chapter
Other antibiotics
Pages 12

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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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