es have only been performed in adults.
Medicinal products that may increase sunitinib plasma concentrations.
In healthy volunteers, concomitant administration of a single dose of sunitinib with the potent CYP3A4 inhibitor ketoconazole resulted in an increase of the combined [sunitinib + primary metabolite] Cmax and AUC0- values of 49% and 51%, respectively.
Administration of sunitinib with potent CYP3A4 inhibitors (e.g. ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice) may increase sunitinib concentrations.
Combination with CYP3A4 inhibitors should therefore be avoided, or the selection of an alternate concomitant medicinal product with no, or minimal potential to inhibit CYP3A4 should be considered.
If this is not possible, the dose of SUTENT may need to be reduced to a minimum of 37.5 mg daily for GIST and MRCC or 25 mg daily for pNET, based on careful monitoring of tolerability (see section 4.2).
Medicinal products that may decrease sunitinib plasma concentrations:
In healthy volunteers, concomitant administration of a single dose of sunitinib with the CYP3A4 inducer rifampicin resulted in a reduction of the combined [sunitinib + primary metabolite] Cmax and AUC0- values of 23% and 46%, respectively.
Administration of sunitinib with potent CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampicin, phenobarbital or herbal preparations containing St. John's Wort/ Hypericum perforatum may decrease sunitinib concentrations. Combination with CYP3A4 inducers should therefore be avoided, or selection of an alternate concomitant medicinal product with no or minimal potential to induce CYP3A4 should be considered. If this is not possible, the dosage of SUTENT may need to be increased in 12.5 mg increments (up to 87.5 mg per day for GIST and MRCC or 62.5 mg per day for pNET), based on careful monitoring of tolerability (see section 4.2).
Anticoagulants
Haemorrhage has been observed rarely in patients treated with sunitinib (see section 4.4 and 4.8). Patients receiving concomitant treatment with anti-coagulants (e.g. warfarin; acenocoumarole) may be periodically monitored by complete blood counts (platelets), coagulation factors (PT/INR), and physical examination
4.6 Pregnancy and lactation
Pregnncy
There are no studies in pregnant women using SUTENT. Studies in animals have shown reproductive toxicity including foetal malformations (see section 5.3). SUTENT should not be used during pregnancy or in any women not using effective contraception, unless the potential benefit justifies the potential risk to the foetus. If SUTENT is used during pregnancy or if the patient becomes pregnant while on treatment with SUTENT, the patient should be apprised of the potential hazard to the foetus.
Women of childbearing potential should be advised to use effective contraception and avoid becoming pregnant while receiving treatment with SUTENT.
Breastfeeding
Sunitinib and/or its metabolites are excreted in rat milk. It is not known whether sunitinib or its primary active metabolite is excreted in human milk. Because active substances are commonly excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women should not breast feed while taking SUTENT.
Fertility
Based on nonclinical findings, male and female fertility may be compromised by treatment with SUTENT (see section 5.3).
4.7 Efects on ability to drive an |
