Drug Class Description
Immunomodulating agent

Generic Name
Lenalidomide

Drug Description
Each Revlimid 5 mg hard capsule contains 5 mg of lenalidomide.Excipient: Each capsule contains 147 mg of anhydrous lactose.Each Revlimid 10 mg hard capsule contains 10 mg of lenalidomide.Excipient: Each capsule contains 294 mg of anhydrous lactose.Each Revlimid 15 mg hard capsule contains 15 mg of lenalidomide.Excipient: Each capsule contains 289 mg of anhydrous lactose.Each Revlimid 25 mg hard capsule contains 25 mg of lenalidomide.Excipient: Each capsule contains 200 mg of anhydrous lactose

Presentation
Hard capsule.Revlimid 5 mg hard capsules: White capsules marked “REV 5 mg”.Revlimid 10 mg hard capsules: Blue-green/pale yellow capsules marked “REV 10 mg”.Revlimid 15 mg hard capsules: Pale blue/white capsules marked “REV 15 mg”.Revlimid 25 mg hard capsules: White capsules marked “REV 25 mg”.

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

Adult Dosage
Treatment must be initiated and monitored under the supervision of physicians experienced in the management of multiple myeloma (MM).AdministrationRevlimid capsules should be taken at about the same time each day. The capsules should not be broken or chewed. The capsules should be swallowed whole, preferably with water, either with or without food. If less than 12 hours has elapsed since missing a dose, the patient can take the dose. If more than 12 hours has elapsed since missing a dose at the normal time, the patient should not take the dose, but take the next dose at the normal time on the following day.Recommended doseThe recommended starting dose of lenalidomide is 25 mg orally once daily on days 121 of repeated 28day cycles. The recommended dose of dexamethasone is 40 mg orally once daily on days 14, 912, and 1720 of each 28day cycle for the first 4 cycles of therapy and then 40 mg once daily on days 14 every 28 days. Dosing is continued or modified based upon clinical and laboratory findings.Lenalidomide treatment must not be started if the Absolute Neutrophil Counts (ANC) < 1.0 x 109/l, and/or platelet counts < 75 x 109/l or, dependent on bone marrow infiltration by plasma cells, platelet counts < 30 x 109/l.Recommended dose adjustments during treatment and restart of treatmentDose adjustments, as summarised below, are recommended to manage grade 3 or 4 neutropenia or thrombocytopenia, or other grade 3 or 4 toxicity judged to be related to lenalidomide.•Dose reduction stepsStarting dose25 mgDose level 115 mgDose level 210 mgDose level 35 mg•Platelet countsThrombocytopeniaWhen plateletsRecommended CourseFirst fall to < 30 x 109 /lInterrupt lenalidomide treatmentReturn to 30 x 109 /lResume lenalidomide at Dose Level 1For each subsequent drop below 30 x 109 /lInterrupt lenalidomide treatmentReturn to 30 x 109 /lResume lenalidomide at next lower dose level (Dose Level 2 or 3) once daily. Do not dose below 5 mg once daily.•Absolute Neutrophil counts (ANC)NeutropeniaWhen neutrophilsRecommended CourseFirst fall to < 0.5 x 109 /lInterrupt lenalidomide treatmentReturn to 0.5 x 109 /l when neutropenia is the only observed toxicityResume lenalidomide at Starting Dose once dailyReturn to 0.5 x 109 /l when dose-dependent haematological toxicities other than neutropenia are observedResume lenalidomide at Dose Level 1 once dailyFor each subsequent drop below < 0.5 x 109 /lInterrupt lenalidomide treatmentReturn to 0.5 x 109 /lResume lenalidomide at next lower dose level (Dose Level 1, 2 or 3) once daily. Do not dose below 5 mg once daily.In case of neutropenia, the physician should consider the use of growth factors in patient management.Paediatric patientsThere is no experience in children and adolescents. Therefore, lenalidomide should not be used in the paediatric age group (017 years).Elderly patientsThe effects of age on the pharmacokinetics of lenalidomide have not been studied. Lenalidomide has been used in clinical trials in multiple myeloma patients up to 86 years of age. The percentage of patients aged 65 or over was not significantly different between the lenalidomide/dexamethasone and placebo/dexamethasone groups. No overall difference in safety or efficacy was observed between these patients and younger patients, but greater pre-disposition of older individuals cannot be ruled out. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it would be prudent to monitor renal function.Use in patients with impaired renal functionLenalidomide is substantially excreted by the kidney, therefore care should be taken in dose selection and monitoring of renal function is advised.No dose adjustments are required for patients with mild renal impairment. The following dose adjustments are recommended at the start of therapy for patients with moderate or severe impaired renal function or end stage renal disease.Renal Function (CLcr)Dose Adjustment Moderate renal impairment (30 CLcr < 50 ml/min)10 mg once daily*Severe renal impairment (CLcr < 30 ml/min, not requiring dialysis)15 mg every other day**End Stage Renal Disease (ESRD) (CLcr < 30 ml/min, requiring dialysis)5 mg once daily. On dialysis days, the dose should be administered following dialysis* The dose may be escalated to 15 mg once daily after 2 cycles if patient is not responding to treatment and is tolerating the treatment.** The dose may be escalated to 10 mg once daily if the patient is tolerating the treatmentUse in patients with impaired hepatic functionLenalidomide has not formally been studied in patients with impaired hepatic function and there are no specific dose recommendations.

