ABSTRACT
Watch for poor response to digoxin; check levels if signs of ↓ effect and consider swapping to liquid digoxin or liquid-containing capsules
ALL VACCINES – LIVE Risk of contracting disease from the vaccine
↓ immunity Avoid live vaccines for at least 6 months after completing chemotherapy
Effect Mechanism Precautions
ARSENIC TRIOXIDE 1. ANTIARRHYTHMICS – amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS – macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/dalfopristin 3. ANTIDEPRESSANTS – TCAs, venlafaxine 4. ANTIEMETICS – dolasetron 5. ANTIFUNGALS – fluconazole, posaconazole, voriconazole 6. ANTIHISTAMINES – terfenadine, hydroxyzine, mizolastine 7. ANTIMALARIALS – artemether with lumefantrine, chloroquine, hydroxychloroquine, mefloquine, quinine 8. ANTIPROTOZOALS – pentamidine isetionate 9. ANTIPSYCHOTICS – atypicals, phenothiazines, pimozide 10. BETA-BLOCKERS – sotalol 11. BRONCHODILATORS – parenteral bronchodilators 12. 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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ANTICANCER AND IMMUNOMODULATING DRUGS CYTOTOXICS Busulfan
≠ Possibly via inhibition of intestinal CYP3A4
Clinical significance unknown. Monitor more closely
BEXAROTENE LIPID-LOWERING DRUGS – GEMFIBROZIL
Gemfibrozil may ≠ bexarotene levels
Uncertain at present Avoid co-administration
BLEOMYCIN BLEOMYCIN ANTICANCER AND
IMMUNOMODULATING DRUGS – CISPLATIN
≠ bleomycin levels, with risk of pulmonary toxicity
Elimination of bleomycin is delayed by cisplatin due to ↓ glomerular filtration. This is most likely with accumulated doses of cisplatin in excess of 300 mg/m2
Monitor renal function and adjust dose of bleomycin as per creatinine clearance. Monitor clinically, radiologically and with lung function tests for pulmonary toxicity
BORTEZOMIB
BORTEZOMIB ANTIDIABETIC DRUGS – CHLORPROPAMIDE
Likely to ≠ hypoglycaemic effect of chlorpropamide
Unknown Watch for and warn patients about symptoms of hypoglycaemia ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia
BUSULFAN
BUSULFAN ANALGESICS – PARACETAMOL Busulfan levels may be ≠ by co-administration of paracetamol
Uncertain; paracetamol probably inhibits metabolism of busulfan
Manufacturers recommend that paracetamol should be avoided for 3 days before administering parenteral busulfan
BUSULFAN ANTIBIOTICS
BUSULFAN MACROLIDES – CLARITHROMYCIN, ERYTHROMYCIN, TELITHROMYCIN
≠ plasma concentrations of busulfan and ≠ risk of toxicity of busulfan such as veno-occlusive disease and pulmonary fibrosis
Busulfan clearance may be ↓ by 25%, and the AUC of busulfan may ≠ by 1500mol/L
Monitor clinically for veno-occlusive disease and pulmonary toxicity in transplant patients. Monitor busulfan blood levels as AUC below 1500mol/L per minute tends to prevent toxicity
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Mechanism Precautions Uncertain Watch for early features of toxicity
BUSULFAN CYCLOPHOSPHAMIDE ≠ incidence of veno-occlusive disease and mucositis when cyclophosphamide is given 24 hours after the last dose of busulfan. Possibly also ↓ effect of cyclophosphamide
There is ↓ clearance and ≠ elimination half-life of cyclophosphamide, and ≠ concentrations of the active metabolite 4-hydroxycyclophosphamide
Administer cyclophosphamide at least 24 hours after the last dose of busulfan
BUSULFAN TIOGUANINE ≠ risk of nodular regenerative hyperplasia of the liver, oesophageal varices and portal hypertension
Mechanism uncertain Monitor liver function and for clinical and biochemical indices of liver toxicity (e.g. ascites, splenomegaly). Ask patients to report any symptoms suggestive of oesophageal bleeding
