Pyrimethamine + sulfadiazine

Upon oral administration, quinine effectively acts in combination with pyrimethamine, sulfadiazine, and/or tetracycline for treating uncomplicated incidents of chloroquine-resistant forms of P. falciparum. Because of the many associated side effects, its use is extremely limited. Currently, the only indication for use is for forms of malaria that are resistant to other synthetic drugs. Synonyms of this drug are bronchopulmin, nicopriv, quinnam, and others. 

The combination is indicated in chloro-quine resistant malaria and prophylaxis. Pyrimethamine-sulfadiazine combination is used for treatment of toxoplasmosis. 

Toxoplasmosis Lymph nodes many organs and tissues Pyrimethamine-sulfadiazine [see antimalarial drugs] other antibacterials [clindamycin] Trimethoprim-sulfamethoxazole another agent [azithromycin, clarithromycin, atovaquone, or dapsone]... 

Caumes E, Boequet H, Guermonprez G, Rogeaux O, Bricaire F, Katlama C, Gentilini M. Adverse cutaneous reactions to pyrimethamine/sulfadiazine and pyrimetha-mine/clindamycin in patients with AIDS and toxoplasmic encephalitis. Clin Infect Dis 1995 21(3) 656-8. 

In a randomized, open, multicenter study in 46 patients with sight-threatening ocular toxoplasmosis, those who took pyrimethamine + sulfadiazine had significantly more adverse events, especially malaise, than those who took pyrimethamine + azithromycin (8). 

The discontinuation of pyrimethamine-sulfadiazine after successful initial therapy may be considered in persons who have a sustained CD4 cell count of greater than 200 cells/mcL for at least 6 months and have completed initial therapy and are asymptomatic. A regimen of sulfadiazine 500 to 1000 mg orally 4 times daily plus pyrimethamine 25 to 50 mg orally and leucovorin 10 to 25 mg orally once daily is recommended for maintenance therapy. Pyrimethamine plus clindamycin also can be considered for maintenance therapy, but this regimen may be associated with a higher relapse rate. A further advantage to the combination of pyrimethamine plus sulfadiazine is that an additional agent for prophylaxis of PCP is unnecessary, which is not the case with the pyrimethamine plus clindamycin combination. ... 

Katlama C, Wit S, O Doherty E, et al. Pyrimethamine-cUndamycin vs pyrimethamine-sulfadiazine as acute and long-term therapy for toxoplasmic encephalitis in patients with AIDS. Clin Infect Dis 1996 22 268-275. 

Toxoplasmosis Pyrimethamine + sulfadiazine TMP-SMX is also prophylactic against Pneumocystis carinii in AIDS... 

The role of spiramycin in the treatment of HIV-associated cryptosporidiosis remains inconclusive and controversial [335, 336]. The drug did hasten clinical recovery and decrease the duration of oocyst excretion in immunocompetent children with cryptosporidial diarrhea [337]. Spiramycin is also used effectively with or without pyrimethamine-sulfadiazine for the treatment of fetal toxoplasmosis [338, 339]. 

Couvreur, J., Thulliez, R, Daffos, F., Aufrant, C, Bompard, Y., Gesquiere, A., and Desmonts, G. (1993). In utero treatment of toxoplasmic fetopathy with the combination pyrimethamine-sulfadiazine. Fetal Diagn. Ther. 8, 45-50. 

Toxoplasmosis may present as a posterior e.g., focal retinochoroiditis, papillitis, vitritis, or retinitis) or occasionally as an anterior uveitis. Treatment is indicated when inflammatory lesions encroach upon the macula and threaten central visual acuity. Several regimens have been recommended with concurrent use of systemic steroids (1) pyrimethamine, sulfadiazine, and folinic acid (leucovorin) (2) pyrimethamine, sulfadiazine, clindamycin, and folinic acid (3) sulfadiazine and... 

Quinine-pyrimethamine-sulfadiazine (or sulfadoxine). In the treatment of choice for infections caused by chloroquine-resistant Plasmodium falciparum ... 

Whereas the anti-malarials that interfere with folic acid metabolism (pyrimethamine, sulfadiazine, chloroguanide, see Section 9.3.3) injure the schizonts only at the time of their division, the nucleic acid combining drugs (especially mepacrine, chloroquine) and quinine injure the schizonts at all times (Josephson et al., 1953) provided that they are in erythrocytes. Thanks to... 

