Background
Decreasing efficacy of sulphadoxine-pyrimethamine for intermittent prevention of malaria in pregnancy
Mechanism of action and development of resistance to SP
Rationale for use of probenecid
Pharmacokinetics
Probenecid
Sulphadoxine-pyrimethamine (SP)
Adverse events
Probenecid
Sulphadoxine-pyrimethamine (SP)
Pregnancy
Probenecid
Author | Study | N | Treatment | Timing of Treatment | SAEs | Infant Outcome |
---|---|---|---|---|---|---|
Cavenee et al. [84] | Treatment of gonorrhoea in pregnancy | 123 | Amoxicillin 3 gm + probenecid 1 gm | 64 patients (25%) treated in 1st trimester of pregnancy | None, one woman reported vomiting several hours after taking the drug | 71 infants were evaluated, 14 treated < 14 week, 1 major malformation (7%), 4 minor malformations (29%); 57 > 14 week, 0 major and 10 minor malformations (18%), overall 1% major and 20% minor malformations, not statistically different from other groups |
Adelson et al. [85] | Treatment of urinary tract infections in pregnancy | 98 | Ampicillin 3.5 gm + probenecid 1 gm | Not stated | 3 patients developed candidal vulvo-vaginitis, 3 patients developed diarrhoea | Not stated |
Brown et al. [86] | Renal clearance of oestrogen in pregnancy | 9 | Probenecid 2.5 gm | Last 6 weeks of pregnancy | None reported | No foetal deaths or stillbirths |
Lee et al. [87] | Gout and pregnancy | 1 | Probenecid 1 gm to 3 gm daily throughout pregnancy | Throughout pregnancy | Anaemia thought related to renal disease | Healthy infant |
Weingold et al. [88] | Gout and pregnancy | 1 | Colchicine and probenecid | Throughout 1st pregnancy and for the first 14 weeks of 2nd pregnancy | Mild anaemia | 1st pregnancy: infant died on DOL4 due to hyaline membrane disease 2nd pregnancy: healthy infant |
Goodrich [55] | Gonorrhoea and pregnancy | 163 | Penicillin G 4.8 × 106 U (n = 158) or ampicillin (n = 5) + probenecid 1 gm | Not stated | None reported | Not stated |
Schackis [89] | Hype-ruricemia and pre-eclampsia | 20* | Probenecid 250 mg twice daily for 7 days | 26-32 weeks gestation | No side-effects to probenecid were recorded | There were 3 intrauterine foetal deaths: 1 from an abruptio placenta (> 1 kg) in the probenecid group and 2 from suspected placental insufficiency (both < 1 kg): 1 each in the probenecid and placebo group. |
Czaczkes et al. [90] | Pre-eclampsia, eclampsia | 18† | Probenecid 0.5 gm 3 times daily for 5-6 days | Not stated | None reported | Not stated |
Sulphadoxine-pyrimethamine
Drug interactions
Probenecid
List of drugs whose concentration or effects are increased by probenecid
-
Antibacterials: Penicillins, Cephalosporins, Carbapenems, Quinolones, Dapsone, Rifampin, Tazobactam
-
Antivirals: Ganciclovir, Valganciclovir, Oseltamavir, Peramavir
-
Antiretrovirals: Zalcitabine, Zidovudine
-
Methotrexate
-
Acetaminophen
-
Non-steroidal anti-inflammatory drugs: Indomethacin, Ketoprofen, Ketorolac, Naproxen, Zomepirac
-
Benzodiazepines: Lorazepam, Midazolam, Nitrazepam
-
Chlorothiazide (thiazide)
-
Loop Diuretics: Bumetanide, Furosemide
-
Mycophenolate
-
Theophylline Derivatives: Dyphylline, Enprofylline but NOT Aminophylline or Theophylline
-
Sulphonylureas: Glimepiride, Glyburide
-
Nitrofurantoin
-
Apazone
-
Entacapone
-
Famotidine
-
Pemetrexed
-
Pralatrexate
-
Sodium Phenylacetate, Sodium Benzoate
Sulphadoxine-pyrimethamine
Drug | Effect of Interaction |
---|---|
Phenytoin
| Serum hydantoin levels and risk of toxicity may be increased due to inhibition of hepatic metabolism by sulphadoxine |
Sulphonylureas (Glimepiride, Glyburide) | The hypoglycemic potential of the sulphonylureas may be increased; the mechanism of this interaction is unknown. |
Vitamin K antagonists (Coumadin, anisindione) | Co-administration with a sulphonamide may increase the plasma concentrations and hypoprothrombinemic effects of coumarin anticoagulants |
Gold salts
| Increase the risk of blood dyscrasias |
Cyclosporine
| Sulphadoxine decreases the serum concentration of cyclosporine while enhancing its nephrotoxic effect |
Drug | Effect of Interaction |
---|---|
Gold salts
| Increased risk of blood dyscrasias |
Methotrexate
| Increased risk of bone marrow suppression |
Dapsone
| Folate antagonists may increase the likelihood of adverse hematologic reactions (e.g., agranulocytosis, anaemia) |
Carvedilol
| Possible for increased serum concentration of the S-carvedilol enