Chloroquine Population Pharmacokinetics in Pre and Post-partum Women
Condition: Vivax Malaria
MeSH terms: Malaria; Malaria, Vivax
Study type: Interventional

Summary: 
      For the treatment of P.vivax the standard treatment is chloroquine. There is a growing body
      of evidence suggesting that pregnant women may require different doses of drugs, including
      antimalarials due to the physiological changes of pregnancy. It is important that any drug
      used in pregnant women it is given at the correct dose. The only way to evaluate this is by
      pharmacokinetic studies. The investigators propose to evaluate the pharmacokinetics of
      chloroquine when use to treat P.vivax in the 2nd or 3rd trimester of pregnancy. The same
      evaluation in the same woman post-partum is required as a control.
    

Detailed description: 
      For the treatment of P.vivax the standard treatment is chloroquine. There is a growing body
      of evidence suggesting that pregnant women may require different doses of drugs, including
      antimalarials, due to the physiological changes of pregnancy. It is important that any drug
      used in pregnant women is given at the correct dose. The only way to evaluate this is by
      pharmacokinetic studies. We propose to evaluate the pharmacokinetics of chloroquine when use
      to treat P.vivax in the 2nd or 3rd trimester of pregnancy. The same evaluation in the same
      woman post-partum is required as a control.

      The two most recent pharmacokinetic publications conclude differently on chloroquine dosing
      in pregnant women: one suggests no dose adjustment and the other that a higher dose is
      probably needed. It is crucial that pregnant women are dosed correctly to maximise cure and
      minimize the chance for recurrence and the harmful effects of malaria. The proposed study on
      the pharmacokinetics of chloroquine treatment in pregnant women will solve this dilemma.

      Pregnant women on the Thai-Burmese border are encouraged to attend antenatal care often for
      early detection and treatment of malaria. Low birth weight due to P.vivax affects
      primigravida and multigravida, not just primarily primigravida as with
      P.falciparum(highlighted in the attached reference). Hence it is important to consider these
      women for radical cure. This is not possible during pregnancy as primaquine is
      contraindicated so the next best time is in the post-partum period. During the post-partum
      period the woman remains in close contact with midwives for infant care and for their
      personal health. The midwives also have a record of malaria attacks during pregnancy.

      We know more about chloroquine than any other antimalarial used in pregnancy. It has been
      widely used for prevention and treatment of malaria in pregnancy and in women with autoimmune
      disease such systemic lupus and rheumatoid arthritis high doses of hydroxychloroquine have
      been given daily including during the first trimester of pregnancy. Although data from
      prospective clinical trials of malaria are limited, this drug is considered safe in all
      trimester of pregnancy and in lactation.

      For treatment of uncomplicated P.vivax WHO recommends chloroquine and primaquine where
      P.vivax remains chloroquine sensitive. A 14 day course of primaquine is recommended for
      radical cure of P.vivax. WHO advises not to use primaquine during pregnancy or in severe
      G6PD. WHO permits the use of primaquine during lactation if the breast fed infant is not G6PD
      deficient.

      The possibility that women with recurrent P.vivax in the same pregnancy may have chloroquine
      resistant P.vivax needs to be considered. While the combination of chloroquine and primaquine
      cannot be used in pregnancy and the safety and efficacy of ACTs are still undergoing
      evaluation we need to explore alternatives to chloroquine for such cases. ACTs are
      recommended for chloroquine resistant P.vivax by WHO and one ACT considered safe in pregnancy
      and lactation is a 7 day course of artesunate-clindamycin.
    

Intervention name(s): Chloroquine
Intervention type(s): Drug
Intervention description(s): Chloroquine phosphate GPO® (Government Pharmaceutical Organization, Thailand) 250 mg (equivalent to chloroquine base 150 mg).
Dosing will be at 0, 24, 48 hrs with 10 mg/kg on day 0 and day 1, and 5 mg/kg on day 2.
Intervention MeSH terms: Chloroquine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chloroquine; Uncomplicated vivax malaria