PL Detail-Document #311003 −This PL Detail-Document gives subscribers
additional insight related to the Recommendations published in−
PHARMACIST’S LETTER / PRESCRIBER’S LETTER October 2015
More. . . Copyright © 2015 by Therapeutic Research Center
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Statin Muscle Symptoms: Managing Statin Intolerance
Muscle symptoms are commonly reported by statin users; however, over 70% of these patients end up tolerating a statin.3,5,8
Statin-associated muscle
symptoms are usually not serious. Although rhabdomyolysis has a mortality rate of almost 8%, it is rare.3 The chart below provides information to
help clinicians prevent and manage statin-associated muscle symptoms. Also download the ACC Statin Intolerance App at http://www.acc.org/Statin
IntoleranceApp.
Abbreviations: ACC = American College of Cardiology; AHA = American Heart Association; BMI = body mass index; CK = creatine kinase;
CoQ10 (coenzyme Q10; ubiquinol); CV = cardiovascular; NLA = National Lipid Association; SCr = serum creatinine; ULN = upper limit of normal
Clinical Question Suggested Approach/Pertinent Information
What adverse muscle effects
can statins cause? Patients may complain of pain, tenderness, stiffness, cramps, weakness, or fatigue.
1
Symptoms usually involve large, proximal muscle groups (e.g., legs, back) symmetrically.4
Symptoms usually occur within 4 to 6 weeks after starting the statin, but can occur after years of treatment.4
Examples of terminology commonly used in the context of statin muscle symptoms (definitions used in
literature/guidelines vary):
Myopathy: general term for muscle disease (Canada),3 or used to denote muscle weakness not due to pain,
and which may or may not be associated with elevated CK (NLA)8
Myalgia: muscle symptoms with CK <ULN3,8
Myositis: muscle symptoms with CK >ULN (Canada);3 muscle inflammation (NLA)
8
Myonecrosis: CK >3 times baseline or ULN adjusted for age, sex, and race (NLA).8 Further divided into
mild, moderate, and severe.
Rhabdomyolysis: muscle symptoms plus myoglobinuria and CK >10 x ULN
(CK >10,000 units/L; Canada);3 myonecrosis with myoglobinuria or acute renal failure (increase
in SCr ≥0.5 mg/dL; NLA)8
How common are statin-
associated muscle
symptoms?
In clinical trials, low- or moderate-intensity statinsa did not increase the risk of muscle symptoms.
1 However, in
practice, up to about 30% of patients complain of muscle symptoms.4
In clinical trials, rhabdomyolysis occurred in <0.06% of patients over about a five-year period.1 In a “real life”
unselected population, rhabdomyolysis may occur in as many as 0.2% of statin users.3
(PL Detail-Document #311003: Page 2 of 5)
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Clinical Question Suggested Approach/Pertinent Information
What are some risk factors
for statin-associated muscle
adverse effects?
Multiple disease states (e.g., renal or hepatic insufficiency) or polypharmacy1,4
History of musculoskeletal symptoms or CK elevation, neuromuscular disease, or personal or family history of
statin or other myopathy1,3
Use of medications or foods (e.g., grapefruit) that increase statin levels1
Age over 75 to 80 years1,3
Asian ancestry1,3
Being female3
Low BMI or small frame3
Frailty3
Physical activity4
Alcohol or drug abuse3
Are certain statins more
commonly associated with
muscle symptoms?
The vast majority of patients who do not tolerate one statin can tolerate the same or a different statin.3,5
Almost half can tolerate the same statin upon rechallenge, usually at the same or higher dose.3
When choosing a different statin, consider one with fewer drug interactions (e.g., rosuvastatin, pravastatin,
fluvastatin), or one that a family member can tolerate.8
Evidence that lipophilicity/hydrophilicity directly affects
muscle symptoms is lacking in humans.8
What can be done to prevent
statin-associated muscle
symptoms?
Before starting a statin, document current or previous muscle symptoms.1
This information may help prevent unnecessary statin discontinuation in the future.1
Do not use gemfibrozil with a statin.1
Screen for drug interactions.1
Adjust dose or use a different statin accordingly.1
Ensure dose is appropriate for renal function.
Our PL Chart, Characteristics of the Various Statins, has information on drug interactions and renal dosing.
