Transcript A Year in Review: Top New Drugs for 2010

Angela Finney M.S.N., A.C.N.P.-B.C.
Approximately 25 new drugs approved
annually.
 Approvals this year include many different
classes and cover a wide range of disease
management.
 New clinical indications
 New routes of administration
 FDA website provides information about all
new approvals.
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Actemra: RA
Amturnide: Hypertension
Bromday: post-op ocular inflammation
Cuvposa: Chronic drooling in children
Egrifta: Lipodystrophy in HIV pts.
Glassia: Alpha-1 Proteinase Inhibitor Deficiency
Kombiglyze XL: Type II DM
Halaven: Breast Cancer
Lastacaft: Allergic conjunctivitis
Latuda: Schizophrenia
Livalo: Dyslipidemia
Moxeza: Bacterial conjunctivitis
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Nucynta: Analgesic
Pradexa: Direct thrombin inhibitor
Safyral: Oral contraceptive
Tekamlo: Hypertension
Teflaro: Antibiotic
Tribenzor: Hypertension
Victoza: GLP-1 receptor agonist for DM
Vimovo: OA, RA, NSAID induced ulcer prevention
Vyvanase: ADHD
Xgeva: Osteolytic bone metastases solid tumors
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Class: Direct Thrombin Inhibitor.
Indications: Prevention of stroke and
Systemic emboli in non-valvular atrial
fibrillation.
Other indications: None at this time, in
U.S. currently under investigation for DVT
tx. and prevention.
Intrinsic XII
Extrinsic
XI
Injectable AT
UFH
Injectable
LMWH
AT
Pentasaccharide
Xa inhibitors
UFH = unfractionated heparin.
AT = antithrombin.
DTI = Direct thrombin Inhibitor
Hirsh. Chest. 2001;119:64S-94S.
Tissue Factor
IX
VII
VIII
X
V
II
Fibrinogen
Fibrin Clot
Oral Warfarin
Oral and
injectable DTIs
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RE-LY study established clinical efficacy.
Conclusions:
1. Significantly more effective than warfarin.
2. Risk of major bleeding was significantly
less.
3. Risk of hemorrhagic stroke was less.
4. All cause mortality was reduced.
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Dosing: 150mg BID
75mg CrCl 15-30
Not recommended < 15
Cost estimated at $230/mo.
No known antidote. If necessary PRC, FFP
or cryoprecipitate. PTT best estimate
anticoagulation effect.
Pre-op discontinuation 1-5 days and cover
with Heparin/LMH.
Specific instruction for conversion from
warfarin to Pradaxa.
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ADR; dyspepsia, abd. pain, diarrhea, GI
bleed.
Bleeding risk: NSAIDA, other antiplatelets.
Doesn’t affect P450 system. Minimal drug
interactions. Avoid Rifampin, St. John’s
wart.
Caution with bleeding risk and
contraindicated in active bleeding.
Absorption: not affected by food. Achieves
effective levels within 1-2 hrs, steady state in
2-3 days.
 Do not open, crush or chew tablets.
 Half life: 12-17 hrs.
 Excretion: primary renal.
 Pregnancy Category C.
 Breastfeeding: Unknown.
 Open pill container only good for 30 days.
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Conversion from
warfarin → dabigatran
Discontinue warfarin. Start dabigatran when INR < 2.0
Conversion from
dabigatran → warfarin
CrCl > 50 ml/min: Start warfarin 3 days prior to stopping dabigatran
CrCl 31-50 ml/min: Start warfarin 2 days prior to stopping dabigatran
CrCl 15-30 ml/min: Start warfarin 1 day prior to stopping dabigatran
CrCl < 15 or on dialysis: no recommendations can be given
**Since dabigatran contributes to INR elevation, warfarin’s effect on the
INR will be better reflected after dabigatran has been stopped for ≥2 days
Conversion from
parenteral anticoagulants
Start dabigatran at the time the next dose of the parenteral drug would be
administered or at the discontinuance of a continuously administered
parenteral drug (e.g. UFH)
Conversion to parenteral
anticoagulants
CrCl ≥ 30 ml/min: Wait 12 hours after the last dose of dabigatran
CrCl < 30 ml/min: Wait 24 hours after the last dose of dabigatran
Invasive or surgical
procedures
If possible, discontinue dabigatran 1-2 days (Clcr ≥50 mL/minute) or
3-5 days (Clcr <50 mL/minute) before invasive or surgical procedures
due to the risk of bleeding; consider longer times for patients undergoing
major surgery, spinal puncture, or insertion of a spinal or epidural catheter
or port. If surgery cannot be delayed, the risk of bleeding is elevated;
weigh risk of bleeding with urgency of procedure. Bleeding risk can be
assessed by the ecarin clotting time (ECT) if available; if ECT is not
available, use of aPTT may provide an approximation of dabigatran’s
anticoagulant activity.
