Medication Administration: Mixing Medications in One Syringe - CE/NCPD

The content in Clinical Skills is evidence based and intended to be a guide to clinical practice. Always follow your organization’s practice.

ALERT

Do not compound IV push medications (combining two or more medications) in a single syringe outside the pharmacy.^{undefined#ref3">3}

Insulin is considered a high-alert medication, and it is strongly recommended that insulin doses be verified by two nurses to prevent errors.⁵ If indicated by the organization’s practice, have the dose of clear insulin verified before mixing. Have the dose verified a second time after the medications are mixed.

Administer a mixture of insulin quickly after preparation. Rapid- or short-acting insulin can bind with intermediate- or long-acting insulin, thus reducing the action of the more rapid-acting insulin.

Do not use a single-dose vial more than once. Multiple use of single-dose vials increases the risk for blood-borne pathogen infections.⁷ Use one needle, one syringe, only one time on one patient.⁷

Take steps to avoid interruptions and distractions when getting medications ready.

OVERVIEW

Some medications must be mixed from two vials or from a vial and an ampule. Mixing compatible medications avoids the need to give a patient more than one injection. Most nursing units have medication compatibility charts. Compatibility charts are in drug reference guides or are posted within patient care areas. If uncertain about medication compatibilities, consult a pharmacist. When mixing medications, fluid must be correctly aspirated from each type of container. When using multidose vials, the nurse must not contaminate the vial’s contents with medication from another vial or ampule.

When mixing medications from a vial and an ampule, the nurse should prepare medications from the vial first and then withdraw medication from the ampule using the same syringe and a filter needle. When mixing medications from two vials, the nurse must not contaminate one medication with another and must ensure that the final dose is accurate. Aseptic technique must be maintained.⁹ Single-dose vials do not contain antimicrobials; therefore, multiple accesses place the patient at risk for infection.⁷

The nurse must give special consideration to the proper preparation of insulin. Insulin is the hormone used to treat diabetes mellitus. Insulin is classified by rate of action, including rapid acting, short acting, intermediate acting, and long acting. A patient with diabetes sometimes requires more than one type of insulin. In addition, some patients require several injections in a day that combine two different insulin preparations to duplicate the normal pattern of their insulin production. Insulin is available in vials.

If more than one type of insulin is required to manage the patient’s diabetes and the types of insulin are compatible, the nurse may mix them in one syringe. This may result in a patient response to insulin that is different from the response that would occur if the insulins were given separately. When mixing insulin in one syringe, the rapid- or short-acting insulin should be drawn up first. Only insulins from the same manufacturer are recommended for mixing.⁹ The Association of Diabetes Care & Education Specialists has a list of recommendations for mixing insulins (Box 1).

Insulin syringes are available in sizes that hold 0.3 to 1 ml and are calibrated in units. Most insulin syringes are U-100s, designed to be used with U-100 strength insulin (Figure 1). Each milliliter of U-100 insulin contains 100 units of insulin. Use U-100 insulin syringes with preattached 25- to 31-G needles when giving U-100 insulin and 1-ml tuberculin syringes when giving U-500 insulin. The U-500 insulin is five times more potent than U-100 insulin. A specific U-500 insulin syringe is available, but the use of the U.S. Food and Drug Administration (FDA)–approved U-500 insulin pen is a better choice for patient safety. U-500 insulin contains 500 units of insulin per 1 ml of fluid and should be used only for patients requiring doses above 200 units a day.⁴ Before use, the nurse must carefully examine the syringe to determine the measurement scale and to ensure use of the correct syringe for preparing the ordered medication.^9,10

To help reduce the impact of pharmaceutical waste on the environment, the Environmental Protection Agency (EPA) released a final rule on the management of hazardous waste pharmaceuticals.² The rule decreases the cost of disposing of certain nicotine products and streamlines the process of disposing of pharmaceutical waste.

If the patient expresses worry about the accuracy of a medication, the medication should not be given. The concern should be explored, the practitioner notified, and the order verified.

