keeping up-to-date, with so medication review · vaccine contains live attenuated cholera bacteria...

Keeping Up-to-Date, with so

Little Time: Newly Approved

Medication Review

Golden L. Peters, PharmD, BCPS

Associate Professor, Pharmacy Practice Department

St. Louis College of Pharmacy

Dr. Peters declares no conflicts of interest, real or apparent, and no

financial interests in any company, product, or service mentioned in

this program, including grants, employment, gifts, stock holdings and

honoraria.

Disclosures and Conflict of Interest

At the conclusion of this program, the pharmacist will be able to:

1. Identify new molecular and biological entities that entered the U.S. drug market in the past year (excluding diagnostic compounds)

2. Describe each agent’s mechanism of action, dosage, adverse reactions, contraindications, and drug interaction profile

3. Recognize special instructions and monitoring parameters for each agent

4. Identify molecular entities that have been approved as generic medications by the FDA in the past year

Pharmacist Objectives

At the conclusion of this program, the pharmacy technician will be

able to:

1. Identify new molecular and biological entities that entered the U.S.

drug market in the past year (excluding diagnostic compounds)

2. Describe each agent’s mechanism of action, dosage, adverse

reactions, contraindications, and drug interaction profile

3. List special instructions and monitoring parameters for each agent

4. Identify molecular entities that have been approved as generic

medications by the FDA in the past year

Technician Objectives

1. What is the recommended starting dose for ertugliflozin?

A. 2.5 mg PO daily

B. 5 mg PO daily

C. 10 mg PO daily

D. 15 mg PO daily

Pre-Test Questions

2. What medical indication was sarilumab approved for?

A. Plaque psoriasis

B. Rheumatoid arthritis

C. Hyperlipidemia

D. Hepatitis C

Pre-Test Questions

3. What is the mechanism of action for naldemedine?

A. Opioid antagonist with binding affinities for mu-, delta-, and

kappa-opioid receptors

B. Unknown

C. Human monoclonal antibody that binds to IL-6 receptors, reduces

inflammatory cytokines

D. Oral factor Xa inhibitor that selectively blocks the active site of

FXa

Pre-Test Questions

4. What is the recommend storage procedure for guselkumab?

A. Store at room temperature

B. Shake vial to reconstitute

C. Protect from light

D. Must store in original packaging

Pre-Test Questions

Newly approved medications

New dosage formulations and combinations

Recent generics

Upcoming generics

Products removed from market

Outline

3A4 inhibitors:

Amiodarone

Cimetidine

Clarithromycin

Diltiazem

Erythromycin

grapefruit juice

Ketoconazole

Verapamil

CYP P450 Substrates

• 3A4 inducers:

• Carbamazepine

• Oxcarbazepine

• Phenobarbital

• Phenytoin

• Pioglitazone

• Rifampin

• Topiramate

• St. John’s wort

• 2D6 inhibitors:

• Amiodarone

• Bupropion

• Diphenhydramine

• Fluoxetine

• Haloperidol

• Paroxetine

• Terbinafine

• Chloroquine

Lexi-Comp, Inc. (Lexi-Drugs® ). Lexi-Comp, Inc.; May 3, 2018

https://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DrugInnovation/UCM536693.pdf

To date in 2018 →

Indication:

Indicated for cholera prevention for travelers ages 18 – 64 visiting areas

with active cholera transmission

Only vaccine available to prevent cholera at this time

Mechanism of Action:

Vaccine contains live attenuated cholera bacteria that replicate in the

gastrointestinal tract of the recipient to provide immunity

Dosing:

Single dose, live attenuated oral vaccine

Administered 10 days or more before travel

Duration of coverage is unknown

(3 – 6 months)

Cholera vaccine (Vaxchora™)

U.S Food and Drug Administration, 2016,

https://www.paxvaxconnect.com/PDF/Vaxchora_Prescribing_Information.pdf

Precautions:

Immunocompromised persons

Adverse Reactions:

Mild headache (18.9%)

Mild tiredness (18.7%)

Mild nausea/vomiting (13.3%)

Mild abdominal pain (12.1%)

Moderate tiredness (12%)

Decreased appetite, mild (11.7%)

