Revlimid 5 mg hard capsulesRevlimid10 mg hard capsulesRevlim - Ireland[爱尔兰药品]

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Revlimid 5 mg hard capsulesRevlimid10 mg hard capsulesRevlim

2014-04-06 21:12:11 来源: 作者: 【大中小】浏览:511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 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

1. NAME OF THE MEDICINAL PRODUCT

Revlimid 5 mg hard capsules

Revlimid10 mg hard capsules

Revlimid 15 mg hard capsules

Revlimid 25 mg hard capsules

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each Revlimid 5 mg hard capsule contains 5 mg of lenalidomide.

Excipient: Each capsule contains 147 mg of anhydrous lactose.

Each Revlimid 10 mg hard capsule contains 10 mg of lenalidomide

Excipient: Each capsule contains 294 mg of anhydrous lactose.

Each Revlimid 15 mg hard capsule contains 15 mg of lenalidomide

Excipient: Each capsule contains 289 mg of anhydrous lactose.

Each Revlimid 25 mg hard capsule contains 25 mg of lenalidomide

Excipient: Each capsule contains 200 mg of anhydrous lactose.

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Hard capsule.

Revlimid 5 mg hard capsules: White capsules marked “REV 5 mg”.

Revlimid 10 mg hard capsules: Blue-green/pale yellow capsules marked “REV 10 mg”.

Revlimid 15 mg hard capsules: Pale blue/white capsules marked “REV 15 mg”.

Revlimid 25 mg hard capsules: White capsules marked “REV 25 mg”.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Revlimid in combination with dexamethasone is indicated for the treatment of multiple myeloma patients who have received at least one prior 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 (MM).

Administration

Revlimid capsules should be taken at about the same time each day. The capsules should not be opened, broken or chewed. The capsules should be swallowed whole, preferably with water, either with or without food. If less than 12 hours has elapsed since missing a dose, the patient can take the dose. If more than 12 hours has elapsed since missing a dose at the normal time, the patient should not take the dose, but take the next dose at the normal time on the following day.

Recommended dose

The recommended starting dose of lenalidomide is 25 mg orally once daily on days 121 of repeated 28day cycles. The recommended dose of dexamethasone is 40 mg orally once daily on days 1-4, 9-12, and 17-20 of each 28-day cycle for the first 4 cycles of therapy and then 40 mg once daily on days 1-4 every 28 days. Dosing is continued or modified based upon clinical and laboratory findings (see section 4.4). Prescribing physicians should carefully eva luate which dose of dexamethasone to use, taking into account the condition and disease status of the patient.

Lenalidomide treatment must not be started if the Absolute Neutrophil Counts (ANC) < 1.0 x 10⁹/l, and/or platelet counts < 75 x 10⁹/l or, dependent on bone marrow infiltration by plasma cells, platelet counts < 30 x 10⁹/l.

Recommended dose adjustments during treatment and restart of treatment

Dose adjustments, as summarised below, are recommended to manage grade 3 or 4 neutropenia or thrombocytopenia, or other grade 3 or 4 toxicity judged to be related to lenalidomide.

• Dose reduction steps

Starting dose	25 mg
Dose level 1	15 mg
Dose level 2	10 mg
Dose level 3	5 mg

• Platelet counts

Thrombocytopenia

When platelets	Recommended Course
First fall to < 30 x 10⁹/l	Interrupt lenalidomide treatment
Return to 30 x 10⁹/l	Resume lenalidomide at Dose Level 1
For each subsequent drop below 30 x 10⁹/l	Interrupt lenalidomide treatment
Return to 30 x 10⁹/l	Resume lenalidomide at next lower dose level (Dose Level 2 or 3) once daily. Do not dose below 5 mg once daily.

• Absolute Neutrophil counts (ANC)

Neutropenia

When neutrophils	Recommended Course
First fall to < 0.5 x 10⁹/l	Interrupt lenalidomide treatment
Return to 0.5 x 10⁹/l when neutropenia is the only observed toxicity	Resume lenalidomide at Starting Dose once daily
Return to 0.5 x 10⁹/l when dose-dependent haematological toxicities other than neutropenia are observed	Resume lenalidomide at Dose Level 1 once daily
For each subsequent drop below < 0.5 x 10⁹/l	Interrupt lenalidomide treatment
Return to 0.5 x 10⁹/l	Resume lenalidomide at next lower dose level (Dose Level 1, 2 or 3) once daily. Do not dose below 5 mg once daily.

In case of neutropenia, the physician should consider the use of growth factors in patient management.

Paediatric patients

There is no experience in children and adolescents. Therefore, lenalidomide should not be used in the paediatric age group (017 years).

