Treatment Of Anemia In

Hemodialysis Patients

Prepared by: Eshraq Al-abweeny

Clinical Pharmacist in drug information center

(DIC)

Clinical Pharmacy Department at KAUH

10-7-2019

Anemia is extremely common among hemodialysis patients.

Symptoms associated with anemia, including fatigue, depression, reduced exercise

tolerance, dyspnea, increased morbidity and mortality related to cardiovascular disease

and an increased risk of hospitalization and hospital length of stay.

All patients should be screened for anemia when they start dialysis, particularly if they

have not been closely followed prior to initiation of dialysis. Patients who are anemic

should be screened for iron deficiency.

The initial evaluation of anemia should include red blood cell (RBC) indices,

reticulocyte count, serum iron, total iron-binding capacity (TIBC), percent transferrin

saturation (TSAT), serum ferritin, serum folate and vitamin B12 levels, and testing for

occult blood in stool .

Introduction

Dialysis patients are often iron deficient due to gastrointestinal bleeding, blood drawing,

operations, and the dialysis treatment itself. Hemodialysis patients lose an average of 1

to 2 g of iron per year.

Anemia is defined by WHO as a hemoglobin (Hb) concentration <13 g/dL for adult

males and postmenopausal women and an Hb concentration <12 g/dL for

premenopausal women.

However, the WHO definition of anemia does not define goals of treatment among

hemodialysis patients. Even when typically treated, hemodialysis patients will still

have anemia as defined above. This is because, among hemodialysis patients, the

treatment of anemia typically involves erythropoiesis-stimulating agents (ESAs) to

avoid severe anemia and reduce the need for blood transfusions but not to normalize

Hb levels.

After the initial screen and evaluation, we continue to routinely monitor all dialysis

patients for anemia and iron deficiency.

How To Treat?

The treatment of anemia includes erythropoiesis-stimulating agents

(ESAs) and/or intravenous (IV) iron.

The goal of treatment is to:

- Mitigate any symptoms due to anemia

- Reduce the likelihood of needing a blood transfusion.

The selection of the individual therapy depends on the severity of anemia and on the

presence of iron deficiency.

Threshold transferrin saturation (TSAT) and ferritin levels for initiating treatment with

iron are different in patients who have an Hb concentration <10 g/dL OR are on an ESA

versus those who have an Hb ≥10 g/dL

TSAT ≤ 20% and ferritin ≤ 200 ng/mL — a loading dose of (IV) iron, provided that

an underlying infection has been excluded, regardless of the Hb and regardless of

whether patients are treated with an ESA.

- Among patients who are not already on an ESA, the loading dose of iron should be

repeated until the TSAT is >20 %.

- Iron should be given prior to the initiation of treatment with an ESA.

- Among patients who are being treated with an ESA , IV iron should be administered

while continuing ESA treatment (unless goal Hb has been reached or exceeded, in which

case the ESA is stopped).

TSAT ≤ 30 % and ferritin ≤ 500 ng/mL and who have Hb <10 g/dL —a loading dose

of (IV) iron, provided that an underlying infection has been excluded.

Among patients who are being treated with an ESA, if the TSAT is ≥30 percent and the

ferritin is <500 ng/mL, we administer a lower dose of maintenance iron.

Iron Therapy

Do not administer IV iron to patients who have ferritin levels above 500 ng/mL, regardless

of the TSAT and Hb, since no studies have proven a benefit of iron among such patients.

For patients who are being treated with an ESA and have Hb <10 g/dL and ferritin

>500 ng/mL, we occasionally increase the ESA dose without giving IV iron, providing the

patient is not on a very high erythropoietin dose already. If the increased ESA dose does not

raise the Hb level sufficiently, we occasionally try supplemental iron with or without a

further increase in erythropoietin dose.

Dosing and Administration of IV Iron

The goal with any loading regimen is to increase Hb levels and raise the TSAT to

approximately >30 %while not exceeding a serum ferritin level of 500 ng/mL.

There are multiple IV iron preparations:

- Sodium ferric gluconate complex in sucrose

- Iron sucrose

- Ferumoxytol

- Ferric carboxymaltose

- Iron dextran

Loading dose iron sucrose( Venofer®), (Ferrasil®) ( 20mg/ml) ( 5 ml) : 100 mg iron sucrose given at each consecutive hemodialysis treatment for a total of

10 doses (1000 mg in total) OR

200 mg over 2–5 minutes on five different occasions within 14-day period.

There is limited experience with administration of 500 mg diluted in a maximum of

250 mL of 0.9% NaCl over 3.5 to 4 hours on day 1 and day 14

Maintenance dose iron sucrose : 25 to 100 mg administered once weekly or every other week

Iron Sucrose

Preparation for Administration of Iron Sucrose :

Adults: Doses ≤200 mg may be administered undiluted or diluted in a maximum

of 100 mL NS. Doses >200 mg should be diluted in a maximum of 250 mL NS.

Do not dilute to concentrations <1 mg/mL.

Administration of iron sucrose :

- Administer IV as a slow IV injection (not for rapid IV injection) or as an IV infusion.

Can be administered through dialysis line.

- Slow IV injection: May administer doses ≤200 mg undiluted by slow IV injection over

2 to 5 minutes. When administering to hemodialysis-dependent patients, give iron

sucrose early during the dialysis session (generally within the first hour).

- Infusion: Infuse diluted doses ≤200 mg over at least 15 minutes; infuse diluted 300 mg

dose over 1.5 hours; infuse diluted 400 mg dose over 2.5 hours; infuse diluted 500 mg

dose over 3.5 to 4 hours (limited experience).

- All patients should be monitored for signs and symptoms of hypersensitivity for at least

30-60 minutes following completion of a dose.

Discontinue immediately for signs/symptoms of a hypersensitivity reaction (shock,

hypotension, loss of consciousness) or if signs of intolerance occur. Equipment for

resuscitation and trained personnel experienced in handling medical emergencies should

always be immediately available.

Storage/Stability of iron sucrose: - Shelf life after first opening the ampoule : should be used immediately.

- Shelf life after dilution with sterile 0.9% NS in an IV bag for 7 days at room

temperature (concentration 1 to 2 mg/mL).

- Store below 25 °c.

- Don’t freeze.

Adverse effects of IV iron include: - Allergic reactions (including anaphylaxis) and nonallergic infusion reactions such as self-

limiting urticaria, palpitations, dizziness, and neck and back spasm , abdominal pain,

nausea, chest pain, shortness of breath, flushing, pruritus, rash, hypotension and an

increased risk of bacterial infection and cardiovascular events.

- The risk of anaphylaxis varies with individual agents. The risk is highest with iron

dextran and generally lower with newer agents .

Erythropoiesis-stimulating agents

We administer (ESAs) to most hemodialysis patients who have a hemoglobin (Hb)

<10 g/dL and are not iron deficient (or no longer iron deficient).

Use ESAs to avoid drop in Hb to <9 g/dL by starting an ESA when Hb is between 9

and 10 g/dL

The optimal target Hb level for hemodialysis patients is not well defined. In most

dialysis patients who are treated with ESAs, we maintain levels between 10 and

11.5 g/dL.

We do not target an Hb concentration >13 g/dL.

We start patient on an ESA after iron stores are replete and if Hb remains less than

10 g/dL.

Dosage adjustments of ESAs for CKD patients (on dialysis):

Do not increase dose more frequently than every 4 weeks (dose decreases may occur

more frequently); avoid frequent dosage adjustments.

If hemoglobin does not increase by >1 g/dL after 4 weeks: Increase dose by 25%

If hemoglobin increases >1 g/dL in any 2-week period: Reduce dose by ≥25%

Inadequate or lack of response over a 12-week escalation period: Further increases are

unlikely to improve response and may increase risks; use the minimum effective dose

that will maintain a hemoglobin level sufficient to avoid RBC transfusions and evaluate

patient for other causes of anemia. Discontinue therapy if responsiveness does not

improve.

Epoetin alfa ( Binocrit® 4000 IU / 0.4 ml pre filled syringe) :

Dosing : 50 -100 units/kg three times per week.

Administration:

- Either IV ( preferred) or subcutaneous.

- Don’t shake.

- In haemodialysed patients, an IV bolus injection may be given during the

dialysis session through a suitable venous port in the dialysis line. Alternatively,

the injection can be given at the end of the dialysis session via the fistula needle

tubing, followed by 10 mL of isotonic saline to rinse the tubing and ensure

satisfactory injection of the product into the circulation.

- A slower administration is preferable in patients who react to the treatment with

“flu-like” symptoms.

- Do not administer by intravenous infusion or in conjunction with other drug

solutions.

Storage: Store refrigerated, you can store it out of the refrigerator and keep at

room temperature for no more than 3 days, don’t freeze.

Epoetin Alfa

Darbepoetin ( Aranesp ® 30 mcg solution for injection pre filled syringe) :

Dosing : 0.45 mcg/kg every week or 0.75 mcg/kg every two weeks.

Administration:

- Either IV ( preferred) or subcutaneous.

- Don’t shake.

Storage: Store in a refrigerator , do not freeze, protect from light.

- When your syringe has been removed from the refrigerator and left at room

temperature for approximately 30 minutes before injection it must either be used within 7

days or disposed.

Adverse effects of erythropoiesis-stimulating agents Hypertension , increased mortality, cardiovascular events, and malignancy, increased risk

of hemodialysis access thrombosis, seizures.

Darbepoetin

16

Estimated Darbepoetin Starting Doses (mcg/week) for Patients with

CKD on Dialysis Based on Previous Epoetin alfa Dose ( Units/ week)

Monitoring ●Anemic but Hb > 10 g /dL on (ESA) treatment – We monitor Hb at

least every three months. We measure TSAT and ferritin if anemia worsens.

●Anemic and treated with ESA administration – We measure Hb at least monthly; in many

dialysis facilities, Hb is routinely checked weekly. Hb should be checked after ESA initiation

and with dose adjustments to assess the response.

●Anemic and on stable ESA regimen – We measure Hb monthly (in many dialysis facilities,

Hb is checked weekly).

• we check Hb whenever clinically indicated (such as after major surgical procedures,

hospitalization, or bleeding).

●For patients on ESA treatment, we evaluate TSAT and serum ferritin at least every three

months.

●When initiating ESA treatment or increasing the ESA dose, we evaluate TSAT and serum

ferritin monthly.

References:

1- Berns,J.(2018). Treatment of anemia in hemodialysis patients. In S.Motwani

(Ed.), UpToDate. Retrieved June 20, 2019, from https://www.uptodate.com/contents/treatment-

of-anemia-in-hemodialysis-patients

2-Berns,J.(2019). Treatment of iron deficiency in hemodialysis patients. In S.Motwani

(Ed.), UpToDate. Retrieved June 20, 2019, from https://www.uptodate.com/contents/treatment-

of-iron-deficiency-in-hemodialysis-patients

3- Binocrit®. Summary of Product Characteristics ( LEAFLET).

4- Aranesp®. Summary of Product Characteristics ( LEAFLET).

5- Epoetin Alfa . In: Lexi-drugs online [database on the Internet]. Hudson (OH): Wolters

Kluwer Clinical Drug Information, Inc.: 2019 [updated 24 June 2019; cited 25 June 2019].

Available from: http://online.lexi.com. Subscription required to view.

6- Darbepoetin Alfa . In: Lexi-drugs online [database on the Internet]. Hudson (OH): Wolters

Kluwer Clinical Drug Information, Inc.: 2019 [updated 21 June 2019; cited 25 June 2019].

Available from: http://online.lexi.com. Subscription required to view.

Thank You