Injectable Meds: Beyond Sterile Prep

Full update September 2020

News stories about mishaps during sterile preparation of medications have been making headlines for what seems like years. This makes sense, because breaches of proper procedures can and have led to serious patient harm, including deaths. However, there are a number of other considerations that pharmacy technicians should be aware of concerning the preparation and dispensing of injectables. These can range from creation and maintenance of documents that help standardize preparation to fielding phone calls from nurses who have questions about administration. This technician tutorial will cover this type of practical information for pharmacy technicians.

Electrolytes 101

You are delivering meds for patients on the general medicine floor at your hospital. You have a dose of vancomycin 1 g to be given every 12 hours to patient Bonnie Bratton. The dose is to infuse over two hours, which you recognize as the usual infusion time for 1 g of vancomycin. You place the dose in the refrigerator, in the bin designated for Bonnie Bratton’s meds.

What does USP Chapter <797> cover?

USP Chapter <797> deals with the sterile preparation of medications, such as those meant for intravenous (IV), intramuscular (IM), ophthalmic, spinal, or subcutaneous injection. This involves everything from proper garbing prior to entering a clean room suite to what can be stored in a clean room suite to actual technique and equipment requirements for sterile compounding. Chapter <797> also has guidance on beyond-use dating of sterile preparations, as well as for single- and multidose containers (e.g., ampules, vials) of sterile meds.

What other information do I need to consider with regard to prepping injectable medications?

Most pharmacies have policies and procedures in place to standardize preparation of injectable medications. For example, a standard diluent, either 5% dextrose (D5W) or 0.9% sodium chloride (normal saline [NS]), may be preferred for IV piggybacks and infusions, unless the medication is incompatible with that diluent (e.g., phenytoin, which can precipitate in D5W), or unless the stability of a prep will be significantly shortened when the preferred diluent is used (e.g., ampicillin/sulbactam, where stability is much shorter in D5W than in NS).

This type of standardization can serve a number of purposes, such as simplifying prep, preventing confusion and mix-ups in the pharmacy, and helping to streamline the ordering process for prescribers.

In addition, a chart that includes more info on diluents (e.g., volume to be used), beyond-use dates, and proper storage (e.g., refrigeration, room temperature) for commonly prepared injectable medications can save time and prevent errors that could lead to a patient getting a med with reduced potency. Pay close attention when looking at these charts (or similar info in the med's package labeling) since prep directions or storage info may differ depending on factors such as the intended route of the med (e.g., IV, intramuscular) or the desired final concentration (e.g., standard adult concentration, standard pediatric concentration). An example of a med that could be confusing is daptomycin (Cubicin and generics, and Cubicin RF). Different daptomycin products can have different storage requirements, dilution instructions, etc. Help make sure your pharmacy's charts are current and include the correct info for products that are in stock, especially when you see a change such as to a new generic.

Other information that can be added to these types of documents, and even to patient-specific labels generated by the pharmacy’s or hospital’s computer system, include special considerations such as when a filter or other device must be used for the administration of a medication or if a drug should be prepared in a particular type of container. These special considerations are typically exceptions to the rule and can be easy to forget if a person doesn’t commonly prepare or dispense these meds. Here are some examples:

  • Phenytoin IV piggybacks should be administered through a 0.22 or 0.5 micron filter due to the risk of precipitation.
  • IV amiodarone drips should be prepped in either a glass bottle or PVC-free bag of D5W to avoid reactions with PVC (although this is NOT necessary for piggybacks used for loading doses, since they are administered over 15 minutes).
  • Doses of “vinca alkaloids” such as vincristine or vinblastine should be prepped in IV piggybacks, not in syringes, to prevent fatal wrong-route errors (i.e., inadvertent intrathecal administration).
  • A light protective covering, such as an opaque bag or foil wrap, must be used for nitroprusside infusions, to prevent degradation of the drug.
  • Epidural infusions (e.g., bupivacaine, ropivacaine) may need to be dispensed with special tubing (i.e., NRFit) that will prevent them from being given intravenously by mistake.
  • Ceftriaxone may need to be diluted with lidocaine instead of sterile water when a dose is intended for intramuscular (IM) injection to reduce pain at the injection site.
  • Remdesivir (Veklury) lyophilized powder, not the solution, should be used to prep most pediatric doses.

