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.

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.

Use of Plaquenil in the treatment of rheumatoid arthritis

Plaquenil has long been used in the treatment of various rheumatic diseases, primarily in patients with RA and systemic lupus erythematosus (SLE). At the end of the 19th century, the English physician JP Payne first identified the clinical effect of quinine in lupus erythematosus. Nevertheless, the drug still continues to be widely used for SLE. Aminoquinoline drugs are now used less frequently in the treatment of RA. Despite the variety of mechanisms of the anti-inflammatory action of Plaquenil, including suppression of the synthesis of cytokines (IL-1, IL-6, TNF-?), inhibition of cartilage destruction induced by IL-1, suppression of interferon synthesis? activated T-lymphocytes, which to a certain extent will modify the activity of the inflammatory process [3–7]), slow development of the drug effect (up to 6 months), less pronounced anti-inflammatory effect put it in the group of 2nd line drugs after more quickly and actively acting cytostatics. In 2008, the AKR published an updated agreement on the use of DMARDs and genetically engineered biologicals (GEBs) [8]. The authors suggest when choosing DMARDs to take into account the main parameters of RA: 1. Duration of RA, which is divided into 3 groups: early RA - disease duration <6 months, average disease duration 6-24 months and established (long-term) RA with a duration of symptoms of more than 24 months. 2. Disease activity, which is divided using various indices (Tables 2 and 3). 3. Prognostically unfavorable signs: active disease (a large number of painful and swollen joints), the presence of erosions at an early stage, increased RF and/or ACCP [9,10], increased ESR and/or CRP [11,12]. A poor prognosis in RA means radiographic progression of joint destruction, loss of function and increased mortality, as well as an increased risk of requiring joint surgery. In accordance with the recommendations of the AKR (2008) [8], treatment of DMARDs is carried out in the form of monotherapy or double and triple combinations (Fig. 1A, B, C) depending on the duration of therapy and the presence of unfavorable prognosis factors. DMARD therapy, according to the authors, can be started or carried out at the stages of the disease in the form of monotherapy, double, triple combinations of DMARDs. In accordance with the 2008 ACR recommendations, Plaquenil (PL) is prescribed to patients without signs of an unfavorable prognosis and with a RA duration of ≥24 months as monotherapy. With higher activity and/or in the presence of unfavorable prognosis factors, Plaquenil is suggested to be used in combination with other DMARDs. A double combination of DMARDs is used for high RA activity in patients with signs of poor prognosis [13,14]. The combination of methotrexate (MTX) and PL is recommended for long duration of RA and low activity (level of evidence C). The combination of methotrexate (MTX) and leflunomide (Lef) is recommended to be prescribed for moderate duration (>6 months) and the presence of poor prognosis factors, and to carry out therapy for as long as high activity is maintained [15]. It is proposed to prescribe MTX in combination with sulfasalazine (SS) for any duration of RA, high activity, and the presence of signs of poor prognosis (level of evidence A for RA duration < 6 months and more than 24 months; level of evidence C for average duration of RA) [13,16– 18]. The combination of SS and PL in accordance with these recommendations is used only in one situation: the average duration of RA (6–24 months) with high activity, but without signs of a poor prognosis. A triple combination of DMARDs—MT+PL+SS—is prescribed in the presence of poor prognosis factors and in moderate/high disease activity, regardless of the duration of the disease [13,18]. Other DMARDs are 2nd and 3rd line drugs and are used if these 4 DMARDs are ineffective or intolerable (methotrexate, leflunomide, Plaquenil, sulfasalazine). Most DMARD combinations have been selected empirically or have been proposed in clinical trials of new drugs. Combinations of glucocorticoids (GC), CC, MTX and aminoquinoline drugs have been evaluated in advanced and early stages of RA [18–20]. Some of these studies have shown that some (but not all) combinations of small molecular weight drugs are more effective than monotherapy. The combination of MT and SS did not reveal any advantages over the isolated administration of MT [19]. Moreover, some combinations are associated with an increase in treatment toxicity, such as the combination of MTX and leflunomide leads to an increase in the frequency of severe intolerance reactions from the liver [20], and the combination of MTX and CC leads to an increase in the incidence of folate deficiency anemia in patients with RA [18]. Jansen et al. [21] also noted the absence of an increase in effect with the combination of MT and CC and an increase in the toxicity of such a combination. It was assumed that the combination of DMARDs would improve efficacy, more rapidly onset of therapeutic action, and reduce toxicity compared to monotherapy with the basic drug [22]. In addition, the administration of a second DMARD may help reduce the development of resistance to a previously prescribed DMARD [22,23]. It is known that for many DMARDs the duration of continuous use for 50% of patients is 1–2 years [24]. The exception is MTX: more than half of patients who started treatment with this drug continue to take it for 5 years [24]. According to the literature, it follows that to reduce the frequency of side effects, drugs with minimal toxicity and good long-term tolerability should be used. We compared the combination of MT and PL with MT monotherapy in a 12-month open study. Our choice of drugs for combination was based on the known relatively low toxicity of MTX and PL in the treatment of RA, and the availability of these drugs for patients. 26 patients received MTX monotherapy (7.5–12.5 mg/week), and 21 received combination therapy with MTX in the same doses and PL (200 mg/day) [25]. Of these, 12 patients began taking MT and PL simultaneously, and 9 patients Plaquenil was added to previously conducted and insufficiently effective MT therapy. Table 4 presents quantitative parameters reflecting RA activity after 6 and 12 months of treatment. As can be seen from Table 4, by 6 months of treatment, clinical improvement was observed in both groups of patients and was manifested in a significant decrease in most of the analyzed parameters (9 out of 10 in group I and 8 out of 10 in group II). At the same time, in group I, the most significant decrease in pain in small and large joints, swelling in large joints and ESR was noted (p<0.001). In group II, pain and painful palpation in large joints decreased most clearly (p<0.001); there was no significant decrease in ESR in this group after 6 months. When treatment was continued for up to 12 months, in the group receiving MT, 7 (39%) patients showed an increase in the severity of a number of signs of joint inflammation, in most cases within the same degree of activity. Most often, there was an increase in pain and swelling in small joints, so that in the group as a whole, only 4 out of 10 indicators significantly decreased. When using a combination of MT and PL after 12 months, an increase in the severity of parameters of joint damage (also within one degree of activity) was observed in only 3 (20%) patients. In general, in group II there was a significant decrease in 8 out of 10 indicators. The degree of positive effect on swelling of large and small joints even increased (p<0.001). Thus, in the first 6 months, MT monotherapy led to a more pronounced effect on the parameters of inflammation in the joints, but with continued treatment, instability of the effect and a decrease in the number of significantly decreased parameters were noted. Combination therapy with MT and PL demonstrated a more stable effect on indicators of joint inflammation. Quantitative assessment of the dynamics of the number of erosions in small joints of the hands and feet, carried out by the modified Sharp method, showed that both MTX monotherapy and the combination of MTX with PL slowed down the progression of erosive arthritis after 12–24 months of continuous therapy. It should be noted that the tolerability of the combined use of MTX and PL was not better than MTX monotherapy. In group I, we observed side effects in 35% of patients, and in group II – in 57%. Therapy was discontinued due to intolerance in 2 (22%) and 3 (33%) patients, respectively. The highest frequency of intolerance symptoms was observed in the first months of treatment. At the same time, among patients receiving a combination of MT and PL, an increase in the level of liver enzymes was most often observed (in 58% of patients), which contradicts the data of J. Fries et al. about better tolerability of the combination of these basic drugs [26]. With sequential administration of MT and PL (with a gap of 3 or more months), the frequency of side effects was slightly lower than with their simultaneous administration, which has already been noted by other authors [27,28]. In the literature, along with a decrease in the hepatotoxicity of MT when combined with PL [26], an increase in the duration of remission after discontinuation of the drug and a reduction in the frequency and duration of exacerbations is noted [22]. A decrease in the bioavailability of MT has also been described when combined with PL [29], which dictates the need to take PL on those days when MT is not taken, which can increase the effectiveness of therapy. Thus, the combination of MT and PL has a more stable effect over time. Plaquenil can be added to MTX therapy when signs of so-called secondary ineffectiveness (decrease in effect) appear, which allows maintaining the achieved improvement. When remission is achieved with a combination of MT and PL, it is possible to discontinue MT and maintain PL therapy, which allows prolongation of remission. Summarizing the literature data and our own experience, we can formulate the following indications for prescribing Plaquenil for RA: 1. Monotherapy: early stage of articular damage (undifferentiated arthritis). 2. Monotherapy: early stage of RA with low activity and no signs of poor prognosis. 3. Combination therapy: decreased effect of MT or insufficient effect (improvement according to ACR criteria >20% and less than 50%). 4. Combination therapy: achieving minimal RA activity and insufficient tolerance to MT. 5. Combination therapy: achieving RA remission and discontinuing MT after 6 months of combining it with PL.

