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Drug Monitoring, Therapeutic

Drug Monitoring, Therapeutic is a topic covered in the Davis's Lab & Diagnostic Tests.

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Rationale
To monitor specific drugs for subtherapeutic, therapeutic, or toxic levels in evaluation of treatment and to detect toxic levels in suspected overdose.

Patient Preparation
There are no food, fluid, activity, or medication restrictions unless by medical direction; note the time and date of the last dose of medication taken. Obtain a culture, if ordered, before the first dose of aminoglycosides. Other considerations prior to medication administration include documentation of adequate renal function with creatinine (Cr) and blood urea nitrogen (BUN) levels, documentation of adequate hepatic function with alanine aminotransferase (ALT) and bilirubin levels, and documentation of adequate hematological and immune function with platelet and white blood cell (WBC) count. Patients receiving methotrexate must be well hydrated and, depending on the therapy, may be treated with sodium bicarbonate for urinary alkalinization to enhance drug excretion. Leucovorin calcium rescue therapy may also be part of the protocol.

Drug* (Anticonvulsants)Route of Administration
CarbamazepineOral
EthosuximideOral
LamotrigineOral
Phenobarbital Oral
Phenytoin Oral
PrimidoneOral
Valproic acid Oral
*Recommended collection time = trough: Immediately before next dose (at steady state) or at a consistent sampling time.
Drug (Antidepressants)Route of AdministrationRecommended Collection Time
Amitriptyline OralTrough: Immediately before next dose (at steady state)
Nortriptyline OralTrough: Immediately before next dose (at steady state)
Protriptyline Oral Trough: Immediately before next dose (at steady state)
Doxepin OralTrough: Immediately before next dose (at steady state)
Imipramine OralTrough: Immediately before next dose (at steady state)
Drug (Antidysrhythmics)Route of AdministrationRecommended Collection Time
AmiodaroneOralTrough: Immediately before next dose
DigoxinOralTrough: 12–24 hr after dose
Never draw peak samples
DisopyramideOralTrough: Immediately before next dose
Peak: 2–5 hr after dose
FlecainideOralTrough: Immediately before next dose
Peak: 3 hr after dose
LidocaineIV15 min, 1 hr, then every 24 hr
ProcainamideIV15 min; 2, 6, 12 hr; then every 24 hr
ProcainamideOralTrough: Immediately before next dose
Peak: 75 min after dose
Quinidine sulfateOralTrough: Immediately before next dose
Peak: 1 hr after dose
Quinidine gluconateOralTrough: Immediately before next dose
Peak: 5 hr after dose
Quinidine polygalacturonateOralTrough: Immediately before next dose
Peak: 2 hr after dose
Drug (Antimicrobials)Route of AdministrationRecommended Collection Time*
AmikacinIV, IMTrough: Immediately before next dose
Peak: 30 min after the end of a 30-min IV infusion
GentamicinIV, IMTrough: Immediately before next dose
Peak: 30 min after the end of a 30-min IV infusion
TobramycinIV, IMTrough: Immediately before next dose
Peak: 30 min after the end of a 30-min IV infusion
Tricyclic glycopeptide and vancomycinIV, POTrough: Immediately before next dose
Peak: 30–60 min after the end of a 60-min IV infusion
*Usually after fifth dose if given every 8 hr or third dose if given every 12 hr. IM = intramuscular; PO = by mouth.
Drug (Antipsychotics, Antimanics)Route of AdministrationRecommended Collection Time
HaloperidolOralPeak: 3–6 hr
Lithium OralTrough: at least 12 hr after last dose; steady state occurs at 90–120 hr
Drug (Immunosuppressants)Route of AdministrationRecommended Collection Time
Cyclosporine Oral or IV12 hr after dose or immediately prior to next dose
Methotrexate Oral or IMVaries according to dosing protocol
EverolimusOralImmediately prior to next dose
SirolimusOralImmediately prior to next dose
TacrolimusOralImmediately prior to next dose
Leucovorin therapy, also called leucovorin rescue, is used in conjunction with administration of methotrexate. Leucovorin, a fast-acting form of folic acid, protects healthy cells from the toxic effects of methotrexate.

