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  • Thalidomide Celgene
    / Neopharm


    Active Ingredient
    Thalidomide 50 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Hard Capsules

    28 X 50 mg

    partial basket chart 12876 20556

    Related information


    Dosage

    Thalidomide 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.
    To reduce central nervous system effects (e.g. drowsiness, somnolence, sedation) during the day, Thalidomide Celgene is normally taken as a single dose in the evening. Thalidomide Celgene 50mg Hard Capsules should be taken at least one hour after food.
    Multiple Myeloma (dosage in adults and adolescents): The required total duration of treatment should be individually determined for each patient depending on tolerability and disease progression.
    Patients with Untreated Multiple Myeloma: In combination with Melphalan and Prednisone: The Thalidomide Celgene recommended oral dose is 200 mg per day. A maximum number of 12 cycles of 6 weeks should be used.
    In combination with Dexamethasone: The Thalidomide Celgene recommended oral dose is 200 mg per day. For induction, 4 cycles of 4 weeks of thalidomide/dexamethasone is recommended.
    For elderly patients of poor performance, tolerability may be improved by starting the patient on 50 mg per day and increasing this dose to 200 mg per day over a 4 week period.
    After Failure of Standard Therapies: Dosing should be initiated at 200mg daily orally and increased by 100mg at weekly intervals to a maximum dose of 400mg daily according to tolerance and toxicity.
    Depending on tolerance and observed toxicity, lower maintenance doses can be used.
    Erythema Nodosum Leprosum (adult dosage): For an episode of cutaneous ENL, dosing should be initiated at 100mg to 300mg/day administered orally once daily preferably at bedtime. Patients weighing less than 50 kilograms should be started at the low end of the dose range. In patients with a severe cutaneous ENL reaction, or in those who have previously required higher doses to control the reaction, thalidomide dosing may be initiated at higher doses up to 400 mg/day once daily at bedtime or in divided doses with water. In patients with moderate to severe neuritis (due to leprosy) or other serious complications (e.g. uveitis), corticosteroids and other appropriate therapy may be started concomitantly and tapered/discontinued when neuritis has improved.
    Dosing with thalidomide should usually continue until signs and symptoms of active reaction have subsided, usually a period of at least 2 weeks. Patients may then be tapered off medication in 50 mg decrements every 2 to 4 weeks. Patients who have a documented history of requiring prolonged maintenance treatment to prevent the recurrence of cutaneous ENL or who flare during tapering, should be maintained on the minimum dose necessary to control the reaction. Tapering off medication should be attempted every 3-6 months, in decrements of 50mg every 2 to 4 weeks.
    Dosage adjustments during treatment: Dosage delay or reduction, dependent upon grade of toxicity, may be necessary. Patients should be monitored for: thromboembolic events; peripheral neuropathy; rash/skin reactions; bradycardia, syncope and somnolence. Dose delay, reduction or discontinuation, dependent upon the NCI CTC grade, may be necessary.
    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. If the patient experiences any thromboembolic events during treatment with thalidomide in combination, discontinue treatment and start standard anticoagulation therapy. 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.
    For full details see prescribing information.


    Indications

    Multiple Myeloma: For the treatment of multiple myeloma after failure of standard therapies.
    In combination with dexamethasone for the treatment of patients with newly diagnosed multiple myeloma.
    In combination with melphalan and prednisone for the treatment of patients with untreated multiple myeloma > or = 65 years or ineligible for high dose chemotherapy.
    Erythema Nodosum Leprosum (ENL):  For the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). Thalidomide is not indicated as monotherapy for such ENL treatment in the presence of moderate to severe neuritis. Thalidomide Celgene is also indicated as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence.


    Contra-Indications

    Known hypersensitivity to thalidomide or to any of the excipients. Patients below 12 years of age. Pregnancy and lactation. Women of child bearing potential who are not using, not willing or not able to use adequate contraceptive measures to prevent pregnancy. Women of childbearing potential where there is an alternative treatment of non-inferior efficacy available. Males who are not able or willing to comply with adequate contraceptive measures.


