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  • Plaquenil
    / Sanofi


    Active Ingredient

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    100 X 200 mg

    full basket chart 1720 16018

    Related information


    Dosage

    Rheumatoid Arthritis: It is cumulative in action and will require several weeks to exert its beneficial therapeutic effects, whereas minor side effects may occur relatively early. Several months of therapy may be required before maximum effects can be obtained.
    Initial dosage: In adults, a suitable initial dosage is from 400 to 600 mg daily, preferably taken at meal times. In a few patients the side effects may require temporary reduction of the initial dosage. Generally, after five to ten days the dose may be gradually increased to the optimum response level, frequently without return of side effects.
    Maintenance dosage: When a good response is obtained (usually in four to twelve weeks) the dose can be reduced to 200 to 400 mg daily (but should not exceed 6 mg/kg per day) and can be continued as maintenance treatment. The minimum effective maintenance dose should be employed. The incidence of retinopathy has been reported to be higher when the maintenance dose is exceeded. If objective improvement (such as reduced joint swelling or increased mobility) does not occur within six months the drug should be discontinued. If a relapse occurs after medication is withdrawn, therapy may be resumed or continued on an intermittent schedule if there are no ocular contraindications. Safe use for the treatment of juvenile rheumatoid arthritis has not been established. Corticosteroids and salicylates may be used in conjunction with this compound, and they can generally be decreased gradually in dosage or eliminated after the drug has been used for several weeks. When gradual reduction of steroid dosage is suggested, it may be done by reducing every four to five days, the dose of cortisone by no more than 5 to 15 mg; of methylprednisolone from 1 to 2 mg and dexamethasone from 0.25 to 0.5 mg.
    Lupus Erythematosus: The dosage depends on the severity of the disease and the patient’s response to treatment. For adults an initial dose of 400-800 mg daily is recommended. This level can be maintained for several weeks and then reduced to a maintenance dose of 200-400 mg daily.
    Malaria: It is active against the erythrocytic forms of P.vivax and P.malariae and most strains of P.falciparum (but not the gametocytes of P.falciparum). It does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exo-erythrocytic forms, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P.falciparum.
    Adults: 400 mg (310 mg base) on exactly the same day of each week.
    Children: The weekly suppressive dose is 5 mg (base) per kg bodyweight but should not exceed the adult dose regardless of weight. Suppressive therapy should begin two weeks prior to exposure. Failing this, in adults an initial loading dose of 800 mg (620 mg base), or in children 10 mg base per kg, may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the endemic area.
    Treatment of the Acute Attack
    Adults: An initial dose of 800 mg followed by 400 mg in six to eight hours and 400 mg on each of two consecutive days. (Total dose of 2 g or 1.55 g base). A single dose of 800 mg (620 mg base) has also proved effective.
    Children: The dosage is calculated on the basis of bodyweight. (Total dose of 25 mg base per kg).
    First dose – 10 mg base per kg (not exceeding a single dose of 620 mg base).
    Second dose – 5 mg base per kg (not exceeding 310 mg base), six hours after first dose.
    Third dose – 5 mg base per kg eighteen hours after second dose.
    Fourth dose- 5 mg base per kg twenty-four hours after third dose.


    Indications

    Malaria, lupus erythematosus, rheumatoid arthritis.


    Contra-Indications

    Plaquenil is contraindicated in: Patients with pre-existing maculopathy of the eye, Patients with known hypersensitivity to 4-aminoquinoline compounds, In the presence of retinal or visual field changes attributable to any 4-aminoquinoline compound, Long-term therapy in children,
    Children under 6 years of age.


    Special Precautions

    Plaquenil is not effective against chloroquine-resistant strains of P.falciparum. Patients should be warned to keep Plaquenil out of the reach of children, as small children are particularly sensitive to the 4-aminoquinolines. Plaquenil should be used with caution or not at all in patients with severe gastrointestinal, neurological or blood disorders. If such severe disorders occur during therapy, the drug should be stopped. Periodic blood counts are advised. When used in patients with porphyria or psoriasis, these conditions may be exacerbated. Plaquenil should not be used in these conditions unless in the judgement of the physician, the benefit to the patient outweighs the possible risk. Cases of cardiomyopathy resulting in cardiac failure, in some cases with fatal outcome, have been reported in patients treated with Plaquenil. Clinical monitoring for signs and symptoms of cardiomyopathy is advised and Plaquenil should be discontinued if cardiomyopathy develops. Chronic toxicity should be considered when conduction disorders (bundle branch block / atrio-ventricular heart block) as well as biventricular hypertrophy are diagnosed. Hydroxyhloroquine has been shown to cause severe hypoglycemia including loss of consciousness that could be life threatening in patients treated with and without antidiabetic medications (see Interactions with other Medicines). Patients treated with hydroxychloroquine should be warned about the risk of hypoglycemia and the associated clinical signs and symptoms. Patients presenting with clinical symptoms suggestive of hypoglycemia during treatment with hydroxychloroquine should have their blood glucose level checked and treatment reviewed as necessary.
    Ophthalmological: Irreversible retinal damage has been observed in some patients who had received long-term or high-dosage 4-aminoquinolone therapy for discoid and systemic lupus erythematosus, or rheumatoid arthritis. Retinopathy has been reported to be dose related. If there is any indication of abnormality in the visual field, or retinal macular areas (such as pigmentary changes, loss of foveal reflex), or any visual symptoms (such as light flashes and streaks) which are not fully explainable by difficulties of accommodation or corneal opacities, the drug should be discontinued immediately and the patient closely observed for possible progression. Retinal changes (and visual disturbances) may progress after cessation of therapy. All patients being treated with hydroxychloroquine should have an initial ophthalmological examination. Ophthalmological testing should be conducted at 6 monthly intervals in patients receiving hydroxychloroquine at a dose of not more than 6 mg per kg body weight per day. Ophthalmological testing should be conducted at 3-4 monthly intervals in the following circumstances:
    Dose exceeds 6 mg per kg ideal (lean) body weight per day. Absolute body weight used as a guide to dosage, could result in an overdose in the obese. Significant renal impairment. Significant hepatic impairment. Elderly. Complaints of visual disturbances. Duration of treatment exceeds 8 years The examination should include slit-lamp microscopy (for corneal opacities) and fundus and visual field studies. A complete eye examination before treatment will determine the presence of any visual abnormalities, either coincidental or due to the disease and establish a baseline for further assessment of the patient’s vision. Corneal changes often subside on reducing the dose or on interrupting therapy for a short period of time, but any suggestion of retinal change or restriction in the visual field is an indication for complete withdrawal of the drug. The use of sunglasses in patients exposed to strong sunlight is recommended, as this may be an amplifying factor in retinopathy. Observe caution in patients with hepatic or renal disease, in whom a reduction in dosage may be necessary, as well as in those taking medicines known to affect these organs. Also observe caution in patents with gastrointestinal, neurological, or blood disorders, in those with a sensitivity to quinine, and in glucose-6-phosphate dehydrogenase deficiency, porphyria and psoriasis.
    Skin reactions: Pleomorphic skin eruptions (morbilliform, lichenoid, purpuric), itching, dryness and increased pigmentation sometimes appear after a few months of therapy. The rash is usually mild and transient. If a rash appears, Plaquenil should be withdrawn and only started again at a lower dose. Patients with psoriasis appear to be more susceptible to severe skin reactions than other patients.
    Haematological reactions: Patients on long-term therapy should have periodic full blood counts. If evidence of agranulocytosis, aplastic anaemia, thrombocytopenia or leukopenia becomes apparent, and cannot be attributed to the disease being treated, Plaquenil should be discontinued.
    Miscellaneous: Gastrointestinal disturbances such as nausea, anorexia, abdominal cramps or rarely vomiting, occur in some patients. The symptoms usually stop on reducing the dose or temporarily stopping the drug. Muscle weakness, vertigo, tinnitus, nerve deafness, headache and nervousness have been reported less frequently. All patients on long-term therapy with this preparation should be questioned and examined periodically, including the testing of knee and ankle reflexes, to detect any evidence of muscular weakness. If weakness occurs discontinue the drug. In the treatment of rheumatoid arthritis, if objective improvement (such as reduced joint swelling, increased mobility) does not occur within six months, the drug should be discontinued. Safe use of the drug in the treatment of juvenile rheumatoid arthritis has not been established. Patients should be warned about driving and operating machinery since hydroxychloroquine can impair visual accommodation and cause blurring of vision. If the condition is not selflimiting, the dosage may need to be temporarily reduced. Suicidal behaviour has been reported in very rare cases in patients treated with hydroxychloroquine.