Ensure the statin dose is appropriate based on cardiovascular risk.1
Consider a moderate-intensity statina instead of a high-intensity statin
a for patients with risk factors for
statin muscle symptoms.1
Avoid simvastatin 80 mg daily.1,3
Before starting, set patient expectations that side effects can be managed if they occur.4
(PL Detail-Document #311003: Page 3 of 5)
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Clinical Question Suggested Approach/Pertinent Information
When should a creatine
kinase be checked? Consider baseline measurement in patients with risk factors.
1
Do not check routinely.1
Elevations >3x the ULN occur in patients with heart disease at a similar rate regardless of statin treatment.1
The clinical importance of an elevated CK without symptoms is unclear.4
Exercise can also cause
increased CK.4
Check in the event of muscle symptoms.1
What is the general approach
to take when a patient
complains of muscle
symptoms?
Continued…
Example approach based on ACC/AHA guidelines, NLA panel, and European consensus panel:
Hold statin for 2 to 4 weeks in the event of intolerable symptoms, weakness, or CK >3 times ULN. If patient
reports weakness, evaluate muscle strength by physical exam, and consider additional testing (e.g., biopsy) if
weakness persists despite statin discontinuation.8
Consider rhabdomyolysis in the event of severe muscle pain or fatigue, generalized weakness, or dark urine.1,4
Check CK, urine for myoglobin, and SCr.1
If rhabdomyolysis is confirmed, treat and do not restart statin at any point in the future.4
Look for other causes of muscle symptoms (e.g., hypothyroidism, vitamin D deficiency, rheumatologic or
musculoskeletal disease, exercise, steroid myopathy, antipsychotics, immunosuppressants, bisphosphonates,
alcohol or drug abuse, drug or food interactions [e.g., fibrates, macrolides, immunosuppressives, protease
inhibitors]).1,3,4,9
Also consider alternate causes of leg cramps.
Check renal and hepatic function.1
Assuming no contraindications:1
rechallenge with same statin at the same or lower dose once symptoms resolve to establish a causal
relationship. If symptoms return, discontinue statin. Once symptoms resolve, start a different statin at a
lower dose, then increase as tolerated.1
OR
start a low or target dose of a different statin once symptoms improve.8 Increase as tolerated.
8 If not
tolerated, try extending the dosing frequency, such as every other day or twice a week.3,6,8
(See more about
alternate dosing options in the next sections.)
OR
for patients at low CV risk, consider lifestyle interventions in lieu of a statin4
Consider adding ezetimibe for certain high-risk patients who can’t tolerate a high-intensity statin, such as those
with a prior cardiovascular event. Ezetimibe is the only non-statin with evidence of improving cardiovascular
outcomes when added to a statin. See our PL Chart, Non-Statin Lipid-Lowering Agents, for considerations
when deciding to start a non-statin, and a comparison of their lipid effects, outcomes, and cost.
Save PCSK9 inhibitors (Praluent, Repatha) as an add-on to statins for familial hypercholesterolemia. Do not
routinely use these agents in other high-risk patients with or without a statin, due to high cost and lack of long-
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Clinical Question Suggested Approach/Pertinent Information
General approach,
continued
term outcome and safety data.
If symptoms/CK elevation does not improve in 2 to 4 weeks, or do not normalize after two months, evaluate
for non-statin cause.1,8
If non-statin cause is found, or predisposing condition has been treated, restart original statin at original dose.1
Use a “take your time” approach and be persistent. Help patients understand the benefits and risks of
continued statin therapy. See our PL Patient Education Handout, What You Should Know About Statins.
When should I stop a statin
due to muscle symptoms? In the event of symptoms, hold statin temporarily pending evaluation.
1 (See General Approach section above for
more information.)
European guidelines recommend permanent discontinuation in patients who experience rhabomyolysis.4
Can I give statins less often
than once daily to reduce
symptoms?
