General
Synonym/Acronym:
N/A
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 Cr and BUN levels, documentation of adequate hepatic function with ALT and TBil levels, and documentation of adequate hematological and immune function with platelet and 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 |
|---|
| Carbamazepine | PO |
| Ethosuximide | PO |
| Lamotrigine | PO |
| Phenobarbital | PO |
| Phenytoin | PO |
| Primidone | PO |
| Valproic acid | PO |
|
| *Recommended collection time = trough: Immediately before next dose (at steady state) or at a consistent sampling time. |
| Drug (Antidepressants) | Route of Administration | Recommended Collection Time |
|---|
| Amitriptyline | PO | Trough: Immediately before next dose (at steady state) |
| Nortriptyline | PO | Trough: Immediately before next dose (at steady state) |
| Protriptyline | PO | Trough: Immediately before next dose (at steady state) |
| Doxepin | PO | Trough: Immediately before next dose (at steady state) |
| Imipramine | PO | Trough: Immediately before next dose (at steady state) |
| Drug (Antidysrhythmics) | Route of Administration | Recommended Collection Time |
|---|
| Amiodarone | PO | Trough: Immediately before next dose |
| Digoxin | PO | Trough: 12–24 hr after dose |
| Never draw peak samples |
| Disopyramide | PO | Trough: Immediately before next dose |
| Peak: 2–5 hr after dose |
| Flecainide | PO | Trough: Immediately before next dose |
| Peak: 3 hr after dose |
| Lidocaine | IV | 15 min, 1 hr, then every 24 hr |
| Procainamide | IV | 15 min; 2, 6, 12 hr; then every 24 hr |
| Procainamide | PO | Trough: Immediately before next dose |
| Peak: 75 min after dose |
| Quinidine sulfate | PO | Trough: Immediately before next dose |
| Peak: 1 hr after dose |
| Quinidine gluconate | PO | Trough: Immediately before next dose |
| Peak: 5 hr after dose |
| Quinidine polygalacturonate | PO | Trough: Immediately before next dose |
| | Peak: 2 hr after dose |
| Drug (Antimicrobials) | Route of Administration | Recommended Collection Time* |
|---|
| Amikacin | IV, IM | Trough: Immediately before next dose |
| Peak: 30 min after the end of a 30-min IV infusion |
| Gentamicin | IV, IM | Trough: Immediately before next dose |
| Peak: 30 min after the end of a 30-min IV infusion |
| Tobramycin | IV, IM | Trough: Immediately before next dose |
| Peak: 30 min after the end of a 30-min IV infusion |
| Tricyclic glycopeptide and vancomycin | IV, PO | Trough: 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, Mood Stabilizers) | Route of Administration | Recommended Collection Time |
|---|
| Haloperidol | PO | Peak: 3–6 hr |
| Lithium | PO | Trough: at least 12 hr after last dose; steady state occurs at 90–120 hr |
| Drug (Immunosuppressants) | Route of Administration | Recommended Collection Time |
|---|
| Cyclosporine | PO or IV | 12 hr after dose or immediately prior to next dose |
| Methotrexate | PO or IM | Varies according to dosing protocol |
| Everolimus | PO | Immediately prior to next dose |
| Sirolimus | PO | Immediately prior to next dose |
| Tacrolimus | PO | Immediately 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 Units | Conversion to SI Units | Therapeutic Range SI Units | Half-Life | Protein Binding | Metabolism | Excretion | Crosses Placenta/Enters Breast Milk |
|---|