BUSULFAN ANTIEPILEPTICS – FOSPHENYTOIN, PHENYTOIN
↓ plasma concentrations of busulfan (by approximately 15%)
Due to induction of glutathione S-transferase by fosphenytoin
Be aware. Clinical significance may be minimal
BUSULFAN ANTIFUNGALS – ITRACONAZOLE
≠ busulfan levels, with risk of toxicity of busulfan, e.g. venoocclusive disease and pulmonary fibrosis
Itraconazole is a potent inhibitor of CYP3A4. Busulfan clearance may be ↓ by 25%, and the AUC of busulfan may ≠ by 1500mol/L
Monitor clinically for veno-occlusive disease and pulmonary toxicity in transplant patients. Monitor busulfan blood levels as AUC below 1500mol/L per minute tends to prevent toxicity
BUSULFAN CALCIUM CHANNEL BLOCKERS
≠ busulfan levels, with risk of toxicity of busulfan, e.g. venoocclusive disease and pulmonary fibrosis, when co-administered with diltiazem, nifedipine or verapamil
Due to inhibition of CYP3A4mediated metabolism of busulfan by these calcium channel blockers. Busulfan clearance may be ↓ by 25%, and the AUC of busulfan may ≠ by 1500mol/L
Monitor clinically for veno-occlusive disease and pulmonary toxicity in transplant patients. Monitor busulfan blood levels as AUC below 1500mol/L per minute tends to prevent toxicity
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IC S293
ANTICANCER AND IMMUNOMODULATING DRUGS CYTOTOXICS Chlorambucil
Additive toxicity Monitor more closely; monitor FBC regularly
Capecitabine is metabolized to fluorouracil ➣ Flurorouracil/capecitabine, below
CARBOPLATIN ➣ Platinum compounds, below
CARMUSTINE
CARMUSTINE ANTICANCER AND IMMUNOMODULATING DRUGS – ETOPOSIDE (HIGH DOSE)
≠ risk of liver toxicity, which usually occurs after 1-2 months after initiating treatment without an improvement in tumour response
Possible additive hepatotoxic effects
Avoid co-administration
CARMUSTINE ANTIEPILEPTICS - PHENOBARBITAL
↓ plasma concentrations of carmustine and ↓ anti-tumour effect in animal experiments
Attributed to induction of liver metabolizing enzymes of carmustine by phenobarbitone, particularly with long-term therapy
Avoid concurrent use. As this study did not show any interaction with phenytoin, phenytoin may be a suitable alternative antiepileptic
CARMUSTINE H2 RECEPTOR BLOCKERS – CIMETIDINE
≠ adverse effects of alkylating agent, e.g. myelosuppression
Additive toxicity Monitor more closely; monitor FBC regularly
CHLORAMBUCIL
CHLORAMBUCIL 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
CHLORAMBUCIL H2 RECEPTOR BLOCKERS – CIMETIDINE
≠ adverse effects of alkylating agent, e.g. myelosuppression
Additive toxicity Monitor more closely; monitor FBC regularly
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Mechanism Precautions
CRISANTASPASE ANTICANCER AND IMMUNOMODULATING DRUGS
CRISANTASPASE METHOTREXATE Administration prior to or concurrently may ↓ efficacy of methotrexate
Crisantaspase inhibits protein synthesis and prevents cell entry to S phase, which leads to ↓ efficacy of methotrexate
Administer crisantaspase shortly after methotrexate or 9-10 days before methotrexate
CRISANTASPASE VINCRISTINE ≠ risk of neurotoxicity if concurrently administered or if crisantaspase is administered prior to vincristine
Uncertain but has been attributed by some to effects of crisantaspase on the metabolism of vincristine
Administer vincristine prior to crisantaspase
CYCLOPHOSPHAMIDE
CYCLOPHOSPHAMIDE ANTICANCER AND IMMUNOMODULATING DRUGS
CYCLOPHOSPHAMIDE 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
