Thalidomide Celgene

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 

 

Thalidomide Celgene 50 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each capsule contains 50 mg of thalidomide. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Hard capsule. 

White opaque capsules marked “Thalidomide Celgene 50 mg”. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Thalidomide Celgene in combination with melphalan and prednisone is indicated as first line treatment 

of patients with untreated multiple myeloma, aged ≥ 65 years or ineligible for high dose 

chemotherapy. 

 

Thalidomide Celgene is prescribed and dispensed according to the Thalidomide Celgene Pregnancy 

Prevention Programme (see section 4.4). 

 

4.2 Posology and method of administration 
 

Treatment must be initiated and monitored under the supervision of physicians with expertise in 

managing immunomodulatory or chemotherapeutic agents and a full understanding of the risks of 

thalidomide therapy and monitoring requirements (see section 4.4). 

 

Posology 

 

The recommended dose of thalidomide is 200 mg orally per day. 

 

A maximum number of 12 cycles of 6 weeks (42 days) should be used. 

 

Table 1: Starting doses for thalidomide in combination with melphalan and prednisone 

Age 

(years) 

ANC* 

(/µL) 

 Platelet Count 

(/µL) 

Thalidomidea,b Melphalanc,d,e Prednisonef 

≤ 75 ≥ 1,500 AND ≥ 100,000 200 mg daily 0.25 mg/kg daily 2 mg/kg daily 

≤ 75 < 1,500 but 

≥ 1,000 

OR < 100,000 but 

≥ 50,000 

200 mg daily 0.125 mg/kg daily 2 mg/kg daily 

> 75 ≥ 1,500 AND ≥ 100,000 100 mg daily 0.20 mg/kg daily 2 mg/kg daily 

> 75 < 1,500 but 

≥ 1,000 

OR < 100,000 but 

≥ 50,000 

100 mg daily 0.10 mg/kg daily 2 mg/kg daily 

* ANC: Absolute Neutrophil Count 

a Thalidomide dosed once daily at bedtime on Days 1 to 42 of each 42-day cycle. 
b Due to the sedative effect associated with thalidomide, administration at bedtime is known to generally improve tolerability. 
c Melphalan dosed once daily on Days 1 to 4 of each 42-day cycle. 
d Melphalan dosing: reduce by 50 % for moderate (creatinine clearance: ≥ 30 but < 50 mL/min) or severe (CrCl: < 30mL/min) renal 

insufficiency 
e Maximum daily melphalan dose: 24 mg (subjects ≤ 75 years old) or 20 mg (subjects > 75 years old). 
f Prednisone dosed once daily on Days 1 to 4 of each 42-day cycle. 

 



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Patients should be monitored for: thromboembolic events, peripheral neuropathy, severe skin 

reactions, bradycardia, syncope, somnolence, neutropenia and thrombocytopenia (see sections 4.4 

and 4.8). Dose delay, reduction or discontinuation, dependent upon the NCI CTC (National Cancer 

Institute Common Toxicity Criteria) grade, may be necessary. 

 

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. 
 

Thromboembolic events 

Thromboprophylaxis should be administered for at least the first 5 months of treatment especially in 

patients with additional thrombotic risk factors. Prophylactic antithrombotic medicinal products, such 

as low molecular weight heparins or warfarin, should be recommended. The decision to take 

antithrombotic prophylactic measures should be made after careful assessment of an individual 

patient’s underlying risk factors (see sections 4.4, 4.5 and 4.8). 

 

If the patient experiences any thromboembolic events, treatment must be discontinued and standard 

anticoagulation therapy started. Once the patient has been stabilised on the anticoagulation treatment 

and any complications of the thromboembolic event have been managed, the thalidomide treatment 

may be restarted at the original dose dependent upon a benefit-risk assessment. The patient should 

continue anticoagulation therapy during the course of thalidomide treatment. 

 

Neutropenia 

White blood cell count and differential should be monitored on an ongoing basis, in accordance with 

oncology guidelines, especially in patients who may be more prone to neutropenia. Dose delay, 

reduction or discontinuation, dependent upon the NCI CTC grade, may be necessary. 

 

Thrombocytopenia 

Platelet counts should be monitored on an ongoing basis, in accordance with oncology guidelines. 

Dose delay, reduction or discontinuation, dependent upon the NCI CTC grade, may be necessary. 

 

Peripheral neuropathy 

Dose modifications due to peripheral neuropathy are described in Table 2. 

 

Table 2: Recommended dose modifications for thalidomide -related neuropathy in first line 

treatment of multiple myeloma 

Severity of neuropathy Modification of dose and regimen 

Grade 1 (paraesthesia, weakness and/or loss of 

reflexes) with no loss of function  

Continue to monitor the patient with clinical 

examination. Consider reducing dose if symptoms 

worsen. However, dose reduction is not 

necessarily followed by improvement of 

symptoms. 

Grade 2 (interfering with function but not with 

activities of daily living) 

Reduce dose or interrupt treatment and continue 

to monitor the patient with clinical and 

neurological examination. If no improvement or 

continued worsening of the neuropathy, 

discontinue treatment. If the neuropathy resolves 

to Grade 1 or better, the treatment may be 

restarted, if the benefit/risk is favourable. 

Grade 3 (interfering with activities of daily 

living) 

Discontinue treatment  

Grade 4 (neuropathy which is disabling) Discontinue treatment 

 

Allergic reactions and severe skin reactions 

Thalidomide interruption or discontinuation should be considered for Grade 2-3 skin rash. 

Thalidomide must be discontinued for angioedema, anaphylactic reaction, Grade 4 rash, exfoliative or 

bullous rash, or if Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or drug reaction 



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with eosinophilia and systemic symptoms (DRESS) is suspected and should not be resumed following 

discontinuation for these reactions. 

 

Elderly population 

No specific dose adjustments are recommended for the elderly ≤ 75 years of age. For patients 

> 75 years of age, the thalidomide recommended starting dose is 100 mg per day. The initial dose of 

melphalan is reduced for elderly > 75 years of age considering baseline bone marrow reserve and renal 

function. The melphalan recommended starting dose is 0.1 to 0.2 mg/kg daily according to bone 

marrow reserve along with a further 50 % dose reduction for moderate (creatinine clearance: ≥ 30 but 

< 50 mL/minute) or severe (CrCl: < 30 mL/minute) renal insufficiency. The maximum daily 

melphalan dose is 20 mg in patients > 75 years of age (see Table 1). 

 

Patients with renal or hepatic impairment 

Thalidomide Celgene has not formally been studied in patients with impaired renal or hepatic function. 

No specific dose recommendations for these patient populations are available. Patients with severe 

organ impairment should be carefully monitored for adverse reactions. 

 

Paediatric population 

There is no relevant use of Thalidomide Celgene in the paediatric population in the indication of 

multiple myeloma. 

 

Method of administration 

Thalidomide Celgene should be taken as a single dose at bedtime, to reduce the impact of somnolence. 

Capsules should not be opened or crushed (see section 6.6). 

 

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. 

 

4.3 Contraindications 

 

• Hypersensitivity to thalidomide or to any of the excipients listed in section 6.1. 

• Women who are pregnant (see section 4.6). 

• 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). 

 

4.4 Special warnings and precautions for use 

 

Teratogenic effects 

Thalidomide is a powerful human teratogen, inducing a high frequency of severe and life-

threatening birth defects. Thalidomide must never be used by women who are pregnant or by 

women who could become pregnant unless all the conditions of the Pregnancy Prevention 

Programme are met. The conditions of the Pregnancy Prevention Programme must be fulfilled for 

all male and female patients. 

 

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

• Premature ovarian failure confirmed by a specialist gynaecologist. 

• Previous bilateral salpingo-oophorectomy, or hysterectomy. 

• XY genotype, Turner’s syndrome, uterine agenesis. 
 

Counselling 



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For women of childbearing potential, thalidomide is contraindicated unless all of the following 

conditions are met: 

• She understands the teratogenic risk to the unborn child 

• She understands the need for effective contraception, without interruption, at least 4 weeks 
before starting treatment, throughout the entire duration of treatment, and at least 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 her doctor if there is a risk of pregnancy 

• She understands the need to commence the treatment as soon as thalidomide 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 thalidomide. 

 

As thalidomide is found in semen, as a precaution all male patients taking thalidomide must meet the 

following conditions: 

• He understands the 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 (even if the man 

has had a vasectomy), during treatment, during dose interruption and for at least 7 days 

following discontinuation of treatment.  

• He understands that if his female partner becomes pregnant whilst he is taking thalidomide or 7 
days after he has stopped taking thalidomide, 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 evaluation and advice. 

 

The prescriber must ensure that: 

• 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 at least 4 weeks 

before start of treatment, during treatment, and until at least 4 weeks after thalidomide treatment 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 preferably to an appropriately trained healthcare professional for contraceptive advice in order 

that contraception can be initiated. 

 

The following can be considered to be examples of effective 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 (MM), 

combined oral contraceptive pills are not recommended (see section 4.5). If a patient is currently using 



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combined oral contraception, she should switch to one of the effective methods listed above. The risk 

of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception. 

 

Pregnancy testing 

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. 

 

Prior to starting treatment 

A medically supervised pregnancy test should be performed during the consultation, when thalidomide 

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 thalidomide. 

