Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low.

PURPOSE: Sertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants. METHOD: Pregnant women with moderate untreated depression were recruited in 2016-2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed. RESULTS: Nine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers', measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants. CONCLUSION: Placental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.

Maternal mood disorders and lithium exposure in utero were not associated with poor cognitive development during childhood.

AIM: This study evaluated whether maternal mood disorders (MMD), particularly bipolar disorder, and lithium treatment during pregnancy influenced the neonatal health and cognition of children born from 2006 to 2010. METHODS: Our study at Karolinska University Hospital, Stockholm, Sweden, focused on women with and without mood disorders and their children. Information on pharmacotherapy, mental health, delivery and neonatal complications was retrospectively collected from electronic patient records. Children were tested in a blinded manner at four to five years of age with the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition. Maternal health, child health and social situations were evaluated. RESULTS: Of the 39 children, 20 were exposed to lithium and MMD during pregnancy, eight were exposed to MMD but not lithium and 11 were not exposed to MMD or lithium. The children's full scale intelligence quotient (IQ), performance IQ and verbal IQ results did not differ significantly between the groups. The processing speed quotient was significantly lower in children exposed to mood disorders, but there was a high level of missing data for this subtest. CONCLUSION: This small, clinical cohort showed no significant association between mothers' prenatal exposure to lithium or mood disorders and their offspring's IQ.

A fast and sensitive method for quantifying lumefantrine and desbutyl-lumefantrine using LC-MS/MS.

A sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for quantification of lumefantrine (LUM) and its metabolite desbutyl-lumefantrine (DBL) in human plasma. Sample preparation was done by protein precipitation using acetonitrile containing deuterated lumefantrine (LUM-d18) and desbutyl-lumefantrine (DBL-d9) as internal standards. Total chromatography time was 2.2min using an Hypersil Gold C18 column (20×2.1mm, 1.9µm), with a gradient using 0.5% formic acid in water (mobile phase A) and 0.5% formic acid in methanol (mobile phase B) at a flow rate of 0.5mL/min. The mass spectrometric quantification was performed in positive electro spray ionization (ESI+) mode using selected reaction monitoring (SRM). Measuring range was 21-529ng/mL for LUM and 1.9-47ng/mL for DBL in plasma. Inter- and intra-assay precision was within 10% coefficient of variation (CV) for all levels of both LUM and DBL. Accuracy was within ±10% for all levels of both LUM and DBL. This method requires 100µL plasma volume and its short retention times allow a high throughput. Samples were stable for a week at +5°C, and up to six months -20°C. The method was successfully applied for plasma LUM and DBL determination in children under 5 years of age with uncomplicated malaria, up to 28 days after a standard 3-day treatment with artemether-lumefantrine.

Selective serotonin reuptake inhibitor use during pregnancy increases the risk of postpartum hemorrhage and anemia: a hospital-based cohort study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are known to increase the risk of gastrointestinal bleeding. OBJECTIVE: Study the risk of bleeding-related complications in relation to SSRI in pregnancy. PATIENTS/METHODS: This was a hospital-based cohort study. All women who gave birth at Karolinska University Hospital in Stockholm over a 5-year period (2007 to 2011) were included in the study. Those women who the electronic maternal health record indicated were using SSRI (n = 500) were considered exposed, and all other women formed a control population (n = 39,594). The main outcome measures were blood loss, postpartum hemorrhage (PPH), PP anemia and length of hospitalization. RESULTS: The absolute risk of PPH and PP anemia for the 1.2% exposed to SSRI were 18.0% and 12.8%, respectively. Women with a vaginal non-surgical delivery who reported use of SSRI during pregnancy had approximately a 2-fold increased risk of both PPH (OR, 2.6; 95% CI, 2.0-3.5) and PP anemia (OR, 2.1; 95% CI, 1.5-2.9), as compared with controls. Blood loss and length of hospitalization were significantly higher among women using SSRI than non-users (arithmetic mean 484 mL vs. 398 mL, 3.8 days vs. 2.4 days, respectively). CONCLUSION: The use of SSRI during pregnancy increases blood loss and doubles the risk of PPH and PP anemia in a setting where SSRI had not been considered a risk factor for increased blood loss. Because PPH is a leading cause of maternal mortality and morbidity, the awareness of bleeding-related complications is important, both in relation to pregnancy and to surgery in general.

