TUGAS

CRITICAL APPRAISAL OF LITERATURES

“COMPLETE ATRIOVENTRICULAR BLOCK ASSOCIATED WITH

CONCOMINANT USE OF METOPROLOL AND PAROXETINE”

OLEH:

MUHAMMAD RAYZA AZMIN

N012231010

PROGRAM STUDI MAGISTER ILMU FARMASI

FAKULTAS FARMASI
UNIVERSITAS HASANUDDIN
MAKASSAR
2023
1. Apakah karakteristik demografis pasien dideskripsikan dengan jelas? Jawab:
YES, SUDAH JELAS.
Dalam jurnal tersebut sudah menjelaskan mengenai usia pasien yaitu seorang wanita berusia
63 tahun, yang telah diobati dengan 20 mg paroxetin dan 0,5 mg alprazolam setiap hari
selama 1 tahun dan dengan 50 mg metoprolol setiap hari selama 15 hari. Tiga hari setelah
presentasi awal dan penghentian pengobatan metoprolol, dia dipindahkan ke klinik kami
untuk dipertimbangkan implantasi alat pacu jantung permanen.
Dapat dilihat pada bagian “Abstrak” bagian case presentation, hal 1
“A 63-year-old woman, who had been treated with 20 mg of paroxetine and 0.5 mg of alprazolam
daily for 1 year and with 50 mg of metoprolol daily for 15 days, presented to a facility else-where
with presyncope and complete atrioventricular block. Three days after her initial presentation and
cessation of metoprolol treatment, she was transferred to our clinic to be considered for permanent
pacemaker implantation. ”.