Normal Findings
Method: Immunoassay for acetaminophen, amikacin, amiodarone, carbamazepine, cyclosporine, digoxin, disopyramide, ethosuximide, flecainide, gentamicin, imipramine, lidocaine, methotrexate, phenobarbital, phenytoin, primidone, procainamide, quinidine, salicylate, tobramycin, valproic acid, and vancomycin. Chromatography for amitriptyline, doxepin, haloperidol, nortriptyline, and protriptyline. Ion-selective electrode for lithium. Liquid chromatography/tandem mass spectrometry for everolimus, lamotrigine, sirolimus, and tacrolimus.

Drug/Class (Analgesics, Anti-inflammatories, and Antipyretics)Therapeutic Range Conventional UnitsConversion to SI unitsTherapeutic Range SI UnitsHalf-Life Protein BindingMetabolismExcretionCrosses Placenta/Enters Breast Milk
Acetaminophen5–20 mcg/mLSI units = Conventional Units × 6.6233–132 micromol/L1–3 hr10%–25% (dose dependent)1° hepatic (CYP2E1, CYP1A2, CYP2D6, UGT)1° renalYes/Yes (small amounts)
Salicylate10–30 mg/dL (anti-inflammatory); 2–10 mg/dL (antipyretic/analgesic)SI units = Conventional Units × 0.0730.7–2.2 mmol/L (anti-inflammatory); 0.15–0.7 mmol/L (antipyretic/analgesic)2–3 hr (low dose)80%–90%1° hepatic (CYP2C19)1° renalYes/Yes
It should be noted that acetaminophen and acetylsalicylic acid are contained in many other medications, such as cold and cough medicines.
Drug/Class (Anticonvulsants)Therapeutic Range Conventional UnitsConversion to SI UnitsTherapeutic Range SI UnitsHalf-Life Protein Binding MetabolismExcretionCrosses Placenta/Enters Breast Milk
Carbamazepine4–12 mcg/mLSI units = Conventional units × 4.2316.9–50.8 micromol/L15–40 hr (single dose); 16–24 hr (repeated dosing)70%–80%Hepatic (CYP3A4)1° renal; 2° fecalYes/Yes
Ethosuximide40–100 mcg/mLSI units = Conventional units × 7.08283.2–708 micromol/L25–70 hr0%–5%Hepatic (CYP3A4, CYP2E1)Renal (20%)Yes/Yes
Lamotrigine1–14 mcg/mLSI units = Conventional units × 3.93.9–54.6 micromol/L25–33 hr (monotherapy)50%–55%Hepatic (UGT1A4) 1° renal; 2° fecalNo information/Yes (Note: Significant binding to tissues containing melanin)
Phenobarbital Adult: 15–40 mcg/mLSI units = Conventional units × 4.31 Adult: 64.6–172.4 micromol/L Adult: 50–140 hr50%–60%Hepatic (CYP2C19)1° renal; 2° fecalYes/Unknown
Child: 15–30 mcg/mLSI units = Conventional units × 4.31 Child: 64.6–129.3 micromol/L Child: 60–180 hr50%–60%Hepatic (CYP2C19)1° renal; 2° fecalYes/Unknown
Phenytoin 10–20 mcg/mLSI units = Conventional units × 3.9640–79 micromol/L7–42 (avg 22) hr85%–95%Hepatic (CYP2C9, CYPC219)1° renal and biliaryYes/Yes
Primidone Adult: 5–12 mcg/mLSI units = Conventional units × 4.58 Adult: 22.9–55 micromol/L4–12 hr0%–20%Hepatic (CYPC219)1° renalYes/No information
Child: 7–10 mcg/mLSI units = Conventional units × 4.58 Child: 32.1–45.8 micromol/L
Valproic acid 50–125 mcg/mLSI units = Conventional units × 6.93346.5–866.2 micromol/L8–15 hr85%–95%Hepatic (not CYP450 dependent)1° renalYes/Yes
Drug/Class (Antidepressants)Therapeutic Range Conventional UnitsConversion to SI UnitsTherapeutic Range SI UnitsHalf-Life Protein Binding MetabolismExcretionCrosses Placenta/Enters Breast Milk
