Abiraterone should be administered without food, at least one hour before or two hours after a meal (modified fasting state). The first step in the event of abiraterone trough levels below target would be to take abiraterone at the same time as a light snack or a low-fat meal based on Chi et al.2 The abiraterone capsules should be taken within 30 minutes of the start of the meal. Concomitant use of (strong) CYP3A4 inducers (including (but not limited to) carbamazepine, phenytoin, phenobarbital, rifampicin, dexamethasone and Hypericum perforatum also known as St. John's wort) should be avoided.
Abiraterone (Zytiga)
Patients who develop Grade 4 hyperuricaemia or Grade 3 hypophosphataemia without clinical symptoms may, at the discretion of the investigator, continue treatment without interruption. Patients who develop grade 3 or 4 lymphopenia without other dose-limiting events (e.g., opportunistic infection) may continue treatment without interruption.
Alectinib (Alecensa)
3 x ULN, reduce dose by one dose level or to previous dose in case of previous dose increase and continue treatment. If a contributing drug is identified and discontinued or its dose adjusted, continue alectinib at the same dose. If a contributing drug is identified and discontinued or its dose adjusted, withhold dosing until recovery of asymptomatic bradycardia or heart rate ≥ 60 beats per minute, reduce alectinib dose by one dose level or to the previous dose level in in the case of a previous dose increase and Continue.
CPK elevation > 5 x ULN Interrupt dosing until recovery to baseline or to ≤ 2.5 x ULN, resume at same dose level. Withhold dosing until recovery to baseline or to ≤ 2.5 x ULN, reduce dose by one dose level or to previous dose level in case of previous dose escalation, and resume dosing. Interrupt dosing if ILD/pneumonitis is suspected and permanently discontinue if treatment-related ILD/pneumonitis is diagnosed.
Axitinib (Inlyta)
Bosutinib (Bosulif)
Patients who develop grade 4 hyperuricemia or grade 3 hypophosphatemia without clinical symptoms may continue study treatment without interruption at the discretion of the investigator. Patients who develop grade 3 or 4 lymphopenia without other dose-limiting events (eg, opportunistic infection) may continue study treatment without interruption. AST/ALT > 5 x ULN Hold dose to ≤ 2.5 x ULN, reduce dose by one dose level and resume treatment.
Crizotinib (Xalkori)
For specific dose modification instructions related to liver enzyme test abnormalities, QTc prolongation, bradycardia, ILD/pneumonitis, ocular disorder, diarrhea, fatigue, nausea and vomiting, and liver function test abnormalities, see lower. Maintain dose until ≤ grade 1 or baseline, reduce dose by two dose levels and resume treatment, escalate one dose level if clinically tolerated. If concomitant medication is identified and discontinued, or its dose adjusted, resume crizotinib at the same dose level.
If a contributing concomitant medication is identified and discontinued or dose adjusted, reduce crizotinib by two dose levels and monitor frequently.
Dabrafenib/Trametinib (Tafinlar/Mekinist)
Concomitant use of P-glycoprotein inhibitors (including (but not limited to) ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir and amiodarone) should be avoided. If the patient's temperature is ≥38.5◦C, therapy with dabrafenib should be interrupted, trametinib should be continued at the same dose. After pyrexia resolves, dabrafenib should be restarted with appropriate antipyretic prophylaxis, either 1) at the same dose level, or 2) reduced by one dose level if the pyrexia recurs and/or is accompanied by other severe symptoms, including dehydration.
If uveitis does not respond to topical ocular therapy, dabrafenib should be withheld until the ocular inflammation resolves, and then dabrafenib should be restarted at a reduced dose level. The benefits and risks should be considered before continuing treatment with dabrafenib in patients with a non-cutaneous malignancy harboring a RAS mutation. If LVEF recovers, trametinib treatment can be resumed, but the dose should be reduced by one dose level with careful monitoring.
For Grade 3 or 4 left ventricular cardiac dysfunction or if LVEF does not recover, trametinib should be permanently discontinued. In patients diagnosed with RVO, treatment with trametinib, given as monotherapy or in combination with dabrafenib, should be permanently discontinued.
Dasatinib (Sprycel)
At the third episode, the dose should be further reduced to 50 mg once daily (for newly diagnosed patients) or discontinued (for patients resistant or intolerant to previous treatment including imatinib). Resume treatment as needed at a reduced dose depending on the initial severity of the side effect Pleural effusion. If the episode does not improve within about a week, a course of diuretics or corticosteroids, or both, should be considered.
After the first episode, reinstitution of dasatinib at the same dose level should be considered. Following a severe (grade 3 or 4) episode, treatment may be resumed as appropriate at a reduced dose, depending on the initial severity of the adverse reaction.
