Download Drug Interactions - Dumfries and Galloway Prescribing Support Team

Drug Interactions
What is a drug interaction?
Stockley defines a drug interaction as having occurred when the “effects of one drug are
changed by the presence of another drug, herbal medicine, food, drink or by some
environmental chemical agent”1.
How do they occur?
Drug interactions are generally pharmacodynamic or pharmacokinetic reactions.
Pharmacodynamic interactions come about because the drugs have similar or antagonistic
effects. Where the effects of two drugs are similar we may see potentiation of effect e.g.
the enhanced hypotensive effect of giving an ACE inhibitor and doxazosin. Where the
effects of the drugs are antagonistic we may see a reduction in the effect of one or both
drugs when they are co-administered e.g. β-agonists and β-antagonists will compete for
receptor sites.
Pharmacokinetic interactions result from one agent affecting the absorption, distribution,
metabolism or excretion of another, either increasing or decreasing the drug(s)’ effect.2 For
example, taking alendronate with food reduces its absorption by 85% when compared with
taking it 2 hours before breakfast1.
How dangerous are drug interactions?
Drug interactions range from the inconsequential to fatal. Determining which will be clinically
significant can be difficult due to wide patient variability.1 Drug interactions leading to
hospitalisation in Dumfries and Galloway in recent times have included;
• Co-prescribing of an NSAID and lithium leading to acute renal impairment
• Co-prescribing of ciprofloxacin and warfarin leading to a significantly raised INR
Appendix 1 of the BNF gives information on drug interactions2. A black dot “•” indicates
potentially hazardous interactions where the combination should be avoided (or prescribed
with caution and appropriate monitoring).
In depth information on specific drug interactions can be found in Stockley1 – see your
Prescribing Support Pharmacist with specific queries.
Top 10 Dangerous Drug Interactions in Long Term Care
The American Society of Consultant Pharmacists and The American Medical Directors
Association compiled nominations from >500 geriatricians to determine which drug
interactions are the most important and how they should be managed.3 Medications were
chosen on their frequency of use in elderly patients and their potential for clinically
significant adverse effects.
Created by the NHS Dumfries and Galloway, Prescribing Support Team, January 2010, review
January 2012
Top 10 Dangerous Drug Interactions in Long Term Care3
Combination of Drugs
Warfarin + NSAIDs
Potential Effect
Serious GI bleed
Warfarin +
Sulphonamides (e.g.
Septrin®
/Cotrimoxazole)
Increased effect of
warfarin
Warfarin + Macrolides
Increased effect of
warfarin is “highly
probable and often
delated”
Increased effect of
warfarin
Warfarin + Quinolones
(especially ciprofloxacin,
ofloxacin, norfloxacin,
levofloxacin)
Warfarin + Phenytoin
ACE inhibitors +
Potassium supplements
Increased effect of
warfarin +/- effect of
phenytoin
Elevated potassium
levels
Preventative Action3
Assess need for NSAID. Try simple analgesics e.g. regular paracetamol.
If NSAID required; ibuprofen is associated with lowest GI risk of nonselective NSAID’s.2
Use NSAIDs at lowest effective dose for shortest possible time.2
Avoid concomitant use. Consider other antibiotics.2
If sulphonamide antibiotic is required, reduce the dose of warfarin by 50%
during antibiotic treatment and for one week after. Monitor INR every other
day for an elevating trend.
Ask the patient to be aware of and report signs of abnormal bleeding.
Avoid concomitant use. Consider alternative antibiotic.
If macrolide must be used, monitor INR every day and adjust warfarin. Ask
the patient to be aware of and report signs of abnormal bleeding.
Use alternative antibiotic where possible.
Monitor INR more frequently – in the case of ciprofloxacin and warfarin,
monitoring INR every other day has been recommended.
Ask the patient to be aware of and report signs of abnormal bleeding.
Monitor INR during co-administration. Baseline phenytoin (pre starting
warfarin) would be helpful. Monitor phenytoin levels during co-administration
Ask the patient to be aware of and report signs of abnormal bleeding.
Adjust/stop potassium supplement as necessary.
Use for short time only and avoid putting on repeat prescription.
Consider other drugs affecting potassium balance (e.g. could high dose
furosemide be reduced?). Check potassium before starting either drug.
K+>5mmol/l should be monitored carefully due to the risk of severe
Created by the NHS Dumfries and Galloway, Prescribing Support Team, January 2010, review January 2012
ACE inhibitors +
spironolactone
Digoxin + Amiodarone
Elevated potassium
levels
Digoxin toxicity
Digoxin + Verapamil
Digoxin toxicity,
bradycardia, heart
block
Theophylline +
Quinolones (especially
ciprofloxacin &
nofloxacin)
Theophylline toxicity
hyperkalemia & ECG changes.
Check potassium before starting combined treatment. K+>5mmol/l should be
monitored carefully due to the risk of severe hyperkalemia & ECG changes.
Confirm both drugs are required – use both only on cardiologist’s
recommendation. Obtain digoxin level before starting amiodarone, then
decrease digoxin dose by 50%. Monitor digoxin levels once weekly for several
weeks/until stable.
Ask patients to report symptoms such as nausea, vomiting, diarrhoea, dizziness
blurred vision, confusion.
