Thalidomide
Thalomid™

Classification:

• Biologic Response Modifiers
• Dermatological Agents
• Disease-Modifying Antirheumatic Drugs (DMARDs)
• Musculoskeletal Agents
• Tumor Necrosis Factor (TNF) Modifiers

Description, Mechanism of Action, Pharmacokinetics

Description: Thalidomide gained attention in the late 1950s and early 1960s as a hypnotic agent and as a treatment for nausea associated with pregnancy but was subsequently discovered to cause severe birth defects, including phocomelia. Makers of thalidomide originally applied to market the drug in the US over 35 years ago but thalidomide was never approved for marketing in the US. In the mid 1960s, thalidomide was given to patients with erythema nodosum leprosum (ENL) as a sedative. These patients experienced rapid and substantial improvement of the painful, erythematous nodules associated with this disease. Controlled trials showed that thalidomide therapy is effective in controlling the signs and symptoms of ENL in > 90% of patients. Thalidomide is also able to maintain complete control of the symptoms in > 90% of patients for up to 14 years. Thalidomide has been recommended as the treatment of choice for moderate to severe ENL in men and women of non-childbearing potential by the Fifth International Leprosy Congress (1973) and by the World Health Organization (1994). Recently, thalidomide has been studied in a wide variety of inflammatory and immunologic disorders including chronic graft-versus-host disease, rheumatoid arthritis, inflammatory bowel disease, lichen planus, Behcet's disease, pyoderma gangrenosum, sarcoidosis, prurigo nodularis, lupus erythematosus, breast and prostate cancers, gliomas, cachexia and HIV-associated diarrhea. In a study of refractory multiple myeloma patients, thalidomide as a single agent produced an overall response rate of 32%.[2141] Thalidomide has orphan drug status for the following conditions: treatment of primary brain malignancies, Crohn's disease, Kaposi's sarcoma, HIV-wasting syndrome, reactional lepromatous leprosy, recurrent aphthous ulcers and stomatitis, treatment of mycobacterium infections, treatment and prevention of graft-versus-host disease, and multiple myeloma. The FDA approved thalidomide (Thalomid™) for the treatment and maintenance therapy of ENL in July 1998. Originally, the manufacturer applied to market the drug under the trade name "Synovir®" but the FDA rejected that name on the grounds that it sounded too similar to antiviral drugs. Thalidomide is the most heavily-regulated drug in the US and may only be obtained through physicians and pharmacies registered in the System for Thalidomide Education and Prescribing Safety (STEPS) Program.

Mechanism of Action: The complete mechanism of action of thalidomide is not completely understood. In vitro and in vivo studies show that thalidomide selectively reduces levels of tumor necrosis factor alpha (TNF-alpha) by accelerating the degradation of TNF-alpha mRNA encoding protein. Thalidomide reduces the half-life of the TNF-alpha mRNA protein from 30 minutes to about 17 minutes. Thalidomide does not affect mRNA levels of interleukin (IL)—1 or IL—6.[1879] TNF-alpha has been associated with the pathology and symptoms of many different diseases including ENL, AIDS, cancers, graft-versus-host disease, tuberculosis and malaria. Symptoms associated with TNF-alpha include fever, weight loss and characteristics of septic shock resulting in endothelial damage, disturbances of lipid metabolism and release of IL—1.[1880] The mechanism of thalidomide is different from the proposed mechanism of pentoxifylline or corticosteroids, which suppress lipopolysaccharide-induced TNF-alpha RNA transcription and translation, respectively. Thalidomide also increases levels of IL—2 and interferon-gamma, augment NK-like activity, and inhibit IL—12 production.[1881] [1882] Recently, thalidomide has been recognized as an inhibitor of angiogenesis due to inhibition of basic fibroblast growth factor (bFGF). bFGF has been shown to stimulate limb growth and its inhibition may be the basis for the limb defects associated with thalidomide.[1883]

