thalidomide

tha-LID-oh-mide

Therapeutic Classification: antineoplastics, Immunosuppressant agents

REMS

Cutaneous manifestations of moderate to severe erythema nodosum leprosum.
Prevention (maintenance) and suppression of recurrent erythema nodosum leprosum.
Newly diagnosed multiple myeloma (in combination with dexamethasone).

Unlabeled Use:

Behçet syndrome.
HIV-associated wasting syndrome.
Aphthous stomatitis (including HIV associated).
Crohn disease.

May suppress excess levels of tumor necrosis factor-alpha and alter leukocyte migration by altering characteristics of cell surfaces.

Therapeutic effects:

Decreased skin lesions in erythema nodosum leprosum and prevention of recurrence.
Slowed progression of multiple myeloma.

Absorption: 67–93% absorbed following oral administration.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Hydrolyzed in plasma to multiple metabolites. Primarily excreted in the urine (92%; <4% as unchanged drug).

Half-Life: 5–7 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2–5 hr	unknown

Contraindicated in:

Hypersensitivity;
Seizure disorders;
Concurrent use of pembrolizumab in patients with multiple myeloma (↑ risk of mortality);
OB:
Pregnancy
;
Lactation: Lactation.

Use Cautiously in:

Rep:
Women of reproductive potential and men with female sexual partners of reproductive potential
;
Pedi: Children <12 yr (safety and effectiveness not established).

CV: bradycardia, edema, orthostatic hypotension, deep vein thrombosis (DVT)(↑ risk with dexamethasone in multiple myeloma)

Derm: drug reaction with eosinophilia and systemic symptoms (dress), rash, stevens-johnson syndrome (SJS), toxic epidermal necrolysis (TEN), photosensitivity

GI: constipation

Hemat: neutropenia, thrombocytopenia

Neuro: dizziness, drowsiness, peripheral neuropathy, seizures

Resp: pulmonary embolism (PE) (↑ risk with dexamethasone in multiple myeloma)

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), TUMOR LYSIS SYNDROME

Drug-drug:

↑risk of CNS depression with barbiturates, sedative/hypnotics, alcohol, chlorpromazine, or other CNS depressants.
Agents that may cause peripheral neuropathy may ↑ risk of peripheral neuropathy.

Drug-Natural Products:

Echinacea and melatonin may interfere with immunosuppression.

Erythema Nodosum Leprosum

PO (Adults ≥50 kg): 100–300 mg once daily initially; up to 400 mg/day has been used, depending on previous response. Every 3–6 mo, attempts should be made to taper and discontinue by 50 mg every 2–4 wk.
PO (Adults <50 kg): 100 mg once daily initially; up to 400 mg/day has been used, depending on previous response. Every 3–6 mo, attempts should be made to taper and discontinue by 50 mg every 2–4 wk.

Multiple Myeloma

PO (Adults ): 200 mg once daily in 28-day treatment cycles.

Capsules: 50 mg; 100 mg; 150 mg; 200 mg

Assess monthly for initial 3 mo and periodically during therapy to detect early signs of peripheral neuropathy (numbness, tingling, or pain in hands and feet). Commonly occurs with prolonged therapy, but has occurred following short-term use or following completion of therapy. May be severe and irreversible. Electrophysiologic testing may be done at baseline and every 6 mo to detect asymptomatic peripheral neuropathy. If neuropathy symptoms occur, discontinue thalidomide immediately to limit further damage. Reinstate therapy only if neuropathy returns to baseline.
Monitor for signs/symptoms of hypersensitivity reaction (erythematous macular rash, fever, tachycardia, hypotension). May require discontinuation of therapy if severe. If reaction recurs when dosing is resumed, discontinue thalidomide.
Monitor for signs/symptoms of bleeding (fatigue, dizziness, pallor, petechiae, epistaxis, tarry stools, coffee ground emesis) during therapy. May require dose interruption, reduction, or discontinuation.
Monitor patients for development of severe cutaneous adverse reactions, including DRESS, SJS, and TEN, including signs/symptoms of prodrome of fever, malaise, mucosal lesions, progressive skin rash, blisters, lymphadenopathy, conjunctivitis, myalgias, hepatitis, or eosinophilia. If a severe cutaneous adverse reaction is suspected, hold thalidomide until etiology of reaction is determined. Consultation with a dermatologist is recommended. If a severe cutaneous adverse reaction or Grade 3 or 4 skin rash is confirmed, permanently discontinue thalidomide.
Assess for signs/symptoms of tumor lysis syndrome (malaise, tachycardia, hypotension, confusion, delirium, arthralgia, myalgia, muscle spasms or twitches, paresthesia, headache, dizziness, nausea, vomiting, dark urine, acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, hypophosphatemia), especially in patients with high tumor burden. Supportive therapy may be necessary based on severity.
Multiple Myeloma:
Monitor for signs/symptoms of venous thromboembolism such as PE (chest pain, dyspnea, tachycardia) or DVT (calf pain or tenderness, lower extremity edema, localized warmth or erythema), especially in patients concurrently taking dexamethasone. Consider prophylaxis depending on patient risk factors.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy with two negative tests. Pregnancy tests with a sensitivity of ≥50 mIU/mL must be done within 10–14 days and 24 hr prior to starting therapy. Once treatment has started, pregnancy tests should occur weekly during 1st 4 wk of use and then every 4 wk in women with a regular menstrual cycle and every 2 wk in women with an irregular cycle.
Monitor WBC with differential during therapy. May ↓ WBC. If ANC ↓ to ≤750 cells/mm³ during therapy, re-evaluate medication regimen; if neutropenia persists, consider discontinuing therapy. May cause thrombocytopenia.
Monitor viral load in HIV-seropositive patients after the 1st and 3rd mo of therapy and every 3 mo thereafter. May ↑ viral load levels.

