Disclaimer:
Medidex is not a provider of medical services and all information is provided for the convenience of the user. No medical decisions should be made based on the information provided on this website without first consulting a licensed healthcare provider.This website is intended for persons 18 years or older. No person under 18 should consult this website without the permission of a parent or guardian.
Aromasin
Overview
What is Aromasin?
A
What does Aromasin look like?
What are the available doses of Aromasin?
Sorry No records found.
What should I talk to my health care provider before I take Aromasin?
Sorry No records found
How should I use Aromasin?
AROMASIN is indicated for adjuvant treatment of postmenopausal
women with estrogen-receptor positive early breast cancer who have received two
to three years of tamoxifen and are switched to AROMASIN for completion of a
total of five consecutive years of adjuvant hormonal therapy.
AROMASIN is indicated for the treatment of advanced breast cancer in
postmenopausal women whose disease has progressed following tamoxifen therapy.
The recommended dose of AROMASIN in early and advanced breast
cancer is one 25 mg tablet once daily after a meal.
In postmenopausal women with early breast cancer who have been treated with
2–3 years of tamoxifen, treatment with AROMASIN should continue in the absence
of recurrence or contralateral breast cancer until completion of five years of
adjuvant endocrine therapy.
For patients with advanced breast cancer, treatment with AROMASIN should
continue until tumor progression is evident.
For patients receiving AROMASIN with a potent CYP 3A4 inducer such as
rifampicin or phenytoin, the recommended dose of AROMASIN is 50 mg once daily
after a meal.
The safety of chronic dosing in patients with moderate or severe hepatic or
renal impairment has not been studied. Based on experience with exemestane at
repeated doses up to 200 mg daily that demonstrated a moderate increase in
non-life threatening adverse events, dosage adjustment does not appear to be
necessary (see and ).
What interacts with Aromasin?
AROMASIN Tablets are contraindicated in patients with a known hypersensitivity to the drug or to any of the excipients.
What are the warnings of Aromasin?
Sorry No Records found
What are the precautions of Aromasin?
AROMASIN Tablets should not be administered to premenopausal
women. AROMASIN should not be coadministered with estrogen-containing agents as
these could interfere with its pharmacologic action.
The pharmacokinetics of exemestane have been investigated in
subjects with moderate or severe hepatic insufficiency (Childs-Pugh B or C).
Following a single 25-mg oral dose, the AUC of exemestane was approximately 3
times higher than that observed in healthy volunteers. The safety of chronic
dosing in patients with moderate or severe hepatic impairment has not been
studied. Based on experience with exemestane at repeated doses up to 200 mg
daily that demonstrated a moderate increase in non-life threatening adverse
events, dosage adjustment does not appear to be necessary.
The AUC of exemestane after a single 25-mg dose was approximately
3 times higher in subjects with moderate or severe renal insufficiency
(creatinine clearance less than 35 mL/min/1.73 m) compared
with the AUC in healthy volunteers. The safety of chronic dosing in patients
with moderate or severe renal impairment has not been studied. Based on
experience with exemestane at repeated doses up to 200 mg daily that
demonstrated a moderate increase in non-life threatening adverse events, dosage
adjustment does not appear to be necessary.
In patients with early breast cancer the incidence of
hematological abnormalities of Common Toxicity Criteria (CTC) grade greater than or equal to 1 was lower
in the exemestane treatment group, compared with tamoxifen. Incidence of CTC
grade 3 or 4 abnormalities was low (approximately 0.1%) in both treatment
groups. Approximately 20% of patients receiving exemestane in clinical studies
in advanced breast cancer, experienced CTC grade 3 or 4 lymphocytopenia. Of
these patients, 89% had a pre-existing lower grade lymphopenia. Forty percent of
patients either recovered or improved to a lesser severity while on treatment.
Patients did not have a significant increase in viral infections, and no
opportunistic infections were observed. Elevations of serum levels of AST, ALT,
alkaline phosphatase and gamma glutamyl transferase less than greater than 5 times the upper value
of the normal range (i.e., greater than or equal to CTC grade 3) have been rarely reported in patients
treated for advanced breast cancer but appear mostly attributable to the
underlying presence of liver and/or bone metastases. In the comparative study in
advanced breast cancer patients, CTC grade 3 or 4 elevation of gamma glutamyl
transferase without documented evidence of liver metastasis was reported in 2.7%
of patients treated with AROMASIN and in 1.8% of patients treated with megestrol
acetate.
In patients with early breast cancer, elevations in bilirubin, alkaline
phosphatase, and creatinine were more common in those receiving exemestane than
either tamoxifen or placebo. Treatment emergent bilirubin elevations (any CTC
grade) occurred in 5.3% of exemestane patients and 0.8% of tamoxifen patients on
the IES, and in 6.9% of exemestane treated patients vs. 0% of placebo treated
patients on the 027 study. CTC grade 3–4 increases in bilirubin occurred in 0.9%
of exemestane treated patients compared to 0.1% of tamoxifen treated patients.
Alkaline phosphatase elevations of any CTC grade occurred in 15.0% of exemestane
treated patients on the IES compared to 2.6% of tamoxifen treated patients, and
in 13.7% of exemestane treated patients compared to 6.9% of placebo treated
patients on study 027. Creatinine elevations occurred in 5.8% of exemestane
treated patients and 4.3% of tamoxifen treated patients on the IES and in 5.5%
of exemestane treated patients and 0% of placebo treated patients on study
027.
Reductions in bone mineral density (BMD) over time are seen with exemestane
use. Table 7 describes changes in BMD from baseline to 24 months in patients
receiving exemestane compared to patients receiving tamoxifen (IES) or placebo
(027). Concomitant use of bisphosphonates, Vitamin D supplementation and Calcium
was not allowed.
Exemestane is extensively metabolized by CYP 3A4, but
coadministration of ketoconazole, a potent inhibitor of CYP 3A4, has no
significant effect on exemestane pharmacokinetics. Significant pharmacokinetic
interactions mediated by inhibition of CYP isoenzymes therefore appear unlikely.