2. Apakah riwayat pasien dideskripsikan dengan jelas dan dipresentasikan dalam bentuk
timeline? Jawab:
YES, SUDAH JELAS.
Dalam jurnal tersebut sudah menyampaikan Riwayat pasien yaitu Seorang wanita berusia 63
tahun dengan riwayat hipertensi dan depresi, yang telah diobati dengan 20 mg paroxetine dan
0,5 mg alprazolam setiap hari selama 1 tahun dan dengan 50 mg metoprolol setiap hari selama
15 hari, dibawa ke fasilitas di tempat lain dengan presinkop dan blok atrioventrikular (AV)
lengkap. Tiga hari setelah presentasi awal dan penghentian pengobatan metoprolol, dia
dipindahkan ke klinik kami untuk dipertimbangkan untuk implantasi alat pacu jantung
permanen. Saat datang, ia tidak menunjukkan gejala: tekanan darah 110/70 mmHg, denyut
jantung 40 denyut/menit, dan elektrokardiografi (EKG) 12-lead menunjukkan blok AV
lengkap dengan jalur QRS yang sempit ritme 40 denyut/menit Hasil dari semua tes diagnostik
tes, termasuk enzim jantung, sel darah lengkap darah lengkap, tes fungsi ginjal, elektrolit,
fungsi tiroid tes, radiografi dada, dan ekokardiografi, adalah normal, dan angiogram koroner
biasa-biasa saja
3. Apakah kondisi klinik pasien saat ini di deskripsikan dengan jelas? Jawab:
YES, SUDAH JELAS.
Dalam jurnal menjelaskan bahwa pasien seorang wanita berusia 63 tahun. Kami berpikir bahwa
blok AV dapat dikaitkan dengan pemberian paroxetine dan metoprolol secara bersamaan. Oleh
karena itu, kami merujuk pasien ke departemen psikiatri, dan pengobatan paroxetine dihentikan
pada hari pertama. Blok AV blok sepenuhnya teratasi pada hari ke 5, yang dikonfirmasi dengan
rekaman Holter 24 jam. Metoprolol Terapi metoprolol (50 mg/d) dimulai kembali pada hari ke-6,
dan pasien dipantau secara ketat untuk bradiaritmia selama 5 hari ke depan hari. Tidak ada
bradiaritmia yang terlihat selama periode ini. Pengobatan metoprolol dihentikan pada hari ke-10,
dan pasien dipulangkan dengan alprazolam (0,5 mg / d), asam asetilsalisilat (100 mg / d), dan
amlodipine (5 mg/d) pada hari ke-12. Satu minggu dan 2 minggu setelah keluar dari rumah sakit,
pasien masih bebas dari bradiaritmia. Dua minggu setelah keluar dari rumah sakit, pasien
mengunjungi departemen psikiatri untuk konsultasi. Alprazolam dihentikan, dan paroxetine
dipulihkan pada 10 mg/d dan secara bertahap ditingkatkan menjadi 20 mg/d. A Rekaman Holter
24 jam, dilakukan 3 minggu setelah keluar dari rumah sakit keluar dari rumah sakit, adalah
normal. Pada masa tindak lanjut 2 tahun pasien, hasilnya tidak adanya bradiaritmia
didokumentasikan dengan cara EKG 12-lead dan rekaman Holter 24 jam. Pada Saat itu pasien
masih menerima pengobatan paroxetine sebesar 20 mg/d. Pada tindak lanjut terakhir yang tersedia,
yang dilakukan pada 26 April 2007, pasien mengonsumsi clonazepam, escitalopram, diltiazem,
dan asam asetilsalisilat, dan sekali lagi terbukti bebas dari bradiaritmia oleh EKG dan rekaman
Holter 24 jam.
4. Apakah tes atau metode diagnostik dan hasil dideskripsikan dengan jelas? Jawab:
YES, SUDAH JELAS
Dapat dilihat pada bagian hal 2
Dalam jurnal tersebut telah menjelaskan hasil pemeriksaan Elektrokardiografi
5. Apakah intervensi atau prosedur pengobatan dideskripsikan dengan jelas? Jawab:
NO, TIDAK JELAS.
Dalam jurnal tersebut pada saat pengobatan terapi diberikan obat metoprolol 50mg/hari,
paroxetine 10mg/hari, alprazolam 0,5mg/hari, asam asetilsalisilat 100/hari, amlodipine 5mg/hari.
Dan pengobatan tindak lanjut akhir pasien memakai clonazepam,escitalopram, diltiazem dan asam
salisilat. Sehingga disimpulkan bahwa prosedur pengobatan tidak jelas, karena tidak menjelaskan
berapa dosis yang digunakan, bagaimana pemakaian obat secara detail.
6. Apakah kondisi klinis pasca intervensi dijelaskan dengan jelas? Jawab:
UNCLEAR.
Tidak dijelaskan secara detail kondisi pasien setelah menerima pengobatan. Namun penulis
menjelaskan pasien terbukti bebas dari bradiaritmia melalui EKG.
7. Apakah kejadian buruk (bahaya) atau kejadian tak terduga diidentifikasi dan dijelaskan?
Jawab:
YES, SUDAH JELAS
Karena dalam kasus tersebut, setelah pemberian obat pada tindak lanjut akhir tidak dijelaskan
apakah ada efek samping yang terjadi pada pasien tetapi terbukti bebas dari bradiaritmia. Adapun
kejadian yang terjadi ketika paroxetine dan metoprolol digunakan secara bersamaan menunjukkan
Blok AV pada pasien yang rentan, seperti pasien lanjut usia, wanita, dan metabolisme metoprolol
yang buruk. Oleh karena itu, detak jantung harus dipantau secara ketat ketika kedua obat ini
digunakan secara bersamaan pada pasein tersebut. Sebagai alternatif metoprolol dapat diganti
dengan atenolol atau bisoprolol yang tidak dimetabolisme melalu jalur yang bergantung pada
CYP2D6. Pada pasien dengan indikasi spesifik untuk metoporlol, penggantian paroxetine dengan
antidepresan alternatife atau pengurangan dosis metoprolol harus dipertimbangkan.
8. Apakah laporan kasus memberikan pelajaran yang bisa dibawa pulang? Jawab:
YES, SUDAH JELAS.
Pelajaran yang dapat diambil bahwa kami menemukan bahwa pemberian paroxetine dan
metoprolol secara bersamaan menunjukkan Blok AV. Bahkan dengan dosis metoprolol yang kecil
dapat menyebabkan bradiaritmia parah bila diberikan secara bersamaan dengan dosis terapeutik
paroxetine, terutama pada pasien yang rentan.

