Mixing it Up With Medications for Reconstitution

Some medications may need to be originally packaged in their solid, dry form (powder, crystals, etc) so that they can be stored for a longer period of time. These meds must be reconstituted before they can be administered to or taken by the patient. Reconstitution refers to the process of adding a liquid such as water, or “diluent,” to a medication in its dry form to produce an aqueous dosage form (suspension, etc). For instance, many oral antibiotic suspensions are packaged as powders and need to be reconstituted (i.e., mixed) with water prior to dispensing. If the patient accidentally takes the medication in the dry powder form instead of in its liquid form, this could cause side effects such as throat irritation, or even lead to an overdose.

All pharmacy technicians should be familiar with the types of meds that need to be reconstituted, the risks of improper reconstitution, and how to prevent errors when dispensing these meds. Additionally, some pharmacy technicians may be directly involved in the reconstitution of medications and need to know how to perform this task properly.

electronic Rx

You receive the above electronic Rx for Evan Bryant, a 10-year-old child. It is for the antibiotic suspension clarithromycin 250 mg/5 mL, take 1 teaspoonful by mouth every 12 hours for 10 days. Since he will be taking 5 mL (1 teaspoon = 5 mL) twice a day for 10 days, you calculate that he will need 100 mL of the drug for the entire course of therapy (5 mL x 2 times a day = 10 mL per day; 10 mL per day x 10 days = 100 mL). You select one 100-mL bottle of clarithromycin 250 mg/5 mL from the shelf. You notice that the bottle contains a powder, and you know that this medication will need to be mixed with water before it’s dispensed.

What are some examples of medications that require reconstitution?

Most meds that need to be reconstituted can be categorized into one of the following groups: meds that need to be reconstituted before they are dispensed to the patient, meds that are reconstituted by the patient, and meds that need to be reconstituted before they are administered to the patient (e.g., injectable meds administered in the hospital setting, some vaccines, etc).

Most medications that require reconstitution are reconstituted in the pharmacy prior to dispensing. Examples include oral antibiotic suspensions (amoxicillin, amoxicillin/clavulanate, azithromycin, cefdinir [U.S.], etc), oseltamivir oral suspension, sildenafil oral suspension (U.S.), certain topical acne antibiotics (clindamycin/benzoyl peroxide gel [BenzaClin] and erythromycin/benzoyl peroxide gel [Benzamycin]), extended-release methylphenidate oral suspension (Quillivant XR [U.S.]), etc. It’s a best practice to wait until the patient is picking up and has paid for their prescription before reconstituting the medication. This helps prevent the drug from being wasted if there’s a change or if it’s returned to stock. Plus waiting until the patient is picking up the Rx helps maximize the beyond-use date. Once the medication is reconstituted, the clock starts ticking on how long it’ll be stable at optimal storage conditions. For example, cefprozil oral powder for suspension must be stored in the refrigerator for no longer than 14 days once reconstituted.

Some medications are intended to be dispensed in their powder form, and the patient must follow directions to reconstitute the med prior to taking it. The most common example of this is with polyethylene glycol (PEG) bowel preps for patients preparing for a colonoscopy (GoLytely, etc). Other examples include cholestyramine powder (Questran [U.S.], Olestyr [Canada], etc) and esomeprazole granules (Nexium). The patient will usually mix these products with water or another compatible liquid right before administration. It’s important for patients to have detailed instructions on acceptable liquids, volume of liquid, and the beyond-use date once reconstituted.

Finally, several injectable medications and some vaccines also require reconstitution. Pharmacy technicians who perform sterile compounding in the hospital are familiar with using diluents to reconstitute injectable medications such as cefazolin, methylprednisolone, daptomycin (Cubicin RF, etc), etc. Certain vaccines, such as shingles (Shingrix); measles, mumps, and rubella (M-M-R II); and chickenpox (varicella; Varivax [U.S.], Varivax III [Canada]), are supplied with a diluent for reconstitution prior to administration.

Where can I find directions for reconstitution?

To find information on whether or not a medication requires reconstitution and the instructions for how to reconstitute, first take a close look at the product label. Often times, reconstitution instructions can be found directly on the drug’s label or outer packaging. For instance, famotidine 40 mg/5 mL powder for oral suspension (U.S.) provides directions for reconstitution directly on the label. The most important pieces of information to look for are which diluent, how much, and how long the medication is good for after reconstituting. If enough information isn’t provided on the label, or if the information isn’t clear, you may need to refer to the full prescribing information. Within the package insert (or product monograph in Canada), reconstitution instructions are usually located in the “dosage and administration section.” You’ll also want to review the “how supplied/storage and handling” (or “storage and stability” in Canadian monographs) section for information on how to store the med and its beyond-use date after reconstitution, if this isn’t included on the drug’s label.

You double-check that Evan’s prescription for clarithromycin 250 mg/5 mL does in fact need to be reconstituted. You examine the bottle you pulled from the shelf and see that there are reconstitution instructions provided on the label. The storage information also states to keep the reconstituted medication at room temperature for up to 14 days, and do not refrigerate. (Refrigeration causes clarithromycin suspension to thicken and the taste to become bitter).

What are the risks of improper reconstitution?

Improper reconstitution can lead to overdoses or treatment failures. For example, there was a case where a mother noticed her child’s ADHD med, Quillivant XR oral suspension (U.S.), was thicker than usual. The pharmacist found that only half of the required water was used to reconstitute the med. Fortunately, the error was caught before the child got a dose, but it could have led to heart issues and other serious side effects. A similar situation that was not caught before the patient received a dose occurred with an 8-month-old child who was given a dose of unmixed amoxicillin/clavulanate. The patient was taken to the emergency department for an overdose because the unreconstituted powder is very concentrated. In addition to overdose risks, swallowing an oral powder meant to be reconstituted can cause throat irritation. On the other hand, reconstituting a drug with too much liquid can lead to the medication being too diluted and not working as well. Using the wrong diluent can lead to problems too, such as powders not dissolving properly, patients needing a repeat dose of a vaccine, vein or skin irritation from injection, etc.

How can I prevent errors when dispensing meds that require reconstitution?

When performing data entry for a prescription that will need to be reconstituted by the patient (e.g., PEG bowel prep, meds that come in powder packs to be mixed with a liquid, etc), ask your pharmacist about including additional directions on the Rx label. For example, labeling esomeprazole 10 mg granules for oral suspension with the sig, “Mix one packet with one tablespoonful (15 mL) of water, then drink, once daily” instead of, “Take one packet daily” may avoid misunderstandings.

Pay close attention to the beyond-use date of the reconstituted med, and make sure this is consistent with the prescribed duration of therapy. For instance, azithromycin oral suspension is usually only good for up to 10 days after reconstitution. If you get a prescription for a 14-day course of therapy, you will need to follow your company’s policy for how to handle entering this prescription, or check with the pharmacist. For example, the prescription may need to be dispensed in two portions, in which case, the patient will have to come back in a few days to pick up the second portion.

Be sure to select the correct product from the shelf. Many antibiotic oral suspensions come in similar names, similar looking packaging, and a number of different strengths and package sizes. For example, in the U.S., amoxicillin suspension comes in 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL strengths and the similar-named amoxicillin/clavulanate suspension comes in 125 mg/5 mL, 200 mg/5 mL, 250 mg/5 mL, 400 mg/5 mL, and 600 mg/5 mL strengths. Ensure you have the right product by comparing the NDC (or DIN in Canada) on the Rx label with the NDC (or DIN) on the package. And always use bar-code scanning to confirm you have the intended med.