 

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 

As thalidomide is found in semen, as a precaution all male patients must use condoms during 

treatment, during dose interruption and for at least 7 days following discontinuation of treatment if 

their partner is pregnant or is of childbearing potential not using effective contraception. 

Male patients should not donate semen or sperm during treatment (including during dose 

interruptions) and for at least 7 days following discontinuation of thalidomide. 

 

Prescribing and dispensing restrictions 

For women of childbearing potential, prescriptions of thalidomide can be for a maximum duration of 

treatment of 4 weeks according to the approved indications dosing regimens (see section 4.2) and 

continuation of treatment requires a new prescription. Ideally, pregnancy testing, issuing a prescription 

and dispensing should occur on the same day. Dispensing of thalidomide should occur within a 

maximum of 7 days of the prescription. 

 

For all other patients, prescriptions of thalidomide can be for a maximum duration of treatment of 

12 weeks and continuation of treatment requires a new prescription. 

 

Additional precautions 

Patients should be instructed never to give this medicinal product to another person and to return any 

unused capsules to their pharmacist at the end of treatment. 

 

Patients should not donate blood during treatment (including during dose interruptions) and for  at 

least 7 days following discontinuation of thalidomide. 

 

Healthcare professionals and caregivers should wear disposable gloves when handling the blister or 

capsule. Women who are pregnant or suspect they may be pregnant should not handle the blister or 

capsule (see section 6.6). 

 

Educational materials 

In order to assist patients in avoiding foetal exposure to thalidomide, the Marketing Authorisation 

Holder will provide educational material to healthcare professionals to reinforce the warnings about 

the teratogenicity of thalidomide, to provide advice on contraception before treatment is started and 

provides guidance on the need for pregnancy testing.  

The prescriber must inform male and female patients about the expected teratogenic risk and the strict 

pregnancy prevention measures as specified in the Pregnancy Prevention Programme and provide 

patients with appropriate educational brochure for patients, patient card and/or equivalent tool in 

accordance to the national implemented patient card system. A national controlled distribution system 

has been implemented in collaboration with each National Competent Authority. The controlled 



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distribution system includes the use of a patient card and/or equivalent tool for prescribing and/or 

dispensing controls, and the collecting of detailed data relating to the indication in order to monitor 

closely the off-label use within the national territory. Ideally, pregnancy testing, issuing a prescription 

and dispensing should occur on the same day. Dispensing of thalidomide to women of childbearing 

potential should occur within 7 days of the prescription and following a medically supervised negative 

pregnancy test result. 

 

Amenorrhea 

The use of thalidomide could be associated with menstrual disorders including amenorrhea. 

Amenorrhea during thalidomide therapy should be assumed to result from pregnancy, until it is 

medically confirmed that the patient is not pregnant. A clear mechanism by which thalidomide can 

induce amenorrhea is not elucidated. The reported events occurred in young (premenopausal) women 

(median age 36 years) receiving thalidomide for non-multiple myeloma indications, had an onset 

within 6 months of initiating treatment and reversed upon discontinuation of thalidomide. In 

documented case reports with hormone evaluation, the event of amenorrhoea was associated with 

decreased estradiol levels and elevated FSH/LH levels. When provided, antiovary antibodies were 

negative and prolactin level was within the normal range. 

 

Cardiovascular disorders 

Myocardial infarction 

Myocardial infarction (MI) has been reported in patients receiving thalidomide, particularly in those 

with known risk factors. Patients with known risk factors for MI, including prior thrombosis, should 

be closely monitored and action should be taken to try to minimise all modifiable risk factors 

(e.g. smoking, hypertension, and hyperlipidaemia). 

 

Venous and arterial thromboembolic events 

Patients treated with thalidomide have an increased risk of venous thromboembolism (such as deep 

vein thrombosis and pulmonary embolism) and arterial thromboembolism (such as myocardial 

infarction and cerebrovascular event) (see section 4.8). The risk appears to be greatest during the first 

5 months of therapy. Thromboprophylaxis and dosing/anticoagulation therapy recommendations are 

provided in section 4.2. 

 

Previous history of thromboembolic events or concomitant administration of erythropoietic agents or 

other agents such as hormone replacement therapy, may also increase thromboembolic risk in these 

patients. Therefore, these agents should be used with caution in multiple myeloma patients receiving 

thalidomide with prednisone and melphalan. Particularly, a haemoglobin concentration above 12g/dl 

should lead to discontinuation of erythropoietic agents. Action should be taken to try to minimize all 

modifiable risk factors (e.g. smoking, hypertension and hyperlipidaemia). 

 

Patients and physicians are advised to be observant for the signs and symptoms of thromboembolism. 

Patients should be instructed to seek medical care if they develop symptoms such as shortness of 

breath, chest pain, arm or leg swelling. 

 

Peripheral neuropathy 

Peripheral neuropathy is a very common, potentially severe, adverse reaction to treatment with 

thalidomide that may result in irreversible damage (see section 4.8). In a phase 3 study, the median 

time to first neuropathy event was 42.3 weeks. 

 

If the patient experiences peripheral neuropathy, follow the dose and schedule modification instruction 

provided in section 4.2. 

 

Careful monitoring of patients for symptoms of neuropathy is recommended. Symptoms include 

paraesthesia, dysaesthesia, discomfort, abnormal co-ordination or weakness. 

 

It is recommended that clinical and neurological examinations are performed in patients prior to 

starting thalidomide therapy, and that routine monitoring is carried out regularly during treatment.  



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Medicinal products known to be associated with neuropathy should be used with caution in patients 

receiving thalidomide (see section 4.5). 

 

Thalidomide may also potentially aggravate existing neuropathy and should therefore not be used in 

patients with clinical signs or symptoms of peripheral neuropathy unless the clinical benefits outweigh 

the risks. 

 

Syncope, bradycardia and atrioventricular block 

Patients should be monitored for syncope, bradycardia and atrioventricular block; dose reduction or 

discontinuation may be required. 

 

Pulmonary hypertension 

Cases of pulmonary hypertension, some fatal, have been reported in patients treated with thalidomide. 

Patients should be evaluated for signs and symptoms of underlying cardiopulmonary disease prior to 

initiating and during thalidomide therapy. 

 

Haematological disorders 

Neutropenia  

The incidence of neutropenia grade 3 or 4 reported as adverse reactions was higher in multiple 

myeloma patients receiving MPT (Melphalan, Prednisone, Thalidomide) than in those receiving MP 

(Melphalan, Prednisone): 42.7 % versus 29.5 % respectively (study IFM 99-06). Adverse reactions 

from post-marketing experience such as febrile neutropenia and pancytopenia were reported with 

thalidomide. Patients should be monitored and dose delay, reduction or discontinuation may be 

required (see section 4.2). 

 

Thrombocytopenia 

Thrombocytopenia, including grade 3 or 4 adverse reactions, has been reported in multiple myeloma 

patients receiving MPT. Patients should be monitored and dose delay, reduction or discontinuation 

may be required (see section 4.2). Patients and physicians are advised to be observant for signs and 

symptoms of bleeding including petechiae, epistaxis and gastrointestinal haemorrhage, especially in 

case of concomitant medicinal product prone to inducing bleeding (see sections 4.5 and 4.8). 

 

Hepatic disorders 

Hepatic disorders, mainly abnormal liver test results, were reported. No specific pattern was identified 

between hepatocellular and cholestatic abnormalities, with some cases having a mixed presentation. 

The majority of the reactions occurred within the first 2 months of therapy and resolved spontaneously 

without treatment after thalidomide discontinuation. Patients should be monitored for liver function, 

particularly in case of pre-existing liver disorder or concomitant use of medicinal product susceptible 

to induce liver dysfunction (see section 4.8). 

 

Allergic reactions and severe skin reactions 

Cases of allergic reactions including angioedema, anaphylactic reaction and severe cutaneous 

reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug 

reaction with eosinophilia and systemic symptoms (DRESS) have been reported with the use of 

Thalidomide. Patients should be advised of the signs and symptoms of these reactions by their 

prescribers and should be told to seek medical attention immediately if they develop these symptoms. 

Thalidomide interruption or discontinuation should be considered for Grade 2-3 skin rash. 

Thalidomide must be discontinued for angioedema, anaphylactic reaction, Grade 4 rash, exfoliative or 

bullous rash, or if SJS, TEN or DRESS is suspected, and should not be resumed following 

discontinuation for these reactions. (see sections 4.2 and 4.8).  

 

Somnolence 

It is very common that thalidomide causes somnolence. Patients should be instructed to avoid 

situations where somnolence may be a problem and to seek medical advice before taking other 

medicinal products known to cause somnolence. Patients should be monitored and dose reduction may 

be required. 

 



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Patients should be advised as to the possible impairment of mental and/or physical abilities required 

for the performance of hazardous tasks (see section 4.7). 

 

Tumour lysis syndrome 

The patients at risk of tumour lysis syndrome are those with high tumour burden prior to treatment. 

These patients should be monitored closely and appropriate precautions taken. 

 

Infections 

Patients should be monitored for severe infections including sepsis and septic shock. 

 

Cases of viral reactivation have been reported in patients receiving thalidomide, including serious 

cases of herpes zoster or hepatitis B virus (HBV) reactivation. 