Complete Atrioventricular Block Associated With Concomitant
Useof Metoprolol and Paroxetine
ORHAN ONALAN, MD; BIRGUL ELBOZAN CUMURCU, MD; AND LUTFU BEKAR, MD
A 63-year-old woman, who had been treated with 20 mg of
paroxetine and 0.5 mg of alprazolam daily for 1 year and with 50
mg of metoprolol daily for 15 days, presented to a facility else-
where with presyncope and complete atrioventricular block. Three
days after her initial presentation and cessation of metoprolol
treatment, she was transferred to our clinic to be considered for
permanent pacemaker implantation. Paroxetine treatment was
discontinued on day 1 and atrioventricular block resolved on day
5, which was confirmed with a 24-hour Holter recording. No
bradyarrhythmia was induced with similar doses of either meto-
prolol or paroxetine alone. At 2- and 3-year follow-up, the patient
was still free of bradyarrhythmia documented with electrocardiog-
raphy and 24-hour Holter recordings. To our knowledge, we report
the first case of complete atrioventricular block associated with
coadministration of paroxetine and metoprolol. Increasing physi-
cians’ awareness of drug-induced severe bradyarrhythmia might
prevent unnecessary implantation of permanent pacemakers.
AV = atrioventricular; AUC = area under the curve; CYP2D6 =
cytochrome P450 2D6; ECG = electrocardiography; SSRI = selective
serotonin reuptake inhibitor
A 63-year-old woman with a history of hypertension
and depression, who had been treated with 20 mg of
paroxetine and 0.5 mg of alprazolam daily for 1 year and
with 50 mg of metoprolol daily for 15 days, presented to a
facility elsewhere with presyncope and complete atrio-
ventricular (AV) block. Three days after her initial pres-
entation and cessation of metoprolol treatment, she was
transferred to our clinic to be considered for implantation
of a permanent pacemaker. At presentation she was asymp-
tomatic: blood pressure was 110/70 mm Hg, heart rate was
40 beats/min, and 12-lead electrocardiography (ECG)
showed complete AV block with a narrow QRS escape
rhythm of 40 beats/min (Figure, A). Results of all diagnostic
tests, including cardiac enzymes, complete blood cell
count, renal function test, electrolytes, thyroid function
tests, chest radiography, and echocardiography, were
normal, and the coronary angiogram was unremarkable.
From the Department of Cardiology (O.O., L.B.) and Department of Psychiatry
(B.E.C.), Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey.
Individual reprints of this article are not available. Address correspondence to
Orhan Onalan, MD, Gaziosmanpasa University Faculty of Medicine, Depart-
ment of Cardiology, Sivas St, 60200, Tokat, Turkey (oonalan@gmail.com).
© 2008 Mayo Foundation for Medical Education and Research
CASE REPORT
ATRIOVENTRICULAR BLOCK WITH METOPROLOL AND PAROXETINE
We thought that AV block could be associated with co-
administration of paroxetine and metoprolol. Therefore,
wereferred the patient to the psychiatry department, and
the paroxetine treatment was discontinued on day 1. The
AV block completely resolved on day 5 (Figure, B and C),
which was confirmed with a 24-hour Holter recording.
Metoprololtherapy (50 mg/d) was reinstated on day 6, and
the patientwas closely monitored for bradyarrhythmia for
the next 5 days. No bradyarrhythmia was seen during this
period (Fig- ure, D and F). Metoprolol treatment was
discontinued on day 10, and the patient was discharged
with alprazolam (0.5 mg/d), acetylsalicylic acid (100
mg/d), and amlodipine (5 mg/d) on day 12 (Figure, F).
One week (Figure, G) and 2 weeks (Figure, H) after
hospital discharge, the patient was still free of
bradyarrhythmia. Two weeks after hospital dis-charge, the
patient visited the psychiatry department for con-sultation.
Alprazolam was discontinued, and paroxetine was
reinstated at 10 mg/d and gradually increased to 20 mg/d.
A 24-hour Holter recording, performed 3 weeks after
hospital discharge, was normal. At the patient’s 2-year
follow-up, the absence of bradyarrhythmia was
documented by means of12-lead ECG (Figure, I) and 24-
hour Holter recording. At that time the patient was still
receiving paroxetine treatment of 20 mg/d. At the latest
