Drug Updates

Eve Van Wagoner, PharmD, BCACP Primary Care Clinical Pharmacist South Jordan Health Center [email protected] October 2017 SAFETY ALERTS/ LABELING CHANGES Opioid addiction medications

• Should not be withheld from patients taking benzodiazepines or other drugs that depress the central nervous system • The harm caused by untreated opioid addiction can outweigh these risks Eluxadoline (Viberzi®) and Pancreatitis • FDA review, patients without a gallbladder + Viberzi = increased risk for pancreatitis • Recommendation: – Avoid prescribing Viberzi in patients who do not have gallbladder, consider alternative options • Warning signs: – New/worsening stomach-area or abdomen pain or pain in upper right side of stomach Restricted use of Codeine and Tramadol • FDA approved for adult use only • New Contraindication: – Children <12 years old to treat pain or cough – Children <18 years old to treat pain after surgery to remove tonsils and/or adenoids (Tramadol) • New Warning: – Recommend against use in adolescents 12-18 years old who are obese, have OSA, or lung disease – Avoid in breastfeeding mothers Invokana and Amputation Risk

• New data from two large clinical trials • Black box warning added to drug label • Recommendation: – Consider factors that may predispose patients to the need for amputations (prior amputation, PVD, neuropathy, diabetic foot ulcers) • Warning signs: – New pain or tenderness, sores or ulcers, or infections in legs or feet ACEs and Neprilysin Inhibitor

• Contraindicated to be used at same time • Do NOT administer ACE/ARB within 36 hours of switching to or from neprilysin inhibitor, such as Entresto® Amphetamine and serotonin syndrome • Warning added to • Examples all amphetamine • Fluoxetine products of • Paroxetine increased risk of • Bupropion serotonin syndrome • Ritonavir • Amphetamines • Cincalcet metabolized • Sertraline through CPY2D6 • Duloxetine Oral contraceptives and Hep C drug combinations • Oral contraceptives containing ethinyl should be discontinued before starting Hep C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir • Potential for ALT elevations more than 5 times the upper limit, up to 20 times the upper limit Orlistat co-administration

• Some medications may not work as well when co-administered with Orlistat, such as – Anticoagulants – Diabetes medications – Thyroid medications – Antiretrovirals NSAIDs and heart conditions

• Warning of increased risk of heart attack, stroke and heart failure added or updated on drug facts labeling for: – Ibuprofen – Naproxen • Warning is already a boxed warning for: – Celecoxib – Diclofenac – Indomethacin Rivaroxaban and Cyp3A4 inhibitors • Avoid rivaroxaban • Examples and combined P-gp – Ketoconazole and Cyp3A4 – Ritonavir inhibitors, especially – Not clarithromycin in patients with CrCl 15-80 mL/min • Many health systems have anticoagulation monitoring available Zyban®/Chantix® and Depression

• Mental health risk is present but serious consequences are minimal • Consider risks of depression exacerbation with benefits of smoking cessation • FDA removed Boxed Warning for serious mental health side effects from Chantix • Many health systems have smoking cessation programs through pharmacists Testosterone and Abuse/dependence • New warning of possible abuse and dependence to include new safety info • Serious adverse outcomes – Heart attack, heart failure, stroke, liver toxicity, aggression, male infertility, depression • Withdrawal symptoms – Depression, fatigue, irritability, insomnia, decreased libido Homeopathic Teething Products

• FDA found inconsistent amounts of belladonna in homeopathic teething tablets • Risk of seizures, difficulty breathing, lethargy, excessive sleepiness, skin flushing, constipation, difficulty urinating Pioglitazone and Bladder Cancer

• Updated review concluded pioglitazone may be linked to increased risk of bladder cancer • Recommendation: – Do not use in active bladder cancer – Consider risks/benefits in patient with history of bladder cancer • Warning signs: – blood in urine, urge to urinate, pain w/ urination Chlorhexidine Gluconate and Allergic Reactions • Increased number of reports of serious allergic reactions • Recommendation: – Ask patients about allergic reactions to antiseptics prior to recommending – Use alternatives when necessary • Warning signs: – Wheezing, difficulty breathing, swelling of face, hives, severe rash, shock NEW DRUG APPROVALS Abaloparatide (Tymlos™)

