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> Legal Report: Framework for the regulatory freedom of information to the patient about the drug – comparative analysis on the example of TWO SIMILAR eye ointments
Legal Report: Framework for the regulatory freedom of information to the patient about the drug – comparative analysis on the example of TWO SIMILAR eye ointments
Publication date: February 19, 2025
Introduction: The ambivalence of the issue and the regulatory context
The issue of informing the patient about the drug is of key importance in the treatment process, because the proper provision of information can affect the effectiveness of the therapy, patient safety and minimizing the risk of adverse effects. From a regulatory perspective, the rules regarding drug leaflets are precisely defined in both national and EU legal acts, but in practice we encounter differences in the formulation of this information by manufacturers, even in relation to products intended for the treatment of the same condition.
A comparative analysis based on the example of the comparative leaflets of two sample drugs, Maxitrol and Floxal – two preparations used in the treatment of blepharitis, although differing in composition and mechanism of action – reveals a certain editorial freedom of the manufacturers in shaping the content of the leaflets.
On the one hand, the law regulates in detail the requirements for the content of leaflets, on the other hand, there is flexibility in their formulation, especially in stylistic and organizational matters. The aim of this report is to provide an in-depth analysis of the legal provisions regulating this issue, as well as to present a comparison of two leaflets, taking into account both their substantive content and form.
Report objectives:
Understand the laws that govern prescription drug information leaflets.
Analysis of the details of the presentation of active substances, dosage, contraindications, etc.
An assessment of the extent to which the drug manufacturer has freedom to edit such information and what the legal consequences of these choices are.
Legal Basis for Prescription Drug Disclosure Obligations
EU law
Within the European Union, the law on information on medicines for patients is harmonised through Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use.
Article 59 of this directive specifies what information must appear on the packaging of medicines and in leaflets, including for prescription medicinal products. These documents are intended to provide the patient with full information about the medicine, including its composition, method of use, contraindications and side effects.
Annex I to Directive 2001/83/EC contains detailed requirements for labelling and package leaflets, imposing the obligation to provide the patient with comprehensive and comprehensible information that can assist him in using the medicine appropriately.
In turn, Regulation 1234/2008 introduces rules on the development and presentation of leaflets, which is important in the context of prescription medicine. This is an element of the regulation that refers to the manufacturer’s obligations to provide full and appropriate documentation, including information leaflets.
National law
In Poland, issues related to the obligations of drug manufacturers to inform patients are regulated by:
Act of 6 September 2001 – Pharmaceutical Law. In particular, Article 64 of this Act states that the drug manufacturer is responsible for attaching an “information leaflet” to the drug, the form and content of which must comply with the requirements specified in EU and national regulations.
The Regulation of the Minister of Health of 19 September 2013 on detailed requirements for labelling, packaging and leaflets of medicines specifies the rules regarding the form, content and layout of leaflets for prescription medicines in Poland. This emphasises the need to provide the patient with understandable and appropriate information to facilitate the correct use of the medicine.
Regulatory rules – what must the leaflet contain?
In principle, the information leaflet must contain certain elements that are regulated by both EU and national regulations. In particular:
Active substances and their concentration
One of the basic obligations of a drug manufacturer is to inform the patient about the content of active substances in the drug. This means that the leaflet should clearly state what active substances the drug contains and in what concentration.
In the case of the first example – MAXITROL (eye ointment), the active substances are:
Dexamethasone – a steroid that has anti-inflammatory effects and reduces the symptoms of inflammation.
Neomycin sulfate and Polymyxin B sulfate – antibiotics that have antibacterial properties.
In the case of the second comparative example: FLOXAL, the active substance is Ofloxacin , an antibiotic from the fluoroquinolone group , with antibacterial action.
In a regulatory context, it is therefore important to:
Precisely indicate the concentration of each active substance. This is of great importance, especially in the case of drugs containing steroids (like MAXITROL), which can lead to serious side effects, such as increased intraocular pressure.
The content of the substance must be consistent with the pharmacopoeia – in the case of medicines used in Poland, the Polish or European Pharmacopoeia indicates what the concentration and acceptable quality of the substance should be.
