Interações de Afatinibe
Afatinibe (Gilotrif) tem 93 interações documentadas nas bulas da FDA e nas fichas informativas que indexamos (graves: 0; moderadas: 88; leves: 5; casos em que uma bula relata não haver interação significativa: 0). Cada item abaixo cita a frase em que se baseia. Esta página de medicamento é um ponto de partida, não um veredito para a sua situação.
Interações segundo a bula
Interações moderadas (88)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Effect of P-glycoprotein (P-gp) Inhibitors and Inducers Concomitant taking of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with GILOTRIF can increase exposure to afatinib [see Clinical Pharmacology (12.3) ]. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Effect of P-glycoprotein (P-gp) Inhibitors and Inducers Concomitant taking of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with GILOTRIF can increase exposure to afatinib [see Clinical Pharmacology (12.3) ]. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-gp Inducers : Co-administration of chronic P-gp inducers orally can decrease afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-gp Inducers : Co-administration of chronic P-gp inducers orally can decrease afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Effect of P-glycoprotein (P-gp) Inhibitors and Inducers Concomitant taking of P-gp inhibitors (including but not limited to ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with GILOTRIF can increase exposure to afatinib [see Clinical Pharmacology (12.3) ]. (bula de Afatinibe, Interações medicamentosas)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
Patients receiving concomitant corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-angiogenic agents, or patients with increasing age or who have an underlying history of gastrointestinal ulceration, underlying diverticular disease or bowel metastases may be at increased risk of perforation. (bula de Afatinibe, Advertências e precauções)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (bula de Afatinibe, Interações medicamentosas)
Menções leves (5)
Concomitant taking of P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and St. (bula de Afatinibe, Interações medicamentosas)
Concomitant taking of P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and St. (bula de Afatinibe, Interações medicamentosas)
Concomitant taking of P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and St. (bula de Afatinibe, Interações medicamentosas)
Concomitant taking of P-gp inducers (including but not limited to rifampicin, carbamazepine, phenytoin, phenobarbital, and St. (bula de Afatinibe, Interações medicamentosas)
Provide patients with an anti-diarrheal agent (e.g., loperamide) for self-administration at the onset of diarrhea and instruct patients to continue anti-diarrheal therapy until loose bowel movements cease for 12 hours. (bula de Afatinibe, Advertências e precauções)
Verifique Afatinibe com tudo o que você toma. Adicione sua lista completa; todos os pares são verificados de uma vez.
Abrir no verificadorNão é aconselhamento médico. A gravidade reflete a redação da bula, não as suas circunstâncias. Um alerta “grave” pode ser rotina sob supervisão, e um “leve” pode ser importante em doses altas. Pergunte a um farmacêutico.