Pancuronium Bromide Injection 4mg/2ml Taj Pharma

NAME OF THE MEDICINAL PRODUCT

Pancuronium Bromide Injection 4mg/2ml Taj Pharma
Pancuronium Bromide Injection 10mg/10ml Taj Pharma

QUALITATIVE AND QUANTITATIVE COMPOSITION
a) Each ml contains:
Pancuronium bromide………………….2mg
b) Each ml contains:
Pancuronium bromide………………….1mg

Each ml also contains 0.15 mmol sodium.

Each 2 ml ampoule contains 4 mg of pancuronium bromide. Each 2 ml ampoule also contains 0.3 mmol sodium.

For the full list of excipients, see section 6.1.

PHARMACEUTICAL FORM

Solution for injection.

Clear, colourless solution.

CLINICAL PARTICULARS

4.1 Therapeutic indications

The active substance of pancuronium bromide is an amino steroid which effectively blocks transmission of motor nerve impulses to the striated muscle receptors. It is a non-depolarising neuromuscular blocking agent with a long duration of action and is used in the following indications:

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

Use in intensive care as a non-depolarising neuromuscular blocker for the treatment of various pathologies e.g. intractable status asthmaticus and tetanus.

4.2 Posology and method of administration

Posology

The use of a peripheral nerve stimulator is recommended for monitoring the neuromuscular block and recovery.

ADULT:

Initial dose: 50-80 micrograms/kg (intubation accomplished within 150-120 seconds) or 80-100 micrograms/kg (intubation accomplished within 120-90 seconds).

Incremental doses: 10-20 micrograms/kg

PAEDIATRIC:

Initial dose: 60-100 micrograms/kg

Incremental doses: 10-20 micrograms/kg

NEONATES:

Doses of pancuronium bromide in neonates up to one month of age must be carefully individualised since neonates are particularly sensitive to non-depolarising neuromuscular blocking agents.

Dosage 30-40 micrograms/kg initially I/V followed by 10-20 micrograms/kg thereafter.

If succinylcholine is used for intubation the administration of pancuronium bromide should be delayed until the patient has clinically recovered from the neuromuscular block induced by succinylcholine.

Following the administration of suxamethonium the dosage of pancuronium bromide may be considerably reduced:

ADULTS:

Initial dose: 20-60 micrograms/kg

Incremental doses 10-20 micrograms/kg

CHILDREN:

Initial dose: 20-60 micrograms/kg

Incremental doses 10-20 micrograms/kg

ELDERLY:

The neuromuscular blocking activity of pancuronium bromide is prolonged in the elderly and lower doses may be necessary.

OBESITY:

In obese patients doses of pancuronium bromide based on a mg/kg basis may lead to over dosage. Dosage must be adjusted according to response.

INTENSIVE CARE:

Pancuronium bromide is longer acting in the intensive care patient, and an intravenous dose of 60 micrograms/kg everyone to one and a half hours, or even less frequently is usually adequate.

IMPAIRED LIVER AND RENAL FUNCTION:

Care must be exercised in patients with impaired liver or renal function. See section 4.4.

Hyperdiuresis may result in a decreased neuromuscular blocking effect.

In the control of tetanus, duration of pancuronium bromide relaxation probably depends upon the severity of the spasm, therefore duration of effect can be variable.

The duration of action depends upon the clinical condition of the patient and the dose administered, but in normal subjects receiving perioperative muscle relaxant doses the duration of action is usually 45-60 minutes.

Pancuronium bromide should not be mixed with other agents in the same syringe, or with solutions for intravenous infusions as a change in pH may cause precipitation.

Discard any unused solution.

Method of administration

Pancuronium bromide should be administered intravenously. It is not recommended to be given by infusion.

The dosage should be individualised as there is a wide variation in individual response to muscle relaxants. When determining the dose, the method of anaesthesia, expected duration of surgery, potential interaction with other drugs that are administered before and during anaesthesia and the condition of the patient should be taken into account.

4.3 Contraindications

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.

4.4 Special warnings and precautions for use

Warnings

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).

Renal Failure:

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.

Impaired Hepatic/Biliary Tract Disease:

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.

4.5 Interaction with other medicinal products and other forms of interaction

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.

4.6 Fertility, pregnancy and lactation

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.

4.7 Effects on ability to drive and use machines

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.

4.8 Undesirable effects

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 of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.

4.9 Overdose

Clinical features: The symptoms are those of prolonged apnoea, respiratory depression and/or muscle weakness. Death may follow acute respiratory failure.

