Sublimax

Sublimax

fentanyl

Manufacturer:

Yichang Humanwell

Distributor:

Endure Medical
Full Prescribing Info
Contents
Fentanyl citrate.
Description
Each mL contains Fentanyl (as citrate) 50 mcg.
Action
Pharmacology: Mechanism of Action: Opioid analgesics bind with stereospecific receptors at many sites within the central nervous system (CNS) to alter processes involving both the perception of and emotional response to pain. Although the precise sites and mechanisms of action have not been fully determined, alterations in the release of various neurotransmitters from afferent nerves sensitive to painful stimuli may be partially responsible for the analgesic effects. It has been proposed that there are multiple subtypes of opioid receptors, each mediating various therapeutic and/or side effects of opioid drugs. The actions of an opioid analgesic may therefore depend upon whether it acts as full agonist or a partial agonist or is inactive at each type of receptor. Fentanyl and its derivatives probably produce their effects via agonist actions at the μ receptor.
Pharmacokinetics: After parenteral doses, fentanyl citrate has a rapid onset and short duration of action. After transmucosal delivery, up to 50% of the dose is rapidly absorbed from the buccal mucosa; the remainder is swallowed and slowly absorbed from the gastrointestinal tract. Some first pass metabolism occurs via this route. The absolute bioavailability of transmucosal delivery is about half that for intravenous fentanyl but varies between formulations. Absorption is slow after transdermal application. Fentanyl is metabolized in the liver by N-dealkylation and hydroxylation via the cytochrome P450 isoenzyme CYP3A4. Metabolites and some unchanged drug are excreted mainly in the urine. The short duration of action is probably due to rapid redistribution into the tissues rather than metabolism and excretion. The relatively longer elimination half-life reflects slower release from tissue depots. About 80% has been reported to be bound to plasma proteins. Fentanyl appears in the CSF. It crosses the placenta and has been detected in breast milk.
Indications/Uses
Short term duration analgesia during pre-medication induction and maintenance of anaesthesia, in immediate post-operative period and respiratory depressant in the management of mechanically ventilated patients under intensive care.
Dosage/Direction for Use
Dosage should be individualized according to age, bodyweight, physical status, and underlying pathological condition, use of other drugs, type of anaesthesia to be used and the surgical procedure involved. Duration of action of fentanyl depends on the dose and the intensity of the pain involved, and may vary from 10 minutes to several hours. Fentanyl is more lipid-soluble than morphine and after standard single intravenous doses has a rapid onset and short duration of action. Fentanyl is rapidly redistributed in the body and has a longer elimination half-life than morphine. High or repeated doses, fentanyl becomes a relatively long-acting drug; to avoid accumulation patients should be monitored and doses adjusted accordingly. Repeated intra-operative doses of fentanyl should be given with care, since not only may the respiratory depression persist into the postoperative period but it may become apparent for the first time postoperatively.
Adult: Premedication: 50 to 100 mcg (1 to 2 mL) may be administered intramuscularly 30 to 60 minutes prior to surgery. Patients with spontaneous respiration: May be given 50 to 200 μg of fentanyl as an initial dose with supplements of 50 μg. It is recommended that doses above 2 μg is per kg body-weight should be used in conjunction with assisted ventilation. Significant respiratory depression follows doses of more than 200 gg. Patients whose ventilation is assisted: May be given 300 to 3500 μg (up to 50 μg per kg) as an initial dose with supplements of 100 to 200 μg or higher depending on the patient's response. High doses have been reported to moderate or attenuate the response to surgical stress.
Adjunct to general anaesthesia: induction 50 to 100 mcg (1 to 2 mL) I.V. initially, repeat at two to three minutes intervals until desired effect is achieved. A reduced dose of 25 to 50 mcg (0.5 to 1 mL) is recommended in elderly and poor risk patients.
Maintenance: 25 to 50 mcg (0.5 to 1 mL) Intravenous or Intramuscular when movement and/or changes in vital signs indicate surgical stress or lightening of analgesia.
Adjunct to regional anaesthesia: 50 to 100 mcg (1 to 2 mL) may be administered Intramuscularly for the control of pain, tachypnoea and emergence delirium. The dose may be repeated in one or two hours as needed.
Post-operatively: 50 to 100 mcg (1 to 2 mL) may be administered intramuscularly for the control of pain, tachypnoea and emergence delirium. The dose may be repeated in one or two hours as needed.
Children: For induction and maintenance in children 2 to 12 years of age, a reduced dose of 20 to 30 mcg (0.4 to 0.6 mL) per 10 kg is recommended.
Overdosage
Symptoms: Narcosis which may be preceded by marked skeletal rigidity, cardiorespiratory depression, accompanied by cyanosis followed by a fall in temperature, circulatory collapse, coma and possibly death.
Treatment: In the presence of hypoventilation or apnea, oxygen should be administered and respiration assisted or controlled as necessary. A patent airway must be maintained. If depressed respiration is associated with muscular rigidity, an intravenous intramuscular blocking agent might be required to facilitate assisted or controlled respiration. The patient should be carefully observed for 24 hours; body warmth and adequate fluid intake should be maintained. If severe or persistent hypotension occurs, the possibility of hypovolaemia should be considered and managed with appropriate parenteral fluid therapy. A specific narcotic antagonist, such as nalorphine or naloxone, should be available for use as indicated to manage respiratory depression. This does not preclude the use of more immediate countermeasures. The duration of respiratory depression following overdosage of Fentanyl is usually longer than the duration of narcotic antagonist action.
Contraindications
Contraindicated to the patients with the following conditions: bronchial asthma; head injuries and increased intracranial pressure; patients susceptible to respiratory depression such as comatose patients who may have head injuries or a brain tumour; myasthenia gravis and patients with hypersensitivity to the drug or any of its components.
Warnings
Adequate facilities should be available for post-operative monitoring and ventilation. Resuscitative equipment, oxygen and a narcotic antagonist should be readily available to manage apnea.
Concomitant neuroleptics: If Fentanyl is administered with neuroleptics, the user should be familiar with the special properties of each drug, particularly with regard to duration of action. In addition, when such a combination is used fluids and other counter measures to manage hypotension should be available.
Total narcotic dose: As with other potent narcotics, the respiratory depressant effect of Fentanyl persists longer than the measured analgesic effect. The total dose of all narcotic analgesics is given during recovery from the anaesthesia. It is recommended that post-operative narcotics, when required, should be used initially in reduced doses, as low as 1/4 to 1/3 of those usually recommended.
Muscle rigidity: Fentanyl may cause rigidity, particularly involving the muscles of respiration. These effects are related to the dose and speed of injection and may be reduced by slow intravenous injection. If this effect occurs, it may be managed by the use of assisted or controlled respiration and, if necessary, by administration of a neuromuscular blocking agent compatible with the patient's conditions.
Drug Dependence: Fentanyl can produce drug dependence of the morphine type and therefore has the potential for being abused.
Respiratory depression: Depression of respiration is the most marked and the dangerous side effect of Fentanyl. In the post-operative period, patients may exhibit delayed depression of respiration. Patients should be monitored for this possibility and appropriate countermeasures taken as necessary.
Use in Pregnancy: Narcotic analgesics may cause respiratory depression in the newborn infant. These products should only be used during labor after weighing the needs of the mother against the risk of the fetus.
Special Precautions
Impaired respiration: Fentanyl should be used with caution in patients with severe impairment of pulmonary function because of the possibility of respiratory depression (e.g. chronic obstructive pulmonary disease, patients with decreased respiratory reserve, or any patient with potentially compromised respiration). In such patients, narcotics may further decrease respiratory drive and increase airway resistance. During anaesthesia, this can be managed by assisted or controlled respiration.
Narcotic antagonists for respiratory depression: Respiratory depression caused by narcotic analgesics can be reversed by narcotic antagonists. However, appropriate surveillance should be maintained because the duration of respiratory depression of dose of Fentanyl employed during anaesthesia is usually longer than the duration of narcotic antagonist action.
Impaired liver kidney function: Fentanyl should be administered with caution to patients with liver and kidney dysfunction because of the importance of these organs in the metabolism and excretion of drugs.