available follow-up, performed on April 26, 2007, the
patient was taking clonazepam, escitalopram, diltiazem,
and acetylsalicylic acid, and againwas shown to be free of
bradyarrhythmia by ECG (Figure, J)and a 24-hour Holter
recording.
DISCUSSION
We have several reasons to conclude that AV block in this
case was associated with coadministration of metopro-
lol and paroxetine. First, the patient was asymptomatic
while she received paroxetine and alprazolam treatment
alone and presented with presyncope and complete AV
block after taking metoprolol. Second, discontinuation
of metoprolol treatment alone for 3 days did not restore
normal rhythm, but complete recovery was observed after
discontinuation of paroxetine. Third, and most important,
similar doses of either metoprolol or paroxetine alone
induced no bradyarrhythmia.
Metoprolol, a widely prescribed cardioselective -
blocker, is extensively metabolized in the liver through O-
ATRIOVENTRICULAR BLOCK WITH METOPROLOL AND PAROXETINE
FIGURE. Electrocardiography (lead 1) at admission (A), during the hospital stay (B, C, D, E, and F),
1 week (G) and 2 weeks (H) after hospital discharge, and at 2-year (I) and 3-year (J) follow-up.
demethylation, -hydroxylation, and N-dealkylation. Invitro
studies have shown that -hydroxylation of meto- prolol is
mediated by cytochrome P450 2D6 (CYP2D6) almost
completely, and O-demethylation of metoprolol is mediated
by CYP2D6 partially.1 Thus, CYP2D6 mediatesan estimated
70% of metoprolol’s metabolism.2 Selective serotonin
reuptake inhibitors (SSRIs) might interfere with the
metabolism of metoprolol by inhibiting CYP2D6.3 Among
SSRIs, paroxetine is one of the most potent CYP2D6
inhibitors.4 In a study of 8 healthy male volun- teers,
Hemeryck et al4 investigated the effect of multiple- dose
paroxetine intake on the stereoselective pharmacoki- netics
and pharmacodynamics of metoprolol. Volunteers were given
a single oral dose of racemic metoprolol (100 mg) before and
after paroxetine treatment (20 mg/d) for 6 days. Paroxetine
treatment increased the mean area under the curve (AUC) of
(R)- and (S)-metoprolol significantly (from 169 to 1340 ng ·
h/mL; P<.001 for [R]-metoprolol and from 279 to 1418 ng ·
h/mL; P<.001 for [S]-met- oprolol), approximately doubling
both maximum plasma concentration and terminal elimination
half-life. In addi- tion, Hemeryck et al4 observed a significant
decrease in the(S)/(R) AUC ratio and a significant increase in
the mean metoprolol metabolic ratio. The AUC of the
metoprolol- induced decrease in exercise heart rate vs time
curve in- creased by 46% (P<.01) after multiple-dose
paroxetine
596 Mayo Clin Proc. • May 2008;83(5):595-599
For personal use. Mass reproduce only with permission fromMayo Clinic Proceedings.
intake, suggesting a more sustained -blockade. Therefore,it is
likely that long-term pretreatment with paroxetine in this case
greatly reduced metoprolol metabolism and en- hanced its
negative effect on the AV node.
We searched 5 electronic databases for smiliar reports. The
search was carried out using the following electronic
databases from the earliest possible dates through August
2007: (1) MEDLINE; (2) EMBASE; (3) Cochrane Central
Register of Controlled Trials (CCTR); (4) Cumulative Index
to Nursing & Allied Health Literature (CINAHL); and (5)
HealthSTAR. No language, date, or other restrictions were
applied. The following strategy was used to search all these
databases; capitalized terms are con- trolled: (1)
ARRHYTHMIA/; (2) HEART BLOCK/; (3)
BRADYCARDIA/; (4) ANTIDEPRESSIVE AGENTS/; (5)
ANTIDEPRESSANT AGENT/; (6) ANTI-ANXIETY
AGENTS/; (7) ANTIANXIETY AGENTS; (8) ANXIOLYTIC
AGENT/; (9) paroxetine; (10) alprazolam; (11) or/1-3; (12)
or/4-10; (13) and/11-12. Additional publications were
examined using the reference lists of identified papers and
published reviews. Overall, of 1477 initial hits, 3 casesof
bradyarrhythmia associated with coadministration of SSRIs
and -blockers were identified.5-7 Konig et al5 reported the first
case of bradycardia after coadministration of paroxetine and
metoprolol. Walley et al6 described a case of symptomatic
bradycardia with coadministration of
• www.mayoclinicproceedings.com

