Narrow Therapeutic Index Drugs

Therapeutic Index (TI) is the ratio between the toxic dose (TD) and effective dose (ED) of a drug

TI = TD/ED

High TI drugs contain a wide margin

Low TI drugs have a narrow safety margin, which requires close monitoring to avoid toxicity

Warfarin (Coumadin)

Monitored using PT-INR Blood Tests; test how long clotting occurs (goal is INR of 2-3)

Side effects of toxicity include heavy bleeding, easy bruising, bleeding gums, nosebleeds, black/brown bowel movements, vomiting blood, severe stomach pain, severe headaches, dizziness

Treatment includes skipping warfarin doses or administering vitamin K to increase clotting

Digoxin (Lanoxin)

Monitored using digoxin and potassium blood levels and kidney function

Side effects of toxicity include lack of appetite, nausea, vomiting, fatigue, diarrhea, confusion, hallucinations, depression, heart rhythm changes, and visual disturbances

Treatment includes stopping digoxin, administering digoxin antibodies, monitoring levels, and supportive care

Cyclosporine (Neoral, Sandimmune)

Monitored using cyclosporine TDM, renal and liver function, Mg and K levels

Causes irreversible kidney damage and neurotoxicity

Tacrolimus (Protopic, Prograf)

Monitored using tacrolimus TDM, liver and kidney function, and electrolyte levels

Causes nephrotoxicity and neurotoxicity

Carbamazepine (Tegretol)

monitored using carbamazepine levels TDM, electrolyte levels, and liver and kidney function, CBC

causes ataxia, dizziness, diplopia, sedation, and persistent headaches

Phenytoin (Dilantin)

monitored using phenytoin TDM, electrolyte levels, Liver and kidney function

toxicity signs: ataxia, diplopia, dizziness, drowsiness, slurred speech, nausea, decreased appetite

Phenobarbital (Solfoton)

monitored using phenobarbital TDM levels, liver and renal function

toxicity signs: slow/shallow breathing, weak pulse, feeling cold, pinpoint pupils, fainting, confusion, sedation

Theophylline (Theo-Dur)

Monitored using theophylline blood levels TDM, and liver function

toxicity signs: seizures, disturbances in heart rhythm, severe vomiting, electrolyte disturbances (low K)

Levothyroxine (Synthroid, Levoxyl)

Monitored using TSH and free T4 Blood levels

toxicity signs: anxiety, hair loss, weight loss, tremors, heart palpitations, flushing od skin, heat intolerance

Lithium (Lithobid, Eskalith)

Monitored using lithium blood levels TDM, Na and TSH

Toxicity signs: muscle weakness, twitching, drowsiness, blurred vision, ringin in ears, confusion, slurred speech, irregular heartbeat, trouble breathing, seizures