Posology : מינונים

4.2   Posology and method of administration
ADCETRIS should be administered under the supervision of a physician experienced in the use of anti-cancer agents.

Posology

Previously Untreated HL
The recommended dose in combination with chemotherapy (doxorubicin [A], vinblastine [V] and dacarbazine [D] [AVD]) is 1.2 mg/kg administered as an intravenous infusion over 30 minutes on days 1 and 15 of each 28-day cycle for 6 cycles (see section 5.1).

Primary prophylaxis with growth factor support (G-CSF), beginning with the first dose, is recommended for all adult patients with previously untreated HL receiving combination therapy (see section 4.4).

Refer to the summary of product characteristics (SmPC) of chemotherapy agents given in combination with ADCETRIS for patients with previously untreated HL.

HL at increased risk of relapse or progression

The recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks.

ADCETRIS treatment should start following recovery from ASCT based on clinical judgment. These patients should receive up to 16 cycles (see section 5.1).

Relapsed or refractory HL

The recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks.

The recommended starting dose for the retreatment of patients who have previously responded to treatment with ADCETRIS is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Alternatively, treatment may be started at the last tolerated dose (see section 5.1).

Treatment should be continued until disease progression or unacceptable toxicity (see section 4.4).

Patients who achieve stable disease or better should receive a minimum of 8 cycles and up to a maximum of 16 cycles (approximately 1 year) (see section 5.1).


Previously untreated sALCL or other CD30-expressing peripheral T-cell lymphomas 
The recommended dose in combination with chemotherapy (cyclophosphamide [C], doxorubicin [H] and prednisone [P] [CHP]) is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks for 6 to 8 cycles (see section 5.1).

Primary prophylaxis with G-CSF, beginning with the first dose, is recommended for all adult patients with previously untreated sALCL or other CD30-expressing peripheral T-cell lymphomas, receiving combination therapy (see section 4.4).

Refer to the SmPCs of chemotherapy agents given in combination with ADCETRIS for patients with previously untreated sALCL or other CD30-expressing peripheral T-cell lymphomas.

Relapsed or refractory sALCL

The recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks.

The recommended starting dose for the retreatment of patients who have previously responded to treatment with ADCETRIS is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Alternatively, treatment may be started at the last tolerated dose (see section 5.1).

Treatment should be continued until disease progression or unacceptable toxicity (see section 4.4).

Patients who achieve stable disease or better should receive a minimum of 8 cycles and up to a maximum of 16 cycles (approximately 1 year) (see section 5.1).

CTCL

The recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks.

Patients with CTCL should receive up to 16 cycles (see section 5.1).

General
Treatment should be continued until disease progression or unacceptable toxicity (see section 4.4).

If the patient’s weight is more than 100 kg, the dose calculation should use 100 kg (see section 6.6).

Complete blood counts should be monitored prior to administration of each dose of this treatment (see section 4.4).

Patients should be monitored during and after infusion (see section 4.4).

Dose adjustments

Neutropenia

If neutropenia develops during treatment it should be managed by dose delays. See Table 1 and Table 2 for appropriate dosing recommendations for monotherapy and combination therapy, respectively
(see also section 4.4).



Table 1: Dosing recommendations for neutropenia with monotherapy

Severity grade of neutropenia                             Modification of dosing schedule (signs and symptoms
[abbreviated description of
CTCAEa])
Grade 1 ( 1.5 times the upper limit of normal (ULN) (unless due to Gilbert syndrome), or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are > 3 times the ULN, or > 5 times the ULN if their elevation may be reasonably ascribed to the presence of HL in the liver. Use of ADCETRIS in combination with chemotherapy should be avoided in patients with moderate and severe hepatic impairment.

Monotherapy

The recommended starting dose in patients with severe renal impairment is 1.2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Patients with renal impairment should be closely monitored for adverse events (see section 5.2).

The recommended starting dose in patients with hepatic impairment is 1.2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Patients with hepatic impairment should be closely monitored for adverse events (see section 5.2).

Elderly

The safety and efficacy in patients aged 65 and older have not been established. No data are available 
Paediatric population

The safety and efficacy of ADCETRIS in children less than 18 years have not yet been established.
Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made.

In nonclinical studies, thymus depletion has been observed (see section 5.3).

Method of administration
The recommended dose of ADCETRIS is infused over 30 minutes.

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.



ADCETRIS must not be administered as an intravenous push or bolus. ADCETRIS should be administered through a dedicated intravenous line and it must not be mixed with other medicinal products (see section 6.2).