Accepted Practice

IV medication interactions and medication compatibility

Medication interactions

Medication interactions result when a medication is used with another medication or substance that modifies the drug’s expected action. Medication interactions can develop between food and drugs, between prescribed and over-the-counter drugs including herbal products, and as drug-to-drug interactions. A medication interaction can increase or decrease the drug’s effect through changes in absorption, distribution, metabolism, or excretion. Since IV medications have a rapid effect, understanding the concept of medication interactions helps you anticipate the potential results of drug combinations.

Synergistic effects develop when the combination of two or more drugs or substances results in a greater effect than that of separate administration would. An example is the combination of opioid analgesics, which are central nervous system (CNS) depressants, and other CNS depressants such as antihistamines or alcohol.

Foods that produce pharmacologic activity can also have a synergistic effect on drugs that have a similar action. For example, patients who take monoamine oxidase inhibitors should avoid foods containing tyramines or tryptophan. Each releases catecholamines, and the combined effect can be life-threatening.

A potentiating effect results when one drug increases the positive or negative effects of another. Often these drugs are given in combination intentionally; a common example is the drug regimen typically prescribed to treat tuberculosis.


Pharmacogenetic research offers new insights about drug interactions and the importance of individualized drug therapy. Because nurses monitor the effects of administered medications, it is important to have a basic understanding of gene-based drug metabolism.

Cytochrome P450 (CYP450) enzymes are essential for the metabolism of many medications. More than 50 drug-metabolizing isoenzymes have been found in humans; so far, 10 have been associated with functional polymorphism, a genetic variation in one or more specific isoenzymes. Unlike genetic defects, polymorphisms occur in more than 1% of humans, and CYP450 polymorphism is thought to be present in as many as 20% of specific populations. CYP polymorphism can make a patient more susceptible to the adverse effects of a medication or reduce a medication’s therapeutic action. Some drugs, hormones, and chemicals found in foods can inhibit or induce the function of CYP450 enzymes, resulting in significant drug interactions.

Because so many drugs and substances have been identified in CYP450 interactions, it is helpful to reference a CYP450 chart. However, there are commonly used drugs associated with CYP450 polymorphism. It is helpful to become familiar with classes of drugs that can have unexpected effects or alter the therapeutic effects of other medications. Common drugs and classifications associated with CYP polymorphism include antidepressants, beta blockers, warfarin, opioids, antiepileptics, azole antibiotics, and statins. Many of these medications are administered intravenously, alone and in multidrug therapy.

Managing medication interactions

Obtaining an accurate medication history at the time of a patient’s admission is essential for preventing some avoidable drug interactions. Patients often neglect to mention their use of over-the-counter preparations, including vitamin supplements and unregulated herbal or alternative-medicine products that can interact with prescribed drug therapy. They might hesitate to divulge the use of these alternative therapies to “traditional” healthcare providers or be unaware of the significant role these preparations can play in clinical outcomes.

When obtaining a family history for significant health risks, ask about any medication reactions in immediate family members. These questions might reveal valuable information about your patient’s potential for gene-based drug responses and medication interactions.

When administering drugs with dose-based responses, such as opioids or anti-hypertensive drugs, use the least amount of drug to provide the desired effect. Do the same for drugs with synergistic characteristics; “start low, go slow” is a good rule of thumb for administering IV medications safely and effectively.

Finally, be sure to document and report all adverse responses to medications to the patient’s primary healthcare provider. Document known and newly diagnosed allergies on your patient’s chart; include them on the medication administration record and the patient’s allergy band. Include medication effects in your patient-education plan. Teach patients and their families about the importance of avoiding known intolerances to medications and medication combinations.

Drug compatibility

While drug interaction refers to the combined systemic effect of medications, intravenous drug compatibility refers to the chemical stability of two or more medications when administered together. The standardized definition of compatibility is:

  • No visible or electronically detected indication of particulate formation, haze, precipitation, color change, or gas evolution
  • Stable (less than 10% decomposition) for at least 24 hours in admixture or for the entire test period (may be less than 24 hours)


Drug incompatibility

Some drugs in combination will create a precipitate or discoloration due to chemical changes. Other drug combinations will be less obvious, but chemical changes could have altered the drugs’ effects. The designation of incompatible is made when a drug is unable to meet both of the preceding criteria.

IV compatibility charts typically provide information about the compatibility of drugs combined in a syringe, combined at the Y-site of injection, if absolute incompatibility exists, or if data are insufficient to administer the drugs together safety. When administering more than two medications in one IV line, determine the compatibility of each medication with the other(s). Most drug reference manuals include compatibility charts listing commonly used IV medications. Often these charts have limited information or unclear data. Many agencies now have computerized tertiary compatibility programs based on the results of published reports from primary drug studies. It is important to access all available resources to determine drug compatibility. If unsure, assume incompatibility.

Managing drug incompatibility

Planning and implementing the administration of multiple scheduled IV medications require problem-solving and collaboration; drugs must be given at the prescribed frequency to maintain therapeutic drug levels and provide optimal benefits for the patient. However, standard administration times can cause conflict in infusion times and delay of therapy. The patient may have limited intravenous access due to inaccessible extremeties or poor peripheral circulation. These challenges are compounded when coadministration of medications is questionable or prohibited by incompatibility findings.

Suggested tools available for solving these problems include the following:

  • Collaborate with other healthcare team members, including pharmacists.
  • Stagger dosing procedures for drug-dose-time management. Check agency policies for staggering charts.
  • Suggest placement of a multilumen central IV access for patients with inaccessible or limited peripheral veins.
  • If coadministration of incompatible agents is unavoidable, infuse the agents as far apart time-wise as possible with a bridge or manifold device (such as using the proximal and distal ports) to allow minimal contact time of the two agents before administering them to the patient. Check your agency’s policy for the use of these devices.
  • Ideally, incompatible agents should be replaced with compatible combinations when possible. Consult with the pharmacist and ask the physician for appropriate substitutions that will provide the same desired effect.
To minimize the risk of incompatibility of IV bolus (push) medications, be sure to flush before and after each medication with at least 10 mL of sterile normal saline or according to your agency’s policy.