Amitriptyline 125–250 ng/mLSI units = Conventional units × 3.6450–900 nmol/L10–50 hr85%–95%Hepatic (CYP2D6)1° renalYes/Yes
Nortriptyline 50–150 ng/mLSI units = Conventional units × 3.8190–570 nmol/L16–90 hr90%–95%Hepatic (CYP2D6)RenalProbable/Yes
Protriptyline 70–250 ng/mL SI units = Conventional units × 3.8 266–950 nmol/L 60–90 hr 91%–93% Hepatic (CYP2D6) RenalNo information/Probable
Doxepin 110–250 ng/mLSI units = Conventional units × 3.58393.8–895 nmol/L10–25 hr75%–85%Hepatic (CYP2D6, CYP2C19, CYP1A2, CYP3A4)RenalProbable/Yes
Imipramine 180–240 ng/mLSI units = Conventional units × 3.57642.6–856.8 nmol/L8–20 hr86%–95%Hepatic (CYP1A2, CYP2C19, CYP2D6)1° renal; 2° fecalProbable/Yes
Drug/Class (Antidysrhythmics)Therapeutic Range Conventional UnitsConversion to SI UnitsTherapeutic Range SI UnitsHalf-Life Protein Binding MetabolismExcretionCrosses Placenta/Enters Breast Milk
Amiodarone 0.5–2.5 mcg/mLSI units = Conventional units × 1.550.8–3.9 micromol/L15–142 (58 avg) days90%–95%1° hepatic (CYP3A, CYP2C8)1° biliaryYes/Yes
Digoxin0.5–2 ng/mLSI units = Conventional units × 1.280.6–2.6 nmol/L36–48 hr20%–30%Hepatic (16%) (not CYP450 dependent)RenalYes/Yes
Disopyramide2.8–7 mcg/mLSI units = Conventional units × 2.958.3–20.6 micromol/L4–10 hr50%–65%Hepatic (CYP3A4)RenalYes/Yes
Flecainide 0.2–1 mcg/mLSI units = Conventional units × 2.410.5–2.4 micromol/L11–27 hr40%–50%Hepatic (CYP2D6)RenalProbable/Yes
Lidocaine 1.5–5 mcg/mLSI units = Conventional units × 4.276.4–21.4 micromol/L1.5–2 hr60%–80%1° hepatic (CYP3a4)RenalYes/Yes
Procainamide 4–10 mcg/mLSI units = Conventional units × 4.2517–42.5 micromol/L2–6 hr10%–20%Hepatic (CYP2D6)RenalYes/Yes
N-acetyl procainamide 10–20 mcg/mLSI units = Conventional units × 4.2542.5–85 micromol/L4–15 hr10%–20%Hepatic (CYP2D6)RenalYes/Yes
Quinidine 2–5 mcg/mLSI units = Conventional units × 3.086.2–15.4 micromol/L6–8 hr70%–90%Hepatic (CYP3A4)Hepatic (20% unchanged in urine)Yes/Yes
Drug/Class (Antimicrobials)Therapeutic Range Conventional UnitsConversion to SI UnitsTherapeutic Range SI UnitsHalf-LifeProtein BindingMetabolismExcretionCrosses Placenta/Enters Breast Milk
Amikacin Peak: 15–30 mcg/mL Trough: 4–8 mcg/mLSI units = Conventional units × 1.71Peak: 26–51 micromol/L Trough: 7–14 micromol/L2–4 hr50%Renal1° renalYes/Yes (small amts)
Gentamicin (standard dosing) Peak: 5–10 mcg/mL Trough: Less than 2 mcg/mLSI units = Conventional units × 2.09Peak: 10.4–20.9 micromol/L Trough: Less than 4.2 micromol/L2–4 hr50%Renal1° renalYes/Yes (small amts)
Tobramycin (standard dosing)Peak: 4–8 mcg/mL Trough: Less than 1 mcg/mLSI units = Conventional units × 2.09Peak: 8.4–16.7 micromol/L Trough: Less than 2.09 micromol/L2–4 hr50%Renal1° renalYes/Yes (small amts)
Tobramycin (once daily dosing)Peak: 8–12 mcg/mL Trough: Less than 0.5 mcg/mLSI units = Conventional units × 2.09Peak: 16.7–25 micromol/L Trough: Less than 1 micromol/L
VancomycinTrough (general) values vary with indication: 5–15 mcg/mLSI units = Conventional units × 0.693–10 micromol/L5–8 hr55%Renal1° renal (IV); feces (oral)Yes/No information
Drug/Class (Antipsychotics and Antimanics)Therapeutic Range Conventional UnitsConversion to SI UnitsTherapeutic Range SI UnitsHalf-Life Protein Binding MetabolismExcretionCrosses Placenta/Enters Breast Milk, Protein Binding (%)
Haloperidol6–24 ng/mLSI units = Conventional units × 2.6616–63.8 nmol/L21–24 hr90%Hepatic (CYP3A4)HepaticYes/Yes
Lithium (chronic) 0.6–1.2 mEq/LSI units = Conventional units × 10.6–1.2 mmol/L18–24 hr0%NoneRenalYes/Yes
Drug/Class (Immunosuppressants)Therapeutic Range Conventional UnitsConversion to SI UnitsTherapeutic Range SI UnitsHalf-Life Protein Binding MetabolismExcretionCrosses Placenta/Enters Breast Milk
Cyclosporine 100–300 ng/mL kidney transplantSI units = Conventional units × 0.83283.2–249.6 nmol/L8–24 hr90%–98%Hepatic (CYP3A4)BiliaryYes/Yes
200–350 ng/mL cardiac, hepatic, pancreatic transplantSI units = Conventional units × 0.832166.4–291.2 nmol/L8–24 hr90%–98%Hepatic (CYP3A4)BiliaryYes/Yes
100–300 ng/mL bone marrow transplantSI units = Conventional units × 0.83283.2–249.6 nmol/L8–24 hr90%–98%Hepatic (CYP3A4)BiliaryYes/Yes
Methotrexate Low dose: Less than 0.5 micromol/L after 48 hrSI units = Conventional units × 1Low dose: Less than 0.5 micromol/L after 48 hr3–10 hr (low dose)35%–50% (dosage dependent/varies individually)Hepatic and intracellular1° renal; 2° fecalYes (embryotoxic)/Yes
High dose: Less than 5 micromol/L at 24 hr; less than 0.5 micromol/L at 48 hr; less than 0.1 micromol/L at 72 hrSI units = Conventional units × 1High dose: Less than 5 micromol/L at 24 hr; less than 0.5 micromol/L at 48 hr; less than 0.1 micromol/L at 72 hr8–15 hr (high dose)35%–50% (dosage dependent/varies individually)Hepatic and intracellular1° renal; 2° fecalYes (embryotoxic)/Yes
EverolimusTransplant: 3–8 ng/mLSI units = Conventional units × 1.04Transplant: 3.1–8.3 nmol/L18–35 hr (kidney); 30–35 hr (liver)75%Hepatic (CYP3A4)1° fecal; 2° renalYes/Yes
Oncology: 5–10 ng/mLSI units = Conventional units × 1Oncology: 5–10 nmol/L18–35 hr75%Hepatic (CYP3A4)1° fecal; 2° renalYes/Yes
SirolimusMaintenance phase: kidney transplant: 4–12 ng/mL; liver transplant: 12–20 ng/mLSI units = Conventional units × 1.1Kidney transplant: 4.4–13.2 nmol/L; liver transplant: 13.2–22 nmol/L57–78 hr92%Hepatic (CYP3A4)1° fecalNo information
TacrolimusMaintenance phase: kidney transplant: 6–12 ng/mL; liver transplant: 4–10 ng/mL; pancreas transplant: 10–18 ng/mL; bone marrow transplant: 10–20 ng/mLSI units = Conventional units × 1.24Kidney transplant: 7.4–14.9 nmol/L; liver transplant: 5–12.4 nmol/L; pancreas transplant: 12.4–22.3 nmol/L; bone marrow transplant: 12.4–24.8 nmol/L10–14 hr99%Hepatic (CYP3A4, CYP3A5)1° fecalYes/Yes
Therapeutic targets for the initial phase post-transplantation are slightly higher than during the maintenance phase and are influenced by the specific therapy chosen for each patient with respect to coordination of treatment for other conditions and corresponding therapies. Therapeutic ranges for everolimus, sirolimus, and tacrolimus assume concomitant administration of cyclosporine and steroids.

