New Drug Update 2012

Nancy Letassy, PharmD, CDE

Professor

University of Oklahoma

College of Pharmacy

NEW MOLECULAR ENTITIES2012

Belviq® (locaserin)

• Approved as an adjunct to a reduced caloric diet and increased activity for chronic weight management in adult with a BMI of >30 or >27 in presence of type 2 diabetes, hypertension, or dyslipidemia

• Serotonin 2c agonist that activates receptor in the brain to decrease food consumption and promote satiety.

Belviq® (locaserin)

Adverse reactions:• Headache, dizziness, euphoria, cognitive

impairment, hallucinations• Fatigue, dry mouth, diarrhea, constipation• Hypoglycemia in patients on a glucose

lowering agent• Bradycardia• Decreased white and red blood cells

Qsymia® (phentermine and topiramate)

• Indicated for chronic weight management in obese or overweight adults with at least one weight-related comorbidity such as hypertension, type 2 diabetes or dyslipidemia

• Combines low doses of phentermine and extended-release topiramate

• Weight loss on average 20 pounds in one year• Previously called Qnexa®

Qsymia® ADR

• cognition, fatigue, dizziness, dysgeusia, insomnia, constipation, dry mouth, tachycardia, depression, anxiety, kidney stones, decreased sweating and increased body temperature, hypokalemia, metabolic acidosis, hypoglycemia, hypotension.

Qsymia® • Ensure adequate fluid

intake to decrease risk of renal stones

• Advise patients to watch for decreased sweating and increased body temperature with increased physical activity in hot weather

Qsymia® ADR

• Monitor for suicidal thoughts and behavior• Monthly pregnancy tests• Monitor blood pressure• Monitor blood glucose in those on glucose

lowering agents• Check potassium, bicarbonate, creatinine,

and other electrolytes

Elelyso® (taliglucerase alfa)• Hydrolytic, lysosomal, glucocerebroside-specific

enzyme indicated for a long-term enzyme replacement therapy (ERT) for adults with a confirmed diagnosis of Type 1 Gaucher disease.

Gaucher Disease

• Most common form: Type 1 non-neurological• Cause: absence of glucocerebrosidase in lysosomes• Fatty material accumulates in spleen and liver• Symptoms can begin early in life or adulthood• Spleen, liver, lungs, brain and bone marrow affected• Increased bruising, fatigue, increased fractures, lung and

kidney impairment, anemia • Autosomal recessive

Treatment of Gaucher Disease

• Current treatment–Enzyme replacement therapy (ERT)

• Cerezyme®: mammalian cell –recombinant–10-15% antibodies; allergic reactions

• VPRIV®: human cell recombinant• Elelyso®: plant cell recombinant

Eleyso®

• Gene for human enzyme is inserted into carrot cells.• Decreases liver and spleen volume, anemia, increases

platelets.• Dose: 60 units/kg IV over 1-2 hours every 2 weeks• Adverse Drug Reactions

– Infusion reactions--Usually mild• Reduce risk by slow infusion rate, pretreat with

antihistamines or corticosteroids– Common ADRs

• URI, throat infections, UTI, extremity pain

CHEMOTHERAPEUTIC AGENTS

Erivedge® (vismodegib)

• First and only oral agent approved for treatment of adults with metastatic basal cell cancer (BCC) or locally advanced BCC recurrent post-surgery or those not candidates for surgery or radiation

Erivedge® MOA

• Designed to inhibit selectively the Hedgehog pathway

• This pathway is active in the proper development of embryos.

• In adults it is less active except for tissue repair and maintenance

• . When it malfunctions it can result is diseases like BCC.

Erivedge® Dosing

• Dose: 150 mg capsule every day until disease progression or until unacceptable adverse reaction.

• Verify pregnancy 7 days before administration.• Embryo-fetal death or severe birth defects can occur• Continue birth control 7 months past last dose. Males

using Erivedge encouraged to use a condom with spermicide even if post-vasectomy while on medication and two months thereafter.

• Do not donate blood or blood products while taking this drug and for 7 months after last dose.

Erivedge® ADRs

• GI: change in how things taste or loss of taste, nausea, diarrhea, decreased appetite, constipation and vomiting

• Joint aches, Muscle spasms• Hair loss• Weight loss• Tiredness

Inlyta® (axitinib)

• Kinase inhibitor for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.

• Inhibits vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3

• These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression.

Inlyta® (axitinib)• 5 to 10 mg PO every 12 hours with a full glass of water.• Reduce dose if liver impairment present or is used with a strong CYP

3A4/5 inhibitor• Avoid grapefruit juice• Both partners need to use effective birth control methods.• Use during pregnancy can cause fetal harm.