Child Dosage
Paediatric patients There is no experience in children and adolescents. Therefore, lenalidomide should not be used in the paediatric age group (0-17 years).

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

Contra Indications
Contraindications • Women who are pregnant. • Women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met (see Special Precautions and Interactions). • Hypersensitivity to the active substance or to any of the excipients.

Special Precautions
Pregnancy warning Lenalidomide is structurally related to thalidomide. Thalidomide is a known human teratogenic active substance that causes severe life-threatening birth defects. If lenalidomide is taken during pregnancy, a teratogenic effect of lenalidomide cannot be ruled out. The conditions of the Pregnancy Prevention Programme must be fulfilled for all patients unless there is reliable evidence that the patient does not have childbearing potential. Criteria for women of non-childbearing potential A female patient or a female partner of a male patient is considered to have childbearing potential unless she meets at least one of the following criteria: • Age = 50 years and naturally amenorrhoeic for = 1 year* • Premature ovarian failure confirmed by a specialist gynaecologist • Previous bilateral salpingo-oophorectomy, or hysterectomy• XY genotype, Turner syndrome, uterine agenesis. *Amenorrhoea following cancer therapy does not rule out childbearing potential. Counselling For women of childbearing potential, lenalidomide is contraindicated unless all of the following are met: • She understands the potential teratogenic risk to the unborn child • She understands the need for effective contraception, without interruption, 4 weeks before starting treatment, throughout the entire duration of treatment, and 4 weeks after the end of treatment • Even if a woman of childbearing potential has amenorrhea she must follow all the advice on effective contraception • She should be capable of complying with effective contraceptive measures • She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy • She understands the need to commence the treatment as soon as lenalidomide is dispensed following a negative pregnancy test • She understands the need and accepts to undergo pregnancy testing every 4 weeks except in case of confirmed tubal sterilisation • She acknowledges that she understands the hazards and necessary precautions associated with the use of lenalidomide. For male patients taking lenalidomide, there is no clinical data available on the presence of lenalidomide in human semen. Male patients taking lenalidomide must meet the following conditions: • Understand the potential teratogenic risk if engaged in sexual activity with a woman of childbearing potential • Understand the need for the use of a condom if engaged in sexual activity with a woman of childbearing potential. The prescriber must ensure that for women of childbearing potential: • The patient complies with the conditions for Pregnancy Prevention Programme, including confirmation that she has an adequate level of understanding • The patient has acknowledged the aforementioned conditions. Contraception Women of childbearing potential must use one effective method of contraception for 4 weeks before therapy, during therapy, and until 4 weeks after lenalidomide therapy and even in case of dose interruption unless the patient commits to absolute and continuous abstinence confirmed on a monthly basis. If not established on effective contraception, the patient must be referred to an appropriately trained health care professional for contraceptive advice in order that contraception can be initiated. The following can be considered to be examples of suitable methods of contraception: • Implant • Levonorgestrel-releasing intrauterine system (IUS) • Medroxyprogesterone acetate depot • Tubal sterilisation • Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses • Ovulation inhibitory progesterone-only pills (i.e., desogestrel) Because of the increased risk of venous thromboembolism in patients with multiple myeloma taking lenalidomide and dexamethasone, combined oral contraceptive pills are not recommended (See Interactions). If a patient is currently using combined oral contraception the patient should switch to one of the effective method listed above. The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception. The efficacy of contraceptive steroids may be reduced during co-treatment with dexamethasone (See Interactions). Implants and levonorgestrel-releasing intrauterine systems are associated with an increased risk of infection at the time of insertion and irregular vaginal bleeding. Prophylactic antibiotics should be considered particularly in patients with neutropenia. Copper-releasing intrauterine devices are generally not recommended due to the potential risks of infection at the time of insertion and menstrual blood loss which may compromise patients with neutropenia or thrombocytopenia. Pregnancy testing According to local practice, medically supervised pregnancy tests with a minimum sensitivity of 25 mIU/ml must be performed for women of childbearing potential as outlined below. This requirement includes women of childbearing potential who practice absolute and continuous abstinence. Ideally, pregnancy testing, issuing a prescription and dispensing should occur on the same day. Dispensing of lenalidomide to women of childbearing potential should occur within 7 days of the prescription. Prior to starting treatment A medically