Methoxy Polyethylene Glycol-Epoetin Beta

Registered South African indications:

• Anaemia associated with chronic kidney disease (CKD)

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Uncontrolled hypertension
• Pregnancy
• Lactation

Cautions

• Renal impairment
• Elderly
• Anaemia associated with cancer
• Anaemia associated with hepatitis C
• Iron deficiency
• Folic acid deficiency
• Vitamin B12 deficiency
• Misuse
• Intercurrent infections
• Inflammatory or traumatic episodes
• Occult blood loss
• Haemolysis
• Severe aluminium toxicity
• Underlying haematologic diseases
• Bone marrow fibrosis
• Haemoglobin concentration > 12 g/dl (7.45 mmol/l)
• Haemoglobinopathies
• Seizures
• Bleeding or a recent history of bleeding requiring transfusions
• Platelet levels greater than 500 x 10⁹/l
• Pre-existing malignancy

Forms avail. in SA and covered in this monograph: inj

Anaemia associated with chronic kidney disease (CKD)

- Patients currently not treated with an Erythropoiesis Stimulating Agent (ESA):

Patients not on dialysis; in order to increase the haemoglobin to > 10 g/dl (6,21 mmol/ l)
IV/SC: 0.6μg/kg, every 2 weeks
OR 
SC: Initial: 1.2μg/kg, every month

Patients on dialysis; in order to increase the haemoglobin to > 11 g/dl (6,83 mmol/ l)
IV/SC: 0.6μg/kg, every 2 weeks

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Hb should not exceed 12g/dl (7.45mmol)

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It is recommended that Hb is monitored every 2 weeks until stabilised, and periodically thereafter.

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Titration: If rise in Hb <1,0g/dl (0.621 mmol/l) per month then uptitrate dose by 25%; Further increases of approx. 25 % may be made monthly until the individual target haemoglobin level is obtained

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Titration: If rise in Hb is >2g/dl (1.24 mmol/l) per month or if the haemoglobin rises rapidly (e.g. more than 1g/dl in any 2-week period) then downtitrate dosage by ≥ 25 % as needed

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If the Hb level >11g/dl (6.83 mmol/l),  interrupt therapy until the Hb level <11g/dl; Then restart at approx. 50 % of the previously administered dose

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Patients treated every 2 weeks whose Hb level >11g/dl (6.83 mmol/l) may be switched to monthly dosing using the dose equal to twice the
previous 2 weekly dose

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After dose interruption, a Hb decrease of approx. 0.35g/dl (0.22 mmol/l) per week is expected

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Dose adjustments should not be made more often than once a month

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- Patients currently treated with an ESA

• Currently treated patients can be converted to methoxypolyethylene glycol-epoetin beta dose administered monthly or every 2 weeks as a single IV/SC injection (see table below for dosing)

Previous weekly epoetin dose (IU/week)	Methoxypolyethylene glycol-epoetin beta dose
	Once monthly	Once every 2 weeks (μg/q2w)
<8000	120	60
8000-16000	200	100
>16000	360	180

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It is recommended that Hb is monitored every 2 weeks until stabilised, and periodically thereafter

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The first injection of methoxypolyethylene glycol-epoetin beta should be administered at the next scheduled dose of the
previously administered epoetin

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Titration: If dose adjustment is required to maintain Hb level >11,0g/dl (6.82 mmol/l), the monthly dose may be adjusted by approx. 25%

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Titration: If rise in Hb is >2g/dl (1.24 mmol/l) per month or if the haemoglobin level is approaching Hb 12g/dl (7.45 mmol/l) then downtitrate dosage by approx. 25 %

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If the Hb continues to increase, interrupt therapy until the Hb decreases; Then restart at approx. 25 % below the previously administered dose

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After dose interruption, a Hb decrease of approx. 0.35g/dl (0.22 mmol/l) per week is expected

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Dose adjustments should not be made more often than once a month

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(See Additional prescribing points for more dosing information)

Not established for use in children below 18 years

Pregnancy

• Contraindicated

Breastfeeding

• Contraindicated

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• No dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Headache
• Hypertensive encephalopathy

Cardiovascular Disorders

• Hypertension
• Hot flush
• Thrombosis
• Pulmonary embolism

Skin and Subcutaneous Tissue Disorders

• Maculopapular rash
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia
• Pure red cell aplasia
• Decreased ferritin values (premature infants)
• Anaphylactic reactions
• Hypersensitivity reactions

Other

• Vascular access thrombosis
• Data from a controlled clinical trial with epoetin alfa or darbepoetin alfa reported an incidence of stroke as common

No information available

• Haemoglobin levels
• Blood pressure
• Hypersensitivity
• Iron levels

Specific cases may require

• Neurologic symptoms of seizures

Special Instructions for Use

• The solution can be administered subcutaneously (SC) or intravenously (IV), according to clinical preference
• Methoxypolyethylene glycol-epoetin beta should not be mixed with other products
• Methoxypolyethylene glycol-epoetin beta is a sterile but unpreserved product
• Do not administer more than one dose per pre-filled
• syringe
• Any unused product remaining in the pre-filled syringe should be discarded
• Only solutions which are clear, colourless to slightly yellowish and free of visible particles must be injected
• Do not shake
• Allow the product to reach room temperature before injecting
• Methoxypolyethylene glycol-epoetin beta can be injected subcutaneously in the abdomen, arm or thigh. All three injection sites are equally suitable for subcutaneous injection with methoxypolyethylene glycol-epoetin beta

Further dosage information

• Since the treatment experience is limited in patients on peritoneal dialysis, regular Hb monitoring and strict adherence to dose adjustment guidance are recommended in these patients
• Treatment interruption:
  Treatment with methoxypolyethylene glycol-epoetin beta is usually long-term. However, it can be interrupted at any time, if necessary
• Missed dose:
  If one dose of methoxypolyethylene glycol-epoetin beta is missed, the missed dose should be administered as soon
  as possible and administration of methoxypolyethylene glycol-epoetin beta is to be restarted at the prescribed dosing frequency

Other 

• Hb levels should not exceed 12d/dl (7.5mmol/l)
• In clinical trials, an increased risk of death, serious cardiovascular events including thrombosis or cerebrovascular events including stroke was observed when ESAs were administered to target a haemoglobin of greater than 12 g/dl (7.5 mmol/l) 

Methoxypolyethylene glycol-epoetin beta stimulates erythropoiesis by interaction with the erythropoietin receptor on progenitor cells in the bone marrow. Methoxy polyethylene glycol-epoetin beta is a continuous erythropoietin receptor activator that shows a different activity at the receptor level characterized by a slower association to and faster dissociation from the receptor, a reduced specific activity in vitro with an increased activity in vivo, as well as an increased half-life, in contrast to erythropoietin.

Injection (per 0.3ml) 30μg

• Mircera pre-filled (Roche) originator (Discontinued: 06/12/2021)

Injection (per 0.3ml) 50μg

• Mircera pre-filled (Roche) originator

Injection (per 0.3ml) 75μg

• Mircera pre-filled (Roche) originator

Injection (per 0.3ml) 100μg

• Mircera pre-filled (Roche) originator

Injection (per 0.3ml) 120μg

• Mircera pre-filled (Roche) originator

Injection (per 0.3ml) 150μg

• Mircera pre-filled (Roche) originator

Injection (per 0.3ml) 200μg

• Mircera pre-filled (Roche) originator

Injection (per 0.3ml) 250μg

• Mircera pre-filled (Roche) originator

Injection (per 0.6ml) 360μg

• Mircera pre-filled (Roche) originator