This information is intended for use by health professionals

1. Name of the medicinal product

Atropine 1% w/v eye drops, solution

2. Qualitative and quantitative composition

1 ml of solution contains 10 mg atropine sulfate.

Excipients with known effect: benzalkonium chloride 0.1 mg/ml

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Eye drops, solution (eye drops)

Clear, colourless solution

4. Clinical particulars
4.1 Therapeutic indications

The medicinal product is used in the treatment of iritis and uveitis to immobilise the iris and ciliary muscle and to prevent or break down adhesions.

It is used for induction of mydriasis and/or cycloplegia in adults and for cycloplegic refraction in children. Since it is a powerful cycloplegic it is used in the determination of refraction in children below six years and children with convergent strabismus.

4.2 Posology and method of administration

Posology

The depth of the angle of the anterior chamber should be assessed before the product is used.

Adults, incl. the elderly

Refraction - One or two drops to be instilled into the eye(s) one hour before refracting.

Uveitis / iritis - One or two drops to be instilled into the eye(s) to a maximum of 4 times daily.

Mydriatics and cycloplegics should be used with caution in the elderly (see section 4.4). The lowest dose required to achieve the desired effect should always be used. Elderly patients are at increased risk of systemic drug reactions when using Atropine (see section 4.4).

Paediatric population

Refraction - One drop to be instilled into each eye twice daily for 1 - 3 days prior to the examination.

Uveitis / iritis - One drop to be instilled into each eye to a maximum of 3 times daily.

The lowest dose required to achieve the desired effect should always be used in children (see sections 4.4 and 4.8).

It is recommended to close the eye as soon as the drops are instilled and to press eyelid in the corner of the nose for a few minutes (nasolacrimal occlusion).

Hepatic and renal failure

Atropine has not been studied in patients with hepatic or renal failure. The lowest possible dose required to achieve the desired effect should be used in patients with reduced or impaired metabolic function (e.g. infants, elderly) who are at a higher risk of systemic adverse effects (see section 4.4.).

Method of administration

The medicinal product is intended for ocular use only.

If the protective strip breaks when opening the cap, it should be removed before using the medicine.

To avoid contamination of the product and the tip of the dropper, care must be taken to avoid contact between the tip of the dropper and the eyelid, the eye area or other surfaces.

Nasolacrimal occlusion or gentle pressure on the eyelid for several minutes is recommended after administration. This may reduce the systemic absorption of the drug and thus reduce the risk of systemic adverse effects.

If more than one topical ocular drug is used, both drugs should be administered at least five minutes apart. Eye ointments should be applied last.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Patients with close-angle glaucoma or tendency towards glaucoma.

Hypersensitivty to alkaloids and belladonna.

4.4 Special warnings and precautions for use

Administration of Atropine may increase the intraocular pressure, especially in patients with a small anterior chamber or narrow anterior chamber angle. Before starting treatment, the intraocular pressure should be measured and the depth of the anterior chamber angle evaluated to avoid glaucoma attacks.

Systemic exposure to Atropine may cause central nervous system disorders (see section 4.8). Elderly patients are at increased risk of systemic adverse effects when using Atropine (see section 4.2.). Due to the risk of hyperthermia, the medicinal product should be used with caution in patients with fever or at increased ambient temperature.

Patients may develop increased photosensitivity and should protect their eyes from bright light (see section 4.8).

Atropine contains benzalkonium chloride, which can cause eye irritation and has been found to discolour soft contact lenses. Contact with soft contact lenses should be avoided.

Patients should remove the contact lenses (soft or hard) before administering Atropine and wait for at least 15 minutes before re-inserting them.

Benzalkonium chloride has been reported to cause irritation and eye dryness and affect the corneal surface. Atropine should be used with caution in patients with dry eye and conditions affecting the cornea. Continuous treatment of these patients requires regular monitoring.

Paediatric population

Due to the risk of serious systemic adverse effects, Atropine should be used with caution in children and particularly in children with low body weight as well as children with increased sensitivity to central nervous system disorders (e.g. children with epilepsy, cerebral disorders, Down syndrome). This is due to the increased risk of central nervous system, cardiac, respiratory and gastrointestinal toxicity associated with systemic exposure to atropine (see section 4.8). The lowest dose of Atropine should be administered to achieve the desired effect.