Pharmacokinetics: Thalidomide is administered orally and is slowly absorbed from the GI tract. The exact bioavailability has not been determined due to poor aqueous solubility of thalidomide. The AUC is proportional to the dose but at doses >200 mg a flattening of the peak concentration curve is noted with an associated delay in the Tmax. Following 200 and 400 mg doses of thalidomide in healthy volunteers the Cmax was 1.76 µg/ml, 2.82 µg/ml, the Tmax was 3.5 hours and 4.3 hours, and AUC was 18.9 µg•hr/ml and 36.4 µg•hr/ml, respectively. The pharmacokinetics seem to differ in patients treated with thalidomide. In patients with Hansen's disease, following thalidomide 400 mg the Cmax was 3.44 µg/ml with a Tmax of 5.7 hours and AUC 46.4 µg•hr/ml and in HIV-positive patients following thalidomide 300 mg the Cmax was 3.47 µg/ml with a Tmax of 3.4 hours and AUC 40.11 µg•hr/ml.[1884] Patients with aphthous ulcers or other conditions affecting the GI tract may have different pharmacokinetic profiles due to potential differences in absorption. Administration of thalidomide with a high fat meal causes minor changes in the AUC and Cmax but increases the Tmax to about 6 hours in healthy volunteers. The exact mechanism of metabolism and elimination of thalidomide is not understood. Thalidomide appears to undergo non-enzymatic hydrolysis in the plasma and is not hepatically metabolized. The half-life seems to be similar in all groups studied with an average half-life of 6—7 hours. Less than 0.7% of the dose is excreted in the urine as unchanged drug and thalidomide is undetectable in the urine 48 hours after a single dose. In addition, only a small amount of thalidomide metabolites may be dectected in the urine 12—24 hours after dosing. The pharmacokinetics of thalidomide in patients with renal or hepatic insufficiency have not been determined.


Indications

• AIDS-associated wasting syndrome†
• aphthous ulcer†
• astrocytoma†
• Behcet's syndrome†
• cachexia†
• Crohn's disease†
• discoid lupus erythematosus†

• erythema nodosum leprosum (ENL)
• graft-versus-host disease†
• Kaposi's sarcoma†
• malignant glioma†
• multiple myeloma†
• prurigo†
• systemic lupus erythematosus (SLE)†

†non-FDA-approved indication

Dosage

For the management of erythema nodosum leprosum (ENL):
NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
•for the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL):
Oral Dosage:
Adults: Thalidomide 200 mg (100—400 mg) PO once daily at bedtime and at least 1 hour after meals. Patients weighing <50 kg should start at the with the lower doses. Patients who have previously required higher doses or those with a severe cutaneous ENL reaction, may start thalidomide at 400 mg/day at bedtime, at least 1 hour after meals. Therapy is continued until the symptoms have resolved and then thalidomide is tapered by reducing the daily dose 50 mg PO every 2—4 weeks.
•for prevention and suppression therapy of the cutaneous manifestations of erythema nodosum leprosum (ENL) recurrence:
Oral Dosage:
Adults: Patients who require thalidomide maintenance treatment to prevent recurrence or flare during tapering should be maintained on the minimum dose required to control the reaction. Tapering of thalidomide should be attempted every 3—6 months by decreasing the daily dose 50 mg/day every 2—4 weeks.

For the treatment of AIDS-associated wasting syndrome† and cancer cachexia†:
NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
Oral Dosage:
Adults: Thalidomide 100 mg PO once daily at bedtime is the typical dose with a range of 50—200 mg/day. In patients with AIDS-associated wasting syndrome, thalidomide has shown to increase lean body mass 10.5% from baseline after 24 weeks of treatment.[1876] Weight gain has continued with continued treatment with thalidomide.

For the treatment of recurrent aphthous ulcer† and stomatitis† in severely immunocompromised patients:
NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
Oral Dosage:
Adults: Thalidomide 100—200 mg PO once daily at bedtime has been studied. If the patient does not respond to lower doses, thalidomide may be increased to 400—600mg/ PO day. In patients with HIV-related aphthous ulcers, > 90% of patients experienced healing of ulcers, decreased pain, improved appetite and increased sense of well-being following 7—28 days of treatment with thalidomide.[1877] Once the ulcers have healed thalidomide is usually discontinued. Retreatment with thalidomide if the ulcers recur is effective.