References 1. ACR Subcommittee of Rheumatoid Arthritis Guidelines “Guidelines for the management of rheumatoid arthritis: 2002 update” Arthr. Rheum., 2002, 46:328–346 2. Arnrett FC, Edworth SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum., 1988;31:315–324 3. Picot S. “Chloroquine inhibits tumor necrosis factor production by human macrophages in vitro” J. Infect. Dis., 1991, V.164:830–831 4. Baker DG, Baumgarten DF, Dwyer JP “Chloroquine inhibits the production of mononuclear cell factor by inhibits of lectin binding” Arthr. Rheum., 1984, V.27: 888–896 5. Rainsford KD “Effects of anti-inflammatory drugs on catabolic-induced cartilage destruction in vitro.” 6. Sperber K., Quraishi H., Kalb TH, et.al. “Selective regulation of cytokine secretion by hydroxychloroquine: inhibition of interleukine 1 alpha (IL-1 alpha) and interleukine 6 in human monocyte and T cell” J. Rheum., 1993, V.20: 803–808 7. Landewe RBM, Dijkmans BAC, van der Woude FJ, et.al. "Long-term cyclosporine in patients with rheumatoid arthritis" Arthr. Rheum., 1994, V.37 (suppl): S–361 8. Saag KG, Teng GG, Patkar NM et.al. “American College of Rheumatology 2008 Recommendations for the Use of Nonbiologic and Biologic Disease—Modifying Antirheumatic Drugs in Rheumatoid Arthritis” Arthr. Care and Res., 2008, 59: 762–784 9. Agrawal S, Misra R, Aggarwal A. “Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA” Clin. Rheumatol., 2007, 26: 201–204. 10. Ates A, Kinikli G, Turgay M, Akay G, Tokgoz G. “Effects of rheumatoid factor isotypes on disease activity and severity in patients with rheumatoid arthritis: a comparative study” Clin Rheumatol., 2007, 26: 538–545. 11. Emery P, Breedveld FC, Dougados M. et.al. “Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide” Ann. Rheum. Dis. 2002, 61: 290–297. 12. Gossec L, Dougados M, Goupille P. et al. “Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study” Ann. Rheum. Dis., 2004, 63: 675–680. 13. Hurst S, Kallan MJ, Wolfe FJ. et.al. “Methotrexate, hydroxychloroquine, and intramuscular gold in rheumatoid arthritis: relative area under the curve effectiveness and sequence effects” J. Rheumatol., 2002, 29: 1639–1645. 14. Strand V, Cohen S, Schiff M. et al., and the Leflunomide Rheumatoid Arthritis Investigators Group. “Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate” Arch. Intern. Med., 1999, 159: 2542–2550. 15. Boers M, Verhoeven AC, Markusse HM. et al. "Randomized comparison of combined step–down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis". Lancet, 1997, 350: 309–318. 16. Kremer J. et.al. Combination leflunomide and methotrexate therapy for patients with active rheumatoid arthritis failing methotrexate therapy: open label extension of a randomized, double–blind placebo controlled trial. J. Rheum., 2004, 31: 1521–31. 17. Smolen JS, Kalden JR, Scott DL. et al, and the European Leflunomide Study Group. "Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomized, multicentre trial" Lancet, 1999, 353:259–266. 18. O'Dell JR, Leff R, Paulsen G et.al. “Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulphasalazine, or a combination of the three medications: results of a two–year randomized, double–blind, placebo–controlled trial” Arthr. Rheum., 2002, 46: 1164–1170 19. O'Dell JR “Conventional DMARD option for the patients with a suboptimal response to methotrexate” J. Rheum. Suppl., 2001, 62: 21–26 20. Weiblatt ME, Dixon JA, Falchuk KR et.al. "Serious liver disease in a patient receiving methotrexate and leflunomide" Arthr. Rheum., 2000, 43: 2609–2611 21. Jansen G., van der Heijden J., Oerlemans R. et.al. “Sulphasalazine is a potent inhibitor of the reduced folate carrier: implications for combination therapies with methotrexate in rheumatoid arthritis” Arthr. Rheum., 2004, 50: 2130–2139 22. Paulus HE “Protocol Development for combination therapy with disease–modifying antirheumatic drugs” Sem. Arthr. Rheum., 1993, V.23, Suppl. 1: 19–25 23. Farr M., Bacon PA “How and when combination therapy should be used? The role of an anchor drug" Brit. J. Rheum., 1995, V.34, Suppl.2: 100–103 24. Pincus T., Marcum SB, Callahan LF “Long-term drug therapy for rheumatoid arthritis in seven rheumatology private practices” J. Rheum., 1992 , V.19:1885–1894 25. E.L. Nasonov “Methotrexate. Prospects for use in rheumatology” Moscow, 2005. pp. 67–69 26. Fries JF, Singh G., Lenert L., Futsr DE “Aspirin, hydroxychloroquine, and hepatic enzyme abnormalities with methotrexate in rheumatoid arthritis” Arthr. Rheum, 1990, 33: 1611–1619 27. Farr M, Kitas GD, Bacon PA “Combination chemotherapy in rheumatoid arthritis” Br. J. Rheum., 1987, 27: 73–74 28. Scott DL, Dwes PT, Tunn E. et al. “Combination therapy with gold and hydroxychloroquine in rheumatoid arthritis: a prospective, randomized, placebo–controlled study” Br. J. Rheum., 28: 128–133 29. Seideman P., Albertoni R., Beck O. et al. "Chloroquine reduced bioavailability of methotrexate in patients with rheumatoid arthritis" Arthr. Rheum., 1993, 37: 830–833