Children should be carefully monitored for 30 minutes after administration of the drug. If the product falls outside the eye, it should be washed immediately.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

The effects of Atropine may be potentiated by the concomitant administration of other products with antimuscarinic properties, e.g. some antihistamines and tricyclic antidepressants.

4.6 Fertility, pregnancy and lactation

Pregnancy

The safety of administration to pregnant women has not been established. However, adverse reactions that have been reported indicate significant systemic exposure even after topical administration, and therefore the risk of effects on the foetus cannot be ruled out. Therefore, atropine should only be used during pregnancy if absolutely required and at the lowest possible dose.

Breastfeeding

Atropine passes into breast milk and the risk of effects on the child cannot be ruled out at therapeutic doses. Therefore, the drug should not be administered during breastfeeding.

Fertility

No studies have been conducted to evaluate the effect of topical ophthalmic atropine on fertility. No effects on fertility have been reported from rat studies.

4.7 Effects on ability to drive and use machines

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

Atropine can cause drowsiness, blurred vision and sensitivity to light. Patients using Atropine should not drive or perform dangerous activities until their vision clears.

4.8 Undesirable effects

The adverse reactions have been classified as follows: very common (≥ 1/10), common (≥1/100, <1/10), uncommon (≥1/1 000, <1/100), rare (≥1/10 000, <1/1 000), very rare (<1/10 000), not know (frequency cannot be estimated from the available data). Within each frequency grouping, the adverse reactions have been presented in order of decreasing seriousness.

Adverse reactions are classified per system organ class, in order of decreasing seriousness.

System Organ Classification

MedDRA Preferred Term

Immune system disorders

Not known: Hypersensitivity

Psychiatric disorders

Common: Hallucinations, confusion, agitation

Not known: Disorientation

Nervous system disorders

Not known: Vertigo, headache, ataxia, slurred speech, anxiety, hyperactivity, convulsions, inability to recognize people, sleepiness

Eye disorders

Common: Photosensitivity, pain in the eye, visual disturbance

Rare: closed-angle glaucoma

Not known: Eyelid edema, blurred vision, prolonged drug effect (mydriasis), conjunctivitis, hyperaemia, eye oedema and secretion

Cardiac disorders

Common: Tachycardia

Not known: Bradycardia

Vascular disorders

Not known: Hypotension, vasodilation

Respiratory, thoracic and mediastinal disorders

Not known: Respiratory depression, decreased pharyngeal, bronchial and nasal secretion

Gastrointestinal disorders

Common: Constipation

Not known: Ileus, bloating, vomiting, decreased gastrointestinal motility and decreased salivary gland secretion

Skin and subcutaneous tissue disorders

Not known: Erythema, rash, decreased sweat glad secretion

Renal and urinary disorders

Not known: Urinary retention

General disorders and administration site conditions

Common: Pyrexia and flushing

Description of selected adverse reactions

This medicinal product causes reactions similar to those of other anticholinergics. Adverse reactions from the central nervous system may occur: ataxia, slurred speech, anxiety, hallucinations, hyperactivity, convulsions, time and space disorientation, and inability to recognize people. Other signs of anticholinergic toxicity include skin rash, sleepiness, tachycardia, hyperpyrexia, vasodilatation, urinary retention, and decreased gastrointestinal motility, decreased salivary and sweat secretion, decreased secretion in the pharynx, bronchi and the nasal cavity. Severe reactions such as hypotension with rapidly progressive respiratory failure (respiratory depression) may occur.

Mydriatics may increase the intraocular pressure and induce a glaucoma attack in patients with a predisposition to acute narrow-angle glaucoma (see section 4.4).

Prolonged use of mydriatics may cause local irritation characterized by conjunctivitis (follicular), ocular hyperaemia, eye oedema, secretion and eczema.

Symptoms of toxicity are usually transient (several hours) but may last up to 24 hours.

Paediatric patients

An increased risk of systemic toxicity has been reported in children, particularly infants born with low weight, or in patients with central nervous system disorders (epilepsy, cerebral disorders, Down syndrome) (see section 4.3 and 4.4). Toxicity may be manifested as central nervous system disorders, cardiac and pulmonary disorders, and disorders of the gastrointestinal tract. In children with low body weight there is a risk of severe gastrointestinal toxicity (transient paralytic ileus / bloating). Intestinal obstruction, bloating and bradycardia have been found in preterm infants or children with low birth weight.

The use of atropine-containing eye drops has been associated with psychotic reactions and behavioural changes in paediatric patients. The effects on the central nervous system are similar to those described above and may cause hyperpyrexia (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store).

4.9 Overdose

Symptoms

Systemic reactions to topical atropine are unlikely at normal doses. Symptoms which can occur following an overdose, however, include anticholinergic effects (as listed in section 4.8 above), cardiovascular changes (tachycardia, atrial arrhythmias, atrio-ventricular dissociation) and central nervous system effects (confusion, ataxia, restlessness, hallucination, convulsions).

Treatment

Supportive therapy should be given as required.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: mydriatics and cycloplegics, ATC code: S01FA01

Atropine is an anticholinergic with a long-lasting mydriatic and cycloplegic effect. Possible inflammation of the eyes significantly reduces its duration of action.

Atropine acts by blocking the cholinergic receptors in the sphincter of the pupil and the ciliary muscle.

5.2 Pharmacokinetic properties

In a healthy volunteer study, systemic bioavailability after administration of 30 μl of 1% atropine in eye drops ranged between 19 and 95%, with the mean bioavailability of 63.5 ± 28.6%. The initial absorption phase in the eye lasts about 1 hour with a maximum plasma concentration (Cmax) of 288.33 ± 72.91 μg/ml at tmax of 27.67 ± 26.85 minutes.

Ocular administration does not affect the elimination kinetics and the terminal half-life and is comparable for atropine administered as an intravenous injection (2.97 ± 1.22 h) and topically as eye drops (2.45 ± 0.76 h). Following intravenous administration of [3H] atropine sulphate, five drug-related peaks were detected in the urine of 1 healthy subject. The unchanged drug and the enantiomer (+) identified later as biologically inactive constitute 57% of the total radioactivity; noratropine (24%) and atropine-A-oxide (15%) are the most important metabolites, and tropin (2%) and tropic acid (3%) are less significant metabolites. Urine incubation with glucuronidase/arylsulfatase appears to contain no glucuronide or sulphate compounds in humans, but in rats a greater amount of glucuronide and sulfate compounds have been identified. In humans, about 75% of the total radioactivity of the drug is excreted in the urine within 13 hours of intravenous administration of [3H] atropine sulphate and 5% of this radioactivity is excreted within 24 hours of administration. Similar metabolism and excretion profile is likely for topical application to the eye in view of the significant systemic absorption of atropine by the route of administration.

5.3 Preclinical safety data

No further data are available for this medicine, which has not already been described in this Summary of Product Characteristics.

6. Pharmaceutical particulars
6.1 List of excipients

Benzalkonium chloride

Boric Acid

Hypromellose

Hydrochloric acid and/or Sodium hydroxide (for pH adjustment)

Water for injections

6.2 Incompatibilities

Not known.

6.3 Shelf life

3 years

After first opening of the bottle: 28 days

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

Keep out of the reach of children.

6.5 Nature and contents of container

Sterile white opaque LDPE bottles sealed with sterile LDPE applicator-droppers and sterile screw caps with a protective ring.

1 bottle of 5 ml or 10 ml, with a package leaflet per carton box.

6.6 Special precautions for disposal and other handling

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

7. Marketing authorisation holder

Aspire Pharma Ltd

Unit 4 Rotherbrook Court

Bedford Road

Petersfield

GU32 3QG

United Kingdom

8. Marketing authorisation number(s)

PL 35533/0162

9. Date of first authorisation/renewal of the authorisation

06/05/2021

10. Date of revision of the text

09/07/2021