supervised pregnancy test should be performed during the consultation, when lenalidomide is prescribed, or in the 3 days prior to the visit to the prescriber once the patient had been using effective contraception for at least 4 weeks. The test should ensure the patient is not pregnant when she starts treatment with lenalidomide. Follow-up and end of treatment A medically supervised pregnancy test should be repeated every 4 weeks, including 4 weeks after the end of treatment, except in the case of confirmed tubal sterilisation. These pregnancy tests should be performed on the day of the prescribing visit or in the 3 days prior to the visit to the prescriber. Men It is not known whether lenalidomide is present in semen. Therefore all male patients should use condoms throughout treatment duration, during dose interruption and for 1 week after cessation of treatment if their partner is of childbearing potential and has no contraception. 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 or semen during therapy or for 1 week following discontinuation of lenalidomide. Educational materials In order to assist patients in avoiding foetal exposure to lenalidomide, the Marketing Authorisation Holder will provide educational material to health care professionals to reinforce the warnings about the potential teratogenicity of lenalidomide, to provide advice on contraception before therapy is started, and to provide guidance on the need for pregnancy testing. Full patient information about the potential teratogenic risk and the strict pregnancy prevention measures as specified in the Pregnancy Prevention Programme should be given by the physician to women of childbearing potential and, as appropriate, to male patients. Other special warnings and precautions for use Venous thromboembolism The combination of lenalidomide with dexamethasone is associated with an increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with multiple myeloma (See Interactions and Adverse Reactions). Concomitant administration of erythropoietic agents or previous history of DVT may also increase thrombotic risk in these patients. Therefore, erythropoietic agents, or other agents that may increase the risk of thrombosis, such as hormone replacement therapy, should be used with caution in multiple myeloma patients receiving lenalidomide with dexamethasone. A haemoglobin concentration above 13 g/dl should lead to discontinuation of erythropoietic agents. 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. Prophylactic antithrombotic medicines, such as low molecular weight heparins or warfarin, should be recommended, especially in patients with additional thrombotic risk factors. The decision to take antithrombotic prophylactic measures should be made after careful assessment of an individual patient’s underlying risk factors. Neutropenia and thrombocytopenia The combination of lenalidomide with dexamethasone in multiple myeloma patients is associated with a higher incidence of grade 4 neutropenia (5.1% in lenalidomide/dexamethasone-treated patients compared with 0.6% in placebo/dexamethasone-treated patients; see Adverse Reactions). Grade 4 febrile neutropenia episodes were observed infrequently (0.6% in lenalidomide/dexamethasone-treated patients compared to 0.0% in placebo/dexamethasone treated patients; see adverse Reactions). Patients should be advised to promptly report febrile episodes. A dose reduction may be required (See Adult Dosage). In case of neutropenia, the physician should consider the use of growth factors in patient management. The combination of lenalidomide with dexamethasone in multiple myeloma patients is associated with a higher incidence of grade 3 and grade 4 thrombocytopenia (9.9% and 1.4%, respectively, in lenalidomide/dexamethasone-treated patients compared to 2.3% and 0.0% in placebo/dexamethasone-treated patients; see section 4.8). Patients and physicians are advised to be observant for signs and symptoms of bleeding, including petechiae and epistaxes. A dose reduction may be required (See Adult Dosage). A complete blood cell count, including white blood cell count with differential count, platelet count, haemoglobin, and haematocrit should be performed at baseline, every week for the first 8 weeks of lenalidomide treatment and monthly thereafter to monitor for cytopenias. The major dose limiting toxicities of lenalidomide include neutropenia and thrombocytopenia. Therefore, co-administration of lenalidomide with other myelosuppressive agents should be undertaken with caution. Renal impairment Lenalidomide is substantially excreted by the kidney. Therefore care should be taken in dose selection and monitoring of renal function is advised in patients with renal impairment (See Adult Dosage). Thyroid function Cases of hypothyroidism have been reported and monitoring of thyroid function should be considered. Peripheral neuropathy Lenalidomide is structurally related to thalidomide, which is known to induce severe peripheral neuropathy. At this time, the neurotoxic potential of lenalidomide associated with long-term use cannot be ruled out. Tumour Lysis Syndrome Because lenalidomide has anti-neoplastic activity the complications of tumour lysis syndrome may occur. 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. Lactose intolerance Revlimid capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Unused capsules Patients should be advised never to give this medicinal product to another person and to return any unused capsules to their pharmacist at the end of the treatment.

