Interference of drugs with laboratory findings
Drug interference refers to the possibility that certain medications or substances may affect the
results of laboratory tests, leading to a misinterpretation of those results. Medications prescribed
by a physician, as well as over-the-counter (OTC) drugs, can significantly influence the
outcomes of laboratory tests, resulting in false-negative or false-positive results. The dosage of
the medication itself can be crucial in determining how much the parameters are elevated or
lowered. Inaccurate results can lead to incorrect diagnoses and treatments, which can be highly
dangerous for the patient. When undergoing laboratory tests, it is important for the patient to
inform the healthcare professional whether they are using any medications, and to provide the
names, dosages, and purposes of those medications. When interpreting the results, it is important
for the healthcare professional to be aware of the potential interference of drugs on specific
parameters.
1.1. Laboratory Practice
Laboratory practice represents a continuous process divided into three phases: pre-analytical
(also the most vulnerable phase of the process), analytical, and post-analytical. Prevention of pre-
analytical errors, as well as subsequent prevention of inappropriate patient treatment due to
incorrect test results, requires ongoing awareness of the primary factors associated with patient
variables, sample collection, and processing. The most important patient characteristics include
age, gender, dietary habits, physiological changes, and medication use. Research conducted in 18
European countries revealed that among 3,600 tested patients, a staggering 68% had consumed at
least one over-the-counter medication or dietary supplement. Additionally, 48% of patients did
not disclose their use of these substances to their physician. Among patients who believed it was
important to inform their doctor about medication or dietary supplement use, 30% did not
consider this information relevant to laboratory professionals. There are several examples of how
medications can affect the results of laboratory tests:
1. Interference with liver function tests - medications such as acetaminophen or statins can affect
liver enzymes and cause changes in liver function tests.
2. Interference with coagulation tests - anticoagulants such as warfarin or heparin can
significantly affect coagulation tests (bleeding time, PT/INR).
3. Interference with electrolytes - diuretics, used to control blood pressure or edema, can affect
electrolyte concentrations such as sodium, potassium, and chloride.
1
,4. Interference with bleeding tests - NSAIDs (nonsteroidal anti-inflammatory drugs) such as
ibuprofen or aspirin can prolong bleeding time.
5. Interference with blood sugar tests - insulin or oral hypoglycemics can affect blood glucose
levels.
6. Interference with hormone tests - contraceptives, thyroid medications, or corticosteroids can
affect hormone test results.
7. Interference with immunological tests - immunosuppressants such as corticosteroids or
cytostatics can affect immunological test results, including antibody measurements.
8. Interference with renal function tests - antibiotics or ACE inhibitors can affect renal function
test results.
1.2. In vivo interferences
In vivo interferences represent changes in the concentration or activity of analytes before sample
collection and analysis. These interferences will always affect the test result, regardless of the
analytical method used. Medications can cause in vivo interferences in several ways. By
prolonging their pharmacological effects, a medication can affect the results of laboratory tests.
Thiazide and loop diuretics will significantly increase the elimination of potassium through the
kidneys. However, low serum potassium concentration may occur even in patients on therapy,
indicating active hypokalemia. Similarly, elevated blood urea nitrogen (BUN) levels may result
from excessive fluid loss during treatment with thiazides and loop diuretics. Other medications
can cause in vivo interferences by exhibiting their toxicological effects. The first signs of organ
damage resulting from medication use are abnormal laboratory test results. For example,
isoniazid and rifampicin can cause hepatotoxicity, and elevated liver transaminases will indicate
inflammatory processes in the liver. Continuous use of high doses of aminoglycoside antibiotics
will lead to acute proximal tubular necrosis. The level of creatinine and aminoglycosides will
vary or increase if the patient does notstop taking antibiotics or if the dose is not reduced. In the
case of bone marrow suppression caused by cyclophosphamides, neutropenia will be evident 10-
14 days after receiving the dose.
Chemical interference may occur if a substance being determined reacts in vivo with the
medication administered before blood sampling for analysis. For example,
ethylenediaminetetraacetic acid (EDTA) can affect the determination of serum calcium. Under
certain conditions, such as lead poisoning or collagen diseases, EDTA is used therapeutically to
reduce lead and calcium concentrations. In patients whose therapy is based on EDTA use,
calcium cannot be determined by colorimetric or fluorometric methods based on the calcium-
EDTA complex. Using atomic absorption spectroscopy, calcium can be determined because the
2
, flame used in atomic absorption spectroscopy destroys the chelating agent. Medications can also
interfere with laboratory findings by negating nonspecific oxidations and reductions necessary
for chemical analysis. Penicillin, streptomycin, and ascorbic acid react with the cupric ion;
however, false-negative results of glucose determination may occur if the copper reduction
method was previously used. If a specific enzyme method, such as glucose oxidase, is used,
ascorbic acid may cause false-negative results by inhibiting the oxidation of the specific
chromogen in the reaction. Monitoring the increase in transaminase activity is particularly
important when using the diazocolorimetric method. Increased activity has been observed in
several patients treated with erythromycin and p-aminosalicylic acid. These interferences can be
eliminated by using the ultraviolet kinetic method.
