New Drug Update 2013

1. New Drug Update 2013 Armando Zuniga, Pharm.D. Drug Information Specialist INTEGRIS Southwest Medical Center

2. Cardiology /Vascular Disease

3. Mipomersen (Kynamro) • Inhibitor of apolipoprotein B-100 synthesis indicated to treat homozygous familial hypercholesterolemia (HoFH) • 1 in 1 million births • Black box warning for hepatoxicity (REMS program) • Prior to treatment ALT, AST, alkaline phosphates and total bilirubin should be measured and routinely monitored • Withhold dosing if >5 ULN. May resume one <3x • Can cause an increase in hepatic fat (hepatic steatosis) with/without increases in transaminases • 200 mg subcutaneous once weekly

4. Ezetimibe/Atorvastatin(Liptruzet) • Combination product indicated to reduce elevated total-C, LDL-C, Apo D, TG, and non-HDL-C and to increase HDL-C in patients with primary or mixed hyperlipidemia • Also indicated to reduce total-C and LDL-C in patient with HoFH • Dose is 10/10 mg through 10/80 mg daily. • Contraindicated in patients with active liver disease or persistent elevated hepatic transaminase levels, pregnancy or nursing mothers. • Adverse events include myopathy and weakness (increased risk with fenofibrates and niacin)

5. Nimodipine (Nymalize) • Indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage (SAH) from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition. • Oral solution of nimodipine, a dihydropyridine calcium channel blocker. • Side effects include hypotension, headache, bradycardia, and nausea. • Dose is 60 mg (20 mL) q4h for 21 days.

6. Apixaban (Eliquis) • A factor Xa inhibitor anticoagulant indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. • Recommended dose is 5 mg twice daily • Reduce dose to 2.5 mg daily for patients with at least 2 of the following • Age > 80 years • Less than 60 kg • Serum creatinine > 1.5 mg/dL • Dose reduction to 2.5 mg for patients on strong inhibitors of CYP3A4 • Ketoconazole • Itraconazole • Ritonavir • Clarithromycin

7. Apixaban (Eliquis) • Interactions • Drug effecting hemostasis • Aspirin and antiplatelet agents • Heparin • Thrombolytics • SSRIs and SNRIs • NSAIDS • Fibrinolytics • Other anticoagulants • Strong Inducers of CYP3A4 • Rifampin • Carbamazepine • Phenytoin • St Johns Wort

8. Apixaban (Eliquis) • Conversions • If converting from warfarin, start apixaban once INR is less than 2 • If converting between other anticoagulants, start at the next scheduled dose • If converting from apixaban to warfarin, start parenteral anticoagulant and warfarin at the next scheduled dose. Discontinue parenteral anticoagulant when INR within target range. • Procedures • Discontinue apixaban 24 - 48 hours prior to procedures

9. Dermatology

10. Brimonidine (Mirvaso) • An alpha agonist indicated in the topical treatment of persistent facial erythema of rosacea in adults. Erythema reduction occurs via direct vasoconstriction. • Applied daily to the forehead, chin, nose, and each cheek • Precautions • Severe cardiovascular disease and potentiation of vascular insufficiency. • Adverse Events • Erythema • Flushing • Burning sensation

11. Endocrinology

12. Canagliflozin (Invokana) • A sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated as adjunct to diet and exercise to improve glycemic control in DM2 • Starting dose is 100 mg daily before first meal of the day. May increase to 300 mg • 100 mg is limited to those patients with eGFR of 45 to 59 mL/min/1.73m2. Do not use in patients with GFR below 45 mL/min/m2 • Monitor for hypotension, renal function, hyperkalemia, hypoglycemia, LDL, and genital mycotic infections • Drug interactions • Digoxin (monitor levels) • Rifampin, phenytoin, phenobarbital, ritonavir – increase to 300 mg. If GRF < 45, consider alternative agent • Adverse events include: mycotic infections, UTI, and increased urination

13. Canagliflozin (Invokana) • A1C Changes • Monotherapy - ~1% change from baseline • Metformin - ~1% • Metformin + sulfonylurea ~0.5% - 1% • Hypoglycemia – increased incidence when combined with insulin secretagogues • Weight changes - ~2% - 5% • Kidney function • Dose dependent increase in creatinine and GFR has been seen and likely related to intravascular volume contraction.