Cholera vaccine (Vaxchora™)


https://www.paxvaxconnect.com/PDF/Vaxchora_Prescribing_Information.pdf

Source: ttp://www.who.int/gho/epidemic_diseases/cholera/epidemics/en/

Indication:

Treatment of opioid-induced constipation in adults with chronic

noncancer pain

Mechanism of action:

Opioid antagonist with binding affinities for mu-, delta-, and kappa-opioid

receptors

Peripherally acting mu-opioid receptor antagonist in the GI tract,

decreasing the constipating effects of opioids

Dosing:

Schedule II

0.2 mg PO qDay

Naldemedine (Symproic™)


https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208854s000lbl.pdf

Contraindications

Known or suspected GI obstruction

Precautions

Gastrointestinal perforation

Crohn disease

Opioid withdrawal

Administration

Discontinue naldemedine if treatment with opioids is also discontinued




Adverse Reactions

Abdominal pain (8-11%)

Diarrhea (7%)

Nausea (4-6%)

Vomiting (3%)

Drug interaction overview

Strong CYP3A4 inducers → decreased efficacy of naldemedine

Moderate or strong CYP3A4 inhibitors → increased naldemedine

concentrations

P-gp inhibitors → increased naldemedine concentrations

Avoid use with another opioid antagonist




Indication:

Treatment of adults with tardive dyskinesia


Unknown

Dosing:

40 mg PO qDay x1 week, then

Increase to 80 mg PO qDay

Hepatic impairment

Moderate-to-severe (Child-Pugh 7-15)

Not to exceed 40 mg/day

Renal impairment

Severe (CrCl <30 mL/min)

Use not recommended

Valbenazine (Ingrezza™)


https://ingrezza.com/HCP/PI

Precautions

Warn patients not to perform activities requiring mental alertness d/t

somnolence

QT prolongation

Not clinically significant at recommending dosing

Coadministration with strong CYP2D6 or 3A4 inhibitors may lead to

clinically significant QT prolongation




Drug Interactions

Strong CYP3A4 inducers

Coadministration not recommended

Strong CYP3A4 inhibitors

Reduce valbenazine dose to 40 mg/day

Strong CYP2D6 inhibitors

Reduce valbenazine dose to 40 mg/day




Adverse Reactions

Somnolence (10.9%)

Anticholinergic effects (5.4%)

Balance disorders/fall (4.1%)

Headache (3.4%)

Akathisia (2.7%)

Vomiting (2.6%)




Indication:

Indicated for adults with moderate - severe RA

With inadequate response or intolerance to ≥1 disease-modifying antirheumatic

drugs (DMARDs)


Human monoclonal antibody that binds to IL-6 receptors, reduces inflammatory

cytokines

Dosing:

200 mg subcut q2wk (prefilled syringe)

Sarilumab (Kevzara™)



Drug interactions

Avoid use with live virus vaccines

Dosing considerations

Assess platelet count prior to initiation and monitor platelets 4 to 8 weeks

after start of therapy and every 3 months thereafter

Initiation not recommended with:

ANC <2000/mm³

Platelets <150,000/mm³

ALT or AST >1.5 x ULN

Test for tuberculosis before initiating




Boxed warning:

Increases risk for developing serious infections that may lead to hospitalization or death

Opportunistic infections reported

Avoid use in patients with active infection

Precautions:

Immunosuppression may result in an increased risk of malignancies

Not recommended with active hepatic disease or hepatic impairment




Adverse Reactions:

ALT >ULN to ≤3 x ULN (38-43%)

AST >ULN to ≤3 x ULN (27-30%)

Injection site reaction (7%)

ANC <1000 cells/³ (4-6%)




Indication:

Skin and skin structure infections


Fluoroquinolone antibiotic: inhibits both bacterial topoisomerase IV and

DNA gyrase enzymes, which are required for bacterial DNA replication,

transcription, repair, and recombination

Dosing:

300 mg IV q12hr for 5-14 days, OR

300 mg IV q12hr, then switch to a 450-mg tablet PO q12hr for 5-14 days,

OR

450 mg PO q12hr for 5-14 days

Delafloxacin (Baxdela™)


https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208610s000,208611s000lbl.pdf

Boxed warning:

Fluoroquinolones have been associated with tendinitis and tendon

rupture, peripheral neuropathy, and CNS effects

Drug interactions:

