Drug Interactions between Kalexate and levomethadyl acetate

GENERALLY AVOID: The concurrent use of levomethadyl acetate and alcohol may result in additive CNS and respiratory depression, hypotension, sedation, or coma. Grapefruit juice may increase the plasma concentrations of orally administered drugs which are substrates of the CYP450 3A4 isoenzyme, such as levomethadyl acetate. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who are known to abuse alcohol should be warned of the risk of potentially fatal overdose if these substances are taken concurrently. Patients who regularly consume grapefruits and grapefruit juice should be monitored for adverse effects and altered plasma concentrations of levomethadyl acetate. A 12-lead ECG should be performed before initiating therapy, 12 to 14 days after initiating therapy, and periodically thereafter. Patients should be advised to immediately seek medical attention if they experience palpitations, dizziness, lightheadedness, fainting, or seizures. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.

GENERALLY AVOID: Potassium in foods can bind to the cation exchange resin and interfere with potassium removal in the treatment of hyperkalemia.

MANAGEMENT: Cation exchange resins should not be mixed with orange juice or other foods with a high potassium content.

ADJUST DOSING INTERVAL: Cation exchange resins may bind to other medications that are administered orally. Reduced systemic absorption and therapeutic efficacy may occur. Manufacturers have reported that polystyrene sulfonate exchange resins can decrease the absorption of lithium and levothyroxine. A more recent study found that sodium polystyrene sulfonate binds to many commonly prescribed oral medications. Another potassium-lowering drug, patiromer, has also been found to bind about half of the medications tested, some of which are commonly used in patients who require potassium-lowering drugs.

MANAGEMENT: To minimize the risk of interaction, patients should be advised to separate the dosing of the cation exchange resin from other orally administered medications by at least 3 hours. The dosing interval should be increased to 6 hours for patients with gastroparesis or other conditions resulting in delayed emptying of food from the stomach into the small intestine. Health care professionals should monitor blood levels and/or clinical response to the other medications when appropriate.

ADJUST DOSING INTERVAL: Simultaneous administration of cation-donating preparations may reduce the potassium exchange capability of cation-exchange resins due to binding of the cation to the resin.

MANAGEMENT: Patients should consider separating the times of administration of the cation-exchange resin and any cation-donating preparation (e.g., mineral supplements; antacids; products containing antacids such as didanosine buffered tablets or pediatric oral solution) by several hours if possible.