14. Alogliptin (Nesina) • Adipeptidyl peptidase-4 (DPP-4) inhibitor indicated as adjunct to diet and exercise to improve glycemic control in adults with DM2 • Dose is 25 mg daily • CrCl 30 – 59 12.5 mg daily • CrCl <30 6.25 mg daily (including ESRD or HD) • Acute pancreatitis and hepatic failure has been reported • Hypoglycemia can occur when combined with other insulin secretagogues (consider a dose reduction of secretagogue) • Adverse events include nasopharyngitis, headache, UTI

15. Alogliptin (Nesina) • A1C change • Monotherapy ~0.6% - 0.9% • +Metformin ~1.2% - 1.6% • +Pioglitazone ~0.8% - 1% • Weight neutral • Combination with metformin • Kazano • 12.5 mg alogliptin/ 500 mg metformin • 12.5 mg alogliptin/ 1000 mg metformin • Oseni • 25 mg alogliptin/ 15 mg pioglitazone • 25 mg alogliptin/ 30 mg pioglitazone • 25 mg alogliptin/ 45 mg pioglitazone

16. Gastroenterology

17. Budesonide (Uceris) • Aglucocorticosteroid indicated for induction of remission in patients with active, mild to moderate ulcerative colitis • MMX technology target delivers budesonide throughout the colon. Once in the colon, the pill matrix forms a hydrogel releasing budesonide. • Dose is 9 mg daily for 8 weeks • Can cause hypercorticism, adrenal suppression and immunosuppression • Adverse events include headache, acne, UTI, abdominal pain, arthralgia, and constipation • Avoid ketoconazole, grapefruit and other 3A4 inhibitors inhibitors of gastric acid

18. Infectious Disease

19. Influenza vaccine (Flublok) • Trivalent influenza vaccine • Recommended for adults 18 – 49 with egg allergies • Manufactured with cell culture technology without live influenza virus • If Guillain-Barré syndrome has occurred within 6 weeks of receipt of a prior influenza vaccine, the decision to give Flublok should be based on careful consideration of potential benefits and risks. • Adverse events include site reactions, headache, fatigue, and myalgia

20. Varicella Zoster Immune Globulin (Human)(VariZIG) • Indicated for post-exposure prophylaxis of varicella (chickenpox) in high risk patient groups including immunocompromised children, newborns, and pregnant women. VariZIG is intended to reduce the severity of chickenpox infections in these patients. • Ideally administered within 96 hours post exposure for greatest efficacy but within 10 days. • Patient groups recommended by CDC to receive VariZIG include the following: • Immunocompromised patients without evidence of immunity. • Pregnant women without evidence of immunity. • Newborn infants whose mothers have signs and symptoms of varicella around the time of delivery (i.e., 5 days before to 2 days after). • Hospitalized premature infants born at ≥28 weeks of gestation whose mothers do not have evidence of immunity to varicella. • Hospitalized premature infants born at <28 weeks of gestation or who weigh ≤1,000 g at birth, regardless of their mothers' evidence of immunity to varicella.

21. neurology

22. Levomilnacipran (Fetzima) • Aserotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of Major Depressive Disorder (MDD) • Initiate dose at 20 mg daily for 2 days then increase to 40 mg. May give up to 120 mg daily (may increase by increments of 40 mg every 2 or more days) • Monitor for suicidality or unusual changes in behavior; serotonin syndrome; bleeding; hyponatremia; bone fracture; activation of mania/hypomania; seizures; akathisia; acute angle closure glaucoma; elevated blood pressure and heart rate; urinary hesitation • Adverse events include: nausea, constipation, increased heart rate, hyperhidrosis, erectile dysfunction, tachycardia, vomiting and palpitations • Avoid MAOIs, serotonergic drugs, ketoconazole. Caution when used with drugs that interfere with hemostasis