1.3. In vitro interferences
1.4. Medications present in a patient's bodily fluids or tissues can directly affect the results of
laboratory testing during the in vitro analytical process. This type of interference heavily depends
on the testing method, as it may strongly impact one method but not others. For instance,
determining the serum levels of digoxin is achieved using radioimmunoassay (RIA) or
immunofluorescence polarization. These analyzes are based on the three-dimensional structure
of the digoxin molecule, and many other drugs with similar chemical structures can cross-react
with the analysis, leading to false-positive or false-negative results. In this scenario, to accurately
determine the concentration of digoxin in serum, another method such as high-pressure liquid
chromatography (HPLC) can be used.
1.5. The tubes used during sampling may contain lithium heparin or sodium fluoride. Heparin
may cause interference in the analysis of aminoglycosides, while sodium fluoride may cause
falsely elevated BUN values when measured on an Ekatchem chemical analyzer. Some
medications can even cause discoloration of bodily fluids, which can lead to interference in
colorimetric, photometric, and fluorometric methods. For example, phenazopyridine can change
the color of urine to red-orange, which can be mistakenly interpreted as blood.
1.6. When determining creatinine using the Jaffe method, the concentration can be as much as
200 μmol/L higher due to interference from cephalosporins (excluding cefotaxime and
ceftazidime) with the mentioned method. Falsely elevated blood glucose levels are determined
using capillary blood glucose measurements in patients receiving intravenous vitamin C. High
doses of intravenously administered vitamin C (6g/day for ≥ 5 days) are associated with lower
mortality rates in patients with sepsis and septic shock. However, the interaction between
vitamin C and glucose determination methods can result in erroneously interpreted pseudo-
hyperglycemia and inappropriately prescribed insulin therapy, leading to dangerous, sometimes
fatal consequences. Since the spectrophotometric hexokinase method does not interfere with
3
Drug interference refers to the possibility that certain medications or substances may affect the
results of laboratory tests, leading to a misinterpretation of those results. Medications prescribed
by a physician, as well as over-the-counter (OTC) drugs, can significantly influence the
outcomes of laboratory tests, resulting in false-negative or false-positive results. The dosage of
the medication itself can be crucial in determining how much the parameters are elevated or
lowered. Inaccurate results can lead to incorrect diagnoses and treatments, which can be highly
dangerous for the patient. When undergoing laboratory tests, it is important for the patient to
inform the healthcare professional whether they are using any medications, and to provide the
names, dosages, and purposes of those medications. When interpreting the results, it is important
for the healthcare professional to be aware of the potential interference of drugs on specific
parameters.
1.1. Laboratory Practice
Laboratory practice represents a continuous process divided into three phases: pre-analytical
(also the most vulnerable phase of the process), analytical, and post-analytical. Prevention of pre-
analytical errors, as well as subsequent prevention of inappropriate patient treatment due to
incorrect test results, requires ongoing awareness of the primary factors associated with patient
variables, sample collection, and processing. The most important patient characteristics include
age, gender, dietary habits, physiological changes, and medication use. Research conducted in 18
European countries revealed that among 3,600 tested patients, a staggering 68% had consumed at
least one over-the-counter medication or dietary supplement. Additionally, 48% of patients did
not disclose their use of these substances to their physician. Among patients who believed it was
important to inform their doctor about medication or dietary supplement use, 30% did not
consider this information relevant to laboratory professionals. There are several examples of how
medications can affect the results of laboratory tests:
1. Interference with liver function tests - medications such as acetaminophen or statins can affect
liver enzymes and cause changes in liver function tests.
2. Interference with coagulation tests - anticoagulants such as warfarin or heparin can
significantly affect coagulation tests (bleeding time, PT/INR).
3. Interference with electrolytes - diuretics, used to control blood pressure or edema, can affect
electrolyte concentrations such as sodium, potassium, and chloride.
1
,4. Interference with bleeding tests - NSAIDs (nonsteroidal anti-inflammatory drugs) such as
ibuprofen or aspirin can prolong bleeding time.
5. Interference with blood sugar tests - insulin or oral hypoglycemics can affect blood glucose
levels.
