Drugs List

Therapeutic Indications

Uses

Pancuronium bromide is a non-depolarising neuromuscular blocking agent which blocks transmission of motor nerve impulses to the striated muscle receptors. It has a long duration of action and is used for the following:

As an adjuvant in surgical anaesthesia to obtain relaxation of skeletal muscles in a wide range of surgical procedures.

For use in patients in intensive care as a non-depolarising neuromuscular blocking agent for the treatment of various pathologies (such as intractable status asthmaticus and tetanus).

Dosage

Due to the complexity and specialist nature of anaesthesia, specific dosing information on this agent is not included.

When using this agent specialist literature, national guidelines and Trust policies should be consulted, to ensure appropriate dosage and assessment of all relevant patients factors.

Administration

For intravenous injection.

Pancuronium bromide should not be administered by infusion.

Handling

Incompatibilities

Precautions and Warnings

Pancuronium should be administered under the supervision of an anaesthetist and only when facilities for controlled ventilation, insufflation with oxygen and endotracheal intubation are immediately available.

The use of a peripheral nerve stimulator is recommended to monitor neuromuscular block and recovery.

Respiration must be assisted in all patients as pancuronium relaxes the respiratory muscles. Before leaving the theatre following anaesthesia, is it essential to ensure that the patient is breathing spontaneously, deeply and regularly.

The neuromuscular blocking effect obtained with pancuronium may be reversed by administering a cholinesterase inhibiting agent (e.g. neostigmine) with an anticholinergic agent (e.g. atropine).

Use with care if there is a danger of regurgitation when intubating the patient (e.g. during crash induction).

If suxamethonium is used for intubation, administration of pancuronium should be delayed until the patient has clinically recovered from its neuromuscular blockade.

The duration of action of pancuronium depends on the clinical condition of the patient and the dose administered. However, in normal subjects receiving perioperative muscle relaxant doses the usual duration of action is 45 to 60 minutes. In the control of tetanus, duration of action depends on the severity of the spasm and will therefore be variable.

Neuromuscular blocking agents may cause anaphylactic reactions. Treatments for these potential reactions must be immediately available.
Patients with a history of anaphylactic reactions to other neuromuscular blocking agents require special precautions as allergic cross-reactivity has been reported.

Pregnancy - see Pregnancy section

Breastfeeding - see Lactation section

Elderly

Use with caution in renal impairment. Hyperdiuresis may cause a decreased neuromuscular blocking effect. Pancuronium is excreted mainly in the renal system. The half life of pancuronium may be prolonged in patients with renal failure resulting in reduced plasma clearance, prolonged duration of action and often, though not always, prolonged recovery from the neuromuscular block.

Use with caution in patients with hepatic impairment. The duration of action may be prolonged in patients with hepatic impairment and biliary tract disease. Resistance to pancuronium may develop due to the increased volume of distribution of the drug. Pancuronium will have a slower onset in these patients and an increased total dosage may be required. This may lead to a prolonged duration of action and extended recovery time.

In obese patients, the dose of pancuronium based on a microgram/kg basis may lead to overdosage. Dose must therefore be adjusted according to response in these patients and based on the ideal body weight of the patient.

Pancuronium has a prolonged neuromuscular blocking effect in intensive care patients. A reduced dose may be adequate.

Patients with carcinomatosis especially those with bronchial carcinoma may show increased sensitivity to this agent and the neuromuscular block may respond poorly to neostigmine.

Use with caution in the following conditions (unless prolonged postoperative respiratory assistance is intended):
Pulmonary disease
Muscular dystrophies
Myasthenia gravis (pancuronium activity prolonged)
Myasthenic syndrome

Use with extreme caution in patients with neuromuscular disease or a history of poliomyelitis as the response to neuromuscular blocking agents may be significantly altered in these patients. The magnitude and direction of this alteration may vary widely.

Use with caution in patients with an increased risk of hypertension.

Conditions that may increase the effect of pancuronium include:
Hypokalaemia (e.g. after severe vomiting, diarrhoea, digitalisation, after diuretic therapy)
Hypermagnesaemia
Hypocalcaemia (after massive transfusions)
Hypoproteinaemia
Dehydration
Acidosis
Hypercapnoea
Cachexia

Electrolyte imbalance, altered pH levels and dehydration should be corrected prior to treatment.

Partial prothromboplastin time and prothrombin time may be reduced by pancuronium. Conditions associated with slower circulation times (such as cardiovascular disease, oedema and increasing age) can result in an increased volume of distribution and an increased onset time.

Use with particular care in the following:
Neonates
Illness
Obstructive jaundice
Altered plasma protein levels

Operations using hypothermic techniques will decrease the neuromuscular blocking effect of pancuronium. The neuromuscular blocking effect will be increased by warming the patient. The activity of pancuronium is prolonged in patients with hypothermia.

Patients should not drive or operate machinery for at least 24 hours following full recovery from the effects of pancuronium.

Pregnancy and Lactation

Pregnancy

The manufacturer states that pancuronium should only be administered during pregnancy if the potential benefits outweigh the possible risks as the safety of pancuronium administration during pregnancy has not been established.

Pancuronium may be used for caesarean section. Pancuronium does not affect Apgar score, foetal muscle tone, or cardiorespiratory adaptation of the neonate. Assays of pancuronium in umbilical blood samples indicate that only very limited placental transfer of pancuronium occurs.

In patients receiving magnesium sulfate for toxaemia of pregnancy, the reversal of neuromuscular blockade caused by pancuronium may be unsatisfactory as magnesium salts enhance neuromuscular block. In these cases, the dose of pancuronium should be reduced.

Briggs (2011) concludes that pancuronium has been administered directly to the foetus during the last half of pregnancy and to the mother at caesarian section without causing foetal harm. Although no teratogenicity was observed in two animal species, the use of pancuronium in early human pregnancy has not been reported. The drug is known to cross the human placenta, at least near term. Placental transfer early in pregnancy has not been reported. Large or repetitive doses and or prolonged dose-to-delivery intervals may potentially result in newborn depression, but the clinical significance of this appears to be low. Transient foetal heart rate changes and occasional sinusoidal-like pattern have been observed after direct foetal administration but without apparent foetal compromise.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Pancuronium should only be administered during breastfeeding if the potential benefits outweigh the possible risks.

The safety of pancuronium administration during breastfeeding has not been established. Briggs (2011) concludes that as pancuronium is a bisquaternary ammonium compound and is ionised at physiological pH, Only the non-ionised form would be available for excretion in the milk and this would probably only be trace amounts. Compounds of this type are poorly absorbed from the gastrointestinal tract.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Increased pulse rate
Tachycardia
Increased blood pressure
Arrhythmias
Salivation
Rash
Local pain (injection site)
Local reaction at injection site
Bronchospasm
Anaphylactoid-like reaction
Itching
Erythema at injection site
Reduced intra-ocular pressure
Miosis

Presentation

Solution for injection containing pancuronium bromide 2mg per ml.

Drugs List

Therapeutic Indications

Uses

Pancuronium bromide is a non-depolarising neuromuscular blocking agent which blocks transmission of motor nerve impulses to the striated muscle receptors. It has a long duration of action and is used for the following:

As an adjuvant in surgical anaesthesia to obtain relaxation of skeletal muscles in a wide range of surgical procedures.

For use in patients in intensive care as a non-depolarising neuromuscular blocking agent for the treatment of various pathologies (such as intractable status asthmaticus and tetanus).

Dosage

Due to the complexity and specialist nature of anaesthesia, specific dosing information on this agent is not included.

When using this agent specialist literature, national guidelines and Trust policies should be consulted, to ensure appropriate dosage and assessment of all relevant patients factors.

Administration

For intravenous injection.

Pancuronium bromide should not be administered by infusion.

Handling

Incompatibilities

Precautions and Warnings

Pancuronium should be administered under the supervision of an anaesthetist and only when facilities for controlled ventilation, insufflation with oxygen and endotracheal intubation are immediately available.

The use of a peripheral nerve stimulator is recommended to monitor neuromuscular block and recovery.

Respiration must be assisted in all patients as pancuronium relaxes the respiratory muscles. Before leaving the theatre following anaesthesia, is it essential to ensure that the patient is breathing spontaneously, deeply and regularly.

The neuromuscular blocking effect obtained with pancuronium may be reversed by administering a cholinesterase inhibiting agent (e.g. neostigmine) with an anticholinergic agent (e.g. atropine).

Use with care if there is a danger of regurgitation when intubating the patient (e.g. during crash induction).

If suxamethonium is used for intubation, administration of pancuronium should be delayed until the patient has clinically recovered from its neuromuscular blockade.

The duration of action of pancuronium depends on the clinical condition of the patient and the dose administered. However, in normal subjects receiving perioperative muscle relaxant doses the usual duration of action is 45 to 60 minutes. In the control of tetanus, duration of action depends on the severity of the spasm and will therefore be variable.

Neuromuscular blocking agents may cause anaphylactic reactions. Treatments for these potential reactions must be immediately available.
Patients with a history of anaphylactic reactions to other neuromuscular blocking agents require special precautions as allergic cross-reactivity has been reported.

Pregnancy - see Pregnancy section

Breastfeeding - see Lactation section

Elderly

Use with caution in renal impairment. Hyperdiuresis may cause a decreased neuromuscular blocking effect. Pancuronium is excreted mainly in the renal system. The half life of pancuronium may be prolonged in patients with renal failure resulting in reduced plasma clearance, prolonged duration of action and often, though not always, prolonged recovery from the neuromuscular block.

Use with caution in patients with hepatic impairment. The duration of action may be prolonged in patients with hepatic impairment and biliary tract disease. Resistance to pancuronium may develop due to the increased volume of distribution of the drug. Pancuronium will have a slower onset in these patients and an increased total dosage may be required. This may lead to a prolonged duration of action and extended recovery time.

In obese patients, the dose of pancuronium based on a microgram/kg basis may lead to overdosage. Dose must therefore be adjusted according to response in these patients and based on the ideal body weight of the patient.

Pancuronium has a prolonged neuromuscular blocking effect in intensive care patients. A reduced dose may be adequate.

Patients with carcinomatosis especially those with bronchial carcinoma may show increased sensitivity to this agent and the neuromuscular block may respond poorly to neostigmine.

Use with caution in the following conditions (unless prolonged postoperative respiratory assistance is intended):
Pulmonary disease
Muscular dystrophies
Myasthenia gravis (pancuronium activity prolonged)
Myasthenic syndrome

Use with extreme caution in patients with neuromuscular disease or a history of poliomyelitis as the response to neuromuscular blocking agents may be significantly altered in these patients. The magnitude and direction of this alteration may vary widely.

Use with caution in patients with an increased risk of hypertension.

Conditions that may increase the effect of pancuronium include:
Hypokalaemia (e.g. after severe vomiting, diarrhoea, digitalisation, after diuretic therapy)
Hypermagnesaemia
Hypocalcaemia (after massive transfusions)
Hypoproteinaemia
Dehydration
Acidosis
Hypercapnoea
Cachexia

Electrolyte imbalance, altered pH levels and dehydration should be corrected prior to treatment.

Partial prothromboplastin time and prothrombin time may be reduced by pancuronium. Conditions associated with slower circulation times (such as cardiovascular disease, oedema and increasing age) can result in an increased volume of distribution and an increased onset time.

Use with particular care in the following:
Neonates
Illness
Obstructive jaundice
Altered plasma protein levels

Operations using hypothermic techniques will decrease the neuromuscular blocking effect of pancuronium. The neuromuscular blocking effect will be increased by warming the patient. The activity of pancuronium is prolonged in patients with hypothermia.

Patients should not drive or operate machinery for at least 24 hours following full recovery from the effects of pancuronium.

Pregnancy and Lactation

Pregnancy

The manufacturer states that pancuronium should only be administered during pregnancy if the potential benefits outweigh the possible risks as the safety of pancuronium administration during pregnancy has not been established.

Pancuronium may be used for caesarean section. Pancuronium does not affect Apgar score, foetal muscle tone, or cardiorespiratory adaptation of the neonate. Assays of pancuronium in umbilical blood samples indicate that only very limited placental transfer of pancuronium occurs.

In patients receiving magnesium sulfate for toxaemia of pregnancy, the reversal of neuromuscular blockade caused by pancuronium may be unsatisfactory as magnesium salts enhance neuromuscular block. In these cases, the dose of pancuronium should be reduced.

Briggs (2011) concludes that pancuronium has been administered directly to the foetus during the last half of pregnancy and to the mother at caesarian section without causing foetal harm. Although no teratogenicity was observed in two animal species, the use of pancuronium in early human pregnancy has not been reported. The drug is known to cross the human placenta, at least near term. Placental transfer early in pregnancy has not been reported. Large or repetitive doses and or prolonged dose-to-delivery intervals may potentially result in newborn depression, but the clinical significance of this appears to be low. Transient foetal heart rate changes and occasional sinusoidal-like pattern have been observed after direct foetal administration but without apparent foetal compromise.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Pancuronium should only be administered during breastfeeding if the potential benefits outweigh the possible risks.

The safety of pancuronium administration during breastfeeding has not been established. Briggs (2011) concludes that as pancuronium is a bisquaternary ammonium compound and is ionised at physiological pH, Only the non-ionised form would be available for excretion in the milk and this would probably only be trace amounts. Compounds of this type are poorly absorbed from the gastrointestinal tract.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Increased pulse rate
Tachycardia
Increased blood pressure
Arrhythmias
Salivation
Rash
Local pain (injection site)
Local reaction at injection site
Bronchospasm
Anaphylactoid-like reaction
Itching
Erythema at injection site
Reduced intra-ocular pressure
Miosis

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store at 2 - 8 degrees C
Keep the container in the outer carton
Do not freeze

Further Information

Last Full Review Date: September 2012

Reference Sources

British National Formulary, 64th Edition (2012) Pharmaceutical Press, London.

BNF for Children (2012-2013) Pharmaceutical Press, London.

Summary of Product Characteristics: Pancuronium Bromide injection. Hospira UK Ltd. Revised December 2007.