ABSTRACT
Not thought to be clinically significant unless a poor CYP2C19 metabolizer. No specific recommendations. Different proton pump inhibitors may interaction differently – monitor if changing therapy or doses
DIGOXIN SUCRALFATE Plasma concentrations of digoxin may be ↓ by sucralfate
Uncertain; possibly sucralfate binds with digoxin and ↓ its absorption
Watch for poor response to digoxin
DIURETICS
CARBONIC ANHYDRASE INHIBITORS – ACETAZOLAMIDE CARBONIC ANHYDRASE INHIBITORS
ANTIARRHYTHMICS
CARBONIC ANHYDRASE INHIBITORS
AMIODARONE, DISOPYRAMIDE, FLECAINIDE
Risk of ≠ myocardial depression Cardiac toxicity directly related to hypokalaemia
Monitor potassium levels closely
CARBONIC ANHYDRASE INHIBITORS
MEXILETINE Effect of mexiletine ↓ by hypokalaemia
Uncertain Normalize potassium levels before starting mexiletine
CARBONIC ANHYDRASE INHIBITORS
ANTIBIOTICS – METHENAMINE
↓ efficacy of methenamine Methenamine is only effective at a low pH; raising the urinary pH ↓ its effect
Avoid co-administration
CARBONIC ANHYDRASE INHIBITORS
ANTIDEMENTIA DRUGS – MEMANTINE
Possibly ≠ memantine levels ↓ renal excretion Watch for early features of memantine toxicity
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Mechanism Precautions
therapeutic effect
≠ renal elimination of lithium Monitor clinically and by measuring blood lithium levels to ensure adequate therapeutic efficacy
CARBONIC ANHYDRASE INHIBITORS
ANTIEPILEPTICS – BARBITURATES, PHENYTOIN
Risk of osteomalacia Barbiturates and phenytoin have a small risk of causing osteomalacia; this may be ≠ by acetazolamide-induced urinary excretion of calcium
Be aware
CARBONIC ANHYDRASE INHIBITORS
ANTIPLATELET AGENTS – ASPIRIN
≠ risk of salicylate toxicity with high-dose aspirin
Uncertain at present Use low-dose aspirin
CARBONIC ANHYDRASE INHIBITORS
BETA-BLOCKERS – SOTALOL
≠ risk of ventricular arrhythmias, particularly torsades de pointes, caused by sotalol
Hypokalaemia, a side-effect of these diuretics, predisposes to arrhythmias during sotalol therapy
Normalize potassium levels before starting sotalol in patients already taking these diuretics. When starting these diuretics in patients already taking sotalol, monitor potassium levels every 4-6 weeks until stable
CARBONIC ANHYDRASE INHIBITORS
BRONCHODILATORS – BETA-2 AGONISTS, THEOPHYLLINE
Risk of hypokalaemia Additive effects Monitor blood potassium levels prior to concomitant administration and during therapy. Administer potassium supplements to prevent hypokalaemia
CARBONIC ANHYDRASE INHIBITORS
CARDIAC GLYCOSIDES Risk of digoxin toxicity ≠ by acetazolamide due to hypokalaemia
Uncertain Monitor potassium levels closely. Watch for digoxin toxicity and check levels
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S109
CARDIOVASCULAR DRUGS DIURETICS Loop diuretics
LOOP DIURETICS 1. ANTICANCER AND IMMUNOMODULATING DRUGS – IL-2 2. ANTIHYPERTENSIVES AND HEART FAILURE DRUGS 3. BETA-BLOCKERS 4. CALCIUM CHANNEL BLOCKERS 5. MUSCLE RELAXANTS – baclofen and tizanidine 6. NITRATES 7. PERIPHERAL VASODILATORS – moxisylyte (thymoxamine) 8. POTASSIUM CHANNEL ACTIVATORS
≠ hypotensive effect. Risk of first-dose ↓ BP greater when ACE inhibitors or angiotensin II receptor antagonists are added to high-dose diuretics. Also, ≠ risk of first-dose ↓ BP with alfuzosin, prazosin and terazosin
Additive hypotensive effect; may be used therapeutically
Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.). Patients with congestive cardiac failure on diuretics should be started on a low dose of alpha-blocker
LOOP DIURETICS ALISKIREN ↓ plasma levels of furosemide Uncertain Watch for poor response to furosemide
