Identifying potential drug interactions in chronic kidney
               disease patients

Marquito, Alessandra Batista; Fernandes, Natália Maria da Silva; Colugnati, Fernando Antonio Basile; Paula, Rogério Baumgratz de

doi:10.5935/0101-2800.20140006

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Brazilian Journal of Nephrology

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Original Articles • J Bras Nefrol 36 (1) • Jan-Mar 2014 • https://doi.org/10.5935/0101-2800.20140006 copy

Identifying potential drug interactions in chronic kidney disease patients

Authorship SCIMAGO INSTITUTIONS RANKINGS

Introduction:

Drug interactions (DIs) are common in clinical practice and are directly related to factors such as polypharmacy, aging, hepatic metabolism and decreased renal function. Individuals with chronic kidney disease (CKD) often require multiple classes of drugs being at important risk for the development of DIs.

Objective:

Identify potential interactions among drugs prescribed to patients with CKD on conservative treatment, and factors associated with their occurrence.

Methods:

Observational cross-sectional study, with analysis of 558 prescriptions. Potential DIs were identified by the database MICROMEDEX^®, software that provides an internationally known pharmacopoeia.

Results:

There was a predominance of males (54.7%), seniors (69.4%), stage 3 CKD (47.5%), overweight and obese patients (66.7%). The most prevalent comorbidities were hypertension (68.5%) and diabetes mellitus (31.9%). Potential DIs were detected in 74.9% of prescriptions. Among the 1364 DIs diagnosed, 5 (0.4%) were contraindicated and 229 (16.8%) of greater severity, which need immediate intervention. Interactions of moderate and low severity were identified in 1049 (76.9%) and 81 (5.9%) prescriptions, respectively. The probability of one DI increased by 2.5 times for each additional drug (CI = 2.18 to 3.03). Obesity, hypertension, diabetes as well as advanced stage of CKD were risk factors strongly associated with DI occurrence.

Conclusion:

Drug associations in individuals with CKD were related to high prevalence of serious DIs, especially in the later stages of the disease

drug combinations; drug interactions; kidney failure, chronic

Severity	PA1	PA2	Frequency (Percent)	Summary	Likely involved mechanism	Clinical management	%/DI (n =1364)
Contraindication (n = 5)	Carbamazepine	Nifedipine	3 (60.0)	Reduces exposure to nifedipine.	Induction of nifedipine metabolism mediated by CYP3A4.	Alternative antihypertensive drug should be considered.	0.2
	Nifedipine	Phenytoin sodium	1 (20.0)	Reduces exposure to nifedipine and increases risk of toxicity by phenytoin (ataxia, hyperreflexia, tremor, nystagmus).	Induction of nifedipine metabolism mediated by CYP3A4 and reduction of phenytoin metabolism.	Alternative antihypertensive drug should be considered.	0.1
	Nifedipine	Phenobarbital	1 (20.0)	Reduces exposure to nifedipine.	Induction of nifedipine metabolism mediated by CYP3A4.	Alternative anti-hypertensive drug should be considered.	0.1
Major (n = 229)	Enalapril maleate	Losartan	50 (21.8)	Increased risk of adverse events (syncope, hypotension, hyperkalemia, altered renal function, acute kidney injury).	Dual blockade of the renin-angiotensin-aldosterone system	Closely monitor renal function if coadministration of ACE inhibitors and ARBs is needed.	3.7
	Allopurinol	Captopril	24 (10.5)	May result in hypersensitivity reaction (Stevens-Johnson syndrome, skin rash, coronary artery spasm with anaphylactic reaction).	Unknown	Monitor hypersensitivity reaction.	1.8
	Allopurinol	Enalapril	21 (9.2)	May result in hypersensitivity reaction (Stevens-Johnson syndrome, skin rash, coronary artery spasm with anaphylactic reaction).	Unknown	Monitor hypersensitivity reaction.	1.5
Moderate (n = 1049)	Furosemide	Acetylsalicylic acid	106 (10.1)	May result in reduced diuretic and anti-hypertensive effect.	Unknown	Monitor diuresis and creatinine clearance.	7.8
	Enalapril	Furosemide	80 (7.6)	May result in postural hypotension (first dose).	Vasodilation and relative intravascular volume depletion.	Monitor hypotension, fluids, andbody weight regularly for up to two weeks after dosage adjustments.	5.9
	Captopril	Furosemide	69 (6.6)	May result in postural hypotension (first dose).	Vasodilation and relative intravascular volume depletion.	Monitor hypotension, fluids, andbody weight regularly for up to two weeks after dosage adjustments.	5.1
Minor (n = 81)	Metformin	Nifedipine	20 (24.7)	May increase metformin absorption.	Unknown	Monitor clinical signs of metformin toxicity, including diarrhea, nausea, and vomiting	1.5
	Furosemide	Hydralazine	18 (22.2)	May increase furosemide diuretic response.	Increased furosemide renal clearance.	Monitor diureticr esponse, serum electrolytes, and creatinine clearance. Adjust dosage if needed.	1.3
	Enalapril	Erythropoietin	10 (12.3)	May result in high maintenance dosages of erythropoietin to sustain hematocrit levels.	Unknown	Monitor patients given high doses of ACEi for erythropoietin effectiveness. When coadministered, higher dosages of erythropoietin may be needed administrados.	0.7

