chapter
Antibiotics – sulphonamides
Pages 5

Advise patients to use additional contraception for the period of intake and for 1 month after stopping co-administration of these drugs (4-8 weeks after stopping rifabutin or rifampicin)

RIFAMPICIN, RIFABUTIN PROGESTOGENS ↓ progesterone levels, which may lead to a failure of contraception or poor response to treatment of menorrhagia

Possibly induction of metabolism of progestogens

Advise patients to use additional contraception for the period of intake and 1 month after stopping co-administration of these drugs

RIFAMPICIN TADALAFIL ↓ tadalafil levels Probable induction of metabolism Watch for poor response RIFAMPICIN THYROID HORMONES ↓ levothyroxine levels Induction of metabolism Monitor TFTs regularly and consider

≠ dose of levothyroxine RIFAMPICIN TIBOLONE ↓ tibolone levels Induction of metabolism of

tibolone Watch for poor response to tibolone; consider ≠ dose

ANTIBIOTICS – SULPHONAMIDES

SULPHONAMIDES ANAESTHETICS – GENERAL ≠ effect of thiopentone but duration of action shortened

Uncertain; possibly displacement from protein-binding sites

Be aware that a smaller dose may be needed

SULPHONAMIDES ANAESTHETICS – LOCAL

SULFADIAZINE LIDOCAINE SOLUTIONS Precipitation of drugs, which may not be immediately apparent

A pharmaceutical interaction Do not mix in the same infusion or syringe

SULPHONAMIDES PRILOCAINE Risk of methaemoglobinaemia; there is a case report of methaemoglobinaemia with topical prilocaine in a patient taking sulphonamides

Additive effect Avoid co-administration

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Mechanism Precautions

Uncertain Avoid co-administration

ANTIBIOTICS – TRIMETHOPRIM

PROCAINAMIDE Procainamide levels are ≠ by trimethoprim

Trimethoprim is a potent inhibitor of organic cation transport in the kidney, and the elimination of procainamide is impaired

Watch for signs of procainamide toxicity; ↓ dose of procainamide, particularly in elderly patients

SULPHONAMIDES ANTIBIOTICS

TRIMETHOPRIM DAPSONE ≠ levels of both drugs Mutual inhibition of metabolism Be aware – watch for ≠ incidence of side-effects

SULPHONAMIDES METHENAMINE Risk of crystalluria 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

SULPHONAMIDES ANTICANCER AND IMMUNOMODULATING DRUGS

CO-TRIMOXAZOLE MERCAPTOPURINE ≠ risk of bone marrow toxicity Additive effect Avoid co-administration SULFAMETHOXAZOLE/ TRIMETHOPRIM

METHOTREXATE ≠ plasma concentrations of methotrexate and risk of toxic effects of methotrexate, e.g. myelosuppression, liver cirrhosis, pulmonary toxicity

Sulfamethoxazole displaces methotrexate from plasma protein-binding sites and also ↓ renal elimination of methotrexate. Trimethoprim inhibits dihydrofolate reductase, which leads to additive toxic effects of methotrexate

Avoid concurrent use. If concurrent use is necessary, monitor clinically and biochemically for blood dyscrasias, liver toxicity, renal toxicity and pulmonary toxicity

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DRUGS TO TREAT INFECTIONS ANTIBIOTICS – SULPHONAMIDES

be fatal, pulmonary toxicity, stomatitis. Haematopoietic suppression can occur abruptly. Other adverse effects include anorexia, dyspepsia, gastrointestinal ulceration and bleeding, pulmonary oedema

The mechanism differs from that caused by sulfamethoxazoletrimethoprim. Sulphonamides such as co-trimoxazole and sulfadiazine are known to cause renal dysfunction – interstitial nephritis, renal failure, which may ↓ excretion of methotrexate. Sulphonamides are also known to compete with methotrexate for renal elimination. Displacement from proteinbinding sites of methotrexate is a minor contribution to the interaction

Although the toxic effects of methotrexate are more frequent with high doses of methotrexate, it is necessary to do FBC, liver and renal function tests before starting treatment even with low doses, repeating these tests weekly until therapy is stabilized and thereafter every 2-3 months. Patients should be advised to report symptoms such as sore throat and fever immediately, and also any gastrointestinal discomfort. A profound drop in white cell or platelet counts warrants immediate stoppage of methotrexate therapy and initiation of supportive therapy