Rosuvastatin is most often used in this strategy because of its long-half life, high potency, and favorable drug
interaction profile.5
Intermittent dosing of rosuvastatin (i.e., 5 mg 2 to 3 times weekly) can reduce LDL by over 30%.3 Rosuvastatin
5 to 10 mg weekly may reduce LDL by 10%.10
Atorvastatin also has a long half-life.8 Atorvastatin 20 mg every other day may be as effective as 20 mg daily in
regard to LDL reduction.6
Intermittent dosing has not been prospectively studied in regard to cardiovascular morbidity or mortality.5
What is the role of coenzyme
Q10 (ubiquinol)? In patients with a history of statin muscle symptoms, confirmed by placebo-controlled crossover rechallenge,
CoQ10 600 mg daily did not affect pain, muscle strength, or aerobic performance vs placebo in patients taking
simvastatin 20 mg daily [Evidence level B; lower-quality RCT].2
Canadian and European consensus panels advise against use of dietary supplements (including vitamin D) for
statin muscle symptoms.3,10
Coenzyme Q10 is well-tolerated if patients insist on trying it.7 However, it can be expensive.
The suggested
dose for statin muscle pain is 100 to 200 mg daily (in divided doses if >100 mg/day).
a. See our PL Chart, 2013 ACC/AHA Cholesterol Guidelines, for a list of high- and moderate-intensity statins.
Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making
clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national
organizations. Information and internet links in this article were current as of the date of publication.
(PL Detail-Document #311003: Page 5 of 5)
Levels of Evidence In accordance with the trend towards Evidence-Based
Medicine, we are citing the LEVEL OF EVIDENCE
for the statements we publish.
Level Definition
A High-quality randomized controlled trial (RCT)
High-quality meta-analysis (quantitative
systematic review)
B Nonrandomized clinical trial
Nonquantitative systematic review
Lower quality RCT
Clinical cohort study
Case-control study
Historical control
Epidemiologic study
C Consensus
Expert opinion
D Anecdotal evidence
In vitro or animal study Adapted from Siwek J, et al. How to write an evidence-based clinical
review article. Am Fam Physician 2002;65:251-8.
Project Leader in preparation of this PL Detail-
Document: Melanie Cupp, Pharm.D., BCPS
References 1. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013
ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S1-45.
2. Taylor BA, Lorson L, White M, Thompson PD. A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. Atherosclerosis 2015;238:329-35.
3. Mancini GB, Tashakkor AY, Baker S, et al. Diagnosis, prevention, and management of statin
adverse effects and intolerance: Canadian Working Group Consensus update. Can J Cardiol 2013;29:1553-68.
4. Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society consensus panel statement of assessment etiology and management. Eur Heart J 2015;36:1012-22.
5. Mampuya WM, Frid D, Rocco M, et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. Am Heart J 2013;166:597-603.
6. Pramanik S, Das AK, Chakrabarty M, et al. Efficacy of alternate-day versus everyday dosing of atorvastatin. Indian J Pharmacol 2012;44:362-5.
7. Jellin JM, Gregory PJ, et al. Natural Medicines Comprehensive Database.
www.naturaldatabase.com. (Accessed September 3, 2015).
8. Rosenson RS, Baker SK, Jacobson TA, et al. An assessment by the statin muscle safety task force: 2014 update. J Clin Lipidol 2014;8(Suppl 3):S58-71.
9. FDA. Information for healthcare professionals: bisphosphonates (marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa). January 7, 2008.
(Last updated August 15, 2013). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124165.htm. (Accessed September 16, 2015).
10. Anderson TJ, Gregoire J, Hegele RA, et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol 2013;29:151-67.
Cite this document as follows: PL Detail-Document, Statin Muscle Symptoms: Managing Statin Intolerance.
Pharmacist’s Letter/Prescriber’s Letter. October 2015.
Evidence and Recommendations You Can Trust…
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Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to www.PharmacistsLetter.com, www.PrescribersLetter.com, or www.PharmacyTechniciansLetter.com
More. . . Copyright © 2015 by Therapeutic Research Center
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PL Detail-Document #311003 −This PL Detail-Document gives subscribers
additional insight related to the Recommendations published in−
PHARMACIST’S LETTER / PRESCRIBER’S LETTER October 2015
New Drug: Repatha (Evolocumab)
What It Is Repatha (evolocumab) is a proprotein
convertase subtilisin kexin type 9 (PCSK9)
inhibitor, one of only two agents available in this
new class of cholesterol lowering drugs.1 PCSK9
inhibitors have shown impressive results in
lowering LDL cholesterol levels. This article will
provide an overview of evolocumab and its role in
the treatment of hypercholesterolemia.
How It Works PCSK9 is an enzyme that binds with high
affinity and specificity to LDL cholesterol
receptors.2 This bound complex then promotes
the degradation of the LDL cholesterol receptors
and prevents them from recycling themselves.2
The result is decreased receptor activity, which
lowers the liver’s ability to remove circulating
LDL cholesterol from the blood.2
Repatha is a human monoclonal antibody that
inhibits the PCSK9 enzyme, stopping it from
binding to the LDL cholesterol receptors.2 This
increases the number of receptors that are
available to bind to and clear LDL cholesterol,
increases the recycling of receptors, and results in
increased LDL cholesterol clearance and lower
LDL cholesterol plasma levels.2
Indications Repatha is indicated as an adjunct to diet and
maximally tolerated doses of statin therapy in
adults with heterozygous familial
hypercholesterolemia (HeFH) or with clinical
atherosclerotic cardiovascular disease who need
further lowering of LDL cholesterol. And, also as
an adjunct to diet and other LDL-lowering
therapies in adults with homozygous familial
hypercholesterolemia (HoFH) who need further
LDL cholesterol lowering.1
How Supplied Repatha is a clear to opalescent, colorless to
pale yellow, preservative-free solution available in
140 mg/mL single-use pre-filled syringes or
autoinjectors.1 Syringes are available individually
and the autoinjectors come in packs of one, two,
or three.1 Each dose of 140 mg costs $542
(WAC), giving an annual cost per patient of about
$14,100 for the every two weeks administration.3
Amgen is offering copay reductions and financial
support assistance that may help reduce the out-
of-pocket cost to patients, see
http://www.Repatha.com for more information.3
Dosage The recommended dose of Repatha is 140 mg
subcutaneously every two weeks or 420 mg
monthly for patients with HeFH or clinical
atherosclerotic cardiovascular disease. Patients
with HoFH should receive 420 mg subcutaneously
monthly. For administration of a 420 mg dose,
give three 140 mg injections within 30 minutes.1
In patients with HoFH, LDL-cholesterol levels
should be measured four to eight weeks after
starting Repatha to assess efficacy.1
If a dose is missed on either the every two
week or monthly schedule, but given within seven
days, the patient can resume their original
schedule. If the dose cannot be administered
within seven days, the patient should wait and
administer on the next scheduled dose of the
original schedule.1
Storage and Administration Repatha should be kept in the refrigerator at
2°C to 8°C (36°F to 46°F) in the original, outer
carton to protect it from light. Repatha can also
be stored at room temperature (up to 25°C
[77°F]), in the original carton, but then must be
used within 30 days.1
To minimize discomfort and ensure the entire
dose is administered, instruct patients to allow
Repatha to warm to room temperature for at least
30 minutes prior to administration. Do not heat
Repatha or leave it in direct sunlight to warm it
(PL Detail-Document #311003: Page 2 of 4)
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up. Patients also need to protect Repatha from
freezing as well as from any extreme heat.1
Before each administration the patient must
check the expiration date and inspect the solution
for any visible particles or discoloration, ensure
the device is not cracked or broken, and that the
orange or gray cap is intact. For the autoinjector,
also ensure that the window of the device is not
yellow. In any of these cases, the product should
be discarded. Instruct the patient on proper
aseptic technique for administration of this
subcutaneous injection, such as to wash their
hands prior to administration, clean the injection
site with an alcohol wipe, and not to touch the
needle. The injection site should be rotated with
each injection and can be in the thigh, abdomen,
or upper arm. The skin at the injection site should
be healthy and intact, free of any damage (e.g.,
tender, bruised, red, etc). It also should not be
injected into an area with stretch marks or scars.
Avoid giving any other injections at the same site.
Let the patient know to safely dispose of their
used needles and syringes in a sharps container, or
a household container that is heavy-duty plastic
and can be sealed.1 For more information on the
safe disposal of medical sharps, go to
http://www.epa.gov/wastes/nonhaz/industrial/med
ical/disposal.htm.
