Treatment methods having reduced drug-related toxicity and methods of identifying the likelihood of patient harm from prescribed medications
AssigneeTabula Rasa Healthcare, Inc.
InventorsJacques TURGEON, Lauren J. STEFFEN, Gabriel BADEA
Life of this patent
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Abstract
Methods of determining whether specific drugs or patients carry an increased risk of causing or developing, respectively, long QT syndrome or Torsades de Pointes and methods of treating such patients.
Claims9
A method for determining whether a compound is associated with an increased risk of long QT syndrome or Torsades de Pointes by determining a drug-specific index, the method comprising the steps of:
- measuring a first index variable comprising determining
- an IC50 value for block of one or more of IKr and IKs,
- a Cmax of the compound at a test dose,
- a daily dose amount of the compound,
- a protein binding value for the compound at a target protein, and
- a drug-drug interaction coefficient (DDIC) for the compound;
- measuring a second index variable comprising determining
- an IC50 value for block of CaV1.2 current, and
- the IC50 value for block of one or more of IKr and IKs;
- measuring a third index variable comprising determining
- an IC50 value for block of NaV1.5 current, and
- the IC50 value for block of one or more of IKr and IKs;
- measuring a fourth index variable comprising determining a qualitative value for the compound's inhibition of hERG trafficking;
- and
- combining the first, second, third, and fourth index variables to provide the drug-specific index, which is indicative of an increased risk of long QT syndrome or Torsades de Pointes.
A method for determining whether a patient undergoing treatment with a compound has an increased risk of long QT syndrome or Torsades de Pointes by determining a patient-specific score, the method comprising the steps of:
- determining a risk variable based on the patient's gender and age;
- measuring the patient's heart rhythm comprising detecting one or more of sinus rhythm, atrial fibrillation, sick sinus syndrome, pause, and heart rate;
- detecting a potassium level in the patient;
- detecting a magnesium level in the patient;
- detecting the presence of one or more diuretics or antiarrhythmics in the patient;
- measuring a drug-specific index for one or more drug therapeutics in the patient's treatment regimen;
- and
- measuring the patient's QT interval.
A method of treating patients having an increased risk of developing long QT syndrome or Torsades de Pointes due to a patient-specific score of greater than about 10, the method comprising administering a therapeutically effective amount of a compound selected from the group consisting of a potassium salt and a magnesium salt.
A method of treating a patient with a compound determined to increase the risk of long QT syndrome or Torsades de Pointes, the method comprising the steps of:
- confirming that the patient does not have an increased risk of developing long QT syndrome or Torsades de Pointes due to a patient-specific score of greater than about 10;
- and
- administering a pharmaceutical composition to the patient comprising a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
A method of treating a patient with a compound determined to increase the risk of long QT syndrome or Torsades de Pointes, the method comprising the steps of:
- administering a pharmaceutical composition to the patient comprising a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier;
- determining whether the patient has an increased risk of developing long QT syndrome or Torsades de Pointes due to a patient-specific score that is indicative of an increased risk of developing long QT syndrome or Torsades de Pointes;
- and
- halting treatment of the patient with the pharmaceutical composition.
Dependencies are inferred from the claim text.