NB. Amiodarone has a very long half-life; it can take 50 days (20 to >100 days)
for the concentration in the blood to halve.
Evaluate need for both drugs – use both only on cardiologist’s recommendation.
Monitor heart rate & ECG. Monitor digoxin levels. Ask patients to report
symptoms such as nausea, vomiting, diarrhoea, dizziness blurred vision,
confusion.
Obtain theophylline level before starting a quinolone. Theophylline toxicity may
occur even when level is within target. Ciprofloxacin reduces theophylline
clearance by 30-84%. Watch for symptoms suggesting toxicity including;
vomiting, agitation, sinus tachycardia, dilated pupils & hyperglycaemia.
Created by the NHS Dumfries and Galloway, Prescribing Support Team, January 2010, review January 2012
Dumfries and Galloway Clinical Handbook Guidance on
Important Drug Interactions
The following drug interactions were identified for the D&G Clinical Handbook.
They’ve been updated using the BNF and Stockley’s Drug Interactions. There is
some overlap with the top 10 dangerous drug interactions identified by the
American Society of Consultant Pharmacists and The American Medical
Directors Association.
DIGOXIN AND QUININE -Combination can lead to doubling of Digoxin
concentration
WARFARIN AND AMIODARONE - Amiodarone inhibits metabolism of
warfarin. Amiodarone has a long half life and drug interaction persists for
considerable time after stopping. It would take some time for side effects of
warfarin to be apparent therefore dose adjustment would be needed. For advice
see Warfarin Induction.
WARFARIN AND BROAD SPECTRUM ANTIBIOTICS - Antibiotics inhibit
metabolism of warfarin leading to increased INR. A particular problem with
ciprofloxacin, Septrin (co-trimoxazole), metronidazole, erythromycin.
AZATHIOPRINE AND ALLOPURINOL - Allopurinol inhibits metabolism of
azathioprine. Consider alternative prophylaxis for gout or reduce dose
azathioprine by 75%2
CICLOSPORIN AND MACROLIDES, AZOLE ANTIFUNGALS- These drugs
lead to ciclosporin toxicity1,2. Best to avoid altogether. Alternatively monitor
serum levels closely.
CICLOSPORIN AND STATINS – Ciclosporin can cause rises in the plasma
levels of atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin. In
some cases patients have developed renal failure and rhabdomyolysis1. Lower
doses of statins are recommended when they are used in conjunction with
ciclosporin (e.g. simvastatin 10mg and atorvastatin 10mg max.)2.
ORAL CONTRACEPTIVE PILL (OCP) AND ANTI-EPILEPTIC DRUGS,
ANTIBACTERIALS - The metabolism/elimination of the OCP is accelerated
giving reduced contraceptive effect. See BNF for specific contraceptive
advice2.
QUINOLONES AND ANTACIDS, IRON PREPARATIONS - These drugs
reduce the absorption of ciprofloxacin. If must be used together then give
ciprofloxacin at least 2hrs before or 6 hrs afterwards, but better to avoid
these combinations.
Created by the NHS Dumfries and Galloway, Prescribing Support Team, January
2010, review January 2012
ACE INHIBITORS AND NSAIDs - Risk of renal impairment as both block the
kidneys' attempts to maintain glomerular capillary pressure in face of falling
renal perfusion. Risk of hyperkalaemia as both have anti-aldosterone effects
THEOPHYLLINES AND CIPROFLOXACIN, CIMETIDINE, ERYTHROMYCIN,
CLARITHROMYCIN - These drugs can lead to theophylline toxicity. Look out
for palpitations, tachycardia, nausea and tremor.
SIMVASTATIN AND MACROLIDES - Increased risk of myopathy when
simvastatin given with clarithromycin or erythromycin (avoid concomitant use)1.
QUINOLONES AND ANTIEPILEPTICS, NSAIDs - Ciprofloxacin increases or
decreases plasma concentration of phenytoin. Possible increased risk of
convulsions when quinolones given with NSAID. Avoid concomitant use in patients
with history of seizures
TRAMADOL AND ANTIEPILEPTICS/CNS MEDICATION - Epileptiform
convulsions have occurred after administration of high doses of tramadol or
after concomitant treatment with drugs which can lower the seizure threshold
or themselves induce cerebral convulsions (eg anti-depressants or antipsychotics). Effects of tramadol reduced by carbamazepine.
See the BNF2 and Stockley’s Drug Interactions1 for more information
and advice.
References:
1.
Stockley’s Drug Interactions
http://www.medicinescomplete.com/mc/stockley/current/whatsnew.htm#ne
ws183 accesssed 13th November 2009.
2. RPS/BMA. BNF 57, BMJ Group/RPS Publishing London, March 2009
3. Joint collaboration of the American Society of Consultant Pharmacists and
the American Medical Directors Association. Multidisciplinary Medication
Management Project, Top 10 Dangerous Drug Interactions in Long Term
Care. www.scoup.net/m3project/topten/ accessed 13th November 2009.
4. D&G Clinical Handbook 2009 available at
http://nhsdandg.onconfluence.com/display/DumfriesHandbook/Enter+Handb
ook
Created by the NHS Dumfries and Galloway, Prescribing Support Team, January
2010, review January 2012