Are specific initiatives required to enhance prescribing of generic atypical antipsychotics in Scotland?: International implications.

BACKGROUND: National and regional authorities in Scotland have introduced multiple measures to appreciably enhance prescribing efficiency for the proton pump inhibitors (PPIs), statins and renin-angiotensin inhibitor drugs. Generic oral risperidone recently became available in Scotland; however, schizophrenia is a complex disease with advice from respected authorities suggesting that treatment should be individualised. AIMS: To assess (i) changes in atypical antipsychotic drug (AAP) utilisation and expenditure following the availability of oral generic risperidone in Scotland; (ii) to determine (a) current INN prescribing rates for risperidone following generic availability and (b) decrease in expenditure/DDD for generic risperidone; (iii) to suggest additional measures that could possibly be introduced in Scotland to further enhance prescribing of generic AAPs; and (iv) to provide guidance to NHS Scotland as well as other European authorities on the implications. METHODS: Retrospective observational study and an interrupted time series design. RESULTS: No appreciable change in the utilisation patterns of risperidone pre- and postgeneric availability. Appreciable INN prescribing averaged 93-98% of total oral risperidone. Generic risperidone was 84% below prepatent loss prices by study end, reducing annual expenditure for oral risperidone in 2010 by GB£3.19mn compared with prepatent loss situation. However, overall expenditure on AAPs increased by 42% from 2005 to 2010. DISCUSSION: As expected, there was no change in utilisation patterns for risperidone, although potential to influence prescribing patterns. Continued high INN prescribing suggests no problems with generic risperidone in practice. Costs will start to decrease as more AAPs lose their patents (olanzapine and quetiapine). There is the possibility to accelerate this reduction through educational activities. CONCLUSION: There is potential to realise some savings with generic AAPs. However, this is limited by the complexity of the disease area. Any measures introduced must aim at increasing the prescribing of generic AAPs first line in suitable patients.

Pharmacokinetics of the nonnucleoside reverse transcriptase inhibitor efavirenz among HIV-infected Ugandans.

BACKGROUND: Pharmacokinetic variability of the nonnucleoside reverse transcriptase inhibitor efavirenz has been documented, and high variation in trough concentrations or clearance has been found to be a risk for virological failure. Africans population exhibits greater variability in efavirenz concentrations than other ethnic groups, and so a better understanding of the pharmacokinetics of the drug is needed in this population. This study characterized efavirenz pharmacokinetics in HIV-infected Ugandans. METHODS: Efavirenz plasma concentrations were obtained for 66 HIV-infected Ugandans initiating efavirenz- based regimens, with blood samples collected at eight time-points over 24 h on day 1 of treatment, and at a further eight time-points on day 14. Noncompartmental analysis was used to describe the pharmacokinetics of efavirenz. RESULTS: The mean steady-state minimum plasma concentration (C(min) ) of efavirenz was 2.9 µg/mL, the mean area under the curve (AUC) was 278.5 h µg/mL, and mean efavirenz clearance was 7.4 L/h. Although overall mean clearance did not change over the 2 weeks, 41.9% of participants showed an average 95.8% increase in clearance. On day 14, the maximum concentration (C(max) ) of efavirenz was >4 µg/mL in 96.6% of participants, while C(min) was <1 µg/mL in only 4.5%. Overall, 69% of participants experienced adverse central nervous system (CNS) symptoms attributable to efavirenz during the 2-week period, and 95% of these participants were found to have efavirenz plasma concentrations >4 µg/mL, although only half maintained a high concentration until at least 8 h after dosing. CONCLUSION: The findings of this study show that HIV-infected patients on efavirenz may exhibit autoinduction to various extents, and this needs to be taken into consideration in the clinical management of individual patients. Efavirenz CNS toxicity during the initial phase of treatment may be related to C(max) , regardless of the sampling time.

Adverse drug reactions in patients admitted on internal medicine wards in a district and regional hospital in Uganda.

