Plaquenil: instructions for use, reviews on forums, price, analogues, treatment of coronavirus

pharmachologic effect

Plaquenil has the following effects:

Antiprotozoal - suppress the vital activity of protozoa that cause infectious diseases. First of all, this concerns pathogens of malaria , so the main effect of the drug is antimalarial.
Immunosuppressive – suppresses an overreaction of the immune system, including allergies to the patient’s own tissues.
Anti-inflammatory – suppresses inflammatory reactions.

Pharmacodynamics and pharmacokinetics

Plaquenil belongs to the group of antimalarial and immunosuppressive drugs from the group of 4-aminoquinoline . The mechanism of its action is not well understood, but it is believed that it is associated with the following properties of this drug:

The ability to suppress the action of toxic free radicals formed during metabolism (antioxidant effect).
The ability to suppress the action of enzymes that cause the breakdown of cartilage tissue.
The ability to suppress the synthesis of prostaglandins - biologically active substances involved in inflammatory processes.
The ability to concentrate in leukocytes and strengthen the membranes of lysosomes - cell structures containing enzymes that can break down nutrients entering the cell. Lysosomes are also involved in the digestion of bacteria captured by leukocytes.
The ability to suppress the synthesis of those types of cytokines (hormone-like proteins synthesized by cells to influence other cells) that activate the immune system. This also helps to reduce autoimmune processes (destruction of the body’s own tissues by immune processes).
The ability to suppress the activity of lymphocytes involved in immune reactions.
The ability to suppress the formation of rheumatoid factor - immunoglobulins (antibodies) that perceive the body's own tissues as foreign structures ( antigens ) and destroy them.
The antimalarial properties of Plaquenil consist in suppressing the vital activity of pathogens of tertian malaria , quartan malaria, malaria ovale, as well as forms of tropical malaria pathogens that are sensitive to it (most pathogens of tropical malaria are insensitive to Plaquenil).

After taking a Plaquenil tablet, its active substance is quickly and almost completely absorbed and enters the blood, and then accumulates in high concentrations in various organs and tissues. The maximum concentration of the active substance in the blood plasma is achieved within approximately 100 minutes. The drug is decomposed in the liver into active and inactive metabolic products ( metabolites ) and is excreted in the urine, but partially also in feces. The active substance Plaquenil crosses the placenta and is excreted in human milk. The drug is excreted slowly; it disappears from the blood plasma no earlier than after a month.

Genetically engineered drugs: addition to basic therapy

monoclonal antibodies has provided new insight into the treatment of autoimmune diseases [11]. A fundamentally new class of drugs has been obtained thanks to the achievements of genetic engineering. To understand the mechanism of action of these drugs, it is worth remembering how immune cells work in health and disease [1], [12].

The immune system is a complex mechanism consisting of many “cogs” - immune cells. Each of them has its own functions and occupies a certain place in the overall structure of the protective system. In response to the arrival of an “enemy” agent (antigen), components of the innate immune system—nonspecific protective factors—are activated. These are neutrophils, eosinophils and basophils, which are the first to stand in the way of harmful effects.

TNF inhibitors

Tumor necrosis factor inhibitors are the first monoclonal antibodies introduced into rheumatological practice. This group includes infliximab, etanercept, certolizumab, golimumab, adalimumab.

Tumor necrosis factor ( TNF ) is a pro-inflammatory cytokine (a substance that stimulates the development of an inflammatory response). Normally, when it is released, vascular cell proliferation, macrophage activation, and lysis of tumor agents occur. These effects play an important role in protecting the body from pathogens. Inflammation can be considered a response to damaging factors.

However, the effect of TNF on joints in rheumatic diseases cannot be called positive. Thus, in rheumatoid arthritis, the cytokine stimulates the proliferation of synovial fibroblasts - cells of the joint lining. This leads to the formation of pannus - growths of aggressive tissue. As the disease progresses, the process of inflammation and destruction spreads to the articular cartilage and underlying bones (Fig. 5). The joint tissues are filled with immune cells - macrophages, T- and B-lymphocytes, neutrophils. These mechanisms underlie the development of chronic inflammation. You can refresh your knowledge about the pathogenesis of rheumatoid arthritis in the article “Rheumatoid arthritis: change the composition of the joints” [3].

Figure 5. Pathological changes in the joint in rheumatoid arthritis. The autoimmune process causes erosions, synovitis (inflammation of the synovial membrane), and destruction of articular cartilage.