Indication in postmenopausal women at high risk Mechanism Human related analog Place in New treatment option therapy Dosing 80 mcg subQ once daily Abaloparatide (Tymlos™) Contraindications None Warnings Risk of osteosarcoma, orthostatic hypotension, hypercalcemia, hypercalciuria and urolithiasis Adverse effects Dizziness, nausea, HA, palpitations, increased uric acid, hypercalcemia Other Use for > 2 years not recommended Tymlos™ vs Forteo™

• Postmenopausal women • Postmenopausal women, only osteoporosis in men, AND • Subcutaneous injection into glucocorticoid-induced abdomen only osteoporosis • 30 doses per pen • Subcutaneous injection into • Room temperature for up thigh or abdomen to 30 days after first use • 28 doses per pen • No REMS program • Must be stored in fridge at • AWP $1950 all times • REMS program • AWP $3597 Valbenazine (Ingrezza™)

Indication Tardive dyskinesia Mechanism VMAT2 inhibitor Place in Once daily option therapy Dosing 40 mg once daily increasing to 80 mg once daily after 1 week *Dose adjust for renal, hepatic, and concurrent CYP3A4/CYP2D6 inhibitors/inducers Valbenazine (Ingrezza™)

Contraindications None. Caution in QT prolongation patients Warnings CNS depression, suicidal ideation, QT prolongation Adverse effects Drowsiness, fatigue, sedation Deutetrabenazine (Austedo™)

Indication Chorea associated with Huntington’s disease (and tardive dyskinesia) Mechanism VMAT2 inhibitor Place in Second treatment option with less therapy frequent dosing Dosing 6 mg once daily, increasing weekly based on response. Administer in 2 divided doses if total daily dose >12 mg/day. MAX 48 mg/day. *Dose adjust with CYP2D6 inhibitors Deutetrabenazine (Austedo™) Contraindications Hepatic impairment, suicidal or untreated depression, dose adjustments w/ tetrabenazine or w/in 14 days of an MAOI or 20 days of reserpine Warnings Depression and suicide, NMS, akathisia, QT prolongation Adverse effects Drowsiness, dry mouth Austedo™ vs Ingrezza™

• Twice daily • Once daily • Follow schedule if • Caution with Cyp2D6 switching from and 3A4 tetrabenazine and/or • No contraindications MAOI • Higher cost • Indicated for Chorea as well • Black box warning for depression and suicide Safinamide (Xadago®)

Indication Parkinson’s disease *Adjunctive treatment to levodopa/carbidopa in patients experiencing “off” episodes Mechanism Inhibitor of MAO-B Dosing 50 mg once daily. Increase to 100 mg once daily after 2 weeks. Safinamide (Xadago®)

Contraindications Severe hepatic impairment, use with MAOIs, opioids, SNRIs, TCAs, and others Warnings CNS depression, hypertension, impulse control disorders, serotonin syndrome Adverse effects Dyskinesia Dupilumab (Dupixent®)

Indication Moderate to severe atopic dermatitis not controlled with topical therapy Mechanism Interleukin-4 receptor alpha antagonist Dosing 2- 300 mg subcutaneous injections then 300 mg every other week Dupilumab (Dupixent®)

Contraindications None Warnings Asthma, conjunctivitis and keratitis, live vaccines Adverse effects Injection site reactions, conjunctivitis, keratitis Naldemedine (Symproic®)

Indication Opioid-induced constipation in patients with non-cancer pain Mechanism Mu antagonist Place in Another option therapy Dosing 0.2 mg once daily Naldemedine (Symproic®)

Contraindications GI obstruction, increased risk for recurrent obstruction Warnings Opioid withdrawal Adverse effects Abdominal pain, diarrhea, nausea, gastroenteritis Plecanatide (Trulance™)

Indication Chronic idiopathic constipation Mechanism Guanylate cyclase-C agonist Place in Another choice for constipation therapy Dosing 3 mg once daily with or without food Plecanatide (Trulance™)

Contraindications <6 years due to the risk of dehydration, gastrointestinal obstruction Warnings Severe diarrhea Adverse effects Diarrhea / glargine (Soliqua™) Indication Type 2 diabetes Mechanism GLP-1 and basal insulin Place in Narrow use therapy Dosing Start at 15 units/5 mcg or 30 units/10 mcg. Max 60 units/20 mcg Lixisenatide/ (Soliqua™) Contraindications Hypersensitivity Warnings Pancreatitis, hypoglycemia, medication error, AKI, immunogenicity, hypokalemia, Adverse effects Same as either separately Administration 1 hour before first meal (Fiasp™)

Indication Type 1 and 2 diabetes in adults Mechanism Binds to insulin receptors facilitating cellular uptake of glucose Place in For patients who forget to inject therapy prior to meals Dosing Unit to unit conversion. Inject within 20 minutes of a meal. Insulin aspart (Fiasp™)

Contraindications Hypoglycemia Warnings Hypersensitivity, hypoglycemia, hypokalemia Adverse effects Hypoglycemia, injection site reactions, weight gain Allopurinol and lesinurad (Duzallo™) Indication Hyperuricemia associated with gout not controlled on allopurinol Mechanism URAT1 inhibitor and xanthine oxidase inhibitor Place in After allopurinol trial to improve therapy continued symptoms Dosing 300/200 mg once daily or 200/200 mg for CrCl of 45-60 mL/min Allopurinol and lesinurad (Duzallo™)

Contraindications Severe renal impairment, ESRD, tumor lysis syndrome Warnings Acute renal failure, rash, hepatotoxicity, bone marrow suppression Adverse effects Headache, flu, reflux, increased blood creatinine Administration Take with breakfast SUPPLY UPDATES Supply updates

• Atenolol 25- and 50-mg tablets • Amoxicillin and Clavulanate ER 1000/62.5-mg • Carisoprodol and aspirin discontinued • Furosemide 20- and 40-mg tablets • Indomethacin 25- and 50-mg tablets • Tanzeum discontinued Drug Info Resource Center-Drug Shortages https://pulse.utah.edu/site/dirc/Pages/Drug-Shortages-update.aspx#Current NEW GENERIC DRUG APPROVALS • Quetiapine ER (Seroquel XR®) • Dexmethylphenidate ER (Focalin XR®) • Pitavastatin (Livalo®) • Fluticasone/salmeterol (Advair Diskus ®) – not available • Memantine-donepezil (Namzaric®) • Dexlansoprazole Delayed Release (Dexilant®) • Ezetimibe and Simvastatin (Vytorin®) • Prasugrel (Effient®) • Sevelamer carbonate (Renvela®) • Scopolamine patch (Transderm®) • Atomoxetine (Strattera®) • Mesalamine Delayed Release (Lialda®) • (Byetta®) – October 2017 • Sildenafil (Viagra®) – December 2017 • Efavirenz (Sustiva®) – December 2017 QUIZ QUESTIONS Quiz question #1

When switching from an angiotensin converting enzyme inhibitor to a neprilysin inhibitor, how long should the patient wait to take the neprilysin inhibitor? A. 24 hours B. 12 hours C. 36 hours D. 42 hours Quiz question #2

Which of the following medications require Risk Evaluation and Mitigation Strategy (REMS)? A. Soliqua ® B. Tymlos ® C. Fiasp ® D. Forteo ® Quiz question #3

Where would you find information regarding drug supply shortages? A. CDC website B. Drug Information website C. Poison control hotline D. Manufacturer websites Quiz question #4

I know how I will use these drug warnings and updates to positively impact my current practice. A. True B. False Questions?

Eve Van Wagoner, PharmD, BCACP Primary Care Clinical Pharmacist South Jordan Health Center [email protected] 801-213-4565