When pulling a vaccine or other injectable med that needs to be reconstituted from the pharmacy stock, make sure to also pick the correct diluent. For example, vaccine diluents should typically be stored next to their associated vaccine. However, keep in mind for frozen vaccines, such as the varicella vaccine, the diluent must be stored in either the refrigerator or at room temperature, NOT in the freezer. So you may have to go to a different location to retrieve the vaccine diluent. Make sure your pharmacy has shelf tags indicating that a diluent is needed and where to find it, to help prevent errors. Also be very careful not to accidentally dispense the diluent by itself. There have been reports of the vaccine diluent being administered to a patient, instead of the vaccine.

Once you have the correct drug (and diluent, if applicable) selected, you will want to label the product. Be sure not to cover any important information like the drug name, expiration date, NDC (or DIN) number, and reconstitution or storage instructions. Affix appropriate auxiliary labels, such as “Shake well” for oral suspensions or “Refrigerate” for products that require refrigeration after reconstitution. Keep in mind that while many antibiotic suspensions can be refrigerated to improve taste, they don’t necessarily have to be refrigerated and may be left at room temp. But be aware of suspensions which require refrigeration (e.g., cefprozil) and suspensions which must NOT be refrigerated (e.g., clarithromycin or clindamycin). Include a “beyond-use” or “discard after” date label, but remember not to fill this in until the product has been reconstituted. Prepare the labeled drug (and the diluent, if applicable) for pharmacist verification prior to reconstitution.

Your pharmacy should have a process in place to help prevent accidentally dispensing unreconstituted meds. For example, consider keeping Rxs that are to be mixed in a separate bin in the pharmacy and attaching a note that says, “ADD WATER” or “RECONSTITUTE.” This will alert the person ringing up the patient that the med needs to be reconstituted BEFORE it leaves the pharmacy. Also, if your pharmacy mails prescriptions, be aware that some pharmacies, state laws, or payers may not allow mailing products that need to be reconstituted prior to dispensing.

When the drug is ready to be reconstituted, follow the tips provided in the next section. Don’t forget to include a calibrated measuring device (oral syringe, etc) with oral suspensions. Send patients to the pharmacist for counseling on how to administer their reconstituted med, or if they will be responsible for reconstituting the med at home, instructions on how to do this.

After entering the Rx into the computer, you scan the bar code on the bottle to make sure you selected the correct product. You place the Rx label and the auxiliary labels “Shake well,” “Do not refrigerate,” and “Use by,” onto the bottle, making sure not to cover any important information. (You don’t fill in the “Use by” date yet, since this will depend on when the med is reconstituted). You attach a note to the Rx label receipt that says “RECONSTITUTE” so that the Rx gets stored appropriately prior to dispensing.

How should I reconstitute meds?

You’ll want to follow the instructions on the product labeling very closely when reconstituting medications. Also keep these best practices in mind depending on the type of med you are reconstituting.

Before reconstituting an oral suspension, be sure to tap and invert the bottle a few times. This helps loosen the powder that may have settled. Neglecting to do this could trap some powder in the bottom of the bottle, preventing water from reaching it. This may result in an incorrect dose.

Follow the product labeling to determine how much water to add. Most pharmacies use distilled or purified water to reconstitute powders for suspension. Water from the tap may have fluoride and other contaminants that may not be desirable and may decrease the drug’s stability. Check with your pharmacist to determine what type of water to use if you are unsure.

When measuring the amount of water to be added, be sure to use a measuring device that is the appropriate size. For the most accurate measurement, use a measuring device that is closest in size to the amount of water you need to add. For example, a 250 mL graduated cylinder should not be used to measure 10 mL of water. Be sure you’re reading the amount of water in the measuring device correctly. You want to read the amount of water at the bottom of the bubble (or meniscus). This will ensure an accurate amount. If you use a calibrated water filtration system, such as Fillmaster, make sure you are trained on how to use the system. You might be able to scan the bar code on the product and/or manually enter the amount of water needed. Either way, double-check to make sure the right amount of water displays on the screen before dispensing it. Also make sure to follow manufacturer instructions for calibration, cleaning, and filter replacement.