Critical Findings and Potential Interventions

Note: The adverse effects of subtherapeutic levels are also important. Care should be taken to investigate signs and symptoms of too little and too much medication.

Timely notification to the requesting health-care provider (HCP) of any critical findings and related symptoms is a role expectation of the professional nurse. A listing of these findings varies among facilities.

Analgesics, Anti-inflammatories, and Antipyretics


Acetaminophen: Greater than 200 mcg/mL (4 hr Postingestion): (SI: Greater than 1,324 micromol/L [4 hr Postingestion])

Signs and symptoms of acetaminophen intoxication occur in stages over a period of time. In stage I (0 to 24 hr after ingestion), symptoms may include gastrointestinal (GI) irritation, pallor, lethargy, diaphoresis, metabolic acidosis, and possibly coma. In stage II (24 to 48 hr after ingestion), signs and symptoms may include right upper quadrant abdominal pain; elevated liver enzymes, aspartate aminotransferase (AST), and alanine aminotransferase (ALT); and possible decreased kidney function. In stage III (72 to 96 hr after ingestion), signs and symptoms may include nausea, vomiting, jaundice, confusion, coagulation disorders, continued elevation of AST and ALT, decreased kidney function, and coma. Intervention may include GI decontamination (stomach pumping) if the patient presents within 6 hr of ingestion or administration of N-acetylcysteine (Mucomyst) in the case of an acute intoxication.


Acetylsalicylic Acid (ASA): Greater than 40 mg/dL: (SI: Greater than 2.9 mmol/L)

Signs and symptoms of salicylate intoxication include ketosis, convulsions, dizziness, nausea, vomiting, hyperactivity, hyperglycemia, hyperpnea, hyperthermia, respiratory arrest, and tinnitus. Possible interventions include administration of activated charcoal as vomiting ceases, alkalinization of the urine with bicarbonate, and a single dose of vitamin K (for rare instances of hypoprothrombinemia).

Anticonvulsants


Carbamazepine: Greater than 20 mcg/mL (SI: Greater than 85 micromol/L)

Signs and symptoms of carbamazepine toxicity include respiratory depression, seizures, leukopenia, hyponatremia, hypotension, stupor, and possible coma. Possible interventions include gastric lavage (contraindicated if ileus is present); airway protection; administration of fluids and vasopressors for hypotension; treatment of seizures with diazepam, phenobarbital, or phenytoin; cardiac monitoring; monitoring of vital signs; and discontinuing the medication. Emetics are contraindicated.


Ethosuximide: Greater than 200 mcg/mL (SI: Greater than 1,416 micromol/L)

Signs and symptoms of ethosuximide toxicity include nausea, vomiting, and lethargy. Possible interventions include administration of activated charcoal, administration of saline cathartic and gastric lavage (contraindicated if ileus is present), airway protection, hourly assessment of neurological function, and discontinuing the medication.


Lamotrigine: Greater than 20 mcg/mL (SI: Greater than 78 micromol/L)

Signs and symptoms of lamotrigine toxicity include severe skin rash, nausea, vomiting, ataxia, decreased levels of consciousness, coma, increased seizures, nystagmus. Possible interventions include administration of activated charcoal, administration of saline cathartic and gastric lavage (contraindicated if ileus is present), airway protection, hourly assessment of neurologic function, and discontinuing the medication.