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One of the TNF inhibitors is the drug infliximab. It has "human" and "mouse" areas. Approximately 25% of all amino acids in the monoclonal antibody are derived from mice. This is a Fab fragment - a specific region responsible for binding to TNF. The Fc fragment of the protein is formed from IgG1, a human antibody.

This structure is associated with the mechanism for obtaining the drug. Initially, an antibody to tumor necrosis factor is synthesized in the mouse. The resulting immunoglobulin is specific to TNF and can already neutralize it, but completely foreign proteins, of course, cannot be introduced into the patient’s body. This will cause an active immune reaction - the production of antibodies against therapeutic agents. Therefore, mouse immunoglobulin domains are replaced with similar regions of human proteins. Antibodies that have fragments of different origins are called chimeric. In fact, they take the best qualities of their predecessors. The mouse part provides high sensitivity to TNF, and the human fragments reduce immunogenicity - the likelihood of developing an immune response.

The mechanism of action of infliximab is clear from its structure. The Fab fragment of the molecule binds tumor necrosis factor, forming a stable complex with it. This interaction completely blocks the activity of the cytokine, preventing its connection with the membrane receptors p55 and p57. Infliximab “neutralizes” both soluble and membrane-associated forms of TNF (Fig. 6). The content of other pro-inflammatory factors, such as IL-1, IL-6, and nitrogen monoxide, also decreases in joint cells.

Figure 6. Main effects of TNF and monoclonal antibodies blocking it (infliximab and etanercept). The targets for monoclonal antibodies are free and membrane-associated forms of tumor necrosis factor. The drugs prevent the cytokine from binding to the receptor, thereby reducing the activity of rheumatoid arthritis.

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Another effective drug from the group of TNF inhibitors, etanercept, . It contains the extracellular part of the receptor for tumor necrosis factor. It “connects” to human IgG1. The hybrid molecule enters into fierce competition for free TNF and neutralizes it before the cytokine has time to contact receptors and trigger an inflammatory response. An additional effect of etanercept that other TNF inhibitors do not have is the neutralization of lymphotoxin. This substance also belongs to pro-inflammatory cytokines. The production of lymphotoxin stimulates proliferative processes in the joints. Accordingly, blocking its action reduces the activity of inflammation in rheumatological diseases [18].

TNF inhibitors have shown good results not only in the treatment of rheumatoid arthritis, but also in other autoimmune pathologies. For example, new drugs are widely used in patients with ankylosing spondylitis. Slowing the progression of pathology in this case is very important, since auto-aggression is aimed at the joint and bone formations of the spine. Over time, the disease turns the spinal column into a “bamboo stick” - a monolithic, rigid formation. Ankylosis develops gradually, but inevitably. Every year the motor abilities of patients become more and more limited. The use of biological drugs can reduce the activity of inflammation in the spine. This slows down the process of ankylosis formation [19].

Interleukin receptor blockers

Interleukins play an important role in the development of autoimmune inflammation , which, like TNF, are proinflammatory cytokines (Fig. 7). The main representatives of this group are IL-6, IL-1, IL-17. The function of interleukins is the control of the processes of differentiation, proliferation and death (apoptosis) of immune cells, which is carried out through the corresponding target genes [20].

Figure 7. The mechanism of action of interleukins in autoimmune inflammation (using the example of IL-6). The cytokine affects T- and B-lymphocytes, hematopoietic cells, and hepatocytes. It stimulates the production of autoantibodies by B cells, as well as the formation of autoreactive T clones, which are directly involved in the autoimmune process. The effect on the bone marrow is to stimulate the production of new blood cells - the number of leukocytes and platelets increases. Inflammation is accompanied by a response of liver cells, the appearance of characteristic symptoms of an autoimmune disease.

[21]

The influence of interleukins is one of the “triggers” of the inflammatory process. Therefore, blocking their activity improves the condition of patients with autoimmune diseases. You can stop the work of interleukins by binding their receptors - molecules that transmit a signal to immune cells. This is the basis of the mechanism of action of monoclonal antibodies from the group of interleukin receptor inhibitors.

