Identification and characterisation of potential drug interaction in a Hospital in Jundiai, Sao Paulo State

Escarabeli, Renata Pereira Munhoz; Naime, Ana Carolina Antunes

doi:10.1590/s2175-97902022e20355

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Brazilian Journal of Pharmaceutical Sciences

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Article • Braz. J. Pharm. Sci. 58 • 2022 • https://doi.org/10.1590/s2175-97902022e20355 copy

Identification and characterisation of potential drug interaction in a Hospital in Jundiai, Sao Paulo State

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

To identify and characterize the most frequent Drug Interaction (DI) in a Jundiaí Hospital. Exploratory, descriptive, and analytical cross-sectional study with a quantitative approach. The source of the study is 100 prescriptions made by the medical service of a hospital in Jundiaí, dispensed from August to October 2018, by the pharmacy of the mentioned hospital for palliative care, mental health, and emergency care. Data plotting in Excel. Of the 100 prescriptions analyzed 60 had at least one type of interaction, 164 DI were found, 14.6% severe, 67.7% moderate, 17.1% minor and 0.6% unspecified. The mechanism of interaction that most appeared in the study was pharmacodynamics, 54.3%, pharmacokinetics were present in 34.1% of DI and 11.6% were not specified. The group most affected by DI was male 33% of prescriptions, female 27%, and 40% showed no interactions. The age group with the most interactions was from 50 to 59 years old. Of the prescriptions that had MI, those with 4 or more interactions were the ones that prevailed. The class of drugs that presented the most interactions was psychotropic drugs. A relevant frequency of interactions was identified by the present study, being the class of psychotropic drugs the most evident and interactions of medium severity the most found, which may be responsible for lowering the clinical condition of patients and the need of possible additional interventions. The data presented may contribute as epidemiological indicators, guiding corrective actions, aiming at the welfare of patients.

Keywords:
Drug Interaction; Polypharmacy; Medicine interaction

GENDER	Number of Prescriptions (%)	Prescriptions DI (%)
Male	48%	33%
Female	52%	27%

Amount DI by Prescription	Frequency in Prescriptions	Frequency in Prescriptions (%)
0	40	40%
1	18	18%
2	8	8%
3	10	10%
≥4	24	24%
DI TOTAL	60	60%

Age Range	Quantity of DI	Percentage of DI
19-29	6	10%
30-39	11	18%
40-49	3	5%
50-59	20	33%
60-69	12	20%
70-79	3	5%
80-90	5	8%

SEVERITY	Amount of Interactions	Percentage of Interactions
Major	24	14,6%
Moderate	111	67,7%
Minor	28	17,1%
Not Specified	1	0,6%
Total	164	100%

Mechanism	Amount	Percentage
Pharmacokinetics	56	34,1%
Pharmacodynamics	89	54,3%
Not Specified	19	11,6%
Total	164	100%

Route	Total	(%)
IV + IV	8	4,8%
IV + SC	1	0,6%
IV + PO	4	2,4%
IM + IV	2	1,2%
SC + IV	1	0,6%
PO + IV	11	6,7%
PO + IM	2	1,2%
PO + SC	1	0,6%
PO + PO	135	81,8%
Total	164	100%

DI Total	164	100%
Presence of at least one Psychotropic	138	84,1%
DI Between Psychotropic	91	55,5%
DI among other categories of drugs	26	15,9%