Medications that are added to your hospital's formulary, and possibly non-formulary meds that are used periodically, should be added to these standardized procedure documents in a timely manner.  Meetings are typically held monthly to review possible formulary changes.  Work with your pharmacist to see how you can help keep these documents current.  This might involve actually collecting information, such as from the drug's package insert or a drug compatibility reference, submitting change requests for computer updates, or making sure any hard copies of such documents located throughout the hospital are switched out when there are updates.

Another aspect of injectable med prep that should be standardized is how “overfill,” or extra solution in an IV bag, syringe, vial, or ampule should be handled. IV bags of diluents typically have a small amount of overfill, and vials and ampules may also have some extra solution. This leads to the need to consider how overfill affects prep of meds. Some meds may need to be added to exact amounts of diluents (e.g., chemo, pediatric dilutions), while the small amount of extra diluent may not matter for other types of meds (e.g., antibiotics, IV fluids). Extra solution in an ampule or vial may need to be accounted for in some cases, or disposed of in a specific manner, such as for controlled substances. You may actually need to overfill some preps, such as doses that require small volumes of meds in syringes. This can help make up for lost volume, such as when a nurse places a needle on a syringe for intramuscular or subcutaneous injection, and a small amount of med stays in the “dead space” of the needle hub. Another type of med that’s commonly overfilled is eye injections. Keep in mind, however, that most meds in syringes are administered with needle-less systems, so you won’t often need to consider overfill in syringes for this reason. Handling overfill consistently is the key, so it’s important to be aware of and follow your pharmacy’s policies.

Some injectable meds will need to be “activated” before use.  These are products that separate ingredients in different chambers of a container, or in different containers that must be assembled.  They offer convenience, partly because they can cut down on the need for sterile compounding.  Instead, the activation step is required to mix the ingredients.  For example, Clinimix parenteral nutrition bags have two chambers with a seal in between.  The seal must be broken so the ingredients can mix prior to use. ADD-Vantage IV products have meds (antibiotics, etc) in vials with special connectors that must be attached to the proprietary IV bags.  This is required for the med and diluent to be mixed.  It is important to read the product labeling prior to activation, since steps for activation differ from product to product.  Otherwise, the ingredients may not mix properly.  This could lead to problems, such as the patient not getting the intended med, dose, etc.  Also, be aware of your pharmacy’s policies on dispensing injectables that require activation.  You may need to activate them prior to dispensing, or nurses may activate them prior to administration.  In the latter case, you may need to add auxiliary labels to remind nurses about the activation step.  Plus, the beyond-use date that you assign may differ depending on factors such whether or not the med is activated, if containers are assembled or dispensed separately, etc.

What other information do I need to consider with regard to dispensing injectable medications?

Of course, you will want to make sure that injectable meds are delivered to the proper place on a patient care unit. If a medication needs to be refrigerated, such as most IV piggybacks, it will need to be placed in a refrigerator on the unit in order to maintain its stability through the assigned beyond-use date. This is often a point of confusion for nurses, especially for meds that come in vials, such as erythropoietin (Epogen, etc). If you receive reorders for these types of meds, make sure that the nurse is checking the refrigerator for the dose prior to redispensing it.

Likewise, a few IV piggybacks must be stored at room temp, such as linezolid (Zyvox. etc) or metronidazole (Flagyl, etc). Because nurses most often expect IV piggybacks to be stored in the fridge, there may be confusion when they’re looking for these meds. Follow the same advice as above when you see reorders. Nurses may be looking in the wrong place for them and think that the dose has not been delivered. Help them out by letting them know that these particular meds are always stored at room temp because refrigeration can lead to problems, such as precipitation. Once they know, they’re not likely to forget!

Also, with regard to special types of devices that must be used with meds, be mindful of what comes from the pharmacy and what is stocked on patient care units such as from central supply or materials management. A good example is the 0.22 micron filter used for phenytoin IV piggybacks, as mentioned in the last section. If these are stocked on the unit as opposed to being sent by pharmacy, you may still get calls from nurses looking for the filters. If you already know the answer, you can save time by letting them know where they can access the filters.

Keep in mind that some injectable meds should not be dispensed to or stocked on patient care units. This is often true for injectables that are meant to be used only for prepping doses (e.g., IV piggybacks, IV infusions), and not for direct administration to patients. Some examples of meds meant for prepping doses include sterile water for injection and potassium chloride 2 mEq/mL. The problem with stocking these meds outside the pharmacy is that they could be accidentally administered directly to a patient, which could lead to serious patient harm or even death. If you’re not sure if a med is meant for prep or direct administration to a patient, check the label for wording such as “must be diluted prior to use” or “for the preparation of IV infusions only.” Follow your pharmacy’s policies on precautions required for these meds. For example, potassium chloride 2 mEq/mL should never be stocked on patient care units, since direct administration to a patient can stop the heart.