 

Some of the cases of herpes zoster reactivation resulted in disseminated herpes zoster, requiring a 

temporary hold of the treatment with thalidomide and adequate antiviral treatment. 

 

Some of the cases of HBV reactivation progressed to acute hepatic failure and resulted in 

discontinuation of thalidomide. Hepatitis B virus status should be established before initiating 

treatment with thalidomide. For patients who test positive for HBV infection, consultation with a 

physician with expertise in the treatment of hepatitis B is recommended. 

 

Previously infected patients should be closely monitored for signs and symptoms of viral reactivation, 

including active HBV infection, throughout therapy. 

 

Acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) 

A statistically significant increase of AML and MDS was observed in one clinical study in patients 

with previously untreated MM receiving the combination of melphalan, prednisone, and thalidomide 

(MPT). The risk increased over time and was about 2 % after two years and about 4 % after three 

years. An increased incidence of second primary malignancies (SPM) has also been observed in 

patients with newly diagnosed MM receiving lenalidomide. Among invasive SPMs, cases of 

MDS/AML were observed in patients receiving lenalidomide in combination with melphalan or 

immediately following high dose melphalan and autologous stem cell transplantation. 

 

The benefit achieved with thalidomide and the risk of AML and MDS must be taken into account 

before initiating treatment with thalidomide in combination with melphalan and prednisone. 

Physicians should carefully evaluate patients before and during treatment using standard cancer 

screening and institute treatment as indicated. 

 

Patients with renal or hepatic impairment 

Studies conducted in healthy subjects and patients with multiple myeloma suggest that thalidomide is 

not influenced to any significant extent by renal or hepatic function (see section 5.2). However, this 

has not formally been studied in patients with impaired renal or hepatic function; therefore patients 

with severe renal or hepatic impairment should be carefully monitored for any adverse events. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

Thalidomide is a poor substrate for cytochrome P450 isoenzymes and therefore clinically important 

interactions with medicinal products that are inhibitors and/or inducers of this enzyme system are 

unlikely. Non-enzymatic hydrolysis of thalidomide, being the primary clearance mechanism, suggests 

that the potential for drug-drug interactions with thalidomide is low. 

 

Increase of sedative effects of other medicinal products 

Thalidomide has sedative properties, thus may enhance the sedation induced by anxiolytics, hypnotics, 

antipsychotics, H1 antihistamines, opiate derivatives, barbiturates and alcohol. Caution should be used 

when thalidomide is given in combination with medicinal products that cause drowsiness. 

 

Bradycardic effect 



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Due to thalidomide’s potential to induce bradycardia, caution should be exercised with medicinal 

products having the same pharmacodynamic effect such as active substances known to induce torsade 

de pointes, beta blockers or anticholinesterase agents. 

 

Medicinal products known to cause peripheral neuropathy 

Medicinal products known to be associated with peripheral neuropathy (e.g. vincristine and 

bortezomib) should be used with caution in patients receiving thalidomide. 

 

Hormonal contraceptives 

Thalidomide does not interact with hormonal contraceptives. In 10 healthy women, the 

pharmacokinetic profiles of norethindrone and ethinyl estradiol following administration of a single 

dose containing 1.0 mg of norethindrone acetate and 0.75 mg of ethinyl estradiol were studied. The 

results were similar with and without co-administration of thalidomide 200 mg/day to steady-state 

levels. However, combined hormonal contraceptives are not recommended due to the increased risk of 

venous thromboembolic disease. 

 

Warfarin 

Multiple dose administration of 200 mg thalidomide q.d. for 4 days had no effect on the international 

normalized ratio (INR) in healthy volunteers. However, due to the increased risk of thrombosis in 

cancer patients, and a potentially accelerated metabolism of warfarin with corticosteroids, close 

monitoring of INR values is advised during thalidomide-prednisone combination treatment as well as 

during the first weeks after ending these treatments. 

 

Digoxin 

Thalidomide does not interact with digoxin. In 18 healthy male volunteers, multiple dose 

administration of 200 mg thalidomide had no apparent effect on the single dose pharmacokinetics of 

digoxin. In addition, single dose administration of 0.5 mg digoxin had no apparent effect on 

thalidomide pharmacokinetics. It is not known whether the effect will be different in multiple 

myeloma patients. 

 

4.6 Fertility, pregnancy and lactation 

 

Women of childbearing potential/Contraception in males and females 

Women of childbearing potential must use one effective method of contraception for at least 4 weeks 

before start of treatment, during treatment including during dose interruptions, and until at least 

4 weeks after thalidomide treatment (see section 4.4). If pregnancy occurs in a woman treated with 

thalidomide, treatment must be stopped immediately and the patient should be referred to a physician 

specialised or experienced in teratology for evaluation and advice. 

 

As thalidomide is found in semen, as a precaution all male patients must use condoms during 

treatment, during dose interruption and for at least 7 days following discontinuation of treatment when 

having sexual intercourse with a pregnant woman or with a woman of childbearing potential who is 

not using effective contraception. This applies even if the man has had a vasectomy. 

If pregnancy occurs in a partner of a male patient taking thalidomide, the female partner should be 

referred to a physician specialised or experienced in teratology for evaluation and advice. 

 

Pregnancy 

Thalidomide is contraindicated during pregnancy and in women of childbearing potential unless all the 

conditions of the Pregnancy Prevention Programme are met (see section 4.3) 

 

Thalidomide is a powerful human teratogen, inducing a high frequency (about 30 %) of severe and 

live-threatening birth defects such as: ectromelia (amelia, phocomelia, hemimelia) of the upper and/or 

lower extremities, microtia with abnormality of the external acoustic meatus (blind or absent), middle 

and internal ear lesions (less frequent), ocular lesions (anophthalmia, microphthalmia), congenital 

heart disease, renal abnormalities. Other less frequent abnormalities have also been described. 

 

Breast-feeding 



 11 

It is unknown whether thalidomide is excreted in human breast milk. Animal studies have shown 

excretion of thalidomide in breast milk. Therefore breast-feeding should be discontinued during 

treatment with thalidomide. 

 

Fertility 

A study in rabbits demonstrated no effect on fertility indices in males or females although testicular 

degeneration was observed in males. 

 

4.7 Effects on ability to drive and use machines 

 

Thalidomide Celgene as per the recommended posology has minor or moderate influence on the 

ability to drive and use machines. 

Thalidomide may cause fatigue (very common), dizziness (very common), somnolence (very 

common) and blurred vision (common) (see section 4.8). Patients should be instructed not to drive 

cars, use machines or perform hazardous tasks while being treated with thalidomide if they feel tired, 

dizzy, sleepy or have blurred vison. 

 

4.8 Undesirable effects 
 

Summary of the safety profile 

Most patients taking thalidomide can be expected to experience adverse reactions. 

The most commonly observed adverse reactions associated with the use of thalidomide in combination 

with melphalan and prednisone are: neutropenia, leukopenia, constipation, somnolence, paraesthesia, 

peripheral neuropathy, anaemia, lymphopenia, thrombocytopenia, dizziness, dysaesthesia, tremor and 

peripheral oedema. 

 

In addition to the adverse reactions outlined above, thalidomide in combination with dexamethasone in 

other clinical studies led to the very common adverse reaction of fatigue; common adverse reactions of 

transient ischaemic event, syncope, vertigo, hypotension, mood altered, anxiety, blurred vision, nausea 

and dyspepsia; and uncommon adverse reactions of cerebrovascular accident, diverticular perforation, 

peritonitis, orthostatic hypotension and bronchitis. 

 

The most clinically important adverse reactions associated with the use of thalidomide in combination 

with melphalan and prednisone or dexamethasone include: deep vein thrombosis and pulmonary 

embolism, peripheral neuropathy, severe skin reactions including Stevens-Johnson syndrome, toxic 

epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms, syncope, 

bradycardia, and dizziness (see sections 4.2, 4.4 and 4.5). 

 

Tabulated list of adverse reactions 

Table 3 contains only the adverse reactions for which a causal relationship with medicinal product 

treatment could reasonably be established observed in the pivotal study and from post-marketing 

experience. Frequencies given are based on the observations during a pivotal comparative clinical 

study investigating the effect of thalidomide in combination with melphalan and prednisone in 

previously untreated multiple myeloma patients.  

 

Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon 

(≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000) and not known (cannot be 

estimated from the available data). Within each frequency grouping, adverse reactions are presented in 

order of decreasing seriousness. 

