Ixazomib- Ninlaro -@- (Nov 2015)- Anti-cancer
Drug Name:Ixazomib- Ninlaro -@- (Nov 2015)- Anti-cancer
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:
Strong CYP3A Inducers
Avoid concomitant administration of NINLARO with strong CYP3A inducers
(such as rifampin, phenytoin, carbamazepine, and St. John’s Wort)
Indication:
NINLAROR (ixazomib) capsules, 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.38
Drug Name - Ixazomib
Active Ingredient- Ninlaro
Date of approval - 11/20/2015
FDA-approved use - To treat people with multiple myeloma who have
received at least one prior therapy
Approved by US FDA on 11/20/2015- (Ref- FDA approved List- 2015)
INDICATIONS AND USAGE
NINLARO is a proteasome inhibitor indicated in combination with lenalidomide
and dexamethasone for the treatment of patients with multiple myeloma who have
received at least one prior therapy.
Adverse Reaction:
The most common adverse reactions (. 20%) are diarrhea, constipation,
thrombocytopenia, peripheral neuropathy, nausea, peripheral edema,
vomiting, and back pain.
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Thrombocytopenia:
Monitor platelet counts at least monthly during treatment and adjust dosing,
as needed.
Gastrointestinal Toxicities:
Adjust dosing for severe diarrhea, constipation,nausea, and vomiting, as needed.
Peripheral Neuropathy:
Monitor patients for symptoms of peripheral neuropathy and adjust dosing, as needed.
Peripheral Edema:
Monitor for fluid retention. Investigate for underlying causes, when appropriate.
Adjust dosing, as needed.
Cutaneous Reactions:
Monitor patients for rash and adjust dosing, as needed.
Hepatotoxicity:
Monitor hepatic enzymes during treatment.
Embryo-Fetal Toxicity: NINLARO can cause fetal harm. Advise females of
reproductive potential of the potential risk to a fetus and to use effective
contraception.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
NINLARO is a proteasome inhibitor indicated in combination with lenalidomide
and dexamethasone for the treatment of patients with multiple myeloma who have
received at least one prior therapy.
DOSAGE AND ADMINISTRATION
Recommended starting dose of 4 mg taken orally on Days 1, 8, and 15
of a 28-day cycle.
Dose should be taken at least one hour before or at least two hours after food.
DOSAGE FORMS AND STRENGTHS
Capsules: 4 mg, 3 mg, and 2.3 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Dosing Instructions
Instruct patients to take NINLARO exactly as prescribed.
Advise patients to take NINLARO once a week on the same day and at approximately the
same time for the first three weeks of a four week cycle.. Advise patients to take
NINLARO at least one hour before or at least two hours after food.
Advise patients that NINLARO and dexamethasone should not be taken at the same time,
because dexamethasone should be taken with food and NINLARO should not be taken
with food.
Advise patients to swallow the capsule whole with water. The capsule should not be
crushed, chewed or opened.
Advise patients that direct contact with the capsule contents should be avoided.
In case of capsule breakage, avoid direct contact of capsule contents with the
skin or eyes. If contact occurs with the skin, wash thoroughly with soap and water.
If contact occurs with the eyes, flush thoroughly with water.
If a patient misses a dose, advise them to take the missed dose as long as the next
scheduled dose is . 72 hours away. Advise patients not to take a missed dose if it is
within 72 hours of their next scheduled dose.
If a patient vomits after taking a dose, advise them not to repeat the dose but resume
dosing at the time of the next scheduled dose.
Advise patients to store capsules in original packaging, and not to remove the capsule
from the packaging until just prior to taking NINLARO.
Thrombocytopenia
Advise patients that they may experience low platelet counts (thrombocytopenia).
Signs of thrombocytopenia may include bleeding and easy bruising.
.
Gastrointestinal Toxicities
Advise patients they may experience diarrhea, constipation, nausea and vomiting and
to contact their physician if these adverse reactions persist. .
Peripheral Neuropathy
Advise patients to contact their physicians if they experience new or worsening symptoms
of peripheral neuropathy such as tingling, numbness, pain, a burning feeling in the feet
or hands, or weakness in the arms or legs.
Peripheral Edema
Advise patients to contact their physicians if they experience unusual swelling of their
extremities or weight gain due to swelling
Cutaneous Reactions Advise patients to contact their physicians if they experience
new or worsening rash .
Hepatotoxicity
Advise patients to contact their physicians if they experience jaundice or right upper
quadrant abdominal pain
Pregnancy
Advise women of the potential risk to a fetus and to avoid becoming pregnant while
being treated with NINLARO and for 90 days following the final dose.
Advise patients to contact their physicians immediately if they or their female partner
become pregnant during treatment or within 90 days of the final dose .
Concomitant Medications
Advise patients to speak with their physicians about any other medication they are
currently taking and before starting any new medications.
Distributed and Marketed by: Takeda Pharmaceutical Company Limited Cambridge,
MA 02139
NINLARO is a registered trademark of Millennium Pharmaceuticals, Inc.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Ixazomib is a reversible proteasome inhibitor. Ixazomib preferentially binds and inhibits
the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.
Ixazomib induced apoptosis of multiple myeloma cell lines in vitro. Ixazomib demonstrated
in vitro cytotoxicity against myeloma cells from patients who had relapsed after multiple
prior therapies, including bortezomib, lenalidomide, and dexamethasone.
The combination of ixazomib and lenalidomide demonstrated synergistic cytotoxic effects
in multiple myeloma cell lines. In vivo, ixazomib demonstrated antitumor activity in a
mouse multiple myeloma tumor xenograft model.
2. Pharmacokinetics
Absorption
After oral administration, the median time to achieve peak ixazomib plasma concentrations
was one hour. The mean absolute oral bioavailability was 58%, based on population
PK analysis. Ixazomib AUC increases in a dose proportional manner over a dose range
of 0.2 to 10.6 mg.
A food effect study conducted in patients with a single 4 mg dose of ixazomib showed
that a high-fat meal decreased ixazomib AUC by 28% and Cmax by 69%
Distribution
Ixazomib is 99% bound to plasma proteins and distributes into red blood cells with a blood-to-plasma ratio of 10. The steady-state volume of distribution is 543 L.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Women should avoid becoming pregnant while being treated with NINLARO.
Risk Summary
NINLARO can cause fetal harm when administered to a pregnant woman.
There are no human data available regarding the potential effect of NINLARO on
pregnancy or development of the embryo or fetus.
Advise women of the potential risk to a fetus and to avoid becoming pregnant while
being treated with NINLARO
2. Lactation
Risk Summary
It is not known whether NINLARO or its metabolites are present in human milk.
Many drugs are present in human milk and as a result, there could be a potential for
adverse events in nursing infants. Advise women to discontinue nursing.
3. Females and Males of Reproductive Potential
Contraception
Male and female patients of childbearing potential must use effective contraceptive
measures during and for 90 days following treatment.
4. Pediatric Use
Safety and effectiveness have not been established in pediatric patients.
5. Geriatric Use
Of the total number of subjects in clinical studies of NINLARO, 55% were 65 and over,
while 17% were 75 and over. No overall differences in safety or effectiveness were
observed between these subjects and younger subjects, and other reported
clinical experience has not identified differences in responses between the elderly
and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
6. Hepatic Impairment
In patients with moderate or severe hepatic impairment, the mean AUC increased by 20% when compared to patients with normal hepatic function. Reduce the starting dose of NINLARO in patients with moderate or severe hepatic impairment.
7. Renal Impairment
In patients with severe renal impairment or ESRD requiring dialysis, the mean AUC increased by 39% when compared to patients with normal renal function. Reduce the starting dose of NINLARO in patients with severe renal impairment or ESRD requiring dialysis. NINLARO is not dialyzable and therefore can be administered without regard to the timing of dialysis .