23. Obstetrics/Gynecology (Women’s Health)

24. Ospemifene (Osphena) • AN estrogen agonist/antagonist indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause • Black Box Warning: In the endometrium, OSPHENA has estrogen agonistic effects. There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy reduces the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Estrogen-alone therapy has an increased risk of stroke and deep vein thrombosis (DVT). OSPHENA 60 mg had cerebral thromboembolic and hemorrhagic stroke incidence rates of 0.72 and 1.45 per thousand women, respectively vs. 1.04 and 0 per thousand women, respectively in placebo. For deep vein thrombosis, the incidence rate for OSPHENA 60 mg is 1.45 per thousand women vs. 1.04 per thousand women in placebo

25. Doxylamine/Pyridoxine (Diclegis) • Afixed dose combination drug product of doxylamine antihistamine, and pyridoxine, a Vitamin B6analog, indicated for the treatment of nausea and vomiting of pregnancy in women who do not respond to conservative management. • Recommended dose is two tablets daily at bedtime. If symptoms are not adequately controlled, increased to a maximum dose of four tablets daily (one in the morning, one mid-afternoon and two at bedtime) • Adverse events include somnolence. Caution with other CNS depressants • Monoamine oxidase (MAO) inhibitors intensify and prolong the adverse central nervous system effects

26. Ospemifene (Osphena) • Recommended dose is 60 mg daily with food • Contraindicated in patients with abnormal genital bleeding; know or suspected estrogen dependent neoplasia; history or active DVT/PE or arterial thromboembolic disease (e.g. stroke or MI); pregnancy • Adverse events include hot flush, vaginal discharge, muscle spasms, hyperhidrosis • Avoid other estrogens or estrogen agonist/antagonists, fluconazole, ketoconazole, or rifampin

27. Paroxetine (Brisdelle) • A selective serotonin reuptake inhibitor indicated for the treatment of moderate to severe vasomotor symptoms associated with menopause • Recommended dose is 7.5 mg at bedtime • Do not use MAOI, thioridazine or pimozide • Side effects include headache, fatigue, N/V • Monitor for suicidality or unusual changes in behavior; Serotonin Syndrome; bleeding; hyponatremia; bone fracture; activation of mania/hypomania; seizures; akathisia; acute angle closure glaucoma

28. Norethindrone, ethinyl estradiol, ferrous fumarate (Lo Minastrin FE) • An estrogen/progestin oral contraceptive indicated to prevent pregnancy • Black Box Warning: Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs should not be used by women who are over 35 years of age and smoke • Do not use in patients with: a high risk of thrombotic diseases; breast cancer or other estrogen or progestin sensitive cancer, liver tumor or disease, or smokers • Adverse events include N/V, headache, dysmenorrhea, acne, weight changes, depression, and breast tenderness

29. Respiratory diseases

30. Fluticasone/ Vilanterolinhalation powder (Breo Ellipta ) • Acombination of fluticasone furoate, an inhaled corticosteroid (ICS), and vilanterol, a long-acting beta2-adrenergic agonist (LABA), indicated for long-term, once-daily, maintenance treatment of airflow obstruction and for reducing exacerbations in patients with COPD. • Black Box Warning: Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, increase the risk of asthma-related death. The safety and efficacy of BREO ELLIPTA in patients with asthma have not been established. BREO ELLIPTA is not indicated for the treatment of asthma. • Dose is one inhalation daily • Adverse events include URTI, oral candidiasis, and headache

31. Fluticasone/ Vilanterolinhalation powder (Breo Ellipta ) • Monitor for signs/symptoms of pneumonia; worsening of infections; hypercorticism and adrenal suppression; hypokalemia; hyperglycemia; glaucoma, increased intraocular pressure, and cataracts • Candida infections of the mouth may occur • Assess for decrease in bone mineral density and monitor periodically • Use caution when used with diuretics as this may cause electrocardiographic changes and/or hypokalemia. • MAOIs and tricyclic antidepressants may potentate effect of vilanterol on the vascular system (QTc prolongation) • Caution when using beta-blockers (bronchospasm) • Not intended to be a rescue inhaler

32. Questions?

33. Opioid Prescribing Guidelines for Oklahoma Health Care Providers in the Office-Based Setting

34. Opioid Treatment for Acute Pain • Opioid medications should only be used for treatment of acute pain when the severity of the pain warrants that choice and after determining that other non-opioid pain medications or therapies will not provide adequate pain relief. • Providers should query the Oklahoma Prescription Monitoring Program (PMP) for patients presenting with acute pain, prior to prescribing an opioid medication. In circumstances where a patient’s pain is resulting from an objectively diagnosed disease process or injury, a provider may prudently opt not to review the Oklahoma PMP. • When opioid medications are prescribed for treatment of acute pain, the number of doses dispensed should be no more than the number of doses needed based on the usual duration of pain severe enough to require opioids for that condition.

