Trilaciclib, sold under the brand name Cosela, is a medication used to reduce the frequency of chemotherapy-induced bone marrow suppression.The most common side effects include fatigue; low levels of calcium, potassium and phosphate; increased levels of an enzyme called aspartate aminotransferase; headache; and infection in the lungs (pneumonia).Trilaciclib may help protect bone marrow cells from damage caused by chemotherapy by inhibiting cyclin-dependent kinase 4/6, a type of enzyme. Trilaciclib is the first therapy in its class and was approved for medical use in the United States in February 2021.Chemotherapy drugs are designed to kill cancer cells but can damage normal tissues as well. The bone marrow is particularly susceptible to chemotherapy damage. The bone marrow makes red blood cells, white blood cells, and platelets (small fragments in the blood) that transport oxygen, fight infection, and stop bleeding. When damaged, the bone marrow produces fewer of these cells, leading to fatigue, increased risk of infection, and bleeding, among other problems. Trilaciclib may help protect the normal bone marrow cells from the harmful effects of chemotherapy. Medical uses
Trilaciclib is indicated to reduce the frequency of chemotherapy-induced bone marrow suppression in adults receiving certain types of chemotherapy for extensive-stage (when the cancer has spread beyond the lungs) small cell lung cancer. History
The effectiveness of trilaciclib was evaluated in three randomized, double-blind, placebo-controlled studies in participants with extensive-stage small cell lung cancer. Combined, these studies randomly assigned 245 participants to receive either an infusion of trilaciclib in their veins or a placebo before chemotherapy.
Because Liddle phenotype usually involves an upregulation of ENaC channels, leading to retention of sodium and water and to hypokalemia, amiloride is useful as an ENaC channel inhibitor due to its promotion of sodium excretion and its potassium-sparing effects, restoring potassium to normal levels.Amiloride can be used as a monotherapy (single-drug therapy) or an adjunctive therapy alongside other diuretics (e.g. hydrochlorothiazide, furosemide) for the treatment of ascites and edema (swelling) due to cirrhosis of the liver. The 2012 clinical practice guidelines by the American Association for the Study of Liver Diseases (AASLD) states that amiloride can be used to treat ascites in place of spironolactone if it isnt tolerated (e.g. due to the side effect of gynecomastia), though amiloride isnt a preferred drug due to cost and lack of efficacy. Specific populations
Diabetics
People with diabetes are at higher risk for kidney problems, which increases their risk for hyperkalemia (high blood potassium). The use of amiloride in people with diabetes requires careful potassium and kidney function monitoring to prevent toxicity. Amiloride must be discontinued for at least 3 days prior to glucose tolerance testing, due to the risk for fatal hyperkalemia. Poor kidney function
People with poor kidney function (e.g. blood urea nitrogen >30 mg/dL, or serum creatinine >1.5 mg/dL) are at high risk for hyperkalemia. Lactation
There is no data on the use of amiloride in women that are breastfeeding. While diuretics can make lactation difficult, it is unlikely that amiloride would induce this effect in the absence of other diuretics.