Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2018 Publisher: Hospira UK Limited, Horizon, Honey Lane, Hurley, Maidenhead, SL6 6RJ, UK
Hypersensitivity to pancuronium or the bromide ion or to any of the excipients listed in section 6.1. Concurrent use of a depolarising neuromuscular blocking agent e.g. suxamethonium.
Anaphylactic reactions can occur following the administration of neuromuscular blocking agents. Precautions for treating such reactions should always be taken. (see section 4.8).
Particularly in the case of previous anaphylactic reactions to neuromuscular blocking agents, special precautions should be taken since allergic cross-reactivity to neuromuscular blocking agents has been reported (see section 4.8).
As pancuronium bromide is excreted mainly in the renal system, the elimination half-life is prolonged in renal failure, resulting in a reduction in plasma clearance and prolonged duration of action.
The prolongation of half-life in patients with renal failure is often but not always associated with an extended duration of neuromuscular blockage. In these patients, the recovery from neuromuscular block may also be prolonged.
The duration of action may be prolonged in these conditions and resistance to neuromuscular blocking action of pancuronium bromide may occur because of the increased volume of distribution of the drug.
In such conditions, the drug has a slower onset and coupled with the increased total dosage requirements, there may be a prolongation of blockade and recovering time in these patients.
Patients with carcinomatosis especially associated with bronchial carcinoma may exhibit a marked sensitivity to this agent, and the neuromuscular block produced may respond poorly to neostigmine.
As with other non-depolarising muscle relaxants pancuronium bromide should be used with care in patients with pre-existing pulmonary, hepatic or renal disease and with particular care in patients with muscular dystrophies, myasthenia gravis and myasthenic syndrome unless it is intended to administer prolonged post-operative respiratory assistance. As is the case with other curariform agents, in cases of neuromuscular disease or after poliomyelitis, pancuronium bromide should be used with extreme caution since the response to neuromuscular blocking agents may be considerably altered in these patients. The magnitude and direction of this alteration may vary widely.
Before administration of pancuronium bromide conditions such as electrolyte disturbance, altered pH, and dehydration should be corrected if possible. Pancuronium bromide should be used cautiously in patients with a tendency to hypertension.
Pancuronium bromide can cause a reduction in the partial prothromboplastin time and prothrombin time. Conditions associated with slower circulation times, e.g. cardiovascular disease, oedema, old age result in an increased volume of distribution which may lead to an increased onset time.
Pancuronium bromide should be used with particular care in neonates, in ill or cachetic patients, in the presence of liver disease or obstructive jaundice (resistant to the effects of drugs) in states with altered plasma protein levels or when there is diminished renal blood flow or renal disease. In operations employing the hypothermic techniques the neuromuscular blocking effect of non-depolarising drugs is decreased and increased by warming the patient.
Pancuronium bromide should be administered in carefully adjusted dosage or under the supervision of a qualified anaesthetist and only when facilities for controlled ventilation, insufflation with oxygen and endotracheal intubation are available for immediate use.
Since pancuronium bromide causes relaxation of the respiratory muscles, respiration must be assisted in all patients. It is essential to ensure that the patient is breathing spontaneously, deeply and regularly before leaving the theatre after anaesthesia. The neuromuscular blockage achieved with pancuronium bromide can be reversed with a cholinesterase inhibiting agent (e.g. neostigmine) in an adequate dose, together with atropine as an anticholinergic agent.
Care should be exercised if there is a danger of regurgitation when intubating the patient, for example during crash induction.
Other conditions which may increase the effect of pancuronium bromide are: hypokalaemia (e.g. after severe vomiting, diarrhoea, digitalisation and diuretic therapy), hypomagnesaemia, hypocalcaemia (after massive transfusions), hypoproteinaemia, dehydration, acidosis, hypercapnia and cachexia.
Suxamethonium. Used prior to pancuronium bromide (for endotracheal intubation) enhances the relaxation effect of the pancuronium bromide and the duration of action. Therefore administration of pancuronium bromide should be delayed until suxamethonium shows signs of wearing off.
Anaesthetics. The following anaesthetics may potentiate the neuromuscular blocking activity of pancuronium bromide: halothane, ether, enflurane, isoflurane, methoxyflurane, cyclopropane, thiopentone, methohexitone, ketamine, fentanyl, gammahydroxybutyrate, etomidate.
The following drugs may influence the duration of action of pancuronium bromide and the intensity of neuromuscular block.