Co-medications that induce CYP 3A4 (e.g., rifampicin, phenytoin, carbamazepine,
phenobarbital, or St. John's wort) may significantly decrease exposure to
exemestane. Dose modification is recommended for patients who are also receiving
a potent CYP 3A4 inducer (see and
).
No clinically relevant changes in the results of clinical
laboratory tests have been observed.
A 2-year carcinogenicity study in mice at doses of 50, 150 and
450 mg/kg/day exemestane (gavage), resulted in an increased incidence of
hepatocellular adenomas and/or carcinomas in both genders at the high dose
level. Plasma AUCs at the high dose were 2575 ±
386 and 5667 ± 1833 ng.hr/mL in males and females (approx. 34 and 75 fold the
AUC in postmenopausal patients at the recommended clinical dose). An increased
incidence of renal tubular adenomas was observed in male mice at the high dose
of 450 mg/kg/day. Since the doses tested in mice did not achieve an MTD,
neoplastic findings in organs other than liver and kidneys remain unknown.
A separate carcinogenicity study was conducted in rats at the doses of 30,
100 and 315 mg/kg/day exemestane (gavage) for 92 weeks in males and 2 years in
females. No evidence of carcinogenic activity up to the highest dose tested of
315 mg/kg/day was observed in females. The male rat study was inconclusive since
it was terminated prematurely at Week 92. At the highest dose, plasma AUC levels in male (1418 ± 287 ng.hr/mL) and female (2318
± 1067 ng.hr/mL) rats were 19 and 31 fold higher than those measured in
postmenopausal cancer patients, receiving the recommended clinical dose.
Exemestane was not mutagenic in vitro in bacteria (Ames test) or mammalian
cells (V79 Chinese hamster lung cells). Exemestane was clastogenic in human
lymphocytes in vitro without metabolic activation but was not clastogenic in
vivo (micronucleus assay in mouse bone marrow). Exemestane did not increase
unscheduled DNA synthesis in rat hepatocytes when tested in vitro.
In a pilot reproductive study in rats, male rats were treated with doses of
125–1000 mg/kg/day exemestane, beginning 63 days prior to and during
cohabitation. Untreated female rats showed reduced fertility when mated to males
treated with greater than or equal to 500 mg/kg/day exemestane (greater than or equal to 200 times the recommended human dose on
a mg/m basis). In a separate study, exemestane was given
to female rats at 4–100 mg/kg/day beginning 14 days prior to mating and through
day 15 or 20 of gestation. Exemestane increased the placental weights at greater than or equal to 4
mg/kg/day greater than or equal to 1.5 times the human dose on a mg/m basis).
Exemestane showed no effects on ovarian function, mating behavior, and
conception rate in rats given doses up to 20 mg/kg/day (approximately 8 times
the recommended human dose on a mg/m basis), however,
decreases in mean litter size and fetal body weight, along with delayed
ossification were evidenced at greater than or equal to 20 mg/kg/day. In general toxicology studies,
changes in the ovary, including hyperplasia, an increase in the incidence of
ovarian cysts and a decrease in corpora lutea were observed with variable
frequency in mice, rats and dogs at doses that ranged from 3–20 times the human
dose on a mg/m basis.
See .
AROMASIN is only indicated in postmenopausal women. However,
radioactivity related to exemestane appeared in rat milk within 15 minutes of
oral administration of radiolabeled exemestane. Concentrations of exemestane and
its metabolites were approximately equivalent in the milk and plasma of rats for
24 hours after a single oral dose of 1 mg/kg C-exemestane. It is not known whether exemestane is excreted
in human milk. Because many drugs are excreted in human milk, caution should be
exercised if a nursing woman is inadvertently exposed to AROMASIN (see ).
The safety and effectiveness of AROMASIN in pediatric patients
have not been evaluated.
The use of AROMASIN in geriatric patients does not require
special precautions.
| IES | IES | 027 | 027 | ||||||
| BMD | ExemestaneN=29 | TamoxifenN=38 | ExemestaneN=59 | PlaceboN=65 | |||||
| Lumbar spine (%) | -3.14 | -0.18 | -3.51 | -2.35 | |||||
| Femoral neck (%) | -4.15 | -0.33 | -4.57 | -2.59 |
What are the side effects of Aromasin?
AROMASIN tolerability in postmenopausal women with early breast
cancer was evaluated in two well-controlled trials: the IES study (see ) and the 027 study (a randomized,
placebo-controlled, double-blind, parallel group study specifically designed to
assess the effects of exemestane on bone metabolism, hormones, lipids and
coagulation factors over 2 years of treatment).
Certain adverse events, expected based on the known pharmacological
properties and side effect profiles of test drugs, were actively sought through
a positive checklist. Signs and symptoms were graded for severity using CTC in
both studies. Within the IES study, the presence of some illnesses/conditions
was monitored through a positive checklist without assessment of severity. These
included myocardial infarction, other cardiovascular disorders, gynecological
disorders, osteoporosis, osteoporotic fractures, other primary cancer, and
hospitalizations.
The median duration of adjuvant treatment was 27.4 months and 27.3 months for
patients receiving AROMASIN or tamoxifen, respectively, within the IES study and
23.9 months for patients receiving AROMASIN or placebo within the 027 study.
Median duration of observation after randomization for AROMASIN was 34.5 months
and for tamoxifen was 34.6 months. Median duration of observation was 30 months
for both groups in the 027 study.
AROMASIN was generally well tolerated and adverse events were usually mild to
moderate. Within the IES study discontinuations due to adverse events occurred
in 6.3% and 5.1% of patients receiving AROMASIN and tamoxifen, respectively, and
in 12.3% and 4.1% of patients receiving exemestane or placebo within study 027.
Deaths due to any cause were reported for 1.3% of the exemestane-treated
patients and 1.4% of the tamoxifen-treated patients within the IES study. There
were 6 deaths due to stroke on the exemestane arm compared to 2 on tamoxifen.
There were 5 deaths due to cardiac failure on the exemestane arm compared to 2
on tamoxifen.
