INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
SUFENTA FORTE® injection

SCHEDULING STATUS:
Schedule 6

PROPRIETARY NAME
(and dosage form):

SUFENTA FORTE^® injection

COMPOSITION
Each mL contains sufentanil citrate 0,075 mg equivalent to 0,05 mg of sufentanil base and 9,0 mg sodium chloride in water for injection.

PHARMACOLOGICAL CLASSIFICATION
A 2.9 Central nervous system depressants. Narcotic analgesics.

PHARMACOLOGICAL ACTION
SUFENTA FORTE injection is an opioid analgesic with hypnotic properties. Intravenous SUFENTA FORTE produces a dose-related attenuation of catecholamine release, particularly noradrenaline.
The pharmacokinetics of intravenous SUFENTA FORTE can be described as a three compartment, model with an average distribution time of 0,72 minutes, a redistribution time of 13,7 minutes and an elimination half-life of 148 minutes. Plasma protein binding is approximately 92,5%, and 80% of the administered dose is excreted in 24 hours. The liver and intestine are the major sites of biotransformation.
SUFENTA FORTE has an immediate onset of action. A dose dependent attenuation of the sympathetic response to surgical stress has been demonstrated at intravenous doses of 8–30 micrograms/kg.
Peak plasma concentrations of sufentanil administered epidurally are reached within 10 minutes and are 4–6 times lower than those after intravenous administration. The addition of adrenaline (50–75 micrograms) further reduces the initial fast absorption by 25–50%.

INDICATIONS
SUFENTA FORTE administered intravenously is indicated:

–	as a primary anaesthetic agent for the induction and maintenance of anaesthesia with 100% oxygen in patients undergoing cardiac surgery associated with the use of cardiopulmonary bypass apparatus;
–	as an analgesic adjunct in the maintenance of balanced general anaesthesia in cardiac surgery associated with the use of cardiopulmonary bypass apparatus, as well as surgical procedures requiring endotracheal intubation and ventilation.

SUFENTA FORTE administered by epidural route is indicated for:

–	the postoperative management of pain following general surgery, thoracic or orthopaedic procedures and Caesarean sections, as an analgesic adjunct to epidural bupivacaine with or without adrenaline during labour and vaginal deliveries.

CONTRA-INDICATIONS
SUFENTA FORTE is contra-indicated in patients with a known intolerance to the medicine or to morphinomimetics in general.
Epidural SUFENTA FORTE should not be given in the presence of severe haemorrhage or shock, septicaemia, infection at the injection site, disturbances in blood morphology and/or anticoagulant therapy or other concomitant therapy or medical conditions which could contra-indicate the technique of epidural administration.

WARNINGS
Safety in pregnancy and lactation has not been established.

DOSAGE AND DIRECTIONS FOR USE
The dosage of SUFENTA FORTE should be individualized. Factors to be considered in determining the dose are age, body mass, physical status, underlying pathological condition, use of other medicines, type of anaesthesia to be used and duration of the surgical procedure.
In obese patients, the dosage of SUFENTA FORTE should be determined on the basis of standard body mass.
Compatibility:
If desired, SUFENTA FORTE may be mixed with sodium chloride or glucose intravenous infusions. Such dilutions are compatible with plastic infusions sets. They should be used within 24 hours of preparation.

ADMINISTRATION AS PRIMARY ANAESTHETIC AGENT WITH 100% OXYGEN.
Droperidol may be given to reduce the incidence of nausea and vomiting.

INTRAVENOUS ADMINISTRATION –ADULTS:
Initial dose: 8–30 micrograms/kg (anaesthetic dose) administered with 100% oxygen and muscle relaxant. SUFENTA FORTE produces sleep at dosages of 8 micrograms/kg and maintains a deep level of anaesthesia without the use of additional anaesthetic agents.
Post operative mechanical ventilation and observation are essential at this dosage level on account of extended post-operative respiratory depression.
Maintenance dose: 0,5–0,75 micrograms /kg as determined by changes in vital signs that indicate surgical stress or lightening of anaesthesia.
Intravenous use in children: For induction and maintenance of anaesthesia in children less than 12 years of age undergoing cardiovascular surgery, an anaesthetic dose of 10–25 micrograms/kg, administered with oxygen, is recommended. Supplemental dosages of 0,5–0,75 micrograms/kg are recommended for maintenance, as determined by changes in vital signs indicating surgical stress or lightening of anaesthesia.

ADMINISTRATION AS AN ANALGESIC ADJUNCT TO NITROUS OXIDE/OXYGEN
Droperidol may be given to reduce the incidence of nausea and vomiting.

INTRAVENOUS ADMINISTRATION –ADULTS:
Initial dose: 1–8 micrograms/kg administered with nitrous oxide/oxygen. The duration of action is 1–8 hours depending on the dose.
Maintenance dose: 0,1–0,5 micrograms/kg as needed when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia. Supplemental dosages should be individualized, and adjusted to the remaining operative time anticipated.

