Bimoptic plus rompharm

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BIMOPTIC PLUS ROMPHARM

Composition:

Active substances: bimatoprost, timolol (in the form of timolol maleate);

1 ml of eye drops, solution contains bimatoprost 0.3 mg; timolol 5.0 mg (in the form of timolol maleate 6.8 mg);

Excipients: citric acid monohydrate; disodium hydrogen phosphate heptahydrate; sodium chloride; benzalkonium chloride; 1 M solution of sodium hydroxide or hydrochloric acid; purified water.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: clear colorless or slightly yellow solution.

Pharmacotherapeutic group. Agents used in ophthalmology. Anti-glaucoma and miotic agents. Beta-adrenergic blockers. Timolol, combinations.

ATC code S01ED51.

Pharmacological Properties

Pharmacodynamics

Bimoptic Plus Rompharm is a combination medicinal product containing bimatoprost and timolol maleate, which reduce elevated intraocular pressure (IOP) through a combined effect, providing a greater effect than each substance alone. Bimoptic Plus Rompharm is a fast-acting medication.

Bimatoprost is a potent ocular hypotensive active substance.

Bimatoprost is an ophthalmic agent that reduces IOP and belongs to the synthetic prostamide class; chemically, it is structurally related to prostaglandin F2α (PGF2α). Bimatoprost does not act on any of the known prostaglandin receptors.

Bimatoprost selectively mimics the effects of newly discovered biosynthesized substances—prostamides. However, prostamide receptors have not yet been structurally identified.

The mechanism of IOP reduction by bimatoprost involves enhanced outflow of aqueous humor through the trabecular meshwork and uveoscleral pathways of the eye.

Timolol is a non-selective beta1- and beta2-adrenergic blocker without intrinsic sympathomimetic activity, membrane-stabilizing effects, direct myocardial depressant action, or local anesthetic activity.

Timol0l reduces IOP by decreasing the production of aqueous humor. The exact mechanism of timolol's action is not fully established but may be related to inhibition of cyclic adenosine monophosphate (cAMP) synthesis caused by endogenous stimulation of beta-adrenergic receptors.

Clinical Effects

The ability of the bimatoprost/timolol combination to reduce IOP is not inferior to the results achieved with adjunctive therapy using bimatoprost (once daily) and timolol (twice daily).

According to published data, administration of bimatoprost/timolol in the evening may be more effective for reducing IOP than morning administration. However, compliance should be considered when choosing between morning or evening dosing.

Children

The safety and efficacy of the fixed combination of bimatoprost/timolol in pediatric patients aged 0 to 18 years have not been established.

Pharmacokinetics

Bimoptic Plus Rompharm Medicinal Product

Plasma concentrations of bimatoprost and timolol were measured in a crossover study comparing monotherapy with the combination product bimatoprost/timolol in healthy volunteers.

Systemic absorption of the drug is minimal and does not differ between combination therapy and administration of each component separately.

In two 12-month studies assessing systemic absorption, no accumulation of either component was observed.

Bimatoprost

In in vitro studies, bimatoprost penetrated well into the cornea and sclera. With topical application of bimatoprost eye drops, systemic exposure is very low, with no accumulation. After instillation of 0.03% bimatoprost solution, one drop in each eye once daily for 2 weeks in healthy volunteers, maximum plasma concentration of bimatoprost was reached within 10 minutes after administration, and its concentration in plasma decreased below the limit of quantification (0.025 ng/mL) within 1.5 hours. Mean values of Cmax and area under the concentration-time curve (AUC0–24 h) for bimatoprost were similar on day 7 and day 14, amounting to 0.08 ng/mL and 0.09 ng•h/mL, respectively, indicating that steady-state concentration of bimatoprost is achieved within the first week of topical administration.

Bimatoprost is moderately distributed in tissues, and the volume of distribution at steady state in humans is 0.67 L/kg. Bimatoprost is primarily present in plasma. Plasma protein binding of bimatoprost is approximately 88%.

Bimatoprost is not extensively metabolized in the human eye and is one of the main circulating substances in blood after topical application. Subsequently, bimatoprost undergoes glucuronidation, oxidation, N-deethylation, and deamination, forming various metabolites.

