ABSTRACT
Advise patients to use additional contraception for the period of antibiotic intake and for 1 month after stopping the antibiotic
TETRACYCLINE SODIUM BICARBONATE ↓ tetracycline levels and possible therapeutic failure
It is suggested that when sodium bicarbonate alkalinizes the urine, the renal excretion of tetracycline is ≠
The interaction can be minimized by separating their dosing by 3-4 hours
TETRACYCLINES STRONTIUM RANELATE ↓ levels of these antibiotics ↓ absorption Avoid co-administration TETRACYCLINES SUCRALFATE ↓ levels of these antibiotics ↓ absorption of these antibiotics Give the antibiotics at least 2 hours
before sucralfate
TETRACYCLINES TRIPOTASSIUM DICITRATOBISMUTHATE
↓ levels of tetracyclines ↓ absorption of tetracyclines Separate doses by 2-3 hours
TETRACYCLINES ZINC ↓ antibiotic levels; less of a problem with doxycycline
↓ absorption Separate doses by at least 2 hours; alternatively, consider giving doxycycline
OTHER ANTIBIOTICS
CHLORAMPHENICOL
CHLORAMPHENICOL ANTICANCER AND IMMUNOMODULATING DRUGS – TACROLIMUS
Toxic blood levels of tacrolimus, usually on the second day of starting chloramphenicol
Attributed to impaired clearance of tacrolimus by chloramphenicol
↓ dose of nearly 80% of tacrolimus may be required to prevent toxicity. Watch for adverse effects (see below). Monitor tacrolimus plasma concentrations
CHLORAMPHENICOL ANTICOAGULANTS – ORAL Occasional episodes of ≠ anticoagulant effect
Uncertain at present Monitor INR every 2-3 days
CHLORAMPHENICOL ANTIDIABETIC DRUGS – SULPHONYLUREAS
Possibly ↓ hypoglycaemic effect of sulphonylureas
Mechanism uncertain. Chloramphenicol is an inhibitor of CYP3A4
Be aware
D R
U G
STO TR
EA TIN
FEC TIO
N S
O TH
ER A
N TIB
IO TIC
S
Mechanism Precautions
therapeutic failure
Induction of hepatic metabolism 1. Avoid co-administration of telithromycin for up to 2 weeks after stopping phenobarbital 2. With the other drugs, monitor for ↓ clinical efficacy, and ≠ their dose as required
CHLORAMPHENICOL PHENYTOIN ≠ phenytoin levels Inhibited metabolism Monitor phenytoin levels
CHLORAMPHENICOL ANTIPSYCHOTICS – CLOZAPINE
≠ risk of bone marrow toxicity Additive effect Avoid co-administration
CHLORAMPHENICOL ANTIVIRALS – STAVUDINE, ZIDOVUDINE
Possible ≠ adverse effects when coadministered with stavudine or zidovudine
Uncertain Use an alternative antibiotic if possible; otherwise monitor closely for peripheral neuropathy and check FBC regularly
CHLORAMPHENICOL CNS STIMULANTS – MODAFINIL
May cause moderate ≠ plasma concentrations of these substrates
Modafinil is a reversible inhibitor of CYP2C19 when used in therapeutic doses
Be aware
CHLORAMPHENICOL H2 RECEPTOR BLOCKERS – CIMETIDINE
≠ adverse effects of chloramphenicol, e.g. bone marrow depression
Additive toxicity Use with caution, monitor FBC regularly
CHLORAMPHENICOL IRON ↓ efficacy of iron Chloramphenicol depresses the bone marrow; this opposes the action of iron
Be aware; monitor FBC and ferritin levels closely
CHLORAMPHENICOL OESTROGENS Reports of ↓ contraceptive effect Possibly alteration of the bacterial flora necessary for recycling ethinylestradiol from the large bowel, although not certain in every case
Advise patients to use additional contraception for the period of antibiotic intake and for 1 month after stopping the antibiotic
CHLORAMPHENICOL VITAMIN B12 ↓ efficacy of hydroxycobalamin Chloramphenicol depresses the bone marrow; this opposes the action of vitamin B12
Be aware; monitor FBC and vitamin B12 levels closely
DRUGS TO TREAT INFECTIONS OTHER ANTIBIOTICS Colistin
DEPOLARIZING
Clindamycin has some neuromuscular blocking activity
Monitor neuromuscular blockade carefully