Side effects
The leaflet must contain full information on possible side effects. The regulations require that the patient be aware of the risks associated with the use of a given drug. In the case of MAXITROL, special attention should be paid to the risk of increased intraocular pressure and the development of glaucoma, which is characteristic of the use of steroids.
The law requires that side effects be clearly and comprehensibly indicated. In addition, information is required about the need to immediately stop using the drug and consult a doctor if side effects occur, especially those that may lead to serious health problems.
Dosage
According to the regulations, the leaflet should precisely specify how the medicine should be used, i.e. what dose of the medicine should be administered and how often. It is also important to indicate how long the medicine should be used. In the case of eye ointments, such information is particularly important, because improper use can lead to serious complications, such as excessive irritation or infection.
Establishing regulatory law: How, when and where should the package insert for a prescription drug be used?
According to legal regulations, the precise definition of the substance is of particular importance.active substances in the leaflet. This is important not only from the point of view of the effectiveness of the therapy, but also the patient’s safety. Explaining this issue comparatively on two similar examples, the information for the patient is written in the following information message:
Maxitrol: Eye ointment contains prednisolone (steroid, 1 mg/ml), neomycin (antibiotic, 3.5 mg/ml) and polymyxin B (antibiotic, 6 mg/ml). In the case of this preparation, because it contains a steroid substance, the risk of increased intraocular pressure and the risk of developing glaucoma must be clearly highlighted in the leaflet, especially in patients at risk.
Floxal: In turn, the ointment contains ofloxacin (an antibiotic from the fluoroquinolone group). In this case, it is important to clearly indicate that this is a drug used to treat bacterial infections, and to include information about potential allergic reactions, including rare but serious skin reactions.
Permanent elements of the leaflet – explanation with examples
Each leaflet must include the following elements:
Name of the drug – full, understandable name, e.g. “Maxitrol, eye ointment” and “Floxal, eye ointment“.
Active substances and their concentration – providing the exact names and doses of active substances, e.g. in Maxitrol: prednisolone 1 mg/ml, neomycin 3.5 mg/ml, polymyxin B 6 mg/ml, and in Floxal: ofloxacin 3 mg/ml.
Indications for use – Both drugs are used to treat inflammation of the eyelids, but the Maxitrol leaflet additionally emphasises the anti-inflammatory effect of the steroid and the risks associated with its long-term use, including the risk of increased pressure in the eye. Floxal focuses more on treating bacterial infections.
Dosage – detailed dosing instructions, adapted to the patient’s age and stage of infection/inflammation.
Contraindications – Maxitrol leaflet should include contraindications relating to glaucoma, as well as contraindications for people with a history of eye diseases associated with increased intraocular pressure.
Side effects – maximum emphasis on the possible risks associated with long-term use of steroid medications in Maxitrol and the risk of developing allergic reactions to ofloxacin in Floxal.
Storage instructions – medicines are usually stored in a cool, dry place, in the case of both ointments – at a temperature below 25°C.
Legal layer of submitting a leaflet: Differences between domestic and foreign manufacturers
Domestic manufacturer vs foreign distributor
The issue of reporting and approving leaflets by domestic and foreign manufacturers may involve different administrative procedures. According to the information made publicly available, if, for example, Maxitrol has the status of a domestic manufacturer, it is the pharmaceutical company that goes through the registration process directly in Poland, which means that the leaflet is already adapted to the requirements of Polish law. In turn, Floxal, as a product of a German company, must be approved by the appropriate Polish regulatory authorities.
In the case of foreign manufacturers, the distributor is responsible for compliance with national regulations and for the documentation, including the leaflet, to be compliant with regulations in Poland. In the case where the distributor is based in Poland, they may also be required to store all documents related to the introduction of the drug to the domestic market.
If the drug manufacturer is based abroad (e.g. Germany), the distributor is responsible for legalizing and introducing the drug to the Polish market. The distributor is obliged to report the drug to the URPL and adapt the leaflet to the requirements of Polish law, although in practice distributors often use documentation prepared by the manufacturer.
From a legal point of view, there is a difference in the notification process and responsibility for preparing leaflets depending on whether the drug manufacturer has a company in Poland or operates through a distributor.
