Dosing and uses of Thalomid (thalidomide)
Adult dosage forms and strengths
capsule
- 50mg
- 100mg
- 150mg
- 200mg
Erythema Nodosum Leprosum (ENL)
Initial: 100-300 mg PO qHs
More severe reaction may start at 400 mg
Continue until active symptoms subsided, at least 2 weeks, THEn
Titrate down by 50 mg increments q2-4Weeks
Multiple Myeloma
200 mg PO qHS in 28 day cycles
Take 40 mg of dexamethasone on days 1-4, 9-12, 17-20 of 28 days
Orphan Indications
GVHd
- Indicated for prevention and treatment of graft versus host disease
- Orphan indication sponsor: Andrulis Research Corporation; 11800 Baltimore Avenue, Suite 113; Beltsville, MD 20705
Mycobacterial infection
- Indicated for treatment of the clinical manifestations of mycobacterial infection caused by Mycobacterium tuberculosis and non-tuberculous mycobacteria
- Orphan indication sponsor: Celgene Corporation; PO Box 4914; 7 Powder Horn Drive; Warren, NJ 07059
Recurrent aphthous ulcers
- Indicated for treatment and prevention of recurrent aphthous ulcers in severely, terminally immunocompromised patients
- Orphan indication sponsor: Andrulis Research Corporation; 11800 Baltimore Avenue, Suite 113; Beltsville, MD 20705
Severe recurrent aphthous stomatitis
- Indicated for treatment of severe recurrent aphthous stomatitis in severely, terminally immunocompromised patients
- Orphan indication sponsor: Celgene Corporation; PO Box 4914; 7 Powder Horn Drive; Warren, NJ 07059
Primary brain malignancies
- Indicated for treatment of primary brain malignancies
- Orphan indication sponsor: Celgene Corporation; 7 Powder Horn Dr; Warren, NJ 07059
HIV-associated wasting syndrome
- Indicated for treatment of HIV-associated wasting syndrome
- Orphan indication sponsor: Celgene Corporation; PO Box 4914; 7 Powder Horn Drive; Warren, NJ 07059
Crohn's disease
- Indicated for treatment of Crohn's disease
- Orphan indication sponsor: Celgene Corporation; 7 Powder Horn Dr; Warren, NJ 07059
Kaposi's Sarcoma
- Indicated for treatment of Kaposi's Sarcoma
- Orphan indication sponsor: Celgene Corporation; 7 Powder Horn Dr; Warren, NJ 07059
Myelodysplastic syndrome
- Indicated for treatment of myelodysplastic syndrome
- Orphan indication sponsor: Celgene Corporation; 86 Morris Avenue; Summit, NJ 07901
Hematopoietic Stem Cell Transplantation (Orphan)
- Indicated for conditioning treatment prior to hematopoietic stem cell transplantation
- Orphan indication sponsor: Adienne Srl; 24128 Bergamo; 64/B Broseta Street; Bergamo; ITALY
Administration
Take with water at bedtime, at least 1 hour after evening meaL
Consider dose reduction, delay, or discontinuation in patients who develop NCI CTC (National Cancer Institute Common Toxicity Criteria) Grade 3 or 4 adverse reactions and/or based on clinical judgment
Other Information
Monitor: WBC & differentiaL
Pediatric dosage forms and strengths
Lepromatous Leprosy (Orphan)
Indicated for treatment and maintenance of reactional lepromatous leprosy
Orphan indication sponsor
- Pediatric Pharmaceuticals, Inc; 718 Bradford Avenue; Westfield, NJ 07090
GVHD in Bone Marrow Transplant (Orphan)
Indicated for prevention and treatment of graft versus host disease in patients receiving bone marrow transplantation
Orphan indication sponsor
- Pediatric Pharmaceuticals, Inc; 718 Bradford Avenue; Westfield, NJ 07090
Thalomid (thalidomide) adverse (side) effects
>10%
Somnolence (37%)
Rash (21%)
Edema (57%)
Hypotension (16%)
Leukopenia (17-35%)
Neutropenia (31%)
Increased bilirubin (14%)
Myalgia (17%)
Arthralgia (13%)
Hematuria (11%)
Thrombosis/embolism (23%)
Headache (12%)
Dyspnea (42%)
1-10%
Asthenia (8%)
General pain (8%)
Impotence (8%)
Malaise (8%)
Pruritus (8%)
Xerostomia (8%)
Flatulence (8%)
Tooth pain (4%)
Impotence (3-8%)
Vertigo (8%)
Constipation (4%)
Diarrhea (4%)
Neck rigidity (4%)
Frequency not defined
Photosensitivity
Bradycardia
Hypo/hypertension
Peripheral neuropathy
Neutropenia
Warnings
Black box warnings
Potential for human birth defects
- If taken during pregnancy, can cause severe birth defects or fetal death
- Major human fetal abnormalities with thalidomide include absence of bones, amelia (absence of limbs), congenital heart defects, external ear abnormalities (including anotia, micro pinna, small or absent external auditory canals), eye abnormalities (anophthalmos, microphthalmos), facial palsy, hypoplasticity of the bones, and phocomelia (short limbs); alimentary tract, urinary tract, and genital malformations also have been documented
- 40% mortality at birth, or shortly afterwards
- Avoid in pregnant women or women who could become pregnant while taking the drug; even a single dose (one 50, 100, or 200 mg capsule) taken by a pregnant woman can cause severe birth defects