N° REPETITIONS	ADMINISTRATION ROUTE	INTERACTIONS	EFFECT	MECHANISM: DESCRIPTION	MECHANISM	GRAVITY
8	PO + PO	VALPROIC ACID + DIAZEPAM	...	Valproate displaces Diazepam from its plasma albumin binding sites and inhibits its metabolism.	Pharmacokinetics	MODERATE
8	PO + IV	CLONAZEPAM + OMEPRAZOLE	Prolongation of half-life leading to increased sedative effects and ataxia.	Decreased oxidative metabolism of Benzodiazepine.	Pharmacokinetics	MODERATE
7	PO + PO	VALPROIC ACID + CLONAZEPAM	May induce absence status in patients with a history of convulsion.	There may be decreased plasma levels of Clonazepam, inducing its hepatic metabolism.	Pharmacokinetics	MODERATE
6	PO + PO	CLONAZEPAM + RISPERIDONE	Respiratory or central nervous system depressant effects may be increased (synergisms).	Synergisms	Pharmacodynamics	MODERATE
6	PO + PO	DIAZEPAM + HALOPERIDOL	The effects of the central nervous system and respiratory depressant may be increased.	Synergism of the depressant effect on the central nervous system.	Pharmacodynamics	MODERATE
5	PO + PO	VALPROIC ACID + CLOZAPINE	Increased sedation and impairment of the central nervous system.	Valproate may slightly increase serum Clozapine levels and Clozapine metabolite levels.	Pharmacokinetics	MINOR
5	PO + PO	VALPROIC ACID + HALOPERIDOL	Respiratory or central nervous system depressant effects may be increased (synergisms).	Synergism of the depressant effect on the central nervous system.	Pharmacodynamics	MODERATE
5	PO + PO	CHLORPROMAZINE + HALOPERIDOL	Increased plasma levels of Haloperidol may occur leading to side effects such as the risk of arrhythmias.	Decreased CYP2D6 enzymatic activity may cause an increased concentration of Haloperidol. Possibly due to inhibition of Haloperidol metabolism by this route. Also, there is possibly an additive or synergistic effect.	Pharmacokinetics	MAJOR
4	PO + PO	VALPROIC ACID + BIPERIDEN	Respiratory or central nervous system depressant effects may be increased	The central nervous system or respiratory depressant effects may be increased additionally or synergistically.	Pharmacodynamics	MODERATE
4	PO + PO	BIPERIDEN + CLOZAPINE	There is a possibility of an increased risk of adverse effects such as central nervous system depression and tardive dyskinesia. Excessive anticholinergic effects may occur in combination, which may result in paralytic ileus, hyperthermia, heatstroke, and anticholinergic intoxication syndrome.	Centrally acting anticholinergic agents may antagonize the therapeutic effects of neuroleptic agents.	Pharmacodynamics	MODERATE
4	PO + PO	BISACODYL + DEXAMETHASONE	Concomitant use with adrenocorticosteroids, such as dexamethasone, may increase the risk of electrolyte imbalance.	The use of laxatives may cause electrolyte loss and increase the risk of hypokalemia associated with corticosteroid therapy. For corticosteroids promote sodium and water retention and potassium excretion. Particularly if administered systemically for longer than short periods.	Pharmacodynamics	MODERATE
3	PO + PO	AMITRIPTYLINE + BACLOFEN	The effects of the central nervous system may be increased. Muscle hypotonia, CNS depression.	Amitriptyline is a tricyclic antidepressant. Potentiates the effect of Baclofen causing a depressing effect on the central nervous system.	...	MODERATE
3	PO + PO	AMITRIPTYLINE + METHADONE	...	Methadone may cause QT interval prolongation. Theoretically, coadministration with other agents that may prolong the QT interval may result in additive effects.	...	MAJOR
3	PO + PO	AMITRIPTYLINE + MORPHINE	May cause irritability, altered consciousness, confusion, and hallucination. Neuromuscular abnormalities and gastrointestinal symptoms such as abdominal cramps, nausea, vomiting, and diarrhea.	Significant increase in plasma morphine.	Pharmacokinetics	MODERATE
3	PO + PO	BIPERIDEN + BUTYLSCOPOLAMINE	...	Agents with anticholinergic properties may have additive effects when used in combination.	Pharmacodynamics	MODERATE