Potentiation: Other non-depolarising muscle relaxants, prior administration of succinylcholine, antibiotics of the polypeptide and aminoglycoside groups, diazepam, propranolol, thiamine (high dose), MAO inhibiting agents, quinidine, magnesium sulfate, protamine, nitroglycerin, narcotic analgesics, diuretics, phenytoin, alpha and beta adrenergic blocking agents, imidazoles, metronidazole, noradrenaline and adrenaline.
Decreased effect: Neostigmine, edrophonium, corticosteroids (high dose), noradrenaline, adrenaline, potassium chloride, calcium chloride, sodium chloride, heparin (temporary decrease), azathioprine, theophylline, pyridostigmine, neuroleptic analgesia and propanidid.
Variable effect: Depolarising muscle relaxants given after the administration of pancuronium bromide may produce potentiation or attenuation of the neuromuscular blocking effect.
The non-depolarising drug increases resistance towards the neuromuscular blocking effect of the depolarising drug. Therefore high doses of a depolarising drug are necessary before muscular relaxation can be obtained. These high doses of a depolarising drug may cause endplate desensitisation and prolong post-operative apnoea.
Unlike a non-depolarising block, a depolarising block cannot be overcome by, and may even be worsened by an anticholinesterase agent.
The duration of action of mivacurium has been found to be significantly increased when given after pancuronium bromide, due to the reduction of plasma cholinesterase activity by pancuroniumbromide.
Influence on the cardiovascular system: Pancuronium bromide does not intensify the hypotension induced by halothane; in addition the cardiac depression is partly restored. The excessive bradycardia induced by neuroleptic analgesia and some of the cholinergic effects of morphine derivatives are counteracted by pancuronium bromide.
Pancuronium bromide should be given with caution to patients receiving chronic tricyclic antidepressant therapy who are anaesthetised with halothane or any inhalation anaesthetic since this enhances the predisposition to the development of cardiac arrhythmias associated with tricyclic antidepressants.
Recent evidence suggests that alkylating drugs (nitrogen mustards) should be considered a possible hazard when given to patients during anaesthesia involving the use of muscle relaxants.
The use of pancuronium bromide in pregnant or breast feeding women with respect to safety has not been established. Therefore the drug should only be administered to pregnant women or lactating women when the attending physician decides that the potential benefits outweigh the risks.
Pancuronium bromide may be used for caesarean section. Pancuronium bromide does not affect Apgar score, foetal muscle tonus nor cardiorespiratory adaptation of the new-born. From assays of pancuronium bromide concentration in umbilical blood samples it is apparent that only very limited placental transfer of pancuronium bromide occurs.
The reversal of neuromuscular block induced by pancuronium bromide may be unsatisfactory in patients receiving magnesium sulfate for toxaemia of pregnancy because magnesium salts enhance neuromuscular blockade. Dosages should be reduced in such cases.
It is not recommended to use potentially dangerous machinery or drive a car within 24 hours after full recovery from the neuromuscular blocking action of pancuronium bromide.
High doses of a depolarising drug may cause end-plate desensitisation and prolong post-operative apnoea.
Cardiac disorders and vascular disorders: Increased pulse rate and cardiac output. Blood pressure may rise. Arrhythmias may occur occasionally.
Eye disorders: Pancuronium bromide decreases intra-ocular pressure and induces miosis, both effects being favourable in ophthalmic surgery.
Gastrointestinal disorders: Salivation is sometimes noted during anaesthesia.
Skin and subcutaneous tissue disorders: Occasional transient rash has been noted.
Immune system disorders: Hypersensitivity
Severe anaphylactoid reactions have been reported uncommonly. In the case of previous anaphylactic reactions to neuromuscular blocking agents, special precautions should be taken since allergic cross reactivity between neuromuscular blocking agents has been reported.
Since neuromuscular blocking agents in general are known to be capable of inducing histamine release both locally and systemically, the possible occurrence of itching and erythematous reactions at the site of injection and/or generalised histaminoid (anaphylactoid) reactions such as bronchospasm and cardiovascular changes should always be taken into consideration when administering these drugs.
General disorders and administration site conditions: Injection Site Reactions: Pain or local skin reactions noted at the site of injection.
Respiratory disorders: Bronchospasm has rarely been reported.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: United Kingdom, Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Do not mix other solutions in the same syringe as a change in pH can cause precipitation.
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