Fluoroquinolones form chelates with:

Antacids containing aluminum or magnesium

Sucralfate

Iron

Multivitamins containing iron or zinc

Administer delafloxacin at least 2 hr before or 6 hr after antacids

or multivitamins containing Mg, Al, Fe, or Zn




Precautions:

Fluoroquinolones are associated with increased risk of peripheral

neuropathy

Adverse Reactions:

Nausea (8%)

Diarrhea (8%)




Indication:

Prophylaxis of VTE in adults hospitalized for acute medical illness who are

at risk for thromboembolic complication


Oral factor Xa inhibitor that selectively blocks the active site of FXa

By directly inhibiting FXa, betrixaban decreases thrombin generation

Coagulation cascade is dependent upon the activation of factor X to FXa

Betrixaban (Bevyxxa™)



Dosing:

Initial single dose: 160 mg PO, THEN 80 mg PO qDay

Recommended duration of treatment: 35-42 days

CrCl ≥15 to <30 mL/min: Initial single dose of 80 mg, then 40 mg PO qDay

x35-42 days

Boxed warning:

Epidural or spinal hematomas may occur (anesthesia patients)

Contraindications:

Active pathological bleeding




Precautions:

No established way to reverse betrixaban’s anticoagulant effect

Can persist for at least 72 hr after the last dose

Adverse Reactions:

Clinically relevant non-major bleeding (2.45%)

Epistaxis (2%)

Hematuria (2%)




Indication:

Indicated for moderate-to-severe chronic plaque psoriasis


Monoclonal antibody that inhibits IL-23, inhibiting the proinflammatory

actions of IL-23

Dosing:

100 mg subcut at week 0, week 4, and q8wk thereafter

Drug interactions

Avoid use of live vaccines

Guselkumab (Tremfya™)



Contraindications:

None

Precautions:

May increase infection risk

Screen for tuberculosis

Adverse Reactions:

Infections, general (23%); compared with 21% in placebo group

Upper respiratory tract infections (14.3%)

Headache (4.6%)

Injection site reactions (4.5%)




Administration:

Remove from refrigerator; allow syringe to reach room temperature (~30

min) before removing syringe cap

For subcut use only; each prefilled syringe is single dose only; inject full

amount

Storage:

Store refrigerated at 2-8°C (36-46°F)

Protect from light until use

Do not freeze

Do not shake




Indication:

Add-on maintenance treatment of severe asthma, with an eosinophilic

phenotype aged ≥12 years


Interleukin-5 receptor monoclonal antibody

IL-5 receptor is expressed on the surface of eosinophils and basophils

Reduces eosinophils and basophils through cell-mediated cytotoxicity

Dosing:

30 mg subcut q4weeks for the first 3 doses, THEN q8weeks

Contraindications:

None

Benralizumab (Fasenra™)


https://www.azpicentral.com/fasenra/fasenra_pi.pdf

Precautions:

Hypersensitivity reactions

Avoid use in acute asthma symptoms or acute exacerbations

Adverse Reactions:

Headache (8%)

Pharyngitis (5%)




Administration:

Prior to administration, warm by leaving carton at room temperature for

about 30 minutes

Once removed from refrigerator, administer within 24 hr or discard

For subcutaneous use only

Administer subcut in upper arm, thigh, or abdomen

Storage:

Refrigerate at 2-8°C (36-46°F)

Store in the original carton to protect from light

Do not freeze

Do not shake




Indication:

Bacterial vaginosis for adult women


Secnidazole is a nitroimidazole derivative

5-nitroimidazoles enters the bacterial cell, the nitro group is turned into

radical anions

These radical anions interfere with bacterial DNA synthesis of susceptible

isolates

Dosing:

1 packet (2 grams) of granules PO qDay, without regard to timing of meals

Secnidazole (Solosec™)



Precautions:

Vulvovaginal candidiasis may occur

Symptomatic infections may require treatment with an antifungal agent

Carcinogenicity has been seen in mice and rats treated long term with

nitroimidazole derivatives, avoid long-term use of secnidazole

Adverse Reactions:

Vulvovaginal candidiasis (8.4-9.6%)

Nausea (3.6-5.3%)

Headache (3.6%)

Diarrhea (2.5%)

Vomiting (2.5%)




