Treatment methods having reduced drug-related toxicity and methods of identifying the likelihood of patient harm from prescribed medications

A method of treating patients having an increased risk of developing long QT syndrome or Torsades de Pointes due to a patient-specific score exceeding a predetermined threshold value, the method comprising:

• one or more steps of (a)-(h):
• (a) determining a risk variable having a value between 0 and 0.5 based on the patient's gender and age;
• (b) determining a risk variable having a value between 0 and 1 based on a measurement of the patient's heart rhythm, the measurement comprising detecting one or more of sinus rhythm, atrial fibrillation, sick sinus syndrome, pause, and heart rate;
• (c) determining a risk variable having a value between 0 and 1 based on a detected potassium level in the patient;
• (d) determining a risk variable having a value between 0 and 1 based on a detected magnesium level in the patient;
• (e) determining a risk variable having a value between 0 and 1 based on a detected presence of one or more diuretics in the patient;
• (f) determining a risk variable having a value between 0 and 9 based on a detected presence of one or more antiarrhythmics in the patient;
• (g) determining a risk variable having a value between 0 and 12 based on calculating a drug-specific index for the one or more drugs in the patient's treatment regimen, including the patient's use of QT-prolonging drugs and/or a presence of drug-drug interactions, by:
• calculating a first index variable for the drug by determining:
• an IC50 value for block of one or more of IKr and IKs for the drug,
• a Cmax of the drug at a test dose,
• a daily dose amount of the drug,
• a protein binding value for the drug at a target protein, and
• a drug-drug interaction coefficient (DDIC) for the drug;
• calculating a second index variable for the drug by determining:
• an IC50 value for block of CaV1.2 current for the drug, and
• the IC50 value for block of one or more of IKr and IKs for the drug;
• calculating a third index variable for the drug by determining:
• an IC50 value for block of NaV1.5 current for the drug, and
• the IC50 value for block of one or more of IKr and IKs for the drug;
• calculating a fourth index variable for the drug based on whether the drug is an inhibitor of hERG trafficking;
• and
• combining the first, second, third, and fourth index variables to provide the drug-specific index, which is indicative of the drug's risk of causing long QT syndrome or Torsades de Pointes,
• wherein the drug is selected from the group consisting of Albuterol, Alfuzosin, Amantadine, Amiodarone, Amitriptyline, Amphetamine, Arsenic trioxide, Astemizole, Atazanavir, Atomoxetine, Azithromycin, Bepridil, Chloral hydrate, Chloroquine, Chlorpromazine, Ciprofloxacin, Cisapride, Citalopram, Clarithromycin, Clomipramine, Clozapine, Cocaine, Desipramine, Dexmethylphenidate, Diphenhydramine, Diphenhydramine, Disopyramide, Dobutamine, Dofetilide, Dolasetron, Domperidone, Dopamine, Doxepin, Dronedarone, Droperidol, Ephedrine, Epinephrine, Erythromycin, Escitalopram, Escitalopram, Famotidine, Felbamate, Fenfluramine, Flecamide, Fluconazole, Fluoxetine, Foscarnet, Fosphenyloin, Galantamine, Gatifloxacin, Gemifloxacin, Granisetron, Halofantrine, Haloperidol, Ibutilide, Imipramine, Indapamide, Isoproterenol, Isoproterenol, Isradipine, Itraconazole, Ketoconazole, Lapatinib, Lapatinib, Levalbuterol, Levofloxacin, Levomethadyl, Lisdexamfetamine, Lithium, Mesoridazine, Metaproterenol, Methadone, Methylphenidate, Midodrine, Moexipril/HCTZ, Moxifloxacin, Nicardipine, Nilotinib, Norepinephrine, Nortriptyline, Octreotide, Ofloxacin, Ondansetron, Oxytocin, Paliperidone, Paroxetine, Pentamidine, Perflutren lipid microspheres, Phentermine, Phenylephrine, Phenylpropanolamine, Pimozide, Probucol, Procainamide, Protriptyline, Pseudoephedrine, Quetiapine, Quinidine, Ranolazine, Risperidone, Ritodrine, Ritonavir, Roxithromycin, Salmeterol, Sertindole, Sertraline, Sibutramine, Solifenacin, Sotalol, Sparfloxacin, Sunitinib, Tacrolimus, Tamoxifen, Telithromycin, Terbutaline, Terfenadine, Thioridazine, Tizanidine, Tolterodine, Trazodone, Trimethoprim-Sulfa, Trimipramine, Vandetanib, Vardenafil, Venlafaxine, Voriconazole, Ziprasidone, and a pharmaceutically acceptable salt thereof;
• and
• (h) determining a risk variable having a value between 0 and 10 based on the patient's QT interval;
• the method further comprising combining the determined risk variables from the one or more of steps (a)-(g) to obtain a patient-specific score, wherein a patient-specific score exceeding a predetermined threshold value is indicative that the patient has an increased risk of long QT syndrome or Torsades de Pointes;
• and administering a therapeutically effective amount of a medication to decrease the patient's risk of developing long QT syndrome or Torsades de Pointes if the patient-specific score exceeds the predetermined threshold.