 

Table 3: Adverse drug reactions (ADRs) reported in pivotal clinical study with thalidomide in 

combination with melphalan and prednisone and from post marketing use  

System Organ Class Frequency Adverse reaction 

Infections and infestations Common Pneumonia 



 12 

System Organ Class Frequency Adverse reaction 

Not Known 

Severe infections (e.g. fatal sepsis including septic 

shock)†,  

Viral infections, including herpes zoster and 

hepatitis B virus reactivation† 

Neoplasms benign, 

malignant and unspecified 

(incl cysts and polyps) 

Common Acute myeloid leukaemia*,^ 

Uncommon Myelodysplastic syndrome*,^ 

Not Known Tumour lysis syndrome† 

Blood and lymphatic 

system disorders 

Very Common 
Neutropenia, Leukopenia, Anaemia, 

Lymphopenia, Thrombocytopenia 

Common Febrile neutropenia†, Pancytopenia† 

Immune System Disorders Not Known 
Allergic reactions (hypersensitivity, angioedema, 

anaphylactic reaction, urticaria) † 

Endocrine Disorders Not Known Hypothyroidism† 

Psychiatric disorders Common Confusional state, Depression 

Nervous system disorders 

Very Common 
Peripheral neuropathy*, Tremor, Dizziness, 

Paraesthesia, Dysaesthesia, Somnolence 

Common Convulsions†, Abnormal coordination  

Not Known 

Posterior reversible encephalopathy syndrome 

(PRES)*,†, Worsening of Parkinson’s disease 

symptoms† 

Ear and labyrinth 

disorders 
Common Hearing impaired or deafness† 

Cardiac disorders 

Common Cardiac failure, Bradycardia 

Uncommon 
Myocardial infarction†, Atrial fibrillation†, 

Atrioventricular block† 

Vascular disorders Common  Deep vein thrombosis* 

Respiratory, thoracic and 

mediastinal disorders 

Common 
Pulmonary embolism*, Interstitial lung disease, 

Bronchopneumopathy, Dyspnea 

Not Known Pulmonary hypertension† 

Gastrointestinal disorders 

Very Common Constipation 

Common Vomiting, Dry mouth 

Uncommon Intestinal obstruction† 

Not Known 
Gastrointestinal perforation†, Pancreatitis†, 

Gastrointestinal haemorrhage† 

Hepatobiliary disorders Not Known Hepatic disorders†  

Skin and subcutaneous 

tissue disorders 

Common  Toxic skin eruption, Rash, Dry skin 

Not Known 

Stevens-Johnson syndrome*,†, Toxic epidermal 

necrolysis*,†, Drug reaction with eosinophilia and 

systemic symptoms*,†, Leukocytoclastic 

vasculitis† 

Renal and urinary 

disorders 
Common Renal failure† 

Reproductive System and 

Breast Disorders 
Not Known 

Sexual dysfunction†, Menstrual disorders 

including amenorrhea† 

General disorders and 

administration site 

conditions 

Very Common  Peripheral oedema 

Common  Pyrexia, Asthenia, Malaise 

* see section 4.8 description of selected adverse reactions 
† identified from post marketing data 

^ Acute myeloid leukaemia and Myelodysplastic syndrome were reported in one clinical study in patients with previously untreated MM 

receiving the combination of melphalan, prednisone and thalidomide (MPT) 

 



 13 

Description of selected adverse reactions 

 

Blood and lymphatic system disorders 

Adverse reactions for haematological disorders are provided compared to the comparator arm, as the 

comparator has a significant effect on these disorders (Table 4). 

 

Table 4: Comparison of haematological disorders for the melphalan, prednisone (MP) and 

melphalan, prednisone, thalidomide (MPT) combinations in study IFM 99-06 (see section 5.1) 

 n (% of patients) 

 MP (n=193) MPT (n=124) 

 Grades 3 and 4* 

Neutropenia 57 (29.5)  53 (42.7)  

Leukopenia 32 (16.6)  32 (25.8) 

Anaemia 28 (14.5)  17 (13.7) 

Lymphopenia 14 (7.3)  15 (12.1)  

Thrombocytopenia 19 (9.8)  14 (11.3) 
* WHO Criteria 

 

Additional adverse reactions from post-marketing experience with thalidomide and not seen in the 

pivotal study include febrile neutropenia and pancytopenia. 

 

Teratogenicity 

The risk of intra-uterine death or severe birth defects, primarily phocomelia, is extremely high. 

Thalidomide must not be used at any time during pregnancy (see sections 4.4 and 4.6). 

 

Venous and arterial thromboembolic events 

An increased risk of venous thromboembolism (such as deep vein thrombosis and pulmonary 

embolism) and arterial thromboembolism (such as myocardial infarction and cerebrovascular event) 

has been reported in patients treated with thalidomide (see section 4.4). 

 

Peripheral neuropathy 

Peripheral neuropathy is a very common, potentially severe, adverse reaction of treatment with 

thalidomide that may result in irreversible damage (see section 4.4). Peripheral neuropathy generally 

occurs following chronic use over a period of months. However, reports following relatively short-

term use also exist. Incidence of neuropathy events leading to discontinuation, dose reduction or 

interruption increases with cumulative dose and duration of therapy. Symptoms may occur some time 

after thalidomide treatment has been stopped and may resolve slowly or not at all. 

 

Posterior reversible encephalopathy syndrome (PRES)/ Reversible posterior leukoencephalopathy 

syndrome (RPLS) 

Cases of PRES/RPLS have been reported. Signs and symptoms included visual disturbance, headache, 

seizures and altered mental status, with or without associated hypertension. A diagnosis of 

PRES/RPLS requires confirmation by brain imaging. The majority of the reported cases had 

recognized risk factors for PRES/RPLS, including hypertension, renal impairment and concomitant 

use of high dose corticosteroids and/or chemotherapy. 

 

Acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) 

AML and MDS were reported in one clinical study in patients with previously untreated multiple 

myeloma receiving the combination of melphalan, prednisone, and thalidomide (see section 4.4). 

 

Allergic reactions and severe skin reactions 

Cases of allergic reactions including angioedema, anaphylactic reaction and severe cutaneous 

reactions including Stevens-Johnson syndrome, TEN and DRESS have been reported with the use of 

thalidomide therapy. If angioedema, anaphylactic reaction, Stevens-Johnson syndrome, TEN or 

DRESS is suspected, use of thalidomide should not be resumed (see section 4.2 and 4.4). 

 

Elderly population 



 14 

The adverse reaction profile reported in patients > 75 years of age treated with thalidomide 100 mg 

once daily was similar to the adverse reaction profile observed in patients ≤ 75 years of age treated 

with thalidomide 200 mg once daily (see Table 3). However, patients with age > 75 years are 
potentially at risk for a higher frequency of serious adverse reactions. 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

Eighteen cases of overdose have been reported in the literature concerning doses up to 14.4 grams. In 

thirteen of these cases, patients took thalidomide alone; amounts ranged from 350 mg to 4000 mg. 

These patients either exhibited no symptoms or exhibited symptoms of drowsiness, irritability, 

“sickness,” and/or headache. In one 2-year-old child who took 700 mg, there was an abnormal plantar 

response in addition to drowsiness and irritability. No fatalities have been reported and all overdose 
patients recovered without sequelae. There is no specific antidote for a thalidomide overdose. In the 

event of an overdose, the patient’s vital signs should be monitored and appropriate supportive care 

given to maintain blood pressure and respiratory status. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: immunosuppressants, other immunosuppressants, ATC code: L04AX02. 

 

Thalidomide has a chiral centre and is used clinically as a racemate of (+)-(R)- and 

(-)-(S)-thalidomide. The spectrum of activity of thalidomide is not fully characterised. 

 

Mechanism of action 

Thalidomide shows immunomodulatory, anti-inflammatory and potential anti-neoplastic activities. 

Data from in vitro studies and clinical trials suggest that the immunomodulatory, anti-inflammatory 

and anti-neoplastic effects of thalidomide may be related to suppression of excessive tumour necrosis 

factor-alpha (TNF-) production, down-modulation of selected cell surface adhesion molecules 

involved in leukocyte migration and anti-angiogenic activity. Thalidomide is also a non-barbiturate 

centrally active hypnotic sedative. It has no antibacterial effects. 

 

Clinical efficacy and safety 

Results from IFM 99-06, a Phase 3, randomised, open label, parallel group, multicentre study have 

demonstrated a survival advantage when thalidomide is used in combination with melphalan and 

prednisone for 12 cycles of 6 weeks in the treatment of newly diagnosed multiple myeloma patients. In 

this study the age range of patients was 65-75 years, with 41 % (183/447) of patients 70 years old or 

older. The median dose of thalidomide was 217 mg and > 40 % of patients received 9 cycles. 

Melphalan and prednisone were dosed at 0.25 mg/kg/day and 2 mg/kg/day respectively on days 1 to 4 

of each 6 weeks cycle. 

 

Further to the per protocol analysis, an update was conducted for the IFM 99-06 study providing an 

additional 15 months follow-up data. The median overall survival (OS) was 51.6 ± 4.5 and 

33.2 ± 3.2 months in the MPT and MP groups, respectively (97.5 % CI 0.42 to 0.84). This 18 month 

difference was statistically significant with a hazard ratio of reduction of risk of death in the MPT arm 

of 0.59, 97.5 % confidence interval of 0.42-0.84 and p-value of < 0.001 (see Figure 1). 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 15 

Figure 1: Overall survival according to treatment 

 
 

Paediatric Population 

The European Medicines Agency has waived the obligation to submit the results of studies with 

thalidomide in all subsets of the paediatric population in multiple myeloma (see section 4.2 for 

information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

Absorption 

Absorption of thalidomide is slow after oral administration. The maximum plasma concentrations are 

reached 1-5 hours after administration. Co-administration of food delayed absorption but did not alter 

the overall extent of absorption. 

 

Distribution 

The plasma protein binding of the (+)-(R) and (-)-(S) enantiomers was found to be 55 % and 65 % 

respectively. Thalidomide is present in the semen of male patients at levels similar to plasma 

concentrations (see section 4.4). The distribution of thalidomide is not influenced by age, gender, renal 

function and blood chemistry variables, to any significant level. 

