Document: Miostat solution for injection, intraocular use ENG SmPC change

• Miostat, solution for intraocular use SmPC
• Miostat solution for injection, intraocular use ENG SmPC

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SUMMARY OF PRODUCT CHARACTERISTICS

Miostat100microgram/mlsolutionfor injection for intraocular use

1 ml solution contains 100 micrograms carbachol.

One 1.5 ml vial contains 150 micrograms carbachol.

For a full list of excipients, see section 6.1.

Solution for injection, intraocular use.

Clear, colourless solution, pH 6.5-7.5.

Miostat isindicated to inducerapid and complete miosis in connection with intraocular surgery. Maximal miosis usually occurswithin a few minutes following instillation.

Method of administration

Miostat is intended for intraocular administration only.

Aseptically remove the vial fromthe blister pack by peeling off the backing paper and put the vial on a sterile tray. Draw the contents up into adry sterile syringe and replace the cannula with an atraumatic cannula prior to intraocular administration. Discard unused portion.

Posology

A maximum of 0.5 ml Miostat (50 micrograms carbachol) is instilled carefully into the anterior chamber. Miostat has been shown to be effective for up to 24 hours following surgery. Effective miosis has been demonstrated in some patients with as little as 5 micrograms of carbachol.

Use in the older population

No dose adjustment is necessary in the older population .

Paediatric patients

Miostat is not recommended for use in children due to a lack of data on efficacy and safety.

Renal and hepatic impairment

Nostudies have been performed to evaluate the effects of impaired renal or hepatic function on carbachol elimination. As systemic exposure to carbachol following intraocular instillation in humans is taken to be minimal, no adjustment in dose is considered necessary in patients with renal or hepatic impairment.

Hypersensitivity to the active substance or any of the excipients.

• Intraocular carbachol 100 microgram/ml should be used with caution in patients with acute cardiac failure, bronchial asthma, peptic ulcer, hyperthyroidism, gastrointestinal spasm, urinary tract obstruction and Parkinson's disease.

• Patients with a history of iritis/uveitis.

• Use of Miostat may induce intraocular inflammation (iris hyperaemia) beyond that caused by surgery.

• In the event of hypotonia, further reduction in intraocular pressure should be avoided.

• The vial stopper contains natural rubber (latex) which may cause severe allergic reactions.

No interaction studies have been performed

Undercertain conditions,cholinergic agonists can prolong the effects of depolarizing muscle relaxants, reduce the effects of stabilising muscle relaxants and prolong the negative chronotropic effect of cardiac glycosides.

Pregnancy

No adequate and well-controlled studies have been performed in pregnant women. The potential risk is felt tobe low, considering the singleadministration of a low dose administered in the eye. Miostat should only be used in pregnant women where the expected benefit outweighs the potential risk tothe foetus.

Breastfeeding

It is not known whether carbachol is eliminated in breast milk. Caution should be exercised when carbachol is administered to nursing mothers.

Fertility

Studies have not been performed to evaluate the effect of topical ocular administration of carbachol on human fertility.

Miostat has a major influence on the ability to drive and use machines.

Miosis may cause blurred vision and difficulty in dark adaptation. Iftemporary blurring of vision occurs following surgery where Miostatwas used, the patient must wait until vision clears before driving or using machinery.

Tabulated summary of adverse reactions

Thefollowingundesirableeffectsareclassifiedaccordingtothefollowingconvention: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), or very rare (<1/10,000), or not known (frequency cannot be estimated from the available data). Within each frequency group, undesirable effects are presented in decreasing order of seriousness. The adverse reactions were obtained from clinical trials and post- marketing spontaneous reports.

