Appamide Plus (Drops) Instructions for Use

Marketing Authorization Holder

Appasamy Ocular Devices (P) Ltd. (Pharma Division) (India)

ATC Code

S01FA56 (Tropicamide in combination with other drugs)

Active Substances

Phenylephrine (Rec.INN registered by WHO)

Tropicamide (Rec.INN registered by WHO)

Dosage Form

Appamide Plus

Eye drops 8 mg+50 mg/1 ml: 5 ml dropper bottle.

Dosage Form, Packaging, and Composition

Eye drops colorless, transparent.

Excipients: chlorobutanol – 5 mg, sodium hydrogen phosphate – 0.28 mg, sodium dihydrogen phosphate – 0.005 mg, sodium chloride – 4.5 mg, disodium edetate – 0.5 mg, water – up to 1 ml.

5 ml – polyethylene dropper bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Diagnostic agent for topical use in ophthalmology (m-cholinoblocker + alpha-adrenomimetic)

Pharmacotherapeutic Group

Diagnostic agent for ophthalmic diseases (m-cholinergic blocker + alpha-adrenergic agonist)

Pharmacological Action

Tropicamide.

An M-cholinoblocking agent, it blocks the receptors of the pupillary sphincter and the ciliary muscle, causing short-term mydriasis and cycloplegia. It slightly increases intraocular pressure. The onset of action is 5 minutes, the optimal time for eye refraction examination is 25-40 minutes (for a 0.5% solution) and 25-30 minutes – after repeated instillation (for a 1% solution). For a 0.8% solution, the time to effect onset will be within the specified ranges. Maximum pupil dilation persists for 1 hour (for a 0.5% solution) and 2 hours (for a 1% solution). The original pupil width is restored after 6 hours.

Phenylephrine.

It has a pronounced stimulating effect on postsynaptic α-adrenergic receptors and a weak effect on cardiac β₁-adrenergic receptors. It has a vasoconstrictor effect (the vasopressor action of phenylephrine is weaker than that of norepinephrine but more prolonged), and it has practically no chronotropic or inotropic effect. After instillation, phenylephrine contracts the pupillary dilator and the smooth muscles of the conjunctival arterioles, thereby causing pupil dilation and conjunctival vasoconstriction, and improves the outflow of intraocular fluid. Pupil dilation occurs within 10-60 minutes after a single instillation and persists for 4-6 hours.

Pharmacokinetics

Tropicamide.

It easily penetrates into the eye tissues and is rapidly absorbed into the bloodstream. The lower limit of quantification for tropicamide in plasma is less than 240 pg/ml, the range is 240 pg/ml – 10 ng/ml.

Phenylephrine.

It easily penetrates into the eye tissues; the peak plasma concentration is observed 10-20 minutes after topical application. Phenylephrine is excreted by the kidneys unchanged (< 20%) or as inactive metabolites.

Indications

Pupil dilation

• For diagnostic ophthalmological procedures;
• Before surgical and laser operations.

ICD codes

Dosage Regimen

Instill 1-2 drops into the conjunctival sac of each eye requiring examination or intervention.

Administer the drops 15-30 minutes prior to the scheduled diagnostic procedure or surgery.

For refractive examination, optimal cycloplegia and mydriasis are typically achieved within 25-40 minutes post-instillation.

Repeat instillation once if required for insufficient mydriasis; this may be necessary in patients with darkly pigmented irises.

Remove contact lenses prior to instillation and reinsert no sooner than 15 minutes afterward.

After instillation, apply gentle pressure with a finger to the lacrimal sac area at the inner canthus for 1-2 minutes to minimize systemic absorption.

Avoid allowing the dropper tip to contact the eye or any other surface to prevent contamination.

Discard the opened bottle 4 weeks after first use, irrespective of the remaining volume.

Do not exceed the prescribed dosage. Monitor patients, particularly the elderly and those with cardiovascular risk factors, for systemic effects.

Adverse Reactions

Local reactions transient burning, conjunctival hyperemia, anterior chamber angle blockade (in case of narrow angle), blurred vision, sensation of eye discomfort, lacrimation, superficial punctate keratitis, increased intraocular pressure, photophobia; rarely – reactive miosis the day after application (repeated instillations of the drug at this time may produce less pronounced mydriasis than the day before; this effect is more common in elderly patients).

Systemic side effects pallor, dry mouth, nausea, vomiting, headache, contact dermatitis, CNS disorders and muscle rigidity, palpitations, tachycardia, arrhythmia, increased blood pressure, reflex bradycardia, coronary artery occlusion, pulmonary embolism; in rare cases (in elderly patients with cardiovascular diseases) – ventricular arrhythmias, myocardial infarction.

Allergic reactions are possible.

Contraindications

• Angle-closure glaucoma;
• Increased intraocular pressure;
• Cardiovascular diseases (including coronary sclerosis, angina pectoris, arrhythmia, hypertensive crisis);
• Thyrotoxicosis;
• Type 1 diabetes mellitus;
• Concomitant use (as well as within 3 weeks after their discontinuation) of MAO inhibitors (MAO);
• Pregnancy;
• Lactation period;
• Age under 18 years;
• Hypersensitivity to the drug components.

With caution: type 2 diabetes mellitus, elderly age (risk of ventricular arrhythmias and myocardial infarction in patients with cardiovascular diseases).

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation.

Pediatric Use

Contraindicated in children under 18 years of age.

Geriatric Use

With caution: elderly age (risk of ventricular arrhythmias and myocardial infarction in patients with cardiovascular diseases).

Special Precautions

Preservatives contained in the drug can be adsorbed by soft contact lenses. The drug may have an irritating effect on the eye when wearing contact lenses, so any contact lenses should be removed before instillation and put back on no earlier than 15 minutes after it.

The drops should be instilled into the lower conjunctival sac. To reduce the risk of systemic side effects, gentle finger pressure on the area of the lacrimal sacs projection at the inner corner of the eye for 1-2 minutes after instillation is recommended. Due to significant contraction of the pupillary dilator 30-45 minutes after instillation, pigment particles from the iris pigment layer may be detected in the aqueous humor of the anterior chamber. The suspension in the chamber fluid must be differentiated from manifestations of anterior uveitis or from the entry of blood cells into the anterior chamber aqueous humor. Preliminary instillation of local anesthetics may increase the systemic absorption of phenylephrine and prolong mydriasis.

Effect on the ability to drive vehicles and operate machinery

During treatment, driving vehicles and engaging in other hazardous activities requiring increased concentration and speed of psychomotor reactions are not recommended, as changes in accommodation and pupil width may reduce visual acuity.

Overdose

No data on overdose of tropicamide and phenylephrine with topical use are available.

Symptoms dry skin and mucous membranes, hyperthermia, tachycardia, mydriasis, agitation, convulsions, coma, respiratory paralysis.

Treatment gastric lavage, intake of activated charcoal; as an antidote – physostigmine (0.03 mg/kg IV slowly), benzodiazepines; to eliminate hyperthermia – cold compresses. To stop the systemic action of phenylephrine – α-adrenergic blockers (5-10 mg phentolamine IV, repeating the injection if necessary).

Drug Interactions

Adrenomimetics enhance, m-cholinomimetics weaken the effect of tropicamide.

Tricyclic antidepressants, phenothiazines, amantadine, quinidine, antihistamines increase the likelihood of systemic side effects of tropicamide.

Atropine enhances the mydriatic effect of phenylephrine.

Concomitant use with MAO inhibitors, as well as within 21 days after their discontinuation, increases the risk of systemic adrenergic effects.

The vasopressor effect of α-adrenomimetics may also be enhanced when used concomitantly with tricyclic antidepressants, propranolol, guanethidine, methyldopa, and m-cholinoblockers.

β-adrenergic blockers increase the risk of a sharp increase in blood pressure.

Phenylephrine increases the risk of cardiovascular depression during inhalational general anesthesia.

Storage Conditions

Store the drug in a place protected from light, at a temperature from 15°C (59°F) to 25°C (77°F). Keep out of the reach of children.

Shelf Life

Shelf life – 2 years.

Shelf life 4 weeks from the moment the bottle is opened (under the same storage conditions). Do not use the drug after the expiration date printed on the packaging.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.