Imnovid 1mg 2mg 3mg 4m ghard capsules - Ireland[爱尔兰药品]

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Imnovid 1mg 2mg 3mg 4m ghard capsules

2014-06-14 23:38:35 来源: 作者: 【大中小】浏览:519次评论:0条

Table of Contents
1. Name of the medicinal product
2. Qualitative and quantitative composition
3. Pharmaceutical form
4. Clinical particulars
4.1 Therapeutic indications
4.2 Posology and method of administration
4.3 Contraindications
4.4 Special warnings and precautions for use
4.5 Interaction with other medicinal products and other forms of interaction
4.6 Fertility, pregnancy and lactation
4.7 Effects on ability to drive and use machines
4.8 Undesirable effects
4.9 Overdose
5. Pharmacological properties
5.1 Pharmacodynamic properties
5.2 Pharmacokinetic properties
5.3 Preclinical safety data
6. Pharmaceutical particulars
6.1 List of excipients
6.2 Incompatibilities
6.3 Shelf life
6.4 Special precautions for storage
6.5 Nature and contents of container
6.6 Special precautions for disposal and other handling
7. Marketing authorisation holder
8. Marketing authorisation number(s)
9. Date of first authorisation/renewal of the authorisation
10. Date of revision of the text
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

1. Name of the medicinal product

Imnovid 1 mg hard capsules

Imnovid 2 mg hard capsules

Imnovid 3 mg hard capsules

Imnovid 4 mg hard capsules

2. Qualitative and quantitative composition

Each hard capsule contains 1 mg of pomalidomide.

Each hard capsule contains 2 mg of pomalidomide.

Each hard capsule contains 3 mg of pomalidomide.

Each hard capsule contains 4 mg of pomalidomide.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Hard capsule.

Imnovid 1 mg hard capsule: Dark blue opaque cap and yellow opaque body, imprinted “POML” in white ink and “1 mg” in black ink, size 4, hard gelatin capsule.

Imnovid 2 mg hard capsule: Dark blue opaque cap and orange opaque body, imprinted “POML 2 mg” in white ink, size 2, hard gelatin capsule.

Imnovid 3 mg hard capsule: Dark blue opaque cap and green opaque body, imprinted, “POML 3 mg” in white ink, size 2, hard gelatin capsule.

Imnovid 4 mg hard capsule: Dark blue opaque cap and blue opaque body, imprinted “POML 4 mg” in white ink, size 2, hard gelatin capsule.

4. Clinical particulars

4.1 Therapeutic indications

Imnovid in combination with dexamethasone is indicated in the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy.

4.2 Posology and method of administration

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

Posology

The recommended starting dose of Imnovid is 4 mg once daily taken orally 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.

Dosing is continued or modified based upon clinical and laboratory findings. Treatment should be discontinued upon progression of disease.

Pomalidomide dose modification or interruption

Instructions for dose interruptions and reductions for pomalidomide related to haematologic adverse reactions are outlined in the table below:

• Pomalidomide dose modification instructions

Toxicity	Dose modification
Neutropenia
• ANC* < 0.5 x 10⁹/l or Febrile neutropenia (fever ≥38.5°C and ANC <1 x 10⁹/l)	Interrupt pomalidomide treatment, follow CBC** weekly.
• ANC return to ≥1 x 10⁹/l	Resume pomalidomide treatment at 3 mg daily.
• For each subsequent drop < 0.5 x 10⁹/l	Interrupt pomalidomide treatment
• ANC return to ≥1 x 10⁹/l	Resume pomalidomide treatment at 1 mg less than the previous dose.
Thrombocytopenia
• Platelet count <25 x 10⁹/l	Interrupt pomalidomide treatment, follow CBC** weekly
• Platelet count return to ≥50 x 10⁹/l	Resume pomalidomide treatment at 3 mg daily
• For each subsequent drop <25 x 10⁹/l	Interrupt pomalidomide treatment
• Platelet count return to ≥50 x 10⁹/l	Resume pomalidomide treatment at 1 mg less than the previous dose

*ANC – Absolute Neutrophil Count; **CBC – Complete Blood Count;

To initiate a new cycle of pomalidomide, the neutrophil count must be ≥1 x 10⁹/l and the platelet count must be ≥ 50 x 10⁹/l.

In case of neutropaenia, the physician should consider the use of growth factors.

For other Grade 3 or 4 adverse reactions judged to be related to pomalidomide, stop treatment and restart treatment at 1 mg less than the previous dose when an adverse reaction has resolved to ≤ Grade 2 at the physician's discretion.

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

• Dexamethasone dose modification instructions

Toxicity	Dose Modification
Dyspepsia = Grade 1-2 Dyspepsia ≥ Grade 3	Maintain dose and treat with histamine (H2) blockers or equivalent. Decrease by one dose level if symptoms persist. Interrupt dose until symptoms are controlled. Add H2 blocker or equivalent and decrease one dose level when dose restarted.
Oedema ≥ Grade 3	Use diuretics as needed and decrease dose by one dose level.
Confusion or mood alteration ≥ Grade 2	Interrupt dose until symptoms resolve. When dose restarted decrease dose by one dose level.
Muscle weakness ≥ Grade 2	Interrupt dose until muscle weakness ≤ Grade 1. Restart with dose decreased by one level.
Hyperglycaemia ≥ Grade 3	Decrease dose by one dose level. Treat with insulin or oral hypoglycaemic agents as needed
Acute pancreatitis	Discontinue patient from dexamethasone treatment regimen.
Other ≥ Grade 3dexamethasone-related adverse events	Stop dexamethasone dosing until adverse event resolves to ≤ Grade 2. Resume with dose reduced by one level.

