Active ingredients: Hydroxychloroquine sulfate
PLAQUENIL 200 mg coated tablets
Why is Plaquenil used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Pesticide - Antirheumatic
THERAPEUTIC INDICATIONS
Adults
PLAQUENIL is indicated for the treatment of active and chronic rheumatoid arthritis and discoid and disseminated lupus erythematosus.
Pediatric population
It is indicated for the treatment of juvenile idiopathic arthritis (in combination therapy), and for systemic erythematosus and discoid lupus.
Contraindications When Plaquenil should not be used
- Retinal and visual field alterations attributable to 4-aminoquinoline compounds;
- hypersensitivity to the active substance and to the 4-aminoquinoline compounds or to any of the excipients;
- in case of pre-existing maculopathies;
- the formulations dosed at 200 mg are contraindicated in children under 6 years of age or in any case weighing less than 31 kg.
Precautions for use What you need to know before taking Plaquenil
Use particular caution in patients with hepatic or renal insufficiency for whom the dose may need to be reduced, as well as for those taking drugs that affect these organs.
Particular caution should also be used in patients with gastrointestinal, neurological or haematological disorders; patients with hypersensitivity to quinine; in case of glucose-6-phosphate dehydrogenase deficiency, porphyria and psoriasis.
Since PLAQUENIL can cause dermatological reactions, it should be used with caution in patients administered drugs with a significant tendency to cause dermatitis.
In the treatment of rheumatoid arthritis, if no objective improvement is detected within six months, it is advisable to discontinue therapy.
The safe use of PLAQUENIL in juvenile rheumatoid arthritis has not been established.
Interactions Which drugs or foods can modify the effect of Plaquenil
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even those without a prescription.
The concomitant administration of hydroxychloroquine and digoxin may lead to an increase in blood levels of digoxin: it is therefore necessary to closely monitor digoxinaemia in patients treated with this combination of drugs.
Since hydroxychloroquine can increase the effects of hypoglycemic treatment it is necessary to reduce the doses of insulin or antidiabetic drugs in general.
There is the possibility of interactions with phenylbutazone or with other drugs that have a tendency to cause dermatitis and with known hepatotoxic preparations.
Warnings It is important to know that:
After prolonged treatment with high doses of quinoline derivatives, peripheral nervous system disorders have been reported in rare cases. It is therefore necessary to follow the prescribed dosage. Irreversible retinal lesions, believed to be dose related, have been observed in some patients who have received high and prolonged doses of 4-aminoquinoline derivatives for the treatment of rheumatoid arthritis and lupus erythematosus. PLAQUENIL, a thorough eye examination should be performed initially which includes the determination of visual acuity, visual field, color vision and fundus examination. These examinations must then be repeated at least once a year.
Retinal toxicity is largely dose related. The risk of retinal damage is slight up to a daily dose of 6.5 mg / kg. Exceeding the recommended daily dose significantly increases the risk of retinal toxicity.
These tests must be repeated more frequently and must be adapted to the individual patient in the following situations:
- daily dosage higher than 6.5 mg / kg of ideal weight (thin person): refer to the ideal body weight (that of the thin person). The use of absolute body weight could lead to an overdose in the obese;
- kidney failure;
- cumulative dose greater than 200 g;
- elderly person;
- decreased visual acuity.
If there are signs of alterations in visual acuity, visual field, color vision and macular areas of the retina - such as pigment changes, loss of the foveal reflex - or any visual symptoms that cannot be fully explained with difficulty in accommodation or corneal opacity, the drug should be discontinued immediately and the patient monitored closely to detect any progression of the alterations. Retinal lesions (and visual disturbances) may worsen even after discontinuation of treatment (see section Undesirable effects).
Very rare cases of suicidal tendencies have been reported in patients treated with hydroxychloroquine.
In patients on long-term therapy it is recommended to periodically check the parameters of the complete blood count and to discontinue the administration of hydroxychloroquine if abnormalities appear.
Younger children are particularly sensitive to the toxic effects of 4-aminoquinolines; it is therefore necessary that patients are warned about the need to store hydroxychloroquine out of the reach of children.
All patients on prolonged treatment with PLAQUENIL should periodically undergo an examination of the musculoskeletal function and of the patellar and achilles reflexes. If muscle weakness occurs, discontinue the drug.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Pregnancy and breastfeeding
Pregnancy
Ask your doctor or pharmacist for advice before taking any medicine.
