Medchem midterm 2 Flashcards
(392 cards)
1
Q
Vincristine Class
A
Antimitotic (M phase specific)- Vinca alkaloid
2
Q
Vincristine Uses
A
Acute leukemia, hodgkin’s lymphoma, non-hodgkins lymphoma, neurosarcoma, Wilm’s tumor.
3
Q
Vincristine Form
A
IV (NO INTRATHECAL)
4
Q
Vincristine Mechanism
A
Binds to microtubules
5
Q
Vincristine Toxicities
A
PERIPHERAL NEUROPATHY, constipation, paresthesis, alopecia, Vesicant.
6
Q
Vincrictine Notes
A
Peripheral neuropathy can be severe. If patient has history of charcot marie foot syndrome, genetic testing may be appropriate. Initially Isolated from a Periwinkle plant
7
Q
Vinblastine Uses
A
Hodgkins Lymphoma, breast cancer
8
Q
Vinblastine Form
A
IV
9
Q
Vinblastine Class
A
Antimitotic (M phase) - vinca alkaloids
10
Q
Vinblastine Mechanism
A
Binds microtubules and changes amino acid metabolism
11
Q
Vinblastine toxicity
A
MYELOSUPPRESSION (leukopenia), leukopenia can be dose limiting. Peripheral neuropathy
12
Q
Vinblastine ADME
A
1/2 life=24 hours, shorter than vincristine. Clearance is hepatic with CYP3A4.
13
Q
Vinblastine Notes
A
Leukocyte count guides dosing
14
Q
Vinorelbine Class
A
Antimitotic (M phase) - vinca alkaloid
15
Q
Vinorelbine use
A
Lung cancer
16
Q
Vinorelbine form
A
IV
17
Q
Vinca alkaloid Notes
A
Light sensitive, intrathecal administration can be fatal
18
Q
Vinorelbine mechanism
A
Binds microtubules, interfere with amino acid and glutathione metabolism, calmodulin-dependent Ca transport, cellular respiration, nucleic acid and lipid biosynthesis
19
Q
Vinorelbine ADME
A
1/2 life=30 hours, hepatic CYP3A4
20
Q
Vinorelbine toxicity
A
Myelosuppression (granulocytopenia), peripheral neuropathy, constipation, paresthesis, alopecia
21
Q
Paclitaxel class
A
Antimitotic (M phase)-taxane
22
Q
Vinorelbine ADME
A
1/2 life=30 hours, hepatic CYP3A4
23
Q
Vinorelbine toxicity
A
Myelosuppression (granulocytopenia), peripheral neuropathy, constipation, paresthesis, alopecia
24
Q
Paclitaxel use
A
Lung, ovarian, breast, prostate
25
Paclitaxel form
IV
26
Paclitaxel formulation
Low aqueous solubility. Mixed with CREMOPHOR/ETHANOL. These components cause infusion complications, can be reduced by premedication.
27
Paclitaxel mechanism
Binds microtubules and over-stabilizes them
28
Paclitaxel toxicity
Myelosuppression, peripheral neuropathy, alopecia
29
Paclitaxel ADME
1/2 life=10-20 hrs depending on dose. Mainly hepatic clearance CYP2C. High binding to albumin
30
Docetaxol Class
Antimitotic (M phase) - Taxane
31
Docetaxol Uses
Lung, breast, prostate, gastric, head and neck
32
Docetaxol Formulation
Low aqueous solubility - formulated in Polysorbate-80/ethanol. Can add infusion complications
33
Docetaxol Mechanism
Binds to microtubules
34
Docetaxol Notes
Purely synthetic material. More potent and toxic than paclitaxel. Binds different part of microtubule so can be used after response to paclitaxel fails.
35
Docetaxol Toxicity
Myelosuppression, hepatotoxicity, peripheral neuropathy, hypersensitivity, alopecia
36
Docetaxol ADME
1/2 life=10-15hrs Clearance mainly hepatic CYP3A4
37
Cabazitaxel Class
Antimitotic (M phase) - taxane
38
Cabazitaxel Uses
Prostate with prednisone for patients already treated with docetaxel.
39
Cabazitaxel Formulation
Low aqueous solubility - formulated in Polysorbate-80/ethanol. Can add infusion complications
40
Cabazitaxel Mechanism
Binds microtubules, more potent than paclitaxel and docitaxel
41
Cabazitaxel Toxicity
Myelosuppression, peripheral neuropathy, hypersensitivity, alopecia
42
Cabazitaxel ADME
Long 1/2 life=95hrs. Clearance hepatic CYP3A4. P-gp doesn't transport it out of the cell as much as Paclitaxel and docetaxel, making it more potent.
43
Ixabepilone Class
Antimitotic (M Phase) - Epothilone
44
Ixabepilone Use
Breast cancer where anthracyclines was not effective.
45
Ixabepilone Formulation
IV, formulated with Cremophor/ethanol. Premedicate
46
Ixabepilone Mechanism
Binds microtubules, different spot than taxanes. Shows antiangiogenic activity
47
Ixabepilone Toxicity
PERIPHERAL NEUROPATHY, myelosuppression, liver toxicity, infusion and allergic reaction (due to formulation)
48
Ixabepilone ADME
Long 1/2 life=50hrs. CYP3A4 clearance
49
Halichondrin Class
Antimitotic (G2/M phase) - Halichondrin
50
Halichondrin Use
Metastatic Breast cancer that has been treated by at least two (taxane and anthracycline) chemo regimens.
51
Halichondrin formulation
Mesylate salt
52
Halichondrin Mechanism
Inhibits growth phase of microtubules (G2/M specific)
53
Halichondrin Toxicity
Myelosuppression (Neutropenia), peripheral neuropathy, alopecia, nausea, constipation. QT prolongation
54
Neutrophil Nadir
The nadir (low point) of neutrophil counts occurs 7-14 days after dosing chemo. It can take 2-3 weeks for neutrophil counts to return to normal. Hence a q3weeks dosing schedule.
55
Irinotecan Class
Topo I inhibitor - Camptothecin
56
Irinotecan Use
Colorectal (part of FOLFIRI)
57
Irinotecan Formulation
IV, contains tertiary amine and is formulated as the HCL salt
58
Irinotecan Mechanism
Prodrug of SN-38, prodrug is soluble, SN-38 is insoluable. SN-38 lactone has closed ring and is active, SN-38 carboxylate has open ring and is inactive. The enzymes necessary to convert the prodrug are in higher concentration in tumor cells.