Dexamethasone dose reduction levels:

Dose reduction levels (≤ 75 years of age): Starting dose 40 mg; dose level -1 20 mg; dose level-2 10 mg on Days 1, 8, 15 and 22 of each 28-day treatment cycle.

Dose reduction levels (> 75 years of age): Starting dose 20 mg; dose level -1 12 mg; dose level-2 8 mg on Days 1, 8, 15 and 22 of each 28-day treatment cycle.

If recovery from toxicities is prolonged beyond 14 days, then the dose of dexamethasone will be decreased by one dose level.

Special populations

Paediatric population

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

Older people

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.

Renal impairment

A study in subjects with renal impairment has not been conducted with pomalidomide. Patients with moderate or severe renal impairment (creatinine clearance <45 mL/min) were excluded from clinical studies. Patients with renal impairment should be carefully monitored for adverse reactions.

Hepatic impairment

A study in subjects with hepatic impairment has not been conducted with pomalidomide. Patients with serum total bilirubin > 2.0 mg/dL were excluded from clinical studies. Patients with hepatic impairment should be carefully monitored for adverse reactions.

Method of administration

Oral use.

Imnovid should be taken at the same time each day. The capsules should not be opened, broken or chewed (see section 6.6). This medicinal product should be swallowed whole, preferably with water, with or without food. If the patient forgets to take a dose of Imnovid 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.

4.3 Contraindications

- Pregnancy.

- Women of childbearing potential, unless all the conditions of the pregnancy prevention programme are met (see sections 4.4 and 4.6).

- Male patients unable to follow or comply with the required contraceptive measures (see section 4.4).

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Teratogenicity

Pomalidomide must not be taken during pregnancy, since a teratogenic effect is expected. Pomalidomide is structurally related to thalidomide. Thalidomide is a known human teratogen that causes severe life- threatening birth defects. Pomalidomide was found to be teratogenic in both rats and rabbits when administered during the period of major organogenesis (see section 5.3).

The conditions of the Pregnancy Prevention Programme must be fulfilled for all patients unless there is reliable evidence that the patient does not have childbearing potential.

Criteria for women of non-childbearing potential

A female patient or a female partner of a male patient is considered of non-childbearing potential if she meets at least one of the following criteria:

• Age ≥ 50 years and naturally amenorrhoeic for ≥ 1 year*

• Premature ovarian failure confirmed by a specialist gynaecologist

• Previous bilateral salpingo-oophorectomy, or hysterectomy

• XY genotype, Turner syndrome, uterine agenesis.

*Amenorrhoea following cancer therapy or during breast-feeding does not rule out childbearing potential.

Counselling

For women of childbearing potential, pomalidomide is contraindicated unless all of the following are met:

• She understands the expected teratogenic risk to the unborn child

• She understands the need for effective contraception, without interruption, 4 weeks before starting treatment, throughout the entire duration of treatment, and 4 weeks after the end of treatment

• Even if a woman of childbearing potential has amenorrhoea she must follow all the advice on effective contraception

• She should be capable of complying with effective contraceptive measures

• She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy

• She understands the need to commence contraceptive measures as soon as pomalidomide is dispensed following a negative pregnancy test

• She understands the need and accepts to undergo pregnancy testing every 4 weeks except in case of confirmed tubal sterilisation

• She acknowledges that she understands the hazards and necessary precautions associated with the use of pomalidomide.

The prescriber must ensure that for women of childbearing potential:

• The patient complies with the conditions of the Pregnancy Prevention Programme, including confirmation that she has an adequate level of understanding

• The patient has acknowledged the aforementioned conditions.

For male patients taking pomalidomide, pharmacokinetic data has demonstrated that pomalidomide is present in human semen. As a precaution, all male patients taking pomalidomide must meet the following conditions:

• He understands the expected teratogenic risk if engaged in sexual activity with a pregnant woman or a woman of childbearing potential

• He understands the need for the use of a condom if engaged in sexual activity with a pregnant woman or a woman of childbearing potential not using effective contraception, during treatment and for 7 days after dose interruptions and/or cessation of treatment. Vasectomised males should wear a condom if engaged in sexual activity with a pregnant woman as seminal fluid may still contain pomalidomide in the absence of spermatozoa.

• He understands that if his female partner becomes pregnant whilst he is taking pomalidomide or 7 days after he has stopped taking pomalidomide, he should inform his treating physician immediately and that it is recommended to refer the female partner to a physician specialised or experienced in teratology for eva luation and advice.

Contraception

Women of childbearing potential must use one effective method of contraception for 4 weeks before therapy, during therapy, and until 4 weeks after pomalidomide therapy and even in case of dose interruption unless the patient commits to absolute and continuous abstinence confirmed on a monthly basis. If not established on effective contraception, the patient must be referred to an appropriately trained health care professional for contraceptive advice in order that contraception can be initiated.

The following can be considered to be examples of suitable methods of contraception:

• Implant

• Levo