6.4.

1 Antiarrhythmics
• amiodarone contains iodine and affects Other drugs
thyroxine metabolism; this complicates the Treatment with drugs that slow cardiac conduction,
diagnosis of thyroid dysfunction; when request- cause bradycardia or cause arrhythmias may
ing thyroid function tests, notify laboratory that potentiate the cardiac adverse effects of digoxin; use
the patient is taking amiodarone combinations carefully and monitor cardiac
• risk of thyroid function abnormalities and liver function.
damage persist for up to a year after stopping Treatment with drugs that inhibit or induce P-gp
treatment; continue monitoring (Table DI-4 p tnZ) l!'ay ~ncrease the risk of adverse
• if dyspnoea or non-productive cough develop, effects or decrJ!se d1goxm' s efficacy.
perform chest x-ray and pulmonary function Renal
tests as soon as possible and monitor closely Predominantly renally cleared (about 70%); reduce
dose in renal impairment.
tab, 100 mg (scored), 30, Aratac, Cordarone X, PBS-R 1
tab, 200 mg (scored), 30, Amdarone, Aratac, Cordarone xa, Elderly
PBS-R 1 May have reduced renal clearance of, and increased
inj, 50 mg/ml, 3 ml, 6, Cordarone X sensitivity to, digoxin; reduce dose and closely
inj, 50 mg/ml, 3 ml, 10, Amiodarone monitor digoxin concentration.
1
severe arrhythmias Pregnancy ■
a generic brands available Safe to use, but dose requirement is not predictable; •
may require increased dose; used to treat fetal
Digoxin arrhythmias.
Cardiac glycoside Breastfeeding
See also Heart failure p 231, Tachyarrhythmias p 280 Safe to use.
For drug interactions see Digoxin p 1012 Adverse effeds
Mode of action May worsen arrhythmia
?lows heart rate and reduces atriove ricular AV) (proarrhythmic effect).
nodal conduction by an increase • a al to and a
reduction~ sympathetic activity creases the force. Digoxin has a narrow therapeutic range; adverse
~yo~rd~a! contracti9-n by increasing the relea~e effects are related to its plasma concentration and
and availab1hty of stored intracellular ~alcium. very few occur at <0.8 microgram/L (1 nanomol/L).
Indications. Digoxin usually has an effect on the ECG and may
AF and atrial flutter result in prolonged PR interval, ST depression or
Heart failure T wave inversion (these changes do not necessarily
indicate digoxin toxicity or myocardial ischaemia).
Precautions
Hyperthyroidism - may decrease digoxin concen- In children, arrhythmias (including sinus brady-
tration and increase sympathetic tone; monitor cardia) are the earliest and most frequent indicators
that digoxin dosage is too high. •
digoxin concentration and alter dose when required,
or combine with another agent; dosage adjustment Common (>1%)
may be required when condition is corrected. anorexia, .nausea, vomiting, diarrhoea, visual
Hypothyroidism-may increase digoxin concen- disturbances (eg blurred vision), drowsiness,
tration; monitor digoxin concentration and alter dizziness, headache, rash, bradycardia, arrhythmia
dose as required; dosage adjustment may be Infrequent (0.1-1 %}
required when condition is corrected. depression, shortened QRS complex, atrial or
Hypokalaemia, hypomagnesaemia, hypercalcaemia, ventricular extrasystoles, paroxysmal atrial tachy-
acidosis, hypoxia-may increase sensitivity to cardia with AV block, ventricular tachycardia or
digoxin (especially hypokalaemia); symptoms of fibrillation, heart block
toxicity may occur at lower digoxin concentrations Rare (<0.1%)
(see Concentration monitoring p 286). thrombocytopenia, seizures, confusion, psychosis,
Cardiac gynae~1astia (long•term use)
Contraindicated in second- or third-degree heart <;Q__osag_4U
block (without pacemaker)A .$lC( involving acces- tailorclose according to renal function, clinical
sory pathway (Wolff-Parkinsl>n-White syndrome), response and concentration monitoring (below).
ventricular tachycardia and fibrillation, hyper- These doses are intended as a guide.
trophic obstructive cardiomyopathy, cor pulmonale loading dose
(acute and chronic) or constrictive pericarditis. Loading dose n1ay not be needed, eg in n1ild heart
In acute MI, ischaemic heart disease or myocarditis, failure; it may sometimes be used for more rapid
digoxin increases risk of arrhythmias. control of ventricular rate in AF and atrial flutter.
Use digoxin cautiously in sick sinus syndrome (risk Digoxin loading can usually be achieved by the oral
of severe bradycardia or sinoatrial block). route.
Digoxin may worsen cardiac function in severe Adult
aortic stenosis because it increases the force of Oral//~, 250-500 micrograms every 4-6 hours
myocardial contraction. accordmg to response, up to a totnl of 1.5 mg.
Digoxin increase~ risk of ~rrh~thmias after DC co1Lfi11ued
cardioversion; w1thhold d1goxm for 1-2 days before
cardioversion or use lowest effective energy.