Phenobarbital: Greater than 60 mcg/mL (SI: Greater than 259 micromol/L)

Signs and symptoms of phenobarbital toxicity include cold, clammy skin; ataxia; central nervous system (CNS) depression; hypothermia; hypotension; cyanosis; Cheyne-Stokes respiration; tachycardia; possible coma; and possible renal impairment. Possible interventions include gastric lavage, administration of activated charcoal with cathartic, airway protection, possible intubation and mechanical ventilation (especially during gastric lavage if there is no gag reflex), monitoring for hypotension, and discontinuing the medication.


Phenytoin (Adults): Greater than 40 mcg/mL (SI: Greater than 158 micromol/L)

Signs and symptoms of phenytoin toxicity include double vision, nystagmus, lethargy, CNS depression, and possible coma. Possible interventions include airway support, electrocardiographic monitoring, administration of activated charcoal, gastric lavage with warm saline or tap water, administration of saline or sorbitol cathartic, and discontinuing the medication.


Primidone: Greater than 15 mcg/mL (SI: Greater than 69 micromol/L)

Signs and symptoms of primidone toxicity include ataxia, anemia, CNS depression, lethargy, somnolence, vertigo, and visual disturbances. Possible interventions include airway protection, treatment of anemia with vitamin B12 and folate, and discontinuing the medication.


Valproic acid: Greater than 200 mcg/mL (SI: Greater than 1,386 micromol/L)

Signs and symptoms of valproic acid toxicity include loss of appetite, mental changes, numbness, tingling, and weakness. Possible interventions include administration of activated charcoal and naloxone and discontinuing the medication.

Antidepressants


Amitriptyline: Greater than 500 ng/mL (SI: Greater than 1,800 nmol/L)
Nortriptyline: Greater than 500 ng/mL (SI: Greater than 1,900 nmol/L)
Protriptyline: Greater than 500 ng/mL (SI: Greater than 1,900 nmol/L)
Doxepin: Greater than 500 ng/mL (SI: Greater than 1,790 nmol/L)
Imipramine: Greater than 500 ng/mL (SI: Greater than 1,785 nmol/L)

Signs and symptoms of cyclic antidepressant toxicity include agitation, drowsiness, hallucinations, confusion, seizures, dysrhythmias, hyperthermia, flushing, dilation of the pupils, and possible coma. Possible interventions include administration of activated charcoal; emesis; gastric lavage with saline; administration of physostigmine to counteract seizures, hypertension, or respiratory depression; administration of bicarbonate, propranolol, lidocaine, or phenytoin to counteract dysrhythmias; and electrocardiographic monitoring.

Antidysrhythmics


Amiodarone: Greater than 2.5 mcg/mL (SI: Greater than 3.9 micromol/L)

Signs and symptoms of pulmonary damage related to amiodarone toxicity include bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Possible interventions include discontinuing the medication, monitoring pulmonary function with chest x-ray, monitoring liver function tests to assess for liver damage, monitoring thyroid function tests to assess for thyroid damage (related to the high concentration of iodine contained in the medication), and electrocardiographic (ECG) monitoring for worsening of dysrhythmia.


Digoxin: Greater than 2.5 ng/mL (SI: Greater than 3.2 nmol/L)

Signs and symptoms of digoxin toxicity include dysrhythmias, anorexia, hyperkalemia, nausea, vomiting, diarrhea, changes in mental status, and visual disturbances (objects appear yellow or have halos around them). Possible interventions include discontinuing the medication, continuous ECG monitoring (prolonged P-R interval, widening QRS interval, lengthening Q-Tc interval, and atrioventricular block), transcutaneous pacing, administration of activated charcoal (if the patient has a gag reflex and CNS function), support and treatment of electrolyte disturbance, and administration of Digibind or DigiFab (digoxin immune Fab). The amount of Digibind or DigiFab given depends on the level of digoxin to be neutralized. Digoxin levels must be measured before the administration of Digibind or DigiFab. Digoxin levels should not be measured for several days after administration of Digibind or DigiFab in patients with normal kidney function (1 wk or longer in patients with decreased kidney function). Digibind or DigiFab cross-reacts in the digoxin assay and may provide misleading elevations or decreases in values depending on the particular assay in use by the laboratory.