Tocilizumab is a drug that blocks IL-6. The receptor for this substance consists of two components: membrane IL-6R (α chain) and glycoprotein g130 (β chain). The membrane part of the receptor binds to IL-6, forming a stable complex. Together they activate the g130 component, causing a change in its structure (homodimerization). A receptor complex of two g130 molecules is formed, which in turn activates JAK1 kinase. This enzyme triggers a cascade of reactions in the cell, which leads to the appearance of the biological effect of the cytokine - the development of inflammation. In some cases, IL-6 binds not the membrane, but the soluble form of the α-chain (Fig. 8). The mechanism of action of the receptor does not change in this case [21].

Tocilizumab works by competitive inhibition. Signaling molecules actively bind to the monoclonal antibody. The vacant place is filled - interleukin cannot form a complex with the receptor, which means it is not able to activate the inflammation process.

Figure 8. Mechanism of action of tocilizumab. The drug binds soluble and membrane IL-6 receptors, blocking signal transmission.

"Modern targets for targeted therapy of rheumatoid arthritis: from monoclonal antibodies to signal molecule blockers"

Tocilizumab is considered one of the safest drugs in the group of monoclonal antibodies. This allows it to be used for juvenile idiopathic arthritis, which occurs before the age of 16 years. Children react particularly acutely to toxic effects, so the drugs used in their treatment should have a minimum number of adverse reactions. The use of tocilizumab allows one to achieve the desired treatment effect without causing severe complications.

Anti-B cell therapy

One of the main elements involved in autoimmune inflammation are B lymphocytes . They produce autoantibodies that bind to healthy cells in the body. The resulting complex of antibody and autoantigen attacks the complement system or cytotoxic lymphocytes. This process underlies the inflammatory response in rheumatic diseases such as systemic lupus erythematosus. A separate article on “Biomolecule” is devoted to it: “Systemic lupus erythematosus: a disease with a thousand faces” [2].

Anti-B cell therapy drugs ( rituximab and belimumab ) block the activity of B cells by binding to their membrane CD20 molecules. Only certain categories of B cells have these substances. They are specific for pre-B lymphocytes and mature B lymphocytes. CD20 is not present in stem elements and pro-B cells, from which new lymphocytic elements will be formed. Membrane molecules of this type are not found in plasma cells that produce immunoglobulins [22].

Thanks to this feature, the CD20 protein is an ideal “victim” for biological drugs. When its activity is “turned off,” neither the formation of new lymphocytes nor the production of normal antibodies is disrupted. One drug with this mechanism of action is rituximab. The monoclonal antibody binds to the CD20 molecule. This leads to the launch of immunological reactions in relation to B-lymphocytes, which ensure the destruction (lysis) of these cells (Fig. 9).

Figure 9. Mechanism of action of rituximab. The Fab fragment of the monoclonal antibody binds to CD20 on the surface of the B lymphocyte. This triggers cell lysis, which can occur in several ways: through the complement system, the apoptosis program, or the aggression of natural killer cells and macrophages.

"Modern targets for targeted therapy of rheumatoid arthritis: from monoclonal antibodies to signal molecule blockers"

Anti-T cell therapy

Blocking the action of T-lymphocytes is possible due to the peculiarities of their activation. In order for a T lymphocyte to enter the autoimmune process and bind to an antigen, it must receive two signals from antigen presenting cells (APCs). The first signal ensures recognition of a specific autoantigen by T-cell receptors. The second signal is a nonspecific process of binding of membrane molecules CD80 and CD86 on the surface of APC with the CD28 receptor of the lymphocyte. The combination of these interactions causes activation of T cells, which in turn stimulate the production of proinflammatory cytokines. This is the main contribution of T lymphocytes to the autoimmune process.

Knowledge of the mechanism of T cell activation was used in the development of monoclonal antibodies. The main representative of anti-T-cell agents is abatacept . The drug is a protein consisting of two parts. The specific part is formed by the CTLA-4 molecule (cytotoxic lymphocyte antigen 4). The nonspecific region is the Fc fragment of human immunoglobulin G1 [23].

The effect of abatacept is aimed precisely at a nonspecific (costimulatory) signal. The CTLA-4 component binds the CD80 and CD86 proteins on the surface of antigen-presenting cells. The CD28 lymphocyte receptor can no longer interact with them, which is why the activation of the T cell is not completed (Fig. 10).

Figure 10. Mechanism of action of abatacept. Abatacept modulates the immune response through binding to CD80/CD86 on antigen presenting cells. This prevents CD80/CD86 from binding to CD28 T cells, i.e. T cell activation is abolished through blocking costimulation.

