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Schedule 7.
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Each mL contains !
hydrochloride 0,544 mg (equivalent to alfentanil base 0,50 mg) and sodium chloride
9,0 mg in water for injection.
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A.2.7 Central nervous system depressants. Narcotic analgesics.
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cAPIFEN* injection is a narcotic analgesic with a pharmacologic profile similar to that of fentanyl. It differs from
fentanyl, however, in that its analgesic potency is four times less than that of fentanyl.
Its depressant effects on the respiratory rate and alveolar ventilation are also shorter than those of fentanyl and in
most cases the clinical analgesic effect lasts longer than significant respiratory depression. The onset of action of
cAPIFEN* is four times more rapid than that of an equi-analgesic dose of fentanyl; the peak analgesic and
respiratory depressant effects occur within 1 minute. The duration of action of cAPIFEN* is three times shorter than
that of an equi-analgesic dose of fentanyl but is clearly dose-related.
The onset of the analgesic action of cAPIFEN* is rapid, the peak effect being reached within 1 minute. The duration
of action is short, 11 minutes at twice and 17 minutes at four times the lowest ED50.
At high doses (> 120 µg/kg), cAPIFEN* induces sleep and can be used as an anaesthetic induction agent. The
induction is smooth, pain-free and devoid of cardiovascular and hormonal stress responses to intubation.
cecovery after cAPIFEN* administration is rapid and smooth. All actions of cAPIFEN* are immediately and
completely reversed by the specific narcotic antagonist naloxone hydrochloride.
cAPIFEN* maintains cardiovascular stability. cAPIFEN* has not been shown to cause histamine release (in doses
used clinically).
cAPIFEN* has a low degree of ionisation (11% at pH = 7,4) which significantly contributes to a rapid distribution.
Tissue distribution is limited : the total distribution volume varies from 0,4 to 1,0 L/kg. cAPIFEN*'s limited
liposolubility and strong plasma protein binding (92%) contribute to its limited volume of distribution.
cAPIFEN* is metabolised mainly in the liver. Only 1% of the active substance is found unaltered in the urine. The
plasma clearance averages 356 mL/minute. The metabolites are inactive and 70-80% of them are eliminated in the
urine.
Elimination is very rapid; the sequential distribution half-lives are 1 and 14 minutes and the terminal half-life is 90-
111 minutes (range 50-150 minutes). Accumulation of alfentanil may occur under the following circumstances:
With prolonged continuous infusion or with repeated administration of single doses and in patients with reduced
plasma clearance e.g. patients with compromised liver function and patients over the age of 65 years.
During average length to long-lasting surgery, analgesia can be maintained by repeating cAPIFEN* injections or by
continuous infusion, subsequent to a bolus dose. Once steady-state has been reached after infusion, the elimination
half-life remains unaltered.
cAPIFEN* is indicated for use as a narcotic analgesic in general anaesthesia for both short (bolus injections) and
long (bolus, supplemented by increments or by infusion) surgical procedures. It may also be used as an anaesthetic
induction agent.
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Alfentanil may cause bradycardia, an effect that may be marked and rapid in onset, but that can be antagonized by
atropine. Bradycardia may be more pronounced when alfentanil is combined with other anaesthetic agents which
depress the heart rate or increase vagal activity. Heart rate should therefore be monitored carefully.
As asystole has been reported on occasions in non-atropinised patients, it is advisable to be prepared to administer
an anticholinergic drug if the heart rate is considered low.
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 cerebral perfusion pressure.
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Patients who have received cAPIFEN* should remain under appropriate surveillance.
cesuscitation equipment and a narcotic antagonist should be available to manage apnoea. The duration of
respiratory depression is dose-related, but short and is immediately reversed by the specific narcotic antagonist,
naloxone hydrochloride.
Because of its weak cholinergic activity, cAPIFEN* should be used with caution in patients with cardiac
arrhythmias.
Patients on chronic opioid therapy or with a history of opioid abuse may require higher doses.
Hyperventilation during anaesthesia may alter the patient's response to CO2, thus affecting respiration
postoperatively.
Opioids may induce hypotension, especially in hypovolaemic patients. Appropriate measures to maintain a stable
arterial pressure should be taken.
It is recommended to reduce the dosage in the elderly or 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
postoperative monitoring.
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Since MAO inhibitors have been reported to potentiate narcotic analgesics, the use of cAPIFEN* in patients who
have received MAO inhibitors within 2 weeks should be avoided.
However, several reports describe the uneventful use of fentanyl (a related opioid) during surgical or anaesthetic
procedures in patients on MAO-inhibitors.
When insufficient anticholinergic is administered or when cAPIFEN* is given in combination with non-vagolytic
muscle relaxants, bradycardia may occur.
Medicines such as barbiturates, benzodiazepines, neuroleptics, halogenic gases and other non-selective central
nervous depressants (e.g alcohol) may potentiate the respiratory depression of narcotics. When patients have
received such medicines, the dose of cAPIFEN* required will be less than usual. Likewise, following the
administration of cAPIFEN*, the dose of the other central nervous system depressant drugs should be reduced.
The concomitant use of erythromycin with cAPIFEN* may significantly inhibit cAPIFEN* clearance and may
increase the risk of prolonged or delayed respiratory depression. Cimetidine reduces the distribution volume and
impairs the clearance of cAPIFEN*. Therefore, smaller doses of cAPIFEN* will be required and the duration of
action may be extended in patients receiving erythromycin or cimetidine. Theoretically, similar consideration may
apply to other hepatic enzyme inhibitors.
A clear colourless solution in 2 mL or 10 mL glass ampoules.
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Cartons containing 5 x 2 mL and 5 x 10 mL ampoules.?