6. Interference with hormone tests - contraceptives, thyroid medications, or corticosteroids can
affect hormone test results.
7. Interference with immunological tests - immunosuppressants such as corticosteroids or
cytostatics can affect immunological test results, including antibody measurements.
8. Interference with renal function tests - antibiotics or ACE inhibitors can affect renal function
test results.
1.2. In vivo interferences
In vivo interferences represent changes in the concentration or activity of analytes before sample
collection and analysis. These interferences will always affect the test result, regardless of the
analytical method used. Medications can cause in vivo interferences in several ways. By
prolonging their pharmacological effects, a medication can affect the results of laboratory tests.
Thiazide and loop diuretics will significantly increase the elimination of potassium through the
kidneys. However, low serum potassium concentration may occur even in patients on therapy,
indicating active hypokalemia. Similarly, elevated blood urea nitrogen (BUN) levels may result
from excessive fluid loss during treatment with thiazides and loop diuretics. Other medications
can cause in vivo interferences by exhibiting their toxicological effects. The first signs of organ
damage resulting from medication use are abnormal laboratory test results. For example,
isoniazid and rifampicin can cause hepatotoxicity, and elevated liver transaminases will indicate
inflammatory processes in the liver. Continuous use of high doses of aminoglycoside antibiotics
will lead to acute proximal tubular necrosis. The level of creatinine and aminoglycosides will
vary or increase if the patient does notstop taking antibiotics or if the dose is not reduced. In the
case of bone marrow suppression caused by cyclophosphamides, neutropenia will be evident 10-
14 days after receiving the dose.
Chemical interference may occur if a substance being determined reacts in vivo with the
medication administered before blood sampling for analysis. For example,
ethylenediaminetetraacetic acid (EDTA) can affect the determination of serum calcium. Under
certain conditions, such as lead poisoning or collagen diseases, EDTA is used therapeutically to
reduce lead and calcium concentrations. In patients whose therapy is based on EDTA use,
calcium cannot be determined by colorimetric or fluorometric methods based on the calcium-
EDTA complex. Using atomic absorption spectroscopy, calcium can be determined because the
2
, flame used in atomic absorption spectroscopy destroys the chelating agent. Medications can also
interfere with laboratory findings by negating nonspecific oxidations and reductions necessary
for chemical analysis. Penicillin, streptomycin, and ascorbic acid react with the cupric ion;
however, false-negative results of glucose determination may occur if the copper reduction
method was previously used. If a specific enzyme method, such as glucose oxidase, is used,
ascorbic acid may cause false-negative results by inhibiting the oxidation of the specific
chromogen in the reaction. Monitoring the increase in transaminase activity is particularly
important when using the diazocolorimetric method. Increased activity has been observed in
several patients treated with erythromycin and p-aminosalicylic acid. These interferences can be
eliminated by using the ultraviolet kinetic method.
1.3. In vitro interferences
1.4. Medications present in a patient's bodily fluids or tissues can directly affect the results of
laboratory testing during the in vitro analytical process. This type of interference heavily depends
on the testing method, as it may strongly impact one method but not others. For instance,
determining the serum levels of digoxin is achieved using radioimmunoassay (RIA) or
immunofluorescence polarization. These analyzes are based on the three-dimensional structure
of the digoxin molecule, and many other drugs with similar chemical structures can cross-react
with the analysis, leading to false-positive or false-negative results. In this scenario, to accurately
determine the concentration of digoxin in serum, another method such as high-pressure liquid
chromatography (HPLC) can be used.
1.5. The tubes used during sampling may contain lithium heparin or sodium fluoride. Heparin
may cause interference in the analysis of aminoglycosides, while sodium fluoride may cause
falsely elevated BUN values when measured on an Ekatchem chemical analyzer. Some
medications can even cause discoloration of bodily fluids, which can lead to interference in
colorimetric, photometric, and fluorometric methods. For example, phenazopyridine can change
the color of urine to red-orange, which can be mistakenly interpreted as blood.
1.6. When determining creatinine using the Jaffe method, the concentration can be as much as
200 μmol/L higher due to interference from cephalosporins (excluding cefotaxime and
ceftazidime) with the mentioned method. Falsely elevated blood glucose levels are determined
using capillary blood glucose measurements in patients receiving intravenous vitamin C. High
doses of intravenously administered vitamin C (6g/day for ≥ 5 days) are associated with lower
mortality rates in patients with sepsis and septic shock. However, the interaction between
vitamin C and glucose determination methods can result in erroneously interpreted pseudo-
hyperglycemia and inappropriately prescribed insulin therapy, leading to dangerous, sometimes
fatal consequences. Since the spectrophotometric hexokinase method does not interfere with
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