| Acetaminophen | 5–20 mcg/mL | SI units = Conventional Units × 6.62 | 33–132 micromol/L | 1–3 hr | 10%–25% (dose dependent) | 1° hepatic (CYP2E1, CYP1A2, CYP2D6, UGT) | 1° renal | Yes/Yes (small amounts) |
| Salicylate | 10–30 mg/dL (anti-inflammatory); 2–10 mg/dL (antipyretic/analgesic) | SI units = Conventional Units × 0.073 | 0.7–2.2 mmol/L (anti-inflammatory); 0.15–0.7 mmol/L (antipyretic/analgesic) | 2–3 hr (low dose) | 80%–90% | 1° hepatic (CYP2C19) | 1° renal | Yes/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 Units | Conversion to SI Units | Therapeutic Range SI Units | Half-Life | Protein Binding | Metabolism | Excretion | Crosses Placenta/Enters Breast Milk |
| Carbamazepine | 4–12 mcg/mL | SI units = Conventional units × 4.23 | 16.9–50.8 micromol/L | 15–40 hr (single dose); 16–24 hr (repeated dosing) | 70%–80% | Hepatic (CYP3A4) | 1° renal; 2° fecal | Yes/Yes |
| Ethosuximide | 40–100 mcg/mL | SI units = Conventional units × 7.08 | 283.2–708 micromol/L | 25–70 hr | 0%–5% | Hepatic (CYP3A4, CYP2E1) | Renal (20%) | Yes/Yes |
| Lamotrigine | 1–14 mcg/mL | SI units = Conventional units × 3.9 | 3.9–54.6 micromol/L | 25–33 hr (monotherapy) | 50%–55% | Hepatic (UGT1A4) | 1° renal; 2° fecal | No information/Yes (Note: Significant binding to tissues containing melanin) |
| Phenobarbital | Adult: 15–40 mcg/mL | SI units = Conventional units × 4.31 | Adult: 64.6–172.4 micromol/L | Adult: 50–140 hr | 50%–60% | Hepatic (CYP2C19) | 1° renal; 2° fecal | Yes/Unknown |
| Child: 15–30 mcg/mL | SI units = Conventional units × 4.31 | Child: 64.6–129.3 micromol/L | Child: 60–180 hr | 50%–60% | Hepatic (CYP2C19) | 1° renal; 2° fecal | Yes/Unknown |
| Phenytoin | 10–20 mcg/mL | SI units = Conventional units × 3.96 | 40–79 micromol/L | 7–42 (avg 22) hr | 85%–95% | Hepatic (CYP2C9, CYPC219) | 1° renal and biliary | Yes/Yes |
| Primidone | Adult: 5–12 mcg/mL | SI units = Conventional units × 4.58 | Adult: 22.9–55 micromol/L | 4–12 hr | 0%–20% | Hepatic (CYPC219) | 1° renal | Yes/No information |
| Child: 7–10 mcg/mL | SI units = Conventional units × 4.58 | Child: 32.1–45.8 micromol/L | | | | | |
| Valproic acid | 50–125 mcg/mL | SI units = Conventional units × 6.93 | 346.5–866.2 micromol/L | 8–15 hr | 85%–95% | Hepatic (not CYP450 dependent) | 1° renal | Yes/Yes |
| Drug/Class (Antidepressants) | Therapeutic Range Conventional Units | Conversion to SI Units | Therapeutic Range SI Units | Half-Life | Protein Binding | Metabolism | Excretion | Crosses Placenta/Enters Breast Milk |
|---|
| Amitriptyline | 125–250 ng/mL | SI units = Conventional units × 3.6 | 450–900 nmol/L | 10–50 hr | 85%–95% | Hepatic (CYP2D6) | 1° renal | Yes/Yes |
| Nortriptyline | 50–150 ng/mL | SI units = Conventional units × 3.8 | 190–570 nmol/L | 16–90 hr | 90%–95% | Hepatic (CYP2D6) | Renal | Probable/Yes |
| Protriptyline | 70–250 ng/mL | SI units = Conventional units × 3.8 | 266–950 nmol/L | 60–90 hr | 91%–93% | Hepatic (CYP2D6) | Renal | No information/Probable |
| Doxepin | 110–250 ng/mL | SI units = Conventional units × 3.58 | 393.8–895 nmol/L | 10–25 hr | 75%–85% | Hepatic (CYP2D6, CYP2C19, CYP1A2, CYP3A4) | Renal | Probable/Yes |
| Imipramine | 180–240 ng/mL | SI units = Conventional units × 3.57 | 642.6–856.8 nmol/L | 8–20 hr | 86%–95% | Hepatic (CYP1A2, CYP2C19, CYP2D6) | 1° renal; 2° fecal | Probable/Yes |
