Selection of medications, interchangeability of medications. Is it legal to replace medications by the decision of an official? “On Amendments to the Federal Law

Rosa Yagudina on what needs to be taken into account in the issue of drug substitutability

CC dossier

Rosa Ismailovna Yagudina, Doctor of Pharmaceutical Sciences, Professor, Head. Department of Organization of Drug Supply and Pharmacoeconomics, Head. laboratory of pharmacoeconomic research of the First Moscow State Medical University named after. I. M. Sechenova (Moscow), editor-in-chief of the journals “Pharmacoeconomics” and “Modern organization of drug supply.”

Generics — this is relevant

Replacing the original drug with a generic, selecting analogues of drugs is a very common situation in the pharmacy. This happens both because the required drug is not on the shelf, and because the patient asks to replace the drug with a cheaper analogue. Generics help save money not only for patients, but also for the healthcare system as a whole. The price of a generic medicine can be almost 80 % lower than the cost of the original one. This has caused some countries to take a closer look at generic substitution issues. The USA, Canada, Germany, Great Britain and a number of other European Union countries have announced that increasing the share of generics in the overall structure of drug consumption is a strategic goal. Global consumption of generics is constantly growing. According to IMS Health, between 2005 and 2010 it grew from $124 billion to $234 billion. According to the company's forecasts, by 2015 the consumption of generics will almost double and amount to 400-430 billion US dollars.

In connection with this growing importance of generics, the question of whether in all cases the original drug can be replaced with a generic one without compromising the treatment process is particularly acute. There are a number of studies that show that in some cases, for certain drugs, such replacement is irrational. The question of the possibility of interchangeability of biotechnological drugs is even more pressing. In the next few years, patent protection for a number of biotechnological drugs will expire and their generic versions—biosimilars—will be introduced to the market (see publication « » in CC No. 3 (116), 2013, — approx. ed.). However, it is already known today that biosimilars are not always completely bioequivalent to the original drugs. At the same time, the issue of interchangeability of biotechnological drugs is relevant not only from the “original - biosimilar” perspective, but also between biosimilars themselves. In this regard, it is very important for practicing pharmacists and pharmacists to know on the basis of which documents and recommendations to make decisions when synonymously replacing biosimilars, as well as other drugs.

Interchangeability and substitutability of drugs - what is the difference

Replacing one drug with another can occur for various reasons and is described by different terms. Specifically, a physician may substitute one drug for another drug of the same class — this is a therapeutic substitution that can only be made by a medical professional. In a pharmacy, without consulting a doctor, one dosage form can be replaced with another, an original drug can be replaced with a generic, or one generic can be replaced with another within the same international nonproprietary name (INN). In all of these cases, the pharmacy specialist needs data on the interchangeability of the drug.

In foreign sources, interchangeability is understood as the medical or pharmaceutical practice of switching from one drug to another that is equivalent to it for the same indications. And the term substitution or substitutability refers to pharmacy practice and characterizes the replacement of one drug in a pharmacy with another equivalent and interchangeable drug without the requirement of consultation with the doctor who prescribed the drug. Legislative regulation of substitution varies in different countries.

In domestic practice, the concepts of interchangeability and substitutability are not legally established. Amendments to the Federal Law “On the Circulation of Medicines” are currently being prepared, including the introduction of the concept of an interchangeable medicinal product into the law. Today, the following interpretation of this term is proposed:

“An interchangeable medicinal product is a medicinal product with proven therapeutic equivalence in relation to the original medicinal product or, if it is not in circulation, in relation to the reference drug, used for the same indications, having the same qualitative and quantitative composition of active substances, as well as medicinal form, dosage and method of administration."

(Draft Federal Law

It should be noted that in the previous version of the amendments to the Federal Law “On the Circulation of Medicines” a slightly different interpretation of the concept of interchangeability was proposed:

“An interchangeable medicinal product is a medicinal product that is not a biological medicinal product, with proven therapeutic equivalence in relation to the original medicinal product or, if it is not in circulation, in relation to the reference drug, used for the same indications, having the same qualitative and quantitative composition of active ingredients, as well as dosage form, dosage and method of administration.”

(Draft Federal Law

“On Amendments to the Federal Law

“On the circulation of medicines”

It would seem that there is a slight difference in concepts. But in fact, this difference (meaning the exclusion of the possibility of interchangeability of biological drugs) is very important, including in the field of public procurement. Considering that many biological drugs are included in various financing programs and the state invests large amounts of money in providing the population with this group of drugs free of charge, this issue is at the center of active discussions in the pharmaceutical community.

