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
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