Other important administration information for
Repatha:1
Do not shake
Do not try to remove any air bubbles
before injecting, these are normal
Plunger may be harder to depress than
other injectables
It can take up to 15 seconds to inject
the full dose
The window of the autoinjector must
be yellow before removing the needle
from the skin to ensure a complete
dose is given
Don’t rub the injection site after giving
the injection
For detailed administration information,
including diagrams, go to http://pi.amgen.com
/united_states/repatha/repatha_ifu_hcp_pt_english
.pdf. And, for additional questions and assistance,
patients can call 844-REPATHA (844-737-2842)
or go to http://www.REPATHA.com.
Adverse Effects The most commonly reported adverse
reactions (>5% and more common than placebo)
in clinical trials are nasopharyngitis, upper
respiratory tract infections, back pain, injection
site reactions, and influenza.1
Other adverse effects reported with Repatha
include myalgia, cough, diarrhea, musculoskeletal
pain, and rarely neurocognitive impairment.4
Some studies have reported elevated creatine
kinase levels and myalgias more often in PCSK9-
treated groups than in placebo groups. One study
reported elevated creatine kinase levels to more
than five times normal in seven patients (1.2%)
taking evolocumab compared to one patient
(0.3%) in the placebo group.5 And, myalgia was
reported in 24 patients (4%) in the evolocumab
group compared to nine patients (3%) in the
placebo group.5
In addition to the liver, the PCSK9 enzyme is
also expressed in pancreatic islets. Because of
this, there is the potential that inhibiting PCSK9
will have an effect on glucose homeostasis with
an increased risk for the development of type 2
diabetes. Current studies with evolocumab, of up
to one year in duration, have not shown an
increased risk of type 2 diabetes.5
There are
ongoing long-term safety outcomes studies that
will offer more information on this potential for
increased risk of the development of diabetes in
patients taking Repatha.
Drug Interactions There have been no drug-drug interactions
reported with Repatha.1
Contraindications Repatha is contraindicated in patients who
have had a serious hypersensitivity reaction to this
medication.1
Precautions If any signs or symptoms of an allergic
reaction occur (e.g., pruritus, rash, urticaria, etc),
Repatha should be discontinued immediately and
the reactions treated.1
The needle covers of Repatha’s syringes and
autoinjectors contain dry natural rubber and may
cause allergic reactions in patients who are
sensitive to latex.1
(PL Detail-Document #311003: Page 3 of 4)
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Use In Pregnancy There is no data available on the use of
Repatha in pregnant women. Animal studies have
shown that evolocumab does cross the placental
barrier.1
Manufacturer Amgen Inc.
Thousand Oaks, CA 91320
805-447-1000
www.amgen.com
Commentary Despite currently available cholesterol
lowering therapy (e.g., statins), there are certain
patient groups who would benefit from additional
options to better manage their hyperlipidemia.6
These patients include those with familial
hyperlipidemia, statin-intolerant patients, those
with a poor response to statins, and patients with
contraindications to statins.6
Repatha significantly reduces LDL cholesterol
levels in patients with high cholesterol [Evidence
Level A; high quality RCT].7 It has shown
efficacy when used as monotherapy, as well as
when added to statins and/or other lipid lowering
therapy, in patients with familial
hypercholesterolemia and in patients who are
intolerant to statin therapy.8
Repatha has shown a reduction in LDL
cholesterol levels ranging from 42% to 65% in
patients with different types of dyslipidemia.5,7
And, the effects were maintained for the duration
of the studies.8
Data from four phase 3
evolocumab studies were pooled to analyze 3152
patients.8 Within these studies, evolocumab was
compared to placebo, ezetimibe, or to standard
lipid-lowering therapy.8 The OSLER 1 and 2
trials were open-label, randomized trials that were
analyzed together.7 They enrolled 4465 patients
who had completed previous evolocumab phase 2
or 3 studies, so called “parent trials.”7 Patients
were randomized to receive evolocumab 140 mg
every two weeks or 420 mg every month by
subcutaneous injection (added to their existing
standard therapy) or standard therapy alone.7 At
one year, there was a 61% reduction in LDL
cholesterol levels in the evolocumab group, from
a mean of 120 mg/dL (6.8 mmol/L) to 48 mg/dL
(2.7 mmol/L), compared to those not treated with
evolocumab (p=<0.001).7
While some studies are reporting beneficial
effects of PCSK9 inhibitors on cardiovascular
events, these studies are preliminary and only
suggestive for benefit on cardiovascular
outcomes.2,9
There are four large, ongoing
randomized controlled trials that have been
designed to assess long-term cardiovascular
outcomes with PCSK9 inhibitors. Results from
these studies are expected by 2017.2
Caution should be used to avoid the overuse of
Repatha at the risk of not optimizing/maximizing
statins, the only LDL cholesterol-lowering drugs
proven to improve cardiovascular outcomes in
dyslipidemic patients. Be cautious of the label
“statin-intolerant” put on some patients. Statins
are commonly discontinued, often due to adverse
events such as muscle pain, but it is important to
know that most patients who are rechallenged are
often on the same statin 12 months later at the
same or a higher dose.10
There are also some
strategies that can be used with statins, such as
alternate day dosing, to increase the tolerability of
these agents.11
For more about managing statin
intolerance, see our PL Chart, Statin Muscle
Symptoms: Managing Statin Intolerance. Also
see our PL Chart, 2013 ACC/AHA Cholesterol
Guidelines, for information on using proven
interventions for reducing CV risk in patients with
dyslipidemia.
