Revolade Ref.[2779] Active ingredients: Eltrombopag

Eltrombopag treatment should remain under the supervision of a physician who is experienced in the treatment of haematological diseases.

Eltrombopag dosing requirements must be individualised based on the patient’s platelet counts. The objective of treatment with eltrombopag should not be to normalise platelet counts but to maintain platelet counts above the level for haemorrhagic risk (> 50,000/µl).

In most patients, measurable elevations in platelet counts take 1-2 weeks (see section 5.1).

Adults

The recommended starting dose of eltrombopag is 50 mg once daily. For patients of East Asian ancestry, eltrombopag should be initiated at a reduced dose of 25 mg once daily (see section 5.2).

Monitoring and dose adjustment

After initiating eltrombopag, adjust the dose to achieve and maintain a platelet count ≥ 50,000/µl as necessary to reduce the risk for bleeding. Do not exceed a dose of 75 mg daily.

Clinical haematology and liver tests should be monitored regularly throughout therapy with eltrombopag and the dose regimen of eltrombopag modified based on platelet counts as outlined in Table 1. During therapy with eltrombopag complete blood counts (CBCs), including platelet count and peripheral blood smears, should be assessed weekly until a stable platelet count (≥ 50,000/µl for at least 4 weeks) has been achieved. CBCs including platelet counts and peripheral blood smears should be obtained monthly thereafter.

The lowest effective dosing regimen to maintain platelet counts should be used as clinically indicated.

Table 1 – Dose adjustments of eltrombopag:

Eltrombopag can be administered in addition to other ITP medicinal products. Modify the dose regimen of concomitant ITP medicinal products, as medically appropriate, to avoid excessive increases in platelet counts during therapy with eltrombopag.

Wait for at least 2 weeks to see the effect of any dose adjustment on the patient’s platelet response prior to considering another dose adjustment.

The standard eltrombopag dose adjustment, either decrease or increase, would be 25 mg once daily. However, in a few patients a combination of different film-coated tablet strengths on different days may be required.

Discontinuation

Treatment with eltrombopag should be discontinued if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after four weeks of eltrombopag therapy at 75 mg once daily.

Patients should be clinically evaluated periodically and continuation of treatment should be decided on an individual basis by the treating physician. The reoccurrence of thrombocytopenia is possible upon discontinuation of treatment (see section 4.4).

Renal impairment

No dose adjustment is necessary in patients with renal impairment. Patients with impaired renal function should use eltrombopag with caution and close monitoring, for example by testing serum creatinine and/or performing urine analysis (see section 5.2).

Hepatic impairment

Eltrombopag should not be used in ITP patients with hepatic impairment (Child-Pugh score ≥ 5) unless the expected benefit outweighs the identified risk of portal venous thrombosis (see section 4.4).

If the use of eltrombopag is deemed necessary for ITP patients with hepatic impairment, the starting dose must be 25 mg once daily. After initiating the dose of eltrombopag in patients with hepatic impairment wait 3 weeks before increasing the dose.

The risk of thromboembolic events (TEEs) has been found to be increased in thrombocytopenic patients (platelet count < 50,000/µl) with chronic liver disease (CLD), without concomitant ITP, treated with 75 mg eltrombopag once daily for two weeks in preparation for invasive procedures (see sections 4.4 and 4.8).

Paediatric population

Revolade is not recommended for use in children and adolescents below age 18 due to insufficient data on safety and efficacy.

Elderly

There are limited data on the use of eltrombopag in patients aged 65 years and older. In the clinical studies of eltrombopag, overall no clinically significant differences in safety of eltrombopag were observed between subjects aged at least 65 years and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

East Asian patients

Initiation of eltrombopag at a reduced dose of 25 mg once daily may be considered for patients of East Asian ancestry (such as Chinese, Japanese, Taiwanese or Korean) (see section 5.2). Patient platelet count should continue to be monitored and the standard criteria for further dose modification followed.

Method of administration

The tablets should be administered orally. Eltrombopag should be taken at least four hours before or after any products such as antacids, dairy products (or other calcium containing food products), or mineral supplements containing polyvalent cations (e.g. iron, calcium, magnesium, aluminium, selenium and zinc) (see sections 4.5 and 5.2).

In the event of overdose, platelet counts may increase excessively and result in thrombotic/thromboembolic complications. In case of an overdose, consider oral administration of a metal cation-containing preparation, such as calcium, aluminium, or magnesium preparations to chelate eltrombopag and thus limit absorption. Closely monitor platelet counts. Reinitiate treatment with eltrombopag in accordance with dosing and administration recommendations (see section 4.2).

In the ITP clinical studies there was one report of overdose where the subject ingested 5000 mg of eltrombopag. Reported adverse events included mild rash, transient bradycardia, ALT and AST elevation, and fatigue. Liver enzymes measured between Days 2 and 18 after ingestion peaked at a 1.6-fold ULN in AST, a 3.9-fold ULN in ALT, and a 2.4-fold ULN in total bilirubin, The platelet counts were 672,000/µl on day 18 after ingestion and the maximum platelet count was 929,000/µl. All events were resolved without sequelae following treatment.

Because eltrombopag is not significantly renally excreted and is highly bound to plasma proteins, haemodialysis would not be expected to be an effective method to enhance the elimination of eltrombopag.

4 years.

This medicinal product does not require any special storage conditions.

Aluminum blisters (PA/Alu/PVC/Alu) in a carton containing 14 or 28 film-coated tablets and multipacks containing 84 (3 packs of 28) film-coated tablets.

Not all pack sizes may be marketed.

Any unused product or waste material should be disposed of in accordance with local requirements.