3	PO + PO	BIPERIDEN + CHLORPROMAZINE	The therapeutic effects of Chlorpromazine may be diminished by centrally acting anticholinergics such as Biperiden.	Anticholinergics antagonize the effects of phenothiazines directly in the central nervous system.	Pharmacodynamics	MODERATE
3	PO + PO	BUTYLSCOPOLAMINE + CLOZAPINE	Increase anticholinergic action, such as dry mouth and constipation.	Increased anticholinergic action.	Pharmacodynamics	MODERATE
3	IV + IV	BUTYLSCOPOLAMINE + DIPYRONE	Risk of severe pressure drop (shock) and agranulocytosis (decreased platelet count).	Difficult assessment due to restriction of studies on Dipyrone	Difficult assessment due to restriction of studies on Dipyrone	MINOR
3	PO + PO	LITHIUM CARBONATE + CLONAZEPAM	The effects of the central nervous system or respiratory depressant may be increased.	The central nervous system or respiratory depressant effects may be increased additionally or synergistically.	Pharmacodynamics	MODERATE
3	PO + PO	CHLORPROMAZINE + DIAZEPAM	Increased effects of the central nervous system and respiratory depressant. Acute dystonic reactions, tardive dyskinesia, and akathisia may occur.	Addiction or synergism.	Pharmacodynamics	MODERATE
3	IV + PO	HALOPERIDOL + METOCLOPRAMIDE	...	Additive anti-dopamine effects.	Pharmacodynamics	MAJOR
3	IV + IV	HALOPERIDOL + ONDANSETRON	Risk of ventricular arrhythmias.	Haloperidol may cause QT prolongation. Extending the QT interval may result in additive effects.	Pharmacodynamics	MAJOR
2	PO + PO	VALPROIC ACID + CHLORPROMAZINE	...	Valproic Antidopaminic Acid Antagonist.	Pharmacodynamics	MINOR
2	PO + PO	VALPROIC ACID + FLUOXETINE	Fluoxetine may increase Valproate levels.	Possible inhibition of hepatic metabolism of Valproate.	Pharmacokinetics	MINOR
2	PO + PO	VALPROIC ACID + RISPERIDONE	...	Co-administration with Risperidone may alter serum Valproic Acid concentrations, although data are conflicting. The mechanism is unknown but may be related to the displacement of Valproate Risperidone from plasma proteins.	Pharmacokinetics	MODERATE
2	PO + PO	AMITRIPTYLINE + CLONAZEPAM	Sedation and increased central nervous system effects, respiratory depressant may be increased.	Synergism.	Pharmacodynamics	MODERATE
2	PO + PO	AMITRIPTYLINE + METRONIDAZOLE	...	Metronidazole may rarely prolong the QT interval of the electrocardiogram. Theoretically, coadministration with other agents that may prolong the QT interval may result in additive effects.	Pharmacodynamics	MINOR
2	PO + PO	BACLOFEN + PHENYTOIN	The effects of the central nervous system or respiratory depressant may be increased.	The central nervous system or respiratory depressant effects may be increased additionally or synergistically.	Pharmacodynamics	MODERATE
2	PO + PO	BIPERIDEN + DIAZEPAM	The effects of the central nervous system or respiratory depressant may be increased.	The central nervous system or respiratory depressant effects may be increased additionally or synergistically.	Pharmacodynamics	MODERATE
2	PO + PO	BIPERIDEN + PROMETHAZINE	The decreased therapeutic effect of Promethazine (phenothiazine) by the central action of anticholinergic(Biperiden).	Probable antagonistic action.	Pharmacodynamics	MODERATE
2	PO + PO	LITHIUM CARBONATE + HALOPERIDOL	...	Haloperidol may cause prolongation of the QT interval.	Pharmacodynamics	MAJOR
2	PO + PO	CLONAZEPAM + ENALAPRIL	The possible hypotensive effect, in case of initiation of treatment and increase of dose.	...	...	MODERATE
2	PO + PO	CLONAZEPAM + METHADONE	Concomitant use of opioids with benzodiazepines or other central nervous system depressants may result in sedation and respiratory depression. There is also a risk of hypotension.	...	...	MAJOR