Enzalutamide (Xtandi)
Erlotinib (Tarceva)
Concomitant use of drugs that increase gastric pH should be avoided. 13 o H2 antagonists: should be administered 2 hours after taking erlotinib. o antacids: should be administered 4 hours before or 2 hours after intake. Concomitant use of (strong) CYP3A4 inhibitors (including (but not limited to) aprepitant, clarithromycin, erythromycin, ketoconazole, itraconazole, diltiazem, verapamil, HIV protease inhibitors, fluoxetine and grapefruit juice) should be avoided.
Everolimus (Afinitor)
Reduce the dose by one dose level or to the previous dose level in case of previous dose escalation. Consider restarting treatment with a dose reduction of one dose level or to the previous dose level in case of previous dose escalation. If stomatitis recurs at grade 2, the dose is withheld until ≤ grade 1, the dose is reduced by one dose level or to the previous dose level in case of previous dose escalation, and treatment is resumed.
3 Withhold dose until ≤ grade 1, reduce dose by one dose level or to previous dose level in case of previous dose escalation, and resume treatment. 3 Temporarily withhold the dose, reduce the dose by one dose level or to the previous dose level in case of previous dose escalation, and resume treatment. 3 – 4 Withhold dose until ≤ grade L), reduce dose by one dose level or to previous dose level in case of previous dose escalation and resume treatment.
4 Withhold dose until ≤ grade L), reduce dose by one dose level or to previous dose level in case of previous dose escalation and resume treatment. Febrile neutropenia 3 Withhold dose until ≤ grade L) and no fever, reduce dose by one dose level or to previous dose level in case of previous dose escalation and resume treatment.
Gefitinib (Iressa)
Imatinib (Glivec)
For treatment-related toxicity: reduce dose by one dose level or to previous dose level in case of previous dose increase and restart. Absolute Neutrophil Count (ANC) and Platelet Count Chronic Phase CML / GIST (standard dosage 400mg OD) ANC/Platelet Count Dosing Advice. Accelerated phase CML / blast crisis CML / Ph+ ALL (standard dosage 600mg OD) ANC/platelet count Dosing advice.
Investigate whether the cytopenia is related to the leukemia (by performing a bone marrow aspiration or biopsy) 2.
Nilotinib (Tasigna)
Treatment should be restarted within 2 weeks at the previous dose if ANC >1.0 x 109/l and/or platelets. For grade 3-4 serum lipase elevations, doses should be reduced to 400 mg once daily or discontinued. For grade 3-4 elevations in bilirubin and hepatic transaminases, doses should be reduced to 400 mg once daily or discontinued.
Olaparib (Lynparza)
Any occurrence Continue treatment at the same dose and initiate supportive measures to relieve symptoms. 1st occurrence Reduce dose by one dose level or to previous dose level in case of previous dose increase and initiate supportive measures for symptomatic relief. Hold dose until toxicity ≤ grade 1, reduce dose by one dose level or to previous dose level in case of previous dose increase, and continue treatment.
Withhold dosing for a minimum of 7 days and until toxicity is ≤ grade 1, reduce dose by one dose level or to previous dose level in case of previous dose increase and resume treatment. Withhold dosing for a minimum of 7 days and until toxicity is ≤ grade 1, reduce dose by one dose level or to previous dose level in case of previous. Restart if the potential benefit outweighs the risk of hepatotoxicity, reduce dose by one dose level or to previous dose level in case of previous dose increase.
Dose changes below are for vemurafenib, cobimetinib can be continued at the same dose level. Withhold dosing until QTc falls below 500 ms, reduce the dose of vemurafenib by one dose level or to the previous dose level in case of previous dose escalation and resume treatment. Dose changes below are for cobimetinib, vemurafenib can be continued at the same dose level.
Palbociclib (Ibrance)
Pazopanib (Votrient)
Targets: (calculated) trough level ≥ 1400 ng/mL, no pharmacokinetic targets are reported in the literature, therefore the mean Cmin of the approved dose is used based on Yu et al.525. Target: (calculated) trough level ≥ 3750 ng/mL, no pharmacokinetic targets are reported in the literature, therefore the average Cmin of the approved dose is used based on Yu et al.5262728. If side effects are not tolerated: Reduce one dose level of vemurafenib and cobimetinib, unless otherwise indicated in the specific dose modification guidelines.
Regorafenib (Stivarga)
Sorafenib (Nexavar)
Sunitinib (Sutent)
Tamoxifen
Vemurafenib/cobimetinib (Zelboraf/Cotellic)
Vismodegib (Erivedge)