CLINDAMYCIN OESTROGENS Reports of ↓ contraceptive effect
Possibly alteration of the bacterial flora necessary for recycling ethinylestradiol from the large bowel, although not certain in every case
Advise patients to use additional contraception for the period of antibiotic intake and for 1 month after stopping the antibiotic
CLINDAMYCIN PARASYMPATHOMIMETICS – NEOSTIGMINE, PYRIDOSTIGMINE
↓ efficacy of neostigmine and pyridostigmine
Uncertain Watch for poor response to these parasympathomimetics and ≠ dose accordingly
COLISTIN
COLISTIN ANTIBIOTICS
COLISTIN AMINOGLYCOSIDES ≠ risk of nephrotoxicity Additive effect Renal function should be carefully monitored
COLISTIN TEICOPLANIN, VANCOMYCIN
≠ risk of nephrotoxicity and ototoxicity
Additive effect Hearing and renal function should be carefully monitored
COLISTIN ANTICANCER AND IMMUNOMODULATING DRUGS
COLISTIN CICLOSPORIN ≠ risk of nephrotoxicity Additive nephrotoxic effects Monitor renal function COLISTIN PLATINUM COMPOUNDS ≠ risk of additive renal and
ototoxicity. The ototoxicity tends to occur when cisplatin is administered early during the course of aminoglycoside therapy
Additive toxic effects Monitor renal function and hearing prior to and during therapy, and ensure the intake of at least 2 L of fluid daily. Monitor serum potassium and magnesium and correct any deficiencies. Most side-effects of aminoglycosides are dose related, and it is necessary to ≠ interval between doses and ↓ dose of aminoglycoside if there is impaired renal function
D R
U G
STO TR
EA TIN
FEC TIO
N S
O TH
ER A
N TIB
IO TIC
S
D R
U G
STO TR
EA TIN
FEC TIO
N S
O TH
ER A
N TIB
IO TIC
S
Mechanism Precautions
Additive effect Monitor renal function closely
COLISTIN DIURETICS – LOOP ≠ 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
COLISTIN MUSCLE RELAXANTS – DEPOLARIZING, NONDEPOLARIZING
≠ efficacy of these muscle relaxants
Colistin has some neuromuscular blocking activity
Monitor neuromuscular blockade carefully
COLISTIN PARASYMPATHOMIMETICS – NEOSTIGMINE, PYRIDOSTIGMINE
↓ efficacy of neostigmine and pyridostigmine
Uncertain Watch for poor response to these parasympathomimetics and ≠ dose accordingly
CYCLOSERINE
CYCLOSERINE ALCOHOL Risk of fits Additive effect; cycloserine can cause fits
Warn patients to drink alcohol minimally while taking cycloserine
CYCLOSERINE ISONIAZID Risk of drowsiness and dizziness Uncertain Be aware; watch for ≠ sedation DAPSONE
DAPSONE ANTIBIOTICS
DAPSONE RIFAMYCINS ↓ levels of dapsone Rifamycins induce metabolism of dapsone
Watch for poor response to dapsone
DAPSONE TRIMETHOPRIM ≠ levels of both drugs Mutual inhibition of metabolism Be aware – watch for ≠ incidence of side-effects
DAPSONE ANTICANCER DRUGS – PORFIMER
≠ risk of photosensitivity reactions Attributed to additive effects Avoid exposure of skin and eyes to direct sunlight for 30 days after porfimer therapy
DAPSONE ANTIGOUT DRUGS – PROBENECID
≠ dapsone levels, with risk of bone marrow suppression
Uncertain Monitor FBC closely
D R
U G
STO TR
EA TIN
FEC TIO
N S
O TH
ER A
N TIB
IO TIC
S553
DRUGS TO TREAT INFECTIONS OTHER ANTIBIOTICS Isoniazid
Uncertain; possible ≠ bioavailability of zidovudine
Use with caution; monitor for peripheral neuropathy
DAPTOMYCIN ANTICANCER DRUGS – CICLOSPORIN
Risk of myopathy Additive effect Avoid co-administration
DAPTOMYCIN LIPID-LOWERING DRUGS – FIBRATES, STATINS
Risk of myopathy Additive effect Avoid co-administration
ETHAMBUTOL
ETHAMBUTOL ANTIVIRALS – DIDANOSINE Possibly ≠ adverse effects (e.g. peripheral neuropathy) with didanosine
Additive side-effects Monitor closely for development of peripheral neuropathy but no dose adjustment is required