Interactions
Erythropoietic agents, or other agents that may increase the risk of thrombosis, such as hormone replacement therapy, should be used with caution in multiple myeloma patients receiving lenalidomide with dexamethasone (See Special Precautions and Adverse Reactions). Oral contraceptives No interaction study has been performed with oral contraceptives. Dexamethasone is known to be a weak to moderate inducer of CYP3A4 and is likely to also affect other enzymes as well as transporters. It may not be excluded that the efficacy of oral contraceptives may be reduced during treatment. Effective measures to avoid pregnancy must be taken (See Special Precautions and Interactions). Results from human in vitro metabolism studies indicate that lenalidomide is not metabolised by cytochrome P450 enzymes suggesting that administration of lenalidomide with drugs that inhibit cytochrome P450 enzymes is not likely to result in metabolic drug interactions in man. In vitro studies indicate that lenalidomide has no inhibitory effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A. Warfarin Co-administration of multiple doses of 10 mg of lenalidomide had no effect on the single dose pharmacokinetics of R- and S- warfarin. Co-administration of a single 25 mg dose of warfarin had no effect on the pharmacokinetics of lenalidomide. However, it is not known whether there is an interaction during clinical use (concomitant treatment with dexamethasone). Dexamethasone is a weak to moderate enzyme inducer and its effect on warfarin is unknown. Close monitoring of warfarin concentration is advised during the treatment. Digoxin Concomitant administration with lenalidomide 10 mg/day increased the plasma exposure of digoxin (0.5 mg, single dose) by 14% with a 90% CI (confidence interval) [0.52%-28.2%]. It is not known whether the effect will be different in the therapeutic situation (higher lenalidomide doses and concomitant treatment with dexamethasone). Therefore, monitoring of the digoxin concentration is advised during lenalidomide treatment. Pregnancy and lactation: Pregnancy (See Contraindications and Special Precautions)Lenalidomide is structurally related to thalidomide. Thalidomide is a known human teratogenic active substance that causes severe life-threatening birth defects. The teratogenic effect of lenalidomide cannot be ruled out. For lenalidomide no clinical data on exposed pregnancies are available. Studies in animals have shown embryofoetal toxicity. Therefore, lenalidomide is contraindicated during pregnancy. Women of childbearing potential should use effective method of contraception. If pregnancy occurs in a woman treated with lenalidomide, treatment must be stopped and the patient should be referred to a physician specialised or experienced in teratology for eva luation and advice. If pregnancy occurs in a partner of a male patient taking lenalidomide, it is recommended to refer the female partner to a physician specialised or experienced in teratology for eva luation and advice. For male patients taking lenalidomide, there is no clinical data available on the presence of lenalidomide in human semen. Therefore male patients taking lenalidomide should use condoms if their partner is of childbearing potential and has no contraception. Lactation It is not known whether lenalidomide is excreted in human milk. Therefore breast-feeding should be discontinued during therapy with lenalidomide.