Characteristic		N (Total = 558)	p _- value	OR (95% CI)
Gender
	Male	305	-	Ref
	Female	253	0.375	0.841 (0.57 - 1.23)
Age
	< or equal to 39	33	-	Ref
	40 to 59	138	0.460	1.34 (0.61 - 2.94)
	> or greater than 60	387	0.019	2.41 (1.15 - 5.06)
Smoking		196	0.866	0.96 (0.64 - 1.44)
Alcohol		87	0.098	0.65 (0.40 - 1.08)
Number of medications
	0 to 4	187	-	Ref
	More than 5	371	0.000	36.80 (21.00 - 64.51)
CKD stage
	1 and 2	103	-	Ref
	3a	107	0.000	3.24 (1.76 - 5.95)
	3b	158	0.000	3.30 (1.90 - 5.71)
	4	153	0.000	3.30 (1.90 - 5.74)
	5	37	0.013	3.04 (1.27 - 728)
BMI, according to WHO
	Low and normal weight	162	-	Ref
	Overweight	195	0.223	1.33 (0.84 - 2.11)
	Obesity	185	0.001	2.47 (1.47 - 4.14)
Baseline disease
	Hypertensive nephropathy	213	0.007	1.76 (1.16 - 2.67)
	Diabetic nephropathy	120	0.032	1.75 (1.05 - 2.94)
	Ischemic nephropathy	25	0.290	1.79 (0.60 - 5.33)
	Chronic glomerulonephritis	26	0.825	0.90 (0.37 - 2.20)
	Reflux nephropathy	5	0.099	0.22 (0.03 - 1.32)
	Unspecified	109	0.189	1.41 (0.84 - 2.35)
Comorbidities
	Diabetes mellitus	178	0.000	2.50 (1.56 - 4.01)
	Hypertension	382	0.000	2.03 (1.36 - 3.02)
	Coronary disease	37	0.373	1.46 (0.63 - 3.42)
	Heart failure	29	0.073	3.02 (0.90 - 10.16)

Factors	p - value	OR (95% CI)
Age
< or equal to 39	0.064	Ref
40 to 59	0.907	0.94 (0.38 - 2.36)
> or greater than 60	0.253	1.65 (0.69 - 3.94)
CKD stage
1 and 2	0.000	Ref
3a	0.001	3.12 (1.61 - 6.05)
3b	0.001	2.75 (1.51 - 5.02)
4	0.000	3.67 (1.97 - 6.83)
5	0.003	4.74 (1.68 - 13.30)
BMI
Low and normal weight	0.004	Ref
Overweight	0.337	1.27 (0.77 - 2.10)
Obesity	0.001	2.58 (1.46 - 4.54)
DM	0.018	1.95 (1.12 - 3.41)
Systemic hypertension	0.013	1.80 (1.13 - 2.87)
CHF	0.173	2.81 (0.63 - 12.47)

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[TFN01t05] **Note: the BMI was calculated based on weight and height measurements according to the formula BMI = body weight (kg)/height2 (cm). The cutoff points for the BMI described by the WHO were used in this study, as follows: low body weight (BMI < 18.5); normal body weight (BMI 18.5-24.99); overweight (BMI 25-29.99); and obesity (BMI > 30.00).