Administration:

Sprinkle entire contents of the packet onto applesauce, yogurt, or

pudding

Take all the mixture within 30 minutes without chewing or crunching the

granules

Not intended to be dissolved in any liquid

Take 1 entire packet at one time

May be taken without regard to the timing of meals

Pregnancy:

Data regarding use in pregnant women are insufficient




Indication:

reduction of elevated intraocular pressure (IOP) in patients with open-

angle glaucoma or ocular hypertension


Dual inhibitor of Rho kinase and the norepinephrine plasma membrane

transport protein

Dosing:

Instill 1 drop in the affected eye(s) qDay in the evening

Netarsudil ophthalmic

(Rhopressa™)


https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf

Adverse Reactions

Hyperemia (53%)

Blurred vision

Increased lacrimation

Erythema of eyelid

Administration:

remove contact lenses prior to instilling ophthalmic solution

may reinsert contact lenses 15 minutes following its administration

Netarsudil ophthalmic

(Rhopressa™)



Indication:

adjunct to diet and exercise to improve glycemic control in adults with

type 2 diabetes mellitus


Glucagon-like peptide-1 (GLP-1) agonist

enhance glucose-dependent insulin secretion by pancreatic beta-cells,

suppresses inappropriately elevated glucagon secretion

slows gastric emptying

Semaglutide (Ozempic™)



Dosing:

0.25 mg subcut qWeek for 4 weeks initially; THEN increase the dosage to 0.5 mg qWeek

If glycemic control not achieved after at least 4 weeks on 0.5-mg dose, can increase to 1 mg

qWeek

Precautions:

History of pancreatitis – consider other options

Not indicated for type 1 diabetes mellitus

Postmarket reports of AKI

Adverse Reactions:

Nausea (15.8-20.3%)

Hypoglycemia (16.7-29.8%)




Administration:

Administer subcut to abdomen, thigh, or upper arm

Administer once weekly, on the same day each week, at any time of the

day

Use a different injection site each week

Storage

Unused pens

Refrigerate

After first use

room temperature




Boxed Warning:

In rodents, semaglutide caused dose-dependent and treatment duration

dependent thyroid C-Cell tumors

Unsure of relevance to human population


Adlyxin™ - lixisenatide

Bydureon® - exenatide injectable solution

Byetta® - exenatide injectable suspension

Ozempic® - semaglutide

Saxenda® - liraglutide

Tanzeum® - albiglutide

Trulicity® - dulaglutide

Victoza® - liraglutide

Xultophy® - liraglutide/insulin degludec

Glucagon-like peptide-1 (GLP-1) agonist

Lexi-Comp, Inc. (Lexi-Drugs® ). Lexi-Comp, Inc.; August 17, 2017

Indication:

Adjunct to diet and exercise to improve glycemic control in adults with

type 2 diabetes mellitus


Selective sodium-glucose transporter-2 (SGLT2) inhibitor

lowers the renal glucose threshold → increased urinary glucose

Dosing:

Recommended starting dose is 5 mg PO qDay in the morning

Maximum of 15 mg qDay

eGFR ≥60 mL/min/1.73 m²: No dosage adjustment necessary

eGFR <30 mL/min/1.73 m²: Contraindicated

Ertugliflozin (Steglatro™)



Adverse Reactions:

Female genital fungal infections (9.1-12.2%)

Volume depletion adverse effects (1.9-4.4%)

Urinary tract infections (4-4.1%)

Ertugliflozin (Steglatro™)



Canagliflozin - Invokana®

Dapagliflozin - Farxiga®

Empagliflozin - Jardiance®

Selective sodium-glucose transporter-2

(SGLT2) inhibitor

Lexi-Comp, Inc. (Lexi-Drugs® ). Lexi-Comp, Inc.; August 17, 2017

Vancomycin

Firvanq

oral solution formulation for C. difficile-associated diarrhea

Benzhydrocodone/APAP

Apadaz

Acute pain

Lamivudine/tenofovir disoproxil fumarate

Cimduo

HIV combination therapy

Amantadine

Osmolex ER

ER formulation

New Dosage Forms

Efavirenz/lamivudine/tenofovir

disoproxil fumarate

Symfi

HIV combination therapy (higher

strength efavirenz than Symfi Lo)