35. Opioid Treatment for Acute Pain • When opioid medications are prescribed for treatment of acute pain, the patient should be counseled to store the medications securely and not to share with others. In order to prevent non-medical use of the medications, it is also recommended that patients dispose of medications when the pain has resolved. • Long duration-of-action opioids (e.g., methadone, buprenorphine, fentanyl, etc.) are rarely indicated for treatment of acute pain. • The use of opioid medications should be re-evaluated carefully, including assessing the potential for abuse, if persistent pain suggests the need to continue opioid medications beyond the anticipated time period of acute pain treatment for that condition. Health care providers should query the Oklahoma Prescription Monitoring Program (PMP) as part of this re-evaluation process. • Health care providers should generally not provide replacement prescriptions for opioid medications that have been lost, stolen, or destroyed.

36. Opioid Treatment for Chronic Pain • Alternatives to opioid treatment should be tried, or previous attempts documented, before initiating opioid treatment. • A comprehensive evaluation should be performed before initiating opioid treatment for chronic pain. For chronic pain patients who are transferring their care to new health care providers, new opioid prescriptions should generally not be written until the previous provider’s records have been reviewed or the previous health care provider has been notified of the transfer of care. • The health care provider should screen for risk of abuse or addiction before initiating opioid treatment. • Prior to the initial prescribing of opioid medications, health care providers should query the Oklahoma Prescription Monitoring Program (PMP). • When opioids are to be used for treatment of chronic pain, a written treatment plan should be established that includes measurable goals for reduction of pain and improvement of function. One health care provider should coordinate a patient’s comprehensive pain care plan and provide all opioid prescriptions required for the plan.

37. Opioid Treatment for Chronic Pain • The patient should be informed of the risks and benefits and any conditions for continuation of opioid treatment, ideally using a written and signed treatment agreement. • Opioid medications should be initiated as a short-term trial to assess the effects of opioid treatment on pain intensity, function, and quality of life. In most instances, the trial should begin with a short-acting opioid medication. • Regular visits with evaluation of progress against goals should be scheduled during the period when the dose of opioids is being adjusted (titration period). During the titration period, and until the patient is clinically stable and is judged to be compliant with therapy, it is recommended that the health care provider check the Oklahoma Prescription MonitoringProgramat least quarterly.

38. Opioid Treatment for Chronic Pain • Once a stable dose has been established (maintenance period), regular monitoring should be conducted at face-to-face visits during which treatment goals, analgesia, activity, adverse effects, and aberrant behaviors are monitored. The Oklahoma Prescription Monitoring Program (PMP) should be queried at least once per year for patients receiving opioid treatment for chronic pain. • Continuing opioid treatment should be a deliberate decision that considers the risks and benefits of chronic opioid treatment for that patient. Patients and health care providers should periodically reassess the need for continued opioid treatment, weaning whenever possible, as part of the comprehensive pain care plan. A second opinion or consultation may be useful in making that decision. • Opioid treatment should be discontinued if adverse effects outweigh benefits; or if aberrant, dangerous, or illegal behaviors are demonstrated.

39. Opioid Treatment for Chronic Pain • Health care providers treating chronic pain patients with opioids should maintain records documenting patient evaluation, treatment plan, discussion of risks and benefits, informed consent, treatments prescribed, results of treatment, and any aberrant behavior observed. • Health care providers should consider consultation for patients with complex pain conditions, patients with serious co-morbidities, including mental illness; patients who have a history or evidence of current drug addiction or abuse; or when the provider is not confident of his/her ability to manage the treatment. • Health care providers should generally not provide replacement prescriptions for opioids that have been lost, stolen, or destroyed. • The administration of intravenous and intramuscular opioids for the relief of exacerbations of chronic pain is discouraged, except in special circumstances.

40. New Hydrocodone Law • Effective November 1, 2013, prescriptions for any medication containing hydrocodone may not be refilled. This applies even if the prescription was written prior to November 1.