Example of analysis of the active substance in both drugs:
Maxitrol – contains dexamethasone, neomycin and polymyxin B. These substances have anti-inflammatory, antibacterial and antimicrobial effects.
Floxal – contains ofloxacin, which is an antibacterial drug from the fluoroquinolone group, active against Gram-positive and Gram-negative bacteria.
An analysis of the leaflets of these products should reveal how these substances are presented, in what concentration and in what form.
Presentation of permanent elements of the leaflet
All leaflets must contain the same basic elements. In the comparison table below, there are outlined the key differences and similarities between the leaflets for both medicines.
Element
Maxitrol
Floxal
Name of the medicine
Maxitrol
Floxal
Active substances
Dexamethasone, Neomycin, Polymyxin B
Ofloxacin ( ofloxacin )
Indications
Treatment of blepharitis and other eye diseases
Treatment of bacterial infections of the anterior segment of the eye
Dosage
1-2 times a day (ointment)
1 drop 4 times a day (eye drops)
Adverse reactions
Increased intraocular pressure, irritation
Eye irritation, allergic reactions
Both leaflets contain all the necessary information, but differ in the way they are written. For example:
Maxitrol is presented as an eye ointment while Floxal is drops.
Maxitrol places more emphasis on potential side effects associated with steroid use, such as increased intraocular pressure, whereas Floxal does not provide such information in the same context.
Further analysis of leaflet content – Details and differences in information presentation
To better understand the impact of leaflets on patients, it is necessary to analyse how specific information is presented in both cases, as well as how different forms of communication may affect patient understanding and use of the medicine.
Description of the active substance: technical details
In the case of Maxitrol and Floxal, the key difference is the type of active substance and their mechanism of action. Both drugs have different therapeutic goals and differ in terms of the method of administration.
Maxitrol (eye ointment) contains three active substances: dexamethasone, neomycin and polymyxin B, which together have anti-inflammatory, antibacterial and antimicrobial effects.
Dexamethasone is a corticosteroid that reduces inflammation. This requires a clear indication in the leaflet that long-term use can lead to serious side effects, such as increased intraocular pressure, which can lead to glaucoma.
Neomycin and Polymyxin B are antibiotics that fight a wide range of bacteria, but the leaflet must state that allergic reactions, such as irritation, may occur.
Additionally, information on dosage is provided in the form of general recommendations: apply the ointment 1-2 times a day. It is worth adding that the dose and frequency depend on the severity of the infection.
Floxal (eye drops) contains ofloxacin, which is an antibiotic from the fluoroquinolone group . Its mechanism is to block the enzymes responsible for bacterial DNA replication, which prevents their growth.
Floxal leaflet must indicate that ofloxacin is effective against Gram-positive and Gram-negative bacteria, but may also cause side effects such as burning or eye irritation. Moreover, information about bacterial resistance to the drug should be included in the case of long-term therapy.
dosage for Floxal is 1 drop 4 times daily, which may be important because eye drops require more precise administration and are usually preferred for short-term bacterial infections.
Highlighting risks and side effects
Both medications have the potential to cause side effects, and their package inserts contain important warnings that may vary depending on how the medication is used.
Maxitrol, for example, therefore, contains warnings related to long-term use of corticosteroids:
Increased risk of glaucoma – the patient should be carefully informed how long he or she can use the medication to avoid the risk of this serious complication.
Increased risk of infections – especially with long-term use of corticosteroids, which may reduce the body’s ability to fight infections.
Warning against use in case of corneal damage – due to the risk of undesirable side effects when used in this case.
Floxal, due to its specificity as an antibiotic, primarily emphasizes the risk of eye irritation, allergies, as well as the possibility of bacterial resistance to ofloxacin in the long term. Floxal leaflet pays special attention to:
Burning, tearing or redness of the eye – which is a common symptom when using antibiotic drops.
Long-term use – may lead to the development of bacterial resistance, therefore the drug is not recommended for long-term use without medical consultation.
Information about interactions with other drugs
For Maxitrol:
The leaflet indicates possible interactions with antiviral drugs, which is important if the patient is using other antiviral drugs for the eyes. The leaflet usually states that simultaneous use with other antibacterial drugs should be avoided, as this may affect the effectiveness of the action.
For Floxal:
Floxal interactions with other drugs are less common, as it is an antibiotic used only for the eyes. However, it is recommended to avoid using it with other drugs with a similar mechanism of action (e.g. other fluoroquinolones ) to avoid overloading the body and unwanted effects. It should also be noted that long-term use of antibiotics may promote the development of resistance, so it is recommended to use it only in the periods recommended by the doctor.
Dosage forms
Dosage forms vary depending on the form of the drug:
Maxitrol is available in the form of an ointment, which requires more precision when applying it. It is recommended to apply it 1-2 times a day, which may be less comfortable than using drops, especially in cases where the patient has to use the medicine for a longer period of time.
Floxal in the form of eye drops is more comfortable because it allows for precise administration of the drug at appropriate intervals. It is recommended to apply 1 drop 4 times a day, which ensures the effectiveness of the drug and at the same time makes it easier for the patient to adapt the treatment to their daily routine.
Examples of Using Technology in Patient Education
There is a possibility of improving communication with the patient using new technologies. One of the tools that could support the education process are mobile applications dedicated to patients taking medications. Such applications may include:
Dosage reminders – the patient receives a notification when the medication needs to be administered at a given time.
Tips on use – e.g. how to apply the ointment or drops, how to avoid interactions with other medications, how to deal with possible side effects.
Safety recommendations – information about when to contact the patient’s doctor or pharmacist if the patient experiences adverse symptoms.
Conclusions and recommendations
Understanding the differences in presentation of information is key to effective use of medicines. Patient leaflets should not only be compliant with legal regulations, but also understandable and accessible.
Recommendations regarding the dosage and use of medications should be precise, because improper use of the drug (e.g. in the case of Maxitrol) may lead to serious health complications.
New technologies can assist patients in the treatment process by enabling them to better understand how to use medications and monitor possible side effects.
It is also worth noting the key role of doctors and pharmacists in explaining to patients the details of the use of medications, especially in the context of long-term use of steroids and antibiotics.
Pharmacokinetic and pharmacodynamic analysis
When we are talking about two different preparations with similar uses, we need to take into account how the active substances are metabolized and how they act on the body, which may affect the length of therapy and the need for monitoring.
Maxitrol ointment
Dexamethasone, a steroid substance, is widely distributed in the body and can enter the bloodstream after application to the eye. After application of Maxitrol ointment to the eye, the concentration of the drug in the eye tissues can persist for up to 24 hours, which may affect the length of its action. However, due to the potential systemic effects of steroids, long-term use requires monitoring the patient to avoid effects such as increased intraocular pressure (glaucoma) and cataracts.
Polymyxin B and Neomycin are antibiotics whose primary purpose is to eliminate bacteria, but it should be noted that minor absorption into the bloodstream may occur following ocular application. In such cases, side effects from these substances may include allergic reactions, as well as antibiotic resistance if overused.
Pharmacokinetics of Floxal
Ofloxacin, like most fluoroquinolones, is well absorbed from the surface of the eye into the bloodstream, but its systemic concentration is minimal. It acts locally on the tissues of the eye, but can also affect other systems, especially with long-term use. Ofloxacin penetrates the tissue of the cornea, vitreous humor, and eye fluids, so it is effective in the treatment of bacterial keratitis or conjunctivitis.
The pharmacokinetics of Floxal is important in the context of long-term use, because it may lead to the development of bacterial resistance, especially in the case of non-compliance with therapeutic recommendations or use of the preparation for too long a period.
Application in specific patient groups – examples of patient information material
Maxitrol in the treatment of children and the elderly
Maxitrol contains steroids, which means it is not recommended for children under 2 years of age unless there is a strong indication. Steroids can cause serious side effects, such as delayed growth, stunted development, and an increased risk of infection.
Special care should be taken in the elderly, as they may be more susceptible to adverse effects associated with corticosteroids, such as increased intraocular pressure and glaucoma. Additionally, the elderly may have weakened immune systems, which increases the risk of infections when using corticosteroids.
Floxal for children, pregnant and breastfeeding women
Floxal also has some limitations when it comes to use in children. Due to the lack of full clinical trials, the use of ofloxacin in children under 1 year of age should be limited. In the case of older children, the doctor should assess the risks and benefits, because long-term use may lead to the development of bacterial resistance.
Pregnant women should avoid using Floxal unless the benefits outweigh the potential risk. Ofloxacin is classified in category C during pregnancy (limited safety data).
Breastfeeding : Ofloxacin passes into breast milk, which may affect the health of the baby. If the drug is used during breast-feeding, the doctor will decide whether to stop breast-feeding.
Patient Education and Communication
Patient education is key for both medications, but because of the differences in how they work, it is important for the patient to understand how to use the medication appropriately.
Maxitrol
The leaflet should contain clear instructions on how to use the ointment, as improper application (e.g. too often or in too large amounts) may lead to unwanted side effects. Due to the steroid action, the patient must be informed about the risk of glaucoma and cataracts.
It is important that the patient understands the risks associated with excessive use of the drug, which may lead to disruption of the functioning of the immune system.
Floxal
In the case of Floxal drops, the patient should be carefully informed about how to use the medicine to avoid bacterial contamination due to incorrect administration (e.g. touching the tip of the bottle to the eye or other surfaces). In addition, because ofloxacin is an antibiotic, the patient should be informed about the importance of completing the entire course of treatment to prevent the development of resistance.
Due to potential eye irritation, the patient should be alert to the possibility of burning, tearing or redness of the eye, which are typical symptoms of using the drops.
Cost and Availability Analysis
Depending on the region, the cost of the drug may be a significant barrier to accessing treatment.
Maxitrol
Maxitrol is a combination product, which can make it more expensive than simple drugs that contain only one active ingredient. However, in many cases, such combination products can be more beneficial because they eliminate the need to use several different drugs.
If the drug is reimbursed, the patient may be required to incur additional costs, depending on the reimbursement policy and the doctor’s recommendation.
Floxal
Floxal may be available in various forms (e.g. drops, ointment) and its price may be relatively lower than in the case of combined preparations, which makes it more accessible to patients who prefer monotherapy (one active substance).
Because Floxal is often used to treat bacterial infections, patients may use this medication more often, which may affect the overall cost of treatment in the long run.
Drug interactions
Maxitrol
Maxitrol contains both antibiotics and a steroid, so potential interactions may involve not only other medications but also the body’s own defense mechanisms. Because dexamethasone is a steroid, it may interact with immunosuppressive drugs such as methotrexate, cyclosporine, and antiviral drugs. Steroids can also alter the metabolism of other drugs.
Interactions with antidiabetic medications (e.g. insulin) may also occur because steroid use may raise blood glucose levels.
Floxal
Floxal (ofloxacin) is an antibiotic from the fluoroquinolone group, which may interact with other drugs. Chelators (e.g. drugs containing calcium, magnesium, iron, including antacids) may reduce the absorption of ofloxacin, which may reduce its effectiveness. It is recommended to use these drugs separately by at least 2 hours.
Other potential interactions include anticoagulant drugs (e.g. warfarin), as fluoroquinolones may increase the anticoagulant effect, which is associated with a risk of bleeding. It is also worth paying attention to interactions with drugs that may affect the renal excretion of ofloxacin, as this may change its concentration in the body.
Monitoring the patient during therapy
Maxitrol
Due to the presence of steroids, patients should be regularly monitored for the development of glaucoma or cataracts, especially with long-term use. The expected change in intraocular pressure may occur after several days or weeks of therapy.
For this reason, the patient’s doctor may recommend regular monitoring of the patient’s intraocular pressure (tonometry) and checking the vision in patients who use Maxitrol for a long time.
In addition, patients who use the drug for a long time should be monitored for possible secondary infections caused by excessive use of antibiotics in the preparation.
Floxal
In the case of Floxal, if the drug is used for a long time, it is important to monitor the patient for the growth of bacterial resistance. When using an antibiotic for a long time, it may happen that the bacteria become resistant to ofloxacin, which may require a change in therapy.
Ofloxacin can also cause hypersensitivity reactions, especially when used in people who are prone to allergic reactions. In this case, the patient should be monitored regularly for symptoms such as itching, skin rash, eye swelling, difficulty breathing, which may indicate an allergic reaction.
Safety of use in long-term therapies
Maxitrol
Long-term use of steroids, such as dexamethasone in Maxitrol, is associated with the risk of weakening the immune system, which can lead to infections. In addition, chronic use of steroids can lead to the development of increased intraocular pressure, cataracts, and skin atrophy in the areas where the drug is applied.
Although Maxitrol is mainly used for short-term treatments, especially for conjunctivitis and keratitis, the therapy should be monitored for the development of the mentioned complications.
Floxal
Floxal is intended for use in acute bacterial infections of the eye, but in long-term use it can lead to the development of bacterial resistance. This can reduce the effectiveness of treatment in the future. In addition, like any antibiotic, Floxal can disturb the balance of bacterial flora in the body, which can lead to fungal infections or other secondary infections.
Therefore, it is recommended that Floxal be used only when there is a clear need, and treatment should not last longer than a few days without consulting a doctor.
Impact on the patient’s quality of life
Maxitrol
Maxitrol is highly effective in treating inflammation and bacterial infections of the eye, but its steroid action is associated with some inconveniences. Due to potential side effects, such as high intraocular pressure, cataracts or the risk of infection, patients must be aware of the need for regular check-ups.
Long-term treatment may be associated with a decrease in the quality of life due to the need to monitor intraocular pressure , which involves frequent visits to the doctor and general caution in using the drug.
Floxal
Floxal is more targeted at treating specific bacterial infections and is relatively safe for short-term use. However, as with Maxitrol, improper use can lead to side effects such as eye irritation or allergic reactions that can affect the patient’s daily functioning, especially if side effects occur as a result of the medication.
Variation in clinical use
Maxitrol
In clinical practice, Maxitrol is preferred in cases where the infection is mixed (e.g. both bacterial and inflammatory), because it contains both an antibiotic and a steroid. It is particularly effective in treating inflammation accompanying bacterial infections of the eye.
Floxal
Floxal is more targeted at bacterial infections and is preferred when the cause of the problem is solely bacteria within the eye. It is the preferred choice for simple bacterial cases where there is no need for anti-inflammatory therapy.
Summary
The provisions on information about medicines for patients aim to ensure that the patient,having pharmaceutical knowledge, will receive appropriate information about the use of the drug.
Maxitrol is a multi-action drug (anti-inflammatory, antibacterial), but due to the presence of a steroid, its use requires caution, especially in the case of long-term treatment. Patients should be educated about the risk of glaucoma and other side effects associated with corticosteroids.
Floxal is a simpler drug (one antibiotic) that is preferred for treating acute bacterial eye infections, but it also carries the risk of developing bacterial resistance if not used as directed. It is worth paying attention to proper patient education regarding the full use of the drug.
Both Maxitrol and Floxal have their unique uses and advantages, but also challenges related to safety and efficacy. In the case of Maxitrol, the main issue is the control of side effects resulting from the steroid (e.g. glaucoma, cataracts, infections), while Floxal requires caution due to the possibility of developing bacterial resistance and the risk of eye irritation.
The regulations on information about a drug for a patient aim to ensure that a patient who does not have pharmaceutical knowledge receives appropriate information about the use of the drug.However, in practice, differences in the form of information presentation may occur, even when complying with regulatory requirements. Basic elements such as active substances, dosage, side effects, are fixed, but manufacturers may have some freedom in choosing the form of presentation of this information, which may affect the patient’s perception and effectiveness of the use of the drug. An important aspect is also the responsibility for reporting the leaflet to the regulatory authorities, which depends on the organizational structure of the company producing or distributing the drug. The basic goal of the regulations on information leaflets is to provide the patient with full, clear and understandable information about the drug they are using. The law in this area, both EU and national, imposes on drug manufacturers the obligation to provide such information that will help the patient to use the drug correctly, avoiding the risk of errors in therapy. In the context of drugs such as Maxitrol and Floxal, which have similar indications but differ in active substances, especially in relation to steroids in MAXITROL, it is crucial for the manufacturer to clearly indicate possible side effects, especially those that may affect the patient’s health, such as increased intraocular pressure. In relation to the registration and reporting process of leaflets, an important difference is the responsibility of the manufacturer or distributor, which may affect the way in which the documentation is prepared and verified.