For the treatment and prevention of chronic graft-versus-host disease† (GVHD):
NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
Oral Dosage:
Adults: Thalidomide 800—1600 mg/day PO has been shown to be effective in patients with chronic GVHD and progressive GVHD.[1878] Thalidomide plasma concentrations of 1—7 mg/L have been shown effective in chronic GVHD with minimal side effects.[1885] Best responses to thalidomide occur in cutaneous GVHD, but the optimal dose and timing of thalidomide in this disease have yet to be determined.
Children: Trials in children with chronic and corticosteroid-dependent, chronic GVHD were treated effectively with thalidomide 12—25 mg/kg/day PO.

For the treatment of Kaposi's sarcoma†:
NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
Oral Dosage:
Adults: In a Phase II trial, thalidomide 200 mg/day PO escalating every 2 weeks as tolerated to a maximum of 1000 mg/day was given to patients for 52 weeks. Reduction in lesions and durable responses were noted in the preliminary results of this trial.[1886]
For the treatment of advanced and refractory multiple myeloma†:
NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
Oral Dosage:
Adults: As a single agent, the dosage studied includes 200 mg/day PO for 14 days with doses increased by 200 mg/day every 2 weeks to tolerance or a maximum dose of 800 mg/day. In 27 patients (32%), the serum or urine myeloma protein levels declined by at least 25%, including 8% with a decline of at least 50%, 7% with a decline of at least 75% and 7% with a decline of at least 90%; 2 patients had a complete response. Decreases of at least 25% were seen within a median of 29 days.[2141] Early studies with thalidomide 400 mg/day PO in combination with dexamethasone, cisplatin, doxorubicin, and etoposide have also shown impressive results in patients with high-risk and refractory multiple myeloma.[2142]

For the treatment of primary malignant glioma† (including astrocytoma†):
NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
Oral Dosage:
Adults: In the context of clinical trials, thalidomide 800—1200 mg/day PO alone and in combination with chemotherapy or radiation has been given to patients with glioblastoma multiformae and astrocytomas. Thalidomide is usually started at 200—400 mg PO once at bedtime then increased by 100—200 mg/day every 3—7 days.

For the treatment of discoid lupus erythematosus†, subacute cutaneous lupus erythematosus†, chronic cutaneous lupus erythematosus†, and the cutaneous manifestations of systemic lupus erythematosus (SLE)†:
Oral Dosage:
Adults: In patients who are refractory to previous treatment, initial doses of thalidomide of 50—400 mg/day PO are given until clinical response was achieved. Doses are gradually tapered and maintained at 25—100 mg PO once daily. Retreatment for relapse with thalidomide 25—100 mg/day PO is usually effective.[1887]

For the treatment of Behcet's syndrome†:
Oral Dosage:
Adults: Thalidomide 100—400 mg/day PO daily for up to 38 months has been effective in improving arthritis, ocular manifestations and skin lesions associated with Behcet's syndrome.[1888]

For the treatment of prurigo†, specifically, prurigo nodularis†:
Oral Dosage:
Adults: Thalidomide 50—300 mg/day PO for an average duration of 12 months produced immediate and pronounced relief of intense pruritus and a significant decrease in the number of skin lesions.[1889]

For the treatment of Crohn's disease†:
NOTE: Thalidomide has been designated an orphan drug by the FDA for this indication.
•in patients with steriod-dependent disease†:
Oral Dosage:
Adults: In a pilot study, twelve patients received thalidomide 50 mg or 100 mg PO once daily at bedtime for 12 weeks. All patients were able to reduce their steroid dosage by >= 50% and 44% of patients discontinued all steroid therapy. In weeks 5—12, 70% of patients responded and 20% achieved a complete remission.[2707]
•in patients with refractory Crohn's disease†:
Oral Dosage:
Adults: In an open trial, 22 patients with refractory Crohn's disease were treated with thalidomide 200 mg or 300 mg PO once daily at bedtime for 12 weeks. At 4 weeks of treatment, there were 12 clinical responses and 4 clinical remissions. At 12 weeks of therapy, 9 (3 luminal and 6 fistula patients) patients achieved a clinical remission.[2708]
<BR
Patients with renal impairment:

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

†non-FDA-approved indication


Administration Guidelines

Oral Administration
•Thalidomide may only be prescribed and dispensed under the conditions outlined in the System for Thalidomide Education and Prescribing Safety (STEPS) Program. The STEPS program is a comprehensive safety program for prescribers, pharmacists, and patients (male and female) to prevent fetal exposure to thalidomide. Prescribers and pharmacists must register to prescribe and dispense thalidomide. All patients must complete an informed consent and participate in a mandatory and confidential monitoring registry. For more information and to register in STEPS program, call Celgene Customer Service at 888—423—5436.
•Thalidomide may be dispensed in no more than a 28-day supply and only on presentation of a prescription written within the previous 7 days. Prescriptions older than 7 days may not be filled.
•Thalidomide has been given in doses up to 1200 mg/day divided into 3—4 daily doses with the larger part of the dose given in the evening to minimize the sedation effects.
•Thalidomide must be dispensed in its original packaging; do not repackage.
•Store at room temperature 59—86 degrees F (15—30 degrees C) and protect from light.


Contraindications/Precautions

breast-feeding
• children
• driving or operating machinery
• females
• human immunodeficiency virus (HIV) infection
• immunosuppression

• leukopenia
• neutropenia
• orthostatic hypotension
• peripheral neuropathy
pregnancy

• Absolute contraindications are in italics.

Thalidomide is contraindicated in pregnancy and in women of childbearing potential (Pregnancy category X) unless other treatment options are not appropriate and the woman complies with all requirements to ensure she can not become pregnant while taking thalidomide. Thalidomide is also contraindicated in sexually active men unless he complies with all of the requirement to ensure his partner does not become pregnant. Thalidomide will cause severe birth defects or death to the fetus following even a single dose (1 capsule, 50 mg) taken by a pregnant women. Women must commit to obstain from sexual intercourse or use two methods of reliable birth control, including at least one highly effective method (e.g., IUD, hormonal contraception or tubal ligation) and one additional effective method (e.g., latex condom, diaphragm, or cervical cap) beginning 4 weeks prior to initiating treatment, during and 4 weeks after completing treatment with thalidomide. Men must use barrier contraception (latex condom), even if he has undergone successful vasectomy, while having sexual intercourse with a woman of childbearing potential. If the patient is between the ages of 12—18 years, their parent or legal guardian must agree to ensure compliance with these conditions. Pregnancy testing and counseling should be done if a woman misses her period or has any abnormal menstrual bleeding. If pregnancy occurs during thalidomide treatment, thalidomide must be immediately discontinued and the patient should be referred to an appropriate physician experienced in reproductive toxicity for further counseling and evaluation.

Females of childbearing potential are defined as sexually mature women who have not undergone a hysterectomy or have not been post-menopausal for at least 24 consecutive months. Women of childbearing potential must have a pregnancy test (sensitivity of at least 50 mIU/ml) 24-hours prior to beginning thalidomide therapy, weekly during the first month of therapy, then monthly thereafter in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles. Women requiring medications that may interfere with the effectiveness of hormonal contraception must use 2 other effective or highly effective methods of contraception. Medications which may interfere with the effectiveness of hormonal contraception include HIV-protease inhibitors, hepatic enzyme inducers and antibiotics.

Patients should be cautioned against donating blood and men should not donate sperm while taking thalidomide.

It is not known if thalidomide is excreted into breast milk. However, due to the potential for severe side effects to the infant, women who are breast-feeding should not receive thalidomide. The decision of whether to continue breast-feeding or to stop thalidomide therapy should be based upon the effects of stopping thalidomide on the mother.

The safety and effectiveness of thalidomide has not been determined in children under the age of 12 years.

Patients with pre-existing peripheral neuropathy or taking other agents known to cause peripheral neuropathy should be closely monitored during treatment with thalidomide. Thalidomide may cause severe and possibly irreversible neuropathies, usually after chronic use. Patients should be examined monthly for the first 3 months of thalidomide therapy and then routinely from then on to detect any early signs of peripheral neuropathy. Clinicians should consider electrophysiologic testing consisting of measurement of sensory nerve action potential (SNAP) amplitudes at baseline and then every 6 months to detect asymptomatic neuropathies.

Patients should be cautioned about driving or operating machinery during thalidomide therapy due to somnolence and drowsiness associated with thalidomide therapy. Patients should also be warned of the potential additive effects with other medications such as barbiturates, H1-blockers, and ethanol.