Most common ADRs (>20%)• GI: diarrhea, decrease in appetite or ability to taste things, weight

loss, nausea, vomiting, constipation, stomach pain, heart burn• redness, pain, swelling, numbness, tingling, or itching or peeling of

the skin on your hands and feet• Hypertension, dysphonia

Inlyta® Warning and Precautions

• The following adverse events have occurred:– Hypertension and hypertensive crises – Arterial and venous thrombotic events fatal and

nonfatal – Cerebral and GI bleeding, fatal and nonfatal– Hypothyroidism, proteinuria, increased liver

enzymes– Fetal harm

Kyprolis® (carflizomib)

• A proteasome inhibitor for advanced multiple myeloma who have not responded to at least two other drugs.

• Multiple myeloma is a malignant increase in plasma cells• Multiple myeloma associated with an increase in

proteasome levels• Proteasomes present in all cells to degrade unneeded or

damaged proteins

Kyprolis® Dosing

• Administered IV on two consecutive days every week for 3 weeks followed by a 12 day rest.

• Dose: 20-27 mg/m2/day• Common side effects (>30%): nausea,

diarrhea, pyrexia, anemia, thrombocytopenia, dyspnea and fatigue

Kyprolis®

Warnings and Precautions• Heart failure and ischemia• Pulmonary complications and hypertension• Liver toxicity and failure• Tumor lysis syndrome• Infusion reactions• Fetal harm

Perjeta® (pertuzumab)

• Approved for use in combination with Herceptin® and docetaxal for HER2 positive metastatic breast cancer who have not received prior anti-HER2 or chemotherapy for metastatic disease.

• HER2 overexpression correlates with aggressive form of breast cancer—25% of all breast tumor

• Dysregulation of HER-mediated signaling pathways results in growth and spread of cancer cells

• Inappropriate signaling may lead to uncontrolled cell proliferation, decreased cell death, angiogenesis and increased cancer cell motility.

Perjeta® (pertuzumab)

• Dose: initial 840 mg IV followed by 420 mg IV every 3 weeks.

• Clinical effect: increases progression free survival by 6.1 months

Perjeta® Serious ADR

• Fetal death and Birth Defects: birth control during treatment and for 6 months after a patient's last dose of Perjeta. Heart problems: reduced heart function and CHF

• Infusion-related reactions: fatigue, loss of taste, allergic reactions, muscle pain, and vomiting

• Severe allergic reactions: may be severe, may happen quickly, and may affect many areas of the body

Xtandi ® (enzalutamide)

• An androgen receptor inhibitor for treatment of metastatic castration-resistant prostate cancer previously treated with docetaxel

• Dose : 160 mg daily

Drug Interactions

Avoid co-administration with:• strong CYP2C8 inhibitors (gemfibrozil) and

moderate to strong CYP 2C8 inducers (rifampin) • 3A4 inducers (carbamazepine, phenytoin,

phenobarbital) or inhibitors (itraconazole), and• Xtandi® is a moderate to strong inducer of 3A4

(cyclosporine), 2C9 (warfarin), 2C19 (omeprazole). This interaction can decrease the effectiveness of these agents.

Zaltrap® (ziv-aflibercept)

• Indicated for use in a multiple drug combination in the treatment of metastatic colorectal cancer resistant to or has progressed following an oxaliplatin-containing regimen

Zaltrap® MAO

• An angiogenesis inhibitor that results in decreased neovascularization and decreased vascular permeability

Zaltrap® Dosing and ADRs• Dose: 4 mg IV over one hour every two weeks.• Administration continues until disease progression or unacceptable

toxicity• Serious adverse reactions:

– Hemorrhage– GI perforation– Compromised wound healing– Fistula formation– Hypertension– Arterial thromboembolic events– Proteinuria– Neutropenia

Stivarga® (regorafenib)

• Recently approved for the treatment of metastatic colorectal cancer.

• Oral novel multikinase inhibitor that blocks multiple enzymes that promote cancer growth

• 29% increase in survival versus placebo• Black box warning—severe and fatal liver toxicity

occurred during treatment

Bosulif® (bosutinib)

• A kinase inhibitor for treatment of chronic myelogenous leukemia (CML) in adults with chronic, accelerated, or blast phase with resistance or intolerance to prior therapy.

