Hospital Pharmacy - July/August 2019 - 227

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Table 2. Clinically Significant Drug Interactions With Sufentanil.1

CYP3A4 inhibitors (eg, macrolide antibiotics
[eg, erythromycin], azole antifungal agents
[eg, ketoconazole], protease inhibitors [eg,
ritonavir])

CYP3A4 inducers (eg, rifampin,
carbamazepine, phenytoin)

Benzodiazepines and other CNS depressants
(eg, alcohol, benzodiazepines and
other sedatives/hypnotics, anxiolytics,
tranquilizers, muscle relaxants, general
anesthetics, antipsychotics, other opioids)
Serotonergic drugs (eg, SSRIs, SNRIs, TCAs,
triptans, 5-HT3 receptor antagonists, drugs
that affect the serotonin neurotransmitter
system [eg, mirtazapine, trazodone,
tramadol], MAOIs [those intended to treat
psychiatric disorders and others, such as
linezolid and IV methylene blue])
MAOIs (eg, phenelzine, tranylcypromine,
linezolid)
Mixed agonist/antagonist and partial agonist
opioid analgesics (eg, butorphanol,
nalbuphine, pentazocine, buprenorphine)
Muscle relaxants

Diuretics
Anticholinergic drugs

Clinical impact

Intervention

Concomitant use can increase sufentanil
plasma concentration, resulting in
increased or prolonged opioid effects.
After stopping a CYP3A4 inhibitor, as
the effects of the inhibitor decline, the
sufentanil plasma concentration will
decrease, resulting in decreased opioid
efficacy or a withdrawal syndrome in
patients who had developed physical
dependence to sufentanil.
Concomitant use can decrease sufentanil
plasma concentration, resulting in
decreased efficacy or onset of a
withdrawal syndrome in patients who
have developed physical dependence
to sufentanil.
After stopping a CYP3A4 inducer, as
the effects of the inducer decline, the
sufentanil plasma concentration will
increase, which could increase or
prolong both the therapeutic effects
and adverse reactions, and may cause
serious respiratory depression.
Due to additive pharmacologic effect,
concomitant use can increase the
risk of hypotension, respiratory
depression, profound sedation, coma,
and death.

If concomitant use is necessary, consider an
alternative medication that permits dose
titration. Monitor patients for respiratory
depression and sedation at frequent
intervals.
If a CYP3A4 inhibitor is discontinued,
consider increasing the sufentanil
sublingual dosage until stable drug effects
are achieved. Monitor for signs of opioid
withdrawal.
If concomitant use is necessary, consider
an alternative medication that permits
dose titration. Monitor for signs of opioid
withdrawal. If a CYP3A4 inducer is
discontinued, consider sufentanil sublingual
dosage reduction and monitor for signs of
respiratory depression.

Concomitant use of opioids with other
drugs that affect the serotonergic
neurotransmitter system has resulted
in serotonin syndrome.

MAOI interactions with opioids may
manifest as serotonin syndrome
or opioid toxicity (eg, respiratory
depression, coma).
May reduce the analgesic effect of
sufentanil sublingual and/or precipitate
withdrawal symptoms.
Sufentanil may enhance the
neuromuscular blocking action of
skeletal muscle relaxants and produce
an increased degree of respiratory
depression.
Opioids can reduce the efficacy of
diuretics by inducing release of
antidiuretic hormone.
Concomitant use may increase the risk
of urinary retention and/or severe
constipation, which may lead to
paralytic ileus.

Reserve concomitant prescribing of these
drugs for patients for whom alternative
treatment options are inadequate. Limit
dosages and durations to the minimum
required. Follow patients closely for signs
of respiratory depression and sedation.
If concomitant use is warranted, carefully
observe the patient, particularly during
treatment initiation and dose adjustment.
Discontinue sufentanil sublingual if
serotonin syndrome is suspected.
Use of sufentanil sublingual is not
recommended for patients taking MAOIs
or within 14 days of stopping such
treatment.
Avoid concomitant use.
Monitor patients for signs of respiratory
depression that may be greater than
otherwise expected and decrease the
muscle relaxant dosage as necessary, or
consider discontinuing use of sufentanil
sublingual.
Monitor patients for signs of diminished
diuresis and/or effects on blood pressure
and increase the diuretic dosage as needed.
Monitor patients for signs of urinary
retention or reduced gastric motility when
sufentanil sublingual is used concomitantly
with anticholinergic drugs.

Note. CNS = central nervous system; SSRIs = selective serotonin reuptake inhibitors; SNRIs = serotonin-norepinephrine reuptake inhibitors; TCAs =
tricyclic antidepressants; MAOI = monoamine oxidase inhibitor; IV = intravenous.

Hospital Pharmacy - July/August 2019

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