Bimatoprost is primarily excreted in urine: approximately 67% of an intravenously administered dose is excreted in urine, and 25% via the gastrointestinal tract. The elimination half-life after intravenous administration is approximately 45 minutes; total plasma clearance is 1.5 L/h/kg.

Elderly Patients

After twice-daily dosing, the mean AUC0–24 h value was 0.0634 ng•h/mL in elderly patients (aged 65 years and older), which was statistically significantly higher than in younger subjects (0.0218 ng•h/mL). However, this finding is not considered clinically relevant, as systemic exposure in both younger and elderly patients was negligible following topical administration of eye drops. No accumulation of bimatoprost in blood was observed over time, and efficacy and safety of the drug were comparable between younger and elderly patients.

Timolol

In patients undergoing cataract surgery, peak timolol concentration in aqueous humor was 898 ng/mL one hour after instillation of 0.5% eye drops.

A small amount of the drug enters the systemic circulation and is metabolized by the liver. The elimination half-life of timolol in plasma is approximately 4–6 hours. Timolol is partially metabolized in the liver, and its metabolites are excreted by the kidneys. Timolol binds only minimally to plasma proteins.

Preclinical Safety Data

Repeated-dose ocular toxicity studies with bimatoprost/timolol did not reveal any special hazard for humans. The ocular and systemic safety profiles of the individual components are well established.

Bimatoprost

Preclinical data revealed no special hazard for humans based on conventional safety studies of pharmacology, genotoxicity, and carcinogenic potential. Studies in rodents resulted in species-specific abortion at systemic exposure levels 33 to 97 times higher than those achieved in humans after ocular administration.

Monkeys treated with daily topical application of 0.03% bimatoprost eye drops for 1 year developed increased iris pigmentation and reversible, dose-dependent periorbital effects characterized by a pronounced upper and/or lower sulcus and widening of the palpebral fissure. Increased iris pigmentation appears to result from increased stimulation of melanin production in melanocytes, not from an increase in the number of melanocytes. No functional or microscopic changes related to periorbital effects were observed, and the mechanism of action of these periorbital changes is unknown.

Timolol

Preclinical data revealed no special hazard for humans based on conventional studies of pharmacological safety, repeated-dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity.

Clinical characteristics.

Indications.

Reduction of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension when monotherapy with topical beta-blockers or prostaglandin analogs has been insufficiently effective.

Contraindications.

Hypersensitivity to timolol, bimatoprost, and/or any of the excipients of the medicinal product.

Increased airway reactivity syndrome, including bronchial asthma in the acute phase and history of previous episodes, severe chronic obstructive bronchopulmonary disease (COPD).

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

Interaction with other medicinal products and other forms of interaction.

No studies on interactions of the fixed combination of bimatoprost/timolol in the form of ophthalmic drops have been conducted.

Antihypertensive/cardiac glycosides. There is a possibility of additive effects leading to arterial hypotension and/or marked bradycardia when ophthalmic drops containing beta-adrenergic blockers are used concomitantly with calcium channel blockers, guanethidine, beta-blockers, parasympathomimetics, antiarrhythmic agents (including amiodarone), and digitalis glycosides.

CYP2D6 inhibitors. Cases of enhanced systemic beta-blockade (e.g., reduced heart rate, depression) have been reported during combined treatment with CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine) and timolol.

Mydriatic agents. Pupillary dilation resulting from concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine) has been observed rarely.

Special precautions for use

Like other ophthalmic medicinal products, bimatoprost/timolol may enter the systemic circulation. There was no observed increase in systemic absorption of the individual active substances. Due to the presence of timolol, a beta-adrenergic component, similar types of cardiovascular, pulmonary, and other adverse reactions as with systemic beta-blockers may occur. The frequency of adverse reactions with local administration of the drug is lower than with systemic use. For information on reducing systemic absorption, see section "Dosage and administration".