 

Biotransformation 

Thalidomide is metabolised almost exclusively by non-enzymatic hydrolysis. In plasma, unchanged 

thalidomide represents 80 % of the circulatory components. Unchanged thalidomide was a minor 

component (< 3 % of the dose) in urine. In addition to thalidomide, hydrolytic products 

N-(o-carboxybenzoyl) glutarimide and phthaloyl isoglutamine formed via non-enzymatic processes 

are also present in plasma and in majority in urine. Oxidative metabolism does not contribute 

significantly to the overall metabolism of thalidomide. There is minimal cytochrome P450 catalysed 

hepatic metabolism of thalidomide. There are in vitro data indicating that prednisone may give rise to 

enzyme induction which could reduce the systemic exposure of concomitantly used medicinal 

products. The in vivo relevance of these findings is unknown. 

 

Elimination 

The mean elimination half-life of thalidomide in plasma following single oral doses between 50 mg 

and 400 mg was 5.5 to 7.3 hours. Following a single oral dose of 400 mg of radio-labelled 

0 

0.2 

0.4 

0.6 

0.8 

1 

0 12 24 36 48 60 72 84 

Time from randomization ( month ) 

51.6 ± 4.5 62/125 MP - T 
33.2 ± 3.2 128/196 MP 

Survival time 
median ± se (month) 

O/N + Treatment 

Proportion  



 16 

thalidomide, the total mean recovery was 93.6 % of the administered dose by day 8. The majority of 

the radioactive dose was excreted within 48 hour following dose administration. The major route of 

excretion was via the urine (> 90 %) while faecal excretion was minor. 

 

There is a linear relationship between body weight and estimated thalidomide clearance; in multiple 

myeloma patients with body weight from 47-133 kg, thalidomide clearance ranged from 

approximately 6-12 L/h, representing an increase in thalidomide clearance of 0.621 L/h per 10 kg body 

weight increase. 

 

Linearity/non-linearity 

Total systemic exposure (AUC) is proportional to dose at single-dose conditions. No time dependency 

of the pharmacokinetics has been observed. 

 

Hepatic and renal impairment 

The extent of thalidomide metabolism by the liver cytochrome P450 system is minimal and intact 

thalidomide is not excreted by the kidney. Measures of renal function (CrCl) and liver function (blood 

chemistry) indicate minimal effect of kidney and liver function on the pharmacokinetics of 

thalidomide. As such the metabolism of thalidomide is not expected to be affected by hepatic or renal 

dysfunction. Data from patients with end-stage renal disease suggest no impact of kidney function on 

thalidomide pharmacokinetics.  

 

5.3 Preclinical safety data 
 

In the male dog, after one year of dosing, reversible bile plugs in canaliculi were observed at 

exposures greater than 1.9-fold the human exposure. 

 

Decreased platelet counts were noted in the mouse and rat studies. The latter appears to be related to 

thalidomide and occurred at exposures greater than 2.4-fold the human exposure. This decrease did not 

result in clinical signs. 

 

In a one-year dog study, enlarged and/or blue discoloration of mammary glands and prolonged estrus 

were observed in females at exposures equal to 1.8 or greater than 3.6-fold the human exposure, 

respectively. The relevance to humans is unknown. 

 

The effect of thalidomide on thyroid function was assessed in both rats and dogs. No effects were 

observed in dogs; however in rats, there was an apparent dose-dependent decrease in total and free T4 

that was more consistent in the female. 

 

No mutagenic or genotoxic effect has been revealed when thalidomide was assayed in a standard 

battery of genotoxicity tests. No evidence of carcinogenicity was observed at exposures approximately 

15, 13 and 39 times the estimated clinical AUC at the recommended starting dose in mice, male rats 

and female rats respectively. 

 

Animal studies have demonstrated differences in species susceptibility to the teratogenic effects of 

thalidomide. In humans, thalidomide is a proven teratogen. 

 

A study in rabbits demonstrated no effect on fertility indices in males or females although testicular 

degeneration was observed in males. 

 

A peri- and postnatal toxicity study performed in rabbits with thalidomide administered at doses up to 

500 mg/kg/day resulted in abortions, increased stillbirths and decreased pup viability during lactation. 

Pups from mothers treated with thalidomide had increased abortions, reduced body weight gain, 

alterations in learning and memory, decreased fertility, and reduced pregnancy index. 

 

 



 17 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Capsule contents 

Starch, pregelatinised 

Magnesium stearate 

 

Capsule shell 

Gelatin 

Titanium dioxide (E171) 

 

Printing ink 

Shellac 

Black iron oxide (E172) 

Propylene glycol 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

5 years 

 

6.4 Special precautions for storage 
 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container 
 

PVC/PCTFE/aluminium blister containing 14 capsules. 

 

Pack sizes: 28 capsules (two blisters) in a wallet card. 

 

6.6 Special precautions for disposal and other handling 

 

Capsules should not be opened or crushed. If powder from thalidomide makes contact with the skin, 

the skin should be washed immediately and thoroughly with soap and water. If thalidomide makes 

contact with the mucous membranes, they should be thoroughly flushed with water. 

 

Healthcare professionals and caregivers should wear disposable gloves when handling the blister or 

capsule. Gloves should then be removed carefully to prevent skin exposure, placed in a sealable plastic 

polyethylene bag and disposed of in accordance with local requirements. Hands should then be washed 

thoroughly with soap and water. Women who are pregnant or suspect they may be pregnant should not 

handle the blister or capsule (see section 4.4). 

 

All unused capsules should be returned to the pharmacist at the end of treatment. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands  

 



 18 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/08/443/001 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 16 April 2008 

Date of latest renewal: 08 February 2018 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


 19 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER (S) RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 



 20 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer(s) responsible for batch release 

 

Celgene Distribution B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic Safety Update Reports (PSUR) 
 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 

agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 

updates of the RMP. 

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile or 

as the result of an important (pharmacovigilance or risk minimisation) milestone being 

reached. 

 

• Additional risk minimisation measures 
1. The MAH shall agree the details of a controlled distribution system with the National Competent 

Authorities and must implement such programme nationally to ensure that: 

• Prior to launch, all doctors and pharmacists who intend to prescribe or dispense Thalidomide 
Celgene receive a Dear Healthcare Professional letter as described below. 

• Prior to prescribing all healthcare professionals who intend to prescribe (and in agreement 
with the National Competent Authority, dispense) Thalidomide Celgene are provided with an 

Educational Healthcare Professional’s Kit containing the following: 

o Educational healthcare professional booklet 
o Educational brochures for patient  
o Patient cards 
o Summary of product characteristics, package leaflet and labelling 

 



 21 

2. The MAH shall implement a Pregnancy Prevention Programme (PPP) in each Member State. 
Details of the PPP should be agreed wth the National Competent Authorities in each Member 

State and put in place prior to the launch of the medicinal product. 

 

3. The MAH should agree the final text of the Dear Healthcare Professional letter and the contents of 
the Educational Healthcare Professional’s Kit with the National Competent Authority in each 

Member State prior to launch of the medicinal product and ensure that the materials contain the 

key elements as described below. 

 

4. The MAH should agree on the implementation of the patient card system in each Member State. 
 

5. Prior to approval by the National Competent Authority and launch of the medicinal product, the 
MAH should ensure that the educational materials are provided to and reviewed by the national 

patients’ organisations or if such an organisation does not exist or can not be involved, by a 

relevant patients group. Patients involved should be preferably naïve to the history of thalidomide. 

Results of the user testing will have to be provided to the national competent authority and final 

materials validated at a national level. 

 

6. The MAH should also agree with each Member State prior to the launch of the product: 

• The most appropriate strategies to monitor the off-label use within national territories 

• The collection of detailed data to understand demographics of target population, indication 
and number of women of child bearing potential in order to monitor closely the off-label use 

within national territory. 

 

7. The MAH shall notify the EMA and the appropriate national patients and victims representatives 
of the proposed launch date before launch in each Member State. 

 

 

Key elements to be included 

 

Dear Healthcare Professional letter 

The Dear Healthcare Professional letter will consist of two parts: 

• Core text as agreed by the CHMP 

• National specific requirements agreed with the National Competent Authority regarding: 
o Distribution of the product 
o Procedures to ensure that all appropriate measures have been performed prior to 

thalidomide being dispensed 

 

Educational Healthcare Professional’s Kit 

The Educational Healthcare Professional’s Kit shall contain the following elements: 

• Healthcare professional booklet 
o History of thalidomide, background on Thalidomide Celgene and its licensed 

indication 

o Posology 

• Maximum duration of treatment prescribed according to the approved indication dosing 
regimens 

o 4 weeks of treatment for women with childbearing potential 
o 12 weeks of treatment for men and women without childbearing potential 

• Teratogenicity and the need to avoid foetal exposure 

• Guidance on handling the blister or capsule of Thalidomide Celgene for healthcare 
professionals and caregivers 

• Obligations of healthcare professionals who intend to prescribe or dispense Thalidomide 
Celgene including 

o The need to provide comprehensive advice and counselling to patients 
o That patients should be capable of complying with the requirements for the safe use of 

thalidomide 

o Need to provide patients with the appropriate patient educational material 



 22 

o Report any pregnancy,  or  adverse events to Celgene and the local health authority (if 
applicable to a Member State) using the forms provided in the “Educational 

Healthcare Professional’s Kit” 

• Safety advice relevant to all patients 
o Description and management of ischaemic heart disease (including myocardial 

infarction) 

o Disposal of unwanted medicinal product 
o Not to donate blood during treatment (including during dose interruptions) and for at 

least 7 days following discontinuation of thalidomide 

 

• Algorithm for Pregnancy Prevention Plan implementation 
o This shall assist with patient categorisation, and determination of required pregnancy 

prevention and testing measures. 