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).

Description of the drug PLAQUENIL

The retinal toxicity of hydroxychloroquine is largely dose dependent. The incidence of retinopathy when using doses up to 6.5 mg/kg of “ideal” body weight is small. Exceeding the recommended daily dose sharply increases the risk of developing retinopathy.

Before starting a long course of treatment with hydroxychloroquine, both eyes should be thoroughly examined. The examination should include determination of visual acuity, examination of the fundus, assessment of color vision and visual fields. During therapy, such examinations should be carried out at least once every 6 months.

Testing should be done more frequently in the following situations:

at a daily dose exceeding 6.5 mg/kg of “ideal” body weight (in patients with increased body weight, using absolute body weight to calculate the dose may lead to an overdose);
with renal failure;
with a total dose of over 200 g;
in elderly people;
if the patient has a decrease in visual acuity of any severity before starting treatment.

If any visual disturbances occur (decreased visual acuity, changes in color vision), hydroxychloroquine should be discontinued immediately and the patient's vision should be carefully monitored, since retinal changes (and visual disturbances) may progress even after discontinuation of hydroxychloroquine.

Cases of cardiomyopathy leading to heart failure have been reported in patients taking hydroxychloroquine. It has been shown that hydroxychloroquine can cause severe hypoglycemia (including loss of consciousness), which can be life-threatening in patients both taking and not taking hypoglycemic drugs. Patients taking hydroxychloroquine should be warned of the risk of hypoglycemia and associated clinical signs and symptoms. In patients who develop clinical symptoms suggestive of hypoglycemia during treatment with hydroxychloroquine, blood glucose concentrations should be determined and therapy reconsidered if necessary.

Caution is recommended when using hydroxychloroquine in patients with liver or kidney disease, who may require dose reductions, or in patients taking medications that may cause adverse effects on these organs.

In patients taking hydroxychloroquine for a long time, a complete blood count should be performed periodically (if hematological abnormalities occur, hydroxychloroquine should be discontinued).

Children are particularly sensitive to the toxic effects of 4-aminoquinolines, so care should be taken to keep hydroxychloroquine out of the reach of children.

