Therapeutic Indications
Intravenous SUFENTA is used both as an analgesic adjunct to nitrous oxide/
oxygen and as a sole anaesthetic in ventilated patients. It is particularly suitable
for longer and more painful interventions where a potent analgesic is required to
help maintain good cardiovascular stability.
INTRAVENOUS SUFENTA is indicated:
- as an analgesic adjunct during induction and maintenance of balanced general
anaesthesia.
- as an anaesthetic agent for induction and maintenance of anaesthesia in patients
undergoing major surgical procedures.

The dosage of SUFENTA should be individualised according to age, body weight,
physical status, underlying pathological condition, use of other drugs, and type of
surgical procedure and anaesthe sia. The effect of the initial dose should be taken
into account in determining supplemental doses.
INTRAVENOUS ADMINISTRATION
- To avoid bradycardia, it is recommended to administer a small intravenous dose
of an anti cho linergic just before induction. Droperidol may be given to prevent
nausea and vomiting.
- Use as analgesic adjunct
In patients undergoing general surgery, doses of SUFENTA of 0.5-5 μg/kg
provide intense analgesia, reducing the sympathetic response to surgical stimulation
and preserving cardiovascular stability. The duration of activity is dosedependent.
A dose of 0.5 μg/kg may be expected to last 50 minutes. Supplemental
doses of 10-25 μg should be individually adjusted to the needs of each
patient and to the anticipated remaining operation time.
- Use as anaesthetic agent
When used in doses of ≥8 μg/kg SUFENTA produces sleep and maintains
a dose-related profound level of analgesia without the use of additional anaesthetic
agents. In addition sympathetic and hormonal responses to surgical stimuli are
attenuated. Supplementary doses of 25-50 μg generally suffice to maintain
cardiovascular stability during anaesthesia.
- Use in the elderly and special patient groups:
As with other opioids the dose should be reduced in elderly and in debilitated
patients
- Use in children:
The safety and efficacy of intravenous SUFENTA in children under 2 years of
age has been docu mented in only a limited number of cases.
For induction and maintenance of anaesthesia in children of 2-12 years of age
undergoing major surgery, an anaesthetic dose of 10-20 μg/kg administered
with 100% oxygen has been used.

SUFENTA is contraindicated in patients with known intolerance to either of its components or to other morphinomimetics. Intravenous use in labour or before clamping of the cord during caesarean section is not recommended due to the possibility of respiratory depression in the newborn infant. See Special warnings and special precautions for use and Pregnancy and lactation.

As with all potent opioids:
Respiratory depression is dose related and can be reversed by specific narcotic
antagonists (naloxone), but a repeated dose of the latter may be necessary because
the respiratory depression may last longer than the duration of action of the opioid
antagonist. Marked respiratory depression accompanies profound analgesia. It
can persist in the postoperative period, and if SUFENTA has been given intravenously
it can even recur. Therefore, patients should remain under appropriate surveillance.
Resuscitation equipment and narcotic antagonists should be readily available.
Hyperventilation during anaesthesia may alter the patient’s responses to CO2,
thus affecting respiration postoperatively.
Induction of muscle rigidity, which may also involve the thoracic respiratory muscles,
can occur, but can be avoided by the following measures: slow I.V. injection
(ordinarily sufficient for lower doses), premedication with benzodiazepines and
the use of muscle relaxants.
Non-epileptic (myo)clonic movements can occur.
Bradycardia and possibly cardiac arrest can occur if the patient has received an
insufficient amount of anticholinergic or when SUFENTA is combined with nonvagolytic
muscle relaxants. Bradycardia can be treated with atropine.
Opioids may induce hypotension, especially in hypovolaemic patients. Appropriate
measures to maintain a stable arterial pressure should be taken.
The use of rapid bolus injections of opioids should be avoided in patients with
compromised intra cerebral compliance; in such patients the transient decrease in
the mean arterial pressure has occasionally been accompanied by a short-lasting
reduction of the cerebral perfusion pressure.
Patients on chronic opioid therapy or with a history of opioid abuse may require
higher doses.
It is recommended to reduce the dosage in the elderly and in debilitated patients.
Opioids should be titrated with caution in patients with any of the following conditions:
uncontrolled hypothyroidism; pulmonary disease; decreased respiratory
reserve; alcoholism; impaired hepatic or renal function. Such patients also require
prolonged post-operative monitoring.
Intravenous use in labour or before clamping of the cord during caesarean section
is not recommended due to the possibility of respiratory depression in the newborn
infant.