• CML due to chromosomal abnormality resulting in the formation of Philadelphia chromosome

• Abnormal fusion of Brc-Abl tyrosine kinase implicated in pathogenesis of CML

• One source of treatment resistance is activation of Src-family kinases.

Bosulif® (bosutinib)• Dose: 500 – 600 mg daily• Avoid use with strong CYP3A inducers or inhibitors• Avoid use with proton pump inhibitors – decrease drug

levels• Common ADR (>20%)

– Diarrhea, nausea, thrombocytopenia, • Serious ADR

– GI toxicity, Hepatic toxicity, fetal toxicity– Fluid retention– Myelosuppression

FluMist Quadrivalent ® (influenza vaccine live)

• Intranasal influenza vaccine containing four strains of the influenza virus.

• Indicated for active immunization for the prevention of disease caused by influenza A subtype and B viruses

• Approved for use in person 2 through 49 years of age

• Administered intranasally—one-half the dose in each nostril

FluMist® Quadrivalent

• Do not administer to persons who have had a server allergic reaction to any component: egg protein, gentamicin, gelatin and arginine

• Do not administer to children and adolescents through 17 who are on aspirin containing therapy because of risk of Reye’s syndrome

Package insert 2012

Menhibrix®

• A vaccine for prevention of Neisseria meningitidis (C and Y) and Haemophilus influenzae type b infections in children.

• Four doses IM at 2, 4, 6, and 12-15 months.

Kalydeco® (ivacaftor)

• Approved for treatment of cystic fibrosis (CF) in patients ≥6 years who have a G551D mutation in the CFTR gene.

• Transmembrane conductance regulator (CFTR) potentiator for cystic fibrosis patients with certain gene mutation

• Treats the underlying mutation not just the symptoms• CFTR functions as an anion channel.• Found in epithelial cells of the lungs, liver, pancreas, GIT,

skin, reproductive tract.• In CF, CFTR defects results in reduced transport of NaCl

resulting in build up of sticky mucus

Kalydeco® (ivacaftor)

• 150 mg tablet every 12 hours with a high fat meal• Promotes weight gain and improved lung function• Costs $294,000/year. Available for only through specialty

pharmacies

Adverse Drug Effects• Headache, URI, nasal congestion, nasopharyngitis• Nausea, diarrhea• Rash, dizziness, abdominal pain

Kalydeco® Drug Interactions

• Strong 3A4 inhibitors like ketoconazole increases levels 8.5-fold; fluconazole 3-fold

• Other drugs like rifampin and St. John’s Wort should be avoided

• Kalydeco® has potential to inhibit 3A4, P-glycoprotein, and 2C9.

• Check levels of cyclosporine, tacrolimus and digoxin and monitor INR (warfarin)

Myrbetriq® (mirabegron)

• Beta-3 adrenergic agonist for overactive bladder

• Simulation promotes relaxation of detrusor muscle in the bladder adding in urination

Myrbetriq® (mirabegron)

• Dosing: 25 to 50 mg QD• Reduce dose in moderate renal impairment• Warnings and Precautions

– Hypertension– Bladder outlet obstruction– Concomitant medications metabolized by

CYP2D6. Myrbetriq® is an inhibitor of this pathway. (digoxin)

Omontys® (peginesatide)

• Erythropoiesis-stimulating agent (ESA) for anemia in dialysis patients

• Not indicated for patients: – with CKD not on dialysis– as a substitute for transfusions in acute situations, – On chemotherapy and have anemia not due to CKD– Without demonstrated benefit

• Initial dosing: 0.04 mg/kg/month (injectable)• Dose conversion from another ESA based on total weekly

dose at that time.

Omontys® (peginesatide)

• Contraindicated in uncontrolled hypertension

• Most common ADRs (>10%): dyspnea, diarrhea, cough, nausea, A-V fistula site complications

• Warning: Increased risk of MI, stroke and thromboembolism when Hgb increased to >11 gm/dl

Package insert

Picato® Gel (ingenol mebutate)

• Inducer of cell death indicated in the topical treatment of actinic keratosis

• Two strengths: 0.015% and 0.05% gel• Lower strength applied to AK on face and

scalp daily for 3 consecutive days• Higher strength applied to AK on trunk and

extremities daily for 2 consecutive days

Picato® Gel (ingenol mebutate)

Warnings and ADRs• Eye disorders: severe eye pain, ptosis, and

edema.• Local skin reactions• : vesiculation, pustulation, pruritis,

erosions, ulcerations, infection• Headache, nasopharyngitis

Stendra® (avanafil)