Lidocaine patch

Ztlido

Post-herpetic neuralgia

Cocaine

Coprelto

Intranasal local anesthetic for

diagnostic or surgical procedures

or nasal cavities


http://pharmacistsletter.therapeuticresearch.com/pl/NewDrugs.aspx?cs=FACULTY

&s=PL&pt=20&yr=2018

Arymo ER® (morphine)

Extended-release tablets for severe pain

Noctiva™ (desmopressin)

New nasal spray formulation for nocturia due to nocturnal polyuria

Vantrela ER® (hydrocodone)

Extended release tablets for severe pain

Consensi™ (amlodipine/celecoxib)

Hypertesion/OA combination product

New Dosage Forms


Eletriptan (Relpaz™)

Oseltamivir (Tamiflu®)

Prasugrel (Effient®)

Sildenafil (Viagra®)

Testosterone (AndroGel®)

Sumatriptan/Naproxen (Treximet™)

Cinacalcet (Sensipar®)

Etanercept (Enbrel®)

Tadalafil (Cialis®) (September 2018)

Vardenafil (Levitra®) (3rd quarter 2018)

Pregabalin (December 2018)

Lurasidone (Lutuda™) (January2019)

Pregabalin (Lyrica®) (July 2019)

Recent Generics


http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspx?cs=FACULTY

&s=PL&dd=290111&pb=&pt=2&fpt=55&menu=ftg

Drugs Withdrawn from Market –

2015 - 2018

Elepsia XR

Levetiracetam extended release

FDA revoked approval

Manufacturing quality problems

Opana ER

Oxymorphone

Benefit no longer outweigh

risk

Zinbryta

Daclizumab

safety concerns

severe liver damage and

immune-related conditions


1. What is the recommended starting dose for ertugliflozin?

A. 2.5 mg PO daily

B. 5 mg PO daily

C. 10 mg PO daily

D. 15 mg PO daily

Pre-Test Questions

2. What medical indication was sarilumab approved for?

A. Plaque psoriasis

B. Rheumatoid arthritis

C. Hyperlipidemia

D. Hepatitis C

Pre-Test Questions

3. What is the mechanism of action for naldemedine?

A. Opioid antagonist with binding affinities for mu-, delta-, and

kappa-opioid receptors

B. Unknown

C. Human monoclonal antibody that binds to IL-6 receptors, reduces

inflammatory cytokines

D. Oral factor Xa inhibitor that selectively blocks the active site of

FXa

Pre-Test Questions

4. What is the recommend storage procedure for guselkumab?

A. Store at room temperature

B. Shake vial to reconstitute

C. Protect from light

D. Must store in original packaging

Pre-Test Questions

• There were 46 NME approved in 2017, there have been ___

NME approved in 2018

• New medications are constantly being reviewed and approved

by the FDA

• This changes the treatment options for patients and

prescribers

• As providers we must be vigilant to keep up with these new

medications and at the very least know where to quickly find

information related to new medications

Take Home Points

Resources & References

FDA New Drug Innovation webpage:

• https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/default.htm

CenterWatch webpage for newly approved medications

• http://www.centerwatch.com/drug-information/fda-approved-drugs/

Pharmacist Letter webpage for newly approved medications

• http://pharmacistsletter.therapeuticresearch.com/pl/NewDrugs.aspx?cs=FACULTY&s=PL

Package Inserts:

www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM506235.pdf

www.accessdata.fda.gov/drugsatfda_docs/label/2017/208854s000lbl.pdf

www.ingrezza.com/HCP/PI


www.accessdata.fda.gov/drugsatfda_docs/label/2017/208610s000,208611s000lbl.pdf



www.azpicentral.com/fasenra/fasenra_pi.pdf


www.accessdata.fda.gov/drugsatfda_docs/label/2017/208254lbl.pdf

www.accessdata.fda.gov/drugsatfda_docs/label/2017/209637lbl.pdf


Resources & References

Questions?

Keeping Up-to-Date, with so

Little Time: Newly Approved

Medication Review

Golden L. Peters, PharmD, BCPS

Associate Professor, Pharmacy Practice Department

St. Louis College of Pharmacy

[email protected]

keeping up-to-date, with so medication review · vaccine contains live attenuated cholera bacteria...

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