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Class: HMG-CoA reductase inhibitor.
Indications: treatment of primary
hyperlipidemia and mixed dyslipidemia.
Pharmacology: Block synthesis of cholesterol
in the liver; inhibiting HMG-CoA, first
enzyme in the cholesterol cascade.
DRUG
Percent LDL
Reductions
Dose Range
Rosuvastatin
52-63%
10-40 mg
Atovastatin
38-54%
10-80 mg
Lovastatin
29-48%
20-80 mg
Pitavastatin
31-41%
1-4 mg
Pravastatin
19-40%
10-40 mg
Fluvastatin
17-33%
20-80%
Reference: Up to Date “Comparisons of Statins” 2011
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Dosing: 1, 2, 4 mg.
Start at 2 mg, increase to 4 mg after 4 weeks.
Renal impairment: CrCl 30-60 1-2 mg.
Precautions: Avoid with severe renal, hepatic
dysfunction.
Monitor warfarin.
Reduce dose with erythromycin, cyclosporine.
Lopid, niacin, fenofibrates increase risk of
myopathy.
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Pregnancy category: X; presumed unsafe for
lactation.
Selectively distributed to liver, excreted in
bile; avoids CYP450.
Half life: 12 hrs.
Can give anytime of day, regardless of food.
Contraindicated: active liver disease,
persistent transaminitis, heavy ETOH use,
severe renal impairment.
ADR: back pain, constipation myalgia,
diarrhea.
1.Increase insulin
secretion
2.Decrease glucagon
secretion
3.Improve beta-cell
function
4.Delays gastric
emptying
5.Reduces hunger
6.Contributes to
weight loss.
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Class: Long acting glucagon-like peptide-1
receptor agonist. ( GLP-1). Incretin mimic.
Indications: Adults; type II DM. Mono-therapy or
combination. Not for IDDM.
Pharmacology: GLP-1 stimulated pancreas
increase insulin production and decrease
glucagon production.
Suppresses appetite, expect 6 # weight loss.
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Dosing: Initiate at 0.6mg SQ daily.
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Cost: $300/ 2 (3ml) pens,
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After one week increased to 1.2mg daily.
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Dose can be increased to 1.8mg if required.
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Expect 1.1% HgbA1c reduction with combo
tx.
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Pregnancy Category C.
Lactation: possibly unsafe.
Half life: 13 hrs.
Common ADR: nausea, vomiting, headache
and diarrhea.
Delays gastric emptying and may impair
absorption of oral medications.
May need to reduce dose of sulfonylurea to
reduce risk of hypoglycemia.
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No studies establishing reduction of DM
induced complications.
Rare side effect: anti-liraglutide antibodies.
Rare cases pancreatitis.
Black Box Warning: risk of thyroid c-cell
tumors.
Contraindicated: family or personal
hx of Multiple Endocrine Neoplasm Syndrome
and medullary thyroid carcinoma.
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Combination of saxigliptin and metformin XR
Onglyza: DDP-4 inhibitor
Indications: Type II DM; adults
Dosing: 5/500 mg.
2.5/1000 mg.
5/1000 mg.
Once a day dosing with evening meal
Confirm renal function before starting
CrCl < 50: 2.5/500mg daily.
 Pregnancy Category B.
 Lactation: possibly unsafe
 Metabolism: extensive liver
 Risk for lactic acidosis.
 Cost: $110/mo.
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Class: 5th generation cephalosporin; broad
spectrum.
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Indications: acute bacterial skin infections
and CAP in adults >18 yrs.
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Effective in gram neg. and multi-drug
resistant gram positive organism.
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Limited use in ICU; no pseudomonas,
enterococcus, or actinetobacter coverage.
Spectrum of Activity
CAP
SS
Strep pneumoniae
MSSA
Klebsiella pneumoniae
MRSA
H-influenza
Strep pyogenes
E-coli
Strep agalactiae
K-octoca
E-coli
MSSA
Reference: Pharmacist Letter
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Dosing: 600mg q. 12 hr IV over 1 hr.