Thalidomide may cause dizziness and orthostatic hypotension. Patients should be cautioned to sit upright for a few minutes before standing up from a lying or seated position.

Neutropenia has been associated with thalidomide treatment. Thalidomide should be used cautiously in patients with immunosuppression and pre-existing leukopenia. Therapy with thalidomide should not be continued if the absolute neutrophil count (ANC) is less than 750/mm3. Routine monitoring of the WBC is recommended every other week during the first 3 months of treatment in HIV-positive and other immunosuppressed patients and monthly in non-immunosuppressed patients.

Thalidomide has been associated with an increase in HIV-RNA levels in human immunodeficiency virus (HIV) infection-seropositive patients in controlled trials. The clinical significance of this increase is unknown and appears to be a transient effect. These studies were performed prior to the availability of effective combination antiretroviral therapy. In HIV-seropositive patients, it is recommended to monitor viral load after the first and third months of thalidomide treatment and every 3 months thereafter.


Drug Interactions

Anxiolytics, Sedatives, and Hypnotics
Barbiturates
 • Chlorpromazine
 • Ethanol

H1-blockers
Opiate agonists
 • Reserpine

Thalidomide may enhance the sedative effects of barbiturates, chlorpromazine, ethanol, H1-blockers, reserpine, opiate agonists, anxiolytics, sedatives, and hypnotics.


Adverse Reactions

• constipation
• dizziness
• drowsiness
• headache
• maculopapular rash
• muscle cramps

• neutropenia
• orthostatic hypotension
• peripheral neuropathy
• sinus bradycardia
• teratogenesis

The most serious and infamous adverse reaction associated with thalidomide is human teratogenesis. Even a single 50 mg dose of thalidomide may cause severe birth defects or death to the fetus. Defects have included amelia (absence of limbs), phocomelia (defective shortened limbs, "flippers") hypoplasia of the bones and absence of bones, anotia (absence of ears), microtia (small ears), facial palsy, anophthalmos, microphthalmos, congenital heart defects, and gastrointestinal and renal abnormalities. The critical period of exposure is from 35—50 days from the last menstrual period. The risk of other severe birth defects outside this critical period is not known but may be significant. Thalidomide should not be given at any time during pregnancy.

Drowsiness and somnolence are commonly associated with thalidomide therapy, especially at doses > 200 mg/day. Drowsiness in the morning following an evening dose has also been reported. Patients usually develop tolerance to this side effect over 1—3 weeks. The severity of drowsiness may be lessened by giving the dose in the evening, starting with a lower dose and slowly increasing the dose 100—200 mg/day once or twice a week. Additive effects may be seen with other drugs (see Drug Interactions).

Severe and irreversible peripheral neuropathy has been reported after chronic thalidomide therapy and rarely after short-term use. The reported incidence of peripheral neuropathies varies from 10—50%. Older age and cumulative doses >14 g thalidomide appear to correlate with the incidence of neuropathy.[1890] Symptoms may appear after thalidomide therapy has been stopped and may resolve slowly or not at all. Early signs of neuropathy include numbness and tingling of the toes and fingers, pain in the hands or feet, muscle cramps, superficial sensory loss in the feet and hands. Patients must be closely monitored for signs of neuropathy on a regular basis. Thalidomide should be stopped immediately at the first complaint of neuropathy to prevent further damage and to increase chance for reversal. Retreatment with thalidomide should only occur if the neuropathy returns to baseline. Medications that may cause peripheral neuropathies should be avoided, if possible, during thalidomide therapy.

Constipation occurs in 3—30% of patients receiving thalidomide with an increased incidence at doses >400 mg/day. Patients should be maintained with a daily bowel regimen, such as milk of magnesia, psyllium or docusate, while receiving thalidomide.

HIV-patients seem to experience rash (24%) and hypersensitivity reactions more frequently than other patient populations treated with thalidomide. In erythema nodosum leprosum patients, the incidence of rash due to thalidomide is <1%. Rash has also been reported in patients with chronic graft-versus-host disease, cancer and pruigo nodularis. The rash is described as a pruritic, eythematous, maculopapular rash over the trunk and back but not the axillae or groin. It usually occurs 2—13 days after starting thalidomide therapy and quickly resolves upon discontinuation. Rechallenge with thalidomide has resulted in more immediate reactions in some cases with fever, tachycardia and rash.[1891]

Overall, the incidence of neutropenia due to thalidomide is <1%; however, there is an increased incidence of neutropenia in HIV-positive patients of 2—20%.

Thalidomide has been reported to increase HIV-viral load during the first few weeks of therapy. In the two studies reported, there was a median increase of 0.3—0.42 log copies at week 4 (written communication, Celgene Corporation. July 1998). The clinical significance of this increase is unknown and appears to be a transient effect. These studies were performed prior to the availability of effective combination antiretroviral therapy. More recent studies have shown an decrease in HIV replication in vitro[1892] and a decrease in HIV-load when given to patients also infected with TB.[1893] At this time, however, the recommendation is to monitor HIV-viral load after the first and third months of thalidomide treatment and every 3 months thereafter in HIV-positive patients.

Other common adverse reactions to thalidomide include dizziness, orthostatic hypotension, and headache. Patients should be warned to sit up for a few minutes before standing from a lying or seated position to help prevent dizziness and orthostatic hypotension. Sinus bradycardia, not requiring treatment or intervention, has been reported in some patients receiving thalidomide therapy. The etiology of the bradycardia is unknown.


Patient Education

Thalidomide capsules

What does thalidomide do?
THALIDOMIDE (Thalomid™) alters the body's immune response. Thalidomide is used to treat diseases and symptoms of diseases caused by abnormalities in the immune system. Thalidomide also may be useful in the treatment of various types of cancer. Thalidomide causes severe birth defects or death to an unborn child and now is only available under strict guidelines.

What should my health care professional know before I take thalidomide?
They need to know if you have any of these conditions:
•pregnant or planning to get pregnant
•breast-feeding or planning to breast-feed
•tingling or numbness in hands or feet or other nerve pain
•low white blood cell count
•low blood pressure

How should I use this medicine?
Thalidomide capsules are taken by mouth with water. Make sure to follow the directions on your prescription bottle. If you are only taking thalidomide once a day, take your dose at bedtime at least 1 hour after the evening meal to decrease the drowsiness effects.

NEVER give this medicine to anyone else.

What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, consult your prescriber or health care professional. You may need to miss a dose or take a double dose, depending on your condition and treatment. Do not take double or extra doses without advice.

What other medicines can interact with thalidomide?
•any medicines that may decrease the effectiveness of birth control pills
•alcohol or any medicines that may cause drowsiness - thalidomide may increase this effect
•any medicines which may cause tingling, numbness or nerve pain

Tell your prescriber or other health care professional about all other medicines you are taking including non-prescription medicines, nutritional supplements, or herbal products. Also, tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medications.

What side effects may I notice from receiving thalidomide?
Side effects that you should report to your prescriber or health care professional as soon as possible:
•irregular menstrual bleeding
•missed menstrual cycle
•new or increased tingling or numbness in hands or feet
•muscle cramps
•rash

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•constipation
•drowsiness
•dizziness
•headache

What do I need to watch for while I receive thalidomide?
Thalidomide causes severe birth defects or death to an unborn child even after just ONE capsule. Both men and women must agree to take precautions against exposure of thalidomide to an unborn child. All patients will receive counseling about the potential birth defects and must agree to follow the conditions outlined in the System for Thalidomide Education and Prescribing Safety (STEPS) Program. The STEPS Program is a program to prevent exposure of thalidomide to an unborn child. The program involves required pregnancy testing, required birth control measures for men and women, doctor and patient education, registration of doctors, pharmacies and patients, and patient consent forms.

You may not donate blood while taking thalidomide. Men are not permitted to donate sperm while taking thalidomide.

Thalidomide causes drowsiness that will decrease as you continue taking the medicine. Be careful driving or operating machinery while taking thalidomide. Take thalidomide at bedtime to decrease this effect.

Thalidomide may cause dizziness. Make sure to sit upright for a few minutes before standing up from a lying or seated position to avoid falling.

You should take a stool softener (docusate) or fiber-product to avoid constipation while taking thalidomide.