LOOP DIURETICS ANAESTHETICS – GENERAL ≠ hypotensive effect Additive hypotensive effect Monitor BP closely, especially during induction of anaesthesia
LOOP DIURETICS ANTIARRHYTHMICS
LOOP DIURETICS AMIODARONE, DISOPYRAMIDE, FLECAINIDE
Risk of arrhythmias Cardiac toxicity directly related to hypokalaemia
Monitor potassium levels every 4-6 weeks until stable, then at least annually
LOOP DIURETICS MEXILETINE Effect of mexiletine ↓ by hypokalaemia
Uncertain Normalize potassium levels before starting mexiletine
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Mechanism Precautions
deafness as a result of concomitant use of furosemide and gentamicin
Both furosemide and gentamicin are associated with ototoxicity; this risk is ≠ if they are used together
If used concurrently patients should be monitored for any hearing impairment
LOOP DIURETICS COLISTIN ≠ risk of ototoxicity and possible deafness as a result of concomitant use of furosemide and colistin
Additive effect If used concurrently, patients should be monitored for any hearing impairment
LOOP DIURETICS TETRACYCLINES Possible risk of renal toxicity Additive effect Some recommend avoiding co-administration; others advise monitoring renal function closely. Doxycycline is likely to be less of a problem
LOOP DIURETICS VANCOMYCIN Risk of renal toxicity Additive effect Monitor renal function closely
LOOP DIURETICS ANTICANCER AND IMMUNOMODULATING DRUGS
LOOP DIURETICS CISPLATIN ≠ risk of auditory toxic effects with cisplatin
Loop diuretics cause tinnitus and deafness as side-effects. Additive toxic effects on auditory system likely
Monitor hearing – test auditory function regularly, particularly if patients report symptoms such as tinnitus or impaired hearing
LOOP DIURETICS PORFIMER ≠ risk of photosensitivity reactions when porfimer is co-administered with bumetanide or furosemide
Attributed to additive effects Avoid exposure of skin and eyes to direct sunlight for 30 days after porfimer therapy
LOOP DIURETICS CICLOSPORIN Risk of nephrotoxicity Additive effect Monitor renal function weekly
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S111
CARDIOVASCULAR DRUGS DIURETICS Loop diuretics
↓ renal excretion of lithium Monitor clinically and by measuring blood lithium levels for lithium toxicity. Loop diuretics are safer than thiazides
LOOP DIURETICS ANTIEPILEPTICS – PHENYTOIN
↓ efficacy of furosemide Uncertain Be aware; watch for poor response to furosemide
LOOP DIURETICS ANTIFUNGALS – AMPHOTERICIN
Risk of hypokalaemia Additive effect Monitor potassium closely
LOOP DIURETICS ANTIPARKINSON’S DRUGS – LEVODOPA
≠ hypotensive effect Additive effect Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)
LOOP DIURETICS ANTIPSYCHOTICS – ATYPICALS, PHENOTHIAZINES, PIMOZIDE
Risk of arrhythmias Cardiac toxicity directly related to hypokalaemia
Monitor potassium levels every 4-6 weeks until stable, then at least annually
LOOP DIURETICS BETA-BLOCKERS – SOTALOL
≠ risk of ventricular arrhythmias, particularly torsades de pointes
Hypokalaemia, a side-effect of these diuretics, predisposes to arrhythmias during sotalol therapy
Normalize potassium levels before starting sotalol in patients already taking these diuretics. When starting these diuretics in patients already taking sotalol, monitor potassium levels every 4-6 weeks until stable
LOOP DIURETICS BRONCHODILATORS – BETA-2 AGONISTS, THEOPHYLLINE
Risk of hypokalaemia Additive effects Monitor blood potassium levels prior to concomitant administration and during therapy. Administer potassium supplements to prevent hypokalaemia
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Mechanism Precautions
Uncertain Monitor potassium levels closely.