Do not confuse Thalomid with thiamine.
REMS: Due to teratogenic effects, thalidomide may be prescribed only by prescribers registered in the Thalomid REMS program. Required components of the Thalomid REMS program include the following: prescribers must be certified with the Thalomid REMS program by enrolling and complying with the REMS requirements; patients must sign a Patient-Physician Agreement Form and comply with the REMS requirements. Women of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements, and men must comply with contraception requirements. Pharmacies must be certified with the Thalomid REMS program, must only dispense to patients who are authorized to receive Thalomid, and must comply with REMS requirements. Information about Thalomid and the Thalomid REMS program is available at www.thalomidrems.com or by calling the REMS Call Center at 1-888-423-5436. Thalidomide is started within 24 hr of a negative pregnancy test with a sensitivity of at least 50 mIU/mL. Pregnancy testing must occur weekly during first month of therapy and then monthly thereafter in women with a regular menstrual cycle. For women with irregular menses, pregnancy testing should occur every 2 wk. If pregnancy occurs, thalidomide should be discontinued immediately. Any suspected fetal exposure must be reported to the FDA and the manufacturer, and patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicity. Even a single dose (1 capsule [regardless of strength]) taken by a pregnant woman during her pregnancy can cause severe birth defects.
Handle intact tablets or capsules with single gloves; use double gloves, respiratory protection, and a protective gown in the preparation of tablets or capsules, including cutting, crushing, manipulating, or handling uncoated tablets. During administration, wear single gloves, and wear eye/face protection if the formulation is hard to swallow or if the patient may resist, vomit, or spit up. If powder from capsules comes into contact with the skin mucous membranes, wash thoroughly with soap and water.
Corticosteroids may be used concurrently with thalidomide for patients with moderate to severe neuritis associated with a severe erythema nodosum leprosum reaction. Use of corticosteroids can be tapered and discontinued when neuritis resolves.
PO: Administer once daily with water, preferably at bedtime and ≥1 hr after the evening meal. If divided doses are used, administer ≥1 hr after meals.

Explain the purpose and side effects of thalidomide. Instruct patient to take as directed. Tell patient to take drug at bedtime ≥1 hr after evening meal. Do not discontinue without notifying health care provider; dose should be tapered gradually. Explain Thalomid REMS program to patient. Keep out of children's reach. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic lab tests will be needed.
Frequently causes drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to immediately report signs/symptoms of thromboembolism (shortness of breath, chest pain, arm/leg swelling).
Advise patient to immediately report signs/symptoms of SJS or TEN (flu-like symptoms, spreading red rash, skin/mucous membrane blistering).
Advise patient to report signs/symptoms of infection, bleeding, or peripheral neuropathy (numbness, tingling, pain, or burning in hands/feet).
Advise patient to change positions slowly to minimize orthostatic hypotension.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Advise patient not to drink alcohol while taking drug.
Instruct patient not to donate blood and male patients not to donate sperm while taking thalidomide and for 1 mo following discontinuation.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Rep:
May cause fetal harm. Inform women of reproductive potential that they must use one highly effective method (IUD, hormonal contraceptive, tubal ligation, partner's vasectomy) and one additional method (latex condom, diaphragm, cervical cap) AT THE SAME TIME for ≥4 wk before, during therapy and interruptions of therapy, and for 4 wk following discontinuation of therapy, even with a history of infertility, unless due to a hysterectomy or patient has been postmenopausal naturally for 24 consecutive mo. Advise female patients to avoid breastfeeding during therapy. Men receiving thalidomide with female partners of reproductive potential must always use a latex condom during and for up to 4 wk following discontinuation, even if they have undergone a successful vasectomy. Thalidomide must be discontinued if pregnancy is suspected or confirmed. Suspected fetal exposure must be reported to FDA via MedWatch at 1-800-FDA-1088 and to manufacturer at 1-888-668-2528. Inform women of reproductive potential that there is a Pregnancy Exposure Registry that monitors pregnancy outcomes in women exposed to thalidomide during pregnancy and that they can contact the Pregnancy Exposure Registry by calling 1-888-423-5436. May impair male fertility.

Resolution of the signs and symptoms of active erythema nodosum leprosum reaction. Usually requires at least 2 wk of therapy; then taper medication in 50-mg decrements every 2–4 wk.
Prevention of recurrent erythema nodosum leprosum. Tapering off medication should be attempted every 3–6 mo in decrements of 50 mg every 2–4 wk.
Decrease in serum and urine paraprotein measurements in patients with multiple myeloma.

Thalomid

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