INTRODUCTION: The burden of both community and hospital acquired adverse drug reactions (ADRs) are some of the important issues in pharmacotherapy. At the time of this study there was very scanty literature in this area from Africa. OBJECTIVE: This study was done to determine the frequency and characteristics of ADRs in patients admitted on medical wards in public hospitals. METHODS: This was a longitudinal observational study on 728 adult patients on medical wards in one regional and one district hospitals. Community and hospital acquired ADRs were assessed. RESULTS: Thirty three patients (4.5%) were admitted with suspected ADR, and an ADR was the reason for hospitalization in 1.5%. Most ADRs were due to antiparasitic products, mainly quinine (61%). Community acquired ADRs prolonged hospital stay, 5.6 days vs 4.0 days (p-value < 0.001). During hospitalization ADRs occurred in 49.5% of the patients. Antiparasitic products, predominantly quinine, were the commonest drugs class associated with ADRs (85.9%). Hospital acquired ADRs did not affect hospital stay, 4.2 days vs 3.9 (p-value 0.129). CONCLUSION: ADRs are an important cause of morbidity in patients, both in the community and in hospitals, and the majority are associated with the commonly used drugs.

Use of a pilot drug information centre.

INTRODUCTION: Provision of access to drug information by prescribers and other health care professionals is important in pharmacotherapy. At the time of this study there was very scanty literature in this area from Africa. OBJECTIVE: To assess use of a pilot drug information centre (DIC) which was set up in a department of Pharmacology and Therapeutics in a university teaching hospital in Uganda. METHODS: This was a situational analysis with a prospective study design. The pilot DIC was established and its use over an eleven-month period was assessed. The received queries were evaluated for source of the query, reason for the query and type of query. RESULTS: During the 11 months 297 queries were received, 72.3% of which were from public hospitals. Most were from prescribing doctors (54.2%). Majority were on drug-drug interaction (41.2%), followed by therapy (23.2%). Out of 197 specific drug requests, 65.5% were on antiretroviral. CONCLUSION: We found that healthcare professionals were enthusiastically using the drug information centre. It is, therefore, necessary and feasible to establish a DIC in Uganda that will enable these professionals to readily access drug information.

Effectiveness of a community intervention on malaria in rural Tanzania - a randomised controlled trial.

BACKGROUND: Malaria infections are a major public health problem in Africa and prompt treatment is one way of controlling the disease and saving lives. METHODS: This cluster-randomised controlled community intervention conducted in 2003-2005 aimed at improving early malaria case management in under five children. Health workers were trained to train community-based women groups in recognizing malaria symptoms, providing first-line treatment for uncomplicated malaria and referring severe cases. Evaluation was through a pre- (2004) and a post-intervention survey (2005). Anaemia prevalence was the primary outcome. RESULTS: 1715 children aged 6-59 months were included in the pre-intervention survey and 2169 in the post-intervention survey. The prevalence of anaemia decreased significantly from 37% [95% CI 34.7-39.3] to 0.5% [95% CI 0.2-0.7] after the intervention (p<0.001); slightly more in the intervention (from 43.9% to 0.8%) than in the control (30.8% to 0.17%) group (p=0.038). Fever and reported fever decreased significantly and the mean body weight of the children increased significantly over the study period in both control and intervention groups. CONCLUSION: The decrease in anaemia was significantly associated with the intervention, whereas the fever and body weight trends might be explained by other malaria control activities or seasonal/climate effects in the area. The community intervention was shown to be feasible in the study context.

A field-adapted sampling and HPLC quantification method for lumefantrine and its desbutyl metabolite in whole blood spotted on filter paper.

A quantitative reverse-phase HPLC method with UV detection, for lumefantrine (LF) and desbutyllumefantrine (DLF) in whole blood spotted on filter paper was developed. The analytes were stabilized on filter paper by treatment of blood with phosphoric acid (1.6 mol/L). Halofantrine was used as internal standard and the analytes were extracted from filter paper using methanol. The methanolic extract was extracted with di-isopropylether after addition of acidic phosphate buffer (pH 2). Chromatographic separation was carried out on a Zorbax Eclipse XDB-phenyl column (4.6 mm x 150 mm, particle size 5 microm) at a flow rate of 1 mL/min using a mobile phase of acetonitrile-ammonium acetate buffer (0.1M ammonium acetate and 0.01 M acetic acid, pH 6.5) (10:90). The absorbance of the compounds was monitored at 335 nm. The average extraction recovery from filter paper ranged between 45-51% for LF and 25-33% for DLF for a concentration range between 300 and 3000 nM. Inter- and intra-assay coefficients of variation for LF and DLF were < or =9.2. Limits of quantification for LF and DLF were 300 nM. The method has been applied in malaria patients. In conclusion, a simple procedure for blood sampling and quantitative measurement of lumefantrine and desbutyllumefantrine suitable for field studies in resource-limited laboratories was developed.

Clinical diagnosis of malaria and the risk of chloroquine self-medication in rural health centres in Burkina Faso.

OBJECTIVE: To assess the quality of healthcare workers' performance with regard to malaria diagnosis and treatment and to assess patients' self-medication with chloroquine (CQ) before and after presentation at a health centre. METHODS: In the rainy season 2004, in five rural dispensaries in Burkina Faso, we observed 1101 general outpatient consultations and re-examined all these patients. CQ whole blood concentrations of confirmed malaria cases were measured before and after treatment. RESULTS: The clinical diagnosis based on fever and/or a history of fever had a sensitivity of 75% and a specificity of 41% when compared to confirmed malaria (defined as an axillary temperature of >/=37.5 degrees C and/or a history of fever and parasites of any density in the blood smear). Few febrile children under 5 years of age were assessed for other diseases than malaria such as pneumonia. No antimalarial was prescribed for 1.3% of patients with the clinical diagnosis malaria and for 24% of confirmed cases, while 2% received an antimalarial drug prescription without the corresponding clinical diagnosis. CQ was overdosed in 22% of the prescriptions. Before and 2 weeks after consultation, 25% and 46% respectively of the patients with confirmed malaria had potentially toxic CQ concentrations. CONCLUSION: As long as artemisinin-based combination therapy remains unavailable or unaffordable for most people in rural areas of Burkina Faso, self-medication with and prescription of CQ are likely to continue despite increasing resistance. Apart from considering more pragmatic first-line regimens for malaria treatment such as the combination of sulfadoxine-pyrimethamine with amodiaquine, more and better training on careful clinical management of febrile children including an appropriate consideration of other illnesses than malaria should be made available in the frame of the IMCI initiative in sub-Saharan Africa.

Antimalarial resistance and DHFR/DHPS genotypes of Plasmodium falciparum three years after introduction of sulfadoxine-pyrimethamine and amodiaquine in rural Tanzania.

We assessed the efficacy of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania, 3 years after their introduction as first- and second-line treatments for uncomplicated malaria, respectively. Under five children with uncomplicated malaria were given standard treatments of either SP (n=66) or AQ (n=30) and treatment outcomes after 14 and 28 days were determined. Total treatment failure of 18 and 42.5% was observed for SP on days 14 and 28, respectively. For AQ, total treatment failure of 27 and 53% was found on day 14 and 28, respectively. On day 14, significantly lower SP total treatment failures were observed in 2004 compared with results from a study conducted in 1999 in the same location. No relationship was detected between clinical outcome and DHFR/DHPS genotypes, but the point mutation prevalence in parasites was higher than in 1999. Pre-treatment blood levels of SP were detected in a quarter of the study children: less than expected. We report unacceptably high levels of total treatment failures, both for first- and second-line treatments for uncomplicated malaria in Tanzania 3 years after their introduction, supporting the decision to replace them with artemisinin-based combination therapy.

A field-adapted HPLC method for determination of amodiaquine and its metabolite in whole blood dried on filter paper.

A reversed-phase high performance liquid chromatographic method was developed and validated for the quantitative determination of amodiaquine (AQ) and its metabolite desethylamodiaquine (DAQ) in whole blood collected on filter paper. The structure analogue 4-(4-dimethylamino-1-methylbutylamino)-7-chloroquinoline was used as internal standard. Upon collection, blood was added to 10% phosphoric acid in a 1:1 ratio and then spotted onto filter paper. The samples were alkalinized (pH approximately 9.2) with potassium hydroxide at the time of assay and the compounds were extracted together with internal standard into di-isopropyl ether and then re-extracted into an aqueous phase with 0.1M phosphate buffer at pH 4. The chromatographic analysis was performed using an Agilent Technologies ChemStation LC System. The absorbance of the compounds was monitored at 333 nm. Mean extraction recoveries of AQ and DAQ were 49 and 48%, respectively. Intra-day and inter-day coefficients of variation were <10.5%. The limit of quantification was 50 nM for both compounds (sample size 100 microl). Both AQ and DAQ that were previously reported to be unstable have been stored on filter paper for at least 19 weeks. The method was applied on samples from healthy volunteers.

