Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) Sunitinib, a tyrosine kinase inhibitor, is marketed for the treatment of advanced-stage and metastatic renal carcinoma, and for second-line treatment of gastrointestinal stromal tumours. Sorafenib arrived on the market almost simultaneously for second-line treatment of kidney cancer. (2) In second-line treatment of kidney cancer, two non comparative trials showed an unusually high rate of at least partial tumour regression with sunitinib (25%, compared to only 2% with sorafenib). Head-to-head trials of the two drugs are lacking. Although indirect comparisons are notoriously unreliable, sunitinib appears to provide longer progression-free survival than sorafenib (about 9 months versus 5.5 months), although overall survival times are similar. (3) Preliminary results of a trial comparing sunitinib with interferon alfa as first-line treatments in 750 patients with kidney cancer show a 6-month event-free survival advantage in the sunitinib arm. The precise overall survival time has not yet been calculated. (4) In 312 patients with gastrointestinal stromal tumours in whom imatinib has failed, a double-blind placebo-controlled trial showed that sunitinib prolonged overall survival time, but potential biases undermine these results. (5) The adverse effect profile of sunitinib appears to be similar to those of imatinib and sorafenib, apart from more thyroid disorders. The principal adverse effects are cutaneous, gastrointestinal, cardiovascular and haematological disorders. Arterial hypertension, sometimes severe, occurred in 16% of patients treated with sunitinib. Other serious adverse events included tumour haemorrhage and pulmonary embolism. A risk of cardiac toxicity leading to heart failure cannot currently be ruled out. (6) Sunitinib is metabolised by cytochrome P450 isoenzyme CYP 3A4, increasing the likelihood of drug interactions. (7) These results support the use of sunitinib as second-line therapy for patients with gastrointestinal stromal tumours. Additional clinical evaluation is needed, however. In first-line treatment of kidney cancer, it is preferable to wait for detailed results of the ongoing trial, especially effects on survival time, before judging the possible advantages and disadvantages of sunitinib compared to interferon alfa. In second-line treatment, sorafenib is better-assessed than sunitinib and should therefore be preferred, pending a direct comparison of the two drugs.
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PMID:Sunitinib: new drug. For some gastrointestinal stromal tumours. 1772 33

(1) The standard anticoagulant therapy for prevention of thrombosis after hip or knee replacement surgery is subcutaneous injection of a low-molecular-weight heparin, such as enoxaparin; (2) Rivaroxaban is an oral factor-Xa inhibitor anticoagulant approved for use in these indications in the European Union; (3) Four double-blind controlled trials in more than 12 000 patients undergoing hip or knee replacement surgery failed to show that rivaroxaban was any more effective than enoxaparin on relevant clinical outcomes; there was no reduction in mortality, nor in the incidence of pulmonary embolism and symptomatic deep venous thrombosis; (4) In the selected populations enrolled in these trials, the bleeding risk was similar in the rivaroxaban and enoxaparin groups. However, it is possible that very underweight or overweight patients have an increased bleeding risk with rivaroxaban; (5) More information is needed on the nephrotoxicity of rivaroxaban, and a risk of mitochondrial toxicity cannot be ruled out. Post-marketing studies also need to focus on the consequences of wound seepage, which is more frequent with rivaroxaban. (6) Rivaroxaban is metabolized by the cytochrome P450 isoenzyme CYP 3A4 and binds to P-glycoprotein, hence a high risk of pharmacokinetic interactions; (7) Rivaroxaban has the advantage of being an oral treatment that does not require laboratory monitoring. However, it seems best to monitor renal function. It should also be noted that there is no effective antidote if severe bleeding occurs; (8) In practice, for frail elderly patients, who are often polymedicated, it seems more prudent to continue using low-molecular-weight heparin, a drug with which we have more experience.
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PMID:Rivaroxaban: new drug. After hip or knee replacement surgery: LMWH is safer. 1974 67

The standard anticoagulant for prevention of venous thromboembolism in patients undergoing hip or knee replacement surgery is a low-molecular-weight heparin (LMWH) such as subcutaneous enoxaparin. Apixaban is the second oral factor Xa inhibitor, after rivaroxaban, to be approved in the European Union for use in these two situations. Three double-blind randomised trials versus enoxaparin in a total of nearly 12 000 patients failed to show that apixaban was more effective in terms of relevant endpoints: mortality, and the incidence of pulmonary embolism and symptomatic deep vein thrombosis. The incidence of bleeding did not differ between the apixaban and enoxaparin groups under the conditions of these trials. Apixaban is mainly metabolised by cytochrome P450 isoenzymes CYP 3A4 and 3A5 and also binds to P-glycoprotein, resulting in a high potential for pharmacokinetic interactions. Renal failure is a risk factor for overdose. Pharmacodynamic interactions are also likely. There is no known antidote for apixaban. In practice, LMWH remains the standard treatment.
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PMID:Apixaban. After hip or knee replacement: LMWH remains the standard treatment. 2301 47