ABSTRACT
Unlikely to be clinically significant
CALCIUM CHANNEL BLOCKERS
X-RAY CONTRAST SOLUTIONS
≠ hypotensive effect when intravenous ionic contrast solutions are given to patients on calcium channel blockers
Additive hypotensive effect Consider using a non-ionic X-ray contrast solution for patients on calcium channel blockers
CARDIAC GLYCOSIDES
DIGITOXIN
DIGITOXIN ANTIARRHYTHMICS
DIGITOXIN AMIODARONE Reports of digitoxin toxicity in two patients on digitoxin after starting amiodarone
Uncertain; thought to be due to inhibition of P-gp-mediated renal clearance of digoxin
Watch for digitoxin toxicity
DIGITOXIN PROCAINAMIDE Single case report of toxicity in a patient taking both digitoxin and procainamide
Uncertain at present Watch for digitoxin toxicity
DIGITOXIN ANTIBIOTICS – RIFAMPICIN Plasma concentrations of digitoxin may be halved by rifampicin
Due to ≠ hepatic metabolism Watch for poor response to digitoxin
DIGITOXIN ANTIEPILEPTICS – BARBITURATES, CARBAMAZEPINE, PHENYTOIN
Plasma concentrations of digitoxin may be ↓ by up to half by barbiturates
Possibly ≠ hepatic metabolism Watch for poor response to digitoxin
DIGITOXIN CALCIUM CHANNEL BLOCKERS
Plasma concentrations of digitoxin may be ≠ by diltiazem and verapamil
Uncertain at present Watch for digitoxin toxicity
DIGITOXIN DIURETICS – SPIRONOLACTONE
Conflicting results from volunteer studies; some showed ≠ (up to onethird) in the half-life of digitoxin, others a ↓ (up to one-fifth)
Uncertain at present Watch for either digitoxin toxicity or a poor response, particularly for the first month after starting spironolactone
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CARDIOVASCULAR DRUGS CARDIAC GLYCOSIDES Digoxin
Both colestipol and colestyramine are ion exchange resins that bind bile sodiums and prevent reabsorption in the intestine; this breaks the enterohepatic cycle of digitoxin
Colestipol and colestyramine should be given at least 1.5 hours after digitoxin
DIGOXIN
DIGOXIN AMINOSALICYLATES Sulfasalazine may ↓ digoxin levels. The manufacturers of balsalazide also warn against the possibility of this interaction in spite of a lack of case reports
Uncertain at present Watch for poor response to digoxin; check levels if signs of ↓ effect
DIGOXIN ANALGESICS
DIGOXIN NSAIDs Diclofenac, indometacin and possibly fenbufen, ibuprofen and tiaprofenic acid ≠ plasma concentrations of digoxin and ≠ risk of precipitating cardiac failure and renal dysfunction
Uncertain; postulated that NSAIDinduced renal impairment plays a role; however, since all NSAIDs have this effect, it is not understood why only certain NSAIDs actually influence digoxin levels
Monitor renal function closely. Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN OPIOIDS ≠ concentrations of digoxin may occur with tramadol
Uncertain at present Watch for digoxin toxicity; check levels and ↓ the dose of digoxin as necessary
DIGOXIN ANTACIDS Plasma concentrations of digoxin may be ↓ by antacids
Uncertain; probably ↓ absorption of digoxin
Watch for poor response to digoxin
DIGOXIN ANTIARRHYTHMICS
DIGOXIN AMIODARONE Amiodarone may ≠ plasma levels of digoxin (in some cases up to fourfold)
Uncertain; thought to be due to inhibition of P-gp-mediated renal clearance of digoxin. Amiodarone is also known to inhibit intestinal P-gp, which may ≠ the bioavailability of digoxin
↓ digoxin dose by one-third to onehalf when starting amiodarone. Monitor digoxin levels; watch for digoxin toxicity, especially for 4 weeks after initiating or adjusting amiodarone therapy
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Mechanism Precautions
digoxin
Uncertain at present Monitor PR and ECG closely
DIGOXIN PROPAFENONE Digoxin concentrations may be ≠ by propafenone