 

• Pregnancy Prevention Programme information 
o Definition of women of childbearing potential  and actions the prescriber should take 

if unsure 

o Information on what is effective contraception 
o Safety advice for women of childbearing potential 

• Need to avoid foetal exposure 

• Pregnancy prevention requirement, definition and need for adequate 
contraceptive methods 

• That if she needs to change or stop using her method of contraception she 
should inform: 

▪ The physician prescribing her contraception that she is on thalidomide 
▪ The physician prescribing thalidomide that she has stopped or 

changed her method of contraception 

• Pregnancy testing requirements 
▪ Advice on suitable tests 
▪ Frequency (before commencing, monthly during treatment and after 

finishing treatment) 

• Need to stop thalidomide immediately upon suspicion of pregnancy 

• Need to tell treating doctor immediately upon suspicion of pregnancy 
o Safety advice for men 

• The need to avoid foetal exposure 

• That thalidomide is found in semen and the need to use condoms if sexual 
partner is pregnant or is a woman with childbearing potential not using effective 

contraception 

• That if his partner becomes pregnant he should inform his treating doctor 
immediately and always use a condom during intercourse 

• That he should not donate semen during treatment (including during dose 
interruptions) and for at least 7 days following discontinuation of thalidomide 

 

• Pregnancy reporting requirements 
o Instruction to stop thalidomide immediately upon suspicion of pregnancy, if female 

patient 

o Need to refer patient to physician specialised or experienced in dealing with 
teratology for advice and evaluation 

o Complete pregnancy reporting form as provided in the “Educational Healthcare 
Professional’s Kit” 

o Local contact details for reporting of any suspected pregnancy 
 

• Pregnancy initial and outcome reporting forms 

• Post-marketing and compliance assessment (as applicable to a Member State) 

• Adverse reaction reporting forms 
 



 23 

• Treatment initiation forms and/or equivalent tool 

• There should be 3 types of treatment initiation forms and/or equivalent tool: 
o Women of childbearing potential 
o Women of non-childbearing potential 
o Male patient 

 

• All treatment initiation forms and/or equivalent tool should contain the following elements: 
o Teratogenicity warning 
o Patients receive appropriate counselling prior to treatment initiation 
o Date of counselling 
o Affirmation of patient understanding regarding the risk of thalidomide and the PPP 

measures 

o Patient details, signature and date 
o Prescriber name, signature and date 
o Aim of this document i.e. as stated in the PPP: “The aim of the treatment initiation 

form is to protect patients and any possible foetuses by ensuring that patients are fully 

informed of and understand the risk of teratogenicity and other adverse reactions 

associated with the use of thalidomide. It is not a contract and does not absolve 

anybody from his/her responsibilities with regard to the safe use of the product and 

prevention of foetal exposure.” 

 

• Treatment initiation forms and/or equivalent tool for women of childbearing potential should 
also include: 

o Confirmation that the physician has discussed the following: 

• The need to avoid foetal exposure 

• That if she is pregnant or plans to be, she must not take thalidomide  

• The need for effective contraception, without interruption, at least 4 weeks 
before starting treatment, throughout the entire duration of treatment, and at 

least 4 weeks after the end of treatment 

• That if she needs to change or stop using her method of contraception she 
should inform: 

▪ The physician prescribing her contraception that she is on thalidomide 
▪ The physician prescribing thalidomide that she has stopped or 

changed her method of contraception 

• The need for pregnancy tests i.e. before treatment, at least every 4 weeks during 
treatment and after treatment 

• The need to stop thalidomide immediately upon suspicion of pregnancy 

• The need to contact their doctor immediately upon suspicion of pregnancy 

• That she should not share the treatment with any other person 

• That she should not donate blood during treatment (including during dose 
interruptions) and for at least 7 days following discontinuation of thalidomide 

• That she should return the capsules to the pharmacist at the end of treatment 
 

• Treatment initiation forms and/or equivalent tool for women with no childbearing potential 
should also include: 

o Confirmation that the physician has discussed the following: 

• That she should not share the treatment with any other person 

• That she should not donate blood during treatment (including during dose 
interruptions) and for at least 7 days following discontinuation of thalidomide 

• That she should return the capsules to the pharmacist at the end of treatment 
 

• Treatment initiation forms and/or equivalent tool for male patients should also include: 
o Confirmation that the physician has discussed the following: 

• The need to avoid foetal exposure 



 24 

• That thalidomide is found in semen and the need to use condoms if sexual 
partner is pregnant or is a woman with childbearing potential not on effective 

contraception 

• That if his partner becomes pregnant he should inform his treating doctor 
immediately and always use a condom 

• That he should not donate blood or semen during treatment (including during 
dose interruptions) and for at least 7 days following discontinuation of 

thalidomide 

• That he should not share the treatment with any other person 

• That he should return the capsules to the pharmacist at the end of treatment 
 

• Patient cards and/or equivalent tools: 
o verification that appropriate counselling has taken place 
o documentation of childbearing potential status 
o check box (or similar) which physician ticks to confirm that patient is using effective 

contraception (if woman of childbearing potential) 

o verification of initial negative pregnancy test prior to start of treatment (if woman of 
childbearing potential) 

o pregnancy test dates and results 
 

• Educational brochures for patients: 
o The educational brochures for patients should be of 3 types: 

• Brochure for women of childbearing potential 

• Brochure for women patients who are not of childbearing potential 

• Brochure for male patients 
 

• All educational brochures for patients should contain the following information 
o That thalidomide is teratogenic 
o That thalidomide may cause  ischaemic heart disease, (including myocardial 

infarction) 

o Description of the patient card and its use in the individual Member State 
o Guidance on handling Thalidomide Celgene for patients, caregivers and family 

members 

o National or other applicable specific arrangements for a prescription for thalidomide 
to be dispensed 

o That thalidomide must not be given to any other person 
o That the patient should not donate blood 
o That the patient should tell their doctor about any adverse events 
o That any unused capsules should be returned to the pharmacist at the end of the 

treatment 

 

• The following information should also be provided in the appropriate educational brochure for 
patients: 

o Women of childbearing potential 

• The need to avoid foetal exposure 

• The need for effective contraception 

• That if she needs to change or stop using her method of contraception she 
should inform: 

▪ The physician prescribing her contraception that she is on thalidomide 
▪ The physician prescribing thalidomide that she has stopped or 

changed her method of contraception 

• The need for pregnancy tests i.e. before treatment, at least every 4 weeks during 
treatment and at least 4 weeks after treatment 

• The need to stop thalidomide immediately upon suspicion of pregnancy 

• The need to contact their doctor immediately upon suspicion of pregnancy 
 



 25 

o Male patients 

• The need to avoid foetal exposure 

• That thalidomide is found in semen and the need to use condoms if sexual 
partner is pregnant or is a woman with childbearing potential not on effective 

contraception 

• That if his partner becomes pregnant he should inform his treating doctor 
immediately and always use a condom 

• That he should not donate semen during treatment (including during dose 
interruptions) and for at least 7 days following discontinuation of thalidomide 



 26 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



 27 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



 28 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

WALLET CARD 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Thalidomide Celgene 50 mg hard capsules 

thalidomide 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains 50 mg of thalidomide. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

28 hard capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

For oral use. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Use only as directed by your doctor. 

 

WARNING: Thalidomide causes birth defects and foetal death. 

 

Patients must follow the Thalidomide Celgene Pregnancy Prevention Programme. 

 

Keep the package intact. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



 29 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

Unused medicinal product should be returned to your pharmacist. 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands  

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/08/443/001 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Thalidomide Celgene 50 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2 D bar code carrying the unique identifier 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



 30 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Thalidomide Celgene 50 mg 

thalidomide 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Celgene Europe B.V. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



 31 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 32 

 

Package leaflet: Information for the patient 

 

Thalidomide Celgene 50 mg hard capsules 

thalidomide 

 

WARNING 

Thalidomide causes birth defects and foetal death. Do not take thalidomide if you are pregnant 

or could become pregnant. You must follow the contraception advice given to you by your 

doctor. 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor, pharmacist or nurse. 

- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 
even if their signs of illness are the same as yours. 

- If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible 
side effects not listed in this leaflet. See section 4. 

 

What is in this leaflet 

1. What Thalidomide Celgene is and what it is used for 

2. What you need to know before you take Thalidomide Celgene 

3. How to take Thalidomide Celgene 
4. Possible side effects 
5. How to store Thalidomide Celgene 

6. Contents of the pack and other information 

 

 

1. What Thalidomide Celgene is and what it is used for 

 

What Thalidomide Celgene is 

Thalidomide Celgene contains an active substance called thalidomide. This belongs to a group of 

medicines which affect how your immune system works. 