metoprolol and fluoxetine, another potent inhibitor of
CYP2D6, in a 54-year-old man with a history of coronary
bypass surgery. In this case, the patient’s heart rate was64
beats/min with metoprolol treatment (100 mg/d) alone.On the
second day of adding fluoxetine treatment (20 mg/d), the
patient developed symptomatic bradycardia (36 beats/min).
His heart rate returned to its previous rate during the next 5
days after fluoxetine treatment was discontinued.
Coadministration of fluoxetine and sotalol inthis case did not
cause bradyarrhythmia. Pae et al7 reportedsinus bradycardia (40
beats/min) and sinus pause (4 seconds)with syncope on the 20th
day of paroxetine coadministration(up to 30 mg/d) in a 78-year-
old woman who was receiving carvedilol (12.5 mg/d)
treatment. The patient had no bradyarrhythmia while
receiving carvedilol alone before paroxetine administration.
Normal heart rate was regained within 5 days after
discontinuation of carvedilol and paroxetine therapy.
Bradyarrhythmia had not recurred after substitution of
paroxetine with mirtazapine in addition to daily treatment with
12.5 mg of carvedilol.
Selective serotonin reuptake inhibitors, without con-
comitant use of -blocker therapy, were also reported to be
associated with bradyarrhythmia in 5 case reports.8-12 Er- furth
et al8 reported bradycardia in 2 cases after paroxetine
administration. In a 65-year-old patient with a history of
hemorrhagic stroke and depression, severe symptomatic
bradycardia (34-40 beats/min) developed after the third dose
of paroxetine (10 mg/d) and resolved quickly after intravenous
administration of atropine (0.5 mg). In a 51- year-old patient
with a history of bipolar affective disorder, asymptomatic
bradycardia developed after the third dose of paroxetine
treatment (10 mg/d). In this case, the heart rate was normal 13
days after cessation of paroxetine treatment.Rothenhausler et
al9 reported a case of sinus bradycardia with syncope in a 32-
year-old patient who ingested a totalof 800 mg of citalopram
to attempt suicide. Therapeutic doses of citalopram have also
been associated with symp- tomatic10 and asymptomatic
bradycardia.11,12 In addition, Gambassi et al13 described a case
of various AV blocks (first-degree and Mobitz type I) associated
with citalopram, which were reversed after discontinuation of
the drug.Citalopram can impair AV conduction by inhibiting
L-typecalcium-channel current.14
Bupropion, a non–tricyclic antidepressant drug, is an
increasingly prescribed aid in smoking cessation. Bupro- pion
inhibits CYP2D6 and therefore can impair metabo- lism of
drug substrates of this enzyme. McCollum et al15 reported a
case of bradycardia in a 56-year-old man when bupropion
(150 mg twice daily) was added to metoprolol (75 mg twice
daily) and diltiazem (240 mg twice daily) treatment. The
patient in this case developed bradycardia with an atrial rate
of 40 beats/min and a junctional escape
Mayo Clin Proc. • May 2008;83(5):595-599
For personal use. Mass reproduce only with permission fromMayo Clinic Proceedings.
ATRIOVENTRICULAR BLOCK WITH METOPROLOL AND PAROXETINE
rhythm of 43 beats/min. The patient was admitted to the
hospital, and all 3 medications were withheld. The next
morning, all symptoms had resolved and normal sinusrhythm
returned.
Ahmed et al16 reported a case of sinus bradycardia with
concomitant use of fluoxetine and pimozide. We found 2 cases
of bradyarrhythmia associated with alprazolam use.17,18
Tollefson et al17 described a case of digitalis in- toxication
when alprazolam was added to ongoing digoxin therapy.
Reduced renal clearance of digoxin was postulated as the
mechanism for this interaction. Mullins18 reported a case of
first-degree AV block in a patient with alprazolamoverdose
(12 mg). Weak calcium-channel blocker activity of
benzodiazepines could be responsible for this effect. These
data suggest that development of complete AV block in our
case is related to alprazolam use. However, thealprazolam dose
in our case was very small (0.5 mg/d)and we did not stop
alprazolam treatment during the patient’s hospital stay.
Further, it should be noted that in our case the AV block
disappeared despite ongoing alpra- zolam treatment.
Metoprolol has proven to be effective in the treatment of
coronary artery disease, hypertension, and chronic heart fail-
ure.19-22 Depression is the most common psychiatric illnessand
is frequently present in patients with cardiovascular disease.
Selective serotonin reuptake inhibitors are consid- ered
relatively safer than other antidepressants for cardiac
patients.23 Thus, SSRIs are often prescribed to cardiacpatients,
and physicians should be aware of serious drug interactions
caused by inhibition of CYP2D6. Paroxetine currently is
among the most widely coprescribed drugs in patients
receiving a CYP2D6 subtrate.24 A study from Nor- way
investigated how frequently CYP2D6 inhibitors are
coadministered with substrates of the enzyme and reportedthat