Time will tell what the final conceptual framework in the law will be, but today it is possible to identify the key questions that face a pharmacy specialist if it is necessary to replace the original drug with a generic or biosimilar.

Interchangeability of drugs: generics and biosimilars

Two issues require separate consideration—the interchangeability of original drugs and generics, as well as original biotechnological drugs and biosimilars.

Generics

In Russia, a generic is a drug that has pharmaceutical (chemical) equivalence and bioequivalence (Federal Law No. 61 “On the Circulation of Medicines”). Pharmaceutical equivalence means that the generic is equivalent to the original drug in terms of the composition of active substances, the strength of action or concentration of active substances, the identity of dosage forms, and the method of administration. Bioequivalence means equivalence in pharmacokinetic parameters. Two drugs are considered bioequivalent if they have the same degree and rate of absorption, distribution and removal of the drug from the body.

It would seem that with pharmaceutical and biological equivalence, drugs should be identical in their effect on the patient. However, there are studies showing that this is not the case in all cases. For example, in 2000, a study was published by the authors S. V. Nedogoda, I. V. Marchenko, T. A. Chalyabi, which studied the clinical effectiveness of four generic enalaprils from well-known manufacturers. The study showed that the effectiveness of the study drugs in achieving the target blood pressure level was lower than that of the original drug, although all generics analyzed were bioequivalent to the original. As a result, a conclusion was made about the different therapeutic equivalence of the generic drugs - enalapril.

Because generic and brand-name drugs may have different therapeutic effects, in some countries not all generic drugs are considered interchangeable. For example, in the USA, since 1984, generics have been recognized as therapeutically equivalent only if they are pharmaceutically equivalent to each other and in equal doses have the same effect with equal severity of side effects in the same patients. The US Food and Drug Administration (FDA) annually publishes a list of approved drugs with proven therapeutic equivalence—the “Orange Book.” In this publication, not all medicines produced under the same INN are recognized as interchangeable. For example, according to the 32nd edition of the Orange Book (2012), fluconazole from several companies was not recognized as therapeutically equivalent, and therefore interchangeable. Generic drugs that the FDA recognizes as therapeutically equivalent to the brand-name drug are automatically considered interchangeable. However, some US states may have specific restrictions on substitution of drugs with a narrow therapeutic index, even if they are considered therapeutically equivalent in the Orange Book. For example, these are cardiac glycosides, immunosuppressants, antiepileptic drugs.

Today, in the countries of the European Union, the USA and other countries, the replacement of original drugs with generics is allowed. Moreover, in some EU countries, the healthcare system even provides for automatic replacement. It implies that if there is at least one generic drug in the pharmacy, the pharmacist is obliged to replace it with the original drug prescribed by the doctor. Some US states also have an automatic replacement system that takes into account the recommendations of the Orange Book.

Biosimilars

According to modern research, producing a biotechnological analogue that is completely similar to the original drug is quite difficult due to the fact that biotechnological drugs are very large molecules with a complex spatial configuration, and it is not always possible to accurately reproduce it. For this reason, it is recognized abroad that biosimilars and original drugs are not in all cases interchangeable and their replacement is carried out by a doctor, not a pharmacist: “Since a biosimilar is similar, but not identical to the original biotechnological drug, the decision to treat with a biosimilar should be made based on doctor’s opinion” — (European Medicines Agency. Q&A document EMEA/74 562/2006 (Rev. 1 22 October 2008)). The US Food and Drug Administration (FDA) recognizes a biosimilar as interchangeable if it is biosimilar to the originator drug; demonstrates similar results when used in any selected patient; shows the same level of safety and effectiveness as the original drug.

Obtaining permission to introduce a biosimilar to the pharmaceutical market does not guarantee interchangeability.

Today, to reduce costs, governments of many countries are interested in the widespread use of biosimilars in the treatment of patients. However, health system experts note that a possible reduction in costs should not yet serve as a reason to allow automatic replacement of original drugs with biosimilars in pharmacies. According to WHO, permission to automatically replace an original biotechnological drug with biosimilar drugs should be decided at the national level, taking into account the safety profile of the drug, as well as scientific and clinical data. In many countries, original biotechnological medicines and biosimilars are not interchangeable and are prescribed by trade name and not by INN (Great Britain, Holland, Poland, Denmark, Norway, Austria, Slovakia, France, etc.). Japan has legislation similar to European legislation regulating the circulation of biosimilar medicines and their interchangeability.

Today it is necessary to create guidelines in all countries of the world to determine the interchangeability of biosimilar medicines at the legislative level. In Russia it is also planned to create a similar document. In particular, it is planned to create a list of interchangeable medicines.