Bimatoprost/timolol should be prescribed with caution:

• to patients with acute eye inflammation (e.g., uveitis), due to the possibility of exacerbating inflammation;
• to patients at risk of macular edema, including cystoid macular edema. Bimoptic Plus Rompharm should be used with caution in aphakic patients, pseudophakic patients with a ruptured posterior lens capsule, and patients with known risk of macular edema (e.g., after intraocular surgery, retinal vein occlusion, inflammatory eye diseases, and diabetic retinopathy).

Cardiac disorders. Patients with cardiovascular diseases (e.g., ischemic heart disease, Prinzmetal's angina, and heart failure) and those on beta-blocker antihypertensive therapy should undergo thorough evaluation. Consideration should be given to therapy with alternative active substances.

Patients with cardiovascular diseases should be monitored for signs of worsening conditions and adverse reactions.

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

Vascular disorders. The drug should be used with caution in patients with severe disorders/peripheral circulatory disturbances (e.g., severe forms of Raynaud's disease or Raynaud's syndrome).

Respiratory disorders. Disorders of the respiratory system, including fatal cases due to bronchospasm, have been reported in patients with asthma after administration of certain ophthalmic beta-blockers.

Bimoptic Plus Rompharm should be prescribed with caution to patients with mild or moderate chronic obstructive bronchopulmonary disease (COPD), and only if the expected benefit outweighs the potential risk to the patient.

Endocrine disorders. Medicinal products that are beta-adrenergic receptor blockers should be used cautiously in patients with spontaneous hypoglycemia or unstable diabetes, as beta-blockers may mask the signs and symptoms of acute hypoglycemia.

Beta-adrenergic blockers may also mask signs of hyperthyroidism.

Corneal disorders. Topical beta-adrenergic receptor blockers may cause dry eye, so they should be prescribed with caution to patients with corneal disorders.

Anaphylactic reactions. In patients with atopic disorders or a history of severe anaphylactic reactions to a wide range of allergens, beta-adrenergic blockers may increase susceptibility to re-exposure to such allergens and may not respond to the usual dose of adrenaline used to treat anaphylactic reactions.

Retinal detachment. Cases of retinal detachment have been reported with drugs that inhibit fluid secretion (e.g., timolol, acetazolamide) following filtration procedures.

Surgical anesthesia. Ophthalmic beta-blocking agents may block the effects of systemic beta-agonists, such as adrenaline. If a patient is taking timolol, this should be communicated to the anesthesiologist.

Effect on liver function. In patients with mild liver disease or initial elevated liver enzyme activity—alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or total bilirubin—bimatoprost did not affect liver function during a study period exceeding 24 months.

There is no information on adverse reactions related to ocular timolol use affecting liver function.

Ocular disorders. Before initiating treatment, patients should be informed about possible eyelash growth, darkening of the eyelids or periorbital area, and increased pigmentation of the iris (brown color), as such reactions have been observed during treatment with bimatoprost and Bimoptic Plus Rompharm. Increased iris pigmentation may become permanent and may lead to differences in eye appearance if only one eye is treated. After discontinuation of Bimoptic Plus Rompharm, iris pigmentation may remain permanent.

After 12 months of treatment with the drug, iris pigmentation was observed in 0.2% of patients. After 12 months of treatment with bimatoprost alone as eye drops, it was observed in 1.5%; no further increase in frequency was observed during 3 years of therapy. Increased iris pigmentation is due to an increase in melanin content in melanocytes, not an increase in their number. The long-term effect of increased iris pigmentation is unknown. Iris color changes during bimatoprost eye drop treatment may not manifest for several months to several years. Treatment does not affect iris nevi or freckles. In some patients, periorbital skin pigmentation disappeared.

Before initiating treatment, patients should be informed about the possibility of developing prostaglandin-associated periorbitopathy (PAP) and increased iris pigmentation, as these disorders have been observed during treatment with Bimoptic Plus Rompharm. Some of these disorders may be irreversible and may cause visual field changes and differences in eye appearance if only one eye is treated (see "Adverse reactions").

Skin disorders.

Hair growth may occur in areas where Bimoptic Plus Rompharm repeatedly contacts the skin surface. Therefore, it is important to use Bimoptic Plus Rompharm according to instructions to avoid runoff onto the cheek or other skin areas.

Other beta-adrenergic blockers. The effect on intraocular pressure (IOP) or known systemic beta-blockade effects may be enhanced if timolol is administered to patients already taking systemic beta-blocking agents. Such patients should be closely monitored for response to treatment. Concomitant use of two locally acting beta-adrenergic blocking agents is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Excipients.

The preservative benzalkonium chloride contained in Bimoptic Plus Rompharm may cause eye irritation.

Patients wearing soft contact lenses should be advised to remove them before instillation of the drug and may reinsert them 15 minutes after administration of eye drops.

Benzalkonium chloride may discolor soft contact lenses. Contact between the drug and soft contact lenses should be avoided.

Benzalkonium chloride has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Therefore, patients with dry eye syndrome or corneal damage should be monitored if Bimoptic Plus Rompharm is frequently or long-term administered.

Other.

The use of the drug in patients with inflammatory eye diseases, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma, and narrow-angle glaucoma has not been studied.

Clinical studies with 0.03% bimatoprost ophthalmic solution have demonstrated that frequent administration of more than one dose of bimatoprost per day may reduce the hypotensive effect in patients with glaucoma and ocular hypertension. Patients using Bimoptic Plus Rompharm with other prostaglandin analogs should have intraocular pressure (IOP) changes monitored.

Use during pregnancy or breastfeeding.

Pregnancy

There are insufficient data on the use of the fixed combination of bimatoprost/timolol in pregnant women. Bimoptic Plus Rompharm should be used during pregnancy only if absolutely necessary. For information on reducing systemic absorption, see section "Dosage and administration".

Bimatoprost

There are insufficient clinical data on use in pregnant women. Animal studies have shown reproductive toxicity at high doses (see "Preclinical safety data").

Timolol

Epidemiological studies have not shown teratogenic effects but have indicated a risk of intrauterine growth retardation with oral use of beta-blockers. In addition, newborns have shown signs of beta-blockade (e.g., bradycardia, arterial hypotension, respiratory depression, and hypoglycemia) when beta-blockers were administered before delivery. Therefore, the newborn should be under close observation during the first days of life. Animal studies with timolol have shown reproductive toxicity at doses significantly higher than those used in clinical practice (see "Preclinical safety data").

Breastfeeding

Timolol

Beta-blockers pass into breast milk. However, with therapeutic doses of timolol as eye drops, the presence of a significant amount of the substance in breast milk causing clinical signs of beta-adrenergic receptor blockade in newborns is unlikely. For information on reducing systemic absorption, see section "Dosage and administration".

Bimatoprost

It is unknown whether bimatoprost passes into human breast milk, but studies in rats have shown the presence of bimatoprost in milk of lactating rats. Bimoptic Plus Rompharm should not be used in women who are breastfeeding.

Fertility

There are no data on the effect of the drug on human fertility.

Ability to influence reaction speed when driving or operating machinery.

Bimoptic Plus Rompharm has a negligible effect on the ability to drive or operate machinery. As with other ophthalmic medicinal products, if temporary blurred vision occurs after instillation, patients should wait until vision clears before driving or operating machinery.

Method of Administration and Dosage

Bimoptic Plus Rompharm is for topical ophthalmic use.

Dosage

Recommended dosage for adults (including elderly patients)

The recommended dose is 1 drop into the conjunctival sac of the affected eye(s) once daily, either in the morning or evening. It should be administered at the same time each day.

Available literature data suggest that evening administration may be more effective in reducing IOP than morning administration. However, when choosing between morning or evening dosing, potential compliance should be taken into account (see "Pharmacodynamics").

If a dose is missed, the next dose should be administered as scheduled. Dose escalation is not recommended — the maximum dose is 1 drop once daily in the affected eye(s). The daily dose should not exceed one drop in the affected eye(s).

Nasolacrimal occlusion or keeping the eyes closed for 2 minutes after instillation may reduce systemic absorption. This, in turn, may reduce systemic adverse effects and increase local drug activity.

Method of Administration

If Bimoptic Plus Rompharm is used together with other ophthalmic agents, a 5-minute interval should be maintained between instillations of each medication.