Hydroxychloroquine crosses the placenta. There are limited data on the use of hydroxychloroquine during pregnancy. It should be noted that CNS side effects such as ototoxicity have been observed after administration of 4-aminoquinoline derivatives at therapeutic doses. (auditory and vestibular toxicity, congenital deafness), retinal haemorrhages and abnormal retinal pigmentation.
Hydroxychloroquine should be avoided in pregnancy unless, in the judgment of the physician, the potential benefits outweigh the possible risks.
Feeding time
Particular attention must be paid in case of breastfeeding by patients treated with hydroxychloroquine, since the drug is excreted in breast milk in small quantities and in consideration of the fact that the child is very sensitive to the toxic effects of 4-aminoquinoline.
Effects on ability to drive and use machines
Driving and using machines are not recommended, as hydroxychloroquine can adversely affect visual accommodation and cause blurred vision. If this is the case, it may be necessary to temporarily reduce the dosage.
Dosage and method of use How to use Plaquenil: Dosage
Rheumatoid arthritis:
The drug acts by accumulation and it takes a few weeks for the first beneficial effects to occur, while mild disturbances can occur relatively soon. It may take several months of treatment before maximum effects can be achieved. If objective improvement is not detected within six months, treatment should be discontinued.
Initial dosage: 400 to 600 mg per day (2 to 3 coated tablets) given with meals or with a glass of milk. In a small percentage of patients, the appearance of unpleasant side effects may require a reduction in the starting dose. Thereafter, after 5-10 days, the dose can be gradually increased to the optimal one, often without recurring side effects.
Maintenance dose: when a good therapeutic response is achieved, usually between 4 and 12 weeks, the dose is reduced in half, from 200 to 400 mg (1 or 2 coated tablets) per day. A higher incidence of retinopathy has been described when this dose is exceeded.
If a relapse occurs after discontinuation of therapy, the drug can be resumed by continuing with intermittent administration, if there are no ocular contraindications.
Corticosteroids and salicylates can usually be used in reduced doses in combination with PLAQUENIL or can be completely discontinued after the drug has been administered for several weeks.
When a gradual reduction in the dose of steroids is indicated, it can be done by reducing the dose every 4 or 5 days: by not more than 5-15 mg of hydrocortisone; 5-10 mg of prednisolone and prednisone; of 1-2.5 mg of methylprednisolone; of 1-2 mg of triamcinolone; of 0.25-0.5 mg of dexamethasone.
Lupus erythematosus:
The average starting dose is 400 mg once or twice a day. This dose can be continued for several weeks or months depending on the patient's response. For maintenance therapy, a lower dose of 200 to 400 mg per day will often suffice. A higher incidence of retinopathy has been described when this maintenance dose is exceeded.
Pediatric population
The lowest effective dose should be used and the dose of 6.5 mg / kg / day should never be exceeded considering an ideal body weight. Therefore the 200 mg tablets are not suitable for use in children with an ideal body weight of less than 31 kg
Overdose What to do if you have taken too much Plaquenil
Overdose of 4-aminoquinoline compounds is particularly dangerous in children in whom doses of as little as 1 or 2 g have been fatal.
The 4-aminoquinoline compounds are rapidly and completely absorbed after ingestion, and in case of accidental overdose (more rarely in relation to the use of lower doses in hypersensitive patients), toxic symptoms consisting of headache, drowsiness, may occur within 30 minutes. visual disturbances, cardiovascular collapse, seizures, hypokalaemia, and rhythm and conduction disturbances including QT interval prolongation, torsade de pointes, ventricular tachycardia and ventricular fibrillation, followed by sudden and potentially fatal respiratory and cardiac arrest. Immediate medical treatment is required. as these effects may appear shortly after overdose. The electrocardiogram may detect atrial arrest, nodal rhythm, prolonged intraventricular conduction time and progressive bradycardia, resulting in ventricular fibrillation and / or cardiac arrest. Treatment is symptomatic and must be ready, with immediate emptying of the stomach causing vomiting (at home before being transported to the hospital) or by gastric lavage until the stomach is completely emptied. Activated charcoal, if introduced through the gastric tube within 30 minutes by ingestion of the tablets and followed by gastric lavage, it can further inhibit the absorption of the drug. To be effective, the dose of activated charcoal must be at least 5 times that of hydroxychloroquine ingested. Any convulsions must be checked before attempting gastric lavage If they are due to cerebral stimulation, it is possible to try to administer ultra-short acting barbiturates; if instead they are due to anoxia, they must be treated with oxygen administration, artificial respiration, or, in case of shock in hypotension, by therapy with circulatory analeptics. Given the importance of breathing support, intubation may be necessary or tracheostomy followed, if necessary, by gastric lavage. In order to reduce the blood concentration of 4-aminoquinolines, exsanguinotransfusion has been suggested. A patient who survives the acute phase and is asymptomatic should be carefully monitored for at least 6 hours. to the forced administration of liquids and an adequate quantity of ammonium chloride can be administered for a few days (in adults, 8 g per day in divided doses) in order to acidify the urine to favor the increase in urinary excretion.
The possibility of parenteral administration of diazepam should be considered as some studies have shown that this treatment reverses the cardiotoxic effects of chloroquine.
Provide breathing support and shock management if necessary.
In case of accidental intake of an excessive dose of the medicine, notify your doctor immediately or go to the nearest hospital
Side Effects What are the side effects of Plaquenil
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Disorders of the blood and lymphatic system
Cases of bone marrow depression have rarely been reported. Haematological conditions such as anemia, aplastic anemia, agranulocytosis, leukopenia and thrombocytopenia have been reported. Hemolysis in subjects with G6P-DH deficiency.
Disorders of the immune system
Cases of urticaria, angioedema and bronchospasm have been reported.
Metabolism and nutrition disorders
Anorexia. Hydroxychloroquine can aggravate porphyria.
Psychiatric disorders
Irritability, nervousness, emotional instability, psychotic nightmares, suicidal tendencies.
Nervous system disorders
Headache, dizziness, nystagmus, nervous deafness, convulsions and ataxia have been reported with this class of drugs.
Eye disorders
Rarely, retinopathy, with pigmentation changes and visual field defects, have been reported. In its initial form, retinopathy appears to be reversible upon discontinuation of hydroxychloroquine therapy. If it has the potential to develop, the risk of progression is possible, even after the end of treatment. There have been reports of maculopathies and macular degeneration which may be irreversible Patients with retinal changes may initially be asymptomatic, or may have scotomatous vision with paracentral and pericentral rings, temporal scotomas and impaired color perception.
They have been reported corneal changes which include edema and opacity, which can be either asymptomatic or can cause disturbances such as halos, blurred vision or photophobia. These signs and symptoms may be transient or reversible after stopping treatment.
Blurring of vision may also occur due to accommodation disorders which are dose dependent and reversible.
Ear and labyrinth disorders
Vertigo, tinnitus, hearing loss.
Cardiac pathologies
Cardiomyopathy has rarely been reported. Chronic toxicity effects should be suspected when conduction disorders (branch block / atrioventricular block) as well as biventricular hypertrophy are noted. Discontinuation of treatment may lead to recovery.
Gastrointestinal disorders
Gastrointestinal disturbances such as nausea, diarrhea, abdominal pain and rarely vomiting may occur. These symptoms resolve quickly by reducing the dose or stopping treatment.
Hepatobiliary disorders
Isolated cases of liver function test abnormalities have been reported and few cases of fulminant hepatic collapse have been published.
Skin and subcutaneous tissue disorders
Skin rashes sometimes occur; pigmentation of the skin and mucous membranes, itching, graying of the hair, alopecia. These effects resolve promptly upon stopping the treatment.
Skin rashes (urticarial, morbilliform, lichenoid, papular macular, purpura, centrifugal circinate erythema) bullous eruptions including very rare cases of erythema multiforme and Stevens-Johnson syndrome, toxic epidermal necrolysis, photosensitivity and exfoliative dermatitis. Very rare cases of acute generalized pustular rash to distinguish from psoriasis although hydroxychloroquine can aggravate psoriasis attacks. At the same time, fever and hyperleukocytosis can occur. The prognosis is generally favorable after discontinuation of treatment.
Musculoskeletal and connective tissue disorders
Musculoskeletal myopathy or neuromyopathies leading to progressive weakness and atrophy of proximal muscle groups have been reported. Myopathy may be reversible after discontinuation of treatment, but recovery can take many months. Minor sensory disturbances, depression of tendon reflexes and abnormal nerve conduction were observed.