2	PO + IV	POTASSIUM CHLORIDE + BUTYLSCOPOLAMINE	Concomitant use of agents with anticholinergic properties may potentiate the risk of high gastrointestinal injury associated with solid oral potassium chloride formulations.	The mechanism involves increased gastrointestinal transit time due to the reduced stomach and intestinal motility by anticholinergic agents, creating a high concentration of potassium ions in the region of a dissolving tablet or capsule and increasing contact time with the gastrointestinal mucosa.	Pharmacodynamics	MAJOR
2	PO + PO	CHLORPROMAZINE + PROMETHAZINE	Excessive parasympatholytic effects may result in paralytic ileus, hyperthermia, heatstroke, and anticholinergic intoxication syndrome.	Anticholinergic agents may have additive effects when used in combination.	Pharmacodynamics	MODERATE
2	PO + PO	DEXAMETHASONE + METHADONE	...	Co-administration with inducers of various CYP450 isoenzymes may decrease plasma concentrations of Methadone, which is metabolised by CYP450 3A4, 2B6, 2C19, 2C9 and 2D6.	Pharmacokinetics	MAJOR
2	PO + PO	DIAZEPAM + CHLORPROMAZINE	Possible respiratory depression.	The effects of the central nervous system and respiratory depressant may be increased additionally or synergistically.	Pharmacodynamics	MODERATE
2	PO + PO	DIAZEPAM + PROMETHAZINE	Increased effects of the central nervous system and respiratory depressant.	synergism	Pharmacodynamics	MODERATE
2	PO + PO	ENALAPRIL + RISPERIDONE	Orthostatic hypotension and syncope associated with vasodilation may occur during initial dosing or parenteral administration.	Phenothiazines and neuroleptic agents may potentiate the hypotensive effect of some medicinal secondary to peripheral alpha-1 blocking activity.	Pharmacodynamics	MODERATE
2	PO + PO	PHENYTOIN + RANITIDINE	The toxic pharmacological effect may occur due to increased phenytoin plasma concentration.	Possible inhibition of hepatic metabolism of phenytoin.	Pharmacokinetics	MODERATE
2	PO + PO	METHADONE + METRONIDAZOLE	...	Metronidazole may rarely prolong the QT interval of the electrocardiogram. Theoretically, coadministration with other agents that may prolong the QT interval may result in additive effects.	Pharmacodynamics	MINOR
1	PO + PO	PHENITOYNE + PARACETAMOL	Increases risk of liver damage.	Induction of paracetamol metabolism and a consequent increase of hepatotoxic metabolites.	Pharmacokinetics	MODERATE
1	PO + PO	ACETYLSALICYLIC ACID + ATENOLOL	Antihypertensive effects of Betablocker may be diminished by Salicylates.	PGs inhibition, and consequent increase in blood pressure	Pharmacodynamics	MODERATE
1	PO + SC	ACETYLSALICYLIC ACID + ENOXAPARIN	May affect hemostasis	...		MAJOR
1	PO + IV	ENOXAPARINA + HYDROCORTISONE	Decreased glomerular filtrate, ulcerations, and gastrointestinal bleeding may occur.	Corticosteroids (enzyme inducers) stimulate the hepatic metabolism of salicylates and may increase acetylsalicylic acid metabolism.	Pharmacokinetics	MODERATE
1	PO + PO	ACETYLSALICYLIC ACID + OMEPRAZOLE	Increased gastric side effects.	The increase in gastric pH mediated by proton pump inhibitors results in faster dissolution and release of salicylate from the enteric-coated product. Increased ionization, reduced absorption, higher concentration of local acetylsalicylic.	Pharmacokinetics	MINOR
1	PO + IV	AMLODIPINE + HYDROCORTISONE	...	Corticosteroids may antagonize the effects of antihypertensive drugs, inducing sodium, and fluid retention.	Pharmacodynamics	MODERATE
1	PO + IM	ATENOLOL + KETOPROFEN	The combination of these medicines may reduce the effects of Atenolol in lowering blood pressure.	Non-steroidal anti-inflammatory drugs may attenuate the antihypertensive effect of beta-blockers. The proposed mechanism is induced inhibition of renal prostaglandin synthesis by Non-steroidal anti-inflammatory, which results in unopposed pressor activity producing hypertension. In addition, Non-steroidal anti-inflammatory may cause fluid retention, which also affects blood pressure.	Pharmacodynamics	MODERATE