Clinical trials with Repatha and other PCSK9
inhibitors show that they are relatively well
tolerated.12
However, studies have been of two
years duration or less, so long-term effects are still
unknown.12
As we have seen with statins, it can
take decades to identify some adverse effects,
such as neurocognitive events and effects on
glycemic control.
For more information on evolocumab and
PCSK9 inhibitors, including Praluent
(alirocumab), another recently released PCSK9
inhibitor, see our PL Detail-Documents, PCSK9
Inhibitors for High Cholesterol and New Drug:
Praluent (Alirocumab).
Conclusion Statins, at target doses, are the only lipid-
lowering drugs proven to improve cardiovascular
outcomes, the primary treatment goal in
dyslipidemic patients. While Repatha
significantly lowers LDL cholesterol levels, it is
important to note that its long-term safety and
(PL Detail-Document #311003: Page 4 of 4)
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effect on cardiovascular outcomes is still
undetermined. For now, this injectable, costly
medication should be reserved for high-risk, hard-
to-treat patients with familial
hypercholesterolemia where lifestyle changes and
optimized statins have not been able to adequately
control their hypercholesterolemia.
Users of this PL Detail-Document are cautioned to use
their own professional judgment and consult any other
necessary or appropriate sources prior to making
clinical judgments based on the content of this
document. Our editors have researched the
information with input from experts, government
agencies, and national organizations. Information and
internet links in this article were current as of the date
of publication.
Levels of Evidence In accordance with the trend towards Evidence-Based
Medicine, we are citing the LEVEL OF EVIDENCE
for the statements we publish.
Level Definition
A High-quality randomized controlled trial (RCT)
High-quality meta-analysis (quantitative
systematic review)
B Nonrandomized clinical trial
Nonquantitative systematic review
Lower quality RCT
Clinical cohort study
Case-control study
Historical control
Epidemiologic study
C Consensus
Expert opinion
D Anecdotal evidence
In vitro or animal study Adapted from Siwek J, et al. How to write an evidence-based
clinical review article. Am Fam Physician 2002;65:251-8.
Project Leader in preparation of this PL Detail-
Document: Annette Murray, BScPharm
References 1. Product information for Repatha. Amgen Inc.
Thousand Oaks, CA 91320. August 2015.
2. Navarese SP, Kolodziejczak M, Schulze V, et al. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia. Ann Intern Med 2015;163:40-51.
3. Amgen. FDA approves Amgen’s new cholesterol-lowering medication Repatha (evolocumab).
August 27, 2015. http://www.amgen.com/media/media_pr_detail.jsp?releaseID=2082837. (Accessed September 4, 2015).
4. Toth PP, Sattar N, Genest J, et al. A comprehensive safety analysis of 6026 patients from phase 2 and 3 short and long term clinical trials with evolocumab [abstract]. J Am Coll Cardiol
2015;65. doi: 10.1016/s0735-1097(15)61351-1. 5. Blom DJ, Hala T, Bolognese M, et al. A 52-week
placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med 2014;370:1809-19.
6. Koren MJ, Lundqvist P, Bolognese M, et al. Anti-PCSK9 monotherapy for hypercholesterolemia. J Am Coll Cardiol 2014;63:2531-40.
7. Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1500-9.
8. FDA. FDA Briefing document Repatha. June 10,
2015. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM450072.pdf. (Accessed September 3, 2015).
9. Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1489-99.
10. Zhang H, Plutzky J, Skentzos S, et al. Discontinuation of statins in routine care settings. Ann Intern Med 2013;158:526-34.
11. Mampuya W, Frid D, Rocco M, et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. Am Heart J 2013;166:597-603.
12. Stone NJ, Lloyd-Jones DM. Lowering LDL cholesterol is good, but how and in whom? N Engl J Med 2015;372:1564-5.
Cite this document as follows: PL Detail-Document, New Drug: Repatha (Evolocumab). Pharmacist’s
Letter/Prescriber’s Letter. October 2015.
Evidence and Recommendations You Can Trust…
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PL Detail-Document #311003 −This PL Detail-Document gives subscribers
additional insight related to the Recommendations published in−
PHARMACIST’S LETTER / PRESCRIBER’S LETTER October 2015
More. . . Copyright © 2015 by Therapeutic Research Center
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Repatha and Praluent Comparison Abbreviations: HeFH=heterozygous familial hypercholesterolemia; HoFH=homozygous familial hypercholesterolemia
REPATHA (Evolocumab)1
PRALUENT (Alirocumab)2
Subcutaneous
Dose
HeFH or clinical atherosclerotic cardiovascular disease: 140 mg
every two weeks or 420 mg monthly
HoFH: 420 mg monthly
75 mg every two weeks, can be increased to 150 mg
every two weeks
Indication Adjunct to diet and maximally tolerated doses of statin therapy in
adults with HeFH or clinical atherosclerotic cardiovascular disease.
Adjunct to diet and other LDL cholesterol-lowering therapies in
adults with HoFH.
Adjunct to diet and maximally tolerated statin therapy in
adults with HeFH or clinical atherosclerotic
cardiovascular disease.
Efficacy 42% to 65% reduction in LDL-cholesterol3,4
40% to 60% reduction in LDL-cholesterol5
Availability
Pre-filled syringes and autoinjectors of 140 mg/mL
Pre-filled syringes and pens of 75 and 150 mg/mL
Administration Can take up to 15 seconds to administer entire dose.
For the 420 mg dose, give three injections of 140 mg within 30
minutes.
For more details on the administration of Repatha, see our PL Detail-
Document, New Drug: Repatha (Evolocumab).
Can take up to 20 seconds to administer entire/full dose.
For more details on the administration of Praluent, see
our PL Detail-Document, New Drug: Praluent
(Alirocumab).
Storage Refrigerate. Can also be stored at room temperature, but must be
used within 30 days.
Refrigerate. Must be discarded if left at room
temperature more than 24 hours.
Cost $542 per dose; about $14,100 per year for every two week dosing
$1120 for 2 doses; $14,600 per year
Allergy Alert
The needle covers of both the syringe and autoinjector contain latex.
Avoid in patients who are allergic to latex.
Devices do not contain latex.
(PL Detail-Document #311003: Page 2 of 2)
Users of this PL Detail-Document are cautioned to use
their own professional judgment and consult any other
necessary or appropriate sources prior to making
clinical judgments based on the content of this document.
Our editors have researched the information with input
from experts, government agencies, and national
organizations. Information and internet links in this
article were current as of the date of publication.
Project Leader in preparation of this PL Detail-
Document: Annette Murray, BScPharm
References 1. Product information for Repatha. Amgen Inc.
Thousand Oaks, CA 91320. August 2015.
2. Product information for Praluent. Sanofi-Aventis.
Bridgewater, NJ 08807. July 2015. 3. Sabatine MS, Giugliano RP, Wiviott SD, et al.
Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med
2015;372:1500-9. 4. Blom DJ, Hala T, Bolognese M, et al. A 52-week
placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med 2014;370:1809-19.
5. Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1489-99.
Cite this document as follows: PL Detail-Document, Repatha and Praluent Comparison. Pharmacist’s
Letter/Prescriber’s Letter. October 2015.
Evidence and Recommendations You Can Trust…
3120 West March Lane, Stockton, CA 95219 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright 2015 by Therapeutic Research Center
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