Drugs such as barbiturates, benzodiazepines, neuroleptics, halogenic gases and
other, non-selective CNS depressants (e.g. alcohol) may potentiate the respiratory
depression of narcotics.
When patients have received such drugs, the dose of SUFENTA required will be
less than usual. Likewise, following the administration of SUFENTA, the dose of
other CNS-depressant drugs should be reduced.
Sufentanil is metabolised mainly via the human cytochrome P450 3A4 enzyme.
However, no in vivo inhibition by erythromycin (a known cytochrome P450 3A4
enzyme inhibitor) has been observed. Although clinical data are lacking, in vitro
data suggest that other potent cytochrome P450 3A4 enzyme inhibitors (e.g.
ketoconazole, itraconazole, ritonavir) may inhibit the metabolism of sufentanil.
This could increase the risk of prolonged or delayed respiratory depression. The
concomitant use of such drugs requires special patient care and observation; in
particular, it may be necessary to lower the dose of SUFENTA.
It is usually recommended to discontinue MAO-inhibitors 2 weeks prior to any
surgical or anaesthetic procedure. However, several reports describe the unevent ful
use of fentanyl, a related opioid, during surgical or anaesthetic procedures in patients
on MAO-inhibitors.

Safety of intravenous sufentanil in human pregnancy has not been established
although studies in animals have not demonstrated any teratogenic effects. See
Preclinical safety data. As with other drugs, risk should be weighed against
potential benefit to the patient.
Intravenous use is not recommended in labour.
If Sufenta is nevertheless administered, an antidote for the child should always
be at hand.
SUFENTA is excreted in breast milk. Caution should be exercised when SUFENTA
is administered to a nursing woman.

Effects on Ability to Drive and Use Machines
Patients should drive or operate a machine only if sufficient time has elapsed
after the administration of SUFENTA.

Undesirable Effects
Clinical Trial Data
The safety of SUFENTA/SUFENTA FORTE was evaluated in 650 sufentanil-treated
subjects who participated in 6 clinical trials. Of these, 78 subjects participated in
2 trials of sufentanil administered intravenously as an anaesthetic agent for induction
and maintenance of anaesthesia in subjects undergoing major surgical procedures
(coronary artery bypass or open-heart). The remaining 572 subjects participated
in 4 trials of epidural sufentanil administered as a postoperative analgesic
or as an analgesic adjunct to epidural bupivacaine during labour and vaginal
deliveries. These subjects took at least 1 dose of sufentanil and provided safety
data. Adverse Drug Reactions (ADRs) that were reported for ≥1% of sufentaniltreated
subjects in these trials are shown in Table 1.

Additional ADRs that occurred in <1% of sufentanil-treated subjects in the 6 clinical
trials are listed in Table 2.

ADRs reported from only the trials of sufentanil administered intravenously as
an anaesthetic agent.
Postmarketing Data
Adverse drug reactions first identified during postmarketing experience with
sufentanil citrate are included in Table 3. In the table, the frequencies are provided
according to the following convention:
Very common ≥1/10
Common ≥1/100 and <1/10
Uncommon ≥1/1000 and <1/100
Rare ≥1/10000 and <1/1000
Very rare <1/10000, including isolated reports
In Table 3, ADRs are presented by frequency category based on spontaneous
reporting rates. The frequency category “not known” is used for ADRs for which
no valid estimate of the incidence rate can be derived from clinical trials.