1	PO + IV	ATENOLOL + FUROSEMIDE	Diuretics and beta-blockers may increase the risk of hyperglycemia and hypertriglyceridemia in some patients, especially in patients with diabetes or latent diabetes.	...	...	MODERATE
1	PO + PO	BIPERIDEN + HALOPERIDOL	The development of tardive dyskinesia and the worsening of schizophrenia-related symptoms are reported when anticholinergic agents are used with Haloperidol.	Decreased serum Haloperidol concentration.	Pharmacokinetics	MODERATE
1	IV + PO	BUTYLSCOPOLAMINE) + PHENYTOIN	Reduced therapeutic efficacy of Buscopan.	Phenytoin and other hydantoins may induce hepatic metabolism of corticosteroid CYP450 3A4 and increase their clearance and decrease half-life.	Pharmacokinetics	MODERATE
1	PO + PO	BUTYLSCOPOLAMINE + BIPERIDEN	...	Agents with anticholinergic properties may have additive effects when used in combination.	Pharmacodynamics	MODERATE
1	PO + IM	CAPTOPRIL + KETOPROFEN	The combination of these drugs may reduce the effects of captopril on the action of lowering blood pressure.	Non-steroidal anti-inflammatory drugs may mitigate the anti-hypertensive effects of ACE inhibitors. The mechanism is the induced inhibition of the synthesis of renal prostaglandins by NSAIDs, which results in pressure activity without opposition producing hypertension. In addition, NSAIDs may cause fluid retention, which also affects blood pressure.	Pharmacodynamics	MODERATE
1	PO + PO	CARVEDILOL + DIPIRONE	Decreases antihypertensive effect.	Difficult assessment due to restriction of studies on Dipyrone	Difficult assessment due to restriction of studies on Dipyrone	MINOR
1	IM + IV	KETOPROPHEN + FUROSEMIDE	It may affect renal function, the hypotensive effect of diuretics may be reduced and, consequently, increased blood pressure. Diuretic effects may be reduced, risk of congestive heart failure associated with the combination.	Concomitant use of non-steroidal anti-inflammatory drugs and diuretics may adversely affect renal function due to inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs that help maintain renal perfusion in dehydrated states. The risk may be increased in patients with dietary sodium restriction. At the same time, the hypotensive effect of diuretics may be reduced because inhibition of prostaglandins may lead to unopposed pressor activity and hence elevation of blood pressure. Natriuretic and diuretic effects may also be reduced as NSAIDs cause sodium and water retention, which may be responsible for the increased risk of congestive heart failure associated with the combination.	Pharmacodynamics	MODERATE
1	IM + IV	KETOPROPHEN + HYDROCORTISONE	The use of hydrocortisone in combination with ketoprofen may increase the risk of side effects on the gastrointestinal tract, such as inflammation (ulceration and bleeding).	The combined use of oral corticosteroids and non-steroidal anti-inflammatory may increase the potential for severe gastrointestinal toxicity, including inflammation, bleeding, ulceration, and perforation.	Pharmacodynamics	MODERATE
1	PO + PO	CLONAZEPAM + LOSARTAN	May result in additive effects on blood pressure and orthostasis.	Many CNS-active psychotherapeutic agents (anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Concomitant administration with antihypertensive agents and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.	Pharmacodynamics	MODERATE
1	IV + IV	DEXAMETHASONE + MIDAZOLAM	...	Certain corticosteroids may decrease the plasma concentration of some benzodiazepines. The mechanism is related to the induction of cytochrome P450 liver enzymes responsible for benzodiazepine metabolism.	Pharmacokinetics	MODERATE
1	PO + PO	DIAZEPAM + FLUOXETINE	...	The mechanism may be related to CNS additive depressive effects and / or inhibition of Benzodiazepine metabolism by CYP450 2C19 and / or 3A4 by fluoxetine.	Pharmacokinetics	MODERATE
