Lab therapeutic incompat

• Therapeutic incompatibility can either be a combination of one drug or another drug, food supplement, or medical condition of a patient that could lead to possible decrease of action of the drug
• Therapeutic incompatibility may also increase the action of the drug, cause an adverse effect, and even fail to have a therapeutic plan for the patient
• Potentiation of therapeutic interactions between 2 or more ingredients

  1. Can be represented by a mathematical equation: 1 + 0 = 2 (2 pertains to the effect)

  2. Can either be desirable or undesirable. All drugs can be therapeutic, but in high doses or toxic doses, they can be poison

  3. Examples of desirable potentiation: Co-amoxiclav, Penicillin with Probenecid
• Destruction of effectiveness of one or more ingredients

  1. 1 + 1 = 0 (antagonism)

  2. Example of destructive effects: Vitamin K and Anticoagulants, Metal-containing compounds (Antacids) mixed concomitantly with Tetracyclines and Fluoroquinolones
• Occurrence of toxic manifestations within the patient

  1. Overreaction of an effect

  2. By adding an object drug and precipitant drug, there could be an increased effect

  3. Synergistic effect

  4. Example of toxic manifestations: Opioids with Barbiturates
• Factors affecting IV compatibility

  pH, Temperature, Degree of Dilution, Length of Time in Solution, Order of Mixing, Other Examples
• Factors affecting IV compatibility

  • pH
  • Temperature
  • Degree of dilution
  • Length of time in solution
  • Order of mixing
• Chemical reaction between an acid and a base


  Yields a salt and water; the salt may form an insoluble ppt
• Increased storage temperature

  Speeds up drug degradation
• Higher temperature


  Results in faster interaction
• More diluted the drugs are in a solution

  Less chance for ion interaction leading to incompatibility
• When mixing two drugs with different stability

  Use the shorter time for the BUD of the final product
• Order of mixing substances in IV admixture preparation

  Should not be added consecutively to prevent pooling or forming a layer on top of the IV fluid
• Mixing or dilution instructions can be found in the package insert
• Drugs that must be protected from light

  • Amphotericin B (antifungal), cisplatin (chemotherapeutic agent), metronidazole (anti-parasitic/anti-protozoal)
• Stability of Cefazolin

  • Stable at room temperature for 24 hours and 14 days if refrigerated
• Stability of antibiotics

  • Generally stable for at least 24 hours up to 7 days upon mixing with a diluent and stored in cool temperature
• Stability of Bactrim in different diluents

  • 5mL/75mL D5W stable for 2 hours, /125mL D5W stable for 6 hours
• Stability of Co-amoxiclav and Ticarcillin + Clavulanic Acid

  • Co-amoxiclav stable for 3 hours after dilution at 25 degrees Celsius, Ticarcillin + Clavulanic Acid stable for 24 hours in PNSS or SWFI, 12 hours in PLR at 25 degrees Celsius
• Stability of Corticosteroids

  • Hydrocortisone (Pharmacort) stable for 4 hours, Methylprednisolone stable for 48 hours after reconstitution, Dexamethasone single use in ampules
• Amber colored containers are used for photosensitive compounds
• Ways to minimize or prevent IV incompatibilities
• Ways to minimize or prevent IV incompatibilities

  • Mix thoroughly when a drug is added to the preparation
  • Minimize the number of drugs mixed together in an IV solution
  • Use freshly prepared solutions for compounding
  • Always check for BUD of preparations
• Check BUD of preparations: IV preparations - at least 24 hours, Syrups and Suspensions - 7 to 14 days, Antibiotics - strictly 7 days, Non-aqueous and Semi-solids
• IV preparation guidelines

  1. Minimize the number of drugs mixed together in an IV solution

  2. Use freshly prepared solutions for compounding

  3. Always check for BUD of preparations
• BUD of preparations

  • IV preparations - at least 24 hours
  • Syrups and Suspensions - 7 to 14 days
  • Antibiotics - strictly 7 days
  • Non-aqueous and Semi-solids (ointments and creams) - 30 days
• Steps before compounding IV products

  1. Always verify correct diluent, IV fluid, drug, and final concentration before compounding

  2. Order of mixing additives affects compatibility

  3. Solutions should be administered promptly after mixing or within the stability window

  4. Always refer to compatibility references

  5. Visually inspect final product after compounding for integrity, leaks, cloudiness, particulates, color, and proper preparation

  6. Ensure proper labeling of final IV product with beyond use date and time
• Parenteral Nutrition (PN) guidelines

  1. Factors for incompatibilities with PN

  2. Criteria for drugs commonly added to PN admixtures

  3. Route of Parenteral Nutrition: Central IV line, Peripheral IV line

  4. How to avoid incompatibilities with PN

  5. Importance of noting the time when PN was opened

  6. Correction of incompatibilities
• Factors for incompatibilities with PN

  • Precipitation of Calcium and Phosphate
  • Creaming/cracking of the liquid emulsion
  • Addition/simultaneous application of drugs to/with PN
• Criteria for drugs commonly added to PN admixtures

  • Stable dosage regimen over 24 hours
  • Pharmacokinetic profile supporting 24-hour infusion
  • Stable PN solution infusion rate
  • Documented chemical and physical stability over 24 hours
• How to avoid incompatibilities with PN

  • Never use PN for electrolyte therapy
  • Be familiar with manufacturer’s recommendation
  • Add divalent cations (calcium and magnesium) and phosphate as organic bound salts
  • Do not add drugs or Iron to PN
  • May piggyback lipids separately
  • Avoid Y-site administration of drugs with PN
• It is important to take note of the time (by hours) when parenteral nutrition was opened. The stability for it is strictly 24 hours
• Correction of incompatibilities

  1. Consult the physician

  2. Use pharmaceutical knowledge
• Preventing or minimizing incompatibilities

  1. Each drug should be mixed thoroughly after it is added to the preparation

  2. Solutions should be administered promptly after they are mixed

  3. The number of drugs mixed together in an IV solution should be kept to a minimum

  4. If a prescription calls for unfamiliar drugs or IV fluids, compatibility references should be consulted

  5. Use Drugs.com to check for drug incompatibilities