Therapeutic drug monitoring (TDM) is a collaborative clinical practice involving pharmacists, doctors, and nurses. A doctor will diagnose a patient and select the drug to treat the disease. A pharmacist will determine the dosage schedule often using weight and kidney function. A nurse will administer the drug as well as draw the blood at designated intervals to determine the drug concentration. A pharmacist and physician will interpret these levels and adjust the medication if indicated.
Each health care professional has an essential role in optimizing the patient’s dosage regimen.
TDM may seem daunting and it may be hard to wrap your head around why you’re doing what you are doing, however once you gain an understanding of the fundamental concepts of TDM, everything will come together and make sense! If you’re ever unsure, remember you can always check in with a senior nurse or doctor.
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TDM is NOT a practice that is standard for most drugs. Most drugs you encounter will be dosed in a standard fashion (i.e. acetaminophen 500mg every 6-8 hours as needed (max dose=4g per 24 hours).
However, some drugs have variable pharmacokinetic properties or narrow therapeutic ranges and as a result TDM is necessary. For example, if your patient has recently had an organ transplant, TDM is often used to ensure that the immunosuppressants are within the therapeutic range to prevent organ rejection while also preventing unwanted adverse effects - like a kidney injury.
Pharmacokinetics is used to describe the absorption, metabolism, distribution, and excretion of the drug or how the body interacts with a drug. For drugs with variable properties, each person’s body will interact with these drugs differently. It’s hard to optimize and dose the drug because even with standard doses, different drug concentrations will be found in each individual’s blood.
Drugs with a narrow therapeutic range have a small range of drug concentration levels where the drug will be safe and effective. Dosing for these sorts of drugs is a balancing act between safety and efficacy.
For example, drug concentrations with lower levels are subclinical and pose a risk of treatment failure while drug concentration with higher levels have a high risk of drug toxicity.
Usually drugs that are the most common candidates for TDM are ones that have severe side effects such as causing kidney failure (nephrotoxic). We use TDM and the monitoring of blood levels to target this narrow range when administering these drugs. Through years of study, target levels have become standardized for drugs and allow for the continued use of necessary but potentially harmful drugs.
Drugs such as mycophenolic acid, lithium, digoxin, aminoglycosides, and vancomycin all follow their own specific guidelines for TDM. The rest of this article will focus on TDM of vancomycin, explaining the rationale behind recommendations and the essential role you have as nurses.
Vancomycin is an antibiotic that you’ll encounter in a variety of different specialities. It‘s used in a wide range of different infections such as
It’s unique as it provides coverage to virtually all gram-positive organisms including bacteria resistant to common antibiotics (i.e. penicillins or cephalosporins). In short, if you see vancomycin being used, the infection is serious (which makes sense if they are admitted into the hospital)! In life threatening infections, subclinical dosing is not an option.
The challenge with vancomycin is it can cause serious adverse effects. If dosed or monitored incorrectly, adverse effects such as nephrotoxicity and neutropenia will occur. If a dose is infused too quickly, a rash can also develop. This is why vancomycin is regularly used in hospitals as they've established guidelines and procedures to make sure TDM is conducted properly and risks of toxicity and subclinical dosing are minimized. Proper monitoring, dose and administration is key.
Choosing vancomycin as the drug of choice will depend on the patient’s clinical status, the type of infection and the susceptibility of the bacteria. Patient factors will also be considered such as allergies and kidney function. Due to poor oral absorption, unless vancomycin is being used to treat an infection of the gut (i.e. C. difficile), you’d typically administer it intravenously. If infused too quickly, and depending on the amount of the drug administered, there’s potential for a rash. Therefore, it should be infused over a 60-120-minute period.
Depending on the setting of practice, the dose of vancomycin is usually calculated by the prescriber or by the pharmacist. The dose of vancomycin is based on the patient’s actual body weight. Depending on the severity of an infection (i.e. vertebral osteomyelitis, MRSA pneumonia, epidural abscess, and septic shock), a loading dose may be given to reach target levels quicker. The dosing interval for maintenance levels is determined by the kidney function and target trough drug concentration level. Kidney function is calculated using the height, weight, and serum creatinine.
Trough concentration (Cmin): Vancomycin demonstrates time dependent killing, therefore trough concentration (the lowest concentration reached by a drug before the next dose is administered) is how we determine if vancomycin levels are in the narrow therapeutic window but not in the range of toxicity and is the relevant pharmacokinetic monitoring parameter. Trough concentrations determine if and how a dose will be adjusted.
