ABSTRACT
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
A N
TIC A
N C
ER A
N D
IM M
U N
O M
O D
U LA
TIN G
D R
U G
S347
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
A N
TIC A
N C
ER A
N D
IM M
U N
O M
O D
U LA
TIN G
D R
U G
S
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
A N
TIC A
N C
ER A
N D
IM M
U N
O M
O D
U LA
TIN G
D R
U G
S349
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
