NEWS HIGHLIGHTS
Published Studies Related to Daraprim (Pyrimethamine)
Intermittent treatment for the prevention of malaria during pregnancy in Benin: a randomized, open-label equivalence trial comparing sulfadoxine-pyrimethamine with mefloquine. [2009.09.15]
BACKGROUND: In the context of the increasing resistance to sulfadoxine-pyrimethamine (SP), we evaluated the efficacy of mefloquine (MQ) for intermittent preventive treatment during pregnancy (IPTp)... CONCLUSIONS: MQ proved to be highly efficacious--both clinically and parasitologically--for use as IPTp. However, its low tolerability might impair its effectiveness and requires further investigations.
Measurement of adherence, drug concentrations and the effectiveness of artemether-lumefantrine, chlorproguanil-dapsone or sulphadoxine-pyrimethamine in the treatment of uncomplicated malaria in Malawi. [2009.08.26]
BACKGROUND: Sulphadoxine-pyrimethamine (SP) is the only single dose therapy for uncomplicated malaria, but there is widespread resistance. At the time of this study, artemether-lumefantrine (AL) and chlorproguanil-dapsone (CPD), both multi-dose regimes, were considered possible alternatives to SP in Malawi. The aim of this study was to investigate the impact of poor adherence on the effectiveness of AL and CPD... CONCLUSION: This study provides reassurance of the effectiveness of AL, even with unsupervised dosing, as it is rolled out across sub-Saharan Africa. Self-reported adherence appears to be an unreliable measure of adherence in this population.
Comparison of sulfadoxine-pyrimethamine, unsupervised artemether-lumefantrine, and unsupervised artesunate-amodiaquine fixed-dose formulation for uncomplicated plasmodium falciparum malaria in Benin: a randomized effectiveness noninferiority trial. [2009.07.01]
BACKGROUND: We compared sulfadoxine-pyrimethamine (SP) with unsupervised artemether-lumefantrine (AL) and unsupervised amodiaquine-artesunate (ASAQ) fixed-dose formulation for the treatment of uncomplicated malaria in children in Benin... CONCLUSIONS: This was the first trial, to our knowledge, to compare unsupervised AL with unsupervised ASAQ fixed-dose formulation; both treatments provided high PCR-adjusted day 28 effectiveness rates. Efficacy rates for SP were surprisingly low. Clinical trials registration. NCT00460369.
Efficacy of sulphadoxine-pyrimethamine with or without artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in southern Mozambique: a randomized controlled trial. [2009.06.26]
BACKGROUND: An artemisinin-based combination therapy, artesunate (AS) plus sulphadoxine-pyrimethamine (SP), was compared to SP monotherapy to provide evidence of further treatment options in southern Mozambique... CONCLUSION: While both treatments were efficacious, AS plus SP significantly decreased the relative hazard of treatment failure compared to SP monotherapy Artesunate plus sulphadoxine-pyrimethamine, but not sulphadoxine-pyrimethamine monotherapy, met the current WHO criteria of >95% efficacy for policy implementation. TRIAL REGISTRATION: NCT00203736 and NCT00203814.
Polymorphism in PfMRP1 (Plasmodium falciparum multidrug resistance protein 1) amino acid 1466 associated with resistance to sulfadoxine-pyrimethamine treatment. [2009.06]
Sulfadoxine-pyrimethamine (SP) remains widely recommended for intermittent preventive treatment against Plasmodium falciparum malaria for pregnant women and infants in Africa. Resistance to SP is increasing and associated primarily with mutations in the P.Moreover, they add to the growing evidence of the potential importance of Pfmrp1 in antimalarial drug resistance.
Clinical Trials Related to Daraprim (Pyrimethamine)
Pyrimethamine to Treat Autoimmune Lymphoproliferative Syndrome [Completed]
This study will examine whether the drug pyrimethamine can shrink lymph nodes and spleen in
patients with autoimmune lymphoproliferative syndrome (ALPS). In this disease, lymphocytes
(white blood cells) do not die as they normally would. As a result, patients have enlarged
lymph glands, spleen, or liver, and other problems that may involve blood cell counts and
autoimmune disease (overactivity of the immune system). Pyrimethamine is an orally
administered antibiotic that has been used to treat or prevent malaria and toxoplasma, and
may be effective in shrinking lymph nodes and spleen.
Patients with ALPS who are between 2 and 70 years of age and have had lymph gland enlargement
for at least 1 year may be eligible for this study. Candidates will be screened with a
medical history and physical examination, blood tests, and possibly a bone marrow test.
Females of reproductive age will be screened with a urine pregnancy test. Women who are
capable of becoming pregnant must use an effective method of birth control during the entire
study period, because, taken during early months of pregnancy, pyrimethamine can cause birth
defects in the fetus. Women who are pregnant or nursing are excluded from the study.