Generic (generic) (in Russian legislation this term corresponds to a synonymous concept - a reproduced medicinal product) - this is a medicinal product containing the same pharmaceutical substance or combination of the same pharmaceutical substances in the same dosage form as the original medicinal product and put into circulation after the original medicinal product goes into circulation (Federal Law No. 61 of April 12, 2010 “On the circulation of medicinal products”).

Original medicine— a medicinal product containing a pharmaceutical substance obtained for the first time or a new combination of pharmaceutical substances, the effectiveness and safety of which are confirmed by the results of preclinical studies of drugs and clinical studies of drugs (Federal Law No. 61 of April 12, 2010 “On the circulation of medicinal products”).

Biotechnological medicines- immunobiological medicinal products produced using genetic engineering (documents of the European Medicines Agency, EMA - European Medicines Agency). There is no definition of a biotechnological drug in Russian legislation. The law only contains a definition of immunobiological drugs.

Immunobiological medicinal products are medicinal products of biological origin intended for immunological diagnosis, prevention and treatment of diseases (Federal Law No. 61 of April 12, 2010 “On the circulation of medicinal products”).

Biosimilar— this is a biotechnological medicinal product similar to the original medicinal product produced for the first time and submitted for registration after the expiration of the patent of the original drug (European Union Directive 2003). The concept of biosimilar is currently absent in Russian legislation. However, the concept of biosimilar (biosimilar) is included in the text of the amendments.

Bioanalog (biosimilar) medicinal product (biosimilar)— a biological medicinal product that is similar to the original biological medicinal product in terms of production technology, pharmaceutical substance (combination of pharmaceutical substances), dosage form, indications for use and put into circulation in compliance with the intellectual rights to the original medicinal product (Draft Federal Law “On Amendments to the Federal Law”) Law “On the Circulation of Medicines” and Article 333.32.1. Part two of the Tax Code of the Russian Federation”).

Replacing a drug in a pharmacy

On July 1, 2013, Order of the Ministry of Health of the Russian Federation of December 20, 2012 No. 1175n “On approval of the procedure for prescribing and prescribing medicines, as well as prescription forms for medicines, the procedure for processing these forms, their recording and storage” comes into force. After this, doctors will only indicate INN in all prescriptions. What does this mean for pharmacy professionals?

After the order comes into force, pharmacy workers bear the responsibility for choosing a medicinal product within the framework of one INN. The pharmacist's recommendation will be one of the key factors when choosing a drug for the patient. In 2010, the research company Synovate Comcon published the results of a survey of patients, showing that among the factors influencing the choice of a drug by a pharmacy visitor, the recommendation of a pharmacy worker is in third place (after the doctor’s recommendation and the availability of discounts).

In 2011, the same company published a study on how pharmacists and pharmacists relate to original drugs and generics. The study showed that 89.7% of respondents believe that the original drug is always better than the generic because more research has been conducted on it. Only 8.7% of respondents reported that original drugs and generics act the same, since they were released under the same INN. Finally, 0.6% of respondents believe that the generic is better because it is cheaper.

Despite this attitude towards original drugs and generics, pharmacy staff are regularly faced with the need to recommend one or another generic drug. This happens when the required drug is not available in the pharmacy and when a particular drug is unaffordable for the patient. How should a pharmacy specialist proceed when choosing the right drug?

Step 1. Recipe examination. First of all, a specialist must examine the recipe. If the prescription is filled out incorrectly, it remains in the pharmacy and is canceled with the stamp “Prescription is invalid.” Also, the pharmacy specialist checks the compatibility, dosage and dosage form of the drug in accordance with the principles of pharmacology, pharmaceutical technology and pharmaceutical chemistry.

Step 2. Dispensing the drug. Next steps depend on how the prescription was written. If it indicates a specific drug, then the pharmacy specialist can only dispense this drug or, in the absence of the required drug, offer a synonymous replacement, a different dosage form or a drug with a different dosage. Dispensing is carried out with mandatory consultation of the patient about the rules for taking the medicine. On the back of the prescription you should indicate the trade name of the drug dispensed, sign and date of dispensing.

If the patient has brought a prescription in which the INN is indicated, the pharmacist must offer him a choice of available synonymous drugs. In this case, several principles need to be taken into account.

Firstly, when choosing one of the synonyms, a situation may arise when the patient purchases a drug with a different dosage. In this case, he must be warned how to take the drug in order to comply with the dosage prescribed by the doctor.

Secondly, when recommending a particular drug, it is necessary to take into account the patient’s ability to pay. If it is necessary for him to purchase a drug at the lowest possible price, then it is advisable to conduct an express assessment of the cost of synonyms and offer the patient the drug whose course of treatment will cost the least.

Thirdly, if the patient has no preference in choosing from several drugs with the same composition, release form, dosage and minor differences in price, then priority is given to the drug that the patient took previously (for a chronic disease), or the drug that lasts longer others are on the pharmaceutical market and have proven their effectiveness and safety in everyday practice.

When choosing a particular drug, a pharmacy specialist may encounter pitfalls. In particular, care must be taken when recommending “pharmaceutical alternatives” (as defined by the FDA) — drugs that contain the same therapeutic components but differ in the form of salts, esters, or complexes of these components. They can have different dosages and strengths. Pharmaceutical alternatives also include slow-release drugs as compared to accelerated or "normal" release drugs.

“Alternatives” can have different effects on the patient’s body, so the pharmacist must not only know, but also take into account the indications and contraindications of such drugs. For example, sodium, potassium and procaine salts have the same pharmacological action, pharmacokinetics, indications for use, interaction and dosage regimen. However, they differ in dosage, side effects and contraindications. For example, the sodium salt is contraindicated for epilepsy (for endolumbar administration), the potassium salt is contraindicated for hyperkalemia, arrhythmia, and the procaine salt has no such contraindications.

To ensure complete safety of patients when replacing drugs in a pharmacy, it is important to develop recommendations for the interchangeability of drugs. In addition, a qualified and responsible approach of pharmacy specialists to counseling patients is of fundamental importance, which is becoming even more important with the introduction of prescribing by international nonproprietary name.

The article was written based on materials:

Yagudina R. I., Arinina E. E., Kondratyeva B. B. “Interchangeability and substitutability of medicines” // “Modern organization of drug supply” No. 1/2013

Cardiomagnyl is a drug that is often prescribed in cardiological and neurological practice to prevent certain diseases and prevent their complications. Let's take a closer look at what are the indications for the use of Cardiomagnyl, and what analogs of it can be recommended if taking this drug is impossible.

The drug Cardiomagnyl is a combination of acetylsalicylic acid and magnesium hydroxide. It is prescribed for primary and secondary prevention of thrombus formation in blood vessels in the following cases:

• cardiovascular diseases accompanied by increased platelet aggregation (thrombosis and acute heart failure) in the presence of risk factors - obesity, hyperlipidemia, arterial hypertension, smoking, old age;
• ischemic type cerebrovascular accidents;
• unstable angina;
• postoperative period after surgical interventions on the heart and blood vessels (including after coronary artery bypass grafting and percutaneous transluminal coronary angioplasty).

Analogues of the drug Cardiomagnyl

Acetylsalicylic acid, which is the main active ingredient of the drug, has analgesic, antipyretic, anti-inflammatory and antiplatelet effects. This is the only antiplatelet drug whose effectiveness when prescribed in the acute phase of ischemic stroke is confirmed by evidence-based medicine.

This substance is part of many other drugs that are recommended for the same indications as Cardiomagnyl. Their main difference from Cardiomagnyl is the absence of magnesium hydroxide, a substance that helps prevent the destruction of the walls of the digestive tract by acetylsalicylic acid. It is this component that increases the safety of Cardiomagnyl with regard to negative effects from the gastrointestinal tract.

However, doctors may recommend other drugs based on acetylsalicylic acid as cheaper analogues of Cardiomagnyl or for other reasons. First of all, analogues of the drug include Aspirin and Acetylsalicylic acid.

Also similar drugs are:

• Aspicor;CardiASK;
• Thrombo ACC;
• Thrombopol et al.

The listed products are available in the form of enteric-coated tablets. After taking these drugs, acetylsalicylic acid is absorbed in the upper part of the small intestine, that is, the release of acetylsalicylic acid in the stomach does not occur, thereby eliminating the risk of damage to the stomach walls.

Cardiomagnyl - analogues without aspirin (acetylsalicylic acid)

In cases where the use of acetylsalicylic acid is contraindicated, the attending physician prescribes other drugs that have antiplatelet properties. They also reduce coagulability and improve the rheological properties of blood, preventing the formation of blood clots in blood vessels. Let's look at a few similar medicines.

Tiklid

A drug whose active ingredient is ticlopidine. This is a new drug, characterized by a selective effect and superior in effect to acetylsalicylic acid.

Trental

A modern medicine based on pentoxifylline, which is often prescribed to patients with circulatory disorders in the vertebrobasilar system and for other treatments. The drug dilates the coronary arteries, increases the tone of the respiratory muscles, reduces blood viscosity, etc.

Clopidogrel

A medicine containing clopidogrel bisulfate. In some cases, the drug is prescribed in combination with acetylsalicylic acid to enhance the antiplatelet effect.