CLINICAL USE

Antiprotozoal agent:Malaria Toxoplasmosis

DOSE IN NORMAL RENAL FUNCTION

Malaria: used in dual drug combinations Malaria prophylaxis: 25 mg weekly Toxoplasmosis: 100–200 mg daily for 2–3 days then 25–100 mg daily for 2–6 weeks (in combination with sulfadiazine)

PHARMACOKINETICS

  • Molecular weight                           :248.7
  • %Protein binding                           :80–90
  • %Excreted unchanged in urine     : 15–30
  • Volume of distribution (L/kg)       :2
  • half-life – normal/ESRD (hrs)      :35–175/Unchanged

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function
  • 10 to 20     : Dose as in normal renal function
  • <10           : Dose as in normal renal function

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Not dialysed. Dose as in normal renal function
  • HD                     :Not dialysed. Dose as in normal renal function
  • HDF/high flux   :Unknown dialysability. Dose as in normal renal function
  • CAV/VVHD      :Not dialysed. Dose as in normal renal function

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugsIncreased antifolate effect with sulphonamides, trimethoprim and methotrexate

  • Anti-epileptics: anticonvulsant effect antagonised; increased antifolate effect with phenytoin
  • Antimalarials: avoid concomitant use with artemether/lumefantrine; increased antifolate effect with proguanil

    ADMINISTRATION

    Reconstition

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    Route

    Oral

    Rate of Administration

    –

    Comments

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    OTHER INFORMATION

    Pyrimethamine should always be administered with a folate supplement to reduce the risk of bone marrow depression.

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