| Drug/Class (Antidysrhythmics) | Therapeutic Range Conventional Units | Conversion to SI Units | Therapeutic Range SI Units | Half-Life | Protein Binding | Metabolism | Excretion | Crosses Placenta/Enters Breast Milk |
|---|
| Amiodarone | 0.5–2.5 mcg/mL | SI units = Conventional units × 1.55 | 0.8–3.9 micromol/L | 15–142 (58 avg) days | 90%–95% | 1° hepatic (CYP3A, CYP2C8) | 1° biliary | Yes/Yes |
| Digoxin | 0.5–2 ng/mL | SI units = Conventional units × 1.28 | 0.6–2.6 nmol/L | 36–48 hr | 20%–30% | Hepatic (16%) (not CYP450 dependent) | Renal | Yes/Yes |
| Disopyramide | 2.8–7 mcg/mL | SI units = Conventional units × 2.95 | 8.3–20.6 micromol/L | 4–10 hr | 50%–65% | Hepatic (CYP3A4) | Renal | Yes/Yes |
| Flecainide | 0.2–1 mcg/mL | SI units = Conventional units × 2.41 | 0.5–2.4 micromol/L | 11–27 hr | 40%–50% | Hepatic (CYP2D6) | Renal | Probable/Yes |
| Lidocaine | 1.5–5 mcg/mL | SI units = Conventional units × 4.27 | 6.4–21.4 micromol/L | 1.5–2 hr | 60%–80% | 1° hepatic (CYP3a4) | Renal | Yes/Yes |
| Procainamide | 4–10 mcg/mL | SI units = Conventional units × 4.25 | 17–42.5 micromol/L | 2–6 hr | 10%–20% | Hepatic (CYP2D6) | Renal | Yes/Yes |
| N-acetyl procainamide | 10–20 mcg/mL | SI units = Conventional units × 4.25 | 42.5–85 micromol/L | 4–15 hr | 10%–20% | Hepatic (CYP2D6) | Renal | Yes/Yes |
| Quinidine | 2–5 mcg/mL | SI units = Conventional units × 3.08 | 6.2–15.4 micromol/L | 6–8 hr | 70%–90% | Hepatic (CYP3A4) | Hepatic (20% unchanged in urine) | Yes/Yes |
| Drug/Class (Antimicrobials) | Therapeutic Range Conventional Units | Conversion to SI Units | Therapeutic Range SI Units | Half-Life | Protein Binding | Metabolism | Excretion | Crosses Placenta/Enters Breast Milk |
|---|
| Amikacin | Peak: 15–30 mcg/mLTrough: 4–8 mcg/mL | SI units = Conventional units × 1.71 | Peak: 26–51 micromol/L Trough: 7–14 micromol/L | 2–4 hr | 50% | Renal | 1° renal | Yes/Yes (small amts) |
| Gentamicin (standard dosing) | Peak: 5–10 mcg/mLTrough: Less than 2 mcg/mL | SI units = Conventional units × 2.09 | Peak: 10.4–20.9 micromol/L Trough: Less than 4.2 micromol/L | 2–4 hr | 50% | Renal | 1° renal | Yes/Yes (small amts) |
| Tobramycin (standard dosing) | Peak: 4–8 mcg/mLTrough: Less than 1 mcg/mL | SI units = Conventional units × 2.09 | Peak: 8.4–16.7 micromol/L Trough: Less than 2.09 micromol/L | 2–4 hr | 50% | Renal | 1° renal | Yes/Yes (small amts) |
| Tobramycin (once daily dosing) | Peak: 8–12 mcg/mL Trough: Less than 0.5 mcg/mL | SI units = Conventional units × 2.09 | Peak: 16.7–25 micromol/L Trough: Less than 1 micromol/L | | | | | |
| Vancomycin | Trough (general) values vary with indication: 5–15 mcg/mL | SI units = Conventional units × 0.69 | 3–10 micromol/L | 5–8 hr | 55% | Renal | 1° renal (IV); feces (oral) | Yes/No information |
| Drug/Class (Antipsychotics and Mood Stabilizers) | Therapeutic Range Conventional Units | Conversion to SI Units | Therapeutic Range SI Units | Half-Life | Protein Binding | Metabolism | Excretion | Crosses Placenta/Enters Breast Milk, Protein Binding (%) |
|---|
| Haloperidol | 6–24 ng/mL | SI units = Conventional units × 2.66 | 16–63.8 nmol/L | 21–24 hr | 90% | Hepatic (CYP3A4) | Hepatic | Yes/Yes |
| Lithium (chronic) | 0.6–1.2 mEq/L | SI units = Conventional units × 1 | 0.6–1.2 mmol/L | 18–24 hr | 0% | None | Renal | Yes/Yes |
