KYPROLIS*
Manufacturer DetailsGENERIC*
USA AND CANADA
Compositions:
Carfizomib- mg,
Carfizomib- mg,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | unit |
List of Related Indications:
- Patients with multiple myeloma who have reeceived two therapies, including treatment with Velcade(bortezomb) and an immunomodulator
List Of Drugs:
- Carfilzomib- Kyprolis- @- (July 2012)- Chemotherapy
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Carfilzomib is primarily metabolized via peptidase and epoxide hydrolase activities,
and as a result, the pharmacokinetic profile of carfilzomib is unlikely to be affected
by concomitant administration of cytochrome P450 inhibitors and inducers.
Carfilzomib is not expected to influence exposure of other drugs
Indication:
KYPROLIS. (carfilzomib) for Injection, for intravenous use
Initial U.S. Approval: 2012
Drug Name- Kyprolis
Active Ingredient - Carfilzomib
To treat patients with multiple myeloma who have received at least two prior
therapies, including treatment with Velcade(Bortezomib) and an immunomodulatory
Indication-
To treat patients with multiple myeloma who have received at least two prior
therapies, including treatment with Velcade(Bortezomib) and an immunomodulator
Approved by FDA on 20-7-2012 (Ref- FDA Approved List- 2012)
SUBSEQUENT APPROVAL-
Proprietary Name- KYPROLIS*
Established Name- Carfilzomib
Applicant- Onyx Pharmaceuticals Inc.
(An Amgen Subsidiary)
Indication- Carfilzomib in combination with Lenalidomide and Dexamethasone
for the treatment of patients with relapsed Multiple Myeloma who
have received one or three pior lines of therapy
Approval Date- July 24,2015
Approved by U.S.FDA as on 24-7-2015 (Ref- FDA approved List- 2015)
Adverse Reaction:
Most commonly reported adverse reactions (incidence . 30%) are fatigue, anemia,
nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia.
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Cardiac Adverse Reactions including heart failure and ischemia:
Monitor for cardiac complications. Treat promptly and withhold KYPROLIS.
Pulmonary Hypertension: Withhold dosing if suspected.
Pulmonary Complications: Monitor for and manage dyspnea immediately;
interrupt KYPROLIS until symptoms have resolved or returned to baseline.
Infusion Reactions: Pre-medicate with dexamethasone to prevent.
Advise patients to seek immediate medical attention if symptoms develop.
Tumor Lysis Syndrome (TLS): Hydrate patients to prevent.
Monitor for TLS and treat promptly.
Thrombocytopenia: Monitor platelet counts; reduce or interrupt dosing
as clinically indicated.
Hepatic Toxicity and Hepatic Failure: Monitor liver enzymes and withhold
dosing if suspected.
Embryo-fetal Toxicity: KYPROLIS can cause fetal harm.
Females of reproductive potential should avoid becoming pregnant while
being treated.
Dosages/ Overdosage Etc:
Indication-
To treat patients with multiple myeloma who have received at least two prior
therapies, including treatment with Velcade(Bortezomib) and an immunomodulator
Indication- Carfilzomib in combination with Lenalidomide and Dexamethasone
for the treatment of patients with relapsed Multiple Myeloma who
have received one or three pior lines of therapy
INDICATIONS AND USAGE
KYPROLIS is a proteasome inhibitor indicated for the treatment of patients with
multiple myeloma who have received at least two prior therapies including
bortezomib and an immunomodulatory agent and have demonstrated disease
progression on or within 60 days of completion of the last therapy.
Approval is based on response rate.
Clinical benefit, such as improvement in survival or symptoms, has not
been verified.
DOSAGE AND ADMINISTRATION
Administer intravenously over 2 to 10 minutes, on two consecutive days each week
for three weeks (Days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest
period (Days 17 to 28).
Recommended Cycle 1 dose is 20 mg/m2/day and if tolerated increase
Cycle 2 dose and subsequent cycles doses to 27 mg/m2/day.
Hydrate patients prior to and following administration.
Pre-medicate with dexamethasone prior to all Cycle 1 doses, during
the first cycle of dose escalation, and if infusion reaction symptoms develop
or reappear.
Modify dosing based on toxicity.
DOSAGE FORMS AND STRENGTHS
Single-use vial: 60 mg sterile lyophilized powder
Patient Information:
PATIENT COUNSELING INFORMATION
Discuss the following with patients prior to treatment with KYPROLIS:
Instruct patients to contact their physician if they develop any of the following
symptoms:
fever, chills, rigors, chest pain, cough, or swelling of the feet or legs.
Advise patients that KYPROLIS may cause fatigue, dizziness, fainting,
and/or drop in blood pressure.
Advise patients not to drive or operate machinery if they experience any of
these symptoms.
Advise patients that they may experience shortness of breath (dyspnea)
during treatment with KYPROLIS. This most commonly occurs within a day of dosing.
Advise patients to contact their physicians if they experience shortness of breath.
Counsel patients to avoid dehydration, since patients receiving KYPROLIS therapy
may experience vomiting and/or diarrhea.
Instruct patients to seek medical advice if they experience symptoms of dizziness,
lightheadedness, or fainting spells.
Counsel females of reproductive potential to use effective contraceptive measures
to prevent pregnancy during treatment with KYPROLIS. Advise the patient that if
she becomes pregnant during treatment, to contact her physician immediately.
Advise patients not to take KYPROLIS treatment while pregnant or breastfeeding.
If a patient wishes to restart breastfeeding after treatment, advise her to discuss
the appropriate timing with her physician.
Advise patients to discuss with their physician any medication they are currently
taking prior to starting treatment with KYPROLIS, or prior to starting any new
medication(s) during treatment with KYPROLIS.
Pharmacology/ Pharmacokinetics:
1.Mechanism of Action
Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor that irreversibly binds
to the N-terminal threonine-containing active sites of the 20S proteasome,
the proteolytic core particle within the 26S proteasome.
Carfilzomib had antiproliferative and proapoptotic activities in vitro in solid and
hematologic tumor cells.
In animals, carfilzomib inhibited proteasome activity in blood and tissue and
delayed tumor growth in models of multiple myeloma, hematologic, and solid tumors.
2. Pharmacokinetics
Absorption: The Cmax and AUC following a single intravenous dose of 27 mg/m2
was 4232 ng/mL and 379 ng.hr/mL, respectively. Following repeated doses
of carfilzomib at 15 and 20 mg/m2, systemic exposure (AUC) and half-life were
similar on Days 1 and 15 or 16 of Cycle 1, suggesting there was no systemic
carfilzomib accumulation. At doses between 20 and 36 mg/m2, there was a
dose-dependent increase in exposure.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category D
Females of reproductive potential should be advised to avoid becoming pregnant
while being treated with KYPROLIS. Based on its mechanism of action and findings
in animals, KYPROLIS can cause fetal harm when administered to a pregnant woman.
Carfilzomib caused embryo-fetal toxicity in pregnant rabbits at doses that were
lower than in patients receiving the recommended dose.
If KYPROLIS is used during pregnancy, or if the patient becomes pregnant while
taking this drug, the patient should be apprised of the potential hazard to the fetus.
2.Nursing Mothers
It is not known whether KYPROLIS is excreted in human milk. Since many drugs are
excreted in human milk and because of the potential for serious adverse reactions
in nursing infants from KYPROLIS, a decision should be made whether to
discontinue nursing or to discontinue the drug, taking into account the importance
of the drug to the mother.
3. Pediatric Use
The safety and effectiveness of KYPROLIS in pediatric patients have not been established.
4. Geriatric Use
In studies of KYPROLIS there were no clinically significant differences observed
in safety and efficacy between patients less than 65 years of age and patients
65 years of age and older.
