New Drug Update 2015

Jess Monitz, PharmD

PGY-1 Pharmacy Resident
Disclosure

The presenter has no disclosures or conflicts of interest

Outline

Introduction

New Medications to Market

Review/Questions
Objectives

1. Match the medications to their appropriate indication

2. Identify therapy limiting side effects of the medications
3. Explain correct storage and preparation directions for
each medication
2015: A Year in Review
 2015: A Year in Review

Impact Approval Designation

Novel Drug Orphan Drug Priority Accelerated Fast Track Breakthrough
Standard Drug Standard Standard

18%
35% 32% 31%
47%
54%
47% 14% 22%
Medications to Review

 Entresto®: Sacubitiril/valsartan
 Praxbind®: Idarucizumab
 Ibrance®: Palbociclib
 Bridion®: Sugammadex
 Avycaz®: Ceftazidime/Avibactam
 Corlanor®: Ivabradine
Sacubitiril/Valsartan
Indications

 Heart failure

 Reduces blood pressure

Mechanism of Action

 Angiotensin receptor neprilysin inhibitor

(ARNI)

 Sacubitril: Prodrug that inhibits neprilysin

leading to increased levels of natriuretic
peptides

 Valsartan: Direct antagonism of

angiotensin II receptors inducing
vasoconstriction through aldosterone,
catecholamine, arginine vasopressin
release
Medication Properties

 Sacubitril is a prodrug converted to its active metabolite by esterases in the blood

 Use of an ACE inhibitor with sacubitril is contraindicated; allow a 36 hour washout period
when switching from or to an ACE inhibitor
Medication Dosing

 Patients previously taking >10 mg/day of enalapril or >160 mg/day of valsartan (or
equivalent dose of another ACE inhibitor or ARB):
 Sacubitril 49 mg and valsartan 51 mg twice daily

 Patients previously taking low doses of an ACE inhibitor (≤10 mg/day of enalapril or ≤160
mg/day of valsartan (or equivalent dose of another ACE inhibitor or ARB):
 Sacubitril 24 mg and valsartan 26 mg twice daily

 Patients not currently taking an ACE inhibitor or an ARB:

 Sacubitril 24 mg and valsartan 26 mg twice daily

 Double the dose as tolerated after 2 to 4 weeks to the target maintenance dose of sacubitril 97 mg
and valsartan 103 mg twice daily
Storage, Preparation, and Administration

 Administer with or without food

 Store in a cool, dry place

Precautions

Side Effects Contraindications

• Hypotension • History of angioedema

• Hyperkalemia with previous ACE or
• Increase serum ARB therapy
creatinine • Use of ACE inhibitors
• Angioedema within 36 hours of dose
• Cough • Use with aliskirin
• Pregnancy
Clinical Trials

 Paradigm-HF
Review
Idarucizumab
Indications

 Reversal of dabigatran (Pradaxa®)

 Indicated for emergent surgery or life-

threatening/uncontrolled bleeding
Mechanism of Action

 Humanized monoclonal antibodies

 Binds to dabigatran and its metabolites

 Neutralizes the anticoagulation affect in minutes

Medication Properties

 Effect on bleeding is observed within minutes and normal blood function is restored in
approximately 12 hours

 Medication effect lasts for up to 24 hours

Medication Dosing

 Administer 5 g as 2 separate, 2.5 mg doses 15 minutes apart

 No dosing adjustments are necessary

 May redose 5 g if patient continues to have elevated labs or needs emergent surgery
Storage, Preparation, and Administration

 Medication is administered undiluted as an IV bolus

 Infusion of each vial should take no longer than 5-10 minutes

 If placed in a bag, medication expires in 1 hour

 Refrigerate medication in original packaging (protect from light)

 Vial is good for 48 hours at room temperature or 6 hours if exposed to light

Precautions

Side Effects Contraindications

•Hypersensitivity •No
•Risk of clotting contraindications
•Fever to a rescue
medication
•Headache
•Hypokalemia
Clinical Trials

 Re-VERSE AD
Review
Palbociclib
Indications

 Estrogen receptor (ER) positive, human epidermal growth factor (HER@) negative
advanced breast cancer in combination with letrozole in post-menopausal women as
initial endocrine based therapy in metastatic disease
Mechanism of Action

Palbociclib

 Inhibits cyclin-dependent kinase (CDK) 4 and 6

 CDK 4 and 6 are downstream signaling pathways
that lead to cell multiplication. Inhibiting this
pathways prevents cells from moving for G1 into S
phase of the cell cycle
Medication Properties

 Must be administered with high-fat, high calorie meal

because absorption increases drastically

 Medication is metabolized by the liver, leading to

many drug-drug interactions

 Medication must be handled like a hazardous

substance
Medication Dosing

 125 mg once daily with food for 21 days, then 7

days off
 Given in combination with letrozole 2.5 mg once daily

 In combination with Cyp3A4 inhibitors (azole

antifungals, verapamil, etc.) dose should be
reduced to 75 mg once daily
Storage, Preparation, and Administration

 Must be administered with a high-fat meal at

approximately the same time each day

 Capsules must be swallowed whole, cannot be

opened
Precautions

Side Effects Warnings

• Fatigue • Neutropenia median

• Peripheral neuropathy onset of 15 days and
• Alopecia duration of 7 days
• Nausea/vomiting (low) • Pulmonary embolism
was observed in trials
• Neutropenia
• Infection
Clinical Trials

 Paloma-1/Trio-18

 Paloma3
Review
Sugammadex
Indications

 Reversal of neuromuscular blockade from

rocuronium or vecuronium

 Immediate reversal of neuromuscular blockade

at 3 minutes after administration of rocuronium
(intubation)
Mechanism of Action

 Selectively binds free molecules of

nondepolarizing neuromuscular blocking
Bridion Mechanism of Action
agents rocuronium or vecuronium

 Does not affect neuromuscular blocker

already bound to receptors
Rocuronium or
vecuronium
Bridion Inactive complex
 Though nondepolarizing neuromuscular
blockers, pancuronium, ciastracurium and
mivacurium fit poorly or not at all in the
complex
Medication Properties

 Onset of effect is less than 3 minutes

 Half-life is increased with renal impairment

 Medication is excreted in the urine unchanged

Medication Dosing

 Routine reversal of rocuronium or vecuronium-induced blockade

 Deep block: 4 mg/kg as a single dose
 Moderate block: 2 mg/kg as a single dose

 Immediate reversal of rocuronium-induced blockade (intubation)

 16 mg/kg as a single dose administered soon (~3 minutes) after administration of a single dose of
1.2 mg/kg of rocuronium
 This dose has not been evaluated following administration of vecuronium
Storage, Preparation, and Administration

 Rapid IV push over 10 seconds

 Compatible with NS, D5W, LR, D5NS

 Store at 25°C

 Protect from light

 Product is only good for 5 days if not protected from light
Precautions

Side Effects Warnings/Precautions Contraindications

•Hypotension •Sugammadex has a high •Hypersensitivity was

•Headache affinity for bone and tooth documented in studies
•Nausea enamel which may cause •CrCl <30 mL/min or dialysis
deposits of the medication
•Vomiting
•Bradycardia can occur within
•Pain at injection site
minutes after administration
and can be treated with
atropine if necessary
•Recurrence of neuromuscular
blockade usually due to
suboptimal dosing
•Only indicated to surgical
reversal of neuromuscular
blockers, use in the intensive
care unit has not been
evaluated
Clinical Trials

 Aurora Trial
Review
Ceftazidime/Avibactam
Indications

 Complicated intra-abdominal infections

 Complicated urinary tract infections including pyelonephritis

 Coverage of gram positive and gram negative organisms, especially those resistant to
carbapenems (e.g. meropenem)
Mechanism of Action