 

Signs and Symptoms
An overdosage of SUFENTA manifests itself as an extension of its pharmacologic
actions. Depending on the individual sensitivity, the clinical picture is determined
primarily by the degree of respiratory depression, which varies from bradypnoea
to apnoea.
Treatment
In the presence of hypoventilation or apnoea, oxygen should be administered and
respiration should be assisted or controlled as indicated. A specific narcotic
antagonist, such as naloxone, should be used as indicated to control respiratory
depression. This does not preclude the use of more immediate countermeasures.
The respiratory depression may last longer than the effect of the antagonist; additional
doses of the latter may therefore be required.
If depressed respiration is associated with muscular rigidity, an intravenous neuromuscular
blocking agent might be required to facilitate assisted or controlled
respiration.
The patient should be carefully observed; body warmth and adequate fluid intake
should be maintained. If hypotension is severe or if it persists, the possibility of
hypovolaemia should be considered, and if present, it should be controlled with
appropriate parenteral fluid administration.

ATC Code N01AH02
Sufentanil is a highly potent opioid analgesic, (7-10 times more potent than fentanyl
in man) with a high safety ratio (LD50/ED50 for the lowest level of analgesia) in
rats; at 25211 this ratio is higher than for fentanyl (277) and for morphine (69.5).
Intravenous sufentanil has a rapid onset of action. Limited accumulation and rapid
elimination from tissue storage sites allow a rapid recovery. Depth of analgesia is
dose-related and can be adjusted to the pain level of the surgical procedure.
Like other narcotic analgesics, sufentanil, depending on the dose and speed of
administration, can cause muscle rigidity, as well as euphoria, miosis and bradycardia.
Histamine assays have not revealed any histamine-releasing potential in patients
administered SUFENTA.
All actions of sufentanil are immediately and completely reversed by a specific
narcotic antagonist, such as naloxone.

Sufentanil is a synthetic opioid with μ-agonist pharmacologic effects
Distribution
In studies with intravenous sufentanil doses ranging from 250 to 1500 μg which
allow prolonged blood sampling and drug measurements, the following were
found: sequential distribution half-lives of 2.3-4.5 min and 35-73 min), a Vc (volume
of distribution of the central compartment) of 14.2 L, a Vdss (distribution volume
at steady state) of 344 L detection limitations. The sequential distribution
half-lives but not the terminal half-life (ranging from 4.1 h after 250 μg to 10-16 h
after 500-1500 μg) determine the decline of the sufentanil plasma concentrations
from therapeutic to recovery levels. Sufentanil pharmacokinetics are linear within
the dose range studied. Plasma protein binding of sufentanil is about 92.5%.
Plasma protein binding in children is lower compared to adults and increases with
age. In newborns sufentanil is about 80.5% bound to proteins compared to 88.5%
in infants and 91.9% in children
Metabolism
The liver and small intestine are the major sites of biotransformation. Sufentanil is
metabolised mainly via the human cytochrome P450 3A4 enzyme.
Elimination
The mean (range) terminal elimination half-life of sufentanil is 784 (656-938) min.
Because of assay detection limitations, the sufentanil elimination half-life was significantly
shorter (240 min) after the 250 μg dose than after 1500 μg. The plasma
clearance is 917 mL/min. Approximately 80% of the administered dose is excreted
within 24 hours and only 2% of the dose is eliminated as unchanged drug.
Special populations
Hepatic Impairment
The volume of distribution is slightly increased and total clearance slightly decreased
in cirrhotic patients compared to controls. This results in a significant prolongation
of half-life by about 30% which warrants a longer period of postoperative surveillance
(see Special warnings and special precautions for use).
Renal Impairment
The volume of distribution at steady state, total clearance, and terminal elimination
half-life in patients on dialysis and undergoing renal transplantation are not different
from healthy controls. The free fraction of sufentanil in this population is not different
from healthy patients.

Preclinical effects were observed only at exposures considered sufficiently in
excess of the maximum human exposure indicating little relevance to clinical use.

The other ingredients of SUFENTA/SUFENTA FORTE are sodium chloride and
water for injection.

The injectable solution must not be mixed with other products.
If desired, SUFENTA/SUFENTA FORTE may be mixed with sodium chloride or
glucose intravenous infusions. Such dilutions are compatible with plastic infusion
sets, they should be used within 24 hours of preparation.

Observe expiry date on the outer pack

Keep ampoule in the outer carton.
Store between 15° and 30° C.
Keep out of reach of children.

2 and 10 ml ampoules at 5 μg/ml and in 1 and 5 ml ampoules at 50 μg/ml.