chapter
Hormones and hormone antagonists
Pages 4

Monitor INR at least weekly until stable at initiation and discontinuation of concurrent therapy

ANASTRAZOLE ANTIDIABETIC DRUGS – REPAGLINIDE

Risk of hypoglycaemia Mechanism unknown Watch for hypoglycaemia. Warn patients about hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

BICALUTAMIDE

BICALUTAMIDE ANTICOAGULANTS – WARFARIN

≠ plasma concentrations of warfarin

Bicalutamide displaces warfarin from protein-binding sites

Monitor INR at least weekly until stable at initiation and discontinuation of concurrent therapy

FLUTAMIDE

FLUTAMIDE ANTICOAGULANTS – WARFARIN

≠ anticoagulant effect Uncertain; possibly inhibition of hepatic enzymes

Monitor INR at least weekly until stable at initiation and discontinuation of concurrent therapy

LANREOTIDE

LANREOTIDE ANTICANCER AND IMMUNOMODULATING DRUGS – CICLOSPORIN

↓ plasma concentrations of ciclosporin and risk of transplant rejection

Lanreotide possibly induces CYP3A4-mediated metabolism of ciclosporin

Avoid co-administration if possible; if not, monitor ciclosporin levels closely

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ANTICANCER AND IMMUNOMODULATING DRUGS HORMONES AND HORMONE ANTAGONISTS Octreotide

Octreotide and lanreotide suppress pancreatic insulin and counterregulatory hormones (glucagon, growth hormone), and delay or ↓ absorption of glucose from the intestine

Essential to monitor blood sugar at least twice a week after initiating concurrent treatment until blood sugar levels are stable. Advise selfmonitoring, and warn patients about hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

LETROZOLE

LETROZOLE TAMOXIFEN ↓ plasma concentrations of letrozole (by approximately 40%) and ↓ efficacy of letrozole

Attributed to induction of enzymes metabolizing letrozole by tamoxifen

Avoid concurrent use outside clinical trials

OCTREOTIDE

OCTREOTIDE ANTICANCER AND IMMUNOMODULATING DRUGS – CICLOSPORIN

↓ plasma concentrations of ciclosporin and risk of transplant rejection

Octreotide is a strong inducer of CYP3A4-mediated metabolism of ciclosporin

Avoid co-administration if possible; if not, monitor ciclosporin levels closely

OCTREOTIDE ANTIDIABETIC DRUGS Likely to alter hypoglycaemic agent requirements

Octreotide and lanreotide suppress pancreatic insulin and counterregulatory hormones (glucagon, growth hormone), and delay or ↓ absorption of glucose from the intestine

Essential to monitor blood sugar at least twice a week after initiating concurrent treatment until blood sugar levels are stable. Advice self monitoring. Warn patients re hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

OCTREOTIDE ANTIPARKINSON’S DRUGS – BROMOCRIPTINE

≠ bromocriptine levels Uncertain Be aware

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Mechanism Precautions

tamoxifen and risk of inadequate therapeutic response

Due to induction of metabolism of tamoxifen by the CYP3A isoenzymes by rifampicin

Avoid concurrent use if possible. Otherwise monitor for clinical efficacy of tamoxifen by ≠ dose of tamoxifen

TAMOXIFEN ANTICANCER AND IMMUNOMODULATING DRUGS

TAMOXIFEN CYTOTOXICS – MITOMYCIN

≠ incidence of anaemia and thrombocytopenia and risk of haemolytic-uraemic syndrome

Mitomycin causes subclinical endothelial damage in addition to the thrombotic effect on platelets caused by tamoxifen, which leads to the haemolytic-uraemic syndrome

Monitor renal function at least twice weekly during concurrent therapy and clinically watch for bleeding episodes, e.g. nose bleeds, bleeding from gums, skin bruising

TAMOXIFEN HORMONES AND HORMONE ANTAGONISTS – LETROZOLE

↓ plasma concentrations of letrozole (by approximately 40%) and ↓ efficacy of letrozole

Attributed to induction of enzymes metabolizing letrozole by tamoxifen

Avoid concurrent use outside clinical trials

TAMOXIFEN AZATHIOPRINE ≠ risk of myelosuppression and immunosuppression. Deaths have occurred following profound myelosuppression and severe sepsis

Additive myelotoxic effects Azathioprine is metabolized to 6-mercatopurine in vivo, which results in additive myelosuppression, immunosuppression and hepatotoxicity

Avoid co-administration

TAMOXIFEN CICLOSPORIN ≠ plasma concentrations of ciclosporin, with risk of toxic effects

Competitive inhibition of CYP3A4mediated metabolism and P-gp transport of these drugs

Watch for toxic effects of ciclosporin

TAMOXIFEN CORTICOSTEROIDS ↓ plasma concentrations of tamoxifen and risk of inadequate therapeutic response

Due to induction of metabolism of tamoxifen by the CYP3A isoenzymes by dexamethasone

Avoid concurrent use if possible. Otherwise monitor for clinical efficacy of tamoxifen by ≠ dose of tamoxifen

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ANTICANCER AND IMMUNOMODULATING DRUGS HORMONES AND HORMONE ANTAGONISTS Toremifene

Uncertain; possibly inhibition of hepatic enzymes. Tamoxifen inhibits CYP3A4

Monitor INR at least weekly until stable at initiation and discontinuation of concurrent therapy

TAMOXIFEN ANTIDEPRESSANTS – ST JOHN’S WORT

↓ plasma concentrations of tamoxifen and risk of inadequate therapeutic response

Due to induction of metabolism of tamoxifen by the CYP3A isoenzymes by St John’s wort

Avoid concurrent use

TAMOXIFEN ANTIEPILEPTICS – CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL

↓ plasma concentrations of tamoxifen and risk of inadequate therapeutic response

Due to induction of metabolism of tamoxifen by the CYP3A isoenzymes by phenytoin

Avoid concurrent use if possible. Otherwise monitor for clinical efficacy of tamoxifen by ≠ dose of tamoxifen

TAMOXIFEN CNS STIMULANTS – MODAFINIL

May cause≠ plasma concentrations of these substrates if CYP2C9 is the predominant metabolic pathway and the alternative pathways are either genetically deficient or affected

Modafinil is a moderate inhibitor of CYP2C9

Be aware

TOREMIFENE

TOREMIFENE ANTIBIOTICS – MACROLIDES

≠ plasma concentrations of toremifene with clarithromycin and erythromycin

Due to inhibition of metabolism of toremifene by the CYP3A4 isoenzymes by clarithromycin

Clinical relevance is uncertain. Necessary to monitor for clinical toxicities

TOREMIFENE ANTICOAGULANTS – WARFARIN

≠ anticoagulant effect Uncertain; possibly inhibition of hepatic enzymes

Monitor INR at least weekly until stable at initiation and discontinuation of concurrent therapy

TOREMIFENE ANTIEPILEPTICS – BARBITURATES, CARBAMAZEPINE, PHENYTOIN

↓ plasma concentrations of toremifene

Due to induction of metabolism of toremifene

Watch for poor response to toremifene