 

What Thalidomide Celgene is used for 

Thalidomide Celgene is used with two other medicines called ‘melphalan’ and ‘prednisone’ to treat 

adults with a type of cancer called multiple myeloma. It is used in people who have recently been 

diagnosed and who have not been prescribed another medicine for their multiple myeloma before who 

are aged 65 years and over, or aged less than 65 years who cannot be treated with high dose 

chemotherapy, which can be very difficult for the body to handle. 

 

What is multiple myeloma 

Multiple myeloma is a type of cancer which affects a certain type of white blood cell, called the 

plasma cell. These cells collect in the bone marrow and divide out of control. This can damage the 

bone and kidneys. Multiple myeloma generally cannot be cured. However, the signs and symptoms 

can be greatly reduced or disappear for a period of time. This is called a ‘remission’. 

 

How Thalidomide Celgene works 

Thalidomide Celgene works by helping the body’s immune system and directly attacking the cancer. It 

works in a number of different ways: 

• by stopping the cancer cells developing 

• by stopping blood vessels growing in the cancer 

• by stimulating part of the immune system to attack the cancer cells. 
 

 



 33 

2. What you need to know before you take Thalidomide Celgene 

 

You will have been given specific instructions by your doctor, particularly on the effects of 

thalidomide on unborn babies (outlined in the Thalidomide Celgene Pregnancy Prevention 

Programme). 

 

You will have been given an educational brochure for patient by your doctor. Read it carefully and 

follow the related instructions. 

 

If you do not fully understand these instructions, please ask your doctor to explain them again before 

you take thalidomide. See also further information in this section under “Warnings and precautions” 

and “Pregnancy and breast-feeding”. 

 

Do not take Thalidomide Celgene 

• if you are pregnant or think you may be pregnant or are planning to become pregnant, as 
Thalidomide Celgene causes birth defects and foetal death. 

• if you are able to become pregnant, unless you are able to follow or comply with the required 
contraceptive measures to prevent you from becoming pregnant (see section 2 “Warnings and 

precautions” and “Pregnancy and breast-feeding”). 

• if you are able to become pregnant, your doctor will record with each prescription that the 
necessary measures have been taken and will provide you with this confirmation. 

• if you are allergic to thalidomide or any of the other ingredients of this medicine listed in section 
6 “Contents of the pack and other information”. 

 

Do not take Thalidomide Celgene if any of the above applies to you. If you are not sure, talk to your 

doctor or pharmacist before taking Thalidomide Celgene. 

 

Warnings and precautions 

Talk to your doctor, pharmacist or nurse before taking this medicine in the following situations: 

 

For women taking Thalidomide Celgene 

Before starting the treatment, you should ask your doctor if you are able to become pregnant, even if 

you think this is unlikely. Even if you do not have a menstrual bleeding following cancer therapy, you 

may become pregnant. 

If you are able to become pregnant: 

• Your doctor will make sure that you have pregnancy tests 
o before treatment 
o every 4 weeks during treatment 
o 4 weeks after stopping treatment 

• You must use one effective method of contraception: 
o for at least 4 weeks before starting treatment  
o during treatment 
o until at least 4 weeks after stopping treatment 

Your doctor will tell you what method of contraception to use. 

 

If you are able to become pregnant, your doctor will record with each prescription that the necessary 

measures, as outlined above, have been taken  

 

For men taking Thalidomide Celgene 

Thalidomide passes into semen. Therefore, do not have unprotected intercourse, even if you had a 

vasectomy. 

• Pregnancy and any exposure during pregnancy must be avoided. Always use a condom: 
o during treatment  
o for at least 7 days after stopping treatment 

• You must not donate semen:  
o during treatment  
o for  at least 7 days after stopping treatment 



 34 

 

For all patients 

Talk to your doctor before taking Thalidomide Celgene if 

• you do not understand the contraception advice given to you by your doctor or if you do not feel 
able to follow this advice. 

• you have had a heart attack, have ever had a blood clot in the past, or if you smoke, have high 
blood pressure or high cholesterol levels. During the treatment with Thalidomide Celgene you 

have an increased risk of developing blood clots in the veins and arteries (see also section 4 

“Possible side effects”).   

• you have experienced or have existing neuropathy i.e. nerve damage causing tingling, abnormal 
co-ordination or pain in your hands or feet (see also section 4 “Possible side effects”).    

• you experienced or have existing slow heart rate (this may be a symptom of bradycardia). 

• you have high blood pressure in the arteries of the lungs (see also section 4 “Possible side 
effects”). 

• you have a fall in the number of white blood cells (neutropenia) accompanied by fever and 
infection. 

• you have a fall in the number of platelets. You will be more prone to bleeding and bruising. 

• you have or have had injury to the liver (hepatic disorders) including abnormal liver test results.  

• you experience or have experienced in the past severe skin reactions called Stevens-Johnson 
syndrome, toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms 

(which is also known as DRESS or drug hypersensitivity syndrome). (For description of 

symptoms see section 4 “Possible side effects”).  

• you have had an allergic reaction whilst taking Thalidomide Celgene such as rash, itching, 
swelling, dizziness or trouble breathing. 

• you have experienced sleepiness.  

• you have experienced fever, chills and severe shaking, and possibly complicated by low blood 
pressure and confusion (these may be symptoms of severe infections).  

• you have or have ever had previous viral infection, particularly varicella zoster, hepatitis B 
infection, or HIV. If you are in doubt, talk to your doctor. Treatment with Thalidomide Celgene 

may cause a virus to become active again in patients who carry it, resulting in a recurrence of the 

infection. Your doctor should check whether you have ever had hepatitis B infection. 

• you have kidney or liver problems (see also section 4 “Possible side effects”).  
 

Your doctor may check if you have a high total amount of tumour throughout the body, including your 

bone marrow. This could lead to a condition where the tumours break down and cause unusual levels 

of chemicals in the body which can lead to kidneys failure (this condition is called Tumour Lysis 

Syndrome) (see also section 4 “Possible side effects”). 

 

Your doctor should evaluate if you develop additional types of haematological malignancies (called 

acute myeloid leukaemia and myelodysplastic syndromes) during your treatment with Thalidomide 

Celgene (see also section 4 “Possible side effects”). 

 

You must not donate blood during Thalidomide Celgene treatment and for at least 7 days after 

stopping treatment. 

 

If you are not sure if any of the above apply to you, talk to your doctor before taking Thalidomide 

Celgene. 

 

Children and adolescents 

Thalidomide Celgene is not recommended for use in children and young people under 18 years. 

 

Other medicines and Thalidomide Celgene 

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This 

includes medicines obtained without a prescription, including herbal medicines. 

 

Make sure you tell your doctor if you are taking any medicines which: 



 35 

• cause sleepiness as thalidomide may increase their effects. This includes sedatives (such as 
anxiolytics, hypnotics, antipsychotics, H1 antihistamines, opiate derivatives and barbiturates). 

• slow the heart rate (induce bradycardia, such as anticholinesterases and beta blockers).  

• are used for heart problems and complications (such as digoxin), or for thinning the blood (such 
as warfarin). 

• are associated with neuropathy such as other treatments for cancer. 

• are used for contraception. 
 

Thalidomide Celgene with food, drink and alcohol 

Do not drink alcohol while you are taking Thalidomide Celgene. This is because alcohol can make you 

sleepy and Thalidomide Celgene can make you even sleepier. 

 

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor or pharmacist for advice before taking this medicine. 

 

Pregnancy 

Thalidomide causes severe birth defects or death to an unborn baby. 

• As little as one capsule taken by a pregnant woman can cause a baby to have serious birth 
defects. 

• These defects can include shortened arms or legs, malformed hands or feet, eye or ear defects, 
and problems with internal organs. 

If you are pregnant, you must not take Thalidomide Celgene. In addition, you must not become 

pregnant while taking Thalidomide Celgene. 

 

You must use one effective method of contraception if you are a woman who is able to become 

pregnant (see section 2, “What you need to know before you take Thalidomide Celgene”). 

 

You must stop treatment and inform your doctor straight away if: 

• You miss or think you have missed a period, or you have unusual menstrual bleeding, or suspect 
you are pregnant. 

• You have heterosexual intercourse without using an effective method of contraception. 
If you do become pregnant during the treatment with thalidomide, you must stop the treatment and 

inform your doctor immediately. 

 

For men taking Thalidomide Celgene who have a female partner who is able to become pregnant, 

please see section 2 “What you need to know before you take Thalidomide Celgene”. If your partner 

becomes pregnant whilst you are taking thalidomide, you should inform your doctor immediately. 

 

Breast-feeding 

Do not breastfeed when taking Thalidomide Celgene as it is not known if thalidomide is passed into 

human breast milk. 

 

Driving and using machines 

Do not drive or use any tools or machines if you experience side effects, such as dizziness, tiredness, 

sleepiness or blurred vision. 

 

 

3. How to take Thalidomide Celgene 

 

Always take Thalidomide Celgene exactly as your doctor or pharmacist has told you to. Check with 

your doctor or pharmacist if you are not sure. 

 

How much to take 

The recommended dose is 200 mg (4 x 50 mg capsules) a day for adults aged 75 years and under or 

100 mg (2 x 50 mg capsules) a day for adults aged over 75 years. However your doctor will choose the 



 36 

dose for you, monitor your progress and may adjust your dose. Your doctor will tell you how to take 

Thalidomide Celgene and for how long you will need to take it (see section 2, “What you need to 

know before you take Thalidomide Celgene”). 