"Modern targets for targeted therapy of rheumatoid arthritis: from monoclonal antibodies to signal molecule blockers"

Indications for use of Plaquenil

Due to the fact that Plaquenil suppresses immune (including autoimmune) and inflammatory reactions, it is used to treat:

rheumatoid arthritis;
juvenile rheumatoid arthritis;
systemic lupus erythematosus;
discoid lupus erythematosus.

Plaquenil is used to treat and prevent acute attacks of three-day malaria, four-day malaria, malaria ovale, as well as tropical malaria caused by strains of malarial plasmodium . Plaquenil is also used for the purpose of complete cure for tropical malaria caused by strains of malarial plasmodium sensitive to this drug.

Doctors have expressed conflicting opinions about the possible therapeutic effectiveness of Plaquenil for coronavirus infection COVID-19 . The French doctor Didier Rault conducted a study in which patients taking Plaquenil had a greatly reduced viral load after 6 days of treatment. When Plaquenil is taken in combination with Azithromycin, an increase in antiviral effect is observed. However, medical experts talk about the possibility of serious side effects and prohibit taking medications with hydroxychloroquine without a doctor’s prescription or for preventive purposes.

Why is it necessary to look for new treatments?

A wide range of antirheumatic drugs are used to treat autoimmune diseases. Classical therapy includes nonsteroidal anti-inflammatory drugs, glucocorticoids, and cytostatics. Depending on the characteristics of the development of the disease, drugs from one or another group are selected [4].

Medicines used for rheumatic diseases

Major immunosuppressants:
antibiotics (cyclosporine, tacrolimus);
antimetabolites (methotrexate, azathioprine, mercaptopurine);
cytostatics (cyclophosphamide).
Minor immunosuppressants:
cuprenil;
gold preparations (auronofin);
heparin;
non-steroidal anti-inflammatory drugs.

Let's figure out why new drugs are needed. As an example, we can consider the classical therapy of one of the most common autoimmune diseases - rheumatoid arthritis [3]. Modern strategies to combat this pathology must comply with the concept of Treat to target - “treatment until the goal is achieved.” It is aimed at remission (disappearance of symptoms) of the disease or a sharp decrease in the activity of arthritis [5], [6].

The “gold standard” in treating the disease is methotrexate (Fig. 2). The drug belongs to the group of basic anti-inflammatory drugs.

Figure 2. Structural formulas of methotrexate and folic acid. The drug ( a ) is similar in structure to folic acid ( b ). It consists of pteridine groups and para-aminobenzoic acid. The active component of methotrexate differs from the structure of folate in the absence of a hydroxyl group (–OH) and the presence of an additional methyl radical (–CH3).

"Wikipedia"

According to the mechanism of action, methotrexate is an antimetabolite. Drugs in this group inhibit physiological reactions in the body by binding to enzymes and turning off their activity. A substance that normally participates in the reaction can no longer enter the biochemical cycle due to increased competition with the components of the drug. The main target for the action of methotrexate is the enzyme that breaks down folic acid, dihydrofolate reductase ( DHF ). This protein acts on the folate entering the body, converting it into its active form. This produces tetrahydrofolic acid. They are involved in the synthesis of building materials for DNA - purine bases and thymidylate.

Methotrexate enters the chain of reactions due to its structural similarity to the folic acid molecule (Fig. 2). Competition for the enzyme leads to the fact that the content of active folate in the tissue is significantly reduced. There is no building material - there are no new DNA molecules, without which cells cannot reproduce. Those tissues whose structural elements are constantly dividing have increased sensitivity to the effects of the drug. These also include bone marrow components from which future immune cells are formed.

Another important point in the work of methotrexate is related to the activity of its polyglutamated metabolites. These molecules are formed after activation of the drug directly in the cells of the human body. They inhibit other enzymes that interact with folic acid. This group includes thymidyl synthetase and AICAR transamylase. The activity of methotrexate derivatives triggers the production of adenosine. It has a powerful anti-inflammatory effect, which reduces the severity of symptoms of rheumatoid arthritis [7].

Methotrexate is convenient to use - it is easily dosed and can be prescribed in long courses. In addition, an important advantage of this drug is its low price, in comparison with modern drugs from imported pharmaceutical companies [8]. Despite all the advantages, treatment with methotrexate does not always lead to a decrease in disease activity. In many patients, the use of the drug is ineffective even in combination with other classical drugs [5]. This is confirmed by analyzing statistics. Studies have shown that when treated with methotrexate and combinations of disease-modifying drugs, only half of patients achieved remission [9], [10].