The folate antagonists, pyrimethamine and sulfadiazine, inhibit the parasite s DHFR/TS synthase enzyme complex and the DHPS, respectively (Fig. 4) (see antimalarial drugs). To avoid deficiency of folic acid in patients treated with antifolate antagonists, folinic acid supplementation is recommended to reduce bone-marrow suppression. 

Currently, the most widely used are sulfisoxazole, sulfamethoxazole, sulfadiazine, sul-famethizole, and trisulfapyrimidine (a mixture of sulfamerazine, sulfamethazine, and sulfadiazine). The first two drugs mentioned are the most widely used. The long-lasting sulfonamide (sulfadioxin) is used only in combination with pyrimethamine (an antagonist of folic acid) for prevention and treatment of tropical fever. 

Pyrimethamine in combination with sulfadiazine or trisnlfapyrimidine is the dmg of choice for toxoplasmosis. A synonym of this combined dmg is daraprim. 

The treatment of choice for toxoplasmosis is pyrimethamine with sulfadiazine a folate supplement is also given to counteract the megaloblastic... 

Sulfadiazine 1-1.5 g orally or i.v. 6-hourly -f Pyrimethamine 50 to 100 mg orally initially, then 25-50 mg daily Sulfadiazine 500 mg orally 6-hourly or 1 g orally 12-hourly -f Pyrimethamine 25 to 50 mg orally daily Prophylaxis for P. carinii with cotrimoxazole is effective prophylaxis for toxoplasmosis... 

Sulfonamides, such as sulfadiazine, in combination with pyrimethamine, are considered the treatment of choice of symptomatic toxoplasmosis. Patients should be well hydrated to prevent crystalluria this problem may be reduced with the use of triple sulfas (trisulfapyrimidine). Some regimens have included a sulfonamide (sul-fadoxine) in combination with pyrimethamine (Fansidar) for the treatment of chloroquine-resistant malaria caused by P. falciparum. 

Sulfadiazine in combination with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis. The combination of sulfadiazine with pyrimethamine, a potent inhibitor of dihydrofolate reductase, is synergistic because these drugs block sequential steps in the folate synthetic pathway blockade (Figure 46-2). The dosage of sulfadiazine is 1 g four times daily, with pyrimethamine given as a 75-mg loading dose followed by a 25-mg once-daily dose. Folinic acid, 10 mg orally each day, should also be administered to minimize bone marrow suppression. 

Pyrimethamine and sulfadiazine have been used for treatment of leishmaniasis and toxoplasmosis. In falciparum malaria, the combination of pyrimethamine with sulfadoxine (Fansidar) has been used (see Chapter 52). 

Sulfadiazine Oral first-line therapy for toxoplasmosis when combined with pyrimethamine... 

Pyrimethamine, in combination with sulfadiazine, is first-line therapy in the treatment of toxoplasmosis, including acute infection, congenital infection, and disease in immunocompromised patients. For immunocompromised patients, high-dose therapy is required followed by chronic suppressive therapy. Folinic acid is included to limit myelosuppression. Toxicity from the combination is usually due primarily to sulfadiazine. The replacement of sulfadiazine with clindamycin provides an effective alternative regimen. 

Acute, congenital, immunocompromised Pyrimethamine plus clindamycin plus folinic acid Pyrimethamine plus sulfadiazine plus folinic acid... 

Toxoplasma Central nervous system infections (cerebral degeneration, meningoencephalitis] Pyrimethamine and sulfadiazine... 

Pyrimethamine may also be combined with other antimalarials such as artemisinin derivatives, but these regimens should only be used if the malarial parasites are not resistant to the specific drugs in the regimen.13 Pyrimethamine can also be combined with a sulfonamide drug such as dapsone, sulfadiazine, or sulfamethoxazole to treat protozoal infections that cause toxoplasmosis, or fungal infections that cause Pneumocystis pneumonia.These agents are administered orally. 

Sulfonamides — Sulfadoxine or sulfadiazine is used with pyrimethamine. 

Pyrimethamine is a fohc acid antagonist (antifol) with pharmacological actions similar to chlorguanide, methotrexate, and trimethoprim. Pyrimethamine may be used in combination with sulfadoxine for suppression and sulfadiazine for treatment of chloroquine-resistant Plasmodium falciparum. 

Body Fluid Range of pH Total Fluid Blood Concentration Ratios for Sulfadiazine (acid, pKa 6.5)1 Total Fluid Blood Concentration Ratios for Pyrimethamine (base, pKa 7.0)1... 

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