Uncertain at present Watch for digoxin toxicity; check digoxin levels if indicated and ↓ digoxin dose as necessary (15-70% is suggested by studies)
DIGOXIN ANTIBIOTICS
DIGOXIN AMINOGLYCOSIDES 1. Gentamicin may ≠ plasma concentrations of digoxin 2. Neomycin may ↓ plasma concentrations of digoxin
1. Uncertain; postulated to be due to impaired renal clearance of digoxin 2. Neomycin ↓ absorption of digoxin; this may be offset in some patients by ↓ intestinal bacterial breakdown of digoxin
1. Monitor digoxin levels; watch for ≠ levels, particularly with diabetes and in the presence of renal insufficiency 2. Monitor digoxin levels; watch for poor response to digoxin
DIGOXIN MACROLIDES Digoxin concentrations may be ≠ by macrolides
Uncertain; postulated that macrolides inhibit P-gp in both the intestine (≠ bioavailability) and kidney (↓ clearance). It is possible that alterations in intestinal flora may also have a role
Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN RIFAMPICIN Plasma concentrations of digoxin may be ↓ by rifampicin
Rifampicin seems to induce P-gpmediated excretion of digoxin in the kidneys
Watch for a ↓ response to digoxin, check plasma levels and ≠ the dose as necessary
DIGOXIN TRIMETHOPRIM, CO-TRIMOXAZOLE
Trimethoprim may ≠ plasma concentrations of digoxin, particularly in elderly people
Uncertain; postulated that trimethoprim ↓ renal clearance of digoxin
Monitor digoxin levels; watch for digoxin toxicity
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CARDIOVASCULAR DRUGS CARDIAC GLYCOSIDES Digoxin
given in tablet form
Cytotoxic-induced damage to the mucosa of the intestine may ↓ absorption; this does not seem to be a problem with liquid or liquid-containing capsule formulations
Watch for poor response to digoxin; check levels if signs of ↓ effect, and consider swapping to liquid digoxin or liquid-containing capsules
DIGOXIN AMINOSALICYLATES Sulfasalazine may ↓ digoxin levels. The manufacturers of balsalazide also warn against the possibility of this interaction in spite of a lack of case reports
Uncertain at present Watch for poor response to digoxin; check levels if signs of ↓ effect
DIGOXIN CICLOSPORIN ≠ plasma digoxin levels, with risk of toxicity. Digoxin may ≠ ciclosporin bioavailability (by 15-20%)
Attributed to inhibition of intestinal P-gp and renal P-gp, which ≠ bioavailability and ≠ renal elimination. Digoxin ≠ bioavailability of ciclosporin due to substrate competition for P-gp
Watch for digoxin toxicity. Monitor plasma digoxin and ciclosporin levels
DIGOXIN CORTICOSTEROIDS Risk of digoxin toxicity due to hypokalaemia
Corticosteroids may cause hypokalaemia
Monitor potassium levels closely. Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN INTERFERON GAMMA Plasma concentrations of digoxin may occur with interferon gamma
Interferon gamma ↓ P-gpmediated renal and biliary excretion of digoxin
Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN PENICILLAMINE Plasma concentrations of digoxin may be ↓ by penicillamine
Uncertain at present Watch for poor response to digoxin
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Mechanism Precautions
Possibly due to tacrolimus-induced hyperkalaemia and hypomagnesaemia
Watch for digoxin toxicity. Monitor potassium and magnesium levels
DIGOXIN ANTIDEPRESSANTS
DIGOXIN ST JOHN’S WORT Plasma concentrations of digoxin seem to be ↓ by St John’s wort
St John’s wort seems to ↓ P-gpmediated intestinal absorption of digoxin
Watch for a ↓ response to digoxin
DIGOXIN TRAZODONE Reports of two cases of ≠ plasma concentrations of digoxin after starting trazodone
Uncertain at present Watch for digoxin toxicity; check levels and ↓ the dose of digoxin as necessary
DIGOXIN ANTIDIABETIC DRUGS – ACARBOSE
Acarbose may ↓ plasma levels of digoxin
Uncertain; possibly ↓ absorption of digoxin
Monitor digoxin levels; watch for ↓ levels
DIGOXIN ANTIDIARRHOEALS – KAOLIN
Possibly ↓ levels of digoxin ↓ absorption Separate doses by at least 2 hours
DIGOXIN ANTIEPILEPTICS Phenytoin may ↓ plasma levels of digoxin
Uncertain at present Watch for poor response to digoxin; check levels if signs of ↓ effect
DIGOXIN ANTIFUNGALS
DIGOXIN AMPHOTERICIN Risk of digoxin ≠ by toxicity due to hypokalaemia
Amphotericin may cause hypokalaemia
Monitor potassium levels closely. Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN ITRACONAZOLE Itraconazole may cause ≠ plasma levels of digoxin; cases reported of digoxin toxicity
Itraconazole inhibits P-gpmediated renal clearance and ≠ intestinal absorption of digoxin
Monitor digoxin levels; watch for digoxin toxicity
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CARDIOVASCULAR DRUGS CARDIAC GLYCOSIDES Digoxin
in the presence of heart failure (class II or more severe) or renal insufficiency. No other ACE inhibitors seem to interact in the same way
Uncertain; postulated to be due to ↓ renal excretion of digoxin
Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN ALPHA-BLOCKERS Possibility of ≠ plasma concentrations of digoxin; no cases of toxicity have been reported with doxazosin or prazosin
Doxazosin inhibits P-gp-mediated elimination of digoxin; mechanism with prazosin uncertain at present
Monitor digoxin levels
DIGOXIN ANGIOTENSIN II RECEPTOR ANTAGONISTS
Telmisartan may ≠ plasma levels of digoxin
Uncertain; telmisartan thought to ≠ rate of absorption of digoxin
Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN ANTIMALARIALS
DIGOXIN CHLOROQUINE, HYDROXYCHLOROQUINE
Chloroquine may ≠ plasma concentrations of digoxin
Uncertain at present Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN MEFLOQUINE Risk of bradycardia Uncertain; probably additive effect; mefloquine can cause AV block
Monitor PR and ECG closely
DIGOXIN QUININE Plasma concentrations of digoxin may ≠ when co-administered with quinine
Uncertain, but seems to be due to ↓ non-renal (possibly biliary) excretion of digoxin
Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN ANTIMUSCARINICS PROPANTHELINE
≠ digoxin levels (30-40%) but only with slow-release formulations
Slowed gut transit time allows more digoxin to be absorbed
Use alternative formulation of digoxin
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Mechanism Precautions
LOPINAVIR)
Uncertain; probably due to inhibition of P-gp-mediated renal excretion of digoxin and ≠ intestinal absorption
Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN ANXIOLYTICS AND HYPNOTICS
Alprazolam and possibly diazepam may ≠ digoxin levels, particularly in the over-65s
Uncertain at present Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN BETA-BLOCKERS
DIGOXIN BETA-BLOCKERS Risk of bradycardia and AV block Additive bradycardia Monitor PR, BP and ECG at least weekly until stable
DIGOXIN CARVEDILOL Carvedilol may ≠ digoxin plasma concentrations, particularly in children
↓ P-gp-mediated renal clearance of digoxin
↓ the dose of digoxin by 25%; watch for signs of digoxin toxicity and monitor digoxin levels
DIGOXIN BRONCHODILATORS – BETA-2 AGONISTS
1. Hypokalaemia may exacerbate digoxin toxicity 2. Salbutamol may ↓ digoxin levels (by 16-22%) after 10 days of concurrent therapy
1. Beta-2 agonists may cause hypokalaemia 2. Uncertain
1. Monitor potassium levels closely 2. Clinical significance is uncertain. Useful to monitor digoxin levels if there is a clinical indication of ↓ response to digoxin
DIGOXIN CALCIUM Risk of cardiac arrhythmias with large intravenous doses of calcium
Uncertain; it is known that calcium levels directly correlate with the action of digoxin; therefore, high levels, even if transient, may ≠ the chance of toxicity
It is recommended that parenteral administration of calcium should be avoided in patients taking digoxin. If this is not possible, administer calcium slowly and in small aliquots
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CARDIOVASCULAR DRUGS CARDIAC GLYCOSIDES Digoxin
case reports of significant toxicity 2. ≠ AV block when digoxin is co-administered with verapamil
1. Verapamil seems to inhibit P-gp-mediated renal and biliary clearance of digoxin. Inhibition of intestinal P-gp would also ≠ the bioavailability of digoxin 2. Additive effect
1. It is recommended to ↓ digoxin doses by 33-50% when starting verapamil; monitor digoxin levels and watch for symptoms/signs of toxicity 2. Monitor ECG closely when co-administering digoxin and verapamil, especially when verapamil is being given parenterally
DIGOXIN DILTIAZEM, NIFEDIPINE, FELODIPINE, LACIDIPINE, LERCANIDIPINE, NICARDIPINE, NISOLDIPINE
Possible ≠ plasma concentrations of digoxin
These calcium channel blockers are thought to ↓ the renal excretion of digoxin
Monitor digoxin levels carefully
DIGOXIN DIURETICS
DIGOXIN CARBONIC ANHYDRASE INHIBITORS, LOOP DIURETICS, THIAZIDES
Risk of digoxin toxicity ≠ due to hypokalaemia
Uncertain Monitor potassium levels closely. Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN POTASSIUM-SPARING DIURETICS AND ALDOSTERONE ANTAGONISTS
Eplerenone and spironolactone may ≠ plasma concentrations of digoxin
Uncertain; spironolactone possibly ↓ the volume of distribution of digoxin
Monitor digoxin levels; watch for digoxin toxicity
DIGOXIN GRAPEFRUIT JUICE Possible ≠ efficacy and ≠ adverse effects
Possibly via altered absorption Most patients have been unaffected; consider if unexpected bradycardia or heart block with digoxin
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Mechanism Precautions
for digoxin 2. Liquorice may ≠ the risk of digoxin toxicity 3. Many herbal medicines contain digoxinlike compounds, e.g. black cohosh root, cayenne pepper
1. Bufalin cross-reacts with the antibody used in some digoxin assays. The mechanism of interaction of danshen and ginseng is uncertain at present 2. Liquorice causes electrolyte imbalances, which may precipitate digoxin toxicity
Ask about Chinese herbal remedies in patients taking digoxin; inform the laboratory when monitoring digoxin levels. Watch for symptoms/signs of toxicity in patients taking liquorice-containing remedies
DIGOXIN LIPID-LOWERING DRUGS
DIGOXIN ANION EXCHANGE RESINS Colestipol and colestyramine both may ↓ digoxin levels
Both colestipol and colestyramine are ion exchange resins that bind bile sodiums and prevent reabsorption in the intestine; this breaks the enterohepatic cycle of digoxin
Colestipol and colestyramine should be given at least 1.5 hours after digoxin
DIGOXIN STATINS High-dose (80 mg) atorvastatin may ≠ digoxin levels
Atorvastatin inhibits intestinal P-gp, which ≠ absorption of digoxin
Watch for digoxin toxicity
DIGOXIN MUSCLE RELAXANTS DIGOXIN DEPOLARIZING Risk of ventricular arrhythmias
when suxamethonium is given to patients taking digoxin
Uncertain; postulated that the mechanism involves rapid efflux of potassium from the cells
Use caution and monitor ECG closely if suxamethonium needs to be used in patients taking digoxin
DIGOXIN NON-DEPOLARIZING Case reports of S-T segment/ T wave changes and sinus/atrial tachycardia when pancuronium given to patients on digoxin
Uncertain Avoid pancuronium in patients taking digoxin
DIGOXIN SKELETAL Risk of bradycardia when tizanidine given with digoxin
Tizanidine has a negative inotropic effect
Monitor PR closely