• PDE5 inhibitor for erectile dysfunction• Dose 50 to 200 mg 30 minutes prior to sexual

activity PRN (no more than one dose in 24 hours)• Do not use with strong CYP3A4 inhibitors• Decrease dose to 50 mg in 24 hours when using a

moderate CYP3A4 inhibitor• Lower dose to 50 mg/day in patients on stable

alpha-blocker therapy

Stendra® (avanafil)

Strong CYP 3A4 inhibitors

• Protease inhibitors—ritinovir

• Macrolide antibiotics—clarithromycin

• Nefazodone• Azole antifungals --

ketoconazole

Moderate CYP 3A4 inhibitors

• Verapamil• Diltiazem• Erythromycin• Fluconazole• Grapefruit juice• Ciprofloxacin

Alpha blockers

• Selective α1-adrenergic blockers include:

• alfuzoxin (Uroxatral)• prazosin (Minipres)• doxazosin (Cardura)• tamsulosin (Flomax)• terazosin (Hytrin)• silodosin (Rapaflo)

Stendra® (avanafil)Warnings and ADRs

• Increased hypotension: concomitant use of alcohol, nitrates, alpha blockers, and other antihypertensives

• Seek immediate attention if patient experience loss of vision or hearing, or an erection lasting >4 hours

• Most common ADRs: headache, flushing, nasal congestion, back pain, and nasopharyngitis

2012 Package insert

Surfaxin ® (lucinactant)

• Synthetic surfactant for prevention of respiratory distress syndrome (RDS) in premature infants

• For intratracheal use only• Not indicated for adult RDS• Dose: 5.8 mL/kg• Up to four doses in first 48 hours of life• Most common ADR: endotracheal tube reflux or

obstruction, pallor

Tudorza Pressair® (aclidinium)

• An anticholinergic oral inhaler for COPD• Approved for long-term maintenance treatment of

bronchospasm• Not for treatment of acute bronchospasm• Not a rescue inhaler• Dose: one inhalation twice daily• Dry powder inhaler delivering 400 mcg per

inhalation

Tudorza Pressair® (aclidinium)

• ADRs and Warnings• Most common ADRs: cough, headache,

nasopharyngitis• May worsen narrow angle glaucoma,

urinary retention, paradoxical bronchospasm, immediate hypersensitivity reactions—use with caution in people with milk protein allergies

Vascepa® (icosapent ethyl)

• An omega 3 fatty acid for treatment of severe hypertriglyceridemia (>500 mg/dl) in adults.

• Dose: 2 gm BID• Monitor liver function periodically• Use with caution in patients with history of

allergies to fish or shellfish• Most common ADR: arthralgias• May prolong bleeding time

Voraxaze® (glucarpidase)

• Injectable carboxypeptidase enzyme for treatment of toxic methotrexate blood levels due to kidney failure

• A recombinant bacterial enzyme that hydrolyzes and inactivates MTX

• Adults & Children Dosing:• <1 month: not recommended. ≥1 month: Give as bolus IV

injection over 5 minutes. 50Units/kg as a single injection. Continue leucovorin therapy until the MTX concentration is below the leucovorin treatment threshold for at least 3 days.

Voraxaze® (glucarpidase)

• Warnings/Precautions:• Not indicated for use in patients who

exhibit the expected clearance of MTX (plasma MTX concentrations within 2 standard deviations of the mean MTX excretion curve specific for the dose of MTX administered) or those with normal or mildly impaired renal function.

Zioptan® (tafluprost)

• Ophthalmic prostaglandin analog to reduce elevated IOP in open angle glaucoma.

• Also approved in ocular hypertension• Dose: one drop in affected eye daily in the evening• Use may cause a:

– permanent darkening of an iris– Reversible darkening of the eyelid– Eyelash growth

• Most common ADR is conjunctival hyperemia

RECENTLY APPROVED

Aubagio® (teriflunomide)• An oral pyrimidine synthesis inhibitor for

relapsing forms of multiple sclerosis• Immunomodulator with anti-inflammatory

properties• Dose: 7 to 14 mg daily• Reduces relapses• Slows progression of physical disability• Reduces number of brain lesions as detected by

MRI

Aubagio® (teriflunomide)ADRs and Warnings

Most common: nausea, diarrhea, alopecia, paresthesias, influenza, increased ALT• Risk of hepatotoxicity and fatal liver

failure• Risk of teratogenicity• Peripheral neuropathy• Hypertension• Severe skin reaction

Linzess® (linaclotide)

• Aguanylate cyclase-C agonist for IBS with constipation and chronic idiopathic constipation.