AMH © 2023 285

6.4.1 Antiarrhythmics
Elderly Administrati on advice
Oral/IV, 125-250 micrograms every 4-6 hours Give IV over at least S minutes; compatible fl .
according to response, up to a total of are sodium chloride 0.9%, glucose 5% and Uids
500 micrograms. glucose/sodiu m chlorid:. . .
Renal impairment Do not give IM (unpredictable absorption, local
CrCl <60 mL/minute, halve dose. irritation).
Maintenance dose counselling
Adult Tell your doctor ~r pharmacist that f~u are taki
Oral, 125-250 microgr~s once daily (rarely digoxin before usmg any other medicines ng
increased up to 500 micrograms daily). including over-the-coun ter and herbal products.
Elderly • Pradice points
Oral, 62.5-125 micrograms once daily. • check renal function and electrolyte concentr
tions before starting digoxin a-
Renal impairment
• onset of effect occurs 0.5-2 hours after initial
Reduce dose according to drug concentration dose of 500-750 micrograms and 5-30 minu~ral
monitoring if necessary.
after initial IV dose of 400-600 micrograms; es
CrCl 30-60 mL/minute, oral 62.5-250 micrograms maximal effect occurs after 1-4 hours (IV) or
once daily. 2-6 hours (oral)
CrCl 10-30 mL/minute, oral 62.5-125 micrograms • regular~y asses_s patients for digox?l toxicity
once daily. (includmg resting heart rate); routine measure-
CrCl <10 mL/minute, oral 62.5 micrograms once ment of pulse rate before giving next dose of
daily or on alternate days. digoxin is not necessary -
Child • assume that any arrhythmia that occurs in a
Use ideal weight (p 1145) rather than actual weight child taking digoxin is due to the drug until
in obese patients. These dose ranges are intended proven otherwise
as a guide, seek specialist advice. • when used to control ventricular rate in AF, aim
Loading for a ventricular rate <110 beats/minute
Give half of the loading dose initially, then a • digoxin is relatively n::ieffecti~e ~ slowing rapid
quarter of the dose Cr12 hours after the initial ventricular rate associated with increased
dose, then the last quarter another Cr12 hours sympathetic tone (eg exercise, hyperthyroidism,
later. fever)
Infant <2 years, oral/IV 30-40 micrograms/kg . • digoxin is not effective in converting AF to sinus
Child >2 years, oral/IV 24-30 micrograms/kg . rhythm or preventing recurrence of AF after
Maintenance cardioversion
Oral, 5-10 micrograms/kg daily in 1 or 2 doses; tab, 62.5 mcg, 200, Lanoxin PG, Sigmaxin-PG, PBS
maximum 250 micrograms daily. tab, 250 mcg (scored), 100, Lanoxin, Sigmaxin, PBS
Concentratio n monitoring oral liquid, 50 mcg/ml, 60 ml. Lanoxin Paediatric Elixir,
See also Tber:..ap,eutlc drug monLtodng p xvi PBS[120 ml]
Steady state is reached after about 7 days if renal inj, 25 mcg/ml, 2 ml, 5, Lanoxin Infant
function is normal (half-life is 36 hours); this may inj, 250 mcg/ml, 2 ml, 5, Lanoxin
be prolonged in renal impairment.
Take blood sample at least 6 hours after a dose to Disopyram ide
allow for distribution. See also Tachyarrhythm ias p 280
The generally accepted therapeutic range is For drug interactions see Disopyramide p 1015
0.5-2 microgram/L (0.6-2.6 nanomol/L) as toxicity
is more common at digoxin concentrations Mode of action
>2 micrograms/L . However, toxic effects can occur Pro~ongs refractory period .of myocardial tissue
at lower concentrations , particularly in the elderly (atria, ventricles, ventricular conduction system: .
or in those with electrolyte disturbance, hypoxia or bypass tracts) and reduces automaticity in Purkin)e
hypothyroidis m. GI symptoms (eg nausea, fibr_es. It ha~ significant anticholinergi c activity,
anorexia) may precede cardiac symptoms (eg which may increase atrioventricula r nodal
arrhythmias). conduction, and it also has a negative inotropic
Heart failure, AF: consider maintaining lower effect.
concentration s of 0.5-0.8 microgram/L Indications
([Link] nanomol/L) in patients with AF and in those Life-threatenin g ventricular tachyarrhythm ias
with heart failure who are in sinus rhythm as: refractory to other treatment
- there may be improved outcomes or reduced Precautions
hospitalisatio ns compared with higher Digoxin toxicihJ-contr aindicated.
concentration s Treatment with flecainide-con traindicated.
- higher concentration s within the therapeutic Electro~yte disturbances (eg hypokalaemia, hyper-
range may be associated with increased risk kalaemia, hypomagnesaemia)-increase risk of
of mortaJity. arrhythmias; correct before starting treatment if
Balance clinical benefit against the incidence of possible.
adverse effects and reduce the dose if appropriate. Risk factors for ar~g_le-closure glaucoma (p 483)-acute
angle-closure crisis may rarely be precipitated.
AMH © 202:
286
 Digoxin