    Special Precautions

    Teratogenic effects: Thalidomide has caused severe birth defects when taken during pregnancy. Thalidomide should never be used by women who are pregnant or who could become pregnant whilst taking the drug or could become pregnant within 4 weeks after stopping the drug. Even a single dose can cause birth defects.
    Paediatric use: 
    It is not recommended to use thalidomide in patients below 12 years of age as safety and efficacy have not been established. There is only limited evidence of efficacy and safety of thalidomide in children 12-17 years of age.
    Drowsiness, somnolence and sedation: Thalidomide frequently causes drowsiness, somnolence and sedation. Patients should be instructed to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness without adequate medical advice. Dose
    reduction may be required. Thalidomide may potentiate the drowsiness caused by alcohol. As with any sedative medication, the potential for impaired consciousness may increase the risk for aspiration of food, vomitus and oral secretions.
    Peripheral neuropathy: Peripheral neuropathy is a very common, potentially severe, side effect of treatment with thalidomide that may be irreversible. 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. If thalidomide is contemplated for long-term use, baseline and 6-monthly sensory nerve action potential (SNAP) data should be collected. Where such monitoring is not feasible, regular clinical assessment is required.
    Neuritis in ENL patients: Thalidomide is known to cause neuritis which may be irreversible. The medicine potentially aggravates existing neuritis and should therefore not be used in such patients unless the clinical benefits outweigh the risks.
    Thrombogenicity: Use of thalidomide in patients with malignant neoplastic disease, including multiple myeloma, has been associated with an increased risk of deep vein thrombosis (DVT) and pulmonary embolus (PE).
    This risk increases significantly when thalidomide is used in combination with
    standard chemotherapeutic agents including melphalan, prednisone or dexamethasone.
    Syncope and bradycardia: Patients receiving thalidomide should be monitored for syncope and bradycardia and dose reduction or discontinuation may be required.
    Infections: Reactivation of hepatitis B virus (HBV) has been reported in patients receiving thalidomide in combination with corticosteroids who have previously been infected with HBV. Some of these cases progressed to acute hepatic failure, and resulted in discontinuation of thalidomide. Caution should be exercised when thalidomide in combination with corticosteroids is used in patients previously infected with HBV.
    These patients should be closely monitored for signs and symptoms of active HBV infection throughout therapy.
    See prescribing information for full details.


    Side Effects

    Nearly all patients can be expected to experience adverse reactions. The most
    commonly observed adverse reactions associated with the use of thalidomide in
    combination with dexamethasone or melphalan and prednisone are: deep vein
    thrombosis, constipation, peripheral oedema, tremor, dizziness, fatigue, somnolence, peripheral neuropathy, neutropenia, lymphopenia, leukopenia, anaemia, thrombocytopenia, paraesthesia and dysaesthesia.
    See prescribing information for full details.


    Drug interactions

    Thalidomide is a poor substrate for cytochrome P450 isoenzymes and therefore clinically important interactions with medicinal products metabolized by this enzyme system are unlikely. Non-enzymatic hydrolysis suggests that the potential for drug-drug interactions with thalidomide is low.
    Increase of sedative effects of other drugs: 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: 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.
    Medications known to cause peripheral neuropathy: Medications known to be associated with peripheral neuropathy should be used with caution in patients receiving thalidomide. (e.g. zalcitabine, vincristine, didanosine and bortezomib).
    Cytotoxic drugs: An increased risk for thrombosis and thrombo-embolic events has been reported in association with the use of thalidomide in combination with cytotoxic drugs e.g. doxorubicin and melphalan.
    Oral contraceptives: Thalidomide does not interact with oral contraceptives. However, combined hormonal contraceptives are not recommended due to the increased risk of venous thrombo-embolic disease. Therefore, effective contraceptive measures to avoid pregnancy must be taken.
    Concomitant therapies that may increase the risk of thromboembolism:
    Erythropoietic agents, or other agents that may increase the risk of thromboembolism, such as oestrogen-containing therapies, should be used with caution in multiple myeloma.
    Warfarin: Thalidomide does not interact with warfarin.
    Digoxin: Thalidomide does not interact with digoxin.
    Important non-thalidomide drug interactions – drugs that interfere with hormonal contraceptives:Concomitant use of glucocorticoids (including dexamethasone and prednisone), HIVprotease inhibitors, griseofulvin, rifampin, rifabutin, phenytoin, or carbamazepine with hormonal contraceptive agents, may reduce the effectiveness of the contraception. Therefore, women of childbearing potential requiring treatment with one or more of these medicines must use two other effective methods of contraception or abstain from heterosexual contact while taking thalidomide.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: (Category X) Thalidomide is a known human teratogen and should not, under any circumstances, be administered during pregnancy, or to women of child-bearing potential, unless they are using two effective means of contraception. A single dose taken by pregnant women can cause birth defects. Thalidomide has been found in the semen of men taking the drug; therefore male patients with female partners of child bearing potential must use adequate contraceptive methods. Contraception must continue for 4 weeks after stopping thalidomide treatment. If a female patient, or female partner of a male patient misses, or is suspected to have missed her period or there is any abnormality in menstrual bleeding, or suspects she is pregnant then a pregnancy test and counselling should be performed. If pregnancy occurs in a patient during thalidomide treatment, thalidomide should be discontinued immediately. The patient or pregnant partner should be referred to an obstetrician or gynaecologist experienced in reproductive toxicity for further evaluation and counselling. See prescribing information for full details.
    Lactation: It is not known whether thalidomide is excreted in human milk. Thalidomide has been detected in the milk of lactating rabbits given thalidomide by oral gavage, at concentrations up to 3.6 times maternal plasma levels. Women who are taking thalidomide should not breast feed; and for 4 weeks from discontinuation of treatment with thalidomide.


    Overdose

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


    Manufacturer
    Celgene International SARL, Switzerland
    Licence holder
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