| Drug |
Interacting condition/drug |
Interaction/Issue |
Advice/action |
| Many commonly prescribed antibiotics and antifungals |
Warfarin |
Altered anticoagulant effect |
Monitor INR more closely and adjust dose as appropriate whilst on antibiotic used for active treatment of infection |
| -azoles e.g. fluconazole, itraconazole, ketoconazole and voriconazole |
Ivabradine |
Increased level of ivabradine – which can lead to increased risk of arrhythmia |
Contra-indicated
Can an alternative be prescribed? Discuss with a pharmacist/microbiologist. If need to continue –azole consider suspending ivabradine (seek pharmacy/cardiology advice) whilst on antifungal. |
| -azoles e.g. fluconazole, itraconazole, ketoconazole and voriconazole |
Ranolazine |
Increased risk of QT prolongation with fluconazole and voriconazole
Itraconazole, ketoconazole and voriconazole increase exposure to ranolazine |
Contra-indicated
Can an alternative be prescribed? Discuss with a pharmacist/microbiologist.
|
| -azoles e.g. fluconazole, itraconazole, ketoconazole and voriconazole |
Domperidone |
Increased risk of QT prolongation |
Contra-indicated
Can an alternative be prescribed? Discuss with pharmacist/microbiologist. |
| -azoles e.g. fluconazole, itraconazole, ketoconazole and voriconazole |
Statins |
Increases exposure to statin – can increase risk of rhabdomyolysis or hepatotoxicity |
Consider suspending statin during course of –azole treatment for all patients. If recent cardiac event discuss with senior clinician/pharmacist and counsel patient on side effects expected. |
| -azoles e.g. fluconazole, itraconazole, ketoconazole and voriconazole |
Direct oral anticoagulants (DOACs) |
Increased risk of bleeding |
Consider alternative to –azole or switch to LMWH. No interaction with fluconazole. |
| -azoles e.g. fluconazole, itraconazole, ketoconazole and voriconazole |
Variety of drugs (see specific advice for statins, DOACs and ivabrainde) |
-azoles can increase or reduce the exposure to the interacting drug. |
Check for any significant interactions using the conflict log on EPMA and/or BNF. Contact a pharmacist for advice. |
| Ketoconazole |
Edoxaban |
Increases plasma levels of edoxaban leading to increased risk of bleeding |
Edoxaban dose reduction may be required- check current version of product licensing for latest advice via: https://www.medicines.org.uk/emc/product/6905/smpc |
Ciprofloxacin
(Quinolone class) |
Epilepsy |
Reduces seizure threshold |
Avoid in patients with epilepsy or only use when the benefits outweigh risks and alternative agents have been considered with microbiologist and documented in the patient’s notes. Ensure patient aware of decision. |
Ciprofloxacin
(Quinolone class) |
Aminophylline & theophylline |
Level of theophylline can be increased and may cause toxicity |
Check baseline level prior to starting antibiotics if possible, but do not delay administration whilst waiting for result. Dose reduction may be required. Discuss with a pharmacist. |
| Ciprofloxacin & levofloxacin |
Myasthenia gravis |
Neuromuscular blocking activity therefore may exacerbate muscle weakness. Can also unmask subclinical myasthenia gravis. |
Fluoroquinolones should be avoided in patients with a history of myasthenia gravis.
Refer to antibiotics in myasthenia gravis for advice. |
| Ciprofloxacin & levofloxacin |
Multi-valent cations (antacids, supplements or feeds containing calcium, iron, magnesium, zinc, sucralfate or bismuth. |
These products bind to fluoroquinolones and reduce its absorption by up to 90%. |
If patients are prescribed antacids or supplements containing calcium, iron, magnesium, zinc or bismuth. It is advised these medications are stopped/withheld for the duration of antibiotic treatment. If this is not possible due to a clinical need, then an alternative antibiotic must be considered.
If ciprofloxacin/levofloxacin and a cation containing product must be prescribed together:
Administration times should be as far apart as possible
Reduce the dosing frequency of the interacting product if possible
In the case of oral nutritional supplements, multiple sips throughout the day should be replaced with set administration times to enable adequate spacing from oral antibiotic administration |
| Clarithromycin & erythromycin |
Aminophylline & theophylline |
Level of theophylline can be increased and may cause toxicity |
Check baseline level prior to starting antibiotics if possible, but do not delay administration whilst waiting for result. Dose reduction may be required. Discuss with a pharmacist. |
| Clarithromycin & erythromycin |
Domperidone |
Increased risk of arrhythmia (QT prolongation) |
Contra-indicated
Can an alternative be prescribed? Discuss with a pharmacist or microbiologist. |
| Clarithromycin & erythromycin |
Ivabradine |
Increased risk of arrhythmia including torsade de pointes |
Combination is contra-indicated. Can an alternative be prescribed? Discuss with a pharmacist or microbiologist. If need to continue consider suspending ivabradine (seek cardiology advice) whilst on antibiotics. |
| Clarithromycin & erythromycin |
Ranolazine |
Increased risk of arrhythmia (QT prolongation) and increased exposure of ranolazine |
Combination is contra-indicated. Can an alternative antibiotic be prescribed? Discuss with a pharmacist or microbiologist. |
| Clarithromycin & erythromycin |
Statins |
Increases exposure to statin – can increase risk of rhabdomyolysis or hepatotoxicity |
Suspend statin during course of antibiotic for all patients. If recent cardiac event discuss with senior clinician or pharmacist. |
| Clarithromycin & erythromycin |
Myasthenia gravis |
Exacerbation of symptoms of myasthenia gravis and trigger new onset of symptoms of myasthenic syndrome has been reported in patients. |
Macrolides should be avoided in patients with a history of myasthenia gravis.
