Posology : מינונים

4.2    Posology and method of administration

Treatment should remain under the supervision of a physician who is experienced in the treatment of hematological diseases.

Posology

Nplate should be administered once weekly as a subcutaneous injection.

Initial dose

The initial dose of romiplostim is 1 mcg/kg based on actual body weight.
Dose calculation

The volume of romiplostim to administer is calculated based on body weight, dose required, and concentration of product.

Table 1. Guidelines for calculating individual patient dose and volume of romiplostim to administer

Individual patient    Individual patient dose (mcg) = weight (kg) × dose in mcg/kg dose (mcg)
Actual body weight at initiation of treatment should always be used when calculating initial dose.
•      In adults, future dose adjustments are based on changes in platelet counts only.
•      In pediatric patients, future dose adjustments are based on changes in platelet counts and changes in body weight.
Reassessment of body weight is recommended every
12 weeks.
If individual         Reconstitute lyophilized product as described in section 6.6. The patient dose is       resulting concentration is 500 mcg/mL.
≥ 23 mcg
Volume to administer (mL) = Individual patient dose
(mcg)/500 mcg/mL
(Round volume to the nearest hundredth mL)
If individual         Dilution is required to ensure accurate dosing. Reconstitute patient dose is       lyophilized product and then dilute the product as described in < 23 mcg              section 6.6. The resulting concentration is 125 mcg/mL.

Volume to administer (mL) = Individual patient dose
(mcg)/125 mcg/mL
(Round volume to the nearest hundredth mL)
Example               10 kg patient is initiated at 1 mcg/kg of romiplostim.

Individual patient dose (mcg) = 10 kg × 1 mcg/kg = 10 mcg
Because the dose is < 23 mcg, dilution is required to ensure accurate dosing. Reconstitute lyophilized product and then dilute the product as described in section 6.6. The resulting concentration is 125 mcg/mL.

Volume to administer (mL) = 10 mcg/125 mcg/mL = 0.08 mL

Dose adjustments
A subject’s actual body weight at initiation of therapy should be used to calculate dose. The once weekly dose of romiplostim should be increased by increments of 1 mcg/kg until the patient achieves a platelet count ≥ 50 × 109/L. Platelet counts should be assessed weekly until a stable platelet count (≥ 50 × 109/L for at least 4 weeks without dose adjustment) has been achieved. Platelet counts should be assessed monthly thereafter and appropriate dose adjustments made as per the dose adjustment table (table 2) in order to maintain platelet 
counts within the recommended range. See table 2 below for dose adjustment and monitoring.
A maximum once weekly dose of 10 mcg/kg should not be exceeded.

Table 2. Dose adjustment guidance based on platelet count
Platelet count
Action
(× 109/L)
< 50                       Increase once weekly dose by 1 mcg/kg
> 150 for two
Decrease once weekly dose by 1 mcg/kg consecutive weeks
Do not administer, continue to assess the platelet count weekly
> 250
After the platelet count has fallen to < 150 × 109/L, resume dosing with once weekly dose reduced by 1 mcg/kg

Due to the interindividual variable platelet response, in some patients platelet count may abruptly fall below 50 × 109/L after dose reduction or treatment discontinuation. In these cases, if clinically appropriate, higher cut-off levels of platelet count for dose reduction (200 × 109/L) and treatment interruption (400 × 109/L) may be considered according to medical judgment.

A loss of response or failure to maintain a platelet response with romiplostim within the recommended dosing range should prompt a search for causative factors (see section 4.4, loss of response to romiplostim).

Treatment discontinuation

Treatment with romiplostim should be discontinued if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after four weeks of romiplostim therapy at the highest weekly dose of 10 mcg/kg.

Patients should be clinically evaluated periodically and continuation of treatment should be decided on an individual basis by the treating physician, and in non-splenectomized patients this should include evaluation relative to splenectomy. The reoccurrence of thrombocytopenia is likely upon discontinuation of treatment (see section 4.4).

Elderly patients (≥ 65 years)

No overall differences in safety or efficacy have been observed in patients < 65 and ≥ 65 years of age (see section 5.1). Although based on these data no adjustment of the dosing regimen is required for older patients, care is advised considering the small number of elderly patients included in the clinical trials so far.

Pediatric population

The safety and efficacy of romiplostim in children under the age of one year has not been established.

Patients with hepatic impairment

Romiplostim should not be used in patients with moderate to severe hepatic impairment (Child-Pugh score ≥ 7) unless the expected benefit outweighs the identified risk of portal venous thrombosis in patients with thrombocytopenia associated to hepatic insufficiency treated with thrombopoietin (TPO) agonists (see section 4.4).

If the use of romiplostim is deemed necessary, platelet count should be closely monitored to minimize the risk of thromboembolic complications.

Patients with renal impairment

No formal clinical trials have been conducted in these patient populations. Nplate should be used with caution in these populations.

Method of administration

For subcutaneous use.
After reconstitution of the powder, Nplate solution for injection is administered subcutaneously. The injection volume may be very small. Caution should be used during preparation of Nplate in calculating the dose and reconstitution with the correct volume of sterile water for injections. If the calculated individual patient dose is less than 23 mcg, dilution with preservative-free, sterile, sodium chloride 9 mg/mL (0.9%) solution for injection is required to ensure accurate dosing (see section 6.6). Special care should be taken to ensure that the appropriate volume of Nplate is withdrawn from the vial for subcutaneous administration – a syringe with graduations of 0.01 mL should be used.

Self-administration of Nplate is not allowed for pediatric patients.

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