All patients taking hydroxychloroquine for a long time should be periodically examined by a neurologist regarding skeletal muscle function and the severity of tendon reflexes. If muscle weakness occurs, hydroxychloroquine should be discontinued.

In very rare cases, suicidal behavior has been reported in patients taking hydroxychloroquine. When using hydroxychloroquine, extrapyramidal disorders may develop.

Hydroxychloroquine is not effective against chloroquine-resistant strains of P. falciparum, and is also not active against extraerythrocytic forms of P. vivax, P. malariae and P. ovale, and therefore it cannot prevent infection by these microorganisms when used for prophylactic purposes, and also cannot prevent relapse of the disease caused by these pathogens.

Impact on the ability to drive vehicles and machinery

During treatment with hydroxychloroquine, caution should be exercised when performing potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

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 .

Plaquenil TB p/o capt 200 mg N 60

Indications for use of the drug Plaquenil

- rheumatoid arthritis; - juvenile rheumatoid arthritis; — lupus erythematosus (systemic and discoid); - malaria (except for those caused by chloroquine-resistant strains of Plasmodium falciparum): - for the prevention and treatment of acute attacks of malaria caused by Plasmodium vivax, Plasmodium ovale and Plasmodium malariae, as well as sensitive strains of Plasmodium falciparum; - for the radical treatment of malaria caused by sensitive strains of Plasmodium falciparum.

Plaquenil release form

Film-coated tablets 200 mg; blister 10 cardboard pack 6;

Pharmacodynamics of the drug Plaquenil

The drug actively suppresses asexual erythrocyte forms, as well as gametes of Plasmodium vivax and Plasmodium malariae, which disappear from the blood almost simultaneously with the asexual forms. Plaquenil has no effect on Plasmodium falciparum gametes. Plaquenil is ineffective against chloroquine-resistant strains of Plasmodium falciparum, and is also inactive against extraerythrocytic forms of Plasmodium vivax, Plasmodium malariae and Plasmodium ovale and therefore cannot prevent infection by these microorganisms when prescribed for prophylactic purposes, and also cannot prevent relapse of the disease caused by these pathogens.

Pharmacokinetics of the drug Plaquenil

After oral administration, hydroxychloroquine is rapidly and almost completely absorbed. In healthy volunteers, after a single dose of 400 mg, Cmax of hydroxychloroquine in plasma was reached after 1.83 hours and ranged from 53 to 208 ng/ml. Plasma protein binding - 45%. The average T1/2 value from plasma varies depending on the time elapsed after taking the drug as follows: 5.9 hours (from reaching Cmax to 10 hours); 26.1 hours (from 10 to 48 hours) and 299 hours (from 48 to 504 hours). In the liver it is partially converted into active ethylated metabolites. The unchanged drug and its metabolites are well distributed in the body. The volume of distribution is 5–10 l/kg. The drug accumulates in tissues with a high level of metabolism (in the liver, kidneys, lungs, spleen - in these organs the concentration exceeds the plasma concentration by 200–700 times; central nervous system, erythrocytes, leukocytes), as well as in the retina and tissues rich in melanin. Hydroxychloroquine and its metabolites are excreted primarily in the urine and, to a lesser extent, in the bile. The release of the drug is slow, terminal T1/2 is about 50 days (from whole blood) and 32 days (from plasma). Within 24 hours, 3% of the administered dose of the drug is excreted in the urine. Hydroxychloroquine crosses the placental barrier and is found in small amounts in breast milk

Using Plaquenil during pregnancy

Hydroxychloroquine crosses the placenta. Data are limited regarding its use during pregnancy. It should be noted that 4-aminoquinolines in therapeutic doses can cause intrauterine damage to the central nervous system, incl. auditory nerve (impaired hearing and vestibular apparatus, congenital deafness), hemorrhages in the retina and abnormal pigmentation of the retina. Therefore, the use of hydroxychloroquine during pregnancy should be avoided unless the potential benefit to the mother outweighs the risk to the fetus. You should carefully consider the need to use the drug during breastfeeding, because it has been shown to be excreted in small amounts into mother's milk, and young children are particularly sensitive to the toxic effects of 4-aminoquinolines.

Contraindications to the use of Plaquenil

- hypersensitivity to 4-aminoquinoline derivatives; - retinopathy; — pregnancy (see “Pregnancy and lactation”); - hereditary lactose intolerance, lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome (due to the presence of lactose in the drug). - children's age when long-term therapy is necessary (children have an increased risk of developing toxic effects); - children under 6 years of age (200 mg tablets are not intended for children with an “ideal” body weight of less than 31 kg). With caution: - visual disorders (decreased visual acuity, impaired color vision, narrowing of visual fields), simultaneous use of drugs that can cause adverse ophthalmological reactions (danger of progression of retinopathy and visual disorders); - hematological diseases (including those with a history); - severe neurological diseases, psychoses (including history); - porphyria cutanea tarda (risk of exacerbation), psoriasis (risk of increased skin manifestations of the disease), simultaneous use of drugs that can cause skin reactions; - renal failure and/or liver failure, hepatitis, concomitant use of drugs that can adversely affect liver and/or kidney function (in case of severe impairment of renal or liver function, the dose should be selected under the control of plasma concentrations of hydroxychloroquine); - deficiency of glucose-6-phosphate dehydrogenase; - severe gastrointestinal diseases; - hypersensitivity to quinine (possibility of cross-allergic reactions).