Refer to antibiotics in myasthenia gravis for advice. |
| Clarithromycin & erythromycin |
Direct oral anticoagulants (DOACs) |
Increases the concentration of the DOAC resulting in an increased risk of bleeding |
Concomitant use should be reviewed and alternative agent
used if possible. If co-prescribing is essential then the patient should be
monitored for signs of bleeding. Patients who require long term macrolide
treatment may be eligible for DOAC monitoring, this should be discussed with
pharmacy. |
| Clarithromycin |
Ticagrelor |
Increased risk of bleeding |
Combination is contra-indicated. Can an alternative antibiotic be prescribed, e.g. erythromycin if a macrolide is needed? Discuss with a pharmacist/microbiologist. |
| Erythromycin |
Edoxaban |
Increases plasma levels of edoxaban leading to increased risk of bleeding |
Edoxaban dose reduction may be required- check current version of product licensing for latest advice via: https://www.medicines.org.uk/emc/product/6905/smpc |
| Co-trimoxazole (contains trimethoprim) |
Methotrexate |
Possible bone marrow suppression, which has been fatal in some cases |
NEVER prescribe trimethoprim or co-trimoxazole not even a short course or a low dose, to patients who are currently receiving methotrexate, who have recently stopped methotrexate or who have had methotrexate recently withheld. |
| Doxycycline |
Multi-valent cations (antacids, supplements or feeds containing calcium, iron, magnesium, zinc, sucralfate or bismuth. |
These products bind to doxycycline and reduce its absorption by up to 90%. |
If patients are prescribed antacids or supplements containing calcium, iron, magnesium, zinc or bismuth. It is advised these medications are stopped/withheld for the duration of antibiotic treatment. If this is not possible due to a clinical need, then an alternative antibiotic must be considered.
If doxycycline and a cation containing product must be prescribed together:
Reduce the dosing frequency of the interacting product if possible
Administration times should be as far apart as possible
In the case of oral nutritional supplements, multiple sips throughout the day should be replaced with set administration times to enable adequate spacing from oral antibiotic administration
If a patient is receiving an enteral feed doxycycline should generally be avoided unless there is a specific feed free window |
| Gentamicin |
Myasthenia gravis |
Inhibits acetylcholine release from presynaptic neuron; also has some postsynaptic curare-like action. Aggravates muscle weakness. Aminoglycosides have been associated with death when used in patients with a history of myasthenia gravis. |
Contra-indicated in myasthenia gravis. DO NOT USE
Refer to antibiotics in myasthenia gravis for advice. |
| Linezolid |
Methadone |
Increases the risk of serotonin syndrome when used in combination |
Can an alternative be prescribed? Discuss with pharmacist or microbiologist. If need to continue linezolid, monitor patient closely for signs of serotonin syndrome and stop treatment as appropriate. |
| Linezolid |
Olanzapine |
Increases risk of myelosuppression when used in combination |
Monitor FBC closely whilst on treatment and adjust dose as appropriate whilst on linezolid |
| Linezolid |
SSRIs and SNRIs |
Increases the risk of serotonin syndrome when used in combination |
Can an alternative be prescribed? Discuss with pharmacist/microbiologist. If need to continue linezolid, suspend SSRI whilst on linezolid |
| Linezolid |
Variety of drugs (see specific advice for SSRIs, methadone and olanzapine) |
Linezolid can increase the risk of serotonin syndrome, myelosuppression and elevate blood pressure in combination with interacting drugs |
Check for any significant interactions using the conflict log on EPMA and/or BNF. Contact a pharmacist for advice. |
| Meropenem |
Sodium valproate |
Meropenem reduces the plasma level of sodium valproate |
Meropenem can significantly reduce plasma levels within a few days by 60-100%. Only use when the benefits outweigh risks and alternative agents have been considered. Always discuss antibiotic choice with a microbiologist |
| Nitrofurantoin |
Renal function <45ml/min |
Renal secretion of nitrofurantoin is reduced, which may reduce the antibacterial efficacy and lead to treatment failure |
Use an alternative antibiotic. Check if any cultures and sensitivities available. If no allergies or sensitivities consider second line agent pivmecillinam. Discuss with microbiologist if unable to use pivmecillinam |
| Rifampicin |
Direct oral anticoagulants
(DOACs) |
Anticoagulant effect decreased |
Consider alternative to rifampicin or switch to LMWH |
| Rifampicin |
Methadone |
Reduced plasma levels and increased urinary excretion of methadone |
Monitor patient for signs of withdrawal, dose of methadone may need to be increased whilst on rifampicin |
| Rifampicin |
Combined hormonal contraceptives |
Reduced efficacy of combined hormonal contraceptives |
Inform patient to use additional methods of contraception throughout duration of treatment. |
| Rifampicin |
Warfarin |
Anticoagulant effect decreased |
Monitor INR closely and adjust dose as appropriate whilst on rifampicin |
| Rifampicin |
Variety of drugs (see specific advice for DOACs, methadone and warfarin) |
Rifampicin can reduce the exposure to the interacting drug |
Check for significant interactions using the conflict log on EPMA and/or BNF. Contact a pharmacist for advice |
| Trimethoprim |
Methotrexate |
Could lead to bone marrow suppression, which has been fatal in some cases. |
NEVER prescribe trimethoprim or co-trimoxazole, not even a short course or a low dose, to patients who are currently receiving methotrexate, who have recently stopped methotrexate or who have had methotrexate recently withheld. |