Edoxaban Tosylate- Savaysa -@- (Jan 2015) - Cardiovascular
Drug Name:Edoxaban Tosylate- Savaysa -@- (Jan 2015) - Cardiovascular
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:
Anticoagulants: Avoid concomitant use
Rifampin: Avoid concomitant use
Indication:
SAVAYSA (edoxaban) tablets for oral use
Initial U.S. Approval: 2015
WARNING
(A) REDUCED EFFICACY IN NONVALVULAR ATRIAL FIBRILLATION
PATIENTS WITH CREATININE CLEARANCE (CRCL) > 95 ML/MIN
(B) PREMATURE DISCONTINUATION OF SAVAYSA INCREASES
THE RISK OF ISCHEMIC EVENTS
(C) SPINAL/EPIDURAL HEMATOMA
See full prescribing information for complete boxed warning.
(A) REDUCED EFFICACY IN NONVALVULAR ATRIAL FIBRILLATION
PATIENTS WITH CRCL > 95 ML/MIN:
SAVAYSA should not be used in patients with CrCL > 95 mL/min.
In the ENGAGE AF-TIMI 48 study, nonvalvular atrial fibrillation patients
with CrCL > 95 mL/min had an increased rate of ischemic stroke
with SAVAYSA 60 mg once daily compared to patients treated with warfarin.
In these patients another anticoagulant should be used (5.1).
(B) PREMATURE DISCONTINUATION OF SAVAYSA INCREASES
THE RISK OF ISCHEMIC EVENTS: Premature discontinuation of any
oral anticoagulant in the absence of adequate alternative anticoagulation
increases the risk of ischemic events.
If SAVAYSA is discontinued for a reason other than pathological bleeding
or completion of a course of therapy, consider coverage with another
anticoagulant as described in the transition guidance (2.4, 5.2, 14).
(C) SPINAL/EPIDURAL HEMATOMA: Epidural or spinal hematomas may
occur in patients treated with SAVAYSA who are receiving neuraxial
anesthesia or undergoing spinal puncture.
These hematomas may result in long-term or permanent paralysis.
Consider these risks when scheduling patients for spinal procedures (5.4).
Proprietary Name- SAVAYSA
Established Name- Edoxaban Tosylate
Applicant- Daichi- Sankyo INc.
Indication- Reduce the risk of stroke and Systemic Embolism in patients
with Nonvalvular Atrial Fibrillation
Approval Date- 1-08-2015
Approved by U.S.FDA on 30-06-2015 (Ref- FDA approved List- 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.1
Drug Name - Edoxaban
Active Ingredient- Savaysa
Date of approval - 1/08/2015
FDA-approved use - To reduce the risk of stroke and dangerous blood clots( systemic embolism) in patients
with Atrial Fibrillation that is not caused by a
heart valve problem
Approved by US FDA on 1/08/2015- (Ref- FDA approved List- 2015)
Adverse Reaction:
Treatment of NVAF: The most common adverse reactions (. 5%) are
bleeding and anemia
Treatment of DVT and PE: The most common adverse reactions (. 1%) are
bleeding, rash, abnormal liver function tests and anemia
Contra-Indications:
CONTRAINDICATIONS
. Active pathological bleeding
WARNINGS AND PRECAUTIONS
.
Bleeding: Serious and potentially fatal bleeding. Promptly evaluate signs
and symptoms of blood loss
Mechanical heart valves or moderate to severe mitral stenosis:
Use is not recommended
Dosages/ Overdosage Etc:
Indication- Reduce the risk of stroke and Systemic Embolism in patients
with Nonvalvular Atrial Fibrillation
Approval Date- 1-08-2015
INDICATIONS AND USAGE
SAVAYSA is a factor Xa inhibitor indicated:
To reduce the risk of stroke and systemic embolism (SE) in patients with
nonvalvular atrial fibrillation (NVAF)
Limitation of Use for NVAF
SAVAYSA should not be used in patients with creatinine clearance
(CrCL) > 95 mL/min because of increased risk of ischemic stroke compared
to warfarin at the highest dose studied (60 mg)
SAVAYSA is indicated for the treatment of deep vein thrombosis (DVT)
and pulmonary embolism (PE) following 5 to 10 days of initial therapy
with a parenteral anticoagulant
DOSAGE AND ADMINISTRATION-
Treatment of NVAF: Assess CrCL before initiating therapy
The recommended dose is 60 mg once daily in patients
with CrCL >50 to . 95 mL/min.
Do not use SAVAYSA in patients with CrCL > 95 mL/min
Reduce dose to 30 mg once daily in patients with creatinine
clearance 15 to 50 mL/min
Treatment of DVT and PE: The recommended dose is 60 mg once daily
The recommended dose is 30 mg once daily for patients
with CrCL 15 to 50 mL/min or body weight less than or equal to 60 kg
or who use certain P-gp inhibitors
DOSAGE FORMS AND STRENGTHS
. Tablets: 60 mg, 30 mg, and 15 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Advise patients of the following:
They may bleed more easily, may bleed longer, or bruise more easily when treated with
SAVAYSA to report any unusual bleeding immediately to their healthcare provider
to take SAVAYSA exactly as prescribed
1.to not discontinue SAVAYSA without
talking to the healthcare provider who prescribed it
2. to inform their healthcare providers that they are taking SAVAYSA before any
surgery, medical, or dental procedure is scheduled
3. to inform their healthcare providers and dentists if they plan to take, or are taking
any prescription medications, over-the-counter drugs or herbal products
4. to inform their healthcare provider immediately if they become pregnant or intend to
become pregnant or are breastfeeding or intend to breastfeed during treatment
with SAVAYSA
5. that if a dose is missed, take SAVAYSA as soon as possible the same day,
and resume the normal dosing schedule the following day.
The dose should not be doubled to make up for a missing dose
6. that if they are having neuraxial anesthesia or spinal puncture, advise patients
to watch for signs and symptoms of spinal or epidural hematoma, such as
back pain, tingling, numbness (especially in the lower limbs), muscle weakness,
and stool or urine incontinence. If any of these symptoms occur, advise the
patient to contact his or her physician immediately
Manufactured by:
Daiichi Sankyo Co., LTD. Tokyo 103-8426 Japan
Distributed by:
Daiichi Sankyo, Inc. Parsippany, NJ 07054 USA
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Edoxaban is a selective inhibitor of FXa. It does not require antithrombin III for
antithrombotic activity. Edoxaban inhibits free FXa, and prothrombinase activity
and inhibits thrombin-induced platelet aggregation. Inhibition of FXa in the
coagulation cascade reduces thrombin generation and reduces thrombus formation
2. Pharmacokinetics
Edoxaban displays approximately dose-proportional pharmacokinetics for doses
of 15 to 150 mg and 60 to 120 mg following single and repeat doses, respectively,
in healthy subjects.
Absorption
Following oral administration, peak plasma edoxaban concentrations are
observed within 1-2 hours. Absolute bioavailability is 62%. Food does not
affect total systemic exposure to edoxaban. SAVAYSA was administered
with or without food in the trials
Pregnancy and lactation:
Use in Specific Populations
1. Pregnancy
Pregnancy Category C
Risk Summary
There are no adequate and well-controlled studies in pregnant women.
SAVAYSA should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
2. Nursing Mothers
It is not known if edoxaban is excreted in human milk. Edoxaban was excreted in the
milk of lactating rats. Because many drugs are excreted in human milk and because
of the potential for adverse reactions in nursing infants from SAVAYSA, a decision
should be made to discontinue nursing or the drug, taking into account the
importance of the drug to the mother.
3. Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
4. Geriatric Use
Of the total patients in the ENGAGE AF-TIMI 48 study, 5182 (74%) were 65 years
and older, while 2838 (41%) were 75 years and older.
Of the 1334 (32%) patients were 65 years and older, while 560 (14%)
patients were 75 years and older. In clinical trials the efficacy and safety of
SAVAYSA in elderly (65 years or older) and younger patients were similar .