FUSIDIC ACID
FUSIDIC ACID ANTIVIRALS – PROTEASE INHIBITORS
Possibly ≠ adverse effects Inhibition of CYP3A4-mediated metabolism of fusidic acid
Avoid co-administration
FUSIDIC ACID LIPID-LOWERING DRUGS – STATINS
Cases of rhabdomyolysis reported when fusidic acid was coadministered with atorvastatin or simvastatin
Uncertain at present Monitor LFTs and CK closely; warn patients to report any features of rhabdomyolysis
ISONIAZID
ISONIAZID ANALGESICS – PARACETAMOL
Risk of paracetamol toxicity at regular therapeutic doses when co-administered with isoniazid
Uncertain; it seems that the formation of toxic metabolites is ≠ in fast acetylators when isoniazid levels ↓ (i.e. at the end of a dosing period)
There have been cases of hepatic pathology; regular paracetamol should be avoided in those taking isoniazid
ISONIAZID ANTACIDS ↓ levels of these antibiotics ↓ absorption Separate isoniazid and antacids by 2-3 hours
ISONIAZID ANTIBIOTICS – CYCLOSERINE
Risk of drowsiness and dizziness Uncertain Be aware; watch for ≠ sedation
D R
U G
STO TR
EA TIN
FEC TIO
N S
O TH
ER A
N TIB
IO TIC
S
Mechanism Precautions Isoniazid causes hyperglycaemia,
the mechanism being uncertain at present
Monitor capillary blood glucose levels closely; ≠ doses of antidiabetic drugs may be needed
ISONIAZID ANTIEPILEPTICS
ISONIAZID CARBAMAZEPINE ≠ carbamazepine levels Inhibited metabolism Monitor carbamazepine levels ISONIAZID ETHOSUXIMIDE Case of ≠ ethosuximide levels with
toxicity Inhibition of metabolism Watch for early features of
ethosuximide toxicity
ISONIAZID PHENYTOIN ≠ phenytoin levels Inhibited metabolism Monitor phenytoin levels
ISONIAZID ANTIFUNGALS – ITRACONAZOLE, KETOCONAZOLE, POSACONAZOLE, VORICONAZOLE
↓ levels of these azoles, with significant risk of therapeutic failure
Isoniazid is a known inhibitor of CYP2E1 and is likely to induce other CYP isoenzymes to varying degrees, usually in a timedependent manner
Avoid co-administration of ketoconazole or voriconazole with isoniazid. Watch for inadequate therapeutic effects of itraconazole. Higher doses of itraconazole may not overcome this interaction, so consider the use of less lipophilic fluconazole, which is less dependent on CYP metabolism
ISONIAZID ANTIVIRALS – NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
≠ adverse effects with didanosine and possibly stavudine
Additive side-effects Monitor closely for the development of peripheral neuropathy, but no dose adjustment is required
ISONIAZID ANXIOLYTICS AND HYPNOTICS – DIAZEPAM
≠ diazepam levels Inhibited metabolism Watch for excessive sedation; consider ↓ dose of diazepam
ISONIAZID BRONCHODILATORS – THEOPHYLLINE
≠ theophylline levels Uncertain Monitor theophylline levels before, during and after co-administration
LINEZOLID ➣ Drugs Acting on the Nervous System, Antidepressants, Monoamine oxidase inhibitors
D R
U G
STO TR
EA TIN
FEC TIO
N S
O TH
ER A
N TIB
IO TIC
S555
DRUGS TO TREAT INFECTIONS OTHER ANTIBIOTICS Metronidazole
SULFADIAZINE
Methenamine is only effective at a low pH, and this is achieved by acidifiers in the formulation. Sulfadiazine crystallizes in an acid environment
Avoid co-administration
METHENAMINE DIURETICS – CARBONIC ANHYDRASE INHIBITORS
↓ efficacy of methenamine Methenamine is only effective at a low pH; raising the urinary pH ↓ its effect
Avoid co-administration
METHENAMINE POTASSIUM CITRATE ↓ efficacy of methenamine Methenamine is only effective at a low pH; raising the urinary pH ↓ its effect
Avoid co-administration
METHENAMINE SODIUM BICARBONATE ↓ efficacy of methenamine Methenamine is only effective at a low pH; raising the urinary pH ↓ its effect
Avoid co-administration
METRONIDAZOLE
METRONIDAZOLE ALCOHOL Disulfiram-like reaction Metronidazole inhibits aldehyde dehydrogenase
Avoid co-ingestion
METRONIDAZOLE ANTICANCER AND IMMUNOMODULATING DRUGS
METRONIDAZOLE BUSULFAN ≠ busulfan levels Uncertain Watch for early features of toxicity METRONIDAZOLE FLUOROURACIL ≠ risk of toxic effects of
fluorouracil (27%), e.g. bone marrow suppression, oral ulceration, nausea and vomiting due to ≠ plasma concentrations of fluorouracil
Metronidazole ↓ clearance of fluorouracil
Avoid co-administration
D R
U G
STO TR
EA TIN
FEC TIO
N S
O TH
ER A
N TIB
IO TIC
S
Mechanism Precautions
Theoretically, drugs that alter gastrointestinal flora may ↓ oral bioavailability of mycophenolic acid products by ↓ bacterial hydrolytic enzymes that are responsible for regenerating mycophenolic acid from its glucuronide metabolites following first-pass metabolism
Avoid co-administration
METRONIDAZOLE ANTICOAGULANTS – ORAL ≠ anticoagulant effect Inhibition of CYP2C9-mediated metabolism of oral anticoagulants
Monitor INR every 2-3 days
METRONIDAZOLE ANTIDEPRESSANTS – LITHIUM
≠ plasma concentrations of lithium, with risk of toxicity
Uncertain Monitor clinically and by measuring blood lithium levels for lithium toxicity
METRONIDAZOLE ANTIEPILEPTICS
METRONIDAZOLE BARBITURATES ↓ levels of these drugs, with risk of therapeutic failure
Induction of hepatic metabolism. Unlikely with topical metronidazole
1. Avoid co-administration of telithromycin for up to 2 weeks after stopping phenobarbital
METRONIDAZOLE PHENYTOIN ≠ phenytoin levels Inhibited metabolism Monitor phenytoin levels METRONIDAZOLE ANTIVIRALS
METRONIDAZOLE DIDANOSINE, STAVUDINE ≠ adverse effects (e.g. peripheral neuropathy) with didanosine and possibly stavudine
Additive effect Monitor closely for peripheral neuropathy during intensive or prolonged combination
D R
U G
STO TR
EA TIN
FEC TIO
N S
O TH
ER A
N TIB
IO TIC
S557
DRUGS TO TREAT INFECTIONS OTHER ANTIBIOTICS Pyrazinamide
Ritonavir and lopinavir oral solutions contain alcohol
Warn patient and give alternative preparation if possible
METRONIDAZOLE DRUG DEPENDENCE THERAPIES – DISULFIRAM
Report of psychosis Additive effect; both drugs may cause neurological/psychiatric side-effects (disulfiram by inhibiting metabolism of dopamine, metronidazole by an unknown mechanism)
Caution with co-administration. Warn patients and carers to watch for early features
METRONIDAZOLE H2 RECEPTOR BLOCKERS – CIMETIDINE
≠ metronidazole levels Inhibited metabolism Watch for ≠ side-effects of metronidazole
METRONIDAZOLE OESTROGENS Reports of ↓ contraceptive effect Possibly alteration of the bacterial flora necessary for recycling ethinylestradiol from the large bowel, although not certain in every case
Advise patients to use additional contraception for the period of antibiotic intake and for 1 month after stopping the antibiotic
NITROFURANTOIN
NITROFURANTOIN ANTACIDS ↓ levels of these antibiotics ↓ absorption Separate nitrofurantoin and antacids by 2-3 hours
NITROFURANTOIN ANTIGOUT DRUGS – PROBENECID, SULFINPYRAZONE
↓ efficacy of nitrofurantoin in urinary tract infections
↓ urinary excretion Watch for poor response to nitrofurantoin
PYRAZINAMIDE
PYRAZINAMIDE ANTIGOUT DRUGS ↓ efficacy of antigout drugs Pyrazinamide can induce hyperuricaemia
Pyrazinamide should not be used in patients with gout
D R
U G
STO TR
EA TIN
FEC TIO
N S
O TH
ER A
N TIB
IO TIC
S
Mechanism Precautions
DALFOPRISTIN
QUINUPRISTIN/ DALFOPRISTIN
1. ANTIARRHYTHMICS – amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS – macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin) 3. ANTICANCER AND IMMUNOMODULATING DRUGS – arsenic trioxide 4. ANTIDEPRESSANTS – TCAs, venlafaxine 5. ANTIEMETICS – dolasetron 6. ANTIFUNGALS – fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES – terfenadine, hydroxyzine, mizolastine 8. ANTIMALARIALS – artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS – pentamidine isetionate 10. ANTIPSYCHOTICS – atypicals, phenothiazines, pimozide 11. BETA-BLOCKERS – sotalol 12. BRONCHODILATORS – parenteral bronchodilators 13. CNS STIMULANTS – atomoxetine
Risk of ventricular arrhythmias, particularly torsades de pointes
Additive effect; these drugs cause prolongation of the Q-T interval
Avoid co-administration
D R
U G
STO TR
EA TIN
FEC TIO
N S
O TH
ER A
N TIB
IO TIC
S559
DRUGS TO TREAT INFECTIONS OTHER ANTIBIOTICS Vancomycin
Additive effect when lidocaine given intravenously
Avoid co-administration of quinupristin/dalfopristin with intravenous lidocaine
QUINUPRISTIN/ DALFOPRISTIN
ANTIBIOTICS – RIFAMPICIN Risk of hepatic toxicity Additive effect Monitor LFTs closely
QUINUPRISTIN/ DALFOPRISTIN
ANTICANCER AND IMMUNOMODULATING DRUGS – CICLOSPORIN
≠ plasma concentrations of immunosuppressants. ≠ risk of infections and toxic effects of ciclosporin
Due to inhibition of CYP3A4mediated metabolism of ciclosporin
Monitor renal function prior to concurrent therapy, and blood count and ciclosporin levels during therapy. Warn patients to report symptoms (fever, sore throat) immediately
QUINUPRISTIN/ DALFOPRISTIN
ANTIMIGRAINE DRUGS – ERGOT DERIVATIVES
≠ ergotamine/methysergide levels, with risk of toxicity
Inhibition of CYP3A4-mediated metabolism of the ergot derivatives
Avoid co-administration
QUINUPRISTIN/ DALFOPRISTIN
ANXIOLYTICS AND HYPNOTICS – MIDAZOLAM
≠ midazolam levels Inhibited metabolism Watch for excessive sedation; consider ↓ dose of midazolam
QUINUPRISTIN/ DALFOPRISTIN
CALCIUM CHANNEL BLOCKERS Plasma levels of nifedipine may be ≠ by quinupristin/ dalfopristin
Quinupristin inhibits CYP3A4mediated metabolism of calcium channel blockers
Monitor BP closely; watch for ↓ BP
TEICOPLANIN
TEICOPLANIN ANTIBIOTICS – AMINOGLYCOSIDES, COLISTIN, VANCOMYCIN
≠ risk of nephrotoxicity and ototoxicity
Additive effect Hearing and renal function should be carefully monitored
VANCOMYCIN
VANCOMYCIN ANTIBIOTICS – AMINOGLYCOSIDES, COLISTIN, TEICOPLANIN
≠ risk of nephrotoxicity and ototoxicity
Additive effect Hearing and renal function should be carefully monitored
D R
U G
STO TR
EA TIN
FEC TIO
N S
O TH
ER A
N TIB
IO TIC
S
Mechanism Precautions
ototoxicity
Additive toxic effects Monitor renal function closely
VANCOMYCIN PLATINUM COMPOUNDS ≠ risk of renal toxicity and renal failure, and of ototoxicity
Additive renal toxicity Monitor renal function and hearing prior to and during therapy, and ensure the intake of at least 2 L of fluid daily. Monitor serum potassium and magnesium, and correct any deficiencies
VANCOMYCIN TACROLIMUS Risk of renal toxicity Additive effect Monitor renal function closely
VANCOMYCIN ANTIFUNGALS – AMPHOTERICIN
Risk of renal failure Additive effect Monitor renal function closely
VANCOMYCIN ANTIVIRALS
VANCOMYCIN ADEFOVIR DIPIVOXIL Possible ≠ efficacy and side-effects Competition for renal excretion Monitor renal function weekly VANCOMYCIN NUCLEOSIDE REVERSE
TRANSCRIPTASE INHIBITORS – TENOFOVIR, ZIDOVUDINE
≠ adverse effects with zidovudine and possibly tenofovir
Additive toxicity Monitor FBC and renal function closely (at least weekly)
VANCOMYCIN DIURETICS – LOOP Risk of renal toxicity Additive effect Monitor renal function closely
VANCOMYCIN (ORAL) LIPID-LOWERING DRUGS – ANION EXCHANGE RESINS
↓ vancomycin levels Inhibition of absorption Separate doses as much as possible