SULPHONAMIDES PORFIMER ≠ risk of photosensitivity reactions Attributed to additive effects Avoid exposure of skin and eyes to direct sunlight for 30 days after porfimer therapy

SULPHONAMIDES ANTICANCER AND IMMUNOMODULATING DRUGS

ANTIBIOTICS – CO-TRIMOXAZOLE

AZATHIOPRINE ≠ risk of leukopenia Additive effects, as co-trimoxazole inhibits white cell production

CO-TRIMOXAZOLE CICLOSPORIN Exacerbates hyperkalaemia induced by ciclosporin

Additive effect Monitor serum potassium levels during co-administration ➣ For signs and symptoms of hyperkalaemia, see Clinical Features of Some Adverse Drug Interactions, Hyperkalaemia

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Additive effect Monitor blood count closely ➣ For signs

CO-TRIMOXAZOLE SIROLIMUS Exacerbates neutropenia caused by sirolimus

CO-TRIMOXAZOLE TACROLIMUS Exacerbates hyperkalaemia induced by tacrolimus

SULPHONAMIDES, TRIMETHOPRIM

ANTICOAGULANTS – ORAL ≠ anticoagulant effect Inhibition of CYP2C9-mediated metabolism of oral anticoagulants

Monitor INR every 2-3 days

SULPHONAMIDES ANTIDIABETIC DRUGS

TRIMETHOPRIM PIOGLITAZONE, ROSIGLITAZONE

≠ in blood levels of rosiglitazone by nearly 40%

Trimethoprim is a relatively selective inhibitor of CYP2C8

Watch for hypoglycaemic events and ↓ dose of rosiglitazone after repeated blood sugar measurements. Warn patients about hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

TRIMETHOPRIM REPAGLINIDE ≠ repaglinide levels (by approximately 40%); risk of hypoglycaemia

Hepatic metabolism inhibited Manufacturers do not recommend concurrent use

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DRUGS TO TREAT INFECTIONS ANTIBIOTICS – SULPHONAMIDES

Inhibited metabolism Monitor phenytoin levels

HEART FAILURE DRUGS – ACE INHIBITORS

trimethoprim is co-administered with ACE inhibitors in the presence of renal failure

Uncertain at present Avoid concurrent use in the presence of severe renal failure

ANTIBIOTICS – SULPHONAMIDES, TRIMETHOPRIM

ANTIMALARIALS – PYRIMETHAMINE

≠ antifolate effect Additive effect Monitor FBC closely; the effect may take a number of weeks to occur

SULPHONAMIDES ANTIPSYCHOTICS – CLOZAPINE

≠ risk of bone marrow toxicity Additive effect Avoid co-administration

SULPHONAMIDES ANTIVIRALS

TRIMETHOPRIM GANCICLOVIR/ VALGANCICLOVIR

Possibly ≠ adverse effects (e.g. myelosuppression) when trimethoprim is co-administered with ganciclovir or valganciclovir

Small ≠ in bioavailability; possible additive toxicity

Well tolerated in a study. For patients at risk of additive toxicities, use only if benefits outweigh risks, and monitor FBC closely

CO-TRIMOXAZOLE NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

≠ adverse effects Additive toxicity ↓ doses as necessary; monitor FBC and renal function closely. Doses of co-trimoxazole used for prophylaxis seem to be tolerated

TRIMETHOPRIM NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Possibly ≠ haematological toxicity Competition for renal excretion Monitor FBC and renal function closely

TRIMETHOPRIM, CO-TRIMOXAZOLE

CARDIAC GLYCOSIDES – DIGOXIN

Trimethoprim may ≠ plasma concentrations of digoxin, particularly in elderly people

Uncertain; postulated that trimethoprim ↓ renal clearance of digoxin

Monitor digoxin levels; watch for digoxin toxicity

TRIMETHOPRIM DIURETICS – POTASSIUMSPARING

Risk of hyperkalaemia when trimethoprim is co-administered with eplerenone

Additive effect Monitor potassium levels closely