1	PO + PO	DIPYRONE + FUROSEMIDE	Decreases diuretic and antihypertensive effect	UNKNOWN	Difficult assessment due to restriction of studies on Dipyrone	NOT SPECIFIED
1	IV + PO	SCOPOLAMINE + PARACETAMOL	Absorption of paracetamol is slower, so it may take longer to start pharmacological action (which may be less than expected).	Decreased gastrointestinal motility caused by the action of Anticholinergics.	Pharmacodynamics	MINOR
1	PO + PO	FLUOXETINE + HALOPERIDOL	...	Haloperidol is metabolised by many routes, including glucuronidation and by enzymes from the cytochrome P450 system (particularly CYP3A4 or CYP2D6). The inhibition of these metabolism routes by other drugs or the decrease in the enzymatic activity of CYP2D6 may result in an increase in haloperidol concentrations and an increased risk of adverse events, including prolongation of the QT interval. medicines characterized as substrates or inhibitors of CYP3A4 or CYP2D6 isoenzymes.	Pharmacokinetics	MODERATE
1	IV + PO	HYDROCORTISONE + PHENYTOIN	Decreased therapeutic efficacy.	Phenytoin and other Hydantoins may induce the hepatic metabolism of CYP450 3A4 in corticosteroids and increase its clearance and shorten its half-life, possibly reducing its therapeutic efficacy.	Pharmacokinetics	MODERATE
1	IV + SC	HYDROCORTISONE + SALBUTAMOL	...	Concomitant use of beta-2 adrenergic agonists and corticosteroids may result in hypokalemia effects. Since beta-2 agonists may sometimes cause prolongation of the QT interval	Pharmacodynamics	MINOR
1	PO + PO	LEVOTHYROXINE + SIMVASTATIN	Possible increase or decrease in thyroid hormone.	...		MINOR
1	PO + PO	LOSARTAN + PREDNISONE	...	Corticosteroids may antagonize the effects of antihypertensive drugs, inducing sodium, and fluid retention. These effects may be more common with natural corticosteroids (cortisone, hydrocortisone) because they have greater mineralocorticoid activity. On the other hand, some calcium channel blockers, such as Diltiazem and verapamil, may increase plasma levels and the effects of corticosteroids, inhibiting their clearance through the metabolism of CYP450 3A4.	Pharmacokinetics	MODERATE
1	PO + PO	LOSARTAN + RISPERIDONE	...	Phenothiazines and neuroleptic agents may potentiate the hypotensive effect of some drugs secondary to peripheral alpha-1 adrenergic blocking activity. Orthostatic hypotension and syncope associated with vasodilation may occur, particularly during initial dosing or parenteral administration of phenothiazine or neuroleptic.	Pharmacodynamics	MODERATE
1	IV + PO	METOCLOPRAMIDE + MORPHINE	Increased sedative effects.	Metoclopramide potentiates CNS depression caused by morphine. The effect of metoclopramide on gastric motility is reduced by morphine.	Pharmacodynamics	MODERATE
1	IV + IV	MIDAZOLAM + MORPHINE	The effects of the central nervous system or respiratory depressant may be increased.	The effects of the central nervous system or respiratory depressant may be increased additionally or synergistically	Pharmacodynamics	MODERATE
1	IV + IV	MIDAZOLAM + OMEPRAZOLE	It prolongs the sedative effect and may cause ataxia.	Omeprazole may increase the pharmacological effects and the serum levels of certain Benzodiazepines through hepatic enzyme inhibition.	Pharmacokinetics	MODERATE
1	PO + PO	OMEPRAZOLE + SIMVASTATIN	Increased adverse effects of simvastatin. Risk of liver and kidney damage.	Omeprazole increases the plasma concentration of simvastatin.	Pharmacokinetics	MODERATE
1	PO + PO	RISPERIDONE + SERTRALINE	Doses greater than 100 mg/day of Sertraline may increase the concentrations of the active antipsychotic fraction of Risperidone.	...		MODERATE

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

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[1] *Correspondence: A. C. A. Naime. Departamento de Farmácia. Centro Universitário Padre Anchieta. Av. Odila Azalim, n° 575 Vila Francisco Eber. CEP: 13210-800, Jundiaí, SP, Brasil. Phone: (19) 99688-4488. E-mail: ana.naime@anchieta.br.