Nplate

Treatment should remain under the supervision of a physician who is experienced in the treatment of haematological 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 dose (mcg) Individual patient dose (mcg) = weight (kg) x dose in mcg/kg 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 paediatric 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.

6. The resulting concentration is 500 mcg/mL. Volume to administer (mL) = Individual patient dose (mcg) / 500 mcg/mL (Round volume to the nearest hundredth mL) If individual patient dose is < 23 mcg Dilution is required to ensure accurate dosing.

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 x 1 mcg/kg = 10 mcg Because the dose is < 23 mcg, dilution is required to ensure accurate dosing.

6. The resulting concentration is 125 mcg/mL. 08 mL 4 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 x 109/L.

Platelet counts should be assessed weekly until a stable platelet count (≥ 50 x 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 (x 109/L) Action < 50 Increase once weekly dose by 1 mcg/kg > 150 for two consecutive weeks Decrease once weekly dose by 1 mcg/kg > 250 Do not administer, continue to assess the platelet count weekly After the platelet count has fallen to < 150 x 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 x 109/L after dose reduction or treatment discontinuation.

5% (248/271). The mean duration of exposure to romiplostim in this study population was 50 weeks. The most serious adverse reactions that may occur during Nplate treatment include: reoccurrence of thrombocytopenia and bleeding after cessation of treatment, increased bone marrow reticulin, thrombotic/thromboembolic complications, medication errors and progression of existing MDS to AML.

The most common adverse reactions observed include hypersensitivity reactions (including cases of rash, urticaria and angioedema) and headache. Tabulated list of adverse reactions Frequencies are defined as: 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) and not known (cannot be estimated from the available data).

Within each MedDRA system organ class and frequency grouping, undesirable effects are presented in order of decreasing incidence. 4 ** Hypersensitivity reactions including cases of rash, urticaria, and angioedema *** Additional adverse reactions observed in paediatric studies **** Additional adverse reactions observed in adult patients with ITP duration up to 12 months Adult population with ITP duration up to 12 months The safety profile of romiplostim was similar across adult patients, regardless of ITP duration.

1). In this integrated analysis, the following adverse reactions (at least 5% incidence and at least 5% more frequent with Nplate compared with placebo or standard of care) occurred in romiplostim patients with ITP duration up to 12 months, but were not observed in those adult patients with ITP duration > 12 months: bronchitis, sinusitis (reported commonly (≥ 1/100 to < 1/10)).

Paediatric population In the paediatric studies, 282 paediatric ITP subjects were treated with romiplostim in 2 controlled and 3 uncontrolled clinical trials. 4 weeks. The overall safety profile was similar to that seen in adults. The paediatric adverse reactions are derived from each of the paediatric ITP randomised safety set (2 controlled clinical trials) and paediatric ITP safety set (2 controlled and 3 uncontrolled clinical trials) where the subject incidence was at least 5% higher in the romiplostim arm compared to placebo and at least a 5% subject incidence in romiplostim-treated subjects.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Reoccurrence of thrombocytopenia and bleeding after cessation of treatment Thrombocytopenia is likely to reoccur upon discontinuation of treatment with romiplostim.

There is an increased risk of bleeding if romiplostim treatment is discontinued in the presence of anticoagulants or anti-platelet agents. Patients should be closely monitored for a decrease in platelet count and medically managed to avoid bleeding upon discontinuation of treatment with romiplostim.

It is recommended that, if treatment with romiplostim is discontinued, ITP treatment be restarted according to current treatment guidelines. Additional medical management may include cessation of anticoagulant and/or antiplatelet therapy, reversal of anticoagulation, or platelet support.

Increased bone marrow reticulin Increased bone marrow reticulin is believed to be a result of TPO receptor stimulation, leading to an increased number of megakaryocytes in the bone marrow, which may subsequently release cytokines. 6 Increased reticulin may be suggested by morphological changes in the peripheral blood cells and can be detected through bone marrow biopsy.

Therefore, examinations for cellular morphological abnormalities using peripheral blood smear and complete blood count (CBC) prior to and during treatment with romiplostim are recommended. 8 for information on the increases of reticulin observed in romiplostim clinical trials.

If a loss of efficacy and abnormal peripheral blood smear is observed in patients, administration of romiplostim should be discontinued, a physical examination should be performed, and a bone marrow biopsy with appropriate staining for reticulin should be considered.

If available, comparison to a prior bone marrow biopsy should be made. If efficacy is maintained and abnormal peripheral blood smear is observed in patients, the physician should follow appropriate clinical judgment, including consideration of a bone marrow biopsy, and the risk-benefit of romiplostim and alternative ITP treatment options should be re-assessed.

1 or to E. coli derived proteins.