Participants will undergo the following tests and procedures:
- CT scan: For this test, the patient lies still in the CT scanner while images are taken
of the neck, chest, and stomach area. A contrast dye is injected into a vein to brighten
the CT images. Very young children will be evaluated on a case by case basis to
determine whether a CT scan will be performed.
- Bone marrow biopsy: Participants undergo this test to rule out underlying bone marrow
disease if they have not had a bone marrow test done in the last six months prior to
enrolling in pyrimethamine study, as pyrimethamine can affect bone marrow function.
Under local anesthesia, a needle is inserted into the back part of the hipbone and a
small amount of marrow is removed. (Children are sedated for this test.)
- Leukapheresis: This is a procedure for collecting a small proportion of circulating
white blood cells while conserving the majority of blood cells. Specifically, blood is
drawn from a needle placed in an arm vein and is directed into a cell separator machine,
which separates the blood cells by spinning. A small proportion of circulating white
cells are removed, and the red cells, platelets, plasma and majority of white cells are
returned to the patient's blood circulation. Only patients who are 7 years of age or
older and weigh at least 55 pounds undergo this procedure. Other participants who choose
not to have apheresis will have about 3 tablespoons of blood drawn instead.
- Pyrimethamine administration: When the above tests are completed, participants begin
taking pyrimethamine. The dose is determined according to the individual's weight and is
gradually increased during the study period. Patients take the drug twice a week for a
total of 12 weeks.
- Blood tests: Blood samples are collected during weeks 2, 4, 6, 8, and 10 after beginning
treatment, and 2 weeks after the last dose of pyrimethamine. The purpose of these blood
tests is to check for possible drug-related side effects. Patients who develop a skin
rash, mouth sores or other side effects may have one or more doses of the treatment drug
withheld. When indicated, the patient will be directed to stop taking the study drug. If
needed, drug side effects will be treated with a vitamin supplement, folinic acid, taken
by mouth, 3 times weekly.
- Evaluations at the NIH Clinical Center will comprise of a pretreatment visit, one end of
treatment visit at the end of 12 weeks and an optional post-treatment visit 3months
after stopping pyrimethamine therapy.
Patients who respond well to treatment may be asked to return to NIH for additional visits at
3, 6, and 12 months after the treatment has ended for repeat evaluations. If their lymph
glands or spleen become much larger after stopping pyrimethamine, they will be offered
treatment for another 12 weeks. If they respond to the second course of treatment, they will
return to NIH again after 3, 6, and 12 months. If the symptoms return again, patients will be
asked to resume treatment for an additional 6 months or more. They will have blood drawn
periodically by their private physician and will return to NIH for evaluation every 12
weeks.
A Randomised Efficacy Study of Combination Antimalarials to Treat Uncomplicated Malaria [Completed]
Intermittent Treatment With Sulfadoxine-Pyrimethamine for Malaria Control in Infants [Active, not recruiting]
The purpose of this study is to assess the effectiveness of Intermittent Preventive Treatment
in Infants (IPTi) with Sulfadoxine-Pyrimethamine to reduce the numbers of malaria attacks,
episodes of anemia, and the overall morbidity and mortality
A Study of Pyrimethamine in the Treatment of Infection by a Certain Parasite in HIV-Positive Patients [Completed]
To determine the manner in which pyrimethamine is metabolized and excreted in patients
currently receiving zidovudine (AZT). An important goal of this measurement is to establish
the optimal dose of pyrimethamine necessary to prevent the development of toxoplasmosis in
AIDS patients or delay the subsequent return of toxoplasmic encephalitis.
Encephalitis caused by Toxoplasma gondii has emerged as the most frequent cause of focal
central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal.
The best treatment for this disease has not been determined. Presently it is standard
practice to administer a combination of pyrimethamine and sulfadiazine. Little is known about
the pharmacokinetics of pyrimethamine in patients with AIDS receiving AZT. Furthermore, there
are reports that patients already exposed to toxoplasmosis may not have uniform absorption of
pyrimethamine.
A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS [Completed]
To collect information on the effectiveness and toxicity of clindamycin plus pyrimethamine
and leucovorin calcium for the treatment of acute toxoplasmic encephalitis in adult patients
with AIDS. Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most
frequent cause of focal central nervous system infection in patients with AIDS. If untreated,
the encephalitis is fatal. At present, it is standard practice to give a combination of
pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of
sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of
therapy difficult. There is some information that high doses of parenteral (such as by
injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus
sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients
with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however,
is costly, requires hospitalization, and is inconvenient for the patient. There is some
indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral
clindamycin may be effective. Leucovorin calcium is useful in preventing
pyrimethamine-associated bone marrow toxicity.
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