SSSI infections 5-14 days.
CAP infections 5-7 days.
Renal impairment:
> 50 CrCl No adjustment
> 30 < 50 400mg q. 12 hr.
15 - 30 300mg q. 12 hr.
< 15/hemodialysis 200mg q. 12 h.r
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Pregnancy Category: B.
Lactation: unknown.
Metabolism: hydrolysis. No effect CYP450.
Excretion: renal.
Half life: 2.6 hrs.
Microbiological cure rate 96%.
No significant drug interactions.
Most common ADR: diarrhea, nausea, rash.
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Indications: Moderate to severe acute pain.
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Class: Mu-opioid agonist. (Schedule II),
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Pharmacology: centrally acting analgesic; dual
mode of action. Agonist of the u-opioid
receptor & norepinephrine re-uptake
inhibitor.
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Dosing 50-100mg every 4-6 hours.
Maximum daily dose 700mg day one,
600mg/day subsequent day.
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Available in 50, 75, 100mg tabs.
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No renal adjustment in mild to moderate
renal disease.
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Moderate hepatic disease: dose at 50mg
q. 8 hrs.
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ADR: Dizziness, somnolence, nausea,
vomiting, fatigue.
Precautions: CNS & respiratory depression,
head injury, liver impairment, seizure
disorder.
Contraindicated: Impaired pulmonary
function.
Drug interactions: Avoid with SSRI, SSNI,
MAO inhibitors due to risk for serotonin
syndrome.
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Primarily metabolized by liver including first
pass metabolism.
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Half life 4 hrs.
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Primarily excreted in urine.
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Pregnancy Category: C
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Lactation: probably unsafe.
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Class: Non-opioid pain reliever; intravenous
form of acetaminophen.
Indications: Mild to moderate pain. Fever
reduction.
IV route reduces liver exposure by ½.
Not for use in children under 2 yrs.
Studies evaluating opioid sparing effects in
post-op pts.
Dosing similar to oral.
 Tribenzor
 Amturnide
 Tekamlo
 Twynsta
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Combination of olmesartan, amlodipine,
HCTZ.
Indications: Failed dual treatment.
Dosing: 20/5/12.5
40/5/12.5
40/5/25
40/10/25
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Cost: $135/mo.
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Combination of aliskiren, amlodipine, HCTZ
Dosing: 150/5/12.5 mg.
300/5/12.5 mg.
300/5/25 mg.
Costs: $105/mo
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Aliskiren and amlodipine combination
Available dosing:
150/5 mg.
150/10 mg.
300/5 mg.
300/10mg.
Cost: $130/mo.
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Telmisartan and amlodipine combination
Available dosing:
40/10 mg.
80/5 mg.
80/10 mg.
Cost: $165/mo
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Dulera®: mometasone/formoterol
Available in 100mcg/5mcg & 200/5mcg
Vimovo®: Naproxen/esomeprazole
Available in 375/20mg or 500/20mg.
Jalyn®: Dutasteride/tamsulosin
Antithrombotic Therapy to Prevent Embolization in Non-valvular Atrial Fibrillation. Up to
Date. 2011. www.uptodate.com..
DeFronza, Ralph, et al. The efficacy and safety of Ssxagliptin when added to metformin
therapy in patients with uncontrolled Type 2 diabetes. Diabetes Care.
http://www.diabetesjournals.org/content/32/9/1649.long
Drusanom George. Pharmocodynamics of ceftaroline fosamil for complicated skin and skin
structure infections. Journal of Antimicrobial Chemotherapy: Volume 65; pg. 33-39.
Gotto, A., Moon. J. Pitavastatin for the treatment of primary hyperlipidemia and mixed
dyslipidemia. Expert Reviewed Cardiovascular Therapy. Aug. 2010: 8 (8) 1079-90.
Hatrick,C., Van Hove, I Efficacy and Tolerability of Tapentadol and oxycodone in patients
awaiting primary joint replacement. Clinical Therapy. Feb. 2009: 31 (2) 260-71.
Nucynta Package Insert. June 2010. PriCare.
Pradaxa Package Insert. April 2010. Boehringer Ingelheim.
Unger, Jeff. Clinical Efficacy of GLP-1 Agonist and their place in the diabetes treatment
algorithm. Journal of American Osteopathic Association. Feb 2011: 111 (2) 2-9.
Victoza Package Insert. Jan 2010. Novo Nordisk.