Elderly patients

The effects of age on the pharmacokinetics of lenalidomide have not been studied. Lenalidomide has been used in clinical trials in multiple myeloma patients up to 86 years of age (see section 5.1). The percentage of patients aged 65 or over was not significantly different between the lenalidomide/dexamethasone and placebo/dexamethasone groups. No overall difference in safety or efficacy was observed between these patients and younger patients, but greater pre-disposition of older individuals cannot be ruled out. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it would be prudent to monitor renal function.

Use in patients with impaired renal function

Lenalidomide is substantially excreted by the kidney, therefore care should be taken in dose selection and monitoring of renal function is advised.

No dose adjustments are required for patients with mild renal impairment. The following dose adjustments are recommended at the start of therapy for patients with moderate or severe impaired renal function or end stage renal disease.

Renal Function (CLcr)	Dose Adjustment
Moderate renal impairment (30 CLcr < 50 ml/min)	10 mg once daily*
Severe renal impairment (CLcr < 30 ml/min, not requiring dialysis)	15 mg every other day**
End Stage Renal Disease (ESRD) (CLcr < 30 ml/min, requiring dialysis)	5 mg once daily. On dialysis days, the dose should be administered following dialysis.

* The dose may be escalated to 15 mg once daily after 2 cycles if patient is not responding to treatment and is tolerating the treatment.

** The dose may be escalated to 10 mg once daily if the patient is tolerating the treatment

After initiation of lenalidomide therapy, subsequent lenalidomide dose modification in renally impaired patients should be based on individual patient treatment tolerance, as described above.

Use in patients with impaired hepatic function

Lenalidomide has not formally been studied in patients with impaired hepatic function and there are no specific dose recommendations.

4.3 Contraindications

• Women who are pregnant.

• Women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met (see sections 4.4 and 4.6).

• Hypersensitivity to the active substance or to any of the excipients.

4.4 Special warnings and precautions for use

Pregnancy warning

Lenalidomide is structurally related to thalidomide. Thalidomide is a known human teratogenic active substance that causes severe life-threatening birth defects. Lenalidomide induced in monkeys malformations similar to those described with thalidomide (see sections 4.6 and 5.3). If lenalidomide is taken during pregnancy, a teratogenic effect of lenalidomide in humans is expected.

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 to have childbearing potential unless 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 does not rule out childbearing potential.

Counselling

For women of childbearing potential, lenalidomide 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 amenorrhea 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 the treatment as soon as lenalidomide 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 lenalidomide.

For male patients taking lenalidomide, pharmacokinetic data has demonstrated that lenalidomide is present in human semen at extremely low levels during treatment and is undetectable in human semen 3 days after stopping the drug in the healthy subject (see section 5.2). As a precaution, all male patients taking lenalidomide must meet the following conditions:

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

• Understand the need for the use of a condom if engaged in sexual activity with a pregnant woman or a woman of childbearing potential.

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.

Contraception

Women of childbearing potential must use one effective method of contraception for 4 weeks before therapy, during therapy, and until 4 weeks after lenalidomide 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

• Levonorgestrel-releasing intrauterine system (IUS)

• Medroxyprogesterone acetate depot

• Tubal sterilisation

• Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses

• Ovulation inhibitory progesterone-only pills (i.e., desogestrel)

Because of the increased risk of venous thromboembolism in patients with multiple myeloma taking lenalidomide and dexamethasone, combined oral contraceptive pills are not recommended (see also section 4.5). If a patient is currently using combined oral contraception the patient should switch to one of the effective method listed above. The risk of venous thromboembolism continues for 4−6 weeks after discontinuing combined oral contraception. The efficacy of contraceptive steroids may be reduced during co-treatment with dexamethasone (see section 4.5).

Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics should be considered particularly in patients with neutropenia.

Copper-releasing intrauterine devices are generally not recommended due to the potential risks of infection at the time of insertion and menstrual blood loss which may compromise patients with neutropenia or thrombocytopenia.

Pregnancy testing

According to local practice, medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/ml must be performed for women of childbearing potential as outlined below. This requirement includes women of childbearing potential who practice absolute and continuous abstinence. Ideally, pregnancy testing, issuing a prescription and dispensing should occur on the same day. Dispensing of lenalidomide to women of childbearing potential should occur within 7 days of the prescription.

Prior to starting treatment

A medically supervised pregnancy test should be performed during the consultation, when lenalidomide is prescribed, or in the 3 days prior to the visit to the prescriber once the patient had been using effective contraception for at least 4 weeks. The test should ensure the patient is not pregnant when she starts treatment with lenalidomide.

Follow-up and end of treatment

A medically supervised pregnancy test should be repeated every 4 weeks, including 4 weeks after the end of treatment, except in the case of confirmed tubal sterilisation. These pregnancy tests should be performed on the day of the prescribing visit or in the 3 days prior to the visit to the prescriber.

Men

Lenalidomide is present in human semen at extremely low levels during treatment and is undetectable in human semen 3 days after stopping the drug in the healthy subject (see section 5.2). As a precaution, and taking into account special populations with prolonged eliminati