59
Irinotecan Toxicity
Myelosuppression (neutropenia), SEVERE/UNPREDICTABLE DIARRHEA and neutropenia can cause sepsis and death. Early diarrhea caused by cholinergic symptoms and can be treated with atropine. Late diarrhea cause is unknown but loperimide can help.
60
Irinotecan ADME
1/2 life=10hrs; 1/2 life of SN-38=10-20hrs. metabolism through hydrolysis of Irinotecan by carboxylesterases and clucuronidation of SN-38
61
Irinotecan Polymorphism
10-15% of Caucasians and African Americans are homozygous for a polymorphism that expresses low levels of enzyme and as a result they glucuronidate SN-38 poorly.
62
Topotecan Class
Topo I inhibitor
63
Topotecan Uses
Lung and ovarian
64
Topotecan Formulation
IV and PO. Contains a tertiary amine so formulated as HCl salt. Not a prodrug, but not as effective as irinotecan.
65
Topotecan Mechanism
Binds directly to Topo I enzyme. Drug interactions are not an issue
66
Topotecan Toxicity
Myelosuppression (leukopenia, neutropenia), thrombocytopenia, diarrhea (not as bad as irinotecan), N/V. Dose adjusted according to AUC. Direct correlation between AUC and leukopenia
67
Topotecan ADME
1/2 life=3 hrs. Renal excretion
68
Topotecan Oral Bioavailability
only 40%. However, if dosed with cyclosporine A, can increase AUC 2-3 fold
69
Doxorubicin Class
Topo II inhibitor - Anthracyclines
70
Doxorubicin Uses
Many uses, leukemias, soft tissue and bone sarcomas, Wilm's tumor, neuroblastoma, breast, ovarian, bladder, thyroid, gastric cancers. Hodgkin's lymphoma
71
Doxorubicin Form
IV (light sensitive)
72
Doxorubicin Mechanism
Intercalates into DNA and inhibits Topo II. Also generates reactive oxygen species
73
Doxorubicin Toxicity
Myelosuppression, CARDIOTOXICITY (believed to be caused by the reactive oxygen species formed). Maximum of 300mg/m2 over a person's lifetime.
74
Doxorubicin ADME
Quick distribution, slow elimination 1/2 life=30-40 hrs. Reduction of 7 position along with hydrolytic removal of the aminoglycone are major routes of metabolism. These metabolites are active and can contribute to cardiotoxicity. Another mechanism of cardiotoxicity involves rubicinol metabolite and its perturbation of Ca2+ channels in the heart
75
Daunorubicin Class
Topo II inhibitor - anthracycline
76
Daunorubicin Use
Leukemias
77
Daunorubicin Form
IV
78
Daunorubicin Mechanism
Intercalates into DNA inhibits topo II, generate reactive oxygen species
79
Daunorubicin Toxicity
Less toxic than doxorubicin, however cardiotoxicity is more of a problem. Max dose of 450 mg/m2 per lifetime. Secondary AML or MDS can occur several laters. Vesicant
80
Daunorubicin ADME
distributes quickly and slow elimination 1/2 life=20 hrs. Rubicinol metabolite occurs faster so it is more cardiotoxic than doxo
81
Idarubicin Class
Topo II inhibitor - anthracycline
82
Idarubicin Uses
Acute myeloid leukemia, breast cancer
83
Idarubicin Form
IV
84
Idarubicin Mechanism
Intercalates into DNA and inhibits Topo II. Generates reactive oxygen species
85
Idarubicin Toxicity
CARDIOTOXICITY, same toxicities as daunorubicin
86
Idarubicin ADME
Similar to other anthracyclines
87
Idarubicin Notes
lack of methoxy group relative to doxo and dauno makes it even more lipophilic and able to penetrate tissue faster, making it more effective.
88
Etoposide Class
Topo II inhibitor - Podophyllotoxin
89
Etoposide Uses
First line small cell lung cancer. Sarcomas, testicular cancer, lymphomas, leukemia, brain cancer.
90
Etoposide Form
IV or PO
91
Etoposide Mechanism
Binds to topo II. Does not possess quinone moiety, therefore no reactive oxygen species and no cardiotoxicity
92
Etoposide Toxicity
HYPOTENSION if given IV too quickly. Drink plenty of water to avoid renal and bladder toxicity.
93
Etoposide ADME
1/2 life=5-10 hrs. Excreted in feces and urine. Renal clearance is correlated with creatinine clearance, useful in dose adjustment.
94
Teniposide Class
Topo II inhibitor - Podophyllotoxin
95
Teniposide Use
Childhood acute lymphoblastic leukemia.
96
Teniposide Formulation
IV only. Formulatred in Cremophor/ethanol.
97
Teniposide mechanism
binds to topo II
98
Teniposide ADME
1/2 life=10 hrs. Less polar than etoposide = less renal excretion
99
Dactinomycin Class
Macrolide antibiotic
100
Dactinomycin Uses
Wilm's tumor, sarcomas
101
Dactinomycin Form
IV, very potent mcg/kg
102
Dactinomycin Mechanism
Intercalates into DNA very well, dissociates from DNA slowly. Can bind irreversibly through quinone system. Interferes with the transcription of DNA in mRNA; can also
form some reactive oxygen species (ROS) and is a substrate of P450 reductase
103
Dactinomycin Toxicities
Myelosuppression, hepatotoxicity, fatigue, infection*, local inflammation if extravasation
occurs, rare but veno occlusion disease can occur; also N/V can be severe and dose limiting.
104
Dactinomycin ADME
Long t1/2 due to minimal metabolic breakdown
105
Dactinomycin Note
Because dactinomycin is
also a bacterial antibiotic, it can interfere with diagnostic assays used to identify the bacteria causing
an infection
106
Mitomycin Class
Macrolide antibiotic
107
Mitomycin Use
Gastric cancer, pancreatic cancer. Administered IV. Also, intravesically for bladder cancer
108
Mitomycin Mechanism
Possibly like other macrolide antibiotics, intercalates into DNA, and can bind irreversibly
through quinone system. Interferes with the transcription of DNA in mRNA. Can be activated by P450
reductase and NADPH quinone oxidoreductase (NQO1) and for ROS. Also substrate of thioredoxin
reductase
109
Mitomycin Notes
presence of aziridine in the molecule. Thus, recent
research has shown that mitomycin need not enter the nuclease and can also inhibit cytosolic
ribosomal (rRNA). This can cause inhibition of all (genome wide) translational silencing. This could be
the most important mechanism.