The failure of classical therapy forces scientists to look for new ways to treat rheumatoid arthritis. It is worth noting that, despite new developments, the fight against the disease still begins with the prescription of methotrexate and its analogues. Additional drugs are used only when the autoimmune process is highly active. In such patients, the use of one drug is often ineffective [7]. Depending on the characteristics of the pathology, a suitable treatment regimen is selected (Fig. 3).

Figure 3. Management tactics for a patient with rheumatoid arthritis when methotrexate is ineffective.

“Pharmacotherapy of rheumatoid arthritis from the perspective of evidence-based medicine: new recommendations”

The ineffectiveness of basic therapy drugs occurs not only in rheumatoid arthritis, but also in other diseases of autoimmune origin (systemic lupus erythematosus, scleroderma, ankylosing spondylitis). This motivates rheumatology specialists to develop other drugs and select new treatment regimens.

Plaquenil - contraindications for use

Plaquenil is contraindicated:

with increased sensitivity to its components in the patient’s body;
with hereditary intolerance to certain types of simple sugars (for example, with lactase deficiency ) and with malabsorption syndrome (insufficient absorption of one or more nutrients in the intestine);
for eye diseases associated with retinal changes ( retinopathy );
children under 6 years old;
during pregnancy and breastfeeding .

The drug is used with caution when:

visual impairments, as well as when using medications that have a negative effect on the visual organs;
blood diseases (including in the past);
severe neurological diseases and psychoses (including in the past);
increased skin sensitivity to light, psoriasis and taking medications that increase skin reactions;
severe diseases of the liver and kidneys and taking medications that negatively affect these organs;
severe diseases of the digestive system;
hypersensitivity to quinine (due to the possibility of cross-allergic reactions).

Literature

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Systemic lupus erythematosus: a disease with a thousand faces;
Rheumatoid arthritis: change the composition of the joints;
Nasonov E.L., Alexandrova E.N., Novikov A.A. (2015). Autoimmune rheumatic diseases - problems of immunopathology and personalized therapy. Bulletin of the Russian Academy of Medical Sciences. 2, 169–182;
Babaeva A.R., Kalinina E.V., Zvonorenko M.S. (2016). New opportunities to improve the effectiveness and safety of treatment of rheumatoid arthritis. Medical alphabet. 22, 5–12;
Josef S Smolen, Robert Landewé, Ferdinand C Breedveld, Maya Buch, Gerd Burmester, et. al.. (2014). EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis
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Nasonov E.L. (2015). Methotrexate for rheumatoid arthritis - 2015: new facts and ideas. Scientific and practical rheumatology. 4, 421–433;
Kanevskaya M.Z. and Gurskaya S.V. (2013). Methotrexate in the treatment of rheumatic diseases. Modern rheumatology. 4, 47–53;
D. T. Felson, J. S. Smolen, G. Wells, B. Zhang, L. H. D. van Tuyl, et. al.. (2011). American College of Rheumatology/European League Against Rheumatism Provisional Definition of Remission in Rheumatoid Arthritis for Clinical Trials. Annals of the Rheumatic Diseases
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Patrick Durez, Jacques Malghem, Adrien Nzeusseu Toukap, Geneviève Depresseux, Bernard R. Lauwerys, et. al.. (2007). Treatment of early rheumatoid arthritis: A randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone. Arthritis Rheum
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Monoclonal antibodies;
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Autophagy, protophagy and others;
Nobel Prize in Medicine or Physiology 2021: for self-criticism;
Zaichik A.M., Poletaev A.B., Churilov L.P. (2013). Recognition of “One’s own” and interaction with “One’s own” as the main form of activity of the adaptive immune system. Bulletin of St. Petersburg State University. Episode 11. Medicine. 1;
Autoimmunity. Modern views on the physiological and pathological aspects of autoimmunity. NSU Electronic Archive;
For the first time in half a century, there is a new drug for lupus;
Nasonov E.L. and Karateev D.E. (2013). The use of genetically engineered biological drugs for the treatment of rheumatoid arthritis: general characteristics (lecture). Scientific and practical rheumatology. 2, 163–169;
Logvinenko S.I., Shcherban E.A., Pridachina L.S., Pridachina A.N., Maslova Yu.Yu., Kashichkina A.A. (2016). Genetic engineering in the treatment of ankylosing spondylitis (Bechterew's disease). Scientific bulletins of BelSU. Series: Medicine. Pharmacy. 19, 179–182;
Masahiko Mihara, Misato Hashizume, Hiroto Yoshida, Miho Suzuki, Masashi Shiina. (2012). IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin.
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Nasonov E.L., Alexandrova E.N., Avdeeva A.S., Panasyuk E.Yu. (2013). Inhibition of interleukin 6 - new possibilities for pharmacotherapy of immunoinflammatory rheumatic diseases. Scientific and practical rheumatology. 4, 416–427;
Suponitskaya E.V., Alexandrova E.N., Aleksankin A.P., Nasonov E.L. (2015). The effect of therapy with genetically engineered biological drugs on B-lymphocyte subpopulations in rheumatic diseases: new data. Scientific and practical rheumatology. 1, 78–83;
Babaeva A.R., Cherevkova E.V., Galchenko O.E., Solodenkova K.S. (2012). Biological agents in the basic therapy of rheumatoid arthritis. Medicinal Bulletin. 7, 3–9;
Muravyov Yu.V. and Muravyova L.A. (2016). Untimely thoughts on the use of genetically engineered biological drugs for rheumatic diseases. Scientific and practical rheumatology. 3, 361–366;
Psoriasis: at war with your own skin.