colestyramine + deferasirox De~t~omethorphan can contribute to serotonin

Colestyramine decreases deferasirox concen- tox1c1ty; administration with other drugs that may
tration and may decrease its efficacy; try to contribute to serotonin toxicity (Table 18-2 p 839)
reduce the effect of the interaction by giving may increase likelihood; avoid combinations or
deferasirox at least 1 hour before, or 4-6 hours monitor clinical course carefully.
after the resin, then monitor clinically and abiraterone + dextromethorpha n
increase deferasirox dose if necessary. Abiraterone increases the concentration of
rifampicin + deferasirox dextromethorphan and the risk of adverse
Rifarnpicin decreases deferasirox concentration effects; avoid combination or watch for adverse
and may decrease its efficacy; avoid a long effects and decrease dextrornethorphan dose if
course of rifampicin, or consider increasing the necessary.
initial deferasirox dose by half, monitoring cinacalcet + dextromethorpha n
clinically and further adjusting the dose if Cinacalcet may increase concentration of dextro-
needed. methorphan and the risk of adverse effects;
theophylline + deferasirox p 1096 avoid combination or watch for adverse effects
Deferiprone and decrease dextromethorphan dose if
antacids + deferiprone necessary.
Deferiprone may theoretically bind to MAOls + dextromethorpha n
aluminium in the GIT, reducing deferiprone Serotonin toxicity. may occur if dextromethor-
absorption and activity; avoid combination with phan is given with an irreversible~ nonsele~ve
aluminium-contain ing antacids. MAOI (phenelzine, tranylcypromme); combi-
Demeclocycline, see Tetracyclines p 1095 nation contraindicated by manufacturers.
Desflurane, see General anaesthetics p 1022, vemurafenib + dextromethorpha n
Desflurane p 1022 Vemurafenib may increase concentration of
Desmopressin dextromethorphan and 1;he ~~~ of adverse
Desmopressin may cause hyponatraemia and effects (probably not by inhibiting CYP2D6);
water retention; giving it with drugs* that may also avoid combination or watch for adverse effects
cause these adverse effects, eg drugs that cause and decrease dextromethorphan dose if
SIADH, NSAIDs, may increase the likelihood of necessary.
their occurrence. Diazepam, see Benzodiazepines p 983,
tolvaptan + desmopressin Diazepam p 984
Tolvaptan antagonises the effect of desmo- Diazoxide
pressin used to prevent or control bleeding; Diazoxide can increase blood glucose concen-
avoid combination as it is not known whether tration, see Drugs affecting blood glucose
increasing the desmopressin dose would concentration p 423.
overcome this. Diazoxide causes hypotension; administration
Desogestrel with ethinylestradiol, see with other drugs* that also reduce BP may ~ance
Combined oral contraceptives p 1002 its hypotensive effect. Take particular care if the
Desvenlafaxine, see SNRls p 1082, hypotensive agents are given IV.
Desvenlafaxine p 1083 Diclofenac. see NSAIDs p 1055, Diclofenac
Dexamethasone , see Corticosteroids p 1004, p 1055
Dexamethasone p 1005 Dicloxaclllin. see Penicillins p 1064,
Dexamfetamine , see Psychostimulants p 1075 Dicloxacillin p 1064
Dexamphetamin e (dexamfetamine), see Dienogest, see Progestogens p 1072
Psychostimulan ts p 1075 Dienogest with estradiol, see Combined oral
Dexchlorphenira mine, see Antihistamines contraceptives p 1002
(sedating) p 969 Digoxin
Dexmedetomidi ne Digoxin can cause arrhythmias; administration
Use of dexmedetomidine with other CNS with other drugs* that can also cause arrhythmias
depressants* may enhance sedation, bradycardia may increase this risk; use con1binations cautiously.
and hypotension; doses should be reduced and Digoxin slows cardiac conduction and causes
titrated carefully. bradycardia; administration with other drugs* that
Dexmedetomidin e may cause hyperkalaemia; also have this effect increases the risk of significant
monitor potassium concentration if taken with bradyarrhythmia; monitor heart rate and adjust
potassium supplements or with other drugs* that drug doses if needed.
can also cause potassium retention. Electrolyte abnormalities, eg hypercalcaemia,
Administration with other drugs* that cause hypokalaemia, increase the risk of arrhythmias,
hypotension and bradycardia may increase these and may also prolong the QT interval, see
adverse effects; reduce dexmedetomidine dose and Prolonged QT interval p 279. Some drugs* may
titrate carefully. affect electrolyte concentrations. Correct abnorn1al-
Dextromethorph an ities if possible.
See also Opioids p 1057 Giving digoxin (a P-gp substrate) with inhibitor? or
~extromethorpha n is metabolised by CYP206; if inducers of this protein ffrny increase the risk ot its
given with drugs that inhibit this enzyme (p 1115) adverse effects or decrease its efficacy, see Table
the risk of ad verse effects may increase. DI-4 Drugs and P-glycoprotein p l l l 7. As digoxin

AMH © 2023 * Check the relevant drug monograph(s) 1009

Digoxin
may interact with many drugs, monitor digoxin ivacaftor + digoxin
concentrat ion (p 286), efficacy and adverse effects Iyacaftor may increase digoxin cone .
when there is any change to drug treatment. nsk of toxicity; monitor digoxin c entratio~ and
The n ber of interactions reflects the fact that and ~linical effects; reduce digox·ondcentration
required.
dl.goxm1 ~s used in drug interaction studies
. t .
in ose as
conducted for d~g r~gis ration. lapatinib + digo><in
,.,ose + dIgoxIn ~apat~ib increases di oxin concen .
~caarlJose may decrease absorption of digoxin· mcreas1;r1g th~ risk of tgxicity; avoidtratio~, .
-~ acarbose and digoxin at ab~ut the same ' or monitor d1goxin concentration .1m~~atio n
fines each day to standardis e this effect; moni- effects a_nd reduce dose if necessa:; chmcal
tor digoxin concentration and increase digoxin macro~•des + digoxin
dose if necessary. Macrolides may increase absorption Of ct· .
amiodarone + digoxin rareIY n:iay 1ead to _digoxin toxicity (especiall
1goxin·
.'
Amiodarone increases digoxin concentrat ion renal failure); monitor digoxin concentr ti yin
and risk of toxicity and also has additive effects • • I effects and decrease
c1mica a 0 nand
digoxin dose if
in slowing cardiac conductio n (the increase in necessary.
digoxin levels may be &reat~r in children). If mirabegro n + digoxin
using together, halve d1goxm dose and monitor Mirabegron may increase digoxin concent ti
digoxin concentration; wa_tch for bradyarrh yth- . h · ra on
w h 1c_ may 1n~rease the risk of adverse effects; '
mia and ECG changes; ad1ust digoxin dose momtor d1goxm concentration and its effects d
further if needed. decrease its dose if necessary. an
carvedilol + digoxin nifedipine + digoxin
Carvedilol may increase digoxin concentration Nifedipine may increase digoxin concentration
and risk of toxicity, especially in children. Both which occasionally results in an increase in '
drugs also cause bradycard ia. Monitor digoxin adverse effects; monitor digoxin concentration
concentration and clinical effects; reduce and its effects and decrease its dose if necessary.
digoxin dose as required. penicillamine + digoxin
colestyramine + digoxin Penicillamine may decrease digoxin concen-
Colestyramine reduces absorption of digoxin tration, reducing its effect; monitor digoxin
and may reduce its clinical effects; give digoxin concentration and clinically; increase digoxin
1 hour before, or 4-6 hours after, colestyramine dose if necessary.
and monitor digoxin concentration and for posaconazole + digoxin
reduced efficacy. Posaconazole may increase digoxin concentra-
diltiazem + digoxin tion, which may increase its adverse effects;
Diltiazem may increase digoxin concentration monitor digoxin concentration and its effects and
and risk of toxicity. Diltiazem also has additive decrease its dose if necessary.
negative effects on heart rate and cardiac quinine + digoxin
conduction; monitor digoxin concentration and Quinine, particularly in antimalarial doses, may
clinical effects; reduce digoxin dose as required. increase digoxin concentration and risk of
glecaprevir with pibrentasvir + digoxin toxicity; monitor digoxin concentration and for
Glecaprevir with pibrentasvir may increase its adverse effects; decrease digoxin dose if
digoxin concentration and risk of toxicity; halve necessary.
the digoxin dose, monitor digoxin concentration rifampicin + digoxin
and clinical effects and adjust digoxin dose as Rifampicin may decrease digoxin concentration
required. and its clinical effect (no interaction with IV
HIV-protease inhibitors + digoxin digoxin); monitor clinical effect and digoxin
Ritonavir (alone and in a low dose with lopina- concentration; increase digoxin dose if necessary.
vir) r~d~ces excretion of digoxin, increasing risk sofosbuvir with velpatasvir + digoxin
of toxtc1ty (the effect may be greater with IV than Sofosbuvir with velpatasvir may increase
oral digoxin); other HIV-Pis are likely to behave digoxin concentration and risk of toxicity; moni-
similarly; monitor digoxin concentration and for tor digoxin concentration and for its adverse
its adverse effects; decrease digoxin dose if effects; reduce digoxin dose as required.
necessary.
sofosbuvir with velpatasvir and
isavuconazole + digoxin voxilaprevir + digoxin
Isavuconazole may increase digoxin concen- Sofosbuvir with velpatasvir and voxilaprevir
tration and risk of toxicity; monitor digoxin may increase digoxin concentration and risk of
concentration and for its adverse effects; reduce !oxicity; monitor digoxin concentration and for
digoxin dose if necessary. its adverse effects; reduce digoxin dose as
itraconazole + digoxin required.
Itraconazole may increase digoxin concentration spironoladone + digoxin
and risk of toxicity. Itraconazole also has nega- Spiro!1olactone increases digoxin concentration
tive inotropic effects. Monitor digoxin concentra- a_nd nsk of toxicity; monitor digoxin concentrn-
tion and clinical effects; reduce dose if necessary ~1on and for adverse effects; reduce digoxin dose
(may need to reduce by at least half). 1f ~ecessary. Some digoxin assays arc affected by
sp1ronolactone.

