COMPOSITION:
Each 1ml ampoule contains:
Glycopyrrolate USP - - - - - - - - - - -0.5 mg
Neostigmine Methylsulphate BP- - 2.5 mg

DESCRIPTION:
Glycopyrrolate is an anti-cholinergic drug, which is a synthetic quaternary ammonium compound.
It inhibits the muscarinic actions of acetylcholine; which results in reduction of gastrointestinal & urinary tract motility. It also inhibits salivary as well as bronchial secretions.
Due to its highly polar quaternary ammonium group, it does not crosses the blood brain barrier in contrast with atropine sulphate or scopolamine hydrobromide, which are non-polar tertiary amines and can cross blood brain barrier.
Neostigmine belongs to "Reversible" Carbamate inhibitors group. These drugs inhibit or inactivate acetyl cholinesterase.They cause acetylcholine to accumulate at cholinergic receptors and as a result causes excessive stimulation of cholinergic receptors throughout the central and peripheral nervous system.
Acetylcholine accumulation causes bradycardia , vasodilation and hypotension. It increases oropharyngeal and bronchial gland secretions, along with that due to smooth muscles contraction it may cause bronchoconstriction.
Neostigmine is routinely used during anaesthesia to reverse the action of non-depolarizing neuromuscular blocking agents.

With intravenous injection, the onset of action of Glycopyrrolate is generally evident within one minute. The vagal blocking effect persists for 2-3 hours while the anti-sialogogue effect persists for 7 hours (period longer than that of atropine).
After I.V. injection Neostigmine absorbs quickly, the distribution half life varies between 1 to 3.5 minutes while elimination half life ranges from 15 to 80 minutes. The major route of elimination is urinary pathway through which 80% of the drug is eliminated.

INDICATION:
Reversal of residual non-depolarising (competitive) neuromuscular block.

DOSAGE AND ADMINISTRATION:

ADULTS AND OLDER PATIENTS;
1-2 ml intravenously over a period of 10-30 seconds (equivalent to neostigmine methylsulphate 2.5 mg with glycopyrrolate 0.5 mg to neostigmine methylsulphate 5 mg with glycopyrrolate 1 mg). Alternatively 0.02 ml/kg intravenously over a period of 10-30 seconds may be used (equivalent to neostigmine methylsulphate 50 micrograms/kg with glycopyrrolate 10 micrograms/kg).

CHILDREN;
0.02 ml/kg intravenously over a period of 10-30 seconds (equivalent to neostigmine methylsulphate 50 micrograms/kg (0.05 mg/kg) with glycopyrrolate 10 micrograms/kg (0.01 mg/kg). Alternatively dilute to 10 ml with water for injections BP, or sodium chloride injection BP 0.9% w/v and administer 1ml per 5 kg bodyweight.
These doses may be repeated if adequate reversal of neuromuscular blockade is not achieved. Total doses in excess of 2 ml are not recommended as this dose of neostigmine may produce depolarising neuromuscular block.

CONTRA-INDICATIONS:
Pyrolate-N injection should not be given to patients with known hypersensitivity to
either of the two active ingredients.
Pyrolate-N injection should not be given to patients with mechanical obstruction of the gastrointestinal or urinary tracts.
Pyrolate-N injection should not be given in conjunction with suxamethonium as neostigmine potentiates the depolarising myoneural blocking effects of this agent.
Caution should be observed while using Glycopyrrolate in newborn infants due to its
benzyl alcohol content.

PRECAUTIONS AND WARNINGS:
Administer with caution to patients with bronchospasm, severe bradycardia or glaucoma.
Administration of anticholinesterase agents to patients with intestinal anastomoses may produce rupture of the anastomosis or leakage of intestinal contents.
Although Pyrolate-N has been shown to have less impact on the cardiovascular system than atropine with neostigmine methylsulphate.
Use with caution in patients with epilepsy or parkinsonism.
This product should be used cautiously in pyrexial patients due to inhibition of sweating.
Do not mix Pyrolate-N injection with any other preparation.

USE IN PREGNANCY & LACTATION:
Although reproduction studies in rats and rabbits revealed no teratogenic effects from glycopyrrolate, safety in human pregnancy and lactation has not been established.
The significance of this for man is not clear. The safety of neostigmine methylsulphate in pregnancy and lactation has not been established.

SIDE EFFECTS:
The glycopyrrolate component of Pyrolate-N injection can give rise to dry mouth, difficulty in micturition, cardiac dysrhythmias, disturbances of visual accommodation and inhibition of sweating.
The neostigmine component of Pyrolate-N injection can give rise to bradycardia, increased oropharyngeal secretions, cardiac dysrhythmias and increased gastrointestinal activity. If severe neostigmine induced muscarinic side effects occur ( bradycardia, increased oropharyngeal secretions, decreased cardiac conduction rate, bronchospasm or increased gastro-intestinal activity etc), these may be treated by the intravenous administration of Pyrolate-N injection (glycopyrrolate) 200-600 micrograms (0.2-0.6 mg).

TREATMENT OF OVERDOSAGE:
The treatment of overdosage depends upon whether signs of anticholinesterase or anticholinergic overdosage are the predominant presenting features. Signs of neostigmine overdosage (bradycardia, increased oropharyngeal secretions, bronchospasm etc), may be treated by the administration of Pyrolate injection (glycopyrrolate 200-600 micrograms) (0.2-0.6 mg).
In severe cases, respiratory depression may occur and artificial ventilation may be necessary in such patients. Signs of glycopyrrolate overdosage (tachycardia, ventricular irritability etc) may be treated by the administration of neostigmine methylsulphate (Neo-Choline) 1000 micrograms (1.0 mg) for each 1000 micrograms (1.0 mg) of glycopyrrolate known to have been administered. As glycopyrrolate is a quaternary ammonium agent, symptoms of overdosage are peripheral rather than central in nature; centrally acting anticholinesterase drugs such as physostigmine are therefore unnecessary to treat glycopyrrolate overdosage.

STORAGE:
Store at room temperature not exceeding 25°C.
Protect from light.

PRESENTATION:
Pyrolate-N injection: Pack of 10 x 1 ml ampoules