Side effects of Plaquenil

Side effects of Plaquenil are related to the mechanism of its main action.

From the senses - with long-term use of the drug, changes in the retina (visual field defects - scotomas ), cornea ( blurred vision , photophobia ), as well as disturbances in accommodation (the ability of the eye to clearly see objects located near or far), tinnitus, decreased hearing
From the nervous system - dizziness , headache , irritable weakness, muscle weakness , gait disturbances, psychosis, convulsive readiness.
From the circulatory system - a toxic effect on the heart muscle ( myocardium ), accompanied by conduction disturbances ( heart block ) or an increase in the volume of the myocardium of both ventricles.
On the part of the hematopoietic organs - suppression of the process of formation of blood cells in the bone marrow and the development of a lack of red blood cells (various types of anemia ), leukocytes (the protective properties of the body are reduced) and platelets bleeding appears ).
From the digestive system - nausea, vomiting, diarrhea, loss of appetite, abdominal pain. With long-term use in large doses, the drug can have a toxic effect on the liver, leading to the development of liver failure .
Side effects of Plaquenil on the skin and mucous membranes are the most common. These are various kinds of rashes, increased skin sensitivity to light, changes in skin and hair pigmentation, skin itching , baldness , exacerbation of various skin diseases, primarily psoriasis . Severe delayed allergic reactions are possible in the form of Stevens-Johnson syndrome (blisters can cover the entire skin and mucous membranes) and the development of acute generalized exanthematous pustulosis (AGEP) in the form of pustules covering the entire skin.
Allergic reactions - urticaria , Quincke's edema , bronchospasm .

Overdose

Symptoms of overdose may include headache, blurred vision, cardiovascular collapse, seizures, hypokalemia, rhythm and conduction disturbances including prolongation of the QT interval, ventricular tachycardia torsade de pointes, ventricular tachycardia and ventricular fibrillation, increased QRS width, bradyarrhythmias, junctional rhythm , AV blockade, which sometimes causes sudden and fatal respiratory and cardiac arrest. These effects may occur soon after an overdose and require immediate medical attention. The contents of the stomach must be removed immediately by inducing vomiting or gastric lavage. Activated charcoal at a dose of at least five times the dose taken may slow further absorption of the drug if activated charcoal is administered into the stomach through a tube after lavage and no later than 30 minutes after taking the drug.

In case of overdose, parenteral administration of diazepam should be considered. It has been proven that this drug can reduce the effects of cardiotoxicity caused by chloroquine.

Instructions for Plaquenil

The instructions for use of Plaquenil provide for its use only as prescribed by a doctor. Plaquenil tablets are taken orally, with meals or with a glass of milk.

In the treatment of rheumatoid arthritis and systemic lupus erythematosus, the therapeutic effect of using Plaquenil develops after several weeks or even months (the drug gradually accumulates in the body), while side effects can appear much earlier. Therefore, the doctor must decide whether to continue treatment with this drug and in what dosage. In any case, the doctor selects an individual effective dosage of the drug (it is 6.5 mg per kg of body weight or 1 - 2 tablets per day). If the therapeutic effect cannot be achieved within six months, then Plaquenil is discontinued.

To prevent malaria, the drug should be taken two weeks before leaving for an area where this disease occurs. It is taken once a week on the same day, 2 tablets (400 mg) during the entire stay in the endemic zone and for another two months after leaving it.

To treat acute attacks of malaria, first take 4 tablets of Plaquenil (800 mg), after 8 hours - 2 tablets (400 mg) and in the next 2 days - 2 tablets (400 mg).

To completely cure tropical malaria (if the pathogen is sensitive to the drug), taking Plaquenil is combined with taking medications belonging to the group of 8-aminoquinoline ( Plasmocide , Plasmoquine , Quinocidum , Primaquine ).

Features of application

Pregnant

The use of hydroxychloroquine sulfate should be avoided during pregnancy unless, in the judgment of a physician, the individual potential benefits of such treatment outweigh the potential risks.

Children

It is necessary to use a minimum effective dose not exceeding 6.5 mg per 1 kg of ideal body weight per day. Therefore, 200 mg tablets are not suitable for use in children with an ideal body weight of less than 31 kg.

Drivers

Carefully

Interaction of Plaquenil with other drugs

Plaquenil can be combined with glucocorticosteroids (GCS), for example Prednisolone , non-steroidal anti-inflammatory drugs (NSAIDs), for example Diclofenac , Ibuprofen , Methotrexate .

Plaquenil enhances (potentiates) the effect of: the cardiac glycoside Digoxin , Insulin and other drugs for the treatment of diabetes, antibiotics from the aminoglycoside ( Neomycin , Gentamicin ).

When taking an H2-antihistamine to reduce the acidity of gastric juice, Cimetidine, the decomposition process of Plaquenil in the liver is suppressed and its concentration in the blood plasma increases. This increases the risk of side effects and overdose.

Antacids - drugs that neutralize the effect of hydrochloric acid in the stomach (for example, Almagel ) help reduce the absorption of Plaquenil. To prevent this from happening, it is recommended to maintain intervals between doses of these drugs of at least 4 hours.

Plaquenil reduces the effectiveness of Proserin, as it is its antagonist.

When using Plaquenil, there is a decrease in the formation of antibodies in response to the administration of human diploid cell rabies .

Not everything is so simple: possible problems when using monoclonal antibodies

Monoclonal antibody preparations have been used in rheumatological practice for quite some time. However, they are not prescribed to everyone - not to every first or even every second patient. The main limitation that doctors and patients face is the truly “exorbitant” cost of drugs in this group. Rheumatic diseases cannot be cured in a week or a month - they require many years (or even lifelong) use of therapy. Therefore, when selecting a drug, not only its effectiveness is important, but also its price.

For example, one pack of methotrexate costs approximately 200 rubles. The price of a package of infliximab is about 43 thousand rubles. The difference is obvious. For a year of treatment with methotrexate, even at the maximum dosage, the patient will spend 1–2 thousand rubles on the medicine (depending on the manufacturer, treatment regimen and the cost of the drug in local pharmacies). The price of annual therapy with infliximab is approximately 700 thousand rubles. It is clear that only a very limited group of patients will be able to provide themselves with this medicine.

Therefore, treatment of rheumatic diseases is carried out according to strict algorithms. If a pathology is detected, the patient is prescribed a basic drug. For example, for rheumatoid arthritis, methotrexate will most likely be the main drug. Doctors will add monoclonal antibodies to the standard treatment regimen only in exceptional cases. In Russia, they are considered reserve drugs—additional drugs that should be “left for later,” even despite their high effectiveness. So, if the severity of symptoms does not decrease for a long time (at least 6 months!), a biological drug can be added to methotrexate. Basic therapy is not canceled.

If the disease is initially highly active, progresses rapidly and is accompanied by extra-articular complications, then the patient can immediately be prescribed a combination treatment with basic drugs and monoclonal antibodies. This is due to the fact that biological drugs work best in the “acute period”, when the severity of symptoms is maximum. In addition, the effect of their use is observed faster. Treatment with infliximab produces results within 2–4 weeks, while methotrexate “starts working” only after several months.