STEPS program
- Available only under a special restricted distribution program called the System for Thalidomide Education and Prescribing Safety (STEPS)
- Only prescribers and pharmacists registered with the program are allowed to prescribe and dispense thalidomide
- Patients must be advised of, agree to, and comply with the requirements of STEPS to receive thalidomide
- Effective contraception must be used by patients for at least 4 wk before beginning thalidomide therapy, during therapy, during dose interruptions, and for 4 wk after discontinuing
- Reliable contraception is indicated even if the patient has a history of infertility, unless infertility is because of hysterectomy or because the patient has been postmenopausal naturally for at least 24 consecutive months
- 2 reliable forms of contraception must be used simultaneously unless continuous abstinence from heterosexual sexual contact is the chosen method; refer women of childbearing potential to a qualified provider of contraceptive methods, if needed
- Sexually mature women who have not undergone a hysterectomy, have not had a bilateral oophorectomy, or who have not been postmenopausal naturally for at least 24 consecutive months are considered to be women of childbearing potential
- Male patients: Because thalidomide is present in the semen of patients receiving the drug, men receiving thalidomide must always use a latex condom during any sexual contact with women of childbearing potential, even if he has undergone a successful vasectomy
Pregnancy testing
- Before prescribing, women of childbearing potential should have 2 negative pregnancy test results (sensitivity of at least 50 milliunits/mL)
- Perform first pregnancy test within 10-14 days and the second test within 24 hr prior to prescribing
- A prescription for a woman of childbearing potential must not be issued until negative pregnancy test results have been verified by the health care provider, and the pharmacist must verify a negative pregnancy test result with the prescriber before dispensing
- If pregnancy occurs, discontinue immediately
- Report any suspected fetal exposure to the Food and Drug Administration (FDA) immediately via MedWatch at (800) FDA-1088 and also to the manufacturer
- Refer the patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling
Patient education (females)
- Female patients: Use in women of childbearing potential is advised only when the patient meets the following conditions: 1) She understands and can reliably carry out instructions
- 2) She is capable of complying with the mandatory contraceptive measures, pregnancy testing, patient registration, and patient survey as described in STEPS program
- 3) She has received both oral and written warnings of the risks of taking thalidomide during pregnancy and of exposing a fetus to the drug
- 4) She has received both oral and written warnings of the risk of possible contraception failure and of the need to use 2 reliable forms of contraception simultaneously, unless continuous abstinence from heterosexual sexual intercourse is the chosen method
- 5) Sexually mature women who have not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months (ie, who have had menses at some time in the preceding 24 consecutive months) are considered to be women of childbearing potential
- 6) She acknowledges, in writing, her understanding of these warnings and of the need for using 2 reliable methods of contraception for 4 wk prior to initiating therapy, during therapy, and for 4 wk after discontinuing therapy
- 7) She has had a negative pregnancy test result, with a sensitivity of at least 50 milliunits/mL, within the 24 hr prior to beginning therapy
- 8) If the patient is between 12-18 years of age, her parent or legal guardian must have read this material and agreed to ensure compliance
Patient education (males)
- Male patients: Contraindicated in sexually mature men unless the patient meets all of the following conditions:
- 1) He understands and can reliably carry out instructions
- 2) He is capable of complying with the mandatory contraceptive measures that are appropriate for men, patient registration, and patient survey as described in STEPS program
- 3) He has received both oral and written warnings of the risks of taking thalidomide and of exposing a fetus to the drug
- 4) He has received both oral and written warnings of the risk of possible contraception failure and of the presence of thalidomide in semen