 

Thalidomide Celgene is taken daily in treatment cycles, each cycle lasting 6 weeks, in combination 

with melphalan and prednisone which are taken on days 1 to 4 of each 6 week cycle. 

 

Taking this medicine 

• Do not break, open or chew the capsules. If powder from a broken Thalidomide Celgene capsule 
makes contact with the skin, wash the skin immediately and thoroughly with soap and water. 

• Healthcare professionals, caregivers and family members should wear disposable gloves when 
handling the blister or capsule. Gloves should then be removed carefully to prevent skin 

exposure, placed in a sealable plastic polyethylene bag and disposed of in accordance with local 

requirements. Hands should then be washed thoroughly with soap and water. Women who are 

pregnant or suspect they may be pregnant should not handle the blister or capsule. 

• Take this medicine by mouth. 

• Swallow the capsules whole with a full glass of water. 

• Do not crush or chew. 

• Take the capsules as a single dose before going to bed. This will make you less likely to feel 
sleepy at other times. 

 

To remove the capsule from the blister, press only one end of the capsule out to push it through the 

foil. Do not apply pressure on the centre of the capsule as this can cause it to break. 

 

 
 

If you take more Thalidomide Celgene than you should 

If you take more Thalidomide Celgene than you should, talk to a doctor or go to a hospital 

straightaway. If possible, take the medicine pack and this leaflet with you. 

 

If you forget to take Thalidomide Celgene 

If you forget to take Thalidomide Celgene at your regular time and 

• less than 12 hours have passed: take your capsules immediately. 

• more than 12 hours have passed: do not take your capsules. Take your next capsules at the usual 
time the next day. 

 

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 

 

 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

The following side effects may happen with this medicine: 

 



 37 

Stop taking Thalidomide Celgene and see a doctor straight away if you notice the following 

serious side effects – you may need urgent medical treatment: 

• Extremely intense and serious skin reactions. The adverse reaction of the skin may appear as 
rashes with or without blisters. Skin irritation, sores or swelling in the mouth, throat, eyes, 

nose and around the genitals, oedema and fever and flulike symptoms may occur. These 

symptoms may be signs of the rare and serious skin reactions Stevens-Johnson syndrome, 

toxic epidermal necrolysis or DRESS syndrome.  

• Allergic reactions such as a localised or generalised pruritic rash, angioedema and 
anaphylactic reaction (serious types of allergic reaction that may be manifested as hives, 

rashes, swelling of eyes, mouth or face, difficulty of breathing, or itching). 

 

Tell your doctor straight away if you notice any of the following serious side effects: 

• Numbness, tingling, abnormal coordination or pain in your hands and feet. 
This may be due to nerve damage (called ‘peripheral neuropathy’), which is a very common side 

effect. It may become very severe, painful and disabling. If you experience such symptoms, speak 

to your doctor straight away, who may reduce the dose or discontinue the treatment. This side 

effect usually happens after you have been taking this medicine for several months but can 

happen sooner than this. It can also happen sometime after treatment has stopped. It may not go 

away, or may go away slowly. 

• Sudden pain in your chest or difficulty in breathing. 
This may be due to blood clots in the arteries leading to your lungs (called ‘pulmonary 

embolism’), which is a common side effect. These can happen during treatment, or after treatment 

has stopped. 

• Pain or swelling in your legs, especially in your lower leg or calves. 
This may be due to blood clots in the veins of your leg (deep vein thrombosis), which is a 

common side effect. These can happen during treatment, or after treatment has stopped. 

• Chest pain spreading to the arms, neck, jaw, back or stomach, feeling sweaty and 
breathless, feeling sick or vomiting. 

These may be symptoms of a heart attack/myocardial infarction (which may be due to blood clots 

in the arteries of your heart). 

• Having difficulty in seeing or speaking, which is temporary. 
These may be symptoms of a stroke (which may be due to a clot in an artery in your brain). 

• Fever, chills, sore throat, cough, mouth ulcers or any other symptoms of infection. 

• Bleeding or bruising in the absence of injury. 
 

Other side effects include: 

 

It is important to note that a small number of patients with multiple myeloma may develop additional 

types of cancer, especially haematological malignancies, and it is possible that this risk may be 

increased with Thalidomide Celgene treatment; therefore your doctor should carefully evaluate the 

benefit and risk when you are prescribed Thalidomide Celgene. 

 

Very common (may affect more than 1 in 10 people) 

• Constipation. 

• Feeling dizzy. 

• Sleepiness, feeling tired. 

• Shaking (tremor). 

• Decreased or abnormal sensation (dysaesthesia). 

• Swelling of hands and feet. 

• Low blood cell counts. This may mean that you are more likely to develop infections. Your 
doctor may monitor your blood cell counts during treatment with Thalidomide Celgene. 

 

Common (may affect up to 1 in 10 people) 

• Indigestion, feeling sick (nausea), being sick (vomiting), dry mouth. 

• Rash, dryness of the skin. 

• A fall in the number of white blood cells (neutropenia) accompanied by fever and infection. 



 38 

• A fall in the number of red and white blood cells and platelets at the same time (pancytopenia). 

• Feeling weak, faint or unsteady, lack of energy or strength, low blood pressure. 

• Fever, feeling generally unwell. 
• Convulsions. 

• A spinning feeling in your head, making it difficult to stand up and move normally. 

• Blurred vision. 

• Chest infection (pneumonia), lung disease. 

• A slow heart rate, heart failure. 

• Depression, confusion, mood changes, anxiety. 

• Hearing decreased or deafness. 

• Kidney disease (renal failure). 
 

Uncommon (may affect up to 1 in 100 people) 

• Inflammation and swelling of the tubes in your lungs (bronchitis). 

• Inflammation of the cells lining your stomach wall. 

• A hole in part of your large bowel (colon) which can cause infection. 

• Bowel obstruction. 

• Fall of blood pressure on standing which may lead to fainting. 

• Irregularities of the heartbeat (heart block or atrial fibrillation), feeling faint or fainting. 
 

Not known (frequency cannot be estimated from the available data) : 

• Underactive thyroid (hypothyroidism).  

• Sexual dysfunction, for example impotence. 
• Severe blood infection (sepsis) accompanied by fever, chills and severe shaking, and possibly 

complicated by low blood pressure and confusion (septic shock). 

• Tumour Lysis Syndrome - metabolic complications that can occur during the treatment of cancer 
and sometimes even without treatment. These complications are caused by the break-down 

products of dying cancer cells and may include the following: changes to blood chemistry; high 

potassium, phosphorus, uric acid, and low calcium consequently leading to changes in kidney 

function, heart beat, seizures, and sometimes death.  

• Injury to the liver (hepatic disorder) including abnormal liver test results. 

• Bleeding from the stomach or bowels (gastrointestinal haemorrhage). 

• Worsening of Parkinson’s disease symptoms (such as tremor, depression or confusion). 

• Pain in the upper abdomen and/or back, which may be severe and which remains for a few  
days, possibly accompanied by nausea, vomiting, fever and a rapid pulse – these symptoms  

may be due to the inflammation of the pancreas (pancreatitis). 

• Increase in blood pressure within blood vessels that supply the lungs which can lead to shortness 
of breath, tiredness, dizziness, pain in the chest, a faster heartbeat, or swelling in the legs or 

ankles (pulmonary hypertension). 

• Viral infections, including herpes zoster (also known as ‘shingles’, a viral disease that causes a 
painful skin rash with blisters) and recurrence of hepatitis B infection (which can cause yellowing 

of the skin and eyes, dark brown-coloured urine, right-sided stomach pain, fever and feeling 

nauseous or being sick). 

• A brain condition with symptoms including vision changes, headache, seizures, and confusion, 
with or without high blood pressure (Posterior Reversible Encephalopathy Syndrome or PRES). 

• A condition affecting the skin caused by inflammation of small blood vessels, along with pain in 
the joints and fever (leukocytoclastic vasculitis). 

 

Reporting of side effects 

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 39 

5. How to store Thalidomide Celgene 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the wallet card and the blister after 

EXP. The expiry date refers to the last day of that month. 

 

Do not use if you notice any damage or signs of tampering. 

 

This medicine does not require any special storage conditions. 

 

At the end of your treatment you should return all unused capsules to the pharmacist or doctor. These 

measures will prevent misuse. 

 

 

6. Contents of the pack and other information 

 

What Thalidomide Celgene contains 

• The active substance is thalidomide. Each capsule contains 50 mg of thalidomide. 

• The other excipients are: 
o The capsule content contains pregelatinised starch and magnesium stearate. 
o The capsule shell contains gelatin and titanium dioxide (E171). 
o The printing ink is composed of shellac, black iron oxide (E172) and propylene 

glycol. 

 

What Thalidomide Celgene looks like and contents of the pack 

Thalidomide Celgene are white hard capsules marked “Thalidomide Celgene 50 mg”. The capsules are 

supplied in a wallet card containing 28 capsules (2 blisters of 14 capsules each). 

 

Marketing Authorisation Holder  

Celgene Europe B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands  

  

Manufacturer 

Celgene Distribution B.V. 

Winthontlaan 6 N  

3526 KV Utrecht  

Netherlands 

 

 

This leaflet was last revised in  

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 

 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET