matthew lacroix pharm.d bcps assistant professor university of new england college of pharmacy april...

NEW DRUG UPDATE 2014

Matthew Lacroix Pharm.D BCPSAssistant ProfessorUniversity of New England College of PharmacyApril 26, 2014

Objectives

Pharmacists objectives1. Discuss the basic pharmacology of the new drugs presented and how the pharmacologic actions relate to both therapeutic and adverse effects.

2. Discuss clinically significant adverse effects and drug interactions, and the appropriate dosing and monitoring of the new drugs presented.

3. Discuss the therapeutic role of the new drugs presented as compared to agents already marketed.

Technician objectives1. List the new drugs presented.

2. Describe clinically significant adverse effects and drug interactions, and the appropriate dosing and monitoring of the new drugs presented.

Conflicts of Interest

Dr. Lacroix has no conflicts to report

Best resource for new drug release

Pharmacist Letter http

://pharmacistsletter.therapeuticresearch.com/pl/NewDrugs.aspx?cs=&s=PL&pt=20&yr=2013

Tend to highlight most important new agents, new formulations, and new biologics

http://pharmacistsletter.therapeuticresearch.com/pl/NewDrugs.aspx?cs=&s=PL&pt=20&yr=2013




How this presentation was developed

There have been about 50 new agents since May 2013 Using the most scientific polling source I could find

(Facebook) I asked about what new medications people most wanted to spend some time on

That list was cross referenced with New Entities list from Pharmacist Letter©

Drugs are introduced in two ways Quick hits

1 slide on the medication as it may be rarer to see in practice Topic reviews

4-5 slides on the medication, focusing on what is unique about the drug, key elements in patient counseling and monitoring, and the product that is currently the most similar to it on the market

Q1) Lurasidone has FDA indications for which of the following

1 2 3 4

0 000

1) bipolar I; Schizophrenia

2)bipolar II; Schizophrenia

3) Bipolar I; Depression

4) Bipolar II; Depression

Lurasidone (Latuda©)

Class: Atypical Antipsychotic Uses

Depressive phase of bipolar Schizophrenia

MOA high affinity for D2, 5-HT2A, and 5-

HT7 receptors; moderate affinity for alpha2C-adrenergic receptors; and is a partial agonist for 5-HT1A receptors

No affinity for muscarinic M1 and histamine H1 receptors


Adverse effects >10% Central nervous system:

Drowsiness extrapyramidal reaction Akathisia parkinsonian-like syndrome

Endocrine & metabolic: Increased serum triglycerides increased serum glucose increased serum cholesterol

Gastrointestinal: Nausea


Renal Dosing At CrCl of 50ml/min reduce dose by 50%

Drug-Drug interactions CYP 450 3A4 substrate

Watch out for strong inhibitors and inducers

Moderate inhibitors (verapamil) PI indicates 50% dose

Pregnancy rating-B Still risk, particularly in 3rd trimester


Key counseling points Patients do experience orthostatic

hypertension Food should be taken with med to

reduce symptoms Clear fluids; preferable non-caffeinated

Available as 20,40,60,80,100, 120 mg tablets

Average cost about $800 for 30 days

Q2) Estrogens (conjugated/equine) and Bazedoxifene is a combination of what two classes of medications?

1) 2) 3) 4)

0 000

1) estrogen derivatives and SERM

2) estrogen and progestogen

3) estrogen and SSRI

4) estrogen and SNRI

Estrogens (conjugated/equine) and Bazedoxifene (Duavee©)

Class: Estrogen Derivative; Selective Estrogen Receptor Modulator (SERM)

Primary uses Postmenopausal osteoporosis prophylaxis Vasomotor symptoms

MOA Conjugated estrogens act as an estrogen

agonist and bazedoxifene acts as an estrogen agonist/antagonist depending on the specific tissue.


Vasomotor symptoms Most common 12-24 months after last

Menses Most common reason treatment is sought May interrupt sleep and cause insomnia Occur in 75%–85% of women, usually

within 12–24 months after the last menstrual period

May cause increased skin temperature, nausea, dizziness, headache, palpitations, diaphoresis, and night sweats


Adverse effects Dizziness Gastrointestinal

Diarrhea Nausea Dyspepsia upper abdominal pain

Neuromuscular Muscle spasm neck pain

Respiratory: Oropharyngeal pain


Renal dosing Not studied- no official recommendation

May consider stopping at 30ml/min

Drug-Drug interactions Anticoagulants

Reduce efficacy- consider different therapy CYP 450 3A4

Estrogen is a substrate so be aware!