Bradycardia: Fentanyl may produce bradycardia, which may be treated with atropine; however it should be used with caution in patients with cardiac bradyarrythmias.
Sphincter of Oddi Spasm: As observed with all narcotic analgesics, episodes suggestive of sphincter of Oddi Spasm may occur with Fentanyl.
Adjunct to conduction anaesthesia: Nitrous oxide has been reported to produce cardiovascular depression when given with high doses of Fentanyl. Certain forms of conduction anaesthesia, such as spinal anaesthesia and some peridural anaesthetics, can alter respiration by blocking intercostals nerves. Through other mechanisms Fentanyl can also alter respiration.
Neuroleptics (i.e. droperidol): Blood pressure may be altered and hypotension can occur.
Adverse Reactions
Respiratory depression occurs with high doses of fentanyl. Unlike morphine, fentanyl is reported not to cause significant histamine release. Transient hypotension may follow intravenous dosage. Muscle rigidity can occur and may require neuromuscular blockers. Other adverse effects includes: nausea, vomiting, constipation, drowsiness, and confusion; tolerance to these generally develops with long-term use. Micturition may be difficult and there may be ureteric or biliary spasm; the latter may be associated with alterations in liver enzyme values. There is also an antidiuretic effect. Dry mouth, dizziness, sweating, facial flushing, headache, vertigo, bradycardia, tachycardia, palpitations, orthostatic hypotension, hypothermia, restlessness, changes of mood, decreased libido or potency, hallucinations, and miosis also occur. These effects tend to occur more commonly in ambulant patients than in those at rest in bed and in those without severe pain. Raised intracranial pressure occurs in some patients. Larger doses of opioids produce respiratory depression and hypotension, with circulatory failure and deepening coma. Convulsions may occur, especially in infants and children. Rhabdomyolysis progressing to renal failure has been reported in overdosage. Death may occur from respiratory failure. Toxic doses vary considerably with the individual and regular users may tolerate large doses. The triad of coma, pinpoint pupils, and respiratory depression is considered indicative of opioid overdosage; dilatation of the pupils occurs as hypoxia develops. Pulmonary edema after overdosage is a common cause of fatalities among opioid addicts. Morphine and some other opioids have a dose-related histamine-releasing effect which may be responsible in part for reactions such as urticaria and pruritus as well as hypotension and flushing. Contact dermatitis has been reported and pain and irritation may occur on injection. Anaphylactic reactions after intravenous injection have been reported rarely.
Drug Interactions
Fentanyl is metabolized via the cytochrome P450 isoenzyme CYP3A4; use with potent inhibitors of this isoenzyme, such as ritonavir and other HIV-protease inhibitors, may increase fentanyl plasma concentrations.
Antivirals: Ritonavir, an inhibitor of the cytochrome P450 isoenzyme CYP3A4, might prolong fentanyl-induced respiratory depression. When Ritonavir is given in healthy subjects; plasma clearance of fentanyl was decreased and the elimination half-life and area under the plasma concentration-concentration-time curve increased.
Benzodiazepines: An additive sedative effect is to be expected when benzodiazepines such as diazepam, lorazepam, and midazolam was given with opioid analgesics in anaesthetic or analgesic regimens however there are also reports of severe respiratory depression with midazolam and fentanyl or sudden hypotension with midazolam and fentanyl or sufentanil. Clearance of midazolam appears to be reduced by fentanyl, possibly as a result of competitive inhibition of metabolism by the cytochrome P450 isoenzyme CYP3A. Synergistic potentiation of the induction of anaesthesia has been reported between midazolam and fentanyl but one study has suggested that midazolam can reduce the analgesic effects of sufentanil.
Propofol: In a study mean blood concentrations of propofol were higher in patients pretreated with fentanyl compared with patients maintained only on nitrous oxide.
Monoamine oxidase (MAO) inhibitors: Severe and unpredictable potentiation by MAO inhibitors has been reported with narcotic analgesics and the use of Fentanyl in patients who have received MAO inhibitors within 14 days.
Storage
Store at temperatures not exceeding 30°C. Protect from light.
ATC Classification
N01AH01 - fentanyl ; Belongs to the class of opioid anesthetics. Used as general anesthetics.
Presentation/Packing
Soln for inj (amp) 50 mcg/mL x 2 mL x 10's.
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