110
Mitomycin Toxicities
Myelosuppression, renal toxicity, pulmonary toxicity, mucositis, alopecia; rare but serious
cardiotoxicity.* *Cardiotoxicity almost always in association with previous anthracycline use. Remember the
important cardiotoxicity of the anthracyclines (daunorubicin, doxorubicin, idarubicin).
111
Mitomycin ADME
Metabolism is hepatic and extrahepatic; renal excretion of parent and metabolites is important
and about 10% of parent drug excreted renally. Metabolism routes are easily saturated and clearance
of the agent is inversely proportional to dose
112
Bleomycin Class
Macrolide Antibiotic
113
Bleomycin Uses
Hodgkin’s lymphoma as component in ABVD (adriamycin/bleomycin/vinblastine/dacarbazine)
regimen, NHL, squamous head and neck cancer, testicular cancer.
114
Bleomycin Mechanism
Intercalates into DNA, then binds DNA covalently. Importantly, the agent also binds Fe
++
and chelate in vivo and leads to generation of reactive oxygen species
115
Bleomycin Toxicities
Neutropenia, thrombocytopenia, pulmonary toxicity.* Myelosuppression is mild. Allergic
reaction can occur (rarely) but can lead to analphylaxis.
116
Bleomycin ADME
Important inactivating enzyme (bleomycin hydrase); hydrolysis of terminal amide leads to the
inactive carboxylate metabolite (change in pKa of amine from 7.3 to 9.4) alters binding to DNA in a
major way; low levels of this enzyme in skin and lung tissues. Renal impairment increase 1/2 life from 2-4 hours to over 20 hrs
117
Bleomycin Notes
Pulmonary toxicity is perhaps the most serious complication of bleomycin
118
Thalidomide Class
Immunomodulator
119
Thalidomide Uses
Multiple myeloma
120
Thalidomide Mechanism
An immunomodulator and can increase in the number of circulating natural killer cells,
and increase plasma levels of interleukin-2 and interferon-gamma. Both these cytokines are associated
with cytotoxic activity. Thalidomide also possesses anti-inflammatory and antiangiogenic properties
121
Thalidomide Toxicities
Teratogenic, DVT, peripheral neuropathy, sedation, constipation
122
Thalidomide ADME
Spontaneously hydrolyses in vivo to multiple “metabolites”; also a substrate of CYP2C19 so
potential PM concern
123
Lenolinamide Class
Immunomodulator
124
Lenolinamide Uses
Multiple Myeloma
125
Lenolinamide Mechanism
A direct anti-tumor effect by inhibition of the
microenvironment support for tumor cells, an immunomodulatory role like thalidomide, induces tumor
cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, anti-angiogenic
and anti-osteoclastogenic effects. Nearly 10-fold more potent than thalidomide
126
Lenolinamide Toxicities
Myelosuppression can be severe and dose limiting. Teratogenic, DVT.
127
Lenolinamide ADME
Much less breakdown compared to thalidomide; about 2/3 of the drug is excreted in the urine.
Lenolinamide is not a substrate or an inducer of CYP450 enzymes
128
Initial steroids formed from cholesterol
Pregnenolones and progesterones
129
Progestins are converted to...
Androgens
129
Androgens are converted to...
Estrogens
130
Most potent androgens and estrogens?
Androgens: testosterone and dihydrotestosterone
Estrogens: Estradiol
130
Hypothalamus secretes GnRH which acts on pituitary to release...?
LH or FSH
131
LH and FSH stimulate cells in testes and ovaries to produce...?
Androgens and estrogens.
131
Degarelix Class
Gonadotropin antagonist
132
Degarelix Uses
Prostate cancer
132
Degarelix Mechanism
A gonadotropin receptor antagonist and blocks release of luteinizing hormone (LH)* and
follicle stimulating hormone (FSH) from the pituitary. A form of chemical castration
133
Degarelix Toxicities
Hot flushes, headache, nausea, weight gain.
133
Degarelix ADME
Because the agent is a peptide (synthetic) it is metabolized by amino acid peptidases
134
LH acts on which cells in males to produce testosterone?
Leydig Cells
134
Flutamide Class
androgen receptor antagonist
135
Flutamide Uses
Hormone dependent prostate cancer (early stage); some rare cases of androgen dependent
breast cancer
135
Flutamide Form
PO
136
Flutamide Mechanism
Binds directly to the androgen receptor and prevents the binding of endogenous
androgens (testosterone and dihydrotestosterone); also, when it binds to the AR it binds in an
“antagonist” way so there is reduced translocation to the nucleus
136
Flutamide Toxicities
Gynecomastia; liver toxicity* that can be severe – has led to death
137
Flutamide ADME
Good absorption and major metabolite (α-hydroxy) which is active is formed mainly by CYP1A2;
potential interaction by CYP1A2 inhibitor (ketoconazole) or inducers; because of the short t1/2 of
flutamide (~ 9 hrs) it must be dosed q.i.d. (4 x 250 mg)
137
Nilutamide Class
androgen receptor antagonist
138
Nilutamide Uses
Hormone dependent prostate cancer (early stage); some rare cases of androgen dependent
breast cancer
138
Nilutamide Form
PO
139
Nilutamide Mechanism
Binds directly to the androgen receptor and prevents the binding of endogenous
androgens (testosterone and dihydrotestosterone); also, when it binds to the AR it binds in an
“antagonist” way so there is reduced translocation to the nucleus
139
Nilutamide Toxicities
Interstitial pneumonitis*, some liver toxicity but less than flutamide
140
Nilutamide ADME
Extensively metabolized by the liver by several P450 enzymes; overall hepatic impairment can
lead to high levels and toxicity of nilutamide; t1/2 of 50-60 hrs; dosed daily (250 mg).
141
Nilutamide Notes
More potent than flutamide
142
Bicalutamide Class
androgen receceptor antagonist
143
Bicalutamide Uses
Hormone dependent prostate cancer (early stage); some rare cases of androgen dependent
breast cancer
144
Bicalutamide Mechanism
Binds directly to the androgen receptor and prevents the binding of endogenous
androgens (testosterone and dihydrotestosterone); also, when it binds to the AR it binds in an
“antagonist” way so there is reduced translocation to the nucleus. Also some data suggest
bicalutamide can cause some decrease in levels of the AR (mechanism unknown)
145
Bicalutamide Toxicities
Liver and lung toxicity less severe than flutamide and nilutamide.
146
MDV3100 Class
Antiandrogen receptor antagonist
147
MDV3100 Uses
Metastatic, castrate resistant prostate cancer
148
MDV3100 Mechanism
Binds directly to the androgen receptor but in an “antagonist” manner so that it does not
cause efficient translocation of the AR into the nucleus. However, the AR which does get translocated
does not interact correctly with the response elements of DNA for proper transcription of mRNA. Also
causes decrease in levels of the AR
149
MDV3100 Toxicities
Well tolerated
150
MDV3100 ADME
Good absorption and CYP2C8 and CYP3A4 primarily responsible for its metabolism; active
metabolite (N-desmethyl) formed by CYP2C8. Long t1/2 of about 6 days and about 8 days for the active
metabolite
151
Castrate Resistant Prostate Cancer
used to describe patients who have low
“castrate levels” of endogenous androgens, yet their tumors continue to grow by support of the low
levels of androgens. The explanation for this phenomenon is that the tumors themselves produce the
androgens and the generation by the testes is no longer necessary.
152
Ketoconazole Class
Androgen synthesis inhibitors
153
Ketoconazole Uses
Exploratory agent for hormone dependent prostate cancer and castrate resistant prostate
cancer
154
Ketoconazole Form
PO
155
Ketoconazole Mechanism
inhibitor of cytochrome P450 C17-hydroxylase/17,20-lyase, also called
CYP17A1
156
Ketoconazole Toxicities
Liver toxicity with chronic use
157
Abiraterone acetate class
androgen synthesis inhibitor
158
Abiraterone use
Metastatic, castrate resistant prostate cancer
159
Abiraterone Mechanism
An acetate prodrug; hydrolysis to abiraterone can occur in the plasma and liver.
Abiraterone (not the prodrug form) binds to CYP17A1 and irreversible inactivates the enzyme. The
enzyme cannot be reactivated; new enzyme must be biosynthesized
160
Abiraterone Toxicities
Hypertension
161
Abiraterone ADME
*Although dosed PO, the bioavailability of this drug is very low (<10%) and it has a positive
“food effect”. When taken with a meal, the Cmax and AUC can increase more than 10-fold. This issue
can be serious if a patient ignores the dosing directions repetitively. Hypertension can lead to heart
failure, especially in elderly men with compromised heart function
162
Abiraterone Form
PO daily with food
163
Tamoxifen Class
ER antagonist
164
Tamoxifen Uses
ER positive breast cancer (early stage)
165
Tamoxifen Mechanism
Binds directly to the ER and prevents the binding of endogenous estrogens (mainly
estradiol); binds to the ER it binds in an “antagonist” way, so there is reduced translocation to the
nucleus. The ER-tamoxifen complex that enters the nucleus does not lead to proper transcription of
genes in DNA
166
Tamoxifen Toxicities
Thromboembolism, steatosis type hepatitis (fatty liver); and tamoxifen is a partial estrogen
agonist in the endometrium so it can promote endometrial cancer which can appear years later. Some
QT prolongation that might occur only with CYP3A4 inhibitors
167
Tamoxifen ADME
4-Hydroxy-Ndesmethyltamoxifen (endoxifen) is a very active metabolite generated by CYP3A4/5 and CYP2D6; therefore
it is susceptible to the CYP2D6 polymorphism and drug-drug interaction issues (e.g. with
antidepressants that are also metabolized by CYP2D6)
168
Toremifene Class
ER antagonist
169
Toremifene Use
ER positive in metastatic breast cancer
170
Toremifene Mechanism
Binds directly to the estrogen receptor and prevents the binding of endogenous estrogens
(mainly estradiol); when it binds to the ER it binds in “antagonist” and “agonist” ways so its
pharmacology is complex. The ER-toremifene complex that enters the nucleus does not lead to proper
transcription of DNA
171
Toremifene Toxicities
QT prolongation, cardiac failure, hot flashes, arthralgia, cataracts after chronic use.
172
Toremifene ADME
t1/2 of about 5 days and partly due to enterohepatic recycling; extensively
metabolized by CYP3A4 to less active N-desmethyl metabolite; use of agents that are strong CYP3A4
inhibitors should be avoided. Not as much 4-hydroxy metabolite formed as for tamoxifen
173
Fulvestrant Class
ER antagonist
174
Fulvestrant Use
ER positive metastatic breast cancer; also for patients with disease progression following prior
antiestrogen therapy.
175
Fulvestrant Mechanism
: ER antagonist as above but also causes down-regulation of the ER, along with some
destruction of the ER
176
Fulvestrant Toxicities
Generally well tolerated but nausea and asthenia; lower rate of arthralgias than preceding
antiestrogens
177
Fulvestrant ADME
Fulvestrant is metabolized in the liver by CYP3A4 but not extensively. No drug interactions
appear to exist with fulvestrant.
178
Enzyme responsible for synthesis of estrogens from androgens
CYP19A1
179
Exemestane Class
Estrogen Synthesis inhibitor
180
Exemestane Use
ER positive breast cancer (both adjuvant setting and later stage); also most commonly used post
tamoxifen; for postmenapausal women only
181
Exemestane Form
PO
182
Exemestane Mechanism
Steroidal inhibitor of CYP19A1 (aromatase) and irreversibly inhibits (kills) the enzyme.
Such an inhibitor is also called a suicide inhibitor because the enzyme attempts to convert it to an
estrogen but the enzyme is killed in the process. *Exemestane mainly inhibits non-ovarian aromatase
(adrenals, adipose tissue, cancer tissues) therefore not to be used for premenapausal women
183
Exemestane Toxicities
Hot flushes, fatigue, arthralgia, insomnia. Because the agent lowers estrogen levels
dramatically, bone density can decrease and lead to osteoporosis over extended use..
184
Exemestane ADME
metabolized mainly by CYP3A4
185
Anastrozole Class
Estrogen Synthesis Inhibitor
186
Anastrozole Uses
ER positive breast cancer (both adjuvant setting and later stage); for postmenapausal women
only
187
Anastrozole Form
PO
188
Anastrozole Mechanism
Non-steroidal inhibitor of CYP19A1 (aromatase) and reversibly inhibits the enzyme.
Anastrozole outcompetes with endogenous androgens for the aromatase enzyme. Anastrozole
preferentially inhibits non-ovarian aromatase (adrenals, adipose tissue, cancer tissues) therefore not to
be used for premenapausal women.* More potent than exemestane.
189
Anastrozole Toxicities
Bone density loss appears more extreme than for tamoxifen. Generally well tolerated but
hot flushes, fatigue, arthralgia, insomnia. Anastrozole lowers estrogen levels quite effectively, so bone
density can decrease and lead to osteoporosis over extended use. Estradiol inhibits osteoclasts which
resorb bone; less estradiol allows for more bone resorption by the osteoclasts
190
Anastrozole ADME
Absorption is rapid and good; metabolism of anastrozole occurs by several P450 enzumes to Ndealkyl and hydroxyl metabolites. Glucuronidation also occurs and excretion is mainly fecal..
191
Anastrozole Note
Because it is non-steroidal, it avoids some off target effects of exemestane
192
Letrazole Class
Estrogen Synthesis Inhibitor
193
Letrazole Uses
ER positive breast cancer (both adjuvant setting and later stage); also commonly used post
tamoxifen; for postmenapausal women only
194
Letrazole Form
PO
195
Letrazole Mechanism
Selective for aromatase and very potent. Non-steroidal inhibitor of CYP19A1 (aromatase)
and reversibly inhibits the enzyme. *Letrazole can inhibit ovarian and non-ovarian aromatase
(adrenals, adipose tissue, cancer tissues).
196
Letrazole Toxicities
Because the agent lowers estrogen levels dramatically, bone density can decrease and lead
to osteoporosis over extended use; arthralgia, and cases of myocardial infarction, but rare (non-QT).
197
Letrazole ADME
Absorbed well; metabolized mainly by the liver especially CYP3A4. The dose of this agent
should be reduced to 50% if severe cirrhosis or liver dysfunction is present.
198
Prednisone Class
Glucocorticoid
199
Prednisone Use
Many types of cancer; has some anti-cancer properties in combination with other agents agent in
some leukemias and multiple myeloma; also aids in comfort, and anti-emetic; seldom used alone.
Administered PO. Dosage levels are variable and depend on the disease being treated as well as the
condition of the patient
200
Prednisone Mechanism
Binds to glucocorticoid receptor. Has many effects but in oncology mainly used for its antiinflammatory and immunosuppressant effects.
201
Prednisone Toxicities
Fluid retention, congestive heart failure, hypertension
202
Tyrosine Kinase Inhibitors
Independent of cell cycle, cytostatic, use phosphorylation
203
Imatinib Class
TKI
204
Imatinib Use
Mainly Ph+ chronic myelogenous leukemia (CML), Ph+ acute lymphocytic leukemia (ALL); also cKit+ cancers of gastrointestinal stromal tissue (GIST). resistance to imatinib can develop somewhat quickly
205
Imatinib Mechanism
targets several tyrosine kinases (esp. bcr-abl, c-kit). The abl gene encodes the
actual TK activity
206
Imatinib Notes
important mutation (T315-I) in the abl gene can exist which causes resistance to imatinib. This mutation prevents access of imatinib to the ATP binding site
207
Imatinib Toxicities
some possible QT prolongation
208
Imatinib ADME
main metabolite (N-desmethyl) is formed by CYP3A4
209
Nilotinib Class
TKI
210
Nilotinib Use
: Ph+ leukemias but after resistance to imatinib has developed
211
Nilotinib Mechanism
targets several tyrosine kinases (esp. bcr-abl, c-kit). About 30-50 times more potent than imatinib. Not active against tumors with the T315-I mutation
212
Nilotinib Toxicities
QT prolongation
213
Nilotinib ADME
Not active against tumors with the T315-I mutation
214
Dasatinib Class
TKI
215
Dasatinib Use
Ph+ leukemias but after resistance to imatinib has developed
216
Dasatinib Mechanism
targets several tyrosine kinases (esp. bcr-abl, c-kit). Also more potent than imatinib and nilotinib against both resistant bcr-abl TK and
non-resistant bcr-abl TK. About 300 times more potent than imatinib for bcr-abl TK. Not active against
tumors with the T315-I mutation
217
Dasatinib Toxicities
QT prolongation
218
Dasatinib ADME
CYP3A4 is the primary enzyme responsible
metabolism. Imatinib can also cause a small amount of
irreversible inhibition of CYP3A4
219
Bosutinib Class
TKI
220
Bosutinib Use
Ph+ leukemias after resistance to imatinib and dasatinib has developed. Still not effective for
tumors with the T315-1 mutation
221
Bosutinib Toxicities
No QT prolongation
222
Gefitinib Class
TKI
223
Gefitinib Use
Advanced or metastatic non-small cell lung cancer after platinum and docetaxel therapy. Later survival studies did not show benefit. Also,
lack of activity in many patients (yet still toxic) led to more restricted use; now withdrawn
224
Gefitinib Mechanism
Inhibits the intracellular TK linked to the epidermal growth factor receptor (EGFR
225
Gefitinib Toxicities
Interstitial pneumonitis. CYP1A1 in lung can generate reactive quinone imine metabolites. *Smokers can generate much more
of the reactive metabolites
226
Gefitinib ADME
metabolized extensively by the liver and mainly by CYP2D6 and CYP3A4
227
Gefitinib Notes
Mutations is EGFR tend to be activating, thus greater TK activity. These mutations tend to be
more common in Asians, women, and non-smokers
228
Erlotinib Class
TKI
229
Erlotinib Uses
Like gefitinib for advanced or metastatic non-small cell lung cancer after platinum and docetaxel
therapy
230
Erlotinib Mechanism
Inhibits the intracellular TK linked to the epidermal growth factor receptor (EGFR)
231
Erlotinib Toxcities
lung toxicity* and some liver toxicity
232
Erlotinib ADME
Erlotinib is metabolized extensively by the liver and mainly by
CYP3A4 and CYP1A1/2
233
Sorafenib Class
TKI
234
Sorafenib Uses
Liver cancer and renal cell carcinoma.
235
Sorafenib Mechanism
Inhibits multiple intracellular cell surface TKs (c-KIT, FLT-3, RET, VEGFR-1, VEGFR-2, VEGFR-
3, and PDGFR-ß) and RAF TKs (CRAF, BRAF and mutant BRAF)
236
Sorafenib Toxicities
QT prolongation
237
Sorafenib ADME
s. Sorafenib is metabolized extensively by
CYP3A4 so drug interactions are possible. sorafenib can competitively inhibit
(moderately) CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4.