Where can I keep my medicine?
Thalidomide may only be prescribed and dispensed by doctors and pharmacies registered in the STEPS program. Pharmacies may only fill a prescription if it is less than 7 days old and may only give you a 28-day supply.

Keep thalidomide out of reach of children and never share this medication with anyone. Return any unused thalidomide to the pharmacy where your prescription was filled. Your pharmacy will accept all unused thalidomide as part of the controlled distribution program.

Do not use beyond the expiration date on the package. Store this medicine at room temperature 59—86ąF (15—30ąC) and protect from light.

NOTE: This information is not intended to cover all possible uses, precautions, interactions, or adverse effects for this drug. If you have questions about the drug(s) you are taking, check with your health care professional.

Costs and Monitoring


Relative Drug Costs
• generic not available

Monitoring Parameters
• pregnancy testing
• CBC

Total Cost of Therapy
• 200 mg PO once daily: $30.00—39.99/day


Product Information

More information about the following products is available:

• THALOMID CAPSULES


References

1876. Thomas S, Kook F, Fang JC. Open label use of thalidomide in adults with HIV-associated wasting (protocol W-002) (abstract 32170). Int Conf AIDS 1998;12:554.

1877. Jacobson JM, Greenspan JS, Spritzler J et al. Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. N Engl J Med 1997;336:1487—93.

1878. Parker PM, Chao N, Nademanee A et al. Thalidomide as salvage therapy for chronic graft-versus-host disease. Blood 1995;86:3604—9.

1879. Klausner JD, Freedman VH, Kaplan G. Short analytical review Thalidomide as an anti-TNF-alpha inhibitor: implications for clinical use. Clin Immunol Immunopathol 1996;81:219—23.

1880. Tracy KJ, Wei H, Manogue KR et al. Cachetin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med 1988;167:1211—27.

1881. Shannon E, Pankey G, Aseffa A et al. Thalidomide enhances production of IL—2 by mononuclear cells of HIV seropositive patients (abstract 165). Program Abstr Intersci Conf Antimicrob Agents Chemother 1996:198.

1882. Moller DR, Wyxocka M, Greenlee BM et al. Inhibition of IL—12 production by thalidomide. J Immunol 1997;159:5157—61.

1883. D'Amato RJ, Loughnan E, Flynn E, et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Assoc Sci 1994;91:4082—85.

1884. Pisctillel SC, Figg WD, Hahn B et al. Single-dose pharmacokinetics of thalidomide in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 1997;41:2797—9.

1885. Broughton BJ, Sheehan TM, Wood J et al. High-performance liquid chromatography assay of plasma thalidomide: stabilization of specimens and determination of tentative therapeutic range for chronic graft-versus-host disease. Ann Clin Biochem 1995;32(pt. 1):79—83.

1886. Yarchoan R, Little RF, Wyvill K et al. A phase II study of oral thalidomide in patients with AIDS-related Kaposi's sarcoma (abstract 22280). Int Conf AIDS 1998;12:318.

1887. Stevens RJ, Andujar C, Edwards J et al. Thalidomide in the treatment of cutaneous manifestations of lupus erythematosus: experience in sixteen consecutive patients. Br J Rheumatol 1997;36:353—9.

1888. Hamza MH. Treatment of Behcet's disease with thalidomide. Clin Rheumatol 1986;5:365—71.

1889. Winklemann RK, Connolly SM, Doyle JA, Padilha-Goncalves A. Thalidomide treatment of prurigo nodularis. Acta Derm Venereol 1984;64:412—7.

1890. Clavaelou P, Colmarino R, D'Incan M et al. Thalidomide-related neuropathy: a prospective, clinical, electromyographical trial. Neurology 1995;45(suppl 4):A168 (26P).

1891. Williams I, Weller IV, Malni J et al. Thalidomide hypersensitivity in AIDS (letter). Lancet 1991:436-7.

1892. Moreira AL, Corral LG, Ye W et al. Thalidomide and thalidomide analogs reduce HIV type 1 replication in human macrophages in vitro. AIDS Res Hum Retroviruses 1997;13:857—63.

1893. Klausner JD, Makonkawkwymoon S, Akarasewi P et al. The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection. J AIDS Hum Retrovir 1996;11:247—57.

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