EPIDURAL ADMINISTRATION:

Proper placement of a needle or catheter in the epidural space should be verified before SUFENTA FORTE is injected to assure that unintentional intravascular or intrathecal administration does not occur. Unintentional intravascular injection of SUFENTA FORTE could result in potentially serious overdose including acute truncal muscular rigidity and apnoea. Unintentional intrathecal injection of the full sufentanil, bupivacaine epidural doses and volume could produce effects of high spinal anaesthesia including prolonged paralysis and delayed recovery. If analgesia is inadequate, the placement and integrity of the catheter should be verified prior to administration of any additional epidural medications. SUFENTA FORTE should be administered by slow injection.

With epidural administration, caution should be exercised in the presence of respiratory depression and in the presence of foetal distress. Epidural administration requires that the patient should be in a high care environment with continuous supervision. The patient should be closely monitored for at least 2 hours after each dose, as early respiratory depression may occur.

Postoperative management of pain –Adults: An initial dose of 30–50 micrograms may be expected to provide adquate pain relief for up to 4–6 hours. Additional boli of 25 micrograms may be administered if there is evidence of lightening of analgesia. There should be a minimum interval of 1 hour between doses.
Analgesic adjunct during labour and vaginal deliveries: The recommended dosage is 10–15 micrograms administered with 10 mL bupivacaine 0,125% with or without adrenaline. SUFENTA FORTE and bupivacaine should be mixed together before administration. Doses can be repeated twice (for a total of three doses) at not less than one hour intervals until delivery.
Epidural use in children: The safety and efficacy of epidural SUFENTA FORTE in paediatric patients has not been established.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Adverse reactions:
Side-effects reported to occur with SUFENTA FORTE are: respiratory depression, apnoea, muscular rigidity (which may involve the thoracic muscles), non-epileptic (myo)clonic muscle movements, transient hypotension, hypertension, bradycardia, arrhythmias, euphoria, dizziness, post-operative nausea and vomiting, laryngospasm, bronchospasm, itching and chills.
Allergic reactions and asystole have been reported.
Recurrence of respiratory depression after the operation has been observed in rare circumstances.
Sedation, urine retention and pruritus have been reported following epidural administration.
Precautions:
Respiratory depression is dose related and can be reversed by the specific narcotic antagonist, naloxone, but a repeated dose of the antagonist may be necessary because the duration of 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 post-operative period, and if SUFENTA FORTE has been given intravenously it can 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 response to CO₂ thus affecting respiration post-operatively. The incidence and severity of early respiratory depression with epidural administration may be less if adrenaline is added.
Vital signs should be monitored routinely.
Induction of muscle rigidity, which may also involve the thoracic respiratory muscles, can occur but the risk may be reduced if intraveneous injections are administered slowly. A neuromuscular blocking agent compatible with the patient's condition may be administered prophylactically to prevent muscle rigidity or to induce muscle relaxation after rigidity occurs.
Because of its weak cholinergic activity, SUFENTA FORTE should be used with caution in patients with cardiac arrhythmias.
Bradycardia and possibly asystole can occur if the patient has received an insufficient amount of anticholinergic of when SUFENTA FORTE is combined with non-vagolytic 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 intracerebral 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.
It is recommended to reduce the dosage in elderly and 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.
Interactions:
Barbiturates, benzodiazepines, neuroleptics, halogenic gases and other non-selective central nervous system depressants (eg. alcohol), may potentiate the respiratory depressive effects of SUFENTA FORTE. When patients have received central nervous system depressants, the dose of SUFENTA FORTE required will be less than usual. Likewise, following the administration of SUFENTA FORTE, the dose of other central nervous system depressants 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 (eg. fluconazole, ketoconazole, itraconazole, ritonavir, diltiazem and cimetidine) may inhibitor 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 FORTE.
Mono-amine oxidase (MOA) inhibitors must be discontinued 2 weeks prior to the administration of sufentanil.
Effects on driving ability and use of machinery:
Patients should only drive or operate a machine if sufficient time has elapsed after administration of SUFENTA FORTE.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
Symptoms:
An overdose of SUFENTA FORTE manifests itself as an extension of its pharmacological 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 intermediate 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.

IDENTIFICATION
A clear colourless solution. Free from visible foreign material.

PRESENTATION
SUFENTA FORTE injections are supplied in cartons containing: 5 x 5 mL ampoules.

STORAGE INSTRUCTIONS
Store below 25°C. Protect from light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER
V/2.9/308

NAME AND BUSINESS ADDRESS OF THE APPLICANT
JANSSEN-CILAG logo

JANSSEN PHARMACEUTICA (PTY) LTD.
(Reg. No. 1980/011122/07)
15th Road, Halfway House, 1685
www.janssencilag.co.za

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
3 June 1994

        Code No.: 024412
                2003H
        Britepak

® = TRADEMARK

Updated on this site: April 2004
Source: Pharmaceutical Industry
SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2004