Sodium bicarbonate Methotrexate

Oral administration of bicarbonate may decrease the absorption of ketoconazole. Increased blood levels of quinidine, flecainide, or sympatiiomimetics may occur when these agents are administered with bicarbonate There is an increased risk of crystalluria when bicarbonate is administered with the fluoroquinolones. Fbssible decreased effects of lithium, methotrexate, chlorpropamide, salicylates, and tetracyclines may occur when these drag s are administered with sodium bicarbonate. Sodium bicarbonate is not administered within 2 hours of enteric-coated drugs the protective enteric coating may disintegrate before the drug reaches the intestine. 

RH is admitted to the pediatric oncology service. She is started on allopurinol and intravenous fluids with sodium bicarbonate to prevent tumor lysis syndrome. According to her risk status, she will receive a three-drug induction with vincristine, dexamethasone, and pegylated asparaginase. She also will receive intrathecal (IT) chemotherapy for CNS prophylaxis with methotrexate, cytarabine, and hydrocortisone. 

Urine alkalinization is a treatment modality that increases elimination of poisons by the intravenous administration of sodium bicarbonate to produce urine with a pH of more than or equal to 7.5 and must be supported by high urine flow. This technique might be useful for the elimination of drugs with an acid pKa such as salicylates (but not recommended for phenobarbital intoxication for which multiple-dose activated charcoal is better), chlorpropamide, 2,4-dichlorophenoyacetic acid, diflunisal, fluoride, mecoprop, methotrexate. Complications include severe alkalemia, hypokalemia, hypocalcemia and coronary vasoconstriction. 

Patients who take methotrexate (3.45) (Figure 3.22) must monitor the pH of their urine several times a day. If the pH rises above 7, the patient must receive a dose of sodium bicarbonate (a weak base) either orally or as an IV solution. Why is the pH of the urine important ... 

Chatterji and Galleli (58) determined that the photodegradation reaction of methotrexate after an initial lag phase follows zero-order kinetics. The photolability of the drug increases at higher dilutions. Bicarbonate ion has also been identified as a catalyst for the photolysis of methotrexate. No photodegradation products were observed, in an infusion solution containing 2mg/mL methotrexate and 0.05 mol sodium bicarbonate, after 12 hours exposure to room radiation. 

Urinary tract Methotrexate-induced renal damage appears to be physicochemical in nature. Both the parent compound and its major metabolite, 7-hydroxymethotrexate, are less soluble at acidic pH values, increasing the risk of precipitation in the kidneys, particularly at high dosages. An amorphous yellow material—very probably methotrexate—has been isolated in the kidneys of patients who died as a result of methotrexate-induced renal dysfunction. For physicochemical reasons, it is recommended that the urine be alkalinized (target urinary pH above 7.5) before intensive methotrexate regimens are started. Supportive agents include sodium bicarbonate orally or intravenously, acetazolamide 500 mg qds, or both in combination [1805, 18F, 182 ]. If there is acute renal insufficiency despite appropriate urinary alkalinization, one may need to use carboxypeptidase G2 as an antidote, which is also appropriate in cases of accidental intrathecal overdose of methotrexate [183", 184 ]. 

The mixture of methotrexate sodium with cytarabine, fluorouracil, hydrocortisone sodium, and prednisolone sodium phosphate produces precipitate upon storage, although it is not observed immediately. A concentration-dependent photodegradation was reported for methotrexate and considered high in the presence of bicarbonate ions and unprotected polybutadiene tubings.226 Methotrexate wastes may be disposed of by oxidation with potassium permanganate and sulfuric acid or by oxidation with aqueous alkaline hypochlorite. 

---