SUPPLIES

See Supplies tab at the top of the page.

EDUCATION

• Give developmentally and culturally appropriate education based on the desire for knowledge, readiness to learn, preferred learning style, and overall neurologic and psychosocial state.
• Teach the patient about the potential side effects and adverse reactions of the medication.
• Provide information about the medication, its indications, and dosing schedule.
• Teach all patients with type 1 diabetes and appropriate patients with type 2 diabetes to prepare and self-administer insulin as ordered.
• Evaluate the patient’s ability to mix insulins by having the patient complete a return demonstration of insulin preparation. If the patient is unable to mix insulins accurately, communicate this to the practitioner and discuss changing the patient’s insulin type to a premixed formula.
• Encourage questions and answer them as they arise.

ASSESSMENT AND PREPARATION

Assessment

1. Clean hands and don appropriate personal protective equipment (PPE) based on the risk of exposure to bodily fluids or infection precautions.
2. Assess the patient for specific contraindications to receiving the medication and advise the practitioner accordingly.
3. Review the patient’s medication history and any medication allergies.
4. Assess the patient’s body build and muscle size if giving subcutaneous or intramuscular medication.
5. Consider the medications to be mixed, their compatibility, and the type of injection to be given.

Preparation

1. Verify the patient’s actual admission weight in kilograms. Reweigh the patient if appropriate.⁶ Do not use stated, estimated, or last documented weight.⁶
2. Get the medication, check against the practitioner’s order, verify the expiration date, and check that the medication and container are clean and intact.

   Do not use medication that is cloudy or precipitated unless such is indicated by its manufacturer as being safe.

3. Review medication reference information pertinent to the medication’s action, purpose, onset of action and peak action, normal dose, and common side effects and implications.
4. Prepare medication for one patient at a time.
   1. Select the ampule or vial from the unit-dose drawer or automated dispensing system.
   2. Compare the label on each medication with the medication administration record (MAR) or computer printout. In the case of insulin, ensure that the correct types of insulin are prepared.

PROCEDURE

1. Clean hands and don appropriate PPE based on the risk of exposure to bodily fluids or infection precautions.
2. Check the rights of medication safety.
3. Label all medications and solutions. The only exceptions are medications that are still in their original container or medications that are given immediately by the person who prepared them.⁸

Mixing Medications From Two Vials

1. Remove the cap covering the top of an unused vial to expose the rubber seal.
2. Disinfect vials by cleansing the access diaphragm using friction and a sterile 70% isopropyl alcohol, ethyl alcohol, iodophor, or other approved antiseptic swab and allow to dry at least 10 seconds.³

   Rationale: Not all drug manufacturers guarantee that rubber seals of unused vials are sterile; therefore, the seal must be swabbed with alcohol while applying friction before preparing the medication. Allowing alcohol to dry prevents it from coating the needle and mixing with the medication.

3. Using a syringe with an attached needleless access device or filter needle, aspirate a volume of air equivalent to the first medication dose (which will come from vial A).
4. Inject the air into vial A, making sure that the needle or needleless access device does not touch the solution (Figure 2A).

   Rationale: Air is injected into vial A to create the positive pressure that will be needed to withdraw the desired dose later.

5. Holding the plunger in place, withdraw the needle or needleless access device and syringe from vial A.

   Rationale: If the plunger is not held in place while the needle or needleless access device is withdrawn, injected air may escape from vial A.

6. Aspirate a volume of air equivalent to the second medication dose (which will come from vial B) into the syringe.
7. Insert the needle or needleless access device into vial B. Inject the air into vial B and then draw up medication from vial B into the syringe (Figure 2B).

   Rationale: Air is injected into vial B to create the positive pressure needed to withdraw the desired dose without aspirating.

8. Withdraw the needle or needleless access device and syringe from vial B, holding the plunger in place. Ensure that the proper volume of medication has been obtained.
9. Determine what the combined volume of the medications should measure on the syringe scale.

   Rationale: Determining the correct combined volume helps prevent accidental withdrawal of too much medication from vial B.

10. Insert the needle or needleless access device into vial A, being careful not to push the plunger and expel medication from the syringe into the vial. Invert the vial and carefully draw up the desired dose of medication from vial A into the syringe (Figure 2C).

    Rationale: Positive pressure within vial A allows fluid to fill the syringe without the need to aspirate.

    If too much medication is withdrawn from vial A, discard the syringe and start over. Do not push medication back into the vial.

11. Withdraw the needle or needleless access device and expel any excess air from the syringe.
12. Check that the fluid level in the syringe reflects the prescribed combined dose. The medications are now mixed.
13. Label the prepared syringe.
14. Replace the filter needle with a needleless system or with the appropriate-size needle according to the route of medication.
15. Compare the practitioner’s original order with the prepared medication and labels from vials.
16. Keep the needle of the prepared syringe sheathed or capped until ready to administer the medication (Table 1).
17. Check the syringe again carefully for the total combined dose of medications before administering to the patient.
18. Place used medication containers, all single-dose or empty multidose vials, and the needle or needleless access device in a puncture-proof and leakproof container.

    Rationale: Correct disposal of medication containers and needles into the appropriate waste receptacle prevents accidental injury to health care team members.¹

Mixing Insulin

1. If the patient takes insulin that is cloudy, roll the bottle of insulin between the hands to resuspend the insulin preparation.
2. Disinfect vials by cleansing the access diaphragm using friction and a sterile 70% isopropyl alcohol, ethyl alcohol, iodophor, or other approved antiseptic swab and allow to dry at least 10 seconds.³

   Rationale: Not all drug manufacturers guarantee that rubber seals of unused vials are sterile; therefore, the seal must be swabbed with alcohol while applying friction before preparing medication. Allowing alcohol to dry prevents it from coating the needle and mixing with the medication.

3. Verify the insulin dose against the MAR.
4. If mixing rapid- or short-acting insulin with either intermediate- or long-acting insulin using an insulin syringe, aspirate a volume of air equivalent to the dose to be withdrawn from the intermediate- or long-acting insulin first (Figure 3).

   Rationale: Short-acting insulin can be mixed with intermediate- or long-acting insulin. The purpose of mixing insulins is to provide short-acting action with intermediate- or long-acting action.

   Do not mix two long-acting insulins together in one syringe.

5. Insert the needle into the vial of intermediate- or long-acting insulin and inject the air into the vial. Do not let the tip of the needle touch the solution.

   Rationale: Air must be introduced into the vial to create the pressure needed to withdraw the dose later without aspirating.

6. Holding the plunger in place, remove the needle and syringe from the vial of intermediate- or long-acting insulin without aspirating medication or allowing air to escape the vial.
7. Using the same syringe, aspirate a volume of air equal to the dose of rapid- or short-acting insulin; then inject the air into the vial of rapid- or short-acting insulin. Invert the vial and allow the correct dose of insulin to flow into the syringe (Figure 4).
8. Remove the syringe from the rapid- or short-acting insulin and remove any air bubbles to ensure an accurate dose.
9. Verify the rapid- or short-acting insulin dose with the MAR and then show the insulin prepared in the syringe to another nurse to verify that the correct dose of insulin was prepared.
10. Determine what the combined volume of the medications should measure on the syringe scale by adding the number of units of both insulins together (e.g., 4 units regular + 10 units neutral protamine Hagedorn [NPH] insulin = 14 units total). Verify the combined dose.
11. Place the needle of the syringe back into the vial of intermediate- or long-acting insulin. Be careful not to push the plunger and inject insulin from the syringe into the vial.
12. Invert the vial and carefully withdraw the desired dose of intermediate- or long-acting insulin into the syringe (Figure 5).
13. Withdraw the needle and check that the fluid level in the syringe equals the prescribed combined dose of insulin.
14. Compare the MAR, computer screen, or computer printout with the prepared medication and labels from the vials.
15. Label the prepared insulin syringe.
16. Keep the needle of the prepared syringe sheathed or capped until ready to administer the medication (Table 1).
17. Check the syringe again carefully for the total combined dose of medications before administering to the patient.
18. Place used medication containers, all single-dose and empty multidose vials, and the needle or needleless access device in a puncture-proof and leakproof container.