Other effects: Weight loss, fatigue, non-light sensitive psoriasis.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date printed on the package
The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
Keep this medicine out of the reach and sight of children.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
COMPOSITION
One coated tablet contains:
Active principle: hydroxychloroquine sulfate 200 mg
Excipients: lactose monohydrate, povidone, corn starch, magnesium stearate, opadry OY-L-28900 (hypromellose, macrogol 400, titanium dioxide, lactose monohydrate).
PHARMACEUTICAL FORM AND CONTENT
30 coated tablets of 200 mg
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
PLAQUENIL 200 MG COATED TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One coated tablet contains:
Active ingredient: Hydroxychloroquine sulfate 200 mg
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Coated tablet.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Adults
PLAQUENIL is indicated for the treatment of active and chronic rheumatoid arthritis and discoid and disseminated lupus erythematosus.
Pediatric population
It is indicated for the treatment of juvenile idiopathic arthritis (in combination therapy), and for systemic erythematosus and discoid lupus.
04.2 Posology and method of administration
Rheumatoid arthritis: the drug acts by accumulation and it takes a few weeks for the first beneficial effects to occur, while mild ailments can occur relatively soon. It may take several months of treatment before maximum effects can be achieved.
If objective improvement is not detected within six months, treatment should be discontinued.
Initial dosage: 400 to 600 mg per day (2 to 3 coated tablets) given with meals or with a glass of milk. In a small percentage of patients, the appearance of unpleasant side effects may require a reduction in the starting dose. Thereafter, after 5-10 days, the dose can be gradually increased to the optimal one, often without recurring side effects.
Maintenance dose: When a good therapeutic response is achieved, usually between 4 and 12 weeks, the dose is reduced in half, from 200 to 400 mg (1 or 2 coated tablets) per day. A higher incidence of retinopathy has been described when this dose is exceeded.
If a relapse occurs after discontinuation of therapy, the drug can be resumed by continuing with intermittent administration, if there are no ocular contraindications.
Corticosteroids and salicylates can usually be used in reduced doses in combination with PLAQUENIL or can be completely discontinued after the drug has been administered for several weeks.
When a gradual reduction in the dose of steroids is indicated, it can be done by reducing the cortisone dose every 4 or 5 days by no more than 5-15 mg of hydrocortisone; 5-10 mg of prednisolone and prednisone; of 1-2.5 mg of methylprednisolone; of 1-2 mg of triamcinolone; of 0.25-0.5 mg of dexamethasone.
Lupus erythematosus: The average starting dose is 400 mg once or twice a day. This dose can be continued for several weeks or months depending on the patient's response. For maintenance therapy, a lower dose of 200 to 400 mg per day will often suffice.
A higher incidence of retinopathy has been described when this maintenance dose is exceeded.
Pediatric population: the minimum effective dose should be used and the dose of 6.5 mg / kg / day should never be exceeded considering an ideal body weight. Therefore the 200 mg tablets are not suitable for use in children with an ideal body weight of less than 31kg.
04.3 Contraindications
Hypersensitivity to the active substance and to 4-aminoquinoline compounds or to any of the excipients.
Retinal and visual field alterations attributable to 4-aminoquinoline compounds.
In case of pre-existing maculopathies.
The formulations dosed at 200 mg are contraindicated in children under the age of 6 years or in any case weighing less than 31 kg.
04.4 Special warnings and appropriate precautions for use
Special warnings
After prolonged treatment with high doses of quinoline derivatives, peripheral nervous system disorders have been reported in rare cases. It is therefore necessary to follow the prescribed dosage. Irreversible retinal lesions, believed to be dose related, have been observed in some patients who have received high and prolonged doses of 4-aminoquinoline derivatives for the treatment of rheumatoid arthritis and lupus erythematosus.
When prolonged therapy with PLAQUENIL is planned, a thorough eye examination should be performed initially, which includes determination of visual acuity, visual field, color vision and fundus examination. These exams must then be repeated at least once a year.
Retinal toxicity is largely dose related. The risk of retinal damage is slight up to a daily dose of 6.5 mg / kg. Exceeding the recommended daily dose significantly increases the risk of retinal toxicity.
These tests must be repeated more frequently and must be adapted to the individual patient in the following situations:
• daily dosage higher than 6.5 mg / kg of ideal weight (thin person): refer to the ideal body weight (that of the thin person). The use of absolute body weight could lead to an overdose in the obese;
• kidney failure;
• cumulative dose greater than 200 g;
• elderly person;
• decreased visual acuity.