To avoid eye injury and contamination of the eye drops, contact between the tip of the dropper and the eye or surrounding tissues should be avoided.

Renal and hepatic impairment

Bimoptic Plus Rompharm has not been studied in patients with hepatic or renal impairment. Therefore, caution should be exercised when treating such patients.

Use in elderly patients

Safety and efficacy data in elderly patients are similar to those in adult patients.

Children

The safety and efficacy of Bimoptic Plus Rompharm in children aged 0 to 18 years have not been established; data are lacking.

The drug should not be administered to patients under 18 years of age.

Overdose

Local overdose of bimatoprost/timolol is unlikely and not associated with toxicity.

There have been no reports of overdose with Bimoptic Plus Rompharm in humans.

In case of overdose, symptomatic and supportive therapy should be administered.

Bimatoprost

If Bimoptic Plus Rompharm is accidentally ingested, the following information may be helpful: in two-week oral toxicity studies in rats and mice, doses of bimatoprost up to 100 mg/kg/day caused no toxicity. When expressed in mg/m², this dose is at least 70 times higher than the accidental ingestion of one bottle of Bimoptic Plus Rompharm by a 10 kg child.

Timolol

Symptoms of timolol overdose may include bradycardia, hypotension, bronchospasm, headache, dizziness, dyspnea, and cardiac arrest. In renal failure, timolol is not effectively removed by hemodialysis. Studies in patients with renal impairment have shown that timolol is poorly dialyzable.

Adverse reactions.

Safety study results of the medicinal product.

Adverse reactions observed during clinical studies with the bimatoprost/timolol medicinal product were limited to those previously identified during use of the active substances—bimatoprost and timolol—separately. No new adverse reactions specific exclusively to the bimatoprost/timolol medicinal product were observed during clinical studies.

Most of the adverse reactions observed during clinical studies with the bimatoprost/timolol medicinal product were ocular in nature and mild in severity. None of the adverse reactions were severe. According to 12-month clinical data, the most frequently reported adverse reaction was conjunctival hyperemia (in most cases very mild or moderate and likely of non-inflammatory nature), observed in approximately 26% of patients and leading to discontinuation in 1.5% of patients.

The list of adverse reactions is presented in the tables below.

Table 1 presents adverse reactions reported during clinical studies of the bimatoprost/timolol medicinal product or in the post-marketing period (for each frequency, adverse reactions are listed in order of manifestation—from severe to mild).

The frequency of occurrence of adverse reactions was defined according to the following criteria:

Very common	>1/10
Common	≥1/100 to <1/10
Uncommon	≥1/1000 to <1/100
Rare	≥1/10000 to <1/1000
Very rare	<1/10 000
Not known	Frequency cannot be estimated from the available data.

Table 1

System Organ Class	Frequency	Adverse Reaction
Immune system disorders	Not known	Hypersensitivity reactions, including signs or symptoms of allergic dermatitis, angioneurotic edema, ocular allergy
Psychiatric disorders	Not known	Insomnia, nightmares
Central nervous system disorders	Common	Headache
	Not known	Dysgeusia, dizziness
Eye disorders	Very common	Conjunctival hyperemia
	Common	Superficial keratitis, corneal erosion, burning sensation, conjunctival irritation, itching, burning sensation in eyes, foreign body sensation, dryness of ocular mucosa, eyelid erythema, eye pain, photophobia, eye discharge, visual disturbance, eyelid itching, decreased visual acuity, blepharitis, eyelid edema, eye irritation, increased lacrimation, eyelash growth
	Uncommon	Iritis, irritation of ocular mucosa, conjunctival edema, eyelid pain, asthenopia, trichiasis, hyperpigmentation of the iris, periorbital changes and eyelid changes associated with atrophy of periorbital fat and skin induration leading to deepening of eyelid sulcus, eyelid ptosis, enophthalmos, lagophthalmos and eyelid retraction, change in eyelash color (darkening)
	Not known	Cystoid macular edema, eye swelling, blurred vision, eye discomfort
Cardiac disorders	Not known	Bradycardia
Vascular disorders	Not known	Hypertension
Respiratory system disorders	Common	Rhinitis
	Uncommon	Dyspnea
	Not known	Bronchospasm (mainly in patients with pre-existing bronchospastic condition), asthma
Skin and subcutaneous tissue disorders	Common	Periorbital pigmentation, hirsutism, hyperpigmentation of skin around the eye
	Not known	Alopecia, skin depigmentation around the eye
General disorders	Not known	Increased fatigue