    Rationale: Correct disposal of medication containers and needles into the appropriate waste receptacle prevents accidental injury to health care team members.¹

Mixing Medications From a Vial and an Ampule

1. Disinfect vials by cleansing the access diaphragm using friction and a sterile 70% isopropyl alcohol, ethyl alcohol, iodophor, or other approved antiseptic swab and allow to dry at least 10 seconds.³

   Rationale: Not all drug manufacturers guarantee that rubber seals of unused vials are sterile; therefore, the seal must be swabbed with alcohol while applying friction before preparing the medication. Allowing alcohol to dry prevents it from coating the needle and mixing with the medication.

2. Using a syringe with an attached needleless access device or an appropriate needle, aspirate a volume of air equivalent to the medication dose.

   Rationale: Air must be introduced into the vial to create the positive pressure needed to withdraw the solution.

3. Inject the air into the vial, making sure that the needle or needleless access device does not touch the solution (Figure 2A).
4. Holding the plunger in place, invert the vial, then allow the correct dose of medication to flow into the syringe.
5. Determine what the combined volume of the medications should measure on the syringe scale.

   Rationale: Determining the correct combined volume helps to prevent accidental withdrawal of too much medication from the ampule.

6. Change the needleless access device or needle to a filter needle.
7. Tap the top of the ampule lightly and quickly with a finger until fluid moves from the neck of the ampule.
8. Place a dry sterile gauze pad around the neck of the ampule. Do not use an alcohol-moistened gauze pad.

   Rationale: Alcohol can leak into the ampule and contaminate the medication.

9. Holding the neck of the ampule with the gauze pad, snap the neck of the ampule quickly and firmly away from the hands.
10. Set the ampule on a flat surface. Insert the filter needle into the center of the ampule opening.
11. Withdraw the medication from the ampule and verify the fluid level in the syringe. The medications are now mixed.
12. Label the medication syringe.
13. Replace the filter needle with a needleless system or with the appropriate-size needle according to the route of medication.
14. Compare the MAR, computer screen, or computer printout with the prepared medication and labels from the vials.
15. Keep the needle of the prepared syringe sheathed or capped until ready to administer medication (Table 1).
16. Check the syringe again carefully for the total combined dose of medications before administering to the patient.
17. Place used medication containers, all single-dose or empty multidose vials, and the needle or needleless access devices in a puncture-proof and leakproof container.

    Rationale: Correct disposal of medication containers and needles into the appropriate waste receptacle prevents accidental injury to health care team members.¹

MONITORING AND CARE

1. Watch the patient for adverse and allergic reactions to the medication. If a reaction occurs, follow the organization’s practice for emergency response.
2. Ask the patient to explain the purpose and side effects of the medication.
3. Assess injection sites for redness, swelling, or drainage.
4. Assess, treat, and reassess pain.

EXPECTED OUTCOMES

• Correct dose of combined medications
• Correct medications combined
• No air bubbles present in the syringe barrel
• Medication administered per the rights of medication safety

UNEXPECTED OUTCOMES

• Air bubbles inside the syringe barrel
• Incorrect medications combined
• Excess or insufficient volume of medication prepared
• Medication not administered per the rights of medication safety

DOCUMENTATION

• Education
• Patient’s response to medication, including any adverse reactions
• Patient’s weight in kilograms per the organization’s practice
• Unexpected outcomes and related interventions
• Comprehensive list of current medications and those recently discontinued

PEDIATRIC CONSIDERATIONS

• Throughout adolescence, children may need the participation or supervision or both of a family member when preparing and self-administering injections.
• With proper education and appropriate demonstration of understanding, many children are able to prepare and administer their own injections, including insulin.
• The nurse should assess the patient’s physical readiness, psychological readiness, psychological readiness, and development in activities of daily living before teaching the patient how to prepare and self-administer injections such as insulin.
• Family education is essential to successful disease management and medication administration with children, especially when preparation and administration of medications in a syringe are required.

OLDER ADULT CONSIDERATIONS

• Physiologic changes in older adults, such as decreased peripheral vision, presbyopia, and reduction in the power of skeletal and voluntary muscle contractions, may make it difficult for them to prepare and self-administer injections.
• The nurse should assess the patient’s physical and psychological readiness and ability to perform activities of daily living before teaching the patient to prepare and self-administer injections such as insulin.

REFERENCES

1. Association of periOperative Registered Nurses (AORN). (2023). Sharps safety. In Guidelines for perioperative practice (pp. 945-968). Denver: Author.
2. Environmental Protection Agency (EPA). (2019). Management standards for hazardous waste pharmaceuticals and amendment to the P075 listing for nicotine. Federal Register, Rules and Regulations, 84(36), 5816-5950. Retrieved June 26, 2024, from https://www.federalregister.gov/documents/2019/02/22/2019-01298/management-standards-for-hazardous-waste-pharmaceuticals-and-amendment-to-the-p075-listing-for
3. Institute for Safe Medication Practices (ISMP). (2015). ISMP safe practice guidelines for adult IV push medications: A compilation of safe practices from the ISMP Adult IV Push Medication Safety Summit. Retrieved June 26, 2024, from https://www.ismp.org/sites/default/files/attachments/2017-11/ISMP97-Guidelines-071415-3.%20FINAL.pdf
4. Institute for Safe Medication Practices (ISMP). (2016). Hardwiring safety into the computer system: One hospital’s actions to provide technology support for U-500 insulin. Retrieved June 26, 2024, from https://home.ecri.org/pages/ismp
5. Institute for Safe Medication Practices (ISMP). (2018). ISMP list of high-alert medications in acute care settings. Retrieved June 26, 2024, from https://www.ismp.org/sites/default/files/attachments/2018-08/highAlert2018-Acute-Final.pdf
6. Institute for Safe Medication Practices (ISMP). (2024). 2024-2025 Targeted medication safety best practices for hospitals. Retrieved June 26, 2024, from https://www.ismp.org/guidelines/best-practices-hospitals
7. Joint Commission, The. (2014). Sentinel event alert 52: Preventing infection from the misuse of vials. Retrieved June 26, 2024, from https://www.jointcommission.org/-/media/tjc/documents/resources/hai/sea_52.pdf
8. Joint Commission, The. (2024). National Patient Safety Goals for the hospital program. Retrieved June 26, 2024, from https://www.jointcommission.org/-/media/tjc/documents/standards/national-patient-safety-goals/2024/npsg_chapter_hap_jan2024.pdf
9. Lilley, L.L., Rainforth Collins, S., Snyder, J.S. (2023). Chapter 9: Photo atlas of drug administration. In Pharmacology and the nursing process (10th ed., pp. 102-134). St. Louis: Elsevier.
10. Reed, A.E. (2025). Chapter 22: Parenteral medications. In A.G. Perry and others (Eds.), Clinical nursing skills & techniques (11th ed., pp. 659-716). St. Louis: Elsevier.

ADDITIONAL READINGS

Schutijser, B.C.F. and others. (2019). Interruptions during intravenous medication administration: A multicentre observational study. Journal of Advanced Nursing, 75(3), 555-562. doi:10.1111/jan.13880

Adapted from Perry, A.G. and others (Eds.). (2025). Clinical nursing skills & techniques (11th ed.). St. Louis: Elsevier.

Clinical Review: Suzanne M. Casey, MSN-Ed, RN

Published: August 2024