Another thing to consider is when a bolus or loading dose of an IV med is needed. These are often larger doses of meds, given at a quicker rate than usual. They may be given before a continuous infusion is started, during a continuous infusion, or as the first dose of or in addition to a regimen of IV piggybacks or pushes. One example is a heparin IV push that’s given before or during a heparin infusion, to help boost the med’s blood thinning effects. Other meds that may require a bolus or loading dose include alteplase, amiodarone, diltiazem, phenytoin, and vancomycin. Boluses and loading doses usually need to be dispensed separately. If you aren’t sure, check with your pharmacist. Something else to consider with boluses and loading doses is that they are often needed quickly. In some cases, you can send these doses right away to get a patient started on their med, and then take time to prep the drip or next dose.

The next day you’re working the same shift and covering the same patient care unit. You see a dose of Bonnie Bratton’s vancomycin in the refrigerator return bin on the patient care unit. This med must have been discontinued. You notice that you have a dose of linezolid (Zyvox) 600 mg IV to deliver for this patient as well. This med will be infused over one hour, and it is administered every 12 hours. Linezolid IV doses are to be kept at room temperature, so you do not place this dose in the refrigerator. Fortunately, there is an auxiliary label on the bag to remind you not to place it in the refrigerator. In addition, doses of linezolid must be kept in their foil overwraps until they are used. So, unlike most doses of IV meds, this one is still in its packaging.

What do IV drug compatibilities involve?

It’s hard to imagine that any pharmacy technician who works in a hospital has not received a phone call from a nurse asking if two or more IV drugs can be administered through the same IV line, at the same time. The situation is somewhat self-explanatory, but here are a few more details to give you a more accurate picture.

If a patient has a peripheral IV line, which means the IV goes into a peripheral vein such as in the arm, the line will have ports, or openings, where IV medications and fluids can be attached to run into the line. These are called “y-sites.” If two IV medications, let’s say the antibiotic cefazolin as an IV piggyback which will be infused over 15 minutes, and the pain medication morphine which is ordered as a continuous infusion, need to be infused together, it is important to know if they are “compatible.” Drugs are considered INcompatible if they chemically deactivate one another, or if they are physically unstable and precipitate into chunks or crystals when they’re mixed. There are experts who perform studies to see whether either of these things happen when certain drugs are mixed. Extensive information on drug compatibilities can be found in certain drug information references. Some hospitals might even create their own charts that include commonly used IV drugs. In our example, a nurse could administer these two meds, cefazolin and morphine, through the same IV line, because they are compatible. (Double-check in a drug info reference to verify this, if you have one available.)

If a patient has a central line (an IV line that’s inserted into a large vein) or a peripherally-inserted central catheter (PICC), things can get a bit more complicated. These have multiple lines, or lumens, attached together, and the solutions that are administered through them will not mix until they reach the patient’s bloodstream. So, you can see that the drugs may not mix directly, as they would in a peripheral IV line.

Now that you have more details about IV compatibilities, it’s easy to understand the information a pharmacist will need in order to answer IV compatibility questions from nurses. When you get one of these calls, ask for the names of the drugs, their scheduled times, and the type of IV line or number of lines the patient has in order to improve efficiency. If you are comfortable with the pharmacist’s preference for which drug information reference to access, you may want to go ahead and get that information ready as well. Ultimately, pharmacists will typically want to speak with nurses themselves to share the information, in addition to any strategies that may be needed due to drug incompatibilities, since an incorrect answer or any kind of mix-up could potentially lead to patient harm.

If drugs are incompatible, the pharmacist may recommend rescheduling one of them so they can be infused at separate times. Or, an IV drug may be switched to an oral formulation if appropriate. Sometimes administration of a dose might need to be delayed if IV access that requires placement by a physician or specially-trained nurse is necessary.

When you return to the pharmacy, you answer a number of phone calls. One of them is from Bonnie Bratton’s nurse. The patient is receiving other IV medications and the nurse wants to know if they can infuse them together with linezolid. You ask the nurse the names of the meds, and they tell you one is ½ normal saline with potassium chloride 20 mEq, which is infusing at 80 mL/hour. The other med is phenytoin. You ask the time that the phenytoin is due and the nurse tells you it is actually a loading dose, which will be given one time. The dose of linezolid is due at the same time. You ask the nurse how many IV lines they have available, and the nurse says that the patient has one peripheral line.

You ask the nurse to please hold for a minute or two and pass this information on to the pharmacist. The pharmacist accesses a reference to find out about drug compatibilities. After a couple of minutes, the pharmacist picks up the phone. The pharmacist asks the nurse a number of additional questions, and then decides to recommend switching the phenytoin to an oral formulation. The pharmacist determined that these two drugs could not be infused at the same time, because they are not compatible.

How should doses of injectable meds that are returned to the pharmacy be handled?

This can be much trickier than simply returning doses to the pharmacy shelves, as is often done for unit dose capsules and tablets. Typically, any partially-used injectable meds will be disposed of by the nurse on the patient care unit, according to hospital policies and procedures. So, pharmacy technicians will be mostly concerned with unused doses of injectable medications that are returned.

You’ll want to follow your pharmacy’s policies and procedures for returning unused doses of injectable meds to the pharmacy. For example, some pharmacies may dispose of any dose of an injectable med that was dispensed in a syringe (e.g., patient-specific insulin doses, pediatric doses) regardless of whether or not they are expired and have been stored properly on the patient care unit. For IV piggybacks such as antibiotics and infusions such as insulin or heparin, these will most often be able to be returned to pharmacy stock if they’re still in date and if they were stored properly after dispensing. If they’re returned to stock, they’ll be able to be reissued to another patient. Again, become familiar with policies and procedures about what is allowed at your hospital.

Later in the day, you return to the patient care unit where Bonnie Bratton is staying. You find the discontinued dose of IV phenytoin in the return bin. You bring the dose back with you to the pharmacy and ask the pharmacist how to handle it. Should the dose be discarded, or can it be kept for reissue to another patient? The pharmacist does some quick checking and tells you that the dose can be reused as long as the beyond-use date has not passed. However, when you check, the beyond-use date has actually passed. The prep is only good for four hours after it’s mixed. Since this is the case, the dose will need to be wasted. However, you do remove the unused 0.22 micron filter that was dispensed with the dose and place it back in the proper bin so it can be dispensed with another med that requires the use of a filter.

Project Leader in preparation of this technician tutorial (360981): Stacy A. Hester, R.Ph., BCPS, Associate Editor; last modified April 2022.

Cite this document as follows: Technician Tutorial, Injectable Meds: Beyond Sterile Prep. Pharmacist’s Letter/Pharmacy Technician’s Letter. September 2020.

---Please continue for a Cheat Sheet about injectable meds---

“Cheat Sheet” for Injectable Meds: Beyond Sterile Prep

What does USP Chapter <797> cover?

USP <797> deals with sterile preparation of meds.

What other information do I need to consider with regard to prepping injectable medications?

Other aspects beyond sterile preparation include:

  • Diluent choice (e.g., normal saline), and the impact of the diluent on med stability
  • Appropriate storage temperatures for injectable meds (e.g., refrigeration, room temp)
  • Whether or not an injectable med has additional requirements such as use of a filter or other device for administration, preparation in a particular type of container (e.g., glass, non-PVC), or protection from light (e.g., foil sleeve)
  • How to handle overfill, or the extra amount of med or diluent in certain containers

What other information do I need to consider with regard to dispensing injectable medications?

  • Proper delivery location (e.g., refrigerator)
  • Whether or not you’re responsible for ensuring nurses have needed supplies (e.g., filters or other devices for administration)
  • Appropriateness of dispensing certain meds to patient care units (e.g., meds meant for prepping doses and not for direct administration to patients)

What do IV drug compatibilities involve?

Nurses may ask if IV meds are compatible, which means that they’ll need to know if they can infuse multiple IV meds through the same IV line at the same time. If you get this question, refer it to the pharmacist. But first, gather needed info:

  • What type or types of IV line does the patient have?
  • What meds need to be infused?
  • What are the due times for the meds?

How should doses of injectable meds that are returned to the pharmacy be handled?

  • Check your pharmacy’s policies to find out how to handle certain injectable meds returned to the pharmacy
  • If a type of med can be returned to stock for reissue to another patient, double check that the beyond-use date hasn’t already passed
  • If the beyond-use date has passed, properly dispose of the med

[September 2020; 360981]