Adverse Reactions
In two Phase III placebo-controlled studies, 353 patients with multiple myeloma were exposed to the lenalidomide/dexamethasone combination and 351 to the placebo/dexamethasone combination. The median duration of exposure to study treatment was significantly longer (44.0 weeks) in the lenalidomide/dexamethasone group as compared to placebo/dexamethasone (23.1 weeks). The difference was accounted for by a lower rate of discontinuation from study treatment due to lower progression of disease in patients exposed to lenalidomide/dexamethasone (39.7%) than in placebo/dexamethasone patients (70.4%). 325 (92%) of the patients in the lenalidomide/dexamethasone group experienced at least one adverse reaction compared to 288 (82%) in the placebo/dexamethasone group. The most serious adverse reactions were: • venous thromboembolism (deep vein thrombosis, pulmonary embolism) (See Special Precautions) • Grade 4 neutropenia (sSee Special Precautions). The most frequently observed adverse reactions which occurred significantly more frequently in the lenalidomide/dexamethasone group compared to the placebo/dexamethasone group were neutropenia (39.4%), fatigue (27.2%), asthenia (17.6%), constipation (23.5%), muscle cramp (20.1%), thrombocytopenia (18.4%), anaemia (17.0%), diarrhoea (14.2%) and rash (10.2%). The adverse reactions observed in patients treated with lenalidomide/dexamethasone are listed below by system organ class and frequency. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Frequencies are defined as: very common (= 1/10); common (= 1/100, < 1/10); uncommon (= 1/1,000, < 1/100); rare (= 1/10,000, < 1/1,000), very rare (< 1/10,000 including isolated reports). In the majority of cases, there was no significant difference in the incidence of specific adverse events between the two treatment arms. Only those adverse reactions marked with * occurred significantly more frequently in the lenalidomide/dexamethasone arm compared to the placebo/dexamethasone arm. Adverse Drug Reactions (ADRs) observed in patients treated with lenalidomide/dexamethasone: Investigations Uncommon: Prolonged prothrombin time, prolonged activated partial thromboplastin time, increased International Normalised Ratio, increased blood alkaline phosphatase, increased blood lactate dehydrogenase, increased C-Reactive Protein, Cytomegalovirus antibody positive Cardiac disorders Common: Atrial fibrillation, palpitations Uncommon: Congestive cardiac failure, pulmonary oedema, heart valve insufficiency, atrial flutter, arrhythmia, ventricular trigeminy, bradycardia, tachycardia, QT prolongation, sinus tachycardia Congenital, familial and genetic disorders Uncommon: Chromosome abnormality Blood and lymphatic system disordersVery Common: Neutropenia*, thrombocytopenia*, anaemia* Common: Febrile neutropenia, pancytopenia, leucopenia*, lymphopenia* Uncommon: Granulocytopenia, haemolytic anaemia, autoimmune haemolytic anaemia, haemolysis, hypercoagulation, coagulopathy, monocytopenia, leucocytosis, lymphadenopathy Nervous system disorders Common: Cerebrovascular accident, syncope, peripheral neuropathy, neuropathy, peripheral sensory neuropathy, dizziness, ageusia, dysgeusia, paraesthesia, headache, tremor*, hypoaesthesia*, somnolence, memory impairment