Disopyramide: Greater than 7 mcg/mL (SI: Greater than 20.6 micromol/L)

Signs and symptoms of disopyramide toxicity include prolonged Q-T interval, ventricular tachycardia, hypotension, and heart failure. Possible interventions include discontinuing the medication, airway support, and ECG and blood pressure monitoring.


Flecainide: Greater than 1 mcg/mL (SI: Greater than 2.41 micromol/L)

Signs and symptoms of flecainide toxicity include exaggerated pharmacological effects resulting in dysrhythmia. Possible interventions include discontinuing the medication as well as continuous ECG, respiratory, and blood pressure monitoring.


Lidocaine: Greater than 6 mcg/mL (SI: Greater than 25.6 micromol/L)

Signs and symptoms of lidocaine toxicity include slurred speech, CNS depression, cardiovascular depression, convulsions, muscle twitches, and possible coma. Possible interventions include continuous ECG monitoring, airway support, and seizure precautions.


Procainamide: Greater than 10 mcg/mL (SI: Greater than 42.5 micromol/L) ; N-Acetyl Procainamide: Greater than 40 mcg/mL (SI: Greater than 170 micromol/L)

The active metabolite of procainamide is N-acetyl procainamide (NAPA). Signs and symptoms of procainamide toxicity include torsade de pointes (ventricular tachycardia), nausea, vomiting, agranulocytosis, and hepatic disturbances. Possible interventions include airway protection, emesis, gastric lavage, and administration of sodium lactate.


Quinidine: Greater than 6 mcg/mL (SI: Greater than 18.5 micromol/L)

Signs and symptoms of quinidine toxicity include ataxia, nausea, vomiting, diarrhea, respiratory system depression, hypotension, syncope, anuria, dysrhythmias (heart block, widening of QRS and Q-T intervals), asystole, hallucinations, paresthesia, and irritability. Possible interventions include airway support, emesis, gastric lavage, administration of activated charcoal, administration of sodium lactate, and temporary transcutaneous or transvenous pacemaker.

Antimicrobials


Amikacin: Greater than 10 mcg/mL (SI: Greater than 17 micromol/L)
Gentamicin: Peak Greater than 12 mcg/mL, Trough Greater than 2 mcg/mL (SI: Peak Greater than 25 micromol/L, Trough Greater than 4 micromol/L)
Tobramycin: Peak Greater than 12 mcg/mL, Trough Greater than 2 mcg/mL (SI: Peak Treater than 25 micromol/L, Trough Greater than 4 micromol/L)
Vancomycin: Trough Greater than 30 mcg/mL (SI: Trough Greater than 21 micromol/L)

Signs and symptoms of toxic levels of the antibiotics gentamicin and tobramycin are similar and include loss of hearing and decreased renal function. Suspected hearing loss can be evaluated by audiometry testing. Impaired renal function may be identified by monitoring blood urea nitrogen and creatinine levels as well as intake and output. The most important intervention is accurate therapeutic drug monitoring so the medication can be discontinued before irreversible damage is done.

Antipsychotics and Antimanics


Haloperidol: Greater than 42 ng/mL (SI: Greater than 112 nmol/L)

Signs and symptoms of haloperidol toxicity include hypotension, myocardial depression, respiratory depression, and extrapyramidal neuromuscular reactions. Possible interventions include emesis (contraindicated in the absence of gag reflex or central nervous system depression or excitation) and gastric lavage followed by administration of activated charcoal.


Lithium: Greater than 2 mEq/L (SI: Greater than 2 mmol/L)

Signs and symptoms of lithium toxicity include ataxia, coarse tremors, muscle rigidity, vomiting, diarrhea, confusion, convulsions, stupor, T-wave flattening, loss of consciousness, and possible coma. Possible interventions include administration of activated charcoal, gastric lavage, and administration of intravenous fluids with diuresis.

Immunosuppressants


Cyclosporine: Greater than 500 ng/mL (SI: Greater than 416 nmol/L)

Signs and symptoms of cyclosporine toxicity include increased severity of expected adverse effects, which include nausea, stomatitis, vomiting, anorexia, hypertension, infection, fluid retention, hypercalcemic metabolic acidosis, tremor, seizures, headache, and flushing. Possible interventions include close monitoring of blood levels to make dosing adjustments, inducing emesis (if orally ingested), performing gastric lavage (if orally ingested), withholding the drug, and initiating alternative therapy for a short time until the patient is stabilized.


Methotrexate: Greater than 5 micromol/L

Signs and symptoms of methotrexate toxicity include increased severity of expected adverse effects, which include nausea, stomatitis, vomiting, anorexia, bleeding, infection, bone marrow depression, and, over a prolonged period of use, hepatotoxicity. The effect of methotrexate on normal cells can be reversed by administration of 5-formyltetrahydrofolate (citrovorum or leucovorin). 5-Formyltetrahydrofolate allows higher doses of methotrexate to be given.


Everolimus: Greater than 15 ng/mL (SI: Greater than 15 mcg/L)

Signs and symptoms of everolimus pulmonary toxicity include hypoxia, pleural effusion, cough, and dyspnea. Possible interventions include dosing adjustments, administration of corticosteroids, and monitoring of pulmonary function with chest x-ray. Use of everolimus is contraindicated in patients with severe hepatic impairment. Concomitant administration of strong CYP3A4 inhibitors may significantly increase everolimus levels.


Sirolimus: Greater than 25 ng/mL (SI: Greater than 28 mcg/L)

Signs and symptoms of sirolimus pulmonary toxicity include cough, shortness of breath, chest pain, and rapid heart rate. Possible interventions include dosing adjustments, administration of corticosteroids, and monitoring of pulmonary function with chest x-ray.


Tacrolimus: Greater than 25 ng/mL (SI: Greater than 31 mcg/L)

Signs and symptoms of tacrolimus toxicity include tremors, seizures, headache, high blood pressure, hyperkalemia, tinnitus, nausea, and vomiting. Possible interventions include treatment of hypertension, administration of antiemetics for nausea and vomiting, and dosing adjustments.

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Citation

Bladh, Mickey Lynn., and Anne M. Van Leeuwen. "Drug Monitoring, Therapeutic." Davis's Lab & Diagnostic Tests, 7th ed., F.A. Davis Company, 2017. Nursing Central, nursing.unboundmedicine.com/nursingcentral/view/Davis-Lab-and-Diagnostic-Tests/425446/all/Drug_Monitoring_Therapeutic.
Bladh ML, Van Leeuwen AM. Drug Monitoring, Therapeutic. Davis's Lab & Diagnostic Tests. 7th ed. F.A. Davis Company; 2017. https://nursing.unboundmedicine.com/nursingcentral/view/Davis-Lab-and-Diagnostic-Tests/425446/all/Drug_Monitoring_Therapeutic. Accessed July 21, 2019.
Bladh, M. L., & Van Leeuwen, A. M. (2017). Drug Monitoring, Therapeutic. In Davis's Lab & Diagnostic Tests. Available from https://nursing.unboundmedicine.com/nursingcentral/view/Davis-Lab-and-Diagnostic-Tests/425446/all/Drug_Monitoring_Therapeutic
Bladh ML, Van Leeuwen AM. Drug Monitoring, Therapeutic [Internet]. In: Davis's Lab & Diagnostic Tests. F.A. Davis Company; 2017. [cited 2019 July 21]. Available from: https://nursing.unboundmedicine.com/nursingcentral/view/Davis-Lab-and-Diagnostic-Tests/425446/all/Drug_Monitoring_Therapeutic.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Drug Monitoring, Therapeutic ID - 425446 A1 - Bladh,Mickey Lynn, AU - Van Leeuwen,Anne M, BT - Davis's Laboratory & Diagnostic Tests UR - https://nursing.unboundmedicine.com/nursingcentral/view/Davis-Lab-and-Diagnostic-Tests/425446/all/Drug_Monitoring_Therapeutic PB - F.A. Davis Company ET - 7 DB - Nursing Central DP - Unbound Medicine ER -