the CYP2D6 substrate metoprolol together with a CYP2D6
inhibitor paroxetine was one of the most fre- quently
prescribed combinations.24
In a randomized placebo-controlled study,25 potential
interactions between carvedilol and fluoxetine were evalu-
ated. Fluoxetine (20 mg) or matching placebo was adminis-
tered to 10 patients with heart failure who were previously
identified as extensive metabolizers of CYP2D6 sub- strates.25
Patients were maintained on a carvedilol dose of 25 or 50 mg
twice daily and given fluoxetine or a placebo for a minimum
of 28 days. Administration of fluoxetine, a potent CYP2D6
inhibitor, resulted in a stereospecific inhi-bition in carvedilol
metabolism without significantly af- fecting blood pressure,
heart rate, or heart rate variability. Goryachkina et al26 noted a
pronounced inhibition of metoprolol metabolism when
paroxetine (20 mg/d) was coadministered to 17 depressed
patients with acute myo- cardial infarction. 26 They found
mean metoprolol concen-
• www.mayoclinicproceedings.com 597
ATRIOVENTRICULAR BLOCK WITH METOPROLOL AND PAROXETINE
tration AUC increased by 400% and mean -hydroxy met-
oprolol concentration AUC decreased by approximately 75%.
Although no serious adverse effects were noted, 2 patients
required a reduction of metoprolol dose because ofexcessive
bradycardia and severe orthostatic hypotension. Goryachkina
et al suggest that the metoprolol dose be adjusted when
paroxetine is initiated and withdrawn.
Because of polymorphism of the CYP2D6 gene, CYP2D6
activity varies markedly among individuals. Consequently,
after short-term administration, metoprolol plasma
concentrations were found to be 3- to 10-foldhigher in poor
metabolizers than in extensive metab- olizers.27,28 Accordingly,
the decrease in heart rate is greatly pronounced in poor
metabolizers.29,30 The effect of the CYP2D6 genotype on
metoprolol plasma concentrations persists during long-term
treatment; poor metabolizers have steady-state concentrations
that are several times higher.31 Some suggest that poor
metabolizers are more susceptible to adverse effects than
extensive metabolizers at standard doses of metoprolol.29,32
Consistent with this suggestion, Wuttke et al33 observed
predominantly poor metabolism of CYP2D6 in patients with
serious met- oprolol-associated adverse events. These findings
suggest that simultaneous administration of potent inhibitors
of CYP2D6 and metoprolol can lead to serious adverse effects
among poor metabolizers.
Sex-related differences in the pharmacokinetics of
metoprolol can cause greater drug exposure in women. 34
Thurmann et al35 investigated potential sex differences in
adverse drug reactions caused by -blockers. The number of
adverse drug reactions associated with the use of CYP2D6-
dependent -blockers (metoprolol, carvedilol, nebivolol, and
propranolol) was significantly higher inwomen than in men
(P=.006), whereas frequencies for the CYP2D6-independent
-blockers (atenolol, sotalol, and bisoprolol) were not
significantly different between men and women (P>.05).
Further, 75% of patients with serious metoprolol-associated
adverse events reported in the study of Wuttke et al33 were
women, and most were poor metabolizers. Independently of
CYP2D6 genotype, women exhibit significantly higher
metoprolol and propranololplasma concentrations than men.36
Finally, depression associated with cardiovascular dis-
ease is particularly prevalent in elderly patients. 37,38 The
cardiac safety profiles of antidepressants in this population
should be noted because patients might be particularly
vulnerable to adverse effects of drugs and often receive
multiple concomitant medications.
The present case demonstrates that complete AV blockcan
develop when paroxetine and metoprolol are pre- scribed
together in susceptible patients, such as older patients,
women, and poor metabolizers of metoprolol.
For personal use. Mass reproduce only with permission fromMayo Clinic Proceedings.
Thus, heart rate should be closely monitored when these2
drugs are used together in such patients. Alternatively,
metoprolol can be substituted with atenolol or bisoprolol,
which are not metabolized via CYP2D6-dependent path-
ways. In a patient with a specific indication for meto- prolol,
substitution of paroxetine with an alternative anti- depressant
or reduction of metoprolol dose should be considered.
CONCLUSION
To our knowledge, we report the first case of complete AV
block associated with coadministration of paroxetine and
metoprolol. Metoprolol, even in relatively small doses, canlead
to severe bradyarrhythmia when coadministered with
therapeutic doses of paroxetine, particularly in susceptible
populations. Increasing physicians’ awareness of drug-in-
duced severe bradyarrhythmia might prevent unnecessary
implantation of permanent pacemakers.
We gratefully acknowledge Maria Lukomsky, for her significant
contribution of expertise in English to this study.
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