As with other ophthalmic medicinal products for local use, Bimoptic Plus Rompharm enters the systemic circulation. Absorption of timolol may cause the same adverse reactions as those observed with systemic beta-blockers. The frequency of systemic adverse reactions to the medicinal product after local ocular administration is lower than with systemic administration. For information on reducing systemic absorption, see section "Instructions for use and dosage".

Additional adverse reactions observed during the use of the active substances (bimatoprost or timol0lol) and which may potentially occur during use of the product are listed in Table 2.

Table 2.

System Organ Class	Adverse Reaction
Immune system disorders	Systemic allergic reactions, including anaphylaxis1
Metabolism and nutrition disorders	Hypoglycemia1
Psychiatric disorders	Depression1, memory loss1, hallucinations1
Central nervous system disorders	Loss of consciousness1, cerebral circulation disorder1, worsening of myasthenia gravis symptoms1, paresthesia1, cerebral ischemia1
Eye disorders	Corneal sensitivity reduction1, diplopia1, ptosis1, retinal detachment after surgical treatment1 (see section "Special precautions"), keratitis1, blepharospasm2, retinal hemorrhage2, uveitis2, darkening of eyelashes, periorbital erythema; very common – prostaglandin-associated periorbitopathy (PAP)2
Cardiac disorders	Atrioventricular block1, cardiac arrest1, arrhythmia1, heart failure1, congestive heart failure1, chest pain1, increased heart rate1, edema1
Vascular disorders	Hypotension1, Raynaud's syndrome1, cold extremities1
Respiratory disorders	Cough1, asthma exacerbation2, COPD exacerbation2
Gastrointestinal disorders	Nausea1,2, diarrhea1, dyspepsia1, dry mouth1, abdominal pain1, vomiting1
Skin and subcutaneous tissue disorders	Psoriasiform eruptions1, psoriasis exacerbation1, skin rash1
Musculoskeletal and connective tissue disorders	Muscle pain1
Reproductive system and breast disorders	Sexual dysfunction1, decreased libido1
General disorders and administration site conditions	Asthenia1,2
Investigations	Liver enzyme alterations2 (liver function tests)

1 Adverse reactions observed with timolol use.

2 Adverse reactions observed with bimatoprost use.

Prostaglandin-associated periorbitopathy (PAP)

Prostaglandin analogs, including Bimoptic Plus Rompharm, may cause periorbital lipoatrophy, which can lead to deepening of the superior sulcus, ptosis, enophthalmos, eyelid retraction, involution of dermatochalasis, and inferior scleral show. These changes are usually mild and may occur as early as one month after initiation of treatment with Bimoptic Plus Rompharm, resulting in visual field changes even in the absence of symptoms. PAP is also associated with periorbital hyperpigmentation or skin depigmentation and hypertrichosis. All of these changes have been reported to be partially or completely reversible upon discontinuation of the drug or switching to alternative therapies.

Adverse reactions to ophthalmic solutions containing phosphates

Very rare cases of corneal calcification associated with the use of ophthalmic solutions containing phosphates have been reported in patients with significantly damaged corneas.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life

3 years.

Shelf life after first opening of the container: 28 days.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging

3 ml in a bottle with a dropper cap, in a cardboard carton.

Prescription status

Prescription only.

Manufacturer

C.T. ROMPHARM COMPANY S.R.L. / S.C. ROMPHARM COMPANY S.R.L.

Manufacturer's address and location of its business operations

Str. Eroilor No. 1A, Otopeni, 075100, Ilfov County, Romania – Rompharm 1 and Rompharm 2 buildings / Eroilor str. No 1A, Otopeni city, 075100, county Ilfov, Romania – building Rompharm 1 and Rompharm 2.