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עמוד הבית / פלקווניל / מידע מעלון לרופא

פלקווניל PLAQUENIL (HYDROXYCHLOROQUINE SULFATE)

תרופה במרשם תרופה בסל נרקוטיקה ציטוטוקסיקה

צורת מתן:

פומי : PER OS

צורת מינון:

טבליות מצופות פילם : FILM COATED TABLETS

Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 PHARMACODYNAMICS PROPERTIES
Pharmacotherapeutic group: Antimalarials, ATC code: P01BA02

Mechanism of Action
Anti-malarial. Plaquenil also exerts a beneficial effect in mild systemic and discoid lupus erythematosus and rheumatoid arthritis. The precise mechanism of action is not known.


Malaria
Like chloroquine phosphate, Plaquenil is highly active against the erythrocytic forms of P.vivax and P.malariae and most strains of P.falciparum (but not the gametocytes of P.falciparum).
Plaquenil does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exo-erythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is highly 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.

Clinical trials
No data available

Pharmacokinetic Properties

5.2 PHARMACOKINETIC PROPERTIES
Absorption
Following oral administration, peak plasma or blood concentrations is achieved in approximately 3 to 4 hours. Mean absolute oral bioavailability is 79% (SD: 12%) in fasting conditions. Food does not modify the oral bioavailability of hydroxychloroquine.

Distribution
Hydroxychloroquine has a large volume of distribution (5500 L when assessed from blood concentrations, 44 000 L when assessed from plasma concentrations), due to extensive tissue accumulation (such as eyes, kidney, liver and lungs) and has been shown to accumulate in blood cells, with a blood to plasma ratio of 7.2. Approximately 50% of hydroxychloroquine is bound to plasma proteins.

Metabolism
Hydroxychloroquine is mainly metabolised to N-desethylhydroxychloroquine, and two other metabolites in common with chloroquine, desethylchloroquine and bidesethylchloroquine. In vitro, hydroxychloroquine is metabolised mainly by CYP2C8, CYP3A4 and CYP2D6 as well as by FMO-1 and MAO-A, with no major involvement of a single CYP or enzyme.

Excretion
Hydroxychloroquine presents a multi-phasic elimination profile with a long terminal half-life ranging from 30 to 50 days. PBPK predictions indicate that the effective accumulation half- life of hydroxychloroquine is about 5.5 days and that 90% of steady state is achieved within 5 weeks in blood after repeated oral administration of 400 mg hydroxychloroquine sulfate once a day in patients with rheumatoid arthritis. Approximately 20-25% of the hydroxychloroquine dose is eliminated as unchanged drug in the urine. After chronic repeated oral administration of 200 mg and 400 mg hydroxychloroquine sulfate once a day in adult patients with lupus or rheumatoid arthritis, the average steady-state concentrations were around 450-490 ng/mL and 870-970 ng/mL in blood, respectively.
The pharmacokinetics of hydroxychloroquine appears to be linear in the therapeutic dose range of 200 to 500 mg/day.

Renal impairment
Renal impairment is not expected to significantly modify the pharmacokinetics of hydroxychloroquine in patients with renal impairment because hydroxychloroquine is mainly metabolised and only 20-25% of the hydroxychloroquine dose is eliminated as unchanged drug in the urine. PBPK predictions show that hydroxychloroquine exposure would increase by 17-30% in patients with severe renal impairment (see Section 4.4 Special warnings and precautions for use – Use in renal impairment).

Hepatic impairment
The effect of hepatic impairment on hydroxychloroquine pharmacokinetics has not been evaluated in a specific PK study. PBPK predictions show that hydroxychloroquine exposure would increase by 41%-57% in patients with moderate and severe hepatic impairment (see Section 4.4 Special warnings and precautions for use – Use in hepatic impairment).

Paediatric use
The pharmacokinetics of hydroxychloroquine in children aged below 18 years of age have not been established.

שימוש לפי פנקס קופ''ח כללית 1994 Rheumatoid arthritis, discoid and systemic lupus erythematosus, polymorphus light eruptions
תאריך הכללה מקורי בסל 01/01/1995
הגבלות תרופה שאושרה לשימוש כללי בקופ'ח

בעל רישום

SANOFI ISRAEL LTD

רישום

044 96 23782 00

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0 ₪

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