CHPPC Module 4, Section 2: IV Compatibility & Stability
MODULE 4: STERILE COMPOUNDING & IV ROOM OPERATIONS

Section 2: IV Compatibility & Stability

Beyond the sterility assured by USP <797>, the safety of an IV medication hinges on its physical and chemical integrity. This section is a deep dive into the critical properties that determine whether a drug solution is safe to administer. You will become an expert in preventing the invisible chemical reactions and physical changes that can turn a therapeutic dose into a harmful substance.

Part 1: Y-Site Compatibility

The Rules of the Road for IV Lines

Most hospitalized patients have limited IV access and are often receiving multiple IV medications simultaneously. To avoid placing multiple IV catheters, nurses will often infuse a secondary “piggyback” medication into a port on the tubing of a primary “maintenance” fluid. This port is called the “Y-site.” When two separate IV solutions mix at this site, they must be physically and chemically compatible.

Retail Pharmacist Analogy: Advanced Drug-Interaction Checking

In community pharmacy, you are a master of checking for drug-drug interactions that occur inside the patient’s body after absorption. Y-site compatibility is the same concept, but it happens outside the body, in the IV tubing, just seconds before the drugs enter the patient’s vein. Instead of a metabolic interaction, you are looking for a direct physical or chemical reaction between two drugs. Your interaction software is your brain, supplemented by specialized IV compatibility resources.

A Gallery of Classic Incompatibilities: The “Never Events”

While you must always check a reference, certain incompatibilities are so common and dangerous they should be committed to memory.

  • Ceftriaxone + Calcium-Containing Solutions: The most infamous incompatibility. Mixing ceftriaxone with any solution containing calcium (including Lactated Ringer’s and PN) forms an irreversible, rock-like precipitate. There have been fatal cases in neonates. These must NEVER be in the same IV line.
  • Phenytoin + Dextrose: Phenytoin immediately precipitates in acidic D5W. It must always be in 0.9% NaCl.
  • Sodium Bicarbonate + Acidic Drugs: Highly alkaline sodium bicarbonate will rapidly degrade acidic catecholamines like norepinephrine or dopamine.
  • Phosphate + Calcium: The constant battle in compounding parenteral nutrition (PN). Concentrations must be carefully managed to prevent the precipitation of calcium phosphate.
Your Y-Site Verification Workflow: A Daily Responsibility
  1. Step 1: Identify All Running IVs. Look at the MAR. Is the patient on a continuous infusion of heparin? You need a complete picture of everything going into their veins.
  2. Step 2: Consult a Compatibility Reference. You must use an approved reference like Trissel’s (via Lexicomp) or the Micromedex IV Compatibility Tool.
  3. Step 3: Intervene if Necessary. If an incompatibility is found, you must contact the nurse with a solution:
    • “Flush, Push, Flush”: Stop the primary infusion, flush the line with saline, give the drug, and flush again.
    • Reschedule Administrations: Change administration times so the two drugs are not given near each other.
    • Obtain New IV Access: Request a new, dedicated IV line for the incompatible medication.

Part 2: The Science of Drug Integrity in Solution

Stability, BUD, and the Invisible Instabilities

Once a sterile drug powder is reconstituted or a liquid drug is diluted in an IV bag, a countdown timer starts. The drug is now subject to chemical degradation and, if sterility is breached, microbial growth. Your role is to understand the factors that affect a drug’s stability and to assign a correct, evidence-based Beyond-Use Date (BUD).

Diluent Limitations: D5W vs. NS is a Critical Choice

The choice of diluent is not arbitrary. For many drugs, it is a critical stability issue. The wrong choice can cause precipitation. You must have the most common diluent-specific drugs memorized.

MUST be in Dextrose (D5W)

Mnemonic: “A DIAbetic Can’t Eat Pie” – Amphotericin, Dalvance/Oritavancin, Infliximab, Amiodarone, Bactrim, Carboplatin, Etoposide, Pentamidine

MUST be in Saline (NS)

Mnemonic: “ACID APE” – Ampicillin, Caspofungin, Infliximab, Daptomycin, Amp/Sulbactam, Phenytoin, Ertapenem

Masterclass: Beyond-Use Dating (BUD)

The final BUD on your CSP is the SHORTER of two competing clocks:

  1. The Sterility Clock (USP <797>): Determined by the CSP Category. For a typical Category 2 IV, this could be up to 10 days in the refrigerator.
  2. The Chemical Stability Clock: Determined by manufacturer/study data. How long is the drug molecule itself stable once diluted?

Worked Example (Meropenem): It’s a Category 2 CSP, so the sterility clock is long (10 days refrigerated). However, its chemical stability in NS is only 24 hours refrigerated. Conclusion: The shorter, 24-hour chemical stability clock dictates the final BUD.

Beyond Precipitation: The Invisible Instabilities

  • Adsorption to PVC: Lipophilic drugs can stick to PVC bags/tubing, reducing the delivered dose.
    • Classic Examples: Nitroglycerin, Insulin, Lorazepam, Amiodarone.
    • Your Role: Ensure these are prepared in non-PVC containers (polyolefin or glass).
  • Light Protection: Some drugs are subject to photodegradation and need a light-protectant bag.
    • Classic Examples: Nitroprusside, Amphotericin B, Micafungin, Doxycycline.
  • Filtration: Some drugs require in-line filters to remove particulates.
    • Classic Examples: Phenytoin (0.22-micron), Amiodarone, Parenteral Nutrition (1.2-micron for lipids).
  • Storage: Most CSPs are refrigerated, but some must NEVER be refrigerated.
    • Classic “Do Not Refrigerate” Examples: Metronidazole, Moxifloxacin, Bactrim.