GLYCOPYRROLATE-NEOSTIGMINE INJECTION - summary of medicine characteristics

Glycopyrrolate and Neostigmine Metilsulfate 0.5mg / 2.5mg per ml Solution for

Injection

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 1ml of solution contains 0.5mg of glycopyrrolate and 2.5mg of neostigmine metilsulfate.

Excipient with known effect

Each 1 ml contains 3 mg (0.13 mmol) sodium

For the full list of excipients, see section 6.1.

Solution for Injection.

Clear, colourless sterile solution for injection intended for parenteral administration presented in 1ml clear, type 1, Ph. Eur. glass ampoules.

4.1 Therapeutic indications

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

4.2 Posology and method of administration

4 CLINICAL PARTICULARS

4.3 Contraindications

CLINICAL PARTICULARS

4.4 Special warnings and precautions for use

4 CLINICAL PARTICULARS

4.5 Interactions with other medicinal products and other forms of interaction

Neostigmine potentiates the depolarising myoneural blocking effects of suxamethonium (see contra-indications above).

There is increased risk of antimuscarinic side effects in patients taking drugs with antimuscarinic effects such as MAOIs, amantadine, clozapine, tricyclic antidepressants and nefopam.

Anticholinesterase drugs enhance neuromuscular transmission in voluntary and involuntary muscle in myasthenia gravis.

Non-depolarizing neuromuscular block induced by the muscle relaxants used in anesthesia; neuromuscular block induced by aminoglycoside antibiotics and antiarrhythmic agents.

Aminoglycosides -Effects of Neostigmine antagonised by aminoglycosides

Chloroquine and Hydroxychloroquine – effects of Neostigmine may be diminished because of potential for Chloroquine and Hydroxychloroquine to increase symptoms of myasthenia gravis

Many drugs have antimuscarinic effects; concomitant use of two or more such drugs can increase side-effects such as dry mouth, urine retention, and constipation; concomitant use can also lead to confusion in the elderly.

Clindamycin – Effects of Neostigmine antagonised by Clindamycin

Lithium – Effects of Neostigmine antagonised by lithium

Muscle Relaxants, non-depolarising – Neostigmine antagonises effects of nondepolarising muscle relaxants

Polymyxins – Effects of Neostigmine antagonised by polymyxins

Procainamide – Effects of Neostigmine antagonised by Procainamide

Propafenone -Effects of Neostigmine possibly antagonised by Propafenone

Propranolol -Effects of Neostigmine antagonised by Propranolol

Quinidine -Effects of Neostigmine antagonised by Quinidine

Suxamethonium -Neostigmine enhances effects of Suxamethonium

Antimuscarinics – Effects of parasympathomi­metics antagonised by antimuscarinics

4.6 Fertility, Pregnancy and lactation

Pregnancy

For use as indicated, animal studies (see section 5.3) are of very limited relevance.

Use in human pregnancy has not been systematically evaluated.

Breast-feeding

May reach breast milk but in amounts probably too small to be harmful.

4.7 Effects on ability to drive and use machines

4.8    Undesirable effects

4.9   Overdose

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

5 PHARMACOLOGICAL PROPERTIES

5.2. Pharmacokinetic properties

Absorption and Biotransformation:

Glycopyrrolate is a quaternary ammonium anti-muscarinic agent. The quaternary ammonium moiety renders glycopyrrolate highly ionised at physiological pH and it thus penetrates the blood brain and placental barriers poorly. Neostigmine metilsulfate is a quaternary ammonium anticholinesterase. Neostigmine undergoes hydrolysis by cholinesterases and is also metabolised in the liver.

Elimination

Glycopyrollate is excreted through bile and urine as unchanged drug.

Neostigmine is rapidly eliminated and is excreted in the urine both as unchanged drug and metabolites.

5.3 Preclinical safety data

Although reproduction studies in rats and rabbits revealed no teratogenic effects from glycopyrrolate, safety in human pregnancy and lactation has not been established.

Diminished rates of conception and of survival at weaning were observed in rats, in a dose related manner. Studies in dogs suggest that this may be due to diminished seminal secretion which is evident at high doses of glycopyrrolate. The significance of this for man is not clear.

6.1 List of excipients

Disodium Hydrogen Phosphate Dodecahydrate BP/PhEur.

Citric Acid Monohydrate BP/Ph.Eur.

Sodium Hydroxide BP/ Ph.Eur.

Water for Injections BP/ Ph.Eur.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3

18 months

6.4

Store below 25°C. Keep the ampoule in the outer carton in order to protect from light.

6.5 Nature and contents of container

Glycopyrrolate Neostigmine Injection is presented in clear glass ampoules packed in cardboard cartons to contain 5 or 10 ampoules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Keep this medicine out of the sight and reach of children.If only part of an ampoule is used, discard the remaining solution.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Mercury Pharmaceuticals Ltd,

Capital House,

85 King William Street,

London

EC4N 7BL,

UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 12762/0580