CYCLOPHOSPHAMIDE BUSULFAN ≠ incidence of veno-occlusive disease and mucositis when cyclophosphamide is given 24 hours after the last dose of busulfan. Possibly also ↓ effect of cyclophosphamide
There is ↓ clearance and ≠ elimination half-life of cyclophosphamide, and ≠ concentrations of the active metabolite 4-hydroxycyclophosphamide
Administer cyclophosphamide at least 24 hours after the last dose of busulfan
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IC S295
ANTICANCER AND IMMUNOMODULATING DRUGS CYTOTOXICS Cyclophosphamide
24 or 72 hours prior to cyclophosphamide
Mechanism is uncertain Administer cyclophosphamide first and then follow with paclitaxel
CYCLOPHOSPHAMIDE PENTOSTATIN ≠ risk of potentially fatal cardiac toxicity
Attributed to interference of adenosine metabolism by cyclophosphamide
Avoid co-administration
CYCLOPHOSPHAMIDE TRASTUZUMAB ≠ risk of cardiac toxicity Possibly additive cardiac toxic effect
Closely monitor cardiac function – clinically and electrocardiographically
CYCLOPHOSPHAMIDE ANTICOAGULANTS – ORAL Episodes of ≠ anticoagulant effect Not understood but likely to be multifactorial
Monitor INR at least weekly until stable during administration of chemotherapy
CYCLOPHOSPHAMIDE ANTIDIABETIC DRUGS – GLIPIZIDE
Blood sugar levels may be ≠ or ↓ Uncertain Need to monitor blood glucose in patients with concomitant treatment at the beginning of treatment and after 1-2 weeks
CYCLOPHOSPHAMIDE ANTIGOUT DRUGS – ALLOPURINOL
≠ risk of bone marrow suppression Uncertain but allopurinol seems to ≠ cyclophosphamide levels
Monitor FBC closely
CYCLOPHOSPHAMIDE CNS STIMULANTS – MODAFINIL
May cause moderate ≠ in plasma concentrations of cyclophosphamide
Modafinil is a reversible inhibitor of CYP2C19 when used in therapeutic doses
Be aware
CYCLOPHOSPHAMIDE H2 RECEPTOR BLOCKERS – CIMETIDINE
≠ adverse effects of alkylating agent, e.g. myelosuppression
1. Additive toxicity 2. Possible minor inhibition of cyclophosphamide metabolism via CYP2C9
Avoid co-administration of cimetidine with cyclophosphamide
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Mechanism Precautions
CYTARABINE 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
CYTARABINE FLUDARABINE ≠ efficacy of cytarabine Uncertain Watch for early features of toxicity of cytarabine
CYTARABINE ANTIFUNGALS – FLUCYTOSINE
↓ flucytosine levels Uncertain Watch for poor response to flucytosine
DACARBAZINE
DACARBAZINE IL-2 ↓ efficacy of dacarbazine ↓ AUC of dacarbazine due to ↓ volume of distribution
The clinical significance is uncertain as both drugs are used in the treatment of melanoma. It may be necessary to monitor clinically and by other appropriate measures of clinical response
DACTINOMYCIN (ACTINOMYCIN D)
DACTINOMYCIN 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
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IC S297
ANTICANCER AND IMMUNOMODULATING DRUGS CYTOTOXICS Docetaxel
Rifampicin ≠ metabolism of dasatinib
Avoid co-administration
DASATINIB H2 RECEPTOR BLOCKERS – FAMOTIDINE
Possible ↓ dasatinib levels Famotidine ≠ metabolism of dasatinib
Consider using alternative acidsuppression therapy
DASATINIB LIPID-LOWERING DRUGS – SIMVASTATIN
Possible ↓ simvastatin levels ≠ metabolism of simvastatin Monitor lipid profile closely and adjust simvastatin dose accordingly when starting and stopping co-administration
DAUNORUBICIN
DAUNORUBICIN ANTICANCER AND IMMUNOMODULATING DRUGS
DAUNORUBICIN 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
DAUNORUBICIN TRASTUZUMAB ≠ risk of cardiac toxicity Possibly additive cardiac toxic effect
Closely monitor cardiac function – clinically and electrocardiographically.
