Download Heart failure drug interactions

January 2017
H
Heart failure drug interactions
eart failure is a chronic condition affecting an
estimated 300,000 Australians. Prevalence is
known to increase with age, reaching 10% among
those aged 65 years or older and 50% in people aged
85 years or more. Symptoms of heart failure include
breathlessness, swollen ankles, weight gain, cough and
fatigue, all of which reduce quality of life. Therapies that
have been shown to improve survival include:
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angiotensin converting enzyme inhibitors (ACEI);
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angiotensin II receptor blockers (ARB);
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beta-blockers; and
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aldosterone antagonists.
A multidisciplinary approach to heart failure
management has clinical and economic benefits.
Pharmacists conducting Residential Medication
Management Reviews (RMMRs) can collaboratively
assess heart failure management with general
practitioners (GPs). Many residents with heart failure
plus other comorbidities require a palliative approach
to reduce symptoms and exacerbations, and improve
quality of life. Care needs to be taken to avoid medicines
that will exacerbate heart failure.
Precipitating factors
Precipitating or exacerbating factors in heart failure
include poor adherence to therapy and lifestyle measures
(excessive fluid, salt or alcohol intake), fluid overload,
anaemia, hyperthyroidism, myocardial infarction and
concomitant medicines.
In 2016, the American Heart Association published a
scientific statement on medicines that may cause or
exacerbate heart failure. This comprehensive article
provides on guide to prescription medications, over-thecounter (OTC) medications, and complementary and
alternate medicines (CAMs) that could exacerbate heart
failure by drug-drug interactions, worsening hypertension
or delivering a high sodium load.
NSAIDs
Non-steroidal anti-inflammatory drugs (NSAIDs) are
widely used to reduce pain and inflammation. Heart
failure and hypertension may worsen with NSAIDs due to
sodium and water retention. There is a significant doserelated increased risk of hospitalisation for heart failure
among people taking COX-2 inhibitors (celecoxib) or
traditional NSAIDs (ie, ibuprofen, diclofenac, naproxen). If
NSAIDs are prescribed, they should be used in the lowest
effective dose for the shortest period of time.
Diabetes
Metformin is considered first-line therapy for the
treatment of type 2 diabetes mellitus. There is
contradictory evidence on the risk of lactic acidosis in
people with heart failure taking metformin. Current
consensus is that metformin is not associated with
an increased risk for lactic acidosis, except perhaps
in people with poor renal function or suffering from
dehydration.
Thiazolidinediones or glitazones such as rosiglitazone
(Avandia) and pioglitazone (Actos) may cause
increased oedema and weight gain by fluid retention.
Thiazolidinediones should be avoided in patients with
symptomatic heart failure. This class of medicines may
also increase the risk of new onset heart failure.
Dipeptidyl Peptidase-4 Inhibitors include alogliptin
(Nesina), linagliptin (Trajenta), saxagliptin (Onglyza),
sitagliptin (Januvia) and vildagliptin (Galvus). They are
also known as DPP-4 inhibitors or gliptins. Saxagliptin
appears to increase the risk of hospitalisation for heart
failure, so should be avoided. Other DPP-4 inhibitors do
not appear to have this adverse effect.
Alpha-blockers
Alpha-blockers such as alfuzosin (Xatral SR), prazosin
(Minipress), tamsulosin (Flomaxtra) and terazosin
(Hytrin), relax the smooth muscle in the bladder neck
and prostate, and decreasing resistance to urinary flow
in men with benign prostatic hypertrophy (BPH). These
medications can exacerbate underlying myocardial
dysfunction and exacerbate heart failure in those with
established disease.
Antihypertensive medications
Dihydropyridine calcium channel antagonists (CCBs)
such as amlodipine (Norvasc), felodipine (Plendil,
Felodur), lercanidipine (Zanidip) and nifedipine (Adalat)
may cause peripheral oedema and hence worsen heart
HEART FAILURE DRUG INTERACTIONS
failure. Diltiazem (Cardizem) and verapamil (Isoptin)
can worsen heart failure more than the dihydropyridine
calcium channel blockers, and are contraindicated in
systolic heart failure. These risks are directly related to
the severity of heart failure.
and effervesce. OTC heartburn medications and cold
treatments may also contain significant amounts of
sodium. Product information or a pharmacist will be able
to advise on the sodium content of any medication.
Antiepileptic medications
Many guidelines recommend that nutritional
supplements should not be used for the treatment of
heart failure. There is evidence that supplementation
with vitamin E in dose of 400 IU/day or more may
increase the risk of developing new-onset heart failure.
Carbamazepine (Tegretol) is an antiepileptic that is also
used as a mood stabilizer and for neuropathic pain. It has
been associated with signs and symptoms of heart failure
in patients without cardiovascular disease.
Pregabalin (Lyrica), widely used for neuropathic pain
as well as epilepsy, may worsen heart failure due to
development of peripheral oedema. The risk of heart
failure exacerbation increases with concomitant use of
pregabalin and thiazolidinediones.
Beta-blocker eye drops
Beta-blocker eye drops, primarily timolol (Timoptol,
Tenopt, Nyogel), used for the treatment of glaucoma
have demonstrated clinically significant issues in
patients with heart failure, including arrhythmias such
as bradycardia, myocardial ischemia, hypotension, and
pulmonary oedema. Betaxolol eye drops (Betoptic,
Betoquin) is less likely to cause problems, but still may
have adverse effects on control of heart failure. They
should generally be avoided in people with heart failure,
as other classes of topical drugs for glaucoma (e.g.
prostaglandin analogues) are available.
QT-Prolonging Medications
Heart failure is a risk factor for torsade de pointes
because of frequent prolongation of the QT interval and
diuretic-induced hypokalaemia and hypomagnesaemia.
Numerous drugs from various therapeutic classes
have been implicated in prolonging the QT interval,
including antibiotics, antidepressants, antipsychotics, and
antiemetics, all of which are commonly used by patients
with heart failure.
Supplements
A number of complementary medicines interact with
cardiovascular medicines used in the treatment of heart
failure and should be avoided, including:
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St John’s wort – digoxin, ACE inhibitors/ARBs,
beta-blockers, calcium channel blockers, amiodarone,
warfarin
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Grapefruit juice - ACE inhibitors/ARBs, betablockers, calcium channel blockers, amiodarone,
warfarin
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Ginseng – warfarin
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Hawthorn – digoxin
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Dang Shen – warfarin
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Black cohosh - ACE inhibitors/ARBs, betablockers, amiodarone
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Green tea - warfarin
Summary
People with heart failure are often taking multiple
medications and have a high pill burden. A wide
range of medications may cause or exacerbate heart
failure, including analgesics, anaesthesia medications,
antidiabetic and antihypertensive medications,
anti-infective medications, anticancer medications,
hematologic medications, psychiatric medications,
urological medications, and OTCs/CAMs. Regular
medication reviews by GPs and pharmacists can identify
unnecessary medicines and potential drug interactions.
Rheumatological medications
The tumor necrosis factor-α (TNF-α) inhibitors
adalimumab (Humira), certolizumab (Cimzia), etanercept
(Enbrel), infliximab (Remicade), and golimumab (Simponi)
play a major role in the management of patients with
rheumatoid arthritis and Crohn’s disease. They may
worsen heart failure and are contraindicated in people
with moderate or severe heart failure.
References
Circulation. 2016;134:00–00. Available at
http://circ.ahajournals.org/content/early/2016/07/11/
CIR.0000000000000426.full.pdf
Sodium-Containing Medications
Sodium restriction is often recommended for patients
with heart failure. Many oral medications contain
sodium, especially those that may be mixed with water
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