Management: Neostigmine at a dose of 2.5mg and Atropine at a dose of 1.2mg can be administered to reverse the neuromuscular block whilst ventilation is continued. When administration of the cholinesterase inhibiting agent fails to reverse the neuromuscular blocking effects of pancuronium bromide ventilation must continue until spontaneous breathing is restored. Repeated dosage of cholinesterase inhibitor can be dangerous.

PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Muscle relaxants, peripherally acting agents, other quaternary ammonium compounds

Mechanism of action

Pancuronium bromide produces pharmacologic effects similar to those of other non-depolarising neuromuscular blocking agents. The drug may produce an increase in heart rate which appears to result from a direct blocking effect on the acetylcholine receptors of the heart. The increase in heart rate appears to be dose related and is minimal with usual doses. Pancuronium bromide causes little or no histamine release and no ganglionic blockade and therefore does not cause hypotension or bronchospasm. Despite its steroidal structure, the drug exhibits no hormonal activity.

5.2 Pharmacokinetic properties

Absorption

Following I/V administration of pancuronium bromide 60 micrograms /kg, muscle relaxation reaches a level suitable for endotracheal intubation within 2-3 minutes, slightly more rapidly than with tubocurarine. The onset and duration of paralysis are dose related. After a dose of 60 micrograms/kg, the effects of the drug begin to subside in about 35-45 minutes. Supplemental doses may increase the magnitude and duration of the neuromuscular blockade. The duration of action depends upon the clinical condition of the patient and the dose administered, but in normal subjects receiving perioperative muscle relaxant doses the duration of action is usually 45-60 minutes.

Distribution

Protein binding of pancuronium bromide does not appear to be substantial. The activity of the drug is not greatly affected by plasma carbon dioxide concentrations or pH. Redistribution is responsible for the termination of activity following single doses. Pancuronium bromide crosses the placenta in small amounts.

Elimination

Plasma concentrations appear to decline in a triphasic manner. In adults with normal renal and hepatic function, the half-life in the terminal phase is about 2 hours. The elimination half-life may be prolonged in patients with impaired renal and/or hepatic function. The drug is eliminated mainly unchanged by the kidneys, although small amounts may be metabolised and some of the drug may be eliminated in the bile.

5.3 Preclinical safety data

None.

PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride, Sodium acetate, Water for injections

6.2 Incompatibilities

Do not mix other solutions in the same syringe as a change in pH can cause precipitation.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Store in a refrigerator (2°C-8°C). Do not freeze. Keep the ampoule in the outer carton in order to protect from light.

6.5 Nature and contents of container

2ml Type I clear glass ampoules.

Pack sizes of 5, 10 and 50.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

For single use only. Discard any unused contents. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

PANCURONIUM BROMIDE INJECTION
4MG/2ML / 10MG/10ML
TAJ PHARMA

PACKAGE LEAFLET: INFORMATION FOR THE USER

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible effects not listed in this leaflet. See section 4.

WHAT IS IN THIS LEAFLET

What Pancuronium Bromide Injection is and what it is used for
What you need to know before you use Pancuronium Bromide Injection
How to use Pancuronium Bromide Injection
Possible side effects
How to store Pancuronium Bromide Injection
Contents of the pack and other information1. WHAT PANCURONIUM BROMIDE INJECTION IS AND WHAT IT IS USED FOR

Pancuronium bromide is one of a group of medicines called ‘non-depolarising’ muscle relaxants.

Pancuronium Bromide Injection is used to relax muscles during surgery, including caesarean section and in intensive care.

You must talk to a doctor if you do not feel better or if you feel worse.

WHAT YOU NEED TO KNOW BEFORE YOU USE PANCURONIUM BROMIDE INJECTION DO NOT USE PANCURONIUM BROMIDE INJECTION

if you are allergic to pancuronium bromide or any of the ingredients of this medicine (listed in section 6.

Warning and precautions

Talk to your doctor or pharmacist or nurse before using Pancuronium Bromide Injection

if you have kidney, liver, lung or heart disease
if you have high blood pressure
if you have cancer, particularly lung cancer
if you suffer from any of the following conditions: myasthenia gravis, myasthenic syndrome (other neuromuscular diseases) or poliomyelitis
if you have fluid retention (you may have swelling around the ankles)
if you have jaundice

Children and elderly

Special care will also be taken in the elderly, newborn babies, patients who are dehydrated or in general poor health and patients who have blood abnormalities, such as altered calcium, magnesium, potassium and protein levels (the doctor may do blood tests to check for such abnormalities).