1010 * Check the relevant drug monograph(s) AMH © 2023

 Direct thrombin inhibitors

St John's wort+ digoxin Dipyridamole *

St John's .wor~ ":'ay decrease [Link] concentra- •. t ti wi·th other drugs that can affect
Adm mis
tion and its chn1cal effect; avoid combination. ra on . • k of bleed-
the clotting process may increase the ~s . . ted .
sucralfate + digoxin . ing (but use antiplatelet agents where mdica ),
sucralfate re?uces absorp~1on of digoxin and monitor closely. .
maY reduce its [Link] and clinical effect; IV dipyridamole may cause severe hypotensio;;
separate adminisO:atio~ by at least 2 hours. administration with other drugs* that lowet B
sulfasalazine + d1gox1n may _result in additional hypotensive effects;
sulfasalazine m~y .decrease digoxin concen- morutor BP closely.
tration an~ its clinic~l ~ffect; ~onitor digoxin adenosine + dipyridamole p 962
concentration and ~hrucally; increase digoxin caffe~ne + dipyridamole . .
dose if necessary. Caffe1;1e may inhibit the action of JY d~pynda-
suvorexant + digoxin m?le m cardiac stress testing, affecting u:it~rpret-
suvorexant may increase digoxin concentration ation of test; do not take products contairung
and risk of toxicity; monitor digoxin concentra- caffeine for 24 hours before cardiac stress
tion and for its adverse effects; reduce digoxin testing.
dose as required. theophylline + dipyridamole
suxamethonium + digoxin p 1093 Theophylline may inhibit the action of IV .
ticagrelor + digoxin dipyridamole in cardiac stress testing, affecting
Ticagrelor may increase digoxin concentration interpretation of test; do not take theophylline
and risk of toxicity; monitor digoxin concentra- for 24 hours before cardiac stress testing.
tion and adverse effects; reduce digoxin dose as Direct thrombin inhibitors
required. Members of this class are argatroban, bivalirudin
tolvaptan + digoxin and dabigatran.
Tolvaptan may increase digoxin concentration Administration with other drugs* that can affect
and risk of toxicity; monitor digoxin concentra- the clotting process may increase the risk of bleed-
tion and clinical effects; reduce digoxin dose as ing (but use antiplatelet agents where indicated);
required. avoid combinations or monitor closely.
vandetanib + digoxin Dabigatran
Vandetanib may increase digoxin concentration See also Direct thrombin inhibitors p 1011
and risk of toxicity; monitor digoxin concentra- Dabigatran etexilate is a substrate of P-gp: the
tion and adverse effects; reduce digoxin dose as concentration of dabigatran may increase if it is
required. Be aware that the long half-lif~ of given with a P-gp inhibitor, increasing the risk of
vandetanib will prolong the effects of this bleeding; its efficacy may decrease if it is given
interaction for weeks. with a P-gp inducer, see Table DI-4 Drugs and
P-glycoprotein p 1117. The extent of any inter-
vemurafenib + digoxin action will depend on other factors as well, eg
Vemurafenib may increase digo?'in c~ncei:i- when each is given. Some drug combinations*
tration and risk of toxicity; morutor d1goxm are contraindicated; avoid combining dabiga-
concentration and for its adverse effects; reduce tran with strong P-gp inducers (eg rifampicin).
digoxin dose as required. amiodarone + dabigatran
venetoclax + digoxin . Amiodarone increases dabigatran concentration
Venetoclax may increase digox~n c?ncentr~tioi:i and the risk of bleeding; reduce dose of dabiga-
~d risk of toxicity; avoid combmatton but if this tran when it is used for prevention of VTE after
1s not possible, give digoxin at least 6 hours knee or hip replacement, see Dosage p 322 in
before venetoclax. Dabigatran; no dose adjustment is necessary if
verapamil + digoxin . using it for other indications.
Verapamil increases digoxin concentration and clarithromycin + dabigatran
risk of toxicity; this is dose-dependent. Verapa- Clarithromycin increases dabigatran concen-
mil also has additive negative eff~cts 01:1 he~rt tration (sometimes to about the same extent as
rate and cardiac conduction; monitor digoxm amiodarone) and the risk of bleeding; use
concentration and clinical effects; reduce combination cautiously .
. digoxin dose as required. elvitegravir with cobicistat + dabigatran
Dihydrococteine, see Opioids P 1057 Cobicistat increases dabigatran concentration
e:[Link], see Calcium channel and anticoagulant effect when it is given with,
oCkers p 994 an~ 2 hou~s af~er, da~i~atran. Avoid combining
giltlazem, see Calcium channel blockers P 994, elvit~grav1r with ~ob1cistat with dabigatran and
~lti11en, p 994 use either warfann or an alternative antiretro-
r•"1tnhydrinate, see Antihistamines viral.
l>leciatlng) p 969 glecaprevir with pibrentasvir + dabigatran
( 1Pl\enhydramine, see Antihistamines
'•dating) p 969 Glecaprevir wi~h pibrentasvir increases dabiga-
tran concent!ahon and possibly its anticoagulant
effect; combtnation is contraindicated.

~Ml-i © 2023 • Check the relevant drug monograph{s) 1011