The incidence of cardiac ischemic events (myocardial infarction, angina and
myocardial ischemia) was 1.6% in exemestane treated patients and 0.6% in
tamoxifen treated patients in the IES study. Cardiac failure was observed in
0.4% of exemestane treated patients and 0.3% of tamoxifen treated patients.
Treatment-emergent adverse events and illnesses including all causalities and
occurring with an incidence of ≥5% in either treatment group of the IES study
during or within one month of the end of treatment are shown in Table 8.
In the IES study, as compared to tamoxifen, AROMASIN was associated with a
higher incidence of events in the musculoskeletal disorders and in the nervous
system disorders, including the following events occurring with frequency lower
than 5% (osteoporosis [4.6% vs. 2.8%], osteochondrosis and trigger finger [0.3%
vs 0 for both events], paresthesia [2.6% vs. 0.9%], carpal tunnel syndrome [2.4%
vs. 0.2%], and neuropathy [0.6% vs. 0.1%]. Diarrhea was also more frequent in
the exemestane group (4.2% vs. 2.2%). Clinical fractures were reported in 94
patients receiving exemestane (4.2%) and 71 patients receiving tamoxifen (3.1%).
After a median duration of therapy of about 30 months and a median follow-up of
about 52 months, gastric ulcer was observed at a slightly higher frequency in
the AROMASIN group compared to tamoxifen (0.7% versus less than 0.1%). The majority of
patients on AROMASIN with gastric ulcer received concomitant treatment with
non-steroidal anti-inflammatory agents and/or had a prior history.
Tamoxifen was associated with a higher incidence of muscle cramps [3.1% vs.
1.5%], thromboembolism [2.0% vs. 0.9%], endometrial hyperplasia [1.7% vs. 0.6%],
and uterine polyps [2.4% vs. 0.4%].
Common adverse events occurring on study 027 are described in Table 9.
A total of 1058 patients were treated with exemestane 25 mg once
daily in the clinical trials program. Exemestane was generally well tolerated,
and adverse events were usually mild to moderate. Only one death was considered
possibly related to treatment with exemestane; an 80-year-old woman with known
coronary artery disease had a myocardial infarction with multiple organ failure
after 9 weeks on study treatment. In the clinical trials program, only 3% of the
patients discontinued treatment with exemestane because of adverse events,
mainly within the first 10 weeks of treatment; late discontinuations because of
adverse events were uncommon (0.3%).
In the comparative study, adverse reactions were assessed for 358 patients
treated with AROMASIN and 400 patients treated with megestrol acetate. Fewer
patients receiving AROMASIN discontinued treatment because of adverse events
than those treated with megestrol acetate (2% vs. 5%). Adverse events that were
considered drug related or of indeterminate cause included hot flashes (13% vs.
5%), nausea (9% vs. 5%), fatigue (8% vs. 10%), increased sweating (4% vs. 8%),
and increased appetite (3% vs. 6%). The proportion of patients experiencing an
excessive weight gain (greater than 10% of their baseline weight) was significantly
higher with megestrol acetate than with AROMASIN (17% vs. 8%). Table 10 shows
the adverse events of all CTC grades, regardless of causality, reported in 5% or
greater of patients in the study treated either with AROMASIN or megestrol
acetate.
Less frequent adverse events of any cause (from 2% to 5%) reported in the
comparative study for patients receiving AROMASIN 25 mg once daily were fever,
generalized weakness, paresthesia, pathological fracture, bronchitis, sinusitis,
rash, itching, urinary tract infection, and lymphedema.
Additional adverse events of any cause observed in the overall clinical
trials program (N = 1058) in 5% or greater of patients treated with exemestane
25 mg once daily but not in the comparative study included pain at tumor sites
(8%), asthenia (6%) and fever (5%). Adverse events of any cause reported in 2%
to 5% of all patients treated with exemestane 25 mg in the overall clinical
trials program but not in the comparative study included chest pain,
hypoesthesia, confusion, dyspepsia, arthralgia, back pain, skeletal pain,
infection, upper respiratory tract infection, pharyngitis, rhinitis, and
alopecia.
The following adverse reactions have been identified during post
approval use of Aromasin. Because reactions are reported voluntarily from a
population of uncertain size, it is not always possible to reliably estimate
their frequency or establish a causal relationship to drug exposure.
Cases of hepatitis including cholestatic hepatitis have been observed in
clinical trials and reported through post-marketing surveillance.
| % of patients | |||||
| Body system and Adverse Eventby MedDRA dictionary | AROMASIN25 mg daily(N=2252) | ||||
| Eye | |||||
| Gastrointestinal | |||||
| General Disorders | |||||
| Musculoskeletal | |||||
| Nervous System | |||||
| Psychiatric | |||||
| Skin & Subcutaneous Tissue | |||||
| Vascular | |||||
| Adverse Event | ExemestaneN=73(% incidence) | PlaceboN=73(% incidence) | |||
| Hot flushes | 32.9 | 24.7 | |||
| Arthralgia | 28.8 | 28.8 | |||
| Increased Sweating | 17.8 | 20.6 | |||
| Alopecia | 15.1 | 4.1 | |||
| Hypertension | 15.1 | 6.9 | |||
| Insomnia | 13.7 | 15.1 | |||
| nausea | 12.3 | 16.4 | |||
| Fatigue | 11.0 | 19.2 | |||
| Abdominal pain | 11.0 | 13.7 | |||
| Depression | 9.6 | 6.9 | |||
| Diarrhea | 9.6 | 1.4 | |||
| Dizziness | 9.6 | 9.6 | |||
| Dermatitis | 8.2 | 1.4 | |||
| Headache | 6.9 | 4.1 | |||
| Myalgia | 5.5 | 4.1 | |||
| Edema | 5.5 | 6.9 | |||
| Anxiety | 4.1 | 5.5 | |||
| Body system and Adverse Event by WHO ARTdictionary | AROMASIN25 mgonce daily(N=358) | Megestrol Acetate40 mg QID(N=400) | |||
| Autonomic Nervous Increased sweating | |||||
| Body as a Whole Fatigue Hot flashes Pain Influenza-like symptoms Edema (includes edema, peripheral edema, leg edema) | |||||
| Cardiovascular Hypertension | |||||
| Nervous Depression Insomnia Anxiety Dizziness Headache | |||||
| Gastrointestinal Nausea Vomiting Abdominal pain Anorexia Constipation Diarrhea Increased appetit | |||||
| Respiratory Dyspnea Coughing |
What should I look out for while using Aromasin?
AROMASIN Tablets are contraindicated in patients with a known hypersensitivity
to the drug or to any of the excipients.
AROMASIN Tablets may cause fetal harm when administered to a
pregnant woman. Radioactivity related to C-exemestane
crossed the placenta of rats following oral administration of 1 mg/kg
exemestane. The concentration of exemestane and its metabolites was
approximately equivalent in maternal and fetal blood. When rats were
administered exemestane from 14 days prior to mating until either days 15 or 20
of gestation, and resuming for the 21 days of lactation, an increase in
placental weight was seen at 4 mg/kg/day (approximately 1.5 times the
recommended human daily dose on a mg/m basis). Prolonged
gestation and abnormal or difficult labor was observed at doses equal to or
greater than 20 mg/kg/day. Increased resorption, reduced number of live fetuses,
decreased fetal weight, and retarded ossification were also observed at these
doses. No malformations were noted when exemestane was administered to pregnant
rats during the organogenesis period at doses up to 810 mg/kg/day (approximately
320 times the recommended human dose on a mg/m basis).
Daily doses of exemestane, given to rabbits during organogenesis caused a
decrease in placental weight at 90 mg/kg/day (approximately 70 times the
recommended human daily dose on a mg/m basis).
Abortions, an increase in resorptions, and a reduction in fetal body weight were
seen at 270 mg/kg/day. There was no increase in the incidence of malformations
in rabbits at doses up to 270 mg/kg/day (approximately 210 times the recommended
human dose on a mg/m basis).
There are no studies in pregnant women using AROMASIN. AROMASIN is indicated
for postmenopausal women. If there is exposure to AROMASIN during pregnancy, the
patient should be apprised of the potential hazard to the fetus and potential
risk for loss of the pregnancy.
What might happen if I take too much Aromasin?
Clinical trials have been conducted with exemestane given as a
single dose to healthy female volunteers at doses as high as 800 mg and daily
for 12 weeks to postmenopausal women with advanced breast cancer at doses as
high as 600 mg. These dosages were well tolerated. There is no specific antidote
to overdosage and treatment must be symptomatic. General supportive care,
including frequent monitoring of vital signs and close observation of the
patient, is indicated.
A male child (age unknown) accidentally ingested a 25-mg tablet of
exemestane. The initial physical examination was normal, but blood tests
performed 1 hour after ingestion indicated leucocytosis (WBC 25000/mm with 90% neutrophils). Blood tests were repeated 4 days after
the incident and were normal. No treatment was given.
In mice, mortality was observed after a single oral dose of exemestane of
3200 mg/kg, the lowest dose tested (about 640 times the recommended human dose
on a mg/m basis). In rats and dogs, mortality was
observed after single oral doses of exemestane of 5000 mg/kg (about 2000 times
the recommended human dose on a mg/m basis) and of 3000
mg/kg (about 4000 times the recommended human dose on a mg/m basis), respectively.
Convulsions were observed after single doses of exemestane of 400 mg/kg and
3000 mg/kg in mice and dogs (approximately 80 and 4000 times the recommended
human dose on a mg/m basis), respectively.
How should I store and handle Aromasin?
Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].Dispense in a tight, light-resistant container as defined in the USP/NF with a child-resistant closure.A Schedule CIII Narcotic.Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].Dispense in a tight, light-resistant container as defined in the USP/NF with a child-resistant closure.A Schedule CIII Narcotic.Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].Dispense in a tight, light-resistant container as defined in the USP/NF with a child-resistant closure.A Schedule CIII Narcotic.AROMASIN Tablets are round, biconvex, and off-white to slightly gray. Each tablet contains 25 mg of exemestane. The tablets are printed on one side with the number "7663" in black. AROMASIN is packaged in HDPE bottles with a child-resistant screw cap, supplied in packs of 30 tablets.30-tablet HDPE bottle NDC 54868-5261-0Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].Rx onlyDistributed byPfizer AROMASIN Tablets are round, biconvex, and off-white to slightly gray. Each tablet contains 25 mg of exemestane. The tablets are printed on one side with the number "7663" in black. AROMASIN is packaged in HDPE bottles with a child-resistant screw cap, supplied in packs of 30 tablets.30-tablet HDPE bottle NDC 54868-5261-0Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].Rx onlyDistributed byPfizer AROMASIN Tablets are round, biconvex, and off-white to slightly gray. Each tablet contains 25 mg of exemestane. The tablets are printed on one side with the number "7663" in black. AROMASIN is packaged in HDPE bottles with a child-resistant screw cap, supplied in packs of 30 tablets.30-tablet HDPE bottle NDC 54868-5261-0Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].Rx onlyDistributed byPfizer AROMASIN Tablets are round, biconvex, and off-white to slightly gray. Each tablet contains 25 mg of exemestane. The tablets are printed on one side with the number "7663" in black. AROMASIN is packaged in HDPE bottles with a child-resistant screw cap, supplied in packs of 30 tablets.30-tablet HDPE bottle NDC 54868-5261-0Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].Rx onlyDistributed byPfizer AROMASIN Tablets are round, biconvex, and off-white to slightly gray. Each tablet contains 25 mg of exemestane. The tablets are printed on one side with the number "7663" in black. AROMASIN is packaged in HDPE bottles with a child-resistant screw cap, supplied in packs of 30 tablets.30-tablet HDPE bottle NDC 54868-5261-0Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].Rx onlyDistributed byPfizer AROMASIN Tablets are round, biconvex, and off-white to slightly gray. Each tablet contains 25 mg of exemestane. The tablets are printed on one side with the number "7663" in black. AROMASIN is packaged in HDPE bottles with a child-resistant screw cap, supplied in packs of 30 tablets.30-tablet HDPE bottle NDC 54868-5261-0Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].Rx onlyDistributed byPfizer AROMASIN Tablets are round, biconvex, and off-white to slightly gray. Each tablet contains 25 mg of exemestane. The tablets are printed on one side with the number "7663" in black. AROMASIN is packaged in HDPE bottles with a child-resistant screw cap, supplied in packs of 30 tablets.30-tablet HDPE bottle NDC 54868-5261-0Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].Rx onlyDistributed byPfizer
Clinical Information
Chemical Structure
No Image foundClinical Pharmacology
Breast cancer cell growth may be estrogen-dependent. Aromatase is
the principal enzyme that converts androgens to estrogens both in pre- and
postmenopausal women. While the main source of estrogen (primarily estradiol) is
the ovary in premenopausal women, the principal source of circulating estrogens
in postmenopausal women is from conversion of adrenal and ovarian androgens
(androstenedione and testosterone) to estrogens (estrone and estradiol) by the
aromatase enzyme in peripheral tissues. Estrogen deprivation through aromatase
inhibition is an effective and selective treatment for some postmenopausal
patients with hormone-dependent breast cancer.
Exemestane is an irreversible, steroidal aromatase inactivator, structurally
related to the natural substrate androstenedione. It acts as a false substrate
for the aromatase enzyme, and is processed to an intermediate that binds
irreversibly to the active site of the enzyme causing its inactivation, an
effect also known as "suicide inhibition." Exemestane significantly lowers
circulating estrogen concentrations in postmenopausal women, but has no
detectable effect on adrenal biosynthesis of corticosteroids or aldosterone.
Exemestane has no effect on other enzymes involved in the steroidogenic pathway
up to a concentration at least 600 times higher than that inhibiting the
aromatase enzyme.
Following oral administration to healthy postmenopausal women,
exemestane is rapidly absorbed. After maximum plasma concentration is reached,
levels decline polyexponentially with a mean terminal half-life of about 24
hours. Exemestane is extensively distributed and is cleared from the systemic
circulation primarily by metabolism. The pharmacokinetics of exemestane are dose
proportional after single (10 to 200 mg) or repeated oral doses (0.5 to 50 mg).
Following repeated daily doses of exemestane 25 mg, plasma concentrations of
unchanged drug are similar to levels measured after a single dose.
Pharmacokinetic parameters in postmenopausal women with advanced breast
cancer following single or repeated doses have been compared with those in
healthy, postmenopausal women. Exemestane appeared to be more rapidly absorbed
in the women with breast cancer than in the healthy women, with a mean t of 1.2 hours in the women with breast cancer and 2.9 hours
in the healthy women. After repeated dosing, the average oral clearance in women
with advanced breast cancer was 45% lower than the oral clearance in healthy
postmenopausal women, with corresponding higher systemic exposure. Mean AUC
values following repeated doses in women with breast cancer (75.4 ng∙h/mL) were
about twice those in healthy women (41.4 ng∙h/mL).
Following oral administration of radiolabeled exemestane, at
least 42% of radioactivity was absorbed from the gastrointestinal tract.
Exemestane plasma levels increased by approximately 40% after a high-fat
breakfast.
Exemestane is distributed extensively into tissues. Exemestane is
90% bound to plasma proteins and the fraction bound is independent of the total
concentration. Albumin and α-acid glycoprotein both
contribute to the binding. The distribution of exemestane and its metabolites
into blood cells is negligible.
Following administration of radiolabeled exemestane to healthy
postmenopausal women, the cumulative amounts of radioactivity excreted in urine
and feces were similar (42 ± 3% in urine and 42 ± 6% in feces over a 1-week
collection period). The amount of drug excreted unchanged in urine was less than
1% of the dose. Exemestane is extensively metabolized, with levels of the
unchanged drug in plasma accounting for less than 10% of the total
radioactivity. The initial steps in the metabolism of exemestane are oxidation
of the methylene group in position 6 and reduction of the 17-keto group with
subsequent formation of many secondary metabolites. Each metabolite accounts
only for a limited amount of drug-related material. The metabolites are inactive
or inhibit aromatase with decreased potency compared with the parent drug. One
metabolite may have androgenic activity (see ).
Studies using human liver preparations indicate that cytochrome P-450 3A4 (CYP
3A4) is the principal isoenzyme involved in the oxidation of exemestane.
Healthy postmenopausal women aged 43 to 68 years were studied in
the pharmacokinetic trials. Age-related alterations in exemestane
pharmacokinetics were not seen over this age range.
The pharmacokinetics of exemestane following administration of a
single, 25-mg tablet to fasted healthy males (mean age 32 years) were similar to
the pharmacokinetics of exemestane in fasted healthy postmenopausal women (mean
age 55 years).
The influence of race on exemestane pharmacokinetics has not been
evaluated.
The pharmacokinetics of exemestane have been investigated in
subjects with moderate or severe hepatic insufficiency (Childs-Pugh B or C).
Following a single 25-mg oral dose, the AUC of exemestane was approximately 3
times higher than that observed in healthy volunteers (see ).
The AUC of exemestane after a single 25-mg dose was approximately
3 times higher in subjects with moderate or severe renal insufficiency
(creatinine clearance less than 35 mL/min/1.73 m) compared
with the AUC in healthy volunteers (see ).
The pharmacokinetics of exemestane have not been studied in
pediatric patients.
Exemestane is metabolized by cytochrome P-450 3A4 (CYP 3A4) and
aldoketoreductases. It does not inhibit any of the major CYP isoenzymes,
including CYP 1A2, 2C9, 2D6, 2E1, and 3A4. In a clinical pharmacokinetic study,
ketoconazole showed no significant influence on the pharmacokinetics of
exemestane. Although no other formal drug-drug interaction studies have been
conducted, significant effects on exemestane clearance by CYP isoenzymes
inhibitors appear unlikely. In a pharmacokinetic interaction study of 10 healthy
postmenopausal volunteers pretreated with potent CYP 3A4 inducer rifampicin 600
mg daily for 14 days followed by a single dose of exemestane 25 mg, the mean
plasma C and AUC of
exemestane were decreased by 41% and 54%, respectively (see and ).
Multiple doses of exemestane ranging from 0.5 to 600 mg/day were
administered to postmenopausal women with advanced breast cancer. Plasma
estrogen (estradiol, estrone, and estrone sulfate) suppression was seen starting
at a 5-mg daily dose of exemestane, with a maximum suppression of at least 85%
to 95% achieved at a 25-mg dose. Exemestane 25 mg daily reduced whole body
aromatization (as measured by injecting radiolabeled androstenedione) by 98% in
postmenopausal women with breast cancer. After a single dose of exemestane 25
mg, the maximal suppression of circulating estrogens occurred 2 to 3 days after
dosing and persisted for 4 to 5 days.
In multiple-dose trials of doses up to 200 mg daily, exemestane
selectivity was assessed by examining its effect on adrenal steroids. Exemestane
did not affect cortisol or aldosterone secretion at baseline or in response to
ACTH at any dose. Thus, no glucocorticoid or mineralocorticoid replacement
therapy is necessary with exemestane treatment.
Exemestane does not bind significantly to steroidal receptors,
except for a slight affinity for the androgen receptor (0.28% relative to
dihydrotestosterone). The binding affinity of its 17-dihydrometabolite for the
androgen receptor, however, is 100-times that of the parent compound. Daily
doses of exemestane up to 25 mg had no significant effect on circulating levels
of androstenedione, dehydroepiandrosterone sulfate, or 17-hydroxyprogesterone,
and were associated with small decreases in circulating levels of testosterone.
Increases in testosterone and androstenedione levels have been observed at daily
doses of 200 mg or more. A dose-dependent decrease in sex hormone binding
globulin (SHBG) has been observed with daily exemestane doses of 2.5 mg or
higher. Slight, nondose-dependent increases in serum luteinizing hormone (LH)
and follicle-stimulating hormone (FSH) levels have been observed even at low
doses as a consequence of feedback at the pituitary level. Exemestane 25 mg
daily had no significant effect on thyroid function [free triiodothyronine
(FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH)].
In study 027 of postmenopausal women with early breast cancer
treated with exemestane (N=73) or placebo (N=73), there was no change in the
coagulation parameters activated partial thromboplastin time [APTT], prothrombin
time [PT] and fibrinogen. Plasma HDL cholesterol was decreased 6–9% in
exemestane treated patients; total cholesterol, LDL cholesterol, triglycerides,
apolipoprotein-A1, apolipoprotein-B, and lipoprotein-a were unchanged. An 18%
increase in homocysteine levels was also observed in exemestane treated patients
compared with a 12% increase seen with placebo.
Non-Clinical Toxicology
AROMASIN Tablets are contraindicated in patients with a known hypersensitivity to the drug or to any of the excipients.AROMASIN Tablets may cause fetal harm when administered to a pregnant woman. Radioactivity related to C-exemestane crossed the placenta of rats following oral administration of 1 mg/kg exemestane. The concentration of exemestane and its metabolites was approximately equivalent in maternal and fetal blood. When rats were administered exemestane from 14 days prior to mating until either days 15 or 20 of gestation, and resuming for the 21 days of lactation, an increase in placental weight was seen at 4 mg/kg/day (approximately 1.5 times the recommended human daily dose on a mg/m basis). Prolonged gestation and abnormal or difficult labor was observed at doses equal to or greater than 20 mg/kg/day. Increased resorption, reduced number of live fetuses, decreased fetal weight, and retarded ossification were also observed at these doses. No malformations were noted when exemestane was administered to pregnant rats during the organogenesis period at doses up to 810 mg/kg/day (approximately 320 times the recommended human dose on a mg/m basis). Daily doses of exemestane, given to rabbits during organogenesis caused a decrease in placental weight at 90 mg/kg/day (approximately 70 times the recommended human daily dose on a mg/m basis). Abortions, an increase in resorptions, and a reduction in fetal body weight were seen at 270 mg/kg/day. There was no increase in the incidence of malformations in rabbits at doses up to 270 mg/kg/day (approximately 210 times the recommended human dose on a mg/m basis).
There are no studies in pregnant women using AROMASIN. AROMASIN is indicated for postmenopausal women. If there is exposure to AROMASIN during pregnancy, the patient should be apprised of the potential hazard to the fetus and potential risk for loss of the pregnancy.
Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of amoxicillin and probenecid may result in increased and prolonged blood levels of amoxicillin.
Chloramphenicol, macrolides, sulfonamides, and tetracyclines may interfere with the bactericidal effects of penicillin. This has been demonstrated ; however, the clinical significance of this interaction is not well documented.
In common with other antibiotics, amoxicillin capsules, amoxicillin for oral suspension, or amoxicillin tablets (chewable) may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.
AROMASIN Tablets should not be administered to premenopausal women. AROMASIN should not be coadministered with estrogen-containing agents as these could interfere with its pharmacologic action.
The pharmacokinetics of exemestane have been investigated in subjects with moderate or severe hepatic insufficiency (Childs-Pugh B or C). Following a single 25-mg oral dose, the AUC of exemestane was approximately 3 times higher than that observed in healthy volunteers. The safety of chronic dosing in patients with moderate or severe hepatic impairment has not been studied. Based on experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non-life threatening adverse events, dosage adjustment does not appear to be necessary.
The AUC of exemestane after a single 25-mg dose was approximately 3 times higher in subjects with moderate or severe renal insufficiency (creatinine clearance less than 35 mL/min/1.73 m) compared with the AUC in healthy volunteers. The safety of chronic dosing in patients with moderate or severe renal impairment has not been studied. Based on experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non-life threatening adverse events, dosage adjustment does not appear to be necessary.
In patients with early breast cancer the incidence of hematological abnormalities of Common Toxicity Criteria (CTC) grade greater than or equal to 1 was lower in the exemestane treatment group, compared with tamoxifen. Incidence of CTC grade 3 or 4 abnormalities was low (approximately 0.1%) in both treatment groups. Approximately 20% of patients receiving exemestane in clinical studies in advanced breast cancer, experienced CTC grade 3 or 4 lymphocytopenia. Of these patients, 89% had a pre-existing lower grade lymphopenia. Forty percent of patients either recovered or improved to a lesser severity while on treatment. Patients did not have a significant increase in viral infections, and no opportunistic infections were observed. Elevations of serum levels of AST, ALT, alkaline phosphatase and gamma glutamyl transferase less than greater than 5 times the upper value of the normal range (i.e., greater than or equal to CTC grade 3) have been rarely reported in patients treated for advanced breast cancer but appear mostly attributable to the underlying presence of liver and/or bone metastases. In the comparative study in advanced breast cancer patients, CTC grade 3 or 4 elevation of gamma glutamyl transferase without documented evidence of liver metastasis was reported in 2.7% of patients treated with AROMASIN and in 1.8% of patients treated with megestrol acetate.
In patients with early breast cancer, elevations in bilirubin, alkaline phosphatase, and creatinine were more common in those receiving exemestane than either tamoxifen or placebo. Treatment emergent bilirubin elevations (any CTC grade) occurred in 5.3% of exemestane patients and 0.8% of tamoxifen patients on the IES, and in 6.9% of exemestane treated patients vs. 0% of placebo treated patients on the 027 study. CTC grade 3–4 increases in bilirubin occurred in 0.9% of exemestane treated patients compared to 0.1% of tamoxifen treated patients. Alkaline phosphatase elevations of any CTC grade occurred in 15.0% of exemestane treated patients on the IES compared to 2.6% of tamoxifen treated patients, and in 13.7% of exemestane treated patients compared to 6.9% of placebo treated patients on study 027. Creatinine elevations occurred in 5.8% of exemestane treated patients and 4.3% of tamoxifen treated patients on the IES and in 5.5% of exemestane treated patients and 0% of placebo treated patients on study 027.
Reductions in bone mineral density (BMD) over time are seen with exemestane use. Table 7 describes changes in BMD from baseline to 24 months in patients receiving exemestane compared to patients receiving tamoxifen (IES) or placebo (027). Concomitant use of bisphosphonates, Vitamin D supplementation and Calcium was not allowed.
Exemestane is extensively metabolized by CYP 3A4, but coadministration of ketoconazole, a potent inhibitor of CYP 3A4, has no significant effect on exemestane pharmacokinetics. Significant pharmacokinetic interactions mediated by inhibition of CYP isoenzymes therefore appear unlikely. Co-medications that induce CYP 3A4 (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, or St. John's wort) may significantly decrease exposure to exemestane. Dose modification is recommended for patients who are also receiving a potent CYP 3A4 inducer (see and ).
No clinically relevant changes in the results of clinical laboratory tests have been observed.
A 2-year carcinogenicity study in mice at doses of 50, 150 and 450 mg/kg/day exemestane (gavage), resulted in an increased incidence of hepatocellular adenomas and/or carcinomas in both genders at the high dose level. Plasma AUCs at the high dose were 2575 ± 386 and 5667 ± 1833 ng.hr/mL in males and females (approx. 34 and 75 fold the AUC in postmenopausal patients at the recommended clinical dose). An increased incidence of renal tubular adenomas was observed in male mice at the high dose of 450 mg/kg/day. Since the doses tested in mice did not achieve an MTD, neoplastic findings in organs other than liver and kidneys remain unknown.
A separate carcinogenicity study was conducted in rats at the doses of 30, 100 and 315 mg/kg/day exemestane (gavage) for 92 weeks in males and 2 years in females. No evidence of carcinogenic activity up to the highest dose tested of 315 mg/kg/day was observed in females. The male rat study was inconclusive since it was terminated prematurely at Week 92. At the highest dose, plasma AUC levels in male (1418 ± 287 ng.hr/mL) and female (2318 ± 1067 ng.hr/mL) rats were 19 and 31 fold higher than those measured in postmenopausal cancer patients, receiving the recommended clinical dose.
Exemestane was not mutagenic in vitro in bacteria (Ames test) or mammalian cells (V79 Chinese hamster lung cells). Exemestane was clastogenic in human lymphocytes in vitro without metabolic activation but was not clastogenic in vivo (micronucleus assay in mouse bone marrow). Exemestane did not increase unscheduled DNA synthesis in rat hepatocytes when tested in vitro.
In a pilot reproductive study in rats, male rats were treated with doses of 125–1000 mg/kg/day exemestane, beginning 63 days prior to and during cohabitation. Untreated female rats showed reduced fertility when mated to males treated with greater than or equal to 500 mg/kg/day exemestane (greater than or equal to 200 times the recommended human dose on a mg/m basis). In a separate study, exemestane was given to female rats at 4–100 mg/kg/day beginning 14 days prior to mating and through day 15 or 20 of gestation. Exemestane increased the placental weights at greater than or equal to 4 mg/kg/day greater than or equal to 1.5 times the human dose on a mg/m basis). Exemestane showed no effects on ovarian function, mating behavior, and conception rate in rats given doses up to 20 mg/kg/day (approximately 8 times the recommended human dose on a mg/m basis), however, decreases in mean litter size and fetal body weight, along with delayed ossification were evidenced at greater than or equal to 20 mg/kg/day. In general toxicology studies, changes in the ovary, including hyperplasia, an increase in the incidence of ovarian cysts and a decrease in corpora lutea were observed with variable frequency in mice, rats and dogs at doses that ranged from 3–20 times the human dose on a mg/m basis.
See .
AROMASIN is only indicated in postmenopausal women. However, radioactivity related to exemestane appeared in rat milk within 15 minutes of oral administration of radiolabeled exemestane. Concentrations of exemestane and its metabolites were approximately equivalent in the milk and plasma of rats for 24 hours after a single oral dose of 1 mg/kg C-exemestane. It is not known whether exemestane is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if a nursing woman is inadvertently exposed to AROMASIN (see ).
The safety and effectiveness of AROMASIN in pediatric patients have not been evaluated.
The use of AROMASIN in geriatric patients does not require special precautions.
AROMASIN tolerability in postmenopausal women with early breast cancer was evaluated in two well-controlled trials: the IES study (see ) and the 027 study (a randomized, placebo-controlled, double-blind, parallel group study specifically designed to assess the effects of exemestane on bone metabolism, hormones, lipids and coagulation factors over 2 years of treatment).
Certain adverse events, expected based on the known pharmacological properties and side effect profiles of test drugs, were actively sought through a positive checklist. Signs and symptoms were graded for severity using CTC in both studies. Within the IES study, the presence of some illnesses/conditions was monitored through a positive checklist without assessment of severity. These included myocardial infarction, other cardiovascular disorders, gynecological disorders, osteoporosis, osteoporotic fractures, other primary cancer, and hospitalizations.
The median duration of adjuvant treatment was 27.4 months and 27.3 months for patients receiving AROMASIN or tamoxifen, respectively, within the IES study and 23.9 months for patients receiving AROMASIN or placebo within the 027 study. Median duration of observation after randomization for AROMASIN was 34.5 months and for tamoxifen was 34.6 months. Median duration of observation was 30 months for both groups in the 027 study.
AROMASIN was generally well tolerated and adverse events were usually mild to moderate. Within the IES study discontinuations due to adverse events occurred in 6.3% and 5.1% of patients receiving AROMASIN and tamoxifen, respectively, and in 12.3% and 4.1% of patients receiving exemestane or placebo within study 027. Deaths due to any cause were reported for 1.3% of the exemestane-treated patients and 1.4% of the tamoxifen-treated patients within the IES study. There were 6 deaths due to stroke on the exemestane arm compared to 2 on tamoxifen. There were 5 deaths due to cardiac failure on the exemestane arm compared to 2 on tamoxifen.
The incidence of cardiac ischemic events (myocardial infarction, angina and myocardial ischemia) was 1.6% in exemestane treated patients and 0.6% in tamoxifen treated patients in the IES study. Cardiac failure was observed in 0.4% of exemestane treated patients and 0.3% of tamoxifen treated patients.
Treatment-emergent adverse events and illnesses including all causalities and occurring with an incidence of ≥5% in either treatment group of the IES study during or within one month of the end of treatment are shown in Table 8.
In the IES study, as compared to tamoxifen, AROMASIN was associated with a higher incidence of events in the musculoskeletal disorders and in the nervous system disorders, including the following events occurring with frequency lower than 5% (osteoporosis [4.6% vs. 2.8%], osteochondrosis and trigger finger [0.3% vs 0 for both events], paresthesia [2.6% vs. 0.9%], carpal tunnel syndrome [2.4% vs. 0.2%], and neuropathy [0.6% vs. 0.1%]. Diarrhea was also more frequent in the exemestane group (4.2% vs. 2.2%). Clinical fractures were reported in 94 patients receiving exemestane (4.2%) and 71 patients receiving tamoxifen (3.1%). After a median duration of therapy of about 30 months and a median follow-up of about 52 months, gastric ulcer was observed at a slightly higher frequency in the AROMASIN group compared to tamoxifen (0.7% versus less than 0.1%). The majority of patients on AROMASIN with gastric ulcer received concomitant treatment with non-steroidal anti-inflammatory agents and/or had a prior history.
Tamoxifen was associated with a higher incidence of muscle cramps [3.1% vs. 1.5%], thromboembolism [2.0% vs. 0.9%], endometrial hyperplasia [1.7% vs. 0.6%], and uterine polyps [2.4% vs. 0.4%].
Common adverse events occurring on study 027 are described in Table 9.
A total of 1058 patients were treated with exemestane 25 mg once daily in the clinical trials program. Exemestane was generally well tolerated, and adverse events were usually mild to moderate. Only one death was considered possibly related to treatment with exemestane; an 80-year-old woman with known coronary artery disease had a myocardial infarction with multiple organ failure after 9 weeks on study treatment. In the clinical trials program, only 3% of the patients discontinued treatment with exemestane because of adverse events, mainly within the first 10 weeks of treatment; late discontinuations because of adverse events were uncommon (0.3%).
In the comparative study, adverse reactions were assessed for 358 patients treated with AROMASIN and 400 patients treated with megestrol acetate. Fewer patients receiving AROMASIN discontinued treatment because of adverse events than those treated with megestrol acetate (2% vs. 5%). Adverse events that were considered drug related or of indeterminate cause included hot flashes (13% vs. 5%), nausea (9% vs. 5%), fatigue (8% vs. 10%), increased sweating (4% vs. 8%), and increased appetite (3% vs. 6%). The proportion of patients experiencing an excessive weight gain (greater than 10% of their baseline weight) was significantly higher with megestrol acetate than with AROMASIN (17% vs. 8%). Table 10 shows the adverse events of all CTC grades, regardless of causality, reported in 5% or greater of patients in the study treated either with AROMASIN or megestrol acetate.
Less frequent adverse events of any cause (from 2% to 5%) reported in the comparative study for patients receiving AROMASIN 25 mg once daily were fever, generalized weakness, paresthesia, pathological fracture, bronchitis, sinusitis, rash, itching, urinary tract infection, and lymphedema.
Additional adverse events of any cause observed in the overall clinical trials program (N = 1058) in 5% or greater of patients treated with exemestane 25 mg once daily but not in the comparative study included pain at tumor sites (8%), asthenia (6%) and fever (5%). Adverse events of any cause reported in 2% to 5% of all patients treated with exemestane 25 mg in the overall clinical trials program but not in the comparative study included chest pain, hypoesthesia, confusion, dyspepsia, arthralgia, back pain, skeletal pain, infection, upper respiratory tract infection, pharyngitis, rhinitis, and alopecia.
The following adverse reactions have been identified during post approval use of Aromasin. Because reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cases of hepatitis including cholestatic hepatitis have been observed in clinical trials and reported through post-marketing surveillance.
Reference
This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"
While we update our database periodically, we cannot guarantee it is always updated to the latest version.
Review
Read user comments about the side effects, benefits, and effectiveness of losartan oral.
Overall User Ratings
514Total User Reviews
User Reviews
Learn about
User Reviews
Professional
Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72Tips
Tips
Interactions
Interactions
A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).