Other medicines and Pancuronium Bromide Injection

Tell your doctor, pharmacist or nurse if you are taking or have recently taken or might take any other medicines. Pancuronium bromide must not be administered along with a “depolarising” muscle relaxant, e.g. suxamethonium.

Other medicines used/taken at the same time as pancuronium bromide may interact, special care may be needed, for example:

other muscle relaxants of the ‘non-depolarising’ type (e.g. mivacurium)
some anaesthetic agents (e.g. halothane, ether, enflurane, isoflurane, methoxyflurane, cyclopropane, thiopentone, methohexitone, ketamine, fentanyl, gammahydroxybutyrate, etomidate)
anticancer medicines belonging to a group called ‘alkylating agents’ (including medicines known as ‘nitrogen mustards’)
some antibiotics (e.g. aminoglycosides, metronidazole) and antifungal medicines (e.g. imidazoles)
medicines affecting the heart or blood pressure (glyceryl trinitrate, propranolol, adrenaline, noradrenaline, alpha blockers, beta blockers, quinidine)
water tablets (diuretics)
medicines used to control anxiety (diazepam
antidepressants (e.g. tricylclic antidepressants, monoamine oxidase inhibitors)
strong pain-killers (e.g. narcotics)
steroid medicines
medicines used to treat a disease affecting the muscles called ‘myasthenia gravis’ (neostigmine, pyridostigmine, edrophonium)
phenytoin (antiepilepsy medicine)
heparin and protamine (medicines used to control the ease with which the blood will clot)
azathioprine (a medicine used to prevent transplant rejection)
theophylline (a medicine used to treat some breathing disorders)
medicines used to increase the level of some salts in the blood (potassium chloride, sodium chloride, calcium chloride)
vitamin B₁ (thiamine) if taken in high doses
magnesium sulfate (used in the treatment of constipation, pre-eclampsia, abnormal heart rhythms)

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your doctor will only use this medicine if the expected benefits outweigh any potential risk to your baby.

Driving and using machines

Do not drive or use machines for 24 hours after full recovery from the muscle relaxant effects of pancuronium bromide.

Pancuronium Bromide Injection contains sodium

This medicinal product contains less than 1 mmol (23 mg) sodium per dose, i.e. essentially ‘sodium free’.

HOW TO USE PANCURONIUM BROMIDE INJECTION

This medicine will be given to you as an injection into a vein.

Dose

The dose of medicine given to you will depend upon your age, your weight, expected duration of surgery, drugs that have been given to you previously and how well your kidneys and liver are working.

The recommended range in adults is typically between 50 and 100 micrograms/kg bodyweight.

If you are given more Pancuronium Bromide Injection than you should

This medicine will be given to you in a hospital, under the supervision of a doctor. It is unlikely that you will be given too much or too little, however, tell your doctor or nurse if you have any concerns.

POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.

During use of pancuronium bromide injection your doctor will be observing you for:

severe allergic reaction – you may experience a sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), and you may feel you are going to faint

If this serious side effect occurs, urgent medical attention will be needed.

After you have come round, if any of the following happen, tell your doctor as soon as possible:

breathing difficulties
unusually rapid heart beat, palpitations or irregular heart beat
pain, itching, local skin reaction or irritation particularly around the injection site
problems with your vision
skin rash
excess production of saliva

Your doctor may monitor for changes in your blood pressure.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

HOW TO STORE PANCURONIUM BROMIDE INJECTION
Keep this medicine out of the sight and reach of children.
Expiry

This medicine must not be used after the expiry date which is stated on the vial ampoule and carton after ‘EXP’. Where only a month and year is stated, the expiry date refers to the last day of that month.

Storage

Store in a refrigerator ( 2ºC-8ºC) . Do not freeze. Keep the ampoule in the outer carton in order to protect from light.

CONTENTS OF THE PACK AND OTHER INFORMATION

What Pancuronium Bromide Injection contains

a) Each ml contains:
Pancuronium bromide………………….2mg

b) Each ml contains:
Pancuronium bromide………………….1mg

The other ingredients are sodium chloride, sodium acetate, and water for injections (see section 2 Pancuronium Bromide Injection contains sodium).

What Pancuronium Bromide Injection looks like and contents of the pack

Pancuronium Bromide Injection is a clear, colourless solution for injection which comes in glass containers called ampoules.

It may be supplied in packs containing: