IMNOVID Hard capsule Ref.[9674] Active ingredients: Pomalidomide

Treatment must be initiated and monitored under the supervision of physicians experienced in the management of multiple myeloma.

Dosing is continued or modified based upon clinical and laboratory findings (see section 4.4).

Posology

Pomalidomide in combination with bortezomib and dexamethasone

The recommended starting dose of Imnovid is 4 mg orally once daily on Days 1 to 14 of repeated 21-day cycles.

Pomalidomide is administered in combination with bortezomib and dexamethasone, as shown in Table 1. The recommended starting dose of bortezomib is 1.3 mg/m² intravenous or subcutaneous once daily, on the days shown in Table 1. The recommended dose of dexamethasone is 20 mg orally once daily, on the days shown in Table 1.

Treatment with pomalidomide combined with bortezomib and dexamethasone should be given until disease progression or until unacceptable toxicity occurs.

Table 1. Recommended dosing scheme for Imnovid in combination with bortezomib and dexamethasone:

* For patients >75 years of age, see Special populations.

Pomalidomide dose modification or interruption

To initiate a new cycle of pomalidomide, the neutrophil count must be ≥1 × 10⁹/l and the platelet count must be ≥50 × 10⁹/l. Instructions on dose interruptions or reductions for pomalidomide related adverse reactions are outlined in the Table 2 and dose levels are defined in Table 3 below.

Table 2. Pomalidomide dose modification instructions∞:

^∞ Dose modification instructions in this table are applicable to pomalidomide in combination with bortezomib and dexamethasone and to pomalidomide in combination with dexamethasone.
^* In case of neutropenia, the physician should consider the use of growth factors. **ANC – Absolute Neutrophil Count; ***CBC – Complete Blood Count.

Table 3. Pomalidomide dose reduction∞:

^∞ Dose reduction in this table is applicable to pomalidomide in combination with bortezomib and dexamethasone and to pomalidomide in combination with dexamethasone

If adverse reactions occur after dose reductions to 1 mg, then the medicinal product should be discontinued.

Strong CYP1A2 inhibitors

If strong inhibitors of CYP1A2 (e.g. ciprofloxacin, enoxacin and fluvoxamine) are co-administered with pomalidomide, reduce the dose of pomalidomide by 50% (see sections 4.5 and 5.2).

Bortezomib dose modification or interruption

For instructions on dose interruptions or reductions for bortezomib related adverse reactions, physicians should refer to bortezomib Summary of Product Characteristics (SmPC).

Dexamethasone dose modification or interruption

Instructions on dose interruptions or reductions for low-dose dexamethasone related adverse reactions are outlined in Tables 4 and 5 below. However, dose interruption or resumption decisions are at the physician’s discretion per Summary of Product Characteristics (SmPC).

Table 4. Dexamethasone dose modification instructions:

If recovery from toxicities is prolonged beyond 14 days, then the dose of dexamethasone will be resumed at one dose level lower than the previous dose.

Table 5. Dexamethasone dose reduction:

Dexamethasone should be discontinued if the patient is unable to tolerate 8 mg if ≤75 years old or 4 mg if >75 years old.

In case of permanent discontinuation of any component of the treatment regimen, continuation of the remaining medicinal products is at the physician’s discretion.

Pomalidomide in combination with dexamethasone

The recommended starting dose of Imnovid is 4 mg orally once daily on Days 1 to 21 of repeated 28-day cycles.

The recommended dose of dexamethasone is 40 mg orally once daily on Days 1, 8, 15 and 22 of each 28-day treatment cycle.

Treatment with pomalidomide combined with dexamethasone should be given until disease progression or until unacceptable toxicity occurs.

Pomalidomide dose modification or interruption

Instructions for dose interruptions or reductions for pomalidomide related adverse reactions are outlined in Table 2 and 3.

Dexamethasone dose modification or interruption

Instructions for dose modification for dexamethasone related adverse reactions are outlined in Table 4. Instructions for dose reduction for dexamethasone related adverse reactions are outlined in Table 6 below. However, dose interruption/resumption decisions are at physician’s discretion per the current Summary of Product Characteristics (SmPC).

Table 6. Dexamethasone dose reduction:

Dexamethasone should be discontinued if the patient is unable to tolerate 10 mg if ≤75 years old or 8 mg if >75 years old.

Special populations

Elderly

Pomalidomide in combination with bortezomib and dexamethasone:

No dose adjustment is required for pomalidomide.

For information on bortezomib given in combination with Imnovid, refer to the respective current SmPC.

For patients >75 years of age, the starting dose of dexamethasone is:

• For Cycles 1 to 8: 10 mg once daily on Days 1, 2, 4, 5, 8, 9, 11 and 12 of each 21-day cycle
• For Cycles 9 and onwards: 10 mg once daily on Days 1, 2, 8 and 9 of each 21-day cycle.

Pomalidomide in combination with dexamethasone:

No dose adjustment is required for pomalidomide.

For patients >75 years of age, the starting dose of dexamethasone is:

• 20 mg once daily on days 1, 8, 15 and 22 of each 28-day treatment cycle.

Hepatic impairment

Patients with serum total bilirubin >1.5 x ULN (upper limit of normal range)were excluded from clinical studies. Hepatic impairment has a modest effect on the pharmacokinetics of pomalidomide (see section 5.2). No adjustment of the starting dose of pomalidomide is required for patients with hepatic impairment as defined by the Child-Pugh criteria. However, patients with hepatic impairment should be carefully monitored for adverse reactions and dose reduction or interruption of pomalidomide should be used as needed.

Renal impairment

No dose adjustment of pomalidomide is required for patients with renal impairment. On haemodialysis days, patients should take their pomalidomide dose following haemodialysis.

Paediatric population

There is no relevant use of pomalidomide in children aged 0-17 years for the indication of multiple myeloma.

Method of administration

Oral use.

Imnovid hard capsules should be taken orally at the same time each day. The capsules should not be opened, broken or chewed (see section 6.6). The capsules should be swallowed whole, preferably with water, with or without food. If the patient forgets to take a dose of pomalidomide on one day, then the patient should take the normal prescribed dose as scheduled on the next day. Patients should not adjust the dose to make up for a missing dose on previous days.

It is recommended to press only on one end of the capsule to remove it from the blister thereby reducing the risk of capsule deformation or breakage.

For information on other medicinal products given in combination with Imnovid, refer to the respective current SmPC.

Pomalidomide doses as high as 50 mg as a single dose in healthy volunteers, and 10 mg as once-daily multiple doses in multiple myeloma patients have been studied without reported serious adverse reactions related to overdose. In studies, pomalidomide was found to be removed by haemodialysis.

In the event of overdose, supportive care is advised.

4 years.

This medicinal product does not require any special storage conditions.

The capsules are packaged in Polyvinyl chloride (PVC)/ polychlorotrifluoroethylene (PCTFE) blisters with push through aluminium foil.

Pack size of 14 or 21 capsules.

Not all pack size may be marketed.

Capsules should not be opened or crushed. If powder from pomalidomide makes contact with the skin, the skin should be washed immediately and thoroughly with soap and water. If pomalidomide makes contact with the mucous membranes, they should be thoroughly flushed with water.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Unused medicinal product should be returned to the pharmacist at the end of treatment.