Epoetin theta

Due to limited experience, the efficacy and safety of epoetin theta could not be assessed in patients with impaired liver function or homozygous sickle cell anaemia.

In clinical trials, patients over 75 years of age had a higher incidence of serious and severe adverse events irrespective of a causal relationship to treatment with epoetin theta. Furthermore, deaths were more frequent in this patient group compared to younger patients.

Epoetins are growth factors that primarily stimulate red blood cell production. Erythropoietin receptors may be expressed on the surface of a variety of tumour cells. As with all growth factors, there is a concern that epoetins could stimulate the growth of any type of malignancy.

In several controlled studies, epoetins have not been shown to improve overall survival or decrease the risk of tumour progression in patients with anaemia associated with cancer. In controlled clinical studies, use of epoetins has shown:

• shortened time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy when administered to target a haemoglobin level in excess of 14 g/dl (8.69 mmol/l),
• shortened overall survival and increased deaths attributed to disease progression at 4 months in patients with metastatic breast cancer receiving chemotherapy when administered to target a haemoglobin value of 12-14 g/dl (7.45-8.69 mmol/l),
• increased risk of death when administered to target a haemoglobin value of 12 g/dl (7.45 mmol/l) in patients with active malignant disease receiving neither chemotherapy nor radiation therapy.

Epoetins are not indicated for use in this patient population.

In view of the above, in some clinical situations blood transfusion should be the preferred treatment for the management of anaemia in patients with cancer. The decision to administer recombinant erythropoietins should be based on a benefit-risk assessment with the participation of the individual patient, which should take into account the specific clinical context. Factors that should be considered in this assessment should include the type of tumour and its stage, the degree of anaemia, life-expectancy, the environment in which the patient is being treated, and patient preference.

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of epoetin theta in pregnant women. Animal studies with other epoetins do not indicate direct harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of epoetin theta during pregnancy.

It is unknown whether epoetin theta/metabolites are excreted in human milk, but data in neonates show no absorption or pharmacological activity of erythropoietin when given together with breast milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from epoetin theta therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

No data are available.

Epoetin theta has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

Approximately 9% of patients can be expected to experience an adverse reaction. The most frequent adverse reactions are hypertension, influenza-like illness and headache.

Tabulated list of adverse reactions

The safety of epoetin theta has been evaluated based on results from clinical studies including 972 patients. Adverse reactions listed below in the following table are classified according to System Organ Class. Frequency groupings are defined according to the following convention: Very common ≥1/10; Common ≥1/100 to <1/10; Uncommon ≥1/1,000 to <1/100; Rare ≥1/10,000 to <1/1,000; Very rare <1/10,000; Not known, cannot be estimated from the available data.

Adverse reactions:

Description of selected adverse reactions

In patients with chronic renal failure, neutralising anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA) associated with epoetin theta therapy has been reported in post marketing setting. If PRCA is diagnosed, therapy with epoetin theta must be discontinued and patients should not be switched to another recombinant epoetin.

One of the most frequent adverse reactions during treatment with epoetin theta is an increase in blood pressure or aggravation of existing hypertension particularly during the initial treatment phase. Hypertension occurs in chronic renal failure patients more often during the correction phase than during the maintenance phase. Hypertension can be treated with appropriate medicinal products.

Hypertensive crisis with encephalopathy-like symptoms (e.g. headaches, confused state, speech disturbances, impaired gait) and related complications (seizures, stroke) may also occur in individual patients with otherwise normal or low blood pressure.

Shunt thrombosis may occur, especially in patients who have a tendency to hypotension or whose arterio-venous fistulae exhibit complications (e.g. stenoses, aneurisms).

Skin reactions such as rash, pruritus or injection site reactions may occur.

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association with epoetin treatment.

Symptoms of influenza-like illness such as fever, chills and asthenic conditions have been reported.