[e-drug] Concurrent use of Co-trimoxazole and ACT in children

["adenrele koleade" <koleadea@yahoo.com>]

Concurrent use of Co-trimoxazole and ACT in children 
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Dear fellow E-druggers,
 
At  a recent technical meeting with members of the Sudan IMCI Strategy Implementation team an issue was brought up for discussion which we would like to share with you all for advice.
 
IMCI strategy being implemented in Sudan is using Co-trimoxazole as 1st line treatment for Pneumonia cases in under 5 children.
ACT [Artesunate plus Sulphadoxine + Pyrimethamine] has been adopted in the country for treatment of malaria cases for the same age group.
 
Would it be right to combine these 2 drugs (i.e. Cotrimoxazole and ACT) for a child under 5 having Pneumonia and Malaria at the same time?

[see moderator comment below. KM]

Thanks. 
 
Adenrele Koleade,
Pharmaceuticals Specialist,
WHO(Sudan),
Khartoum.
koleadea@yahoo.com
Mobile: 249912160795 

[Moderator: there are no known interactions between artesunate and other drugs. And of course no between sulphadoxine and sulphmethoxazole. However, pyrimethamine is more problematic:
1. Summary: Coadministration of pyrimethamine with cotrimoxazole, an antifolic drug, may increase the risk of bone marrow suppression (Prod Info Daraprim(R), 2003). Coadministered cotrimoxazole and pyrimethamine may result in megaloblastic anemia or pancytopenia (Ansdell et al, 1976; Fleming et al, 1974; Borgstein & Tozer, 1974). The extent to which sulfamethoxazole and trimethoprim individually contribute to this interaction is unknown. 
2. Adverse Effect: an increased risk of megaloblastic anemia and pancytopenia 
3. Clinical Management: Avoid giving cotrimoxazole (sulfamethoxazole/trimethoprim), an antifolic agent, and pyrimethamine concomitantly. Should it become clinically necessary to coadminister these agents, aggressively monitor complete blood counts and observe the patient for bruising and excessive bleeding. Consider adding leucovorin (folinic acid) to therapy. 
4. Severity: major 
5. Onset: delayed 
6. Documentation: good 
7. Probable Mechanism: additive dihydrofolate reductase inhibition 
8. Literature Reports: 
a. A 27-year-old female patient was receiving pyrimethamine 25 mg weekly plus cotrimoxazole for malaria prophylaxis. The patient developed megaloblastic anemia which resolved with oral iron therapy and discontinuation of both drugs. The reaction was thought to be due to the additive inhibition by both drugs of dihydrofolate reductase (Ansdell et al, 1976). 
b. A 43-year-old female was taking pyrimethamine 50 mg weekly for malaria prophylaxis. After signs of a urinary tract infection developed, she self-treated with cotrimoxazole (trimethoprim 320 mg/sulfamethoxazole 800 mg per day) for ten days prior to admission. On admission, the patient was found to have diffuse petechial hemorrhages and widespread bruising. Her hemoglobin level was 9.4 g/dl, hematocrit 30%, platelets 28,000/mm(3), and white blood cell count 3100/mm(3); red blood cells exhibited anisocytosis, some poikilocytosis, occasional multilobed polymorphs, and no macrocytes. Bone marrow aspiration showed grossly megaloblastic erythropoiesis, numerous giant metamyelocytes, and scanty megakaryocytes. All medications were stopped except for chloroquine for malaria prophylaxis. She responded rapidly to treatment with hydroxocobalamin and folic acid (Fleming et al, 1974). 
c. An in vitro study using bone marrow was undertaken to determine the mechanism of pyrimethamine-induced megaloblastosis (Waxman & Herbert, 1969). Pyrimethamine was found to cause defective deoxyuridine conversion to thymidylate, thereby interfering with effective DNA synthesis.]