| Drug/Class (Immunosuppressants) | Therapeutic Range Conventional Units | Conversion to SI Units | Therapeutic Range SI Units | Half-Life | Protein Binding | Metabolism | Excretion | Crosses Placenta/Enters Breast Milk |
|---|
| Cyclosporine | 100–300 ng/mL kidney transplant | SI units = Conventional units × 0.832 | 83.2–249.6 nmol/L | 8–24 hr | 90%–98% | Hepatic (CYP3A4) | Biliary | Yes/Yes |
| 200–350 ng/mL cardiac, hepatic, pancreatic transplant | SI units = Conventional units × 0.832 | 166.4–291.2 nmol/L | 8–24 hr | 90%–98% | Hepatic (CYP3A4) | Biliary | Yes/Yes |
| 100–300 ng/mL bone marrow transplant | SI units = Conventional units × 0.832 | 83.2–249.6 nmol/L | 8–24 hr | 90%–98% | Hepatic (CYP3A4) | Biliary | Yes/Yes |
| Methotrexate | Low dose: Less than 0.5 micromol/L after 48 hr | SI units = Conventional units × 1 | Low dose: Less than 0.5 micromol/L after 48 hr | 3–10 hr (low dose) | 35%–50% (dosage dependent/varies individually) | Hepatic and intracellular | 1° renal; 2° fecal | Yes (embryotoxic)/Yes |
| Drug/Class (Immunosuppressants) | Therapeutic Range Conventional Units | Conversion to SI Units | Therapeutic Range SI Units | Half-Life | Protein Binding | Metabolism | Excretion | Crosses Placenta/Enters Breast Milk |
| 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 hr | SI units = Conventional units × 1 | 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 hr | 8–15 hr (high dose) | 35%–50% (dosage dependent/varies individually) | Hepatic and intracellular | 1° renal; 2° fecal | Yes (embryotoxic)/Yes |
| Everolimus | Transplant: 3–8 ng/mL | SI units = Conventional units × 1.04 | Transplant: 3.1–8.3 nmol/L | 18–35 hr (kidney); 30–35 hr (liver) | 75% | Hepatic (CYP3A4) | 1° fecal; 2° renal | Yes/Yes |
| Oncology: 5–10 ng/mL | SI units = Conventional units × 1 | Oncology: 5–10 nmol/L | 18–35 hr | 75% | Hepatic (CYP3A4) | 1° fecal; 2° renal | Yes/Yes |
| Sirolimus | Maintenance phase: kidney transplant: 4–12 ng/mL; liver transplant: 12–20 ng/mL | SI units = Conventional units × 1.1 | Kidney transplant: 4.4–13.2 nmol/L; liver transplant: 13.2–22 nmol/L | 57–78 hr | 92% | Hepatic (CYP3A4) | 1° fecal | No information |
| Tacrolimus | Maintenance 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/mL | SI units = Conventional units × 1.24 | Kidney 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/L | 10–14 hr | 99% | Hepatic (CYP3A4, CYP3A5) | 1° fecal | Yes/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. Potential interventions depend on the length of time the toxicity has persisted. Toxicity noted within 1 hr may be treated with gastric decontamination (stomach pumping) or if alert, administration of activated charcoal. Those with a high level of acetaminophen may be treated within 8 hr of ingestion with N-acetyl-cysteine (NAC) to protect against liver toxicity. Acute toxicity can lead to renal failure. Recommended interventions include hemodialysis, and the administration of NAC to see if it helps. Transplant referral may be considered.
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. Potential interventions include administration of activated charcoal and gastric lavage within 60 minutes of ingestion; whole bowel irrigation may be considered in some cases; alkalinization of the urine with bicarbonate; hemodialysis, and a single dose of vitamin K (for rare instances of hypoprothrombinemia). Consider intubation for those with worsening mental and respiratory status.
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. Potential interventions include gastric lavage within 60 min of ingestion; whole bowel irrigation with protected airway (complications include ileus or bowel obstruction); administration of multi-dose activated charcoal; charcoal hemoperfusion; hemodialysis or plasmapheresis; intravenous lipid emulsion; airway protection and support; administration of fluids and vasopressors for hypotension; benzodiazepine (lorazepam, diazepam) to prevent seizures; cardiac monitoring; sodium bicarbonate (wide QRS greater than 100 msec); monitoring of vital signs; and discontinuing the medication. Emesis induction not recommended due to risk of CNS depression and seizures. 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. Potential interventions include administration of activated charcoal; charcoal hemoperfusion; cathartics; emesis unless obtunded, convulsing, or comatose (no emetics); gastric lavage (contraindicated if ileus is present); hemodialysis; airway protection and support; assisted ventilation or intubation if needed; suction as necessary; beta agonist such as albuterol for severe bronchospasm; hourly assessment of neurological function; administer diazepam or lorazepam for seizures; anticipate and treat shock; monitor and treat cardiac arrhythmias. Discontinue 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. Potential interventions include frequent vital signs; induced emesis with airway protection; administration of multiple dose activated charcoal; administration of saline cathartic and gastric lavage (contraindicated if ileus is present); airway protection and support; hourly assessment of neurologic function; medication discontinuation; hemodialysis may be considered.
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. Potential interventions include administration of activated charcoal; consider gastric lavage; airway protection and support; possible intubation and mechanical ventilation (especially during gastric lavage if there is no gag reflex); monitoring for hypotension; forced alkaline diuresis; hemodialysis; administration of bemegride as a CNS stimulant; and medication discontinuation.
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. Potential interventions include airway protection and support; intubation with assisted or mechanical ventilation; monitor for and manage hypotension with isotonic solution bolus; initiate vasopressors (norepinephrine or dopamine); cardiac (ECG) monitoring with ACLS bradycardia management (atropine, epinephrine, transcutaneous or transvenous pacing); administration of activated charcoal within 1 hr of ingestion unless depressed metal state; benzodiazepines, phenobarbital or levetiracetam for persistent seizures; not recommended are induced emesis, gastric lavage, or whole bowel irrigation; hemodialysis is controversial and should be used with caution; 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. Potential interventions include symptom management; supportive treatment; urine alkalinization; forced diuresis; possible hemodialysis; airway protection and support; assisted or mechanical ventilation; possible albuterol for bronchospasam; seizure management with diazepam or lorazepam; suction as needed; no emetics or forced emesis due to aspiration risk; cautiously treat hypotension with fluids considering overload risk; medication discontinuation.
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. Potential interventions include airway protection and support with assisted or mechanical ventilation; hypotension management with boluses of isotonic crystalloid and vasopressors; possible benzodiazepines for seizure management; administration of activated charcoal within 2 hours of ingestion unless there is aspiration risk due to patient sedation; activated charcoal can be given more than 2 hr after ingestion if the medication was enteric coated; administration of L-carnitine for those who present with altered mental status; opioid antagonist naloxone to reverse CNS depression; consider hemodialysis and hemoperfusion; and discontinuation of 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. Potential interventions include administration of activated charcoal within 2 hr of ingestion with protected airway; no emesis induction; airway protection and support; assisted airway or mechanical ventilation; use of benzodiazepines, phenobarbital, or propofol for seizure management; intralipid emulsion, sodium bicarbonate for the hemodynamically unstable, dysrhythmias; temporary pacemaker; fluids and vasopressors (norepinephrine) for hypotension; gastric lavage for the significantly toxic; and cardiac (ECG) 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. Potential interventions include activated charcoal for acute oral ingestions; 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 cardiac (ECG) monitoring for worsening of dysrhythmia, bradycardia, VT; temporary pacemaker; monitor for hypotension, vasopressors; discontinuing the medication.