System organ classification	Frequency	Preferred term
Nervous system disorders	Uncommon	headache
Eye disorders	Uncommon Rare Not known	intraocular pressure increased retinal detachment, corneal degeneration (bullous keratopathy), uveitis, iritis corneal opacity, corneal oedema visual impairment, anterior chamber inflammation, drug effect prolonged, (miosis), eye pain, ocular hyperaemia, eye inflammation, and blurred vision
Gastrointestinal disorders	Not known	epigastric discomfort, vomiting and nausea

Description of selected adverse reactions. The following undesirable effects have been observed following topical miotic therapy:

System organ classification	Frequency	Preferred term
Nervous system disorders	Common	headache
Eye disorders	Common Uncommon Rare	ciliary muscle spasm, ciliary hyperaemia, conjunctival hyperaemia, photophobia, blurred vision vascular changes in the iris (vasodilation) retinal detachment
Vascular disorders	Uncommon	flushing
Gastrointestinal disorders	Uncommon	abdominal pain, epigastric discomfort
Skin and subcutaneous tissue disorders	Uncommon	hyperhidrosis
Renal and urinary disorders	Uncommon	urinary urgency

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of benefit/risk balance of the medicinal product. Health care professionals are asked to report any suspected adverse reactions via the national reporting system listed in

In the event of overdose, carbacholmay cause the same systemic symptoms as cholinesterase inhibitors: Headache, salivation, syncope, bradycardia, hypotension, cardiac failure, abdominal cramps, vomiting, asthma and diarrhoea. In cases of severe toxicity. Atropine sulphate (1 to 2mg) should be given subcutaneously or intramuscularlytocontrolthemuscariniceffects. Repeatthetreatmentevery2to4 hours if necessary. Convulsions can be controlled with a short-acting barbiturate.

Pharmacotherapeutic group: Antiglaucoma preparations and miotics; Parasympathomimetics.

ATC code: S01EB02

Carbacholisa parasympathomimetic agent that induces miosis by cholinergic action on the motor nerve endings of the sphincter muscle inthe iris. Potentcholinergic agents produce constriction of the iris and ciliary body resulting in lowering of intraocular pressure. The clinical studies carried out in cataract surgery serveas a model to demonstrate efficacy in other intraocular surgical procedures.

Plasma levels of carbachol have not beenstudiedfollowing intraocular administration of carbachol to humans, but pharmacokinetic data from animal studies demonstrate that intravenously injected carbacholis rapidly eliminatedfrom the plasma. In animals, excretion is mainly through the urine. Carbachol is metabolised to choline in plasma following intravenous administration.

Instudies in rabbits, Miostat was injected directly into the vitreous body or into the anterior chamber under simulated surgical conditions and the expected pharmacological effects of a miotic were noted. An increased frequency of iritis wasfound, but there was no significant ocular or retinal toxicity. Transient vasodilation of the iris was seen, attributable to the cholinergic properties ofMiostat, but the treatment caused no increase in inflammatory cells or flare values.

Nostudies on reproductive toxicity or carcinogenic or mutagenic potential have been performed.

Sodium chloride,

Potassium chloride (E508),

Calcium chloride dihydrate (E509),

Magnesium chloride hexahydrate (E511),

Sodium acetate trihydrate (E262),

Sodium citrate (E311),

Sodium hydroxide (E524) and/or hydrochloric acid (E507) (to adjust pH)

Water for injection.

Intheabsenceofcompatibilitystudies,thismedicinalproductmustnotbemixedwithother medicinal products.

2 years.

After opening: The solution should be used immediately.

This medicinal product does not require any special storage conditions.

Type I glass vials. 1.5 ml vial with rubber stopped and aluminium overseal in a PVC/Tyvek blister pack.

Each carton contains 12 vials.

Miostat is intended for single use only. Miostat contains no preservative, and consequently any unused solution must be discarded. Only clear solution free from particles should be used.

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

7. MARKETING AUTHORISATION HOLDER

<To be completed nationally>

8. MARKETING AUTHORISATION NUMBER(S)

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10. DATE OF REVISION OF THE TEXT

2014-03-12