238
Sorafenib Notes
It has been proposed that the numerous but rare toxicities caused by sorafenib are due to the
multiple TKs that sorafenib inhibits
239
Sunitinib Class
TKI
240
Suntitinib Uses
Renal cell carcinoma
241
Suntitinib Mechanism
multiple cell surface TKs (PDGF-R, VEGF-R, c-KIT, RET, FLT-3, CSF-1R). Some of
these TKs are known to be important in renal cell cancer signaling (e.g. VEGF-R, RET)
242
Suntitinib Toxicities
rare but
| possible severe hepatotoxicity that has caused deaths. also QT prolongation.
243
Suntitinib ADME
The elimination t1/2 of sunitinib is about 50 hrs, while that of the
active metabolite is about 100 hrs
244
Suntitinib Notes
in spite of targeting many TKs, sunitinib has failed in several late stage trials for
cancers such as breast, colorectal, non-small cell lung, and prostate cancer.
245
Axitinib Uses
Renal cell carcinoma that has become resistant to other agents
246
Axitinib Mechanism
Inhibits several VEGF TK enzymes including VEGFR-1, VEGFR-2, VEGFR-3, PDGFR. Note that
this agent is more specific than sunitinib
247
Axitinib Toxicities
no apparent QT prolongation.
248
Axitinib Class
TKI
249
Axtomob ADE
The elimination t1/2 is short and ranges from 3-6 hrs
250
Lapatinib Class
TKI
251
Lapatinib Uses
: Advanced breast cancer in combination with capecitabine for patients with HER2+ breast cancer;
also in combination with letrazole for postmenapausal patients that have ER+ and HER2+ breast cancer
252
Lapatinib Mechanism
: A dual inhibitor and targets EGFR-1 and HER2/neu TKs
253
Lapatinib Toxicities
QT prolongation; rare but potentially serious
| hepatotoxicity*
254
Temsirolimus Class
mTOR
255
Temsirolimus Uses
: Renal cell carcinoma (RCC).Formulated in ethanol/vitamin E/ polyethylene
glycol which can cause allergic reactions
256
Temsirolimus Mechanism
Inhibitor of the kinase of mTOR. This kinase is actually a serine-threonine kinase.In RCC, the mTOR signaling was well established as an important pathway,
therefore the development of temsirolimus was rationally driven.
257
Temsirolimus ADME
Temsirolimus is metabolized extensively by CYP3A4 and a good substrate for the efflux
transported Pgp
258
Everolimus Class
mTOR
259
Everolimus Uses
RCC but after failure of sorafenib or sunitinib;
260
Everolimus Mechanism
: Inhibitor of the kinase of mTOR (mTOR1 specifically). This kinase is actually a serinethreonine kinase
261
Everolimus P13K
tend to be serine/threonine kinases which specifically
| phophorylate serine or threonine residues.
262
Everolimus LY2904002
serine/threonine-protein kinase. There are 500+ protein kinases in humans, and so far about 125 of these are serine/threonine
kinases.
263
Perifosine Class
mTOR; It acts as an Akt inhibitor and a PI3K inhibitor.
264
CAL101 Class
mTOR; A P13K inhibitor
265
Vorinostat Class
HDAC
266
Vorinostat Uses
Cutaneous T-cell lymphoma
267
Vorinostat Mechanism
Vorinostat inhibits the enzymatic activity of histone deacetylases (HDACs). HDAC1, HDAC2
and HDAC3 and HDAC6 are inhibited at nanomolar concentrations.
268
Vorinostat Toxicities
rare but potentially serious pulmonary
| embolism and anemia
269
Vorinostat ADME
Major pathway of metabolism involve glucuronidation of vorinostat. CYP enzymes do not play a large role in the metabolism of vorinostat.
270
Vorinostat Notes
The anticonvulsant valproic acid (VPA) is a weak HDAC inhibitor and is also glucuronidated.
There can be severe thrombocytopenia and/or GI bleeding if vorinostat is administered with VPA, due
to competition for glucuronidation.
271
Bortezomib Class
Protezome inhibitors
272
Bortezomib Uses
Multiple myeloma and mantle cell lymphoma.
273
Bortezomib Mechanism
: Inhibit the action of proteasomes; bortezomib causes accumulation of damaged proteins
which signals for an increase in apoptosis. For unknown reasons, multiple myeloma and mantle cell
lymphoma cells are more sensitive to proteosome inhibition than normal cells.
274
Bortezomib ADME
: Multiple CYP enzymes participate in the metabolism of bortezomib; drug interactions are not
expected except for strong inducers (e.g. rifampin, phenytoin) or strong inhibitors (e.g. ketoconazole,
ritonavir) are co-administered.
275
Carfilzomib Class
Protezome inhibitors
276
Carfilzomib Uses
Multiple myeloma. Formulation includes
| sulfobutylether β- cyclodextrin.
277
Carfilzomib Mechanism
Irreversibly binds to and
| inhibits the chymotrypsin-like activity of the 20S proteasome.
278
Carfilzomib Toxicities
Quite toxic; sudden cardiac arrest;
279
Carfilzomib ADME
High renal excretion; very short t1/2 of 1 hr or shorter; rapidly and extensively metabolized into
peptide fragments and the diol of carfilzomib, CYP enzymes play only minor role in overall
metabolism; metabolites have no known biologic activity.
280
Rituximab Class
naked antibodies
281
Rituximab Uses
: Refractory B-cell non-Hodgkin’s lymphoma; greater than 90% of B-cell NHL have the CD20
antigen. also for CD20+ CLL. CD20 is called the B-cell antigen.
282
Rituximab Mechanism
chimeric antibody. CD20 antigens
283
Rituximab Toxicities
Potential severe immune/allergic reactions, severe mucotaneous reactions, tumor lysis
syndrome, progressive multifocal leukoencephalopathy (PML)* (all in black box warning).
284
Rituximab Notes
*Immunodeficiency or immunosuppression allows JCV (John Cunningham virus) to reactivate.
In the brain it causes the usually fatal PML by destroying oligodendrocytes. JC virus is very common in
the human population (70-90% of humans have it).
285
Trastuzumab Class
naked antibodies
286
Trastuzumab Uses
Breast cancer but only if HER2+, in combination with chemotherapy. The over-expression of this HER2 protein occurs in nearly 30% of breast
cancer patients. gastric cancer
287
Trastuzumab Toxicities
Immune/allergic reactions, pulmonary edema, cardiotoxicity (all in black box warning).
288
Alemtuzumab Class
naked antibodies
289
Aletuzumab Uses
Chronic lymphocytic leukemia (B-cell) as a single agent for previously untreated patients.
290
Alemtuzumab Toxicities
Severe immune/allergic reactions, severe myelosuppression, serious infections* (all in black
box warning).
291
Alemtuzumab Notes
In addition to premedicating for immune reactions, important to premedicate with antibiotics
to prevent infections* (e.g. trimethoprim/sulfamethoxazole for Pneumocystis carinii pneumonia (PCP).
292
Cetuximab Class
naked antibodies
293
Cetuximab Uses
r metastatic colorectal cancer (CRC) with FOLFIRI but only for KRAS mutation negative; locally or regionally advanced squamous cell cancer of the head and neck in
combination with 5-FU and platinum or with radiation.
294
Cetuximab Mechanism
binds to EGFR-1 on cell surface. KRAS signaling
is downstream (internal in the cell) and mutations in KRAS cause activation of signaling independent of
EGFR-1 signaling which occurs at the cell surface.
295
Cetuximab Toxicities
Severe immune/allergic reactions, cardiopulmonary arrest (black box warnings)
296
Cetuximab Notes
Martha Stewart (insider trading)
297
Bevacizumab Class
naked antibodies
298
bevacizumab Uses
Colorectal cancer in combination with 5-FU based therapy (FOLFOX or FOLFIRI); non squamous
non-small cell lung cancer in combination with carboplatin and paclitaxel; glioblastoma as a single
agent
299
Bevacizumab Mechanism
binds to vascular endothelial growth factor (VEGF), which is the
ligand that binds to the vascular endothelial growth receptor (VEGF-R2).
300
Bevacizumab Toxicities
Bleeding, GI perforations, stroke; cardiotoxicity especially with anthracyclines (all black box).
301
Panitumbumab Class
naked antibodies
302
Panitumumab Uses
: Similar to cetuximab; for metastatic CRC, but as a single agent for the treatment of epidermal
growth factor receptor (EGFR-1) expressing tumors*, with disease progression on or following
fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens (i.e. FOLFOX or
FOLFIRI).
303
Panitumumab Toxicities
: Similar to cetuximab; still high incidence of dermatologic toxicity (rash) and immune/allergic
reactions (black box warning).
304
Panitumumab Notes
Panitumumab is not to be used for treatment of patients with KRAS mutation-positive mCRC
or for whom KRAS mCRC status is unknown. KRAS signaling is downstream (internal in the cell) and
mutations in KRAS cause activation of signaling independent of EGFR-1 signaling
305
Ofatumumab Class
naked antibodies
306
Ofatumumab Uses
: Chronic lymphocytic leukemia (B-cell) that is refractory to fludarabine and alemtuzumab
307
Ofatumumab Mechanism
binds specifically to the loop regions of the CD20
308
Ofatumumab Toxicities
```
Immune/allergic reactions (no black box)*; cytopenias (esp. neutropenia), progressive
multifocal leukoencephalopathy (PML), pneumonia, hepatitis B reactivation**
```
309
Ofatumumab Notes
* Infusion reactions less since humanized and they tend to decrease with continued dosing;
* *infections are actually quite common and can be of bacterial, viral, or fungal origin.
310
Ipilumumab Class
naked anitbodies
311
Ipilumumab Uses
Metastatic melanoma, unresectable. Useful as single agent.
312
Ipilumumab Mechanism
```
binds to the cytotoxic T-lymphocyte-associated
antigen 4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation.This enhances the immune response.
```
313
Ipilumumab Toxicities
Severe and potentially fatal immune/allergic reactions due to T-cell activation (black box
warning)
314
Ipilumumab Notes
*CTLA-4 is the T-cell “off switch”, while CD28 is the “on switch”. **Good example of high
clinical hurdle, so lower regulatory hurdle.
315
Pertuzumab Class
naked antibodies
316
Pertuzumab Uses
Breast cancer but only if HER2+, in combination with trastuzumab (Herceptin) and docetaxel.
317
Pertuzumab Mechanism
t binds specifically to the cell surface receptor HER2 similar to
trastuzumab but specifically at the dimerization domain
318
Pertuzumab Notes
Approval based on comparison trial that showed pertuzumab + trastuzumab + docetaxel was
more efficacious based on progression free survival (PFS) than placebo + trastuzumab + docetaxel.
319
Ibritumomab Class
Antibody conjugates
320
Ibritumomab Uses
: Relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL); previously
untreated follicular NHL. Complicated procedure for use.*
321
Ibritumomab Mechanism
: Same antibody as in Rituxan that targets the CD20 antigen but conjugated to a
radioisotope, Yttrium 90. ) so short lived. Remember that antibodies that target proteins or
receptors on cell surfaces are internalized.
322
Ibritumomab Toxicities
: Serious immune/allergic reactions, severe and prolonged cytopenias, and severe cutaneous
reactions (all black box).
323
Ibritumomab Notes
The therapeutic use of Zevalin actually includes the use of Rituximab first (Day 1). Rituximab
is again on Day 7 and then followed by Zevalin 4 hrs later. **Because t1/2 of isotope is so short it is
important to calculate/confirm the radiochemical purity of the dose given.
324
Tositumomab Class
Antibody conjugates
325
Tositumomab Uses
: Refractory B-cell non-Hodgkin’s lymphoma after relapse following treatment with rituximab.
Note: Given in 2-step procedure involving a (1) dosimetric dose and a (2) therapeutic dose. The
dosimetric dose is given to assess biodistribution and tumor burden in the body, as well as subsequent
drop in platelet counts. Then based on information from the dosimetric dose, the therapeutic dose is
calculated and administered.
326
Tositumomab Mechanism
Mouse antibody that targets CD20 antigen, so similar conjugate as Rituxan and Zevalin but
incorporates different radioisotope (iodine 131;
327
Tositumomab Toxicities
: Severe immune/allergic reactions, severe cytopenias (thrombocytopenia, neutropenia),
infections, radiation exposure (all black box).
328
Tositumomab Notes
Important limitation of use is that only one treatment can be given. This is the way the clinical
trial was done
329
Brentuximab Vedotin Class
Antibody conjugates
330
Brentuximab Vedotin Uses
odgkin’s lymphoma after failure of stem cell transplant (ASCT) or after failure of at least two
prior multi-agent chemotherapy regimens. systemic
anaplastic large cell lymphoma (SALCL)
331
Brentuximab Vedotin Mechanism
A chimeric antibody-drug conjugate consisting of three components: 1) the chimeric IgG1
antibody specific for human CD30, 2) the microtubule disrupting agent MMAE*, and 3) a proteasecleavable linker that covalently attaches MMAE to the antibody
332
Brentuximab Vedotin Toxicities
Progressive multifocal leukoencephalopathy (PML) secondary to JC infection** (black box
warning)
333
Brentuximab Vedotin Notes
MMAE is monomethylauristatin E (antimitotic) which is extremely toxic and failed in early
clinical trials.
334
Trastuzumab Emtansine Class
Antibody conjugates
335
Trastuzumab Emtasine Uses
: Potentially for HER2+ breast cancer, following progression after treatment with trastuzumab +
chemotherapy.
336
Trastuzumab Emtasine Mechanism
Combines the targeting specificity of trastuzumab with the cell killing power of emtansine
(DM1). Emtansine (DM1) is an antimitotic agent that prevents the assembly of microtubules.
337
Trastuzumab Emtasine Notes
Positive results reported in August 2012 that T-DM1 versus capecitabine plus lapatanib in
patients previously treated with trastuzumab and a taxane chemotherapy, showed improved
progression-free survival in patients treated with T-DM1 (median 9.6 vs. 6.4 months), along with
improved overall survival (median 30.9 vs. 25.1 months).
338
Denosumab Class
Antibody conjugates
339
Denosumab Uses
For prevention of skeletal-related events related to bone metastases in patients with solid
tumors
340
Denosumab Mechanism
A human IgG2 monoclonal antibody that binds to human RANK ligand (RANKL). RANKL is a
transmembrane protein involved in the formation, function, and survival of osteoclasts, the cells
responsible for bone resorption. Thus, denosumab binds RANKL* and prevents it from activating its
receptor, RANK, on the surface of osteoclasts. Increased osteoclast activity, stimulated by RANKL, is a
mediator of bone pathology in solid tumors with bone metastases.
341
Denosumab Toxicities
hypocalcemia, osteonecrosis of the jaw
342
Denosumab Notes
Note this agent binds to a ligand,
| not a receptor.
343
Granulocyte macrophage colony-stimulating factor, GM-CSF Class
Supportive Agents
344
Granulocyte macrophage colony-stimulating factor, GM-CSF Uses
: For leukopenia to shorten time to white cell depletion recovery during chemotherapy, and to
reduce the incidence of severe and life-threatening infections
345
Granulocyte macrophage colony-stimulating factor, GM-CSF Mechanism
neutrophils, macrophages and myeloid derived dendritic cells.
346
Granulocyte macrophage colony-stimulating factor, GM-CSF Toxicities
Drugs which may potentiate the myeloproliferative effects such as lithium and
corticosteroids, should be used with caution.
347
Granulocyte colony-stimulating factor, G-CSF Class
Supportive Agents
348
Granulocyte colony-stimulating factor, G-CSF Uses
: For neutropenia, to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in
patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a
significant incidence of severe neutropenia with fever
349
Granulocyte colony-stimulating factor, G-CSF Mechanism
Regulates the production of neutrophils within the bone marrow and affects neutrophil
progenitor proliferation
350
Granulocyte colony-stimulating factor, G-CSF Toxicities
Drugs which may potentiate the myeloproliferative effects
| such as lithium and corticosteroids, should be used with caution.
351
Epoetin Class
Supportive Agents
352
Epoetin Uses
For the treatment of anemia in patients with non-myeloid malignancies where anemia is due to
the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there is a minimum of
two additional months of planned chemotherapy.
353
Darbopoietin Class
Supportive Agents
354
Darbopoietin Uses
for the treatment of anemia in patients with non-myeloid malignancies where
anemia is due to the effect of concomitant myelosuppressive chemotherapy, and upon initiation, there
is a minimum of two additional months of planned chemotherapy.
355
Bisphosphonates Class
Supportive Agents
356
Bisphosphonates Uses
Also for reducing skeletal events associated with cancer
| such as multiple myeloma or breast cancer
357
Ondansetron Class
Antiemetics
358
Ondansetron Uses
Prevention of nausea and vomiting caused by emetogenic chemotherapy or radiation.
Administered PO as tablet, disintegrating tablet, or solution (2-3 times daily)
359
Ondansetron Mechanism
A serotonin 5-HT3 receptor antagonist;
360
Ondansetron Toxicities
Generally well tolerated,
361
Ondansetron ADME
Elimination t1/2 about 4-6 hrs.
362
Ondansetron Notes
```
Originally approved (1991) without QT warning. QT warning added in June 2012 (no black
box).
```
363
Granisitron Class
Antiemetics
364
Granisitron Uses
As for ondansetron; prevention of nausea and vomiting caused by emetogenic chemotherapy or
radiation. Administered PO as tablet or solution, (1-2 times daily). Also IV solution and transdermal
patch.
365
Granisitron ADME
Elimination t1/2 about 9-12 hrs.
366
Bisphosphonates Class
Supportive Agents
367
Bisphosphonates Uses
Also for reducing skeletal events associated with cancer
| such as multiple myeloma or breast cancer
368
Ondansetron Class
Antiemetics
369
Ondansetron Uses
d
370
Ondansetron Mechanism
d
371
Ondansetron Toxicities
d
372
Ondansetron
d
373
Ondansetron Notes
```
Originally approved (1991) without QT warning. QT warning added in June 2012 (no black
box).
```
374
Granisitron Class
Antiemetics
375
Granisitron Uses
As for ondansetron; prevention of nausea and vomiting caused by emetogenic chemotherapy or
radiation. Administered PO as tablet or solution, (1-2 times daily). Also IV solution and transdermal
patch.
376
Granisitron ADME
Elimination t1/2 about 9-12 hrs.
377
Palonsetron Class
Antimetics
378
Palonsetron Uses
As for ondansetron and granisetron; prevention of nausea and vomiting caused by emetogenic
chemotherapy or radiation. Administered IV.
379
Palonsetron Mechanism
As for ondansetron and granisetron; more potent than either.
380
Palonsetron ADME
Elimination t1/2 about 40 hrs.
381
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