If there are signs of alterations in visual acuity, visual field, color vision and macular areas of the retina - such as pigment changes, loss of the foveal reflex - or any visual symptoms that cannot be fully explained with difficulty in accommodation or corneal opacity, the drug should be discontinued immediately and the patient monitored closely to detect any progression of the changes. Retinal lesions (and visual disturbances) may worsen even after discontinuation of treatment (see section 4.8 Undesirable effects) .
Very rare cases of suicidal tendencies have been reported in patients treated with hydroxychloroquine.
Hydroxychloroquine has been shown to cause severe hypoglycaemia including loss of consciousness which can be life threatening in patients treated with and without antidiabetic medicinal products. Patients on hydroxychloroquine therapy should be advised of the risk of hypoglycaemia and related clinical signs and symptoms Patients who, during treatment with hydroxychloroquine, present clinical symptoms attributable to hypoglycaemia should undergo blood glucose monitoring and re-evaluation of therapy, if deemed necessary.
Precautions for use
Use particular caution in patients with hepatic or renal insufficiency for whom the dose may need to be reduced, as well as for those taking drugs that affect these organs.
Particular caution should also be used in patients with gastrointestinal, neurological or haematological disorders; patients with hypersensitivity to quinine; in case of glucose-6-phosphate dehydrogenase deficiency, porphyria and psoriasis.
In patients on long-term therapy it is recommended to periodically check the parameters of the complete blood count and to discontinue the administration of hydroxychloroquine if abnormalities appear.
Young children are particularly sensitive to the toxic effects of 4-aminoquinolines; therefore patients should be advised to keep PLAQUENIL out of the reach of children.
All patients on prolonged treatment with PLAQUENIL should periodically undergo an examination of the musculoskeletal function and of the patellar and achilles reflexes. If muscle weakness occurs, discontinue the drug.
In the treatment of rheumatoid arthritis, if no objective improvement is detected within six months, it is advisable to discontinue therapy.
Since PLAQUENIL can cause dermatological reactions, it should be used with caution in patients administered drugs with a significant tendency to cause dermatitis.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
In patients treated with PLAQUENIL, cases of cardiomyopathy, resulting in heart failure, have been reported, some of which were fatal. Clinical monitoring for signs and symptoms of cardiomyopathy is advised and treatment with PLAQUENIL should be discontinued if cardiomyopathy develops. The existence of chronic toxicity must be considered when conduction disorders (branch block / atrioventricular block) as well as biventricular hypertrophy are evident.
04.5 Interactions with other medicinal products and other forms of interaction
The concomitant administration of hydroxychloroquine and digoxin may lead to an increase in blood levels of digoxin: it is therefore necessary to closely monitor digoxinaemia in patients treated with this combination of drugs.
Since hydroxychloroquine can increase the effects of hypoglycemic treatment it is necessary to reduce the doses of insulin or antidiabetic drugs in general.
There is the possibility of interactions with phenylbutazone or with other drugs that have a tendency to cause dermatitis and with known hepatotoxic preparations.
Halofantrine prolongs the QT interval and should not be administered with other drugs, which have the potential to induce cardiac arrhythmias, including hydroxychloroquine. Furthermore, if hydroxychloroquine is administered concomitantly with other arrhythmogenic drugs, such as amiodarone and moxifloxacin, it could increase the risk of ventricular arrhythmias.
An increase in the plasma level of cyclosporine has been reported when cyclosporine and hydroxychloroquine are co-administered.
Hydroxychloroquine may lower the seizure threshold. Concomitant administration of hydroxychloroquine with other antimalarial drugs known to lower the seizure threshold (eg mefloquine) may increase the risk of seizures.
Furthermore, the activity of antiepileptic drugs could be impaired when co-administered with hydroxychloroquine.
In a single dose interaction study, chloroquine was reported to reduce the bioavailability of praziquantel. It is not known whether such an effect exists when hydroxychloroquine and praziquantel are co-administered. By extrapolation, given the similarity in structure and pharmacokinetic parameters between hydroxychloroquine and chloroquine, a similar effect can also be expected for hydroxychloroquine.
There is a theoretical risk of inhibition of intracellular activity of? -Galactosidase when hydroxychloroquine is co-administered with agalsidase.
04.6 Pregnancy and lactation
Pregnancy
Hydroxychloroquine crosses the placenta. There are limited data on the use of hydroxychloroquine during pregnancy. It should be noted that central nervous system side effects such as ototoxicity have been observed after administration of 4-aminoquinoline derivatives at therapeutic doses. (auditory and vestibular toxicity, congenital deafness), retinal haemorrhages and abnormal retinal pigmentation.
Hydroxychloroquine should be avoided in pregnancy unless, in the judgment of the physician, the potential benefits outweigh the possible risks.
Feeding time
Particular attention must be paid in case of breastfeeding by patients treated with hydroxychloroquine, since the drug is excreted in breast milk in small quantities and in consideration of the fact that the child is very sensitive to the toxic effects of 4-aminoquinoline.
04.7 Effects on ability to drive and use machines
Driving and using machines are not recommended, as hydroxychloroquine can adversely affect visual accommodation and cause blurred vision. If this is the case, it may be necessary to temporarily reduce the dosage.
04.8 Undesirable effects
The following adverse reactions are classified by system organ class and frequency using the following convention: very common (≥1 / 10); common (≥1 / 100
Disorders of the blood and lymphatic system
Not known: bone marrow depression anemia, aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia.
Hemolysis in subjects with G6P-DH deficiency.
Disorders of the immune system
Not known: urticaria, angioedema, bronchospasm.
Metabolism and nutrition disorders
Common: anorexia.
Hypoglycaemia (see section 4.4). Frequency: not known.
Hydroxychloroquine can aggravate porphyria.
Psychiatric disorders
Common: affective lability
Uncommon: nervousness
Not known: psychosis, suicidal tendencies, irritability.
Nervous system disorders
Common: headache
Uncommon: dizziness
Not known: nystagmus, nervous deafness, convulsions and ataxia.
Eye disorders
Common: Blurred vision, due to accommodation disturbances, which are dose dependent and reversible.
Uncommon: retinopathy, with changes in pigmentation, and visual field defects. In its initial form, retinopathy appears to be reversible upon discontinuation of hydroxychloroquine therapy. If it has the potential to develop, the risk of progression is possible, even after the end of treatment. Patients with retinal changes may be initially asymptomatic, or they may have scotomatous vision with paracentral and pericentral rings, temporal scotomas and altered perception of color.
Corneal changes including edema and opacity have been reported, which can be either asymptomatic or can cause disturbances such as halos, blurred vision or photophobia. These signs and symptoms may be transient or reversible after stopping treatment.
Not known: There have been reports of maculopathies and macular degeneration which may be irreversible.
Ear and labyrinth disorders
Uncommon: dizziness, tinnitus
Not known: hearing loss
Cardiac pathologies
Not known: cardiomyopathy, which can lead to heart failure, and in some cases fatal
The existence of chronic toxicity should be considered when conduction disorders (branch block / atrioventricular block) as well as biventricular hypertrophy occur. Discontinuation of treatment may lead to recovery.
Gastrointestinal disorders
Very common: nausea, abdominal pain
Common: diarrhea, vomiting
These symptoms resolve quickly by reducing the dose or stopping treatment
Hepatobiliary disorders
Uncommon: liver function test abnormalities
Not known: fulminant hepatic failure
Skin and subcutaneous tissue disorders
Common: skin rash; itch.
Uncommon: skin and mucosal pigmentation disorders, graying of hair, alopecia.
These effects resolve promptly upon stopping the treatment.
Not known: Bullous eruptions including erythema multiforme, Stevens-Johnsone syndrome toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome), photosensitivity, exfoliative dermatitis, acute generalized pustular rash (AGEP).
AGEP must be distinguished from psoriasis although hydroxychloroquine can aggravate psoriasis attacks. At the same time, fever and hyperleukocytosis can occur. Prognosis is generally favorable after discontinuation of treatment.
Skin rashes (urticarial, morbilliform, lichenoid, papular maculo, purpura, centrifugal circinate erythema) have been reported
Musculoskeletal and connective tissue disorders
Uncommon: sensory-motor disorders.
Not known: musculoskeletal myopathy or neuromyopathies leading to progressive weakness and atrophy of proximal muscle groups.
Myopathy may be reversible after discontinuation of treatment, but recovery can take many months.
Depression of tendon reflexes and abnormal nerve conduction.
Other effects:
Weight loss, fatigue, non-light sensitive psoriasis.
04.9 Overdose
Overdose of 4-aminoquinoline compounds is particularly dangerous in children in whom doses of as little as 1 or 2 g have been fatal.
The 4-aminoquinoline compounds are rapidly and completely absorbed after ingestion, and in case of accidental overdose (more rarely in relation to the use of lower doses in hypersensitive patients), toxic symptoms consisting of headache, drowsiness, may occur within 30 minutes. visual disturbances, cardiovascular collapse, seizures, hypokalaemia, rhythm and conduction disturbances including QT interval prolongation, torsade de pointes, ventricular tachycardia and ventricular fibrillation, followed by sudden and potentially fatal respiratory and cardiac arrest. Immediate medical treatment is required. as these effects may appear shortly after overdose. The electrocardiogram may detect atrial arrest, nodal rhythm, prolonged intraventricular conduction time and progressive bradycardia, resulting in ventricular fibrillation and / or cardiac arrest. Treatment is symptomatic and must be ready, with immediate emptying of the stomach causing vomiting (at home before being transported to the hospital) or by gastric lavage until the stomach is completely emptied. Activated charcoal, if introduced through the gastric tube within 30 minutes by ingestion of the tablets and followed by gastric lavage, it can further inhibit the absorption of the drug. To be effective, the dose of activated charcoal must be at least 5 times that of hydroxychloroquine ingested. Any convulsions must be checked before attempting gastric lavage If they are due to cerebral stimulation, it is possible to try to administer ultra-short acting barbiturates; if instead they are due to anoxia, they must be treated with oxygen administration, artificial respiration, or, in case of shock in hypotension, by therapy with circulatory analeptics. Given the importance of breathing support, intubation may be necessary or tracheostomy followed, if necessary, by gastric lavage. In order to reduce the blood concentration of 4-aminoquinolines, exsanguinotransfusion has been suggested. A patient who survives the acute phase and is asymptomatic should be carefully monitored for at least 6 hours. to the forced administration of liquids and an adequate quantity of ammonium chloride can be administered for a few days (in adults, 8 g per day in divided doses) in order to acidify the urine to favor the increase in urinary excretion.
The possibility of parenteral administration of diazepam should be considered as some studies have shown that this treatment reverses the cardiotoxic effects of chloroquine.
Provide breathing support and shock management if necessary.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antiparasitic, antirheumatic. ATC code: P01BA02.
Hydroxychloroquine, an antimalarial belonging to the 4-aminoquinolinic family, is also a drug with a slow-acting antirheumatic action.
The therapeutic action of hydroxychloroquine is based on various pharmacological effects such as: interaction with sulfhydryl groups, modulation of enzymatic activity (in particular phospholipase, NADH-cytochrome C reductase, cholinesterase, protease and hydrolase), DNA fixation; stabilization of lysosomal membranes; inhibition of prostaglandin synthesis, polymorphonuclear chemotaxis and phagocytosis; possible interference with the production of interleukin 1 by monocytes and inhibition of the release of superoxide by neutrophils. Both the antirheumatic effect and the antimalarial effect can be explained in relation to the concentration reached in the intracellular acid vesicles and by increasing their pH.
05.2 Pharmacokinetic properties
Hydroxychloroquine is rapidly absorbed after oral administration. On average, its bioavailability is approximately 74%. The drug is widely distributed in the body and accumulates in blood cells and other tissues such as the liver, lungs, kidneys and eyes. The molecule is partially converted in the liver into active ethylated metabolites and then eliminated mainly via the kidney, in unchanged form in an amount ranging from 23 to 25%. Elimination also occurs via the biliary route. Excretion is slow, the terminal elimination half-life is approximately 50 days (total blood) and 32 days (plasma). Hydroxychloroquine crosses the placenta and passes into milk. maternal is comparable to that of chloroquine.
05.3 Preclinical safety data
The LD50 tested in mice by the intravenous and oral route was 56 mg / kg and 2620 mg / kg, respectively.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Lactose monohydrate; povidone; cornstarch; magnesium stearate; opadry OY-L-28900 (hypromellose, macrogol 400, titanium dioxide, lactose monohydrate).
06.2 Incompatibility
There are no known pharmaceutical incompatibilities.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
None.
06.5 Nature of the immediate packaging and contents of the package
Blister pack containing 30 coated tablets of 200 mg.
06.6 Instructions for use and handling
Not relevant.
07.0 MARKETING AUTHORIZATION HOLDER
sanofi-aventis S.p.A. - Viale L. Bodio, 37 / B - Milan
08.0 MARKETING AUTHORIZATION NUMBER
AIC: 013967056
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Renewal: 01/06/2010
10.0 DATE OF REVISION OF THE TEXT
December 2013