Depending on the infection, trough level targets are usually between 10-20mg/L. This is the standardized level where the drug is appropriate (effective and high enough to prevent bacteria from developing resistance) and safe (minimizing risk of neutropenia and nephrotoxicity).
Trough concentration can provide valuable information to the team. For example, the level can indicate if the patient is at risk of determining toxic effects before they occur. Trough concentrations should be drawn after drug levels reach a steady state (this is usually between dose 3-5) and within 30 minutes of the next dose.
Trough concentrations should only be drawn when there is an indication of adverse effects or if the patient is not medically improving in order to determine if the drug level is in the therapeutic range. However, patient factors such as unstable renal function, obesity, severe illness or an altered volume of distribution (i.e. elderly have different pharmacokinetic properties which further challenge how vancomycin will be dosed) will lead to routine vancomycin serum trough concentration monitoring.
In hospitals, patients usually meet the criteria for routine vancomycin serum trough concentration monitoring. This means when vancomycin is being initiated, you will usually see an order for trough concentrations levels when the drug reaches a steady state.
Complete blood count with differential (CBC): As neutropenia is a serious adverse effect of vancomycin, a CBC is drawn at baseline and weekly thereafter to ensure no adverse effects are occurring. Neutropenia is reversible upon discontinuation of the drug. For efficacy, normalization of white blood cell counts is also monitored for resolution of infection.
Serum creatinine (SCr): Vancomycin confers the risk of nephrotoxicity. Depending on your site, different guidelines will apply however SCr should be monitored at least weekly. If SCr increases significantly, trough levels are drawn to assess if the current dose is appropriate.
*Peak concentration levels are not monitored as they are not correlated with better clinical outcomes.
On admission, make sure you gather the list of known allergies and adverse reactions. Allergies are always important as they will impact medication options. Gathering allergies can also prevent unnecessary drug errors from occurring.
On admission, you’ll also need to report the height and weight - as the dose of vancomycin is calculated using the actual weight. The dosing interval is calculated using kidney function (which height and weight is needed to calculate).
As nurses, you’re responsible for drawing the trough concentration, documenting the time of administration of doses and flagging trough level greater than 20mg/L to the prescriber or pharmacist. Since you are on the floor and are directly interacting with patient’s, you’re often the first to notice any adverse reactions (i.e. rashes)!
If the team does not have information readily available when vancomycin is selected, treatment cannot be delivered quickly.
This is extremely important! Failure to do so will provide inaccurate information to the team. As an example, if a level is taken two hours before the next dose, the level obtained may be higher than the true trough concentration. If a trough level is inaccurate and falsely elevated, a dose may be adjusted inappropriately or withheld which can result in therapeutic failure.
Because vancomycin dosing is very exact, following the dosing times as directed is extremely important.
If any changes occur, such as an early trough level or a change in dose administration time, always notify the pharmacy as this will affect serum drug concentrations and the pharmacist’s ability to interpret the value.
Failure to communicate will result in wasted time and wasted money. As an example, if a pharmacist receives a level but is not confident that it is a true trough because the administration time was not properly documented, they may order a repeat level. This means additional costs to the healthcare system for repeat levels and if an adjustment is needed, it will not be done promptly.
TDM of vancomycin is done to ensure a therapeutic drug concentration, prevent treatment failure and to minimize toxic effects. Nurses, doctors, and pharmacists all have an important role in ensuring the success and safety of the treatment.
As a nurse, you are primarily responsible for gathering patient data and have an essential role in the monitoring of vancomycin. Ensuring dosing at indicated times, serum drug levels are drawn within 30 minutes of the next dose and proper communication to other care team members, allows for successful collaboration of the team.
While a thorough understanding of the pharmacokinetic properties of vancomycin or dosing guidelines for vancomycin are not necessary in a nurse’s scope of practice, an understanding of the rationale of recommendations and the importance of their role in TDM is essential for patient outcomes.
All the factual information in this post is supported by Bugs & Drugs; a reference recommended for treatment of infectious diseases and appropriate microbial use. It is peer reviewed, evidence based and frequently updated.
Azra Chatur, BScPharm
Azra is a pharmacy graduate from the University of Alberta. All aspects of pharmacy and healthcare interest her but the majority of her experience has been focussed on long term care, geriatrics and community pharmacy. Writing is her passion and she is excited to be able to share her pharmaceutical knowledge with nurses! If you have questions don’t hesitate to connect with her on Linkedin.