- 5) He has been instructed that he must always use a latex condom during any sexual contact with women of childbearing potential, even if he has undergone a successful vasectomy
- 6) He acknowledges, in writing, his understanding of these warnings and of the need to use a latex condom during any sexual contact with women of childbearing potential, even if he has undergone a successful vasectomy; women of childbearing potential are considered to be sexually mature women who have not undergone a hysterectomy, have not had a bilateral oophorectomy, or who have not been postmenopausal for at least 24 consecutive months (ie, who have had menses at any time in the preceding 24 consecutive months)
- 7) If the patient is between 12-18 years of age, his parent or legal guardian must have read this material and agreed to ensure compliance
Venous thromboembolic events
- Significantly increases risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients treated for multiple myeloma; this risk increases significantly when used with standard chemotherapeutic agents, including dexamethasone
- In one controlled trial, the rate of venous thromboembolic events was 22.5% in patients receiving thalidomide in combination with dexamethasone compared with 4.9% in patients receiving dexamethasone alone (P = 0.002)
- Observe for signs and symptoms of thromboembolism and instruct patients to seek medical care if they develop shortness of breath, chest pain, or arm or leg swelling
- Preliminary data suggest that patients who are appropriate candidates may benefit from concurrent prophylactic anticoagulation or aspirin treatment
Contraindications
Hypersensitivity
Pregnancy: highly teratogenic (even single dose)
- Women of childbearing age MUST be on two reliable forms of contraception
- Discontinue immediately if pregnancy occurs
- Report any suspected fetal exposure to thalidomide to FDA MedWatch program 1-800-FDA-1088
Males must use latex condoms during any sexual contact with women of childbearing potential even after undergoing successful vasectomy
Cautions
Increased risk of venous thromboembolism reported in patients with multiple myeloma treatment (see Black box warnings)
Ischemic heart disease (including myocardial infarction) and stroke observed
Drowsiness and somnolence may occur; instruct patients to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness
Peripheral neuropathy reported; examine patients at monthly intervals for the first 3 months of therapy and periodically thereafter; consider electrophysiological testing, consisting of measurement of sensory nerve action potential (SNAP) amplitudes at baseline and thereafter every 6 months in an effort to detect asymptomatic neuropathy
Dizziness and orthostatic hypotension may occur; advise patients to sit upright for a few minutes prior to standing up from a recumbent position
Neutropenia may require dose interruption and/or dose reduction
Thrombocytopenia, including Grade 3 or 4 occurrences, reported in association with the clinical use of thalidomide; monitor blood counts, including platelet counts; dose reduction, delay, or discontinuation may be required; monitor for signs and symptoms of bleeding including petechiae, epistaxis, and gastrointestinal bleeding, especially if concomitant medication may increase the risk of bleeding
May increased HIV viral load when used in HIV-seropositive patients; clinical significance unknown, measure viral load after the first and third months of treatment and every 3 months thereafter
Monitor for bradycardia and possible syncope; dose reduction or discontinuation may be required Stevens-Johnson syndrome and toxic epidermal necrolysis reported; do not resume following discontinuation for these reactions
Monitor patients with a history of seizures or at risk for the development of seizures closely for clinical changes that could precipitate acute seizure activity
Tumor lysis syndrome may occur; monitor patients at risk (eg, those with high tumor burden prior to treatment) and take appropriate precautions
Hypersensitivity to the drug and its components reported
Pregnancy and lactation
Pregnancy category: X
Lactation: not known if excreted in breast milk, not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Thalomid (thalidomide)
Mechanism of action
Suppresses tumor necrosis factor alpha; down-modulates cell surface adhesion molecules involved in leukocyte migration
Anticancer activity may be due to inhibition of angiogenesis
Pharmacokinetics
Bioavailability: 90%
Protein Bound: 55-66%
Peak plasma time: 3-6 hr
Half-Life: 5-7 hr
Peak plasma concentration: 1.15-3.2 mcg/mL
Vd: 122 L
Metabolism: Liver
Clearance: 1.15 mL/min
Excretion: Urine