Uncommon: Intracranial haemorrhage, intracranial venous sinus thrombosis, thrombotic stroke, cerebral ischaemia, transient ischaemic attack, leukoencephalopathy, neurotoxicity, polyneuropathy, peripheral motor neuropathy, dysaesthesia, aphonia, dysphonia, disturbance in attention, ataxia, balance impaired, postural dizziness, burning sensation, cervical root pain, dyskinesia, hyperaesthesia, motor dysfunction, myasthenic syndrome, oral paraesthesia, psychomotor hyperactivity, anosmia Eye disorders Common: Blurred vision, cataract, reduced visual acuity, lacrimation increased Uncommon: Blindness, retinal arteriosclerosis, retinal vein thrombosis, keratitis, visual disturbance, eyelid oedema, conjunctivitis, eye pruritus, eye redness, eye irritation, dry eye Ear and labyrinth disorders Common: Vertigo Uncommon: Deafness, hypoacusia, tinnitus, ear pain, ear pruritus Respiratory, thoracic and mediastinal disorders Common: Pulmonary embolism, dyspnoea*, exertional dyspnoea, bronchitis, cough, pharyngitis, nasopharyngitis, hoarseness, hiccups Uncommon: Bronchopneumopathy, asthma, respiratory distress, pulmonary congestion, pleuritic pain, nasal congestion, throat secretion increased, laryngitis, sinus congestion, sinus pain, rhinorrhoea, dry throat Gastrointestinal disorders Very Common: Constipation, diarrhoea, nausea, increase and decrease in weight Common: Vomiting, dyspepsia, upper abdominal pain, gastritis, abdominal distension, abdominal pain, stomatitis, dry mouth, flatulence Uncommon: Gastrointestinal haemorrhage, peptic ulcer haemorrhage, oesophagitis, gastrooesophageal reflux disease, colitis, caecitis, gastroduodenitis, aptyalism, proctitis, gastroenteritis, oesophageal pain, dysphagia, odynophagia, haemorrhoids, epigastric discomfort, aphthous stomatitis, cheilitis, glossodynia, gingivitis, lip ulceration, tongue ulceration, oral pain, toothache, sensitivity of teeth, gingival bleeding, oral hypoaesthesia, lip pain, coated tongue Renal and urinary disorders Common: Renal failure Uncommon: Acute renal failure, urinary frequency, renal tubular necrosis, cystitis, haematuria, urinary retention, dysuria, acquired Fanconi Syndrome, urinary incontinence, polyuria, increased blood urea, increased blood creatinine, nocturia Skin and subcutaneous tissue disorders Very common: Rash* Common: Face oedema, dry skin, pruritus*, erythema, folliculitis, skin hyperpigmentation, exanthema, increased sweating, night sweats, alopecia Uncommon: Erythema nodosum, urticaria, eczema, erythrosis, erythematous rash, pruritic rash, papular rash, hyperkeratosis, contusion, skin fissures, acne, dermatitis acneiforme, lichen sclerosus, decubitus ulcer, pigmentation lip, prurigo, rosacea, photosensitivity reaction, seborroeic dermatitis, skin burning sensation, skin desquamation, skin discolouration Musculoskeletal and connective tissue disorders Very Common: Muscle cramp*, muscle weakness Common: Steroid myopathy, myopathy, myalgia, arthralgia, back pain, bone pain, pain in limb, chest wall pain, peripheral swelling Uncommon: Osteonecrosis, muscle atrophy, amyotrophy, pain in foot, muscle spasms, musculoskeletal pain, night cramps, groin pain, pain in jaw, neck pain, spondylitis, joint stiffness, joint swelling, musculoskeletal stiffness, limb