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). Potential interventions include discontinuing the medication; continuous cardiac (ECG) monitoring (prolonged P-R interval, widening QRS interval, lengthening Q-Tc interval, and atrioventricular block); transcutaneous pacing; administration of multidose activated charcoal (if the patient has a gag reflex and CNS function)most effective when given within 6 to 8 hr of ingestion; monitoring electrolyte levels potassium, calcium, serum creatinine, and digoxin; support and treatment of electrolyte disturbance; administration of atropine for the hemodynamically unstable bradyarrhythmic; administration of lidocaine for VT; 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. If Digibind or DigiFab is not available, multidose activated charcoal, atropine, and antidysrhythmics phenytoin or lidocaine may be used. Hemodialysis may be used with severe toxicity. Binding resins such as cholestyramine and colestipol may break enterohepatic circulation.
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. Potential interventions include gastrointestinal decontamination by lavage; multidose activated charcoal and cathartic; discontinuing the medication; airway protection and support; cardiac (ECG) monitoring and treatment for bradyarrhythmia, ventricular tachycardia, torsade de pointes; hemodialysis or hemoperfusion for large dose ingestion; administration of diazepam, phenytoin, or phenobarbital for seizures; administration of fluids and vasopressors for hypotension.
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. Potential interventions include discontinuing the medication; gastrointestinal decontamination, gastric lavage unless unconscious within 1 hr of ingestion; administer atropine, pacing prior to intubation and lavage to prevent vagal stimulation; administer activated charcoal unless contraindicated; continuous cardiac (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. Potential interventions include continuous cardiac (ECG) monitoring; airway protection and support; and seizure precautions and administration of benzodiazepines, barbiturates, propofol; oxygen hyperventilation to raise the seizure threshold; administration of lipid emulsions to bind free circulating local anesthetics.
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. Potential interventions include airway protection and support; emesis; cardiac (ECG) monitoring, asystole, heart block, ventricular arrhythmias; gastric lavage; seizure precautions; administration of sodium lactate; monitor for hypotension; and administration of hypertonic sodium bicarbonate.
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, torsades de pointes), asystole, hallucinations, paresthesia, and irritability. Potential interventions include airway protection and support; hypoxia management; administration of sodium lactate; monitoring potassium and magnesium; cardiac (ECG) monitoring and temporary transcutaneous or transvenous pacemaker, cardioversion; administer magnesium sulfate for torsades de pointes; medication discontinuation.
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. Potential interventions include supportive treatment; airway support and protection; oxygen administration and mechanical ventilation; managing fluid and electrolytes; monitor for superinfections; monitor for nephrotoxicity; assess for ototoxicity; consider hemodialysis; medication discontiunation.
Antipsychotics and Mood Stabilizers
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. Potential interventions include emesis induction (contraindicated in the absence of gag reflex or central nervous system depression or excitation) and gastric lavage followed by administration of activated charcoal; airway protection and support; airway maintenance with use of oropharyngeal airway, endotracheal tube, tracheostomy, mechanical ventilation; manage hypotension with IV fluids, concentrated albumin, vasopressors phenylephrine or norepinephrine; cardiac (ECG) monitorng, dysrhythmias, torsades de pointes, Q-T prolongation; discontinue medication.
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. Potential interventions include whole bowel irrigation; gastric lavage; administration of intravenous fluids with diuresis, electrolyte management; consider hemodialysis; peritoneal dialysis if hemodialysis is unavailable; discontinue medication; consider anticonvulsant medication.
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. Potential interventions include close monitoring of blood levels to make dosing adjustments; inducing emesis (if orally ingested); performing gastric lavage (if orally ingested); airway protection and support; assisted or mechanical ventilation; seizure precautions; withholding the drug, and initiating alternative therapy for a short time until the patient is stabilized. Medications that may be considered to help decrease drug levels are rifampicin, rifabutin, isoniazid, barbiturates, phenytoin, carbamazepine, intravenous trimethoprim, intravenous sulfadimidine, imipenem, cephalosporins, terbinafine, ciprofloxacin, ticlopidine, octreotide, and nefazodone.
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. Potential interventions include immediate toxicity treatment with administration of leucovorin, thymidine, glucarpidase; adequate fluid hydration; urinary alkalinization with sodium bicarbonate; consider hemodialysis and hemoperfusion.
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.
Davis's Lab & Diagnostic Tests
