thalidomide

Therapeutic Classification: 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:

Bechet’s syndrome.
HIV-associated wasting syndrome.
Aphthous stomatitis (including HIV associated).
Crohn’s 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, thromboembolic events (↑ risk with dexamethasone in multiple myeloma)

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

GI: constipation

Hemat: neutropenia, thrombocytopenia

Neuro: dizziness, drowsiness, peripheral neuropathy, seizures

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

Drug-drug:

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

Drug-Natural Products:

Concurrent use with 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 in decrements of 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 in decrements of 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 symptoms occur, discontinue thalidomide immediately to limit further damage. Reinstate therapy only if neuropathy returns to baseline.
Monitor for signs 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 and symptoms of bleeding (petechiae, epistaxis, gastrointestinal bleeding) during therapy. May require dose interruption, reduction, or discontinuation.
Monitor for side effects (constipation, oversedation, peripheral neuropathy); may require discontinuation or dose reduction until side effects resolve.
Multiple Myeloma: Assess for venous thromboembolism (dyspnea, chest pain, arm or leg swelling) periodically during therapy, especially in patients concurrently taking dexamethasone. Consider prophylaxis depending on patient risk factors.

Lab Test Considerations:

Assess pregnancy status prior to starting therapy. Pregnancy tests with a sensitivity of at least 50 mIU/mL must be done within 10–14 days and within 24 hr of starting therapy. Once treatment has started, pregnancy tests should occur weekly during first 4 wk of use, then every 4 wk in females with a regular menstrual cycle and every 2 wk in females with an irregular cycle.Monitor WBC with differential and platelet count during therapy. May cause ↓ WBC. Do not initiate therapy with an absolute neutrophil count (ANC) ≤750/mm³. If ANC ↓ to ≤750/mm³ during therapy, re-evaluate medication regimen; if neutropenia persists, consider discontinuing therapy. May cause thrombocytopenia.
- May cause ↑ viral load levels in patients with HIV.

Do not confuse Thalomid with thiamine.
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 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. Female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements, and males 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, 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.
- If health care professionals or other caregivers are exposed to body fluids from patients receiving thalidomide, use appropriate precautions, such as wearing gloves to prevent the potential cutaneous exposure to thalidomide or washing the exposed area 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 at least 1 hr after the evening meal. If divided doses are used, administer at least 1 hr after meals.

Instruct patient to take thalidomide as directed. Do not discontinue without notifying health care professional; dose should be tapered gradually. Explain Thalomid REMS program to patient.
Advise patient that thalidomide should not be shared with others.
Frequently causes drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Advise patient to change positions slowly to minimize orthostatic hypotension.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Advise patient to notify health care professional immediately if pain, numbness, tingling, or burning in hands or feet or shortness of breath, chest pain, swelling of arms or legs occur.
Instruct patient not to donate blood and male patients not to donate sperm while taking thalidomide and for 1 mo following discontinuation.
Rep: May cause fetal harm. Inform females 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 at least 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. Males 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 females there is a Pregnancy Exposure Registry that monitors pregnancy outcomes in females exposed to thalidomide during pregnancy and that they can contact the Pregnancy Exposure Registry by calling 1-888-423-5436. May impair male fertility.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications. Concomitant use of HIV-protease inhibitors, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, or certain herbal supplements such as St. John's wort with hormonal contraceptive agents may reduce the effectiveness of contraception during and for up to one mo after discontinuation of these concomitant therapies. Women requiring treatment with one or more of these drugs must use two other effective or highly effective methods of contraception or abstain from heterosexual sexual contact while taking thalidomide.

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.

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