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Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
These agents are used primarily to treat toxoplasmosis. Pyrimethamine, a folic acid antagonist, is also used to treat malaria. There are no adequate scientific studies of its use during pregnancy, but Hengst (1992) reported no increase in the malformation rate in 64 newborns whose mothers had taken this drug during the first half of pregnancy. Spiramycin has been used extensively in Europe during the first trimester with no apparent adverse fetal effects. Sulfadiazine, a sulfonamide, has not been reported to be teratogenic when used in the first trimester. However, as with all sulfonamides, it could potentially be related to hyperbilirubinemia in the newborn, especially in the premature infant.
Toxoplasma gondii
Published in Peter D. Walzer, Robert M. Genta, Parasitic Infections in the Compromised Host, 2020
Pyrimethamine is a folic acid antagonist and when used in anti-Toxoplasma doses may cause significant bone marrow suppression. Folinic acid (leucovorin) is transported across human cell membranes but not across Toxoplasma cell membranes and therefore may be a useful adjunct to prevent the bone marrow toxicity of pyrimethamine but maintain its therapeutic efficacy. In contrast, folic acid seems to have an adverse effect on the action of pyrimethamine and sulfadiazine (380). Folinic acid at a dose of 5-10 mg/day should be given orally or parenterally along with pyrimethamine. Other less serious side effects with pyrimethamine include gastrointestinal distress, headaches, and a bad taste in the mouth.
A Case of Toxoplasmosis in Pregnancy
Published in Meera Chand, John Holton, Case Studies in Infection Control, 2018
If T. gondii DNA had been detected in amniotic fluid, it would have indicated that foetal infection was likely to have taken place. As spiramycin does not cross the placenta, the treatment of choice in this situation would be an oral combination regimen of pyrimethamine (an antagonist of dihydrofolate reductase) and sulfadiazine (a sulfonamide drug), along with folinic acid supplementation to prevent bone marrow suppression. This treatment should be continued in the mother through pregnancy. Trimethoprim-sulfamethoxazole has also been used. Clindamycin is an alternative agent if there has been a history of sulfonamide allergy. Other options are azithromycin, dapsone, and atovaquone, but experience of their use in this context is limited. Pyrimethamine is generally felt to be the pivotal drug in the treatment regimen but should not be given in the first trimester as it is teratogenic.
Infection-related stillbirth: an update on current knowledge and strategies for prevention
Published in Expert Review of Anti-infective Therapy, 2021
Samia Aleem, Zulfiqar A. Bhutta
IPT with sulfadoxine-pyrimethamine (SP) during pregnancy is recommended year-round with a 3 dose regimen in areas that are malaria endemic, starting in the second trimester [14]. This recommendation is based on a systematic review and meta-analysis of trials that compared regimens containing three or more doses for IPT, versus the previous standard of two doses [15]. Seven trials comprising 6281 pregnancies in sub-Saharan Africa were included in the study, which found that IPT with 3 or more doses of SP was associated with a higher birth weight and a lower risk of low birth weight compared to 2 doses [15]. This study however did not assess the effect on rates of stillbirth. A Cochrane review from 2014 which included 17 chemoprevention trials, enrolling 20,256 pregnant women found that malaria chemoprevention reduced the risk of antenatal parasitemia by nearly 61%, and reduced low birthweight by nearly 27% [16]. Notably, no effect was seen on perinatal mortality, spontaneous abortions, or stillbirths; these analyses, however, were underpowered to detect clinically significant differences [16].
Higher Drug Prices from Anticompetitive Conduct: Three Case Studies
Published in Journal of Legal Medicine, 2019
In addition to increasing price, Turing initiated another less widely understood move—it changed the distribution scheme for the drug. Before its acquisition by Turing, pyrimethamine was available without restriction to patients seeking to fill prescriptions at local pharmacies and to hospitals seeking to stock the product for inpatient use. But in the months before the price hike, apparently as a condition of the sale to Turing, pyrimethamine was switched to a controlled distribution system called Daraprim Direct, in which prescriptions or supplies of the product could be obtained only from a single source: Walgreen’s Specialty Pharmacy.84 As a result, hospitals could no longer obtain the drug from a general wholesaler, and patients could no longer find it at a local pharmacy.
Pharmacotherapy for the prevention of malaria in pregnant women: currently available drugs and challenges
Published in Expert Opinion on Pharmacotherapy, 2018
Brioni R. Moore, Timothy M. E. Davis
Both sulfadoxine and pyrimethamine are well absorbed and reach peak plasma concentrations approximately 4 h after administration (range 2–6 h) [67]. Both drugs are highly (>87%) protein bound, resulting in prolonged clearance with a mean elimination t1/2 of 169 h and 111 h for sulfadoxine and pyrimethamine, respectively [67]. However, there has been significant differences in pharmacokinetic parameters between studies in pregnancy [20,68–70]. A recent pharmacokinetic study of IPTp-SP concluded that pregnancy resulted in a three-fold increased clearance of sulfadoxine but an 18% decrease in the clearance of, and thus greater exposure to, pyrimethamine [68,70]. The unexpected sulfadoxine result was in the context of studies showing increased (Mali, Mozambique, Zambia [69]), similar (Sudan, Kenya [69,71];) or reduced (PNG, Uganda [19,70,72];) exposure. However, the studies showing reduced clearance in pregnancy utilized lactating women as controls. The expression of CYP enzymes can be upregulated during breastfeeding and so pyrimethamine clearance may be relatively high with the result that pregnancy may be wrongly interpreted as showing a reduced clearance [73].