Tapticom

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TAPTIQOM® (TAPTIQOM®)

Composition:

Active substances: tafluprost, timolol;

1 ml of eye drops contains 0.015 mg of tafluprost and 5 mg of timolol, equivalent to 6.84 mg of timolol maleate;

Excipients: glycerin; sodium hydrogen phosphate, dodecahydrate; disodium edetate, polysorbate 80, sodium hydroxide and/or concentrated hydrochloric acid, water for injections.

One dropper bottle (0.3 ml) of eye drops contains 4.5 μg of tafluprost and 1.5 mg of timolol.

One eye drop (approximately 30 μl) contains about 0.45 μg of tafluprost and 0.15 mg of timolol.

Pharmaceutical form. Eye drops.

Main physicochemical properties: clear, colorless solution. Practically free from visible particles.

Pharmacotherapeutic group.

Medicinal products used in ophthalmology. Antiglaucoma and miotic agents. Beta-adrenoreceptor blockers. ATC code S01ED51.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Tapcom® is a fixed-combination product containing two active substances – tafluprost and timolol. These two active substances reduce intraocular pressure (IOP) through complementary mechanisms of action, and their combined effect results in an additive reduction of IOP compared to either agent alone.

Tafluprost is a fluorinated analogue of prostaglandin F2ɑ. Tafluprost acid, the biologically active metabolite of tafluprost, is a highly potent and selective agonist of the human prostaglandin FP receptor.

Pharmacodynamic studies in animals indicate that tafluprost reduces intraocular pressure by increasing uveoscleral outflow of ocular fluid.

Timolol maleate is a non-selective beta-adrenergic receptor blocking agent. The precise mechanism of timolol maleate in reducing intraocular pressure is not fully understood, although fluorescein studies and tonographic data suggest that its primary action is through reduced aqueous humor formation. However, a slight increase in outflow facility has also been observed in some studies.

Clinical efficacy

In a 6-month study (n = 400) of patients with open-angle glaucoma or ocular hypertension and mean untreated IOP between 24 and 26 mmHg, the IOP-lowering effect of Tapcom® (once daily in the morning) was compared to the concomitant use of 0.0015% tafluprost (once daily in the morning) and 0.5% timolol (twice daily). Tapcom® was non-inferior (not inferior) to the concomitant use of 0.0015% tafluprost and 0.5% timolol. The mean diurnal reduction in IOP from baseline was 8 mmHg in both groups at the primary endpoint of 6 months (reduction ranged from 7 to 9 mmHg in both groups at different time points during the day at study visits).

In another 6-month study (n = 564), Tapcom® was compared with the respective monotherapies in patients with open-angle glau游戏副本

Clinical characteristics.

Indications.

Reduction of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension who respond inadequately to topical monotherapy with beta-blockers or prostaglandin analogues and require combination therapy, and for whom preservative-free ophthalmic drops are indicated.

Contraindications.

Hypersensitivity to the active substances or to any of the excipients of the medicinal product.

Respiratory irritation, as well as bronchial asthma or history of bronchial asthma, severe chronic obstructive pulmonary disease.

Sinus bradycardia, sick sinus syndrome, sinoatrial block, second- or third-degree atrioventricular block not controlled by a pacemaker, severe heart failure or cardiogenic shock.

Interaction with other medicinal products and other forms of interaction.

No specific studies on interactions with other medicinal products have been conducted.

Reduction in blood pressure and/or marked bradycardia may be potentiated when ophthalmic beta-blocker solutions are used concomitantly with oral calcium antagonists (calcium channel blockers), beta-adrenergic blockers, antiarrhythmic agents (including amiodarone), digitalis glycosides, parasympathomimetics, or guanethidine. In addition, patients receiving systemic alpha-blocking agents, reserpine, antiarrhythmic drugs of class I (e.g., quinidine), or clonidine should be observed for possible exacerbation of adverse reactions.

Oral beta-adrenergic blockers may potentiate the rebound hypertension that may occur following discontinuation of clonidine.

Concomitant use of CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine) and timolol has been reported to result in potential systemic beta-blockade (e.g., reduced heart rate, depression).

Concomitant treatment with barbiturates, analgesics, or ergot alkaloids may enhance adverse central nervous system reactions.

Rarely, mydriasis has been reported with concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine).

Special precautions for use.

Systemic effects

Since the response to beta-blockers may vary, measurement of intraocular pressure is recommended 2–4 weeks after starting treatment. Thereafter, patients should have regular ophthalmic examinations, as the response to timolol maleate may change with prolonged use.

As with other topically applied ophthalmic agents, tafluprost and timolol are absorbed systemically. Due to the presence of the beta-adrenergic blocking component, timolol, the same cardiovascular, pulmonary and other adverse reactions as seen with systemic beta-blockers may occur. The frequency of systemic adverse reactions (SARs) following topical ophthalmic administration is lower than with systemic administration. For information on reducing systemic absorption, see section "Dosage and administration".

Cardiac disorders

Patients with cardiovascular disorders (such as ischemic heart disease/coronary insufficiency, Prinzmetal’s angina, and heart failure) and hypotension should be carefully evaluated before initiating treatment with beta-blockers, and therapy with agents containing other active substances should be considered.

Patients with cardiovascular disorders should be monitored for worsening of their condition and for any adverse reactions.

Due to the negative effect on impulse conduction time, beta-blockers should be used with great caution in patients with first-degree heart block.

Vascular disorders

Patients with severe peripheral circulatory disturbances (i.e., severe forms of Raynaud’s disease or Raynaud’s syndrome) should be treated with caution.

Respiratory disorders

Adverse respiratory reactions, including death due to bronchospasm, have been reported in asthmatic patients following the use of some ophthalmic beta-blockers. Tapticom® should be used with caution in patients with mild to moderate chronic obstructive pulmonary disease (COPD) and only if the expected benefit outweighs the potential risk.

Hypoglycemia/diabetes mellitus

Beta-blockers should be used with caution in patients prone to spontaneous hypoglycemia or in patients with labile diabetes mellitus, as beta-blockers may mask the symptoms of acute hypoglycemia.

Hyperthyroidism

Beta-blockers may mask the symptoms of hyperthyroidism.

Corneal disorders

Ophthalmic beta-blockers may cause dry eyes. Patients with corneal disorders should be treated with caution.

Other beta-blockers

The effect on intraocular pressure or known systemic effects of beta-blockers may be enhanced when timolol (a component of Tapticom®) is administered to patients already receiving systemic beta-blockers. The response to treatment in such patients should be closely monitored. Concomitant use of two topical beta-adrenergic blocking agents is not recommended.

Angle-closure glaucoma

In patients with angle-closure glaucoma, the primary goal of therapy is to reopen the angle. This requires pupillary constriction with a miotic agent. Timolol has little or no effect on the pupil. When using timolol to reduce elevated intraocular pressure in the presence of angle-closure glaucoma, it should be used in combination with a miotic agent, not as monotherapy.

Anaphylactic reactions

Patients with a history of atopy or a history of severe anaphylactic reactions to a variety of allergens may be unresponsive to the usual doses of adrenaline used to treat anaphylactic reactions while taking beta-blockers.

Choroidal detachment

Choroidal detachment has been reported with the use of aqueous suppressants (such as timolol, acetazolamide) following filtering surgery.

Surgery and anaesthesia

Ophthalmic beta-blockers may block the systemic effects of beta-agonists such as adrenaline. The anaesthesiologist should be informed that the patient is receiving timol0l.

Myasthenia gravis

Worsening of the general condition has been reported in patients with myasthenia gravis treated with timolol eye drops.

Before initiating treatment, patients should be informed about the possibility of eyelash growth, darkening of the eyelid skin, and increased pigmentation of the iris associated with tafluprost treatment. Some of these changes may be permanent and may lead to a difference in appearance between the eyes when only one eye is treated.

Iris pigmentation changes occur slowly and may go unnoticed for several months. Eye color changes are mainly observed in patients with mixed-colored irises, such as blue-brown, gray-brown, yellow-brown, or green-brown. The risk of irreversible heterochromia is evident when the drug is used in only one eye.

There is a potential for hair growth in areas where tafluprost solution repeatedly comes into contact with the skin surface.

There is no experience with tafluprost in neovascular, angle-closure, narrow-angle, or congenital glaucoma. Experience with tafluprost in aphakic patients or those with pseudoexfoliative glaucoma is limited.

Caution should be exercised when prescribing tafluprost to aphakic patients, pseudophakic patients with a ruptured posterior lens capsule or anterior chamber lenses, or patients with known risk factors for cystoid macular edema or iritis (inflammation of the iris)/uveitis (inflammation of the uveal tract of the eye).

Use during pregnancy or breastfeeding.

Pregnancy

There are no adequate data or limited data on the use of Tapticom® in pregnant women.

Women of childbearing potential should use effective contraception during treatment with Tapticom®.

Tapticom® should not be used during pregnancy except in cases of clear necessity.

Tafluprost

There are no adequate data on the use of tafluprost in pregnant women. Tafluprost may have harmful pharmacological effects on pregnancy and/or the fetus/newborn. Animal studies have demonstrated toxicity on reproductive function. The potential risk to humans is unknown.

Timolol

There are no adequate data on the use of timolol in pregnant women. Timolol should not be used during pregnancy except in cases of clear necessity. See section "Dosage and administration" for information on reducing systemic absorption.

Epidemiological studies have not shown a teratogenic effect, but have demonstrated a risk of intrauterine growth retardation with oral administration of beta-blockers. In addition, signs and symptoms of beta-blocker effects (e.g., bradycardia, hypotension, dyspnea/respiratory distress, and hypoglycemia) have been observed in newborns exposed to beta-blockers before delivery. However, if Tapticom® is used before delivery, the newborn should be closely monitored by a physician during the first days of life.

Breastfeeding

Beta-blockers are excreted in breast milk. However, with therapeutic doses of timolol in eye drops, it is unlikely that the amount of drug present in breast milk would cause clinical symptoms in the infant. See section "Dosage and administration" for information on reducing systemic absorption.

It is not known whether tafluprost and/or its metabolites are excreted in human breast milk. Available toxicological data have demonstrated excretion of tafluprost and/or its metabolites into animal milk. However, with therapeutic doses of tafluprost in eye drops, it is unlikely that the amount of tafluprost present in human breast milk would cause clinical symptoms in the infant.

As a precautionary measure, breastfeeding is not recommended if treatment with Tapticom® is necessary.

Fertility

There are no data on the effect of Tapticom® on human fertility.

Ability to drive and use machines.

No studies on the effect of Tapticom® on the ability to drive and use machines have been conducted. If adverse reactions such as transient blurred vision occur after instillation, the patient should wait until vision clears before driving or operating machinery.

Method of Administration and Dosage

Doses

The recommended therapy is instillation of 1 drop of the ophthalmic solution into the conjunctival sac of the affected eye(s) once daily.

If a dose is missed, treatment should be continued with the next scheduled dose. The dose should not exceed 1 drop in the affected eye(s) once daily.

Tapticom® is a sterile preservative-free solution. It is intended for single use only; one tube-dispenser is sufficient for treatment of both eyes. Any unused solution or its remnants must be immediately discarded.

Elderly Patients

No dosage adjustment is required for elderly patients.

Renal and Hepatic Impairment

The use of tafluprost and timolol ophthalmic drops in patients with renal or hepatic impairment has not been studied; therefore, Tapticom® should be used with caution in such patients.

Method of Administration

Ophthalmic Use

To reduce the risk of eyelid skin pigmentation, patients should wipe off excess liquid from the skin.

Reduction of systemic absorption may be achieved by applying nasolacrimal occlusion or by closing the eyelids for 2 minutes. This may result in decreased systemic side effects and increased local activity.

If more than one ophthalmic medicinal product is prescribed, an interval of at least 5 minutes should be maintained between instillation of each agent.

Contact lenses must be removed prior to instillation of ophthalmic drops and at least 15 minutes should elapse before they are reinserted.

Patients should be advised to avoid direct contact between the eye and the dropper tip, as this may lead to ocular injury.

Patients should also be informed that improper handling of ophthalmic solutions may lead to contamination with common bacteria known to cause ocular infections. Use of contaminated solutions may result in serious eye injury and subsequent loss of vision.

Children

Safety and efficacy of Tapticom® in children (under 18 years of age) have not been established. Data are lacking. Tapticom® is not administered to children.

Overdose

Overdose with topical tafluprost is unlikely to occur or be associated with toxicity.

There have been reports of accidental overdose with timolol, resulting in symptoms of systemic poisoning similar to those observed with systemic beta-adrenergic blockers; even a few drops may cause arrhythmia, transient slowing of pulse rate, reduction in blood pressure, and bronchospasm (see also section "Adverse Reactions").

In case of Tapticom® overdose, treatment should be symptomatic and supportive, using adrenergic agonists (e.g., isoprenaline, dobutamine, and possibly dopamine). Timolol is not effectively removed by hemodialysis.

Adverse Reactions

In clinical studies, over 484 patients were treated with Tapticom®. The most frequently reported treatment-related adverse reaction was conjunctival/ocular hyperemia, occurring in approximately 7% of patients participating in clinical trials. In most cases, this reaction was mild, and in 1.2% of patients, it led to discontinuation of treatment.

Adverse reactions reported in clinical studies with Tapticom® were limited to those previously observed with either of its active ingredients—tafluprost or timolol. No new adverse reactions specific to Tapticom® were observed in clinical studies. The majority of reported adverse reactions were ocular, mild to moderate in severity, and not serious.

As with other topically applied ophthalmic medicinal products, tafluprost and timolol are systemically absorbed. This systemic absorption may lead to adverse reactions similar to those observed with systemic beta-blockers. However, the frequency of systemic adverse reactions following topical ophthalmic administration is lower than with systemic administration. The adverse reactions listed below include those observed within the class of ophthalmic beta-blockers.

The following adverse reactions have been reported with Tapticom® during clinical studies (within each frequency category listed below, adverse reactions are listed in decreasing order of frequency).

The frequency of possible adverse reactions listed below was determined using the following conventional terms: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); not known (cannot be estimated from available data).

Tapticom® (tafluprost/timolol combination)

Nervous system disorders

Uncommon: headache

Eye disorders

Common: conjunctival/ocular hyperemia, eye pruritus, eye pain, eyelash changes (increased length, thickness, and number of eyelashes), eyelash discoloration, eye irritation, foreign body sensation in the eye, blurred vision, photophobia (light sensitivity).

Uncommon: unusual sensation in the eye, dry eye, eye discomfort, conjunctivitis, eyelid erythema, eye allergy, eyelid edema, superficial punctate keratitis, increased lacrimation, anterior chamber inflammation, asthenopia (eye strain), blepharitis (inflammation of the eyelids).

Additional adverse reactions observed with either of the active substances (tafluprost or timolol) and which may also occur with Tapticom® are listed below.

Tafluprost

Eye disorders: Decreased visual acuity, increased iris pigmentation, pigmentation of the eyelids, conjunctival edema, eye discharge, cellular reaction in the aqueous humor, cellular opalescence in the anterior chamber, allergic conjunctivitis, conjunctival pigmentation, conjunctival follicles, deepening of the eyelid sulcus, iritis (iris inflammation)/uveitis (inflammation of the uvea), macular edema/cystoid macular edema.

Skin and subcutaneous tissue disorders: eyelid hypertrichosis.

Respiratory system disorders: exacerbation of bronchial asthma, dyspnea (shortness of breath/difficulty breathing).

Timolol

Immune system disorders: signs and symptoms of allergic reactions, including angioneurotic edema, urticaria, single and multiple rashes, anaphylactic reaction, pruritus.

Metabolism and nutrition disorders: hypoglycemia.

Psychiatric disorders: depression, sleep disturbances (insomnia), nightmares, memory loss, nervousness, hallucinations.

Nervous system disorders: dizziness, syncope, paresthesia, worsening of myasthenia gravis, hemorrhagic stroke, cerebral ischemia.

Eye disorders: keratitis, decreased corneal sensitivity, visual disturbances including refractive changes (due to discontinuation of miotics in some cases), ptosis (drooping of the eyelid), diplopia (double vision), choroidal detachment following filtering surgery, lacrimation, corneal erosion.

Ear and labyrinth disorders: tinnitus (ringing in the ears).

Cardiac disorders: bradycardia, chest pain, palpitations, edema, arrhythmia, congestive heart failure, cardiac arrest, heart block, atrioventricular block, heart failure.

Vascular disorders: hypotension, claudication, Raynaud's phenomenon, cold extremities (hands and feet).

Respiratory, thoracic and mediastinal disorders: dyspnea (shortness of breath/difficulty breathing), bronchospasm (particularly in patients with pre-existing bronchospastic disease), respiratory disorders, cough.

Gastrointestinal disorders: nausea, dyspepsia (indigestion), diarrhea, dry mouth, dysgeusia (disturbance of taste), abdominal pain, vomiting.

Skin and subcutaneous tissue disorders: alopecia (hair loss), psoriasiform rash or exacerbation of psoriasis, skin rash.

Musculoskeletal and connective tissue disorders: systemic lupus erythematosus, myalgia (muscle pain), arthropathy (joint disease).

Reproductive system and breast disorders: Peyronie's disease (fibrous induration of the penis), decreased libido (sex drive), sexual dysfunction.

General disorders and administration site conditions: asthenia (general weakness)/fatigue, thirst.

Rare cases of corneal calcification have been reported following the use of phosphate-containing eye drops in some patients with significant corneal damage.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals are encouraged to report any suspected adverse reactions.

Shelf life

3 years. After opening the foil pouch, store for 28 days.

After single use, the dropper tube should be discarded together with any remaining eye drops.

Storage conditions

Store at 2 to 8 °C (in the refrigerator) in the original packaging.

After opening the foil pouch, store at temperatures not exceeding 25 °C in a place protected from light.

Keep out of the reach of children.

Packaging

0.3 mL in a dropper tube. 10 dropper tubes in a pouch. 3 pouches (each containing 10 dropper tubes) in a cardboard box.

Prescription status

Prescription only.

Manufacturer

Santen AT / Santen Oy

Manufacturer's address

Kelloportinkatu 1, Tampere, 33100, Finland / Kelloportinkatu 1, Tampere, 33100, Finland

Marketing Authorization Holder

Santen AT, Finland / Santen Oy, Finland

Address of the Marketing Authorization Holder

Niittyhaankatu 20, 33720 Tampere, Finland / Niittyhaankatu 20, 33720 Tampere, Finland