based on the total weekly ESA dose at the time of conversion.

    Table1: Mircera Starting Doses for Adult Patients Currently Receiving an ESA

    Previous Weekly Epoetin alfa Dose (units/week)	Previous Weekly Darbepoetin alfa Dose (mcg/week)	Mircera Dose
    		Once Monthly (mcg/month)	Once Every Two Weeks (mcg/every two weeks)
    Less than 8000 units	Less than 40 mcg	120 mcg	60 mcg
    8000 units to 16000 units	40 mcg to 80 mcg	200 mcg	100 mcg
    More than 16000 units	More than 80 mcg	360 mcg	180 mcg
    ).
• •Conversion from Another ESA:
  • •Dosed once monthly or once every two weeks based on total weekly epoetin alfa or darbepoetin alfa dose at time of conversion (
    2.2 For Adult Patients with CKD

    Prefilled syringes are not designed for administration of partial doses. Round doses to the closest dose achievable with the prefilled syringes.

    When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. A single hemoglobin excursion may not require a dosing change.

    • •Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments.
    • •If the hemoglobin rises rapidly (e.g., more than 1 g/dL in any 2-week period), reduce the dose of Mircera by approximately 25% to the closest dose achievable with the prefilled syringes to reduce rapid responses.
    • •If the hemoglobin continues to rise following a dose reduction, discontinue Mircera until the hemoglobin level begins to decrease, at which point therapy should be restarted with a dose that is approximately 25% below the previously administered dose.
    • •For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by approximately 25% to the closest dose achievable with the prefilled syringes.
    • •For patients who do not respond adequately over a 12-week escalation period, increasing the Mircera dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue Mircera if responsiveness does not improve.

    Administer Mircera either intravenously or subcutaneously. When administered subcutaneously, Mircera should be injected in the abdomen, arm or thigh.

    For Adult Patients with CKD

    on dialysis

    :

    • •Initiate Mircera treatment when the hemoglobin level is less than 10 g/dL.
    • •If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of Mircera.
    • •The recommended starting dose of Mircera for the treatment of anemia in
      adult
      CKD patients who are not currently treated with an ESA is 0.6 mcg/kg body weight administered once every two weeks as a single intravenous or subcutaneous injection. The intravenous route is recommended for patients receiving hemodialysis because the intravenous route may be less immunogenic
      [see Adverse Reactions ]
      .
    • •Once the hemoglobin has been stabilized, Mircera may be administered once monthly using a dose that is twice that of the every-two-week dose and subsequently titrated as necessary.

    For Adult Patients with CKD

    not on dialysis

    :

    • •Consider initiating Mircera treatment only when the hemoglobin level is less than 10 g/dL
      and
      the following considerations apply:
      • oThe rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion
        and
        ,
      • oReducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal.
    • •If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of Mircera, and use the lowest dose of Mircera sufficient to reduce the need for RBC transfusions.
    • •The recommended starting dose of Mircera for the treatment of anemia in
      adult
      CKD patients who are not currently treated with an ESA is 1.2 mcg/kg body weight administered once every month as a single subcutaneous injection. Alternatively, a starting dose of 0.6 mcg/kg body weight may be administered once every two weeks as a single intravenous or subcutaneous injection.
    • •Once the hemoglobin has been stabilized, Mircera may be administered once monthly using a dose that is twice that of the every-two-week dose and subsequently titrated as necessary.

    Refer patients who self-administer Mircera to the Instructions for Use

    [see Patient Counseling Information ]

    .

    Conversion from Epoetin alfa or Darbepoetin alfa to Mircera in Adult Patients with CKD

    Mircera can be administered once every two weeks or once monthly to patients whose hemoglobin has been stabilized by treatment with an ESA (see Table 1). The dose of Mircera, given as a single intravenous or subcutaneous injection, should be based on the total weekly ESA dose at the time of conversion.

    Table1: Mircera Starting Doses for Adult Patients Currently Receiving an ESA

    Previous Weekly Epoetin alfa Dose (units/week)	Previous Weekly Darbepoetin alfa Dose (mcg/week)	Mircera Dose
    		Once Monthly (mcg/month)	Once Every Two Weeks (mcg/every two weeks)
    Less than 8000 units	Less than 40 mcg	120 mcg	60 mcg
    8000 units to 16000 units	40 mcg to 80 mcg	200 mcg	100 mcg
    More than 16000 units	More than 80 mcg	360 mcg	180 mcg
    ).

• •Conversion from another ESA: dosed once every 4 weeks based on total weekly epoetin alfa or darbepoetin alfa dose at time of conversion (
  2.2 For Adult Patients with CKD

  Prefilled syringes are not designed for administration of partial doses. Round doses to the closest dose achievable with the prefilled syringes.

  When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. A single hemoglobin excursion may not require a dosing change.

  • •Do not increase the dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently. Avoid frequent dose adjustments.
  • •If the hemoglobin rises rapidly (e.g., more than 1 g/dL in any 2-week period), reduce the dose of Mircera by approximately 25% to the closest dose achievable with the prefilled syringes to reduce rapid responses.
  • •If the hemoglobin continues to rise following a dose reduction, discontinue Mircera until the hemoglobin level begins to decrease, at which point therapy should be restarted with a dose that is approximately 25% below the previously administered dose.
  • •For patients who do not respond adequately, if the hemoglobin has not increased by more than 1 g/dL after 4 weeks of therapy, increase the dose by approximately 25% to the closest dose achievable with the prefilled syringes.
  • •For patients who do not respond adequately over a 12-week escalation period, increasing the Mircera dose further is unlikely to improve response and may increase risks. Use the lowest dose that will maintain a hemoglobin level sufficient to reduce the need for RBC transfusions. Evaluate other causes of anemia. Discontinue Mircera if responsiveness does not improve.

  Administer Mircera either intravenously or subcutaneously. When administered subcutaneously, Mircera should be injected in the abdomen, arm or thigh.

  For Adult Patients with CKD

  on dialysis

  :

  • •Initiate Mircera treatment when the hemoglobin level is less than 10 g/dL.
  • •If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of Mircera.
  • •The recommended starting dose of Mircera for the treatment of anemia in
    adult
    CKD patients who are not currently treated with an ESA is 0.6 mcg/kg body weight administered once every two weeks as a single intravenous or subcutaneous injection. The intravenous route is recommended for patients receiving hemodialysis because the intravenous route may be less immunogenic
    [see Adverse Reactions ]
    .
  • •Once the hemoglobin has been stabilized, Mircera may be administered once monthly using a dose that is twice that of the every-two-week dose and subsequently titrated as necessary.

  For Adult Patients with CKD

  not on dialysis

  :

  • •Consider initiating Mircera treatment only when the hemoglobin level is less than 10 g/dL
    and
    the following considerations apply:
    • oThe rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion
      and
      ,
    • oReducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal.
  • •If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of Mircera, and use the lowest dose of Mircera sufficient to reduce the need for RBC transfusions.
  • •The recommended starting dose of Mircera for the treatment of anemia in
    adult
    CKD patients who are not currently treated with an ESA is 1.2 mcg/kg body weight administered once every month as a single subcutaneous injection. Alternatively, a starting dose of 0.6 mcg/kg body weight may be administered once every two weeks as a single intravenous or subcutaneous injection.
  • •Once the hemoglobin has been stabilized, Mircera may be administered once monthly using a dose that is twice that of the every-two-week dose and subsequently titrated as necessary.

  Refer patients who self-administer Mircera to the Instructions for Use

  [see Patient Counseling Information ]

  .

  Conversion from Epoetin alfa or Darbepoetin alfa to Mircera in Adult Patients with CKD

  Mircera can be administered once every two weeks or once monthly to patients whose hemoglobin has been stabilized by treatment with an ESA (see Table 1). The dose of Mircera, given as a single intravenous or subcutaneous injection, should be based on the total weekly ESA dose at the time of conversion.

  Table1: Mircera Starting Doses for Adult Patients Currently Receiving an ESA

  Previous Weekly Epoetin alfa Dose (units/week)	Previous Weekly Darbepoetin alfa Dose (mcg/week)	Mircera Dose
  		Once Monthly (mcg/month)	Once Every Two Weeks (mcg/every two weeks)
  Less than 8000 units	Less than 40 mcg	120 mcg	60 mcg
  8000 units to 16000 units	40 mcg to 80 mcg	200 mcg	100 mcg
  More than 16000 units	More than 80 mcg	360 mcg	180 mcg
  ).
• •In patients less than 6 years of age, maintain the same route of administration as the previous ESA when switching from another ESA to Mircera.

Injection: 30 mcg, 50 mcg, 75 mcg, 100 mcg, 120 mcg, 150 mcg, 200 mcg, or 250 mcg in 0.3 mL clear, colorless to slightly yellowish solution in single-dose prefilled syringes

Injection: 360 mcg in 0.6 mL clear, colorless to slightly yellowish solution in single-dose prefilled syringes

Available data from a small number of published case reports and postmarketing experience with Mircera use in pregnancy are insufficient to identify a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Chronic kidney disease is associated with maternal and embryo-fetal risks

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.