Pregnancy category X


Key counseling points Swallow tablet whole Any abnormal bleeding should be report to PCP Any signs of chest pain, stroke like symptoms Take at same time every day

Available as 0.45-20mg tablet $133.03 for 30

Most like Prempro

Replaces the progestin with the SERM

Ospemifene(Osphena)

Class: SERM Indication: use for Dyspareunia 60 mg once daily Not indicated for use for vasomotor

symptoms CYP 3A4, 2C9 drug drug interactions

Q3)Fluticasone/vilanterol inhalers most resemble which current inhaler on the market?

1) 2) 3) 4)

0 000

1) Advair HFA2) Advair DPI3) Serevent diskus4) Proair HFA

Fluticasone and Vilanterol(Breo Ellipta©)

Class: Combo long acting B2 agonist; inhaled corticosteroid

Primary Use COPD exacerbation reduction

MOA Fluticasone is a corticosteroid with anti-

inflammatory activity, immunosuppressive properties, and antiproliferative actions.

Vilanterol, a long-acting beta2-agonist, relaxes bronchial smooth muscle by selective action on beta2-receptors with little effect on heart rate.


Adverse effects Cardiovascular:

Hypertension peripheral edema

Central nervous system: Headache

Gastrointestinal: Oropharyngeal

candidiasis Diarrhea

Neuromuscular Arthralgia back pain bone fracture

Respiratory Nasopharyngitis upper respiratory

tract infection Pneumonia


Renal dosing Inhaled-no adjustment needed

Drug-Drug interactions The same as all other combo inhalers

Pregnancy class C


Counseling points Unique inhaler delivery system http://youtu.be/Cq8uQi_ETls Other key points are similar to other

combo products (Advair) Available as 100/25mcg inhaler

Cost of ~$121 for 30 day supply (slightly cheaper)

http://youtu.be/Cq8uQi_ETls

http://youtu.be/Cq8uQi_ETls

Umeclidinium/vilanterol (Anoro Ellipta©)

Long acting anticholinergic/Beta-agonist for COPD

Avoid other anticholinergics Potassium needs to be monitored,

supplemental potassium held until patient is stabilized on medication

Dosing: once daily (14 doses per inhaler)

Q4) dapagliflozin reduces A1C by what percent?

1) 2) 3) 4)

0 000

1) 0.5%2) 1%3) 1.5%4) 2%

Dapagliflozin(Farxiga©)

Class: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor

Use Treatment of type 2 DM

MOA inhibits sodium-glucose cotransporter 2 (SGLT2) in the

proximal renal tubules, reduces reabsorption of filtered glucose from the

tubular lumen SGLT2 is the main site of filtered glucose reabsorption reduction of filtered glucose reabsorption and lowering

of RTG result in increased urinary excretion of glucose, thereby reducing plasma glucose concentrations.


Adverse effects Endocrine

Mild hypoglycemia Dyslipidemia

Gastrointestinal Nausea Constipation

Hematologic Increased hematocrit

(1%, hematocrit >55%)

Infection Influenza

Neuromuscular Back pain

Respiratory Nasopharyngitis

Genitourinary: Fungal vaginosis urinary tract infection increased urine

output genitourinary fungal

infections dysuria


Renal dosing eGFR <60 mL/minute/1.73 m2:

Initial: Use not recommended. persistent decrease in eGFR to <60

mL/minute/1.73 m2, dapagliflozin should be discontinued.

Drug-Drug Interactions No significant CYP450 interactions Caution in concurrent steroid use

Pregancy Category: C Advise discontinuation in 2nd and 3rd trimesters


Counseling points Make sure to report soreness in genitals

to PCP High risk of infection secondary to

medication You may initially need to void more

frequently You may feel dizziness with this

medication, check BG. If normal consider checking BP, consult with PCP

Available as 5 and 10mg capsule Cost ~$347 for 30 day supply

Alogliptin/metformin(Kazano©)Alogliptin/pioglitazone(Oseni©)

Combo DPP-4 and biguanide Combo DPP-4 and Thiazolidinedione

Q5) Qudexy XR an extended release formulation for what currently available anticonvulsant?

