Rolapitant - Varubi -@-(Sep 2015)- Antinemetic
Drug Name:Rolapitant - Varubi -@-(Sep 2015)- Antinemetic
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
BCRP and P-gp Substrates with a Narrow Therapeutic Index:
inhibition of BCRP and P-gp by VARUBI can increase plasma concentrations of the
concomitant drug and potential for adverse reactions.
See full prescribing information for specific examples.
Strong CYP3A4 Inducers (e.g., rifampin): significantly reduced plasma
concentrations of rolapitant can decrease the efficacy of VARUBI;
avoid use of VARUBI in patients who require chronic administration of such drugs.
Indication:
VARUBI (rolapitant) tablets, for oral use
Initial U.S. Approval: 2015
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.23
Drug Name - Rolapitant
Active Ingredient- Varubi
Date of approval - 9/02/2015
FDA-approved use - To prevent delayed phase chemotherapy induced
nausea and vomiting (emesis)
Approved by US FDA on 9/02/2015- (Ref- FDA approved List- 2015)
INDICATIONS AND USAGE
VARUBI is a substance P/neurokinin 1 (NK1) receptor antagonist indicated
in combination with other antiemetic agents in adults for the prevention of
delayed nausea and vomiting associated with initial and repeat courses of
emetogenic cancer chemotherapy, including, but not limited to, highly
emetogenic chemotherapy.
Adverse Reaction:
Most common adverse reactions (. 5%) are:
. Cisplatin Based Highly Emetogenic Chemotherapy: neutropenia and hiccups
. Moderately Emetogenic Chemotherapy and Combinations of
Anthracycline and Cyclophosphamide: decreased appetite, neutropenia
and dizziness
Contra-Indications:
CONTRAINDICATIONS
Concurrent use with thioridazine, a CYP2D6 substrate
WARNINGS AND PRECAUTIONS
Interaction with CYP2D6 Substrates with a Narrow Therapeutic Index:
The inhibitory effect of a single dose of VARUBI on CYP2D6 lasts
at least 7 days and may last longer.
Avoid use of pimozide; monitor for adverse reactions if concomitant use
with other CYP2D6 substrates with a narrow therapeutic index
cannot be avoided
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
VARUBI is a substance P/neurokinin 1 (NK1) receptor antagonist indicated
in combination with other antiemetic agents in adults for the prevention of
delayed nausea and vomiting associated with initial and repeat courses of
emetogenic cancer chemotherapy, including, but not limited to, highly
emetogenic chemotherapy.
DOSAGE AND ADMINISTRATION
The recommended dosage is 180 mg rolapitant administered approximatel
1 to 2 hours prior to the start of chemotherapy
Administer in combination with dexamethasone and a 5-HT3 receptor antagonist,
see full prescribing information for dosing information
No dosage adjustment for dexamethasone is required.
DOSAGE FORMS AND STRENGTHS
Tablets: 90 mg of rolapitant
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Drug Interactions
Advise patients to tell their healthcare provider when they start or stop taking
any concomitant medications. VARUBI is a moderate CYP2D6 inhibitor and can
increase plasma concentrations of CYP2D6 substrates if they are co-administered.
The inhibitory effect of VARUBI on CYP2D6 lasts at least 7 days and may last
longer than 7 days after a single dose
Manufactured for: TESARO, Inc. 1000 Winter St., #3300, Waltham, MA 02451
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Rolapitant is a selective and competitive antagonist of human substance P/NK1 receptors.
Rolapitant does not have significant affinity for the NK2 or NK3 receptors or for
a battery of other receptors, transporters, enzymes and ion channels.
Rolapitant is also active in animal models of chemotherapy-induced emesis.
2. Pharmacokinetics
Absorption
Following a single dose administration of 180 mg VARUBI under fasting conditions
to healthy subjects, rolapitant was measurable in plasma between 30 minutes and
the peak plasma concentration (Cmax) for rolapitant was reached in about 4 hours
and mean Cmax was 968 ng/mL (%CV:28%).
Following multiple oral doses 9 to 45 mg once daily of rolapitant, accumulation
of rolapitant was approximately 5-fold.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
There are no available data on VARUBI use in pregnant women to inform any
drug-associated risks.
In the U.S. general population, the estimated background risk of major birth
defects and miscarriage in clinically recognized pregnancies is 2% to 4%
and 15% to 20%, respectively.
2. Lactation
Risk Summary
There are no data on the presence of rolapitant in human milk, the effects of rolapitant
in the breastfed infant, or the effects of rolapitant on milk production.
Rolapitant hydrochloride administered orally to lactating female rats was present
in milk
The developmental and health benefits of breastfeeding should be considered
along with the mother’s clinical need for VARUBI and any potential adverse
effects on the breastfed infant from VARUBI or from the underlying maternal
condition or the use of concomitant chemotherapy
3. Pediatric Use
Safety and efficacy of VARUBI have not been established in pediatric patients.
4. Geriatric Use
Of the 1294 subjects treated with VARUBI, 25% were 65 years and over,
while 5% were 75 and over. No overall differences in safety or efficacy
were reported between the elderly subjects and younger subjects,
but greater sensitivity of some older individuals cannot be ruled out.