CYP3A5 genotype has an impact on the metabolism of the HIV protease inhibitor saquinavir.

CYP3A is the main enzyme subfamily involved in the metabolism of the HIV protease-inhibitor saquinavir. We hypothesized that individuals homozygous for CYP3A5*1 might have a higher oral clearance of saquinavir, compared with subjects lacking functional CYP3A5 alleles. A single-dose pharmacokinetic trial of saquinavir soft gel capsules, 1,200 mg, was performed in 16 black Tanzanian healthy volunteers with two functional CYP3A5 alleles (*1/*1) and in 18 volunteers without functional CYP3A5 alleles (both alleles being either *3, *6, or *7). The median area under the plasma concentration-time curve (AUC)0-24 reached among subjects with two functional alleles was 1,410 ng h/ml (interquartile range (IQR) 826-1,929), whereas it was 2,138 ng h/ml (IQR 1,380-3,331) in subjects without (P=0.0533, Mann-Whitney U-test). The median ratio of saquinavir over its M2 plus M3 hydroxy metabolites in urine was 64 (IQR 52-73) in subjects with two functional alleles, whereas it was 145 (IQR 89-181) in those without (P=0.000078, Mann-Whitney U-test). In conclusion, saquinavir is metabolized by CYP3A5. The median AUC0-24 for saquinavir among individuals with two functional CYP3A5 alleles was 34% lower than among those with no functional alleles. To clarify the clinical importance of the CYP3A5 polymorphism, further studies should be conducted on saquinavir, dosed to steady state, in the presence of ritonavir boosting.

Lack of impact of artesunate on the disposition kinetics of sulfadoxine/pyrimethamine when the two drugs are concomitantly administered.

OBJECTIVE: To determine the effect of artesunate (AT) on the disposition kinetics of sulfadoxine/pyrimethamine (SP) in humans. METHODS: In a randomized cross-over study, 16 healthy volunteers were given a dose of three SP tablets containing 500 mg of sulfadoxine (SDX) and 25 mg of pyrimethamine (PYR) (=SP group), while the second arm received three SP tablets + two AT tablets of 200 mg in total followed by 100 mg AT for the next 4 days (SP+AT group). Blood samples (100 microl) were collected by means of a finger prick and dried on filter paper. The blood spots were wrapped in polythene folders and stored at room temperature until analysis. The samples were assayed using high-performance liquid chromatographic methods. RESULTS: The peak concentration C(max)), time required to attain peak concentration (T(max)), half-life (t ((1/2))) and area under the plasma concentration-time curve (AUC) were determined. The C(max) of SDX were 92.9 and 98.9 microg/ml for the SP and SP+AT arms, respectively; for PYR, these were 0.86 and 0.79 microg/ml, respectively. The T(max) of SDX were 10 and 8 h for the SP and SP+AT arms, respectively; for PYR, these were 4.0 and 3.0 h, respectively. The AUC(0-288) of SDX were 15,840 and 18,876 microg/ml h for the SP and SP+AT arms, respectively; for PYR, they were 124 and 112 microg/ml h, respectively. The t ((1/2)) of values for SDX were 165 and 180 h for the SP and SP+AT arms, respectively; for PYR, these were 158 and 177 h, respectively. There was no statistically significant difference between the C(max), T(max), AUC(0-288) and t ((1/2)) between the two arms (p > 0.05). CONCLUSION: Taking AT concomitantly with SP does not have any impact in the disposition of SP.

Pharmacokinetics of quinine and its metabolites in pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria.