1) 2) 3) 4)

0 000

1) Topiramate2) Phenytoin3) Carbamazipine4) Ethosuximide

Topiramate(Qudexy XR ©; Trokendi XR©)

Class: Anticonvulsant Use:

Extended release formulations for epilepsy as mono- or adjunctive therapy

Both are new extended release formulations Qudexy XR is indicated for age 2 or greater Trokendi XR is indicated for age 6 or greater NOT BIOEQUVALANTS

MOA Not fully described (AKA we don’t know but think something

from below is involved) Blocks neuronal voltage-dependent sodium channels enhances GABA(A) activity antagonizes AMPA/kainate glutamate receptors weakly inhibits carbonic anhydrase


Adverse Effects >10% Central nervous system:

Paresthesia Drowsiness Dizziness Nervousness Fatigue Ataxia psychomotor retardation impaired speech memory impairment abnormal behavior confusion

Endocrine Decreased serum

bicarbonate Gastrointestinal

Anorexia Nausea

Ophthalmic Visual disturbance

Renal Increased serum

creatinine


Renal dosing CrCL <70 ml/min reduce dose by 50%

Drug-Drug interactions Oral contraceptives Anything that causes sleepiness;fatigue Pregnancy category: D


Counseling points Same as topiramate noting side effects may

last longer as the half life is about 5 times as long as IR topiramate

Avoid beer, wine, or mixed drinks within 6 hours before or 6 hours after taking this drug.

Available as 25, 50, 100, 200 mg (Tokendi XR) Price range from ~$200 to ~$700 depending

on strength for 30 tablets Qudexy XR approved March 2014, expected

shortly on shelves

Vortioxetine(Brintellix©)

Class: SSRI Initial indication for Major depressive

disorder Major substrate of CYP 2D6 Major side effect

sexual disorder Up to 30% of both men and women

GI Up to 30% dose dependent, tolerance can

build

Q6) Simeprevir and and sofosbuvir are new medications introduced for the treatment of what disease at the end of 2013?

1) 2) 3) 4)

0 000

1) COPD2) Menopause3) Hepatitis C4) bipolar disorder

Hepatitis C

Simeprevir (Olysio) Oral: 150 mg once daily (in combination with

peginterferon alfa and ribavirin). Treatment duration is indication and response-specific.

Focus on HCV-RNA detection/undectable Cost: 150 mg (28): $26544.00

Sofosbuvir (Sovaldi) Oral: 400 mg daily with concomitant ribavirin and

with or without peginterferon alfa (maximum: 400 mg daily).

Genotype specific for duration requirements Costs : 400 mg (28): $33600.00

Hydrocodone(Zohydro ER)

New stand alone product Highly controversial Starting dose is 10mg in opioid naïve

patients and titrated up q3-7 days Side effects are similar to

hydrocodone/APAP with less liver side effects

C-II

Hydrocodone(Zohydro ER)

Conversion from transdermal fentanyl: Treatment with hydrocodone ER may be started 18 hours after the removal of the fentanyl transdermal patch. For every fentanyl 25 mcg per hour transdermal patch, initially substitute hydrocodone ER 10 mg every 12 hours. Monitor the patient closely.

Previous Oral Opioid Oral Dosage

Approximate Oral

Conversion Factor2

Hydrocodone 10 mg 1Oxycodone 10 mg 1Methadone3 10 mg 1

Oxymorphone 5 mg 2

Hydromorphone 3.75 mg 2.67Morphine 15 mg 0.67Codeine 100 mg 0.1

1Approximate equivalent doses for conversion from current opioid therapy to hydrocodone ER.2Ratio for converting oral opioid dose to approximate hydrocodone ER equivalent dose.3Monitor closely; ratio between methadone and other opioid agonists may vary widely as a function of previous drug exposure. Methadone has a long half-life and may accumulate in the plasma.

Questions?

matthew lacroix pharm.d bcps assistant professor university of new england college of pharmacy april...

Documents

new drugs

depression slide

new formulations

new biologics

nausea slide

days slide

market slide

new entities list