Side effects of the drug Plaquenil

On the part of the organ of vision: retinopathy with changes in pigmentation and defects in the visual fields can develop, although rarely. In the early form, these effects are usually reversible when hydroxychloroquine is stopped. If the condition remains undiagnosed and retinal lesions continue to develop further, there may be a risk of their progression even after discontinuation of the drug. Retinal changes may initially be asymptomatic, or manifest as paracentral or pericentral scotomas, transient scotomas, and color vision impairment. Corneal changes may occur, including swelling and clouding. They may be asymptomatic or cause visual disturbances such as halos, blurred vision, or photophobia. When treatment is stopped, these changes may reverse. Visual disturbances associated with accommodation disturbances may also occur, which are dose-dependent and reversible. From the skin: sometimes there are skin rashes; Itching, changes in pigmentation of the skin and mucous membranes, hair discoloration and alopecia are also described. These changes usually resolve quickly after treatment is stopped. Bullous rashes have been reported, including very rare cases of erythema multiforme and Stevens-Johnson syndrome, photosensitivity and isolated cases of exfoliative dermatitis. Very rare cases of acute generalized exanthematous pustulosis (AGEP) must be distinguished from psoriasis, although hydroxychloroquine can also provoke an exacerbation of psoriasis. OHEP may be accompanied by fever and hyperleukocytosis. After discontinuation of the drug, the outcome is usually favorable. From the gastrointestinal tract: nausea, diarrhea, anorexia, abdominal pain and rarely vomiting. These symptoms usually disappear immediately after the dose is reduced or the drug is discontinued. From the hepatobiliary system: with long-term use in large doses, hepatotoxic effects may develop. There are reports of isolated cases of liver dysfunction and several cases of sudden onset liver failure. From the side of the central nervous system: infrequently - dizziness, tinnitus, hearing loss, headache, irritability, emotional instability, psychosis, convulsions, muscle weakness, ataxia. From the peripheral nervous system and muscles: cases of skeletal muscle myopathy or neuromyopathy have been reported, leading to progressive weakness and atrophy of proximal muscle groups. Myopathy may be reversible after discontinuation of the drug, but full recovery may take several months. At the same time, mild sensory changes, suppressed tendon reflexes, and decreased nerve conduction may occur. From the cardiovascular system: there are rare reports of the development of cardiomyopathy. Chronic cardiac toxicity may be suspected when conduction abnormalities (bundle branch block/AV conduction disturbances) or biventricular hypertrophy are detected. If the drug is discontinued, these changes may reverse. From the hematopoietic organs: cases of suppression of bone marrow hematopoiesis have been rarely reported. Rare cases of anemia have been reported, incl. aplastic, agranulocytosis, leukopenia and thrombocytopenia. Hydroxychloroquine may precipitate or worsen porphyria. From the immune system: urticaria, angioedema, bronchospasm.

Method of administration and dosage of the drug Plaquenil

Note: All doses are for hydroxychloroquine sulfate and are not equivalent to doses for the base. Inside, during meals or with a glass of milk. Treatment of RA. Hydroxychloroquine has cumulative activity. It takes several weeks of taking the drug for its therapeutic effect to manifest itself, while side effects may appear relatively early. The necessary therapeutic effect develops after several months of taking the drug. If there is no objective improvement in the patient's condition within 6 months of taking hydroxychloroquine, the drug should be discontinued. Adults (including older adults) should take the minimum effective dose. They should not exceed 6.5 mg/kg/day (calculated based on “ideal” body weight, not actual body weight) and can be either 200 or 400 mg/day. In patients able to take 400 mg daily Initially, 400 mg daily in divided doses. When obvious improvement is achieved, the dose can be reduced to 200 mg. If the effect decreases, the maintenance dose can be increased to 400 mg. For children. The minimum effective dose should be used. The dose should not exceed 6.5 mg/kg (based on “ideal” body weight). Therefore, the 200 mg tablets are not suitable for children with an “ideal” body weight of less than 31 kg. Use of the drug Plaquenil for combination therapy of RA. Plaquenil can be safely used in combination with corticosteroids, salicylates, NSAIDs, methotrexate and other second-line therapeutic agents. After several weeks of using the drug Plaquenil, the doses of corticosteroids and salicylates may be reduced or these drugs may be discontinued. Doses of GCS should be reduced gradually every 4-5 days: the dose of cortisone - by no more than 5-15 mg, the dose of hydrocortisone - by no more than 5-10 mg, the dose of prednisolone and prednisone - by no more than 1-2.5 mg , the dose of methylprednisolone and triamcinolone - no more than 1-2 mg and dexamethasone - no more than 0.25-0.5 mg. Treatment of SLE. The initial average dose in adults is 400 mg 1 or 2 times a day. It should be given over several weeks or months depending on the patient's response. For long-term maintenance therapy, it is sufficient to use the drug in a lower dose - from 200 to 400 mg. Treatment of malaria Prevention of acute attacks of malaria caused by P. malariae and susceptible strains of Plasmodium falciparum Adults - 400 mg weekly on the same day of the week. For children, the weekly dose is 6.5 mg/kg (for calculation, the “ideal” body weight is taken), however, regardless of body weight, it should not exceed the dose for adults. If conditions allow, preventive therapy should begin 2 weeks before entering an endemic area. If this is not possible, then an initial double (loading) dose can be prescribed: adults - 800 mg, children - 12.9 mg/kg of “ideal” body weight (but not more than 800 mg), divided into two doses with a 6-hour interval. Preventive treatment should be continued for 8 weeks after leaving the endemic area. Treatment of acute attacks of malaria For adults, an initial dose of 800 mg is followed by a dose of 400 mg after 6 or 8 hours, and then 400 mg on 2 subsequent days (for a total of 2 g of hydroxychloroquine sulfate). Alternative treatment: A single dose of 800 mg has also been shown to be effective. Doses for adults can also be calculated based on “ideal” body weight, similar to the calculation of doses for children (see below). For children, a total dose of 32 mg/kg of “ideal” body weight (but not higher than 2 g) is prescribed for 3 days as follows: first dose - 12.9 mg/kg (single dose not more than 800 mg); second dose - 6.5 mg/kg (not more than 400 mg) 6 hours after the first; third dose - 6.5 mg/kg (not more than 400 mg) 18 hours after the second dose; fourth dose - 6.5 mg/kg (not more than 400 mg) 24 hours after the third dose. Radical treatment of malaria caused by Plasmodium malariae and Plasmodium vivax For radical treatment of malaria caused by Plasmodium malariae and Plasmodium vivax, simultaneous administration of 8-aminoquinolone derivatives is necessary.

Overdose with Plaquenil

An overdose of 4-aminoquinolines is especially dangerous in children; even 1–2 g of the drug can be fatal. Symptoms: headache, visual disturbances, collapse, convulsions, hypokalemia, rhythm and conduction disturbances, followed by cardiac and respiratory arrest. Treatment: because These effects can develop very quickly after taking a large dose of the drug; in these cases, appropriate measures should be started immediately. Induction of vomiting or gastric lavage through a tube should be performed immediately. To slow down absorption, prescribe activated carbon in a dose at least 5 times higher than the dose of the drug taken. Parenteral administration of diazepam is advisable (a decrease in the cardiotoxicity of chloroquine against its background has been described). If necessary, artificial ventilation and antishock therapy should be performed. After relief of overdose symptoms, continued medical supervision is required for at least 6 hours.

Interactions of the drug Plaquenil with other drugs

Digoxin. It has been reported that hydroxychloroquine is capable of increasing plasma concentrations of digoxin; therefore, in order to avoid the development of glycoside toxicity when taking these drugs simultaneously, it is necessary to reduce the dose of digoxin while monitoring its plasma concentrations. Medicines used to treat diabetes mellitus. Because hydroxychloroquine may potentiate the effects of insulin and oral hypoglycemic agents, it may be necessary to reduce the dosage of these antidiabetic agents when initiating hydroxychloroquine. Antacids. May reduce the absorption of hydroxychloroquine. Therefore, when using antacids and hydroxychloroquine simultaneously, the interval between their administration should be at least 4 hours. With hydroxychloroquine, the following interactions with other drugs that have been described for chloroquine, but have not yet been observed when taking hydroxychloroquine, cannot be excluded. Aminoglycosides. Potentiation of their direct blocking effect on neuromuscular transmission. Cimetidine. Suppresses the metabolism of antimalarial drugs, which can lead to an increase in their plasma concentrations and increase the risk of developing their side effects, especially toxic ones. Neostigmine and pyridostigmine. Antagonism of action. Any intradermal human diploid cell rabies vaccine. Decreased antibody production in response to primary immunization with intradermal human diploid cell rabies vaccine.

Special instructions when taking Plaquenil

General Retinal toxicity is largely dose dependent. The incidence of retinopathy at doses up to 6.5 mg/kg of “ideal” body weight is low. Exceeding the recommended daily dose sharply increases the risk of developing retinopathy and accelerates its onset. Before starting a long course of treatment with the drug, a thorough examination of both eyes should be performed. The examination should include determination of visual acuity, examination of the fundus, assessment of color vision and visual fields. During therapy, such examination should be carried out at least once every 6 months. Examination should be more frequent in the following situations: - with a daily dose exceeding 6.5 mg/kg of “ideal” body weight (in obese patients, using absolute body weight to calculate the dose may lead to an overdose); - in case of renal failure; - with a total dose of over 200 g; - in elderly people; - with reduced visual acuity. If any visual disturbances occur (decreased visual acuity, changes in color vision), the drug should be discontinued immediately and the patient’s visual condition should be carefully monitored, because Retinal changes (and visual disturbances) may progress even after drug discontinuation. It is recommended to exercise caution when prescribing hydroxychloroquine to patients with liver and kidney diseases, who may require a dose reduction of the drug, as well as due to the possibility of the drug affecting the function of these organs (in case of severe impairment of kidney or liver function, the dose should be selected under the control of plasma concentrations of hydroxychloroquine) . In patients receiving long-term treatment, a complete blood count should be performed periodically; if hematological disorders occur, hydroxychloroquine should be discontinued. Children are particularly sensitive to the toxic effects of 4-aminoquinolines, so care should be taken to keep hydroxychloroquine out of the reach of children. All patients receiving the drug for a long time should be periodically examined by a neurologist regarding the functions of skeletal muscles and the severity of tendon reflexes. If muscle weakness occurs, the drug should be discontinued. In malaria, Plaquenil is ineffective against chloroquine-resistant strains of Plasmodium falciparum, and is also inactive against extra-erythrocytic forms of Plasmodium vivax, Plasmodium malariae and Plasmodium ovale and therefore cannot prevent infection by these microorganisms when prescribed to prevent acute attacks of malaria, and also cannot prevent relapse of the disease caused by these pathogens. Impact on the ability to drive a car and perform work associated with increased danger. Patients should be careful when driving or performing work that requires increased attention, because Hydroxychloroquine may impair accommodation and clarity of vision. If this condition does not go away on its own, the dose may be temporarily reduced.

Storage conditions for the drug Plaquenil

List B.: At a temperature not exceeding 25 °C.

Shelf life of Plaquenil

36 months

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 ).

Plaquenil®

Plaquenil is for oral use only. The drug is taken with food or with a glass of milk.

All drug doses are based on hydroxychloroquine sulfate and are not equivalent to base doses.

Treatment of rheumatoid arthritis

Hydroxychloroquine has cumulative activity. It takes several weeks of taking the drug for its therapeutic effect to manifest itself, while side effects may appear relatively early. The necessary therapeutic effect develops after several months of taking the drug. If there is no objective improvement in the patient's condition within 6 months of taking hydroxychloroquine, the drug should be discontinued.

Adults (including the elderly)

the drug is prescribed in the minimum effective dose. The dose should not exceed 6.5 mg/kg body weight per day (calculated based on ideal, not actual body weight) and can be either 200 mg or 400 mg/day.

In patients able to take 400 mg daily, the initial dose is 400 mg daily in divided doses. When obvious improvement is achieved, the dose can be reduced to 200 mg. If effectiveness decreases, the maintenance dose can be increased to 400 mg.

For children

the drug is prescribed in the minimum effective dose. The dose should not exceed 6.5 mg/kg body weight (based on ideal body weight), therefore 200 mg tablets are not intended for children weighing less than 31 kg.

The use of Plaquenil in combination with corticosteroids, salicylates, NSAIDs, methotrexate and other second-line therapeutic agents is safe. After several weeks of using Plaquenil, the doses of corticosteroids and salicylates may be reduced or these drugs may be discontinued. Doses of GCS should be reduced gradually every 4-5 days: the dose of cortisone - by no more than 5-15 mg, the dose of hydrocortisone - by no more than 5-10 mg, the dose of prednisolone and prednisone - by no more than 1-2.5 mg, dose methylprednisolone and triamcinolone - no more than 1-2 mg and dexamethasone - no more than 0.25-0.5 mg.

Treatment of systemic lupus erythematosus

For adults

prescribed at an initial average dose of 400 mg 1-2 times a day for several weeks or months, depending on the patient’s response. For long-term maintenance therapy, it is sufficient to use the drug in a lower dose of 200 to 400 mg.

Treatment of malaria

To prevent acute attacks of malaria

caused by Plasmodium malariae and susceptible strains of Plasmodium falciparum,
to adults
at a dose of 400 mg weekly on the same day of the week.
For children,
the weekly dose is 6.5 mg/kg (ideal body weight is used for calculation), however, regardless of body weight, the dose for children should not exceed the dose for adults.

If conditions allow, then preventive therapy

should begin 2 weeks before entering an endemic area.
If this is not possible, then an initial double (loading) dose can be prescribed: adults
- 800 mg,
children
- 12.9 mg/kg of ideal body weight (but not more than 800 mg), divided into two doses with a 6-hour interval. Prophylactic treatment should be continued for 8 weeks after leaving the endemic area.

For the treatment of acute attacks of malaria
in adults
, the drug is prescribed at a dose of 800 mg, then after 6-8 hours - 400 mg, then in the next 2 days - 400 mg (for a total of 2 g of hydroxychloroquine sulfate).

Alternative treatment:

The effectiveness of a single dose of 800 mg has also been proven.

The dose for adults, as well as for children, can be calculated taking into account ideal body weight.

For children

the drug is prescribed in a total dose of 32 mg/kg (but not more than 2 g) for 3 days according to the following scheme:

first dose – 12.9 mg/kg (no more than a single dose of 800 mg);

second dose – 6.5 mg/kg (not more than 400 mg) 6 hours after the first dose;

third dose – 6.5 mg/kg (not more than 400 mg) 18 hours after the second dose;

fourth dose – 6.5 mg/kg (not more than 400 mg) 24 hours after the third dose.

For the radical treatment of malaria caused by Plasmodium malariae and Plasmodium vivax

, simultaneous administration of 8-aminoquinolone derivatives is necessary.

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 .

Plaquenil, 60 pcs., 200 mg, film-coated tablets

Note: All doses are for hydroxychloroquine sulfate and are not equivalent to doses for the base.

Inside, during meals or with a glass of milk.

Treatment of RA. Hydroxychloroquine has cumulative activity. It takes several weeks of taking the drug for its therapeutic effect to manifest itself, while side effects may appear relatively early. The necessary therapeutic effect develops after several months of taking the drug. If there is no objective improvement in the patient's condition within 6 months of taking hydroxychloroquine, the drug should be discontinued.

Adults (including older adults) should take the minimum effective dose. They should not exceed 6.5 mg/kg/day (calculated based on “ideal” body weight, not actual body weight) and can be either 200 or 400 mg/day.

In patients able to take 400 mg daily

Initially - 400 mg daily, in several doses. When obvious improvement is achieved, the dose can be reduced to 200 mg. If the effect decreases, the maintenance dose can be increased to 400 mg.

For children. The minimum effective dose should be used. The dose should not exceed 6.5 mg/kg (based on “ideal” body weight). Therefore, the 200 mg tablets are not suitable for children with an “ideal” body weight of less than 31 kg.

Use of the drug Plaquenil for combination therapy of RA. Plaquenil can be safely used in combination with corticosteroids, salicylates, NSAIDs, methotrexate and other second-line therapeutic agents. After several weeks of using the drug Plaquenil, the doses of corticosteroids and salicylates may be reduced or these drugs may be discontinued. Doses of GCS should be reduced gradually every 4-5 days: the dose of cortisone - by no more than 5-15 mg, the dose of hydrocortisone - by no more than 5-10 mg, the dose of prednisolone and prednisone - by no more than 1-2.5 mg , the dose of methylprednisolone and triamcinolone - no more than 1-2 mg and dexamethasone - no more than 0.25-0.5 mg.

Treatment of SLE. The initial average dose in adults is 400 mg 1 or 2 times a day. It should be given over several weeks or months depending on the patient's response. For long-term maintenance therapy, it is sufficient to use the drug in a lower dose - from 200 to 400 mg.

Treatment of malaria

Prevention of acute attacks of malaria caused by P. malariae and susceptible strains of Plasmodium falciparum

Adults: 400 mg weekly on the same day of the week.

For children, the weekly dose is 6.5 mg/kg (for calculation, the “ideal” body weight is taken), however, regardless of body weight, it should not exceed the dose for adults.

If conditions allow, preventive therapy should begin 2 weeks before entering an endemic area. If this is not possible, then an initial double (loading) dose can be prescribed: adults - 800 mg, children - 12.9 mg/kg of “ideal” body weight (but not more than 800 mg), divided into two doses with a 6-hour interval. Preventive treatment should be continued for 8 weeks after leaving the endemic area.

Treatment of acute attacks of malaria

For adults, an initial dose of 800 mg is followed by a dose of 400 mg after 6 or 8 hours, and then 400 mg on 2 subsequent days (for a total of 2 g of hydroxychloroquine sulfate).

Alternative treatment: A single dose of 800 mg has also been shown to be effective.

Doses for adults can also be calculated based on “ideal” body weight, similar to the calculation of doses for children (see below).

For children, a total dose of 32 mg/kg of “ideal” body weight (but not higher than 2 g) is prescribed over 3 days as follows:

first dose - 12.9 mg/kg (single dose not more than 800 mg); second dose - 6.5 mg/kg (not more than 400 mg) 6 hours after the first; third dose - 6.5 mg/kg (not more than 400 mg) 18 hours after the second dose; fourth dose - 6.5 mg/kg (not more than 400 mg) 24 hours after the third dose.

Radical treatment of malaria caused by Plasmodium malariae and Plasmodium vivax

For radical treatment of malaria caused by Plasmodium malariae and Plasmodium vivax, simultaneous administration of 8-aminoquinolone derivatives is necessary.

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.

Place of Plaquenil in modern therapy of rheumatoid arthritis

About the article

8050

Regular issues of "RMZh" No. 7 dated 04/06/2009 p. 487

Category: Rheumatology

Authors: Imametdinova N.V. Chichasova G.R. , Nasonov E.L.

For quotation:

Imametdinova N.V. Chichasova G.R., Nasonov E.L. Place of Plaquenil in modern therapy of rheumatoid arthritis. RMJ. 2009;7:487.

The anti-inflammatory effect of antimalarial drugs was noted almost 200 years ago. Quinine and cinchonine, the active components of the cinchona tree, were isolated back in 1820. At the end of the 19th century, the English physician JP Payne first identified the clinical effect of quinine in lupus erythematosus. Subsequently, two synthetic aminoquinoline analogues - chloroquine diphosphate and hydroxychloroquine sulfate (Plaquenil - Pl) began to be widely used in rheumatology. It has been noted that, despite their approximately equal effectiveness, chloroquine is approximately 2–3 times more toxic than hydroxychloroquine [1].

Pl has various mechanisms of action. In the treatment of rheumatic diseases, the most significant are its anti-inflammatory, analgesic and immunomodulatory effects [2]. In addition, Pl causes hypoglycemic, hypolipidemic, antiplatelet, antioxidant, antimicrobial and antiproliferative effects, which is of general therapeutic importance. Among the basic anti-inflammatory drugs (DMARDs) used in the treatment of rheumatoid arthritis (RA), Pl occupies a special place. This is due to the fact that its positive effect in patients with RA in comparison with placebo becomes significant with long-term treatment (at least 6 months), while the effectiveness of different doses of the drug is approximately the same [3]. In the 60–70s of the last century, before the concept of early “aggressive” treatment of RA was widely introduced into practice, antimalarial drugs were prescribed at the onset of the disease to the vast majority of patients. It should be noted that with highly active variants of the onset of RA, aminoquinoline drugs did not allow achieving a pronounced effect within several months, either in relation to the clinical manifestations of RA or in relation to the radiological progression of the disease. However, an analysis of the course of RA in a large group of patients (more than 600 patients) showed that the prescription of aminoquinoline drugs in the earliest stages of the disease (up to 6 months), even if they are insufficiently effective and the need to replace them with other DMARDs at the stages of treatment and observation, all was associated with a more favorable outcome after 15–20 years of illness compared with patients who were prescribed DMARDs after 1–3 years of illness [4]. At the present stage, treatment of RA is focused on suppressing the activity of the disease as quickly as possible, which leads to a decrease in the progression of destruction in the joints and preservation of the functional ability of patients [5]. The current availability of a sufficient range of DMARDs, the effect of which develops much faster, within 1–3 months (methotrexate, leflunomide, alkylating cytostatics), makes their early prescription in patients with active RA more justified. According to modern recommendations [6], methotrexate and leflunomide are recognized as first-line drugs among DMARDs for RA, and Pl has become prescribed much less frequently. There appear to be several situations where the use of Pl may be useful. At the onset of the development of articular syndrome, accurate nosological verification of the diagnosis is not possible in all patients. Both RA and diffuse connective tissue diseases (DCTD) can debut with the same symptoms - with symmetrical polyarthritis with slight morning stiffness, the absence of reliable laboratory markers (rheumatoid factor, antinuclear factor, etc.). In this situation, Pl may be the drug of choice, since it is also successfully used in the treatment of DBST. It is known that Pl is able to suppress the synthesis of cytokines (IL-1, IL-6, TNF-

Plaquenil price

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

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