In order to distribute the drug evenly throughout the suspension, you’ll want to be sure to add the total volume of water in two steps. There may not be enough room for all of the water to go into the bottle at first because the powder is taking up space in the bottle. Generally, you’ll want to add about one-half of the total amount of water for reconstitution. Shake the bottle vigorously to suspend the powder. Make sure to invert the bottle several times when mixing to ensure any powder adhering to the bottom of the bottle is mixed well. If you use a calibrated water filtration system, it should be set up to deliver half of the total amount of water first, followed by the rest of the water once prompted by the user. Don’t forget to dispense the remaining quantity of water. Carefully open the container and add the remainder of the water to the bottle. Be sure to shake vigorously again after adding the additional water.

When reconstituting vaccines, be sure to use the diluent provided by the manufacturer for that particular vaccine and double-check the expiration date. You’ll typically withdraw the entire volume of diluent; but be sure to read the instructions in the product labeling to verify this. During reconstitution, you should use aseptic technique and infection prevention measures since vaccines are injected into a patient. Before reconstituting the vaccine, you should wash your hands with soap and water and don gloves, if required by your company policy. Use a new sterile syringe for each reconstitution. Remove the cap from the diluent vial, then disinfect the rubber stopper by wiping an alcohol swab firmly in one direction. To prevent rubber fragments from entering the diluent vial, insert the sterile syringe needle at an angle with the opening (or bevel) facing up. Withdraw the entire contents (unless directed otherwise by the product labeling) and inject the diluent into the vaccine vial, being sure to enter the vaccine vial at an angle with the needle opening facing upwards. Rotate or shake the vaccine vial thoroughly to dissolve the powder. The last step is to inspect the appearance of the reconstituted vaccine and compare its color and appearance to the description in the package insert. If there is discoloration, particles floating, or obvious evidence of unsuccessful reconstitution, get the pharmacist involved to determine if the vaccine needs to be marked as “Do Not Use.” Be aware that vaccines should only be reconstituted right before they will be administered. This is because once reconstituted, the vaccine needs to be used within a short timeframe. For example, after reconstitution, Shingrix must be used within six hours and Varivax is only good for 30 minutes (in Canada, Varivax III is only good for 90 minutes).

The reconstitution of other injectable meds typically occurs in the hospital setting as part of sterile compounding. The process described for reconstituting vaccines is similar for reconstituting other injectable meds (except you’ll likely be performing reconstitution in a “hood”). However, other injectable meds don’t typically come with their own vial of diluent. You will need to determine from the product labeling which diluent you can use (e.g., sterile water, normal saline, D5W, etc) and the specific volume that must be drawn up. For example, meropenem 1-gram vials should be reconstituted with 20 mL of sterile water. Don’t just assume that the same/similar drug requires the same amount of diluent or even the same type of diluent. To illustrate, meropenem 500 mg vials need to be reconstituted with 10 mL of sterile water versus 20 mL of water for the 1-gram vials. And Cubicin (U.S.) is reconstituted with normal saline, while Cubicin RF is reconstituted with bacteriostatic or sterile water. Plus, you will need to check for any special instructions for reconstitution, such as if the vial shouldn’t be shaken due to a tendency of a med to foam excessively or because of the type of med (e.g., protein). As with reconstituted vaccines, reconstituted injectable meds must be used within a specific timeframe, so you’ll want to note the date and time the product was reconstituted on the vial. And follow pharmacy policies and procedures for having a pharmacist double-check that the med was reconstituted correctly.

Later that day, Evan’s mother is at the pharmacy counter to pick up his Rx. You check the Rx will call area and don’t see anything there. You look up his medication profile and see the clarithromycin Rx you filled earlier in the day. You check the spot where your pharmacy usually keeps meds that need to be reconstituted and find Evan’s Rx. It’s just you and the pharmacist working right now, and the pharmacist is on the phone helping a patient. You ring up Evan’s mother and then proceed to reconstitute the clarithromycin. The pharmacy has a calibrated water filtration system that allows you to scan the bar code on the bottle. After scanning the bottle, the system displays the total volume of water that will be added. You double-check this with what is listed in the reconstitution directions on the bottle and see that it is the correct amount. Before dispensing any water, you make sure to shake the powder. The calibrated water filtration system dispenses half of the water first, allowing you time to shake the suspension before dispensing the remaining amount. You make sure to shake the bottle very well after the second portion of water is dispensed and then write in the “Use by” date. By now, the pharmacist is off the phone, so you ask her if she could counsel Evan’s mother on how to administer the medication.

Prepared by the Editors of Therapeutic Research Center (361180).

Cite this document as follows: Technician Tutorial, Mixing it Up With Medications for Reconstitution. Pharmacist’s Letter/Pharmacy Technician’s Letter. November 2020.

“Cheat Sheet” for Reconstituting Meds

What does “reconstitution” refer to and why do some meds need to be reconstituted?

Reconstitution refers to the process of taking a medication that is in its dry form and adding a liquid, such as water, to it. This liquid may be referred to as the “diluent.” Some medications may need to be packaged in their solid, dry form (powder, crystals, etc), so that they can be stored for a longer period of time. These meds need to be reconstituted before they can be administered to or taken by the patient.

Which meds require reconstitution before they are dispensed or administered to the patient?

  • Oral powder suspension dosage forms such as antibiotics (amoxicillin, amoxicillin/clavulanate, azithromycin, cefdinir [U.S], etc), oseltamivir, sildenafil (U.S.), famotidine (U.S.), extended-release methylphenidate (Quillivant XR [U.S.]), etc.
  • Certain topical acne antibiotics such as clindamycin/benzoyl peroxide gel (BenzaClin) and erythromycin/benzoyl peroxide gel (Benzamycin).
  • Some vaccines such as shingles (Shingrix), measles (M-M-R II), chickenpox (varicella; Varivax [U.S.], Varivax III [Canada]), etc.
  • Many injectable meds available as a powder for injection used in the hospital setting such as cefazolin, methylprednisolone, daptomycin, etc.

Which meds may require reconstitution by the patient (i.e., after dispensing)?

Some medications are intended to be dispensed in their powder form and the patient must follow directions to reconstitute the med prior to taking. The most common example of this is with polyethylene glycol (PEG) bowel preps for patients preparing for a colonoscopy (GoLytely, etc). Other examples include cholestyramine powder (Questran [U.S.], Olestyr [Canada], etc) and esomeprazole granules (Nexium).

Where can directions for reconstitution be found?

Usually instructions for reconstitution can be found directly on the drug’s outer label/packaging and in the “dosage and administration section” of the package insert. The “how supplied/storage and handling” (or “storage and stability” in Canadian monographs) section has info on how to store the med and its beyond-use date after reconstitution.

What are some of the risks of improper reconstitution?

Overdoses, treatment failures, powders not dissolving properly, patients needing a repeat dose of a vaccine, vein or skin irritation (for injectable meds), throat irritation (if a powder is consumed in error), etc.

How can I prevent errors when dispensing meds that require reconstitution?

  • Include detailed instructions for patients who need to reconstitute a med at home.
  • Make sure to choose the right diluent for vaccines and injectable meds.
  • Affix the correct auxiliary labels, being careful not to cover any important information.
    • Calculate the correct beyond-use date and include this as an auxiliary label.
  • Flag Rxs that will need to be reconstituted before dispensing and place them in a designated area.
  • Reconstitute meds correctly:
    • Oral suspensions – shake powder to loosen, then mix total volume of water in two steps.
    • Vaccines & other injectables – use aseptic technique (wash hands, wipe rubber stopper with alcohol, etc), measure the correct diluent volume, note date and time of reconstitution on the reconstituted product.
  • Send patients to the RPh for counseling on administration and/or how to reconstitute, if applicable.

[November 2020; 361180]

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