 Ceftazidime: Inhibits bacterial cell

wall synthesis causing the bacteria to
lyse

 Avibactam: Inactivates beta-

lactamases and protects ceftazidime
from degradation

Avycaz
Medication Properties

 Avycaz 2.5 g contains 2 g ceftazidime and 0.5 g avibactam

 Eliminated in the urine

Medication Dosing

 2.5 g IV every 8 hours for 5-14 days

 Dose is reduced for patients with renal impairment

Storage, Preparation, and Administration

 Store at room temperature and protect from light

 Supplied as a powder that is reconstituted with 10 mLs NS

 Store vials at room temperature and protect from light

 Mixed solutions are good for 12 hour at room temperature or 24 hours refrigerated
Precautions

Side Effects Contraindications

• Constipation • Allergy to penicillins or

• Abdominal pain cephalosporins
• Anxiety • Previous neurotoxicity
• Renal impairment
• Dizziness
• C.diff
Clinical Trials

 Urinary tract: Recapture 1 and 2

 Intra-abdominal: Reclaim 1 and 2

Review
Ivabradine
Indications

 Stable systolic heart failure

 Ejection fraction of <35
 Heart rate >70
 Used a beta blocker at the highest tolerated dose

 Inappropriate sinus tachycardia (off-label)

Mechanism of Action

 Funny Channel Antagonist

 Works only on channels that are

hyperpolarized

 No effects on repolarization or heart

contractility
Medication Properties

 Metabolized in the liver by Cyp3A4 causing lots of drug interactions

 Azole antifungals, HIV medications, diltiazem, verapamil, digoxin, amiodarone

 Must be taken with food, availability of the medication is doubled

Medication Dosing

 Recommended starting dose is 5 mg twice daily with meals

 Dose can be increased to 7.5 mg twice daily after two weeks to achieve a resting heart
rate of 50-60 beats per minute
 Heart rate >60 bpm: Increase by 2.5 mg twice daily
 Heart rate <50 or symptoms of bradycardia: Decrease by 2.5 mg twice daily

 Patients with a history of conduction defects, bradycardia, hemodynamic compromise,

or they elderly may want to initiate therapy at 2.5 mg BID
Storage, Preparation, and Administration

 Administer with meals

 Store in a cool, dry place

Precautions
Side Effects
• Luminous phenomena
• Increased uncorrected Qt interval
with heart rate slowing
• New onset atrial fibrillation
• Bradycardia
• Conduction disturbances
• Risk of fetal toxicity
Contraindications
• Acute decompensate heart failure
• Blood pressure less than 90/50
mmHg
• Sick sinus syndrome, sinoatrial block,
or 3rd degree AV block
• Resting heart rate less than 60 bpm
prior to treatment
• Severe hepatic impairment
• Pacemaker dependence
Clinical Trials

 Systolic Heart Failure: SHIFT Trial

 Stable Coronary Heart Disease:

Beautiful and Signify Trials

 Inappropriate Sinus Tachycardia

Review
Questions

1. Choose the correct match between the drug and its indication c. Ivabradine
a. Ceftazidime/avibactam = heart failure d. Sugammadex
b. Idarucizumab = breast cancer
c. Palbociclib = reversal of dabigatran 4. Which medication is classified as a hazardous drug and appropriate
precautions should be followed
d. Sugammadex = Reversal of roncuronium
a. Idarucizumab
e. Ivabradine = intra-abdominal infections
b. Sacubitiril/valsartan
c. Ceftazidime/avibactam
2. Which side effect limits the use of ivabradine?
d. Palbociclib
a. Bradycardia (slow heart rate)
b. Nausea
5. Which medication causes therapy limiting hypotension (low blood
c. Skin rash pressure)?
d. Headache a. Ivabradine
b. Sugammadex
3. Which medication is dispensed as 2 vials that are drawn into 1 syringe c. Sacubitiril/valsartan
and administered as a bolus?
d. Ceftazidime/avibactam
a. Palbociclib
b. Idarucizumab