The use of biological drugs is permissible in cases where the patient develops intolerance to basic drugs. Patients experience severe side effects from the medication, which further worsens their condition. The use of drugs with a different mechanism of action, including monoclonal antibodies, allows minimizing side effects [18].

The prescription and sale of biological drugs is controlled by the state. Many drugs from the group of monoclonal antibodies (infliximab, etanercept, tocilizumab, golimumab) are included in the “List of Vital and Essential Medicines”. In accordance with it, a list of medications is formed that are supplied to hospitals throughout Russia. Of course, biological drugs are not available in every hospital today. They are usually used in regional centers or specialized hospitals.

If they are unable to provide themselves with medications, patients receive disability and undergo therapy at state expense. This right is enshrined in the current “Program of State Guarantees for the Provision of Free Medical Care.” Treatment with biological drugs is provided for rheumatoid arthritis, ankylosing spondylitis, SLE, dermatopolymyositis, juvenile arthritis and other diseases. At the same time, doctors must determine clear indications for prescribing this or that drug. Getting expensive treatment is quite difficult - you need to undergo a full examination and collect documents. However, the provision of a state quota for many patients is the last chance for a full life.

Another difficulty that can be encountered when using biological drugs is adverse reactions. In parallel with the accumulation of data on the effectiveness of the use of drugs, new undesirable effects from their use are being identified. Most of these reactions are associated with the process of immunosuppression. By suppressing the activity of immune cells, monoclonal antibodies reduce the body's protective function. Anti-infective and anti-tumor immunity are primarily affected [18], [24].

Paradoxically, the use of new drugs against autoimmunity can cause acute autoimmune reactions. All biological drugs are protein molecules that are foreign to the body to one degree or another. Therefore, when therapeutic agents penetrate the patient’s body, the immune system can recognize them as antigens. An active immune response appears - antibodies are produced against the components of the drug.

Autoimmune syndromes provoked by drug administration are usually represented by vasculitis, SLE, antiphospholipid syndrome, and psoriasis [25]. Infliximab, which contains foreign murine fragments, is highly immunogenic. Fully “human” drugs provoke immunity less actively. But even with their use, there is a high risk of developing adverse autoimmune reactions. To eliminate these disorders, it is necessary to adjust the patient’s treatment regimen. It includes additional immunosuppressants that will suppress complications. This may be why combinations of biological drugs with disease-modifying drugs are often more effective than isolated therapy, even with the newest drugs [24].

Despite all possible difficulties, monoclonal antibodies have firmly entered the register of drugs used in rheumatology. The future of biologics and their place in rheumatology will depend on the results of many years of research that remain to be done. But even now we can say that the development of therapeutic monoclonal antibodies is an important step towards defeating autoimmune inflammation.

Analogues of Plaquenil

Level 4 ATX code matches:
Immard

Delagil

Analogues are drugs from different drug groups that are used to treat the same diseases. Analogues of Plaquenil are:

Delagil is a 6-aminoquinoline and has the same indications for use as Plaquenil;
Medicines belonging to the group of 8-aminoquinoline with antimalarial action: Plazmocid , Plazmokhin , Khinocid , Primaquin .

Reviews of Plaquenil

Reviews of Plaquenil mainly depend on the correctness of its purpose. In addition, this drug is not suitable for everyone; in some patients it immediately causes side effects.

Reviews about Plaquenil on the forums are mostly positive. Patients who have taken it for long courses for systemic connective tissue diseases note that side effects are very rare, the drug combines well with other anti-inflammatory and analgesic drugs and helps reduce their dosage.

Negative reviews of Plaquenil are due to the drug's side effects, which are rare but can be significant.

Plaquenil price

The price of Plaquenil in Moscow pharmacies ranges from 500 to 600 rubles per package (60 tablets).

Online pharmacies in RussiaRussia
Online pharmacies in UkraineUkraine

ZdravCity

Plaquenil tablets p.p.o.
200 mg 60 pcs. Sanofi-Aventis S.A. 426 rub. order

Pharmacy Dialogue

Plaquenil (tab.p.pl/vol. 200 mg No. 60)Sanofi Aventis
516 RUR order

Pharmacy24

Plaquenil 200 mg No. 60 tablets Sanofi Aventis SA, Spain
548 UAH.order

Note!

Description of the drug Plaquenil table. p/o 200 mg No. 60*** on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.