    Side Effects

    Blurring of vision, corneal changes, retinal changes.
    For full details see prescribing information.


    Drug interactions

    It has been suggested that 4-aminoquinolines are pharmacologically incompatible with monoamine oxidase inhibitors.
    Concomitant hydroxychloroquine and digoxin therapy may result in increased serum digoxin concentrations. Consequently serum digoxin concentrations should be closely monitored in patients receiving concomitant therapy. As hydroxychloroquine may enhance the effects of a hypoglycaemic treatment, a decrease in doses of insulin or antidiabetic drugs may be required. Halofantrine prolongs the QT interval and should not be administered with other drugs that have the potential to induce cardiac arrhythmias, including hydroxychloroquine. Also there may be an increased risk of inducing ventricular arrhythmias if hydroxychloroquine is used concomitantly with other arrhythmogenic drugs, such as amiodarone and moxifloxacin. Increased plasma cyclosporin level have been reported when cyclosporin and hydroxychloroquine are co-administered. Hydroxychloroquine can lower the convulsive threshold. Co-administration of hydroxychloroquine with other anitmalarials known to lower the convulsion threshold (e.g. mefloquine) may increase the risk of convulsions. The activity of antiepileptic drugs might be impaired if co-administered with hydroxychloroquine. In a single-dose interaction study, chloroquine has been reported to reduce the bioavailability of praziquantel. It is not known if there is a similar effect when hydroxychloroquine and praziquantel are co-administered. Per extrapolation, due to the similarities in structure and pharmacokinetic parameters between hydroxychloroquine and chloroquine, a similar effect may be expected for hydroxychloroquine. There is a theoretical risk of inhibition of intra-cellular α-galactosidase activity when hydroxychloroquine is co-administered with agalsidase.


    Pregnancy and Lactation

    Pregnancy: Hydroxychloroquine crosses the placenta. Data are limited regarding the use of hydroxychloroquine during pregnancy. It should be noted that 4-aminoquinolines in therapeutic doses have been associated with central nervous system damage, including ototoxicity (auditory and vestibular toxicity, congenital deafness), retinal hemorrhages and abnormal retinal pigmentation. The use of this drug in the treatment of malaria or suppression of malaria in high risk situations may be justified if the treating physician considers the risk to the foetus is outweighed by the benefits to the mother and foetus.
    Nursing Mothers: Careful consideration should be given to using hydroxychloroquine during lactation, since it has been known to be excreted in small amounts in human breast milk and it is known that infants are extremely sensitive to the toxic effects of 4-aminoquinones.
    See prescribing information for full details.


    Overdose

    Symptoms: Overdose with the 4-aminoquinolines is dangerous. Children are particularly sensitive to these compounds and a number of fatalities have been reported following the accidental ingestion of chloroquine, sometimes in relatively small doses (0.75 or 1 gram in one 3 year old child). The 4-aminoquinolines are very rapidly and completely absorbed after ingestion and toxic symptoms following overdose may occur within 30 minutes. Toxic symptoms consist of headache, drowsiness, visual disturbances, hypokalemia, cardiovascular collapse and convulsions followed by sudden and early respiratory and cardiac arrest. The ECG may reveal atrial standstill, nodal rhythm, prolonged intraventricular conduction time, including QT prolongation, torsade de pointe, ventricular tachycardia and progressive bradycardia leading to ventricular fibrillation and/or cardiac arrest. Immediate medical attention is required as these may appear shortly after the overdose.
    Treatment: Treatment is symptomatic and must be prompt. Emesis is not recommended because of the potential for CNS depression, convulsions and cardiovascular instability. Gastric lavage may be indicated if performed soon after ingestion or in patients who are comatose. In obtunded or comatose patients receiving gastric lavage the airway should be protected. Activated charcoal should be administered. The dose of activated charcoal should be at least five times the estimated amount of hydroxychloroquine ingested. Consideration should be given to using diazepam parentally as there have been reports that it may decrease cardiotoxicity. Respiratory support and management of shock should be instituted as necessary.


    Manufacturer
    Sanofi Winthrop Industrie, France
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