• Acts locally in intestines with minimal systemic exposure. Relieves constipation by increasing frequency of bowel movements

• Dose: 145-290 mg daily• ADRs: diarrhea, abdominal pain, abdominal

distension

SIGNIFICANT NEW DOSAGE FORMS

New Acne Products• Ximino® (minocycline)

– Extended release capsule formulation (45, 90, 135 mg capsules) for inflammatory moderate to severe acne

• Fabior® (tazarotene) – retinoid topical foam formulation 0.1% for the treatment of acne

vulgaris in patients >12 years and older

• Absorica® (isotretinoin)– capsule formulation for severe recalcitrant nodular acne– oral Lidose® technology—drug is dissolved in a lipid melt matrix.

The mixture is filled into a hard gelatin capsule and then cooled. When it is ingested the capsule melts at body temperature

– More uniform absorption regardless of dietary intake

New Diabetes Products T2DM

• Janumet XR ® (sitagliptin/metformin) sitagliptin 50 to 100 mg in combination with metformin 1,000 mg extended release.

• Jentadueto® (linagliptin/metformin) linagliptin 2.5 mg (DPP-4) plus increasing doses of 500, 850 and 1000 mg of metformin.

• Take one tablet twice daily with meals.• Bydureon® (exenatide) extended release, weekly injectable

suspension

New Asthma/allergic Rhinitis Products

• Asthmanefrin® (reacepiniphrine) – An OTC non-CFC inhaler for mild asthma– Indicated for temporary relief of asthma symptoms in children and adults

>4 years of age• Dymista® (aselastine/fluticasone)

– Works better for nasal allergy symptoms than nasal fluticasone alone– Azelastine may cause a bitter taste in mouth

• Zetonna ® (ciclesonide) – Dry aerosol version of the aqueous nasal spray of Omnaris ®

– One spray per nostril• Qnasl ® (beclomethasone)

– dry powder nasal spray for allergic rhinitis in people >12 years of age

Binosto ® (alendronate)

• New effervescent tablet formulation for osteoporosis

• Strawberry flavored tablet containing 70 mg alendronate

• Rapid dissolution in 4 oz of water

Pharmacist’s Letter Oct 2011

Cosopt PF®

(dorzolamide/timolol)• Combination of a carbonic anhydrase

inhibitor and beta adrenergic blocker• Indicated for treatment of elevated

IOP• Dose one drop in affected eye twice

daily

Package insert

Giazo® (balsalazide)

• Indicated for the treatment of mildly to moderately active ulcerative colitis in male patients 18 years of age and older

• Converted to mesalamine• Dose: three 1.1 g tablets to be taken BID for

up to 8 weeks

Korlym® (mifepristone)

• To control hyperglycemia secondary to hypercortisolism in adults with endogenous Cushing’s syndrome who have type 2 diabetes or glucose intolerance and have failed surgery or are not candidates for surgery

• Dose: 300 to 1200 mg/daily• Reduce dose when using strong

CYP3A inhibitors

Rayos ® (prednisone)

• Delayed release tablet (1, 2 and 5 mg) formulation of low dose prednisone

• Indicated for inflammatory conditions like RA, asthma, COPD, psoriatic arthritis, polymyalgia rheumatica

• Creates a four-hour lag time compared to immediate-release

Sklice® (ivermectin)

• Topical treatment of head lice infestation in patients >6 months

• Lotion applied to dry hair in an amount sufficient to thoroughly coat the hair and scalp.

• After 10 minutes, rinse off with water.

• For single use. Discard any unused portion.

Subsys® (fentanyl)

• Sublingual spray indicated for treatment of breakthrough cancer pain in opioid-tolerant adults taking other opioid pain meds around the clock

• One time use • Dose: limited to 4/day• Can cause fatal respiratory

depression; avoid concomitant use with CYP3A4 inhibitors

Suprenza® (phentermine)

• Sympathomimetic indicated for the short-term adjunct to a weight loss program (exercise, caloric restriction, behavioral modification) in management of obesity for patients with a BMI >30 or >27 in presence of other risk factors

• One daily, dissolve tablet on tongue for people >16 years of age.

New Pancrelipase Products

All contain porcine derived lipases, proteases and amylases for the treatment of exocrine pancreatic insufficiency

Products are not interchangeable.

• Pertzye® (pancrelipase)– Indicated for children >12 months and adults

• Ultresa® (pancrelipase)– delayed-release capsule for children and adults– Dosed according to weight and age

• Viokace® (pancrelipase)– Indicated for adults– To be taken with a proton pump inhibitor