OBJECTIVES: The study was conducted in New Halfa teaching hospital, eastern Sudan to investigate the pharmacokinetics of quinine in pregnant Sudanese women. METHODS: Sixteen (eight pregnant and eight non-pregnant) Sudanese women infected with Plasmodium falciparum malaria were given a single dose of quinine hydrochloride (10 mg/kg body weight) as intravenous infusion over 2 h. The women were treated with intramuscular artemether. Plasma was collected before quinine administration and up to 72 h thereafter. These were analysed for quinine and its metabolites, 3-hydroxyquinine, (10R)-10,11-dihydroxyquinine and (10S)-10,11-dihydroxyquinine using high-performance liquid chromatography. RESULTS: The two groups were well matched in their basic characteristics. There was no significant difference in the mean maximum plasma concentration attained (C(max)), the mean time at which C(max) was attained, the elimination half-life (t(1/2)) and the total area under the plasma concentration vs. time curve (AUC) of quinine and its metabolites between the pregnant in non-pregnant women. CONCLUSION: There was no significant difference in quinine metabolism between pregnant and non-pregnant women and there is no need to adjust quinine dose when treating pregnant women.

Assessing health worker performance in malaria case management of underfives at health facilities in a rural Tanzanian district.

OBJECTIVE: To study the quality of malaria case management of underfives at health facilities in a rural district, 2 years after the Tanzanian malaria treatment policy change in 2001. METHODS: Consultations of 117 sick underfives by 12 health workers at 8 health facilities in Mkuranga District, Tanzania were observed using checklists for history taking, counselling and prescription. Diagnoses and treatment were recorded. Exit interviews were performed with all mothers/guardians and blood samples taken from the underfives for the detection of malaria parasites and antimalarial drugs. Quality of care was measured using indicators adopted from the integrated management of childhood illnesses multi-country evaluation. RESULTS: Quality of care measured by indicator scores averaged 31% of what was considered optimal. The poorest results were for history taking. Nevertheless, 89% of febrile children were treated with antimalarials, in line with national guidelines for fever treatment. Of these, 61% had a parasitaemia > or =2000/microl. There was no difference in treatment given to those with parasitological malaria compared with those without parasites. Pre-treatment levels of chloroquine and sulphadoxine/pyrimethamine were low and detected in 2% and 13%, respectively. CONCLUSION: Although most febrile children were given antimalarial treatment, quality of care in terms of history taking and counselling was sub-optimal. Despite this, the study community had changed behaviour from self-treatment to seeking care at health facilities. This is encouraging for introduction of artemisinin-based combination therapies policies as one could focus resources into improving care at health facilities and still reach out with treatment to most febrile children.

Improved efficacy with amodiaquine instead of chloroquine in sulfadoxine/pyrimethamine combination treatment of falciparum malaria in Uganda: experience with fixed-dose formulation.

Amodiaquine (AQ) is an affordable compound, chemically related to chloroquine (CQ) but often effective against CQ resistant Plasmodium falciparum. In Uganda, a pre-packed fixed-dose combination of CQ plus sulfadoxine/pyrimethamine (CQ+SP) called Homapak is used in the home based management of fever program (HBM). We performed a single blind randomized trial to determine the efficacy of AQ+SP in comparison with the fixed-dose CQ+SP (Homapak) in the treatment of uncomplicated falciparum malaria in Ugandan children aged 6 months to 5 years. The study was done in 2004 at Walkuba Health Center, a sub-urban area in Jinja district, Uganda. Primary outcome was the day 14 per protocol clinical and parasitological response according to the WHO. A total of 183 children were included (mean age 28 months) and 90% completed 28 days of follow up. The day 14 adequate clinical and parasitological response was 70.9% for CQ+SP and 97.4% for AQ+SP (p<0.001). In those given CQ+SP, treatment failure rates for the 6 months to 2 years age group were much higher (48.2%) than in the older children (18.2%, p=0.004). The day 28 PCR adjusted parasitological failure rates were also higher in the CQ+SP (31.3%) than in the AQ+SP group (13.1%) (p=0.003), with a higher gametocyte carriage among the CQ+SP group. We conclude that the efficacy of AQ+SP was significantly superior to the fixed-dose CQ+SP (Homapak), particularly among the youngest children. Thus, AQ could be used instead of CQ in combination with SP to improve the effectiveness against falciparum malaria in Uganda.