discomfort, toe deformities, local swelling Endocrine disorders Common: Cushingoid-like symptoms Uncommon: Adrenal suppression, adrenal insufficiency, acquired hypothyroidism, increased and decreased thyroid stimulating hormone, hirsutism Metabolism and nutrition disorders Common: Hyperglycaemia, anorexia, hypocalcaemia, hypokalaemia, dehydration, hypomagnesaemia, fluid retention Uncommon: Metabolic acidosis, diabetes mellitus, hyponatraemia, hypercalcaemia, hyperuricaemia, hypoalbuminaemia, cachexia, failure to thrive, gout, hypophosphataemia, hyperphosphataemia, increased appetite Infections and infestations Common: Pneumonia*, lower respiratory tract infection, Herpes Zoster, Herpes Simplex, urinary tract infection, upper respiratory tract infection, sinusitis, oral candidiasis, oral fungal infection Uncommon: Septic shock, meningitis, neutropenic sepsis, sepsis, Escherichia sepsis, Clostridium difficile sepsis, Enterobacter bacteraemia, subacute endocarditis, bronchopneumonia, lobar pneumonia, bacterial pneumonia, pneumococcal pneumonia, Pneumocystis carinii pneumonia, primary atypical pneumonia, acute bronchitis, respiratory tract infection, herpes zoster ophthalmic, post-herpetic neuralgia, prostate infection, sinobronchitis, oesophageal candidiasis, infective bursitis, erysipelas, cellulitis, tooth abscess, chronic sinusitis, furuncle, pustular rash, ear infection, fungal infection, genital candidiasis, candida infection, influenza, tinea, fungal foot infection, anal warts Injury, poisoning and procedural complications Uncommon: Wound complication Neoplasms benign, malignant and unspecified (including cysts and polyps) Uncommon: Basal cell carcinoma, glioblastoma multiforme Vascular disorders Common: Deep vein thrombosis*, limb venous thrombosis, hypotension*, hypertension, orthostatic hypotension, flushing Uncommon: Circulatory collapse, thrombosis, ischaemia, peripheral ischaemia, intermittent claudication, phlebitis, pallor, petechiae, haematoma, postphlebitic syndrome, thrombophlebitis, superficial thrombophlebitis General disorders and administration site conditions Very Common: Fatigue*, asthenia*, peripheral oedema Common: Pyrexia, rigors, mucosal inflammation, oedema, lethargy, malaise Uncommon: Hyperpyrexia, chest pain, chest tightness, pain, difficulty in walking, abnormal gait, thirst, chest pressure sensation, feeling cold, feeling jittery, influenza-like illness, submandibular mass, fall, impaired healing Immune system disorders Uncommon: Acquired hypogammaglobulinaemia Hepatobiliary disorders Uncommon: Abnormal liver function tests, increased alanine aminotransferase, increased aspartate aminotransferase, increased blood bilirubin Reproductive system and breast disorders Common: Erectile dysfunction, gynaecomastia, metrorrhagia, nipple pain Psychiatric disorders Very Common: Insomnia Common: Confusional state, hallucinations, depression, aggression, agitation, mood alteration, anxiety, nervousness, irritability, mood swings Uncommon: Psychotic disorder, hypomania, delusion, mental status changes, sleep disorder, abnormal dreams, depressed mood, affect lability, listless, loss of libido, nightmare, personality change, panic attack, restlessness.

Manufacturer
Celgene

Drug Availability
(POM)

Updated
12 August 2009