Hydroxychloroquine: analogues, when prescribed

Pharmacological action, pharmacodynamics and pharmacokinetics

Hydroxychloroquine has the following pharmacological effects:

Antiprotozoal.
Antimalarial.
Immunosuppressive.
Anti-inflammatory.

The drug disrupts the replication of Plasmodium genetic material, and therefore is very effective in treating all forms of malaria.

After administration, the maximum concentration of the drug in the blood is determined after 1-2 hours. Hydroxychloroquine has high bioavailability, as well as the ability to accumulate in the respiratory, hepatolienal and central nervous systems.

The drug is able to overcome the placental barrier and penetrate to the fetus. It is excreted mainly in urine and partly in feces.

Hydroxychloroquine tablet p/o film 200mg 30 pcs

The drug is taken orally only. Each dose should be taken with a meal or with a glass of milk. TREATMENT OF MALARIA 1. Prevention of acute attacks of malaria caused by P. malariae and susceptible strains of P. Falciparum For adults - 400 mg weekly, on the same day of the week.

For children, the weekly dose is 6.5 mg/kg body weight (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. Prophylactic treatment should be continued for 8 weeks after leaving the endemic area.

2. Treatment of acute attacks of malaria.

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

Alternative treatment: A single dose of 800 mg has been proven 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 three days as follows: first dose: 12.9 mg/kg body weight (single dose not more than 800 mg); second dose: 6.5 mg/kg body weight (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.

3.Radical treatment of malaria caused by P. malariae and P. vivax.

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

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.

1.Adults (including the elderly).

The minimum effective dose should be taken. They should not exceed 6.5 mg/kg body weight/day (calculated based on “ideal” body weight, not actual body weight) and can be either 200 or 400 mg per day.

2.In patients able to take 400 mg daily.

Initially, 400 mg daily, divided into 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.

3. Children over 6 years old and weighing more than 31 kg.

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

4.Use of the drug Hydroxychloroquine for combination therapy of RA.

Hydroxychloroquine can be safely used in combination with corticosteroids, salicylates, nonsteroidal anti-inflammatory drugs, methotrexate, and other second-line therapeutic agents. After several weeks of using Hydroxychloroquine, the doses of corticosteroids and salicylates may be reduced or these drugs may be discontinued. Doses of glucocorticosteroids 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 SYSTEMIC LUPUS ERYTHEMATOSUS The initial average dose in adults is 400 mg 1 or 2 times a day. Hydroxychloroquine 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 of 200 to 400 mg.

TREATMENT OF PHOTODERMATITIS: up to 400 mg/day. Treatment should be limited to periods of maximum solar exposure.

Indications and contraindications

Hydroxychloroquine is indicated for use in the following diseases:

Rheumatic pathology (SLE, rheumatoid arthritis).
Various forms of malaria.

Absolute contraindications to taking the drug are:

Individual intolerance.
Pregnancy period.
Childhood.
Retinopathy.

Relative contraindications:

Decreased visual acuity, the presence of scotomas, color blindness and acquired color vision disorders.
Porphyria.
Severe mental and neurological pathology.
Psoriasis.
Hepatitis, cirrhosis, liver failure.
Decompensated diseases of the gastrointestinal tract.
Acute and chronic renal failure.

Side effects and overdose

The drug is quite toxic and causes many adverse reactions from most organs and systems:

Organ of vision: metamorphopsia, retinopathy, corneal edema, accommodation disorders.
Skin and mucous membranes: hypo- or hyperpigmentation, itching, rash, hair loss, psoriasis.
Digestive tract: dyspeptic disorders, lack of appetite, stool disorders, abdominal pain, liver failure.
Central nervous system: dizziness, emotional instability, irritability, convulsions, disturbances of consciousness.
CVS: myocardial hypertrophy, various blockades and conduction disorders.
Hematopoietic organs: decrease in the number of blood cells.
Allergic reactions: urticaria, angioedema, anaphylactic shock.

Overdose of Hydrosichloroquine can be acute or chronic. In the first case, the patient suffers from headaches, severe weakness, hypotension, and visual disturbances. In severe cases, convulsions, disturbances of consciousness, respiratory arrest and cardiac arrest may develop. Chronic intoxication is characterized by myocardial hypertrophy.

The patient urgently needs to rinse the stomach with clean water, give adsorbents and an antidote (ammonium chloride). Forced diuresis is also performed.

Publications in the media

(Hydroxychlorequinum) INN

Synonyms. Plaquenil.

Composition and release form. Hydroxychloroquine tablets 0.2 g.

Indications. Malaria; rheumatoid arthritis, systemic lupus erythematosus, scleroderma, skin diseases caused by sunlight.

Pharmachologic effect. Active against erythrocyte forms of plasmodium. It has anti-inflammatory and moderate immunosuppressive activity. Interacts with free radicals, stabilizes lysosome membranes, suppresses the reactivity of lymphocytes, inhibits the chemotaxis of leukocytes, inhibits the activity of neutral proteases and collagenase contained in rheumatoid nodules that destroy cartilage tissue. Unlike chloroquine, the drug is better tolerated by patients.

Pharmacokinetics. Well absorbed from the gastrointestinal tract into the blood. Bioavailability 74%. Peak plasma concentration is 3.2 hours. Distributed to the kidneys, liver, lungs. The concentration in erythrocytes is 2-5 times higher than in blood plasma. Plasma protein binding - 45%. Metabolized in the liver to active metabolites. It is excreted from the body very slowly in the urine and partially in bile. May be present in urine for several months or even years after treatment is stopped.

Side effects. Dizziness, tinnitus, hearing loss, headache, agitation; muscle weakness; neuromuscular blockade; decreased visual acuity, pigment deposition in the cornea; nausea, vomiting, anorexia, diarrhea, cramping abdominal pain; skin rash, hair loss, skin depigmentation.

Contraindications. Retinopathy, pregnancy, hypersensitivity to the drug, psoriasis, glucose-6-phosphate dehydrogenase deficiency, blood diseases; liver dysfunction; neurological disorders.

Adverse reactions when interacting with other drugs. Hydroxychloroquine increases the concentration of digoxin in the blood. Aminoglycoside antibiotics potentiate the direct blocking effect of hydroxychloroquine at the neuromuscular junction. The interval between doses of hydroxychloroquine and antacids containing magnesium and calcium hydroxides should be at least 4 hours (due to the formation of complexes that are difficult to absorb). Hydroxychloroquine increases plasma concentrations of penicillamine, increasing the risk of hematological and cutaneous reactions.

Information for the patient. For the course of treatment of malaria, 2 g is prescribed. For connective tissue diseases, 0.4 g is usually used 2 times a day. The drug is taken after meals. Missed dose: Take the missed dose as soon as possible; do not take it at all if there is almost no time left before the next dose; do not take double doses. With long-term treatment with the drug, monitoring of vision, blood patterns, kidney and liver function is necessary.

Hydroxychloroquine: instructions for use

The drug is taken orally with or after meals. The tablets should be taken with milk.

The treatment regimen depends on the disease and the severity of its manifestations.

For rheumatoid arthritis, drug therapy is carried out for several months. The dosage for adult patients is 6.5 milligrams per kilogram of body weight per day.

Treatment for systemic lupus erythematosus is also long-term. The daily dose is from 0.2 to 0.4 grams.

Treatment for malaria lasts 3 days. The course dose is 2 grams of Hydroxychloroquine.

Hydroxychloroquine, 30 pcs., 200 mg, film-coated tablets

Hydroxychloroquine tablets should be taken orally with 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 Hydroxychloroquine for combination therapy of RA. Can be safely used in combination with GCS, salicylates, NSAIDs, methotrexate and other second-line therapeutic agents. After several weeks of using the drug, 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.

Interaction with other medications

The drug slows down the excretion of cardiac glycosides, especially Digoxin, which leads to overdose and intoxication.

Hydroxychloroquine increases the effectiveness of insulin and a number of other hypoglycemic medications, increases the toxicity of antibacterial drugs from the aminoglycoside group and reduces the intensity of antibody formation when administered rabies vaccine.

Antacids impair the absorption of the drug, so the interval between taking them should be at least 4 hours.

Chloroquine/hydroxychloroquine in the treatment of patients with COVID-19

Doctors all over the world are currently searching for drugs to effectively treat patients with COVID-19. On April 21, during “Scientific Tuesday”, which was traditionally held online, clinical data on the use of two actively discussed drugs in drug therapy: chloroquine and hydroxychloroquine were presented to the research staff of the Federal State Budgetary Institution “National Medical Research Center for TPM” of the Ministry of Health of Russia. The report was made by a senior researcher at the Department of Clinical Cardiology of the National Medical Research Center for Therapy and Preventive Medicine, Ph.D. Yu.V. Mareev.

According to in vitro (test tube) studies, chloroquine and hydroxychloroquine suppressed the effect of the SARS-CoV-2 virus, which causes COVID-19. The possibility of using the drug in the treatment of COVID-19 was actively discussed after the publication of the work of P. Gautret et al. [1], which showed that on the 6th day of treatment, among patients who were given hydroxychloroquine, compared with those who were not given it, there were fewer virus-positive patients (according to PCR tests). And among the patients who were given a combination of hydroxychloroquine and azithromycin, there was not a single virus-positive patient on the 6th day of treatment. At the same time, this study has a number of limitations. First of all, it is necessary to note its small size (42 patients). Also, there was no randomization in the work, which means the results could be due to differences in patient characteristics rather than the actual effect of the drugs. In addition, it is worth noting that 6 patients were excluded from the hydroxychloroquine group, as well as the fact that clinical outcomes were not analyzed.

In addition, two more randomized studies were done in China. In the first study involving 30 people [2], there was no difference in the number of patients in whom the virus was absent on the 7th day of treatment according to PCR tests. The groups also did not differ in the time it took for body temperature to normalize. In a second study involving 62 people [3], the hydroxychlorine group showed faster normalization of body temperature and cough, as well as more pronounced positive dynamics according to lung CT.

It is obvious that the first clinical studies on the use of hydroxychloroquine, conducted in France and China, do not provide a definitive answer about the drug’s place in the treatment of COVID-19. Therefore, a number of randomized controlled trials have now been launched that will study the role of hydroxychloroquine and chloroquine both in the treatment of patients with COVID-19 and in the prevention of infection in medical personnel involved in the treatment of such patients. In this case, an important issue is both determining the feasibility of using drugs in general and finding optimal doses. Confirmation of the importance of the latter are the results of the ChloroCOVID-19 study [4], which was originally planned to compare the effectiveness of high and low doses of chloroquine, but after a trend towards an increased risk of death with a high dose of the drug was recorded, this part of the study was completed ahead of schedule.

As noted, speaking in the discussion, the head of the department of preventive pharmacotherapy, MD, Professor S.Yu. Martsevich, “in this case we saw randomized studies, the quality of which was very low; they did not meet the most basic requirements for such studies. Therefore, the evidentiary value of these randomized trials is low. However, according to him, there is an opinion that in exceptional cases the effectiveness of the drug can be confirmed without conducting an RCT. However, for this to happen, two conditions must be met: the evidence of the drug’s effects and the presence of competent studies of a lesser degree of evidence, namely, observational studies. Now, according to Sergei Yuryevich, the results of a large French observational study [5], based on a register of patients in four clinics, are being prepared for publication. This study showed a complete lack of effect of hydroxychloroquine.

Regarding the prevention of COVID-19 using this drug, its use is undesirable given the lack of convincing data and potential side effects. According to Professor S.Yu. Martsevich, this especially applies to patients with cardiovascular diseases.

Update: After the meeting, another observational study with hydroxychloroquine was published on medrxiv.org. This work assessed the risk of death and the need for mechanical ventilation (ALV) in 368 COVID 19 patients observed in veterans' clinics in the United States[6]. The work compared patients receiving hydroxychloroquine, a combination of hydroxychloroquine and azithromycin, and patients not receiving hydroxychloroquine. It should be noted that this is not a randomized trial, but a retrospective analysis of data. Patients receiving hydroxychloroquine or a combination of hydroxychloroquine and azithromycin had more severe disease, so the authors performed statistical analyzes to account for these differences. According to the work, the risk of death of patients was higher in patients receiving hydroxychloroquine compared to patients who did not receive it, but the risk of death in patients receiving a combination of hydroxychloroquine and azithromycin did not differ from those who did not receive hydroxychloroquine. The risk of mechanical ventilation did not differ between groups. The results of the work should be treated with caution (which was also indicated by the authors of the article), since any statistical analysis has its limitations, and statistical analysis cannot take into account differences in characteristics that were not included in the database. Thus, only the results of large RCTs will answer the question of the effectiveness and safety of hydroxychloroquine in patients with COVID 19.

Links:

[1] P. Gautret et al., “Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial,” Int. J. Antimicrob. Agents, p. 105949, Mar. 2020.

[2] J. CHEN et al., “A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19),” J Zhejiang Univ (Med Sci), vol. 49, no. February, pp. 1–10, Mar. 2022.

[3] Z. Chen et al., “Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial,” medRxiv, p. 2020.03.22.20040758, Apr. 2022.

[4] MGS Borba et al., “Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded , phase IIb clinical trial (CloroCovid-19 Study),” medRxiv, p. 2022.04.07.20056424, Apr. 2022.

[5] M. Mahevas et al., “No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial,” medRxiv, p. 2020.04.10.20060699, Apr. 2022.

[6] J. Magagnoli et al., “Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19,” medRxiv, p. 2020.04.16.20065920, Apr. 2022.

Reviews of Hydroxychloroquine

There are a lot of reviews about the drug on the Internet. They are left by patients with rheumatic diseases and people who have had malaria.

Most consumers note the high effectiveness of the drug. It helps cope with infection and manifestations of rheumatic pathology. However, some patients are dissatisfied with the long-term development of the effect and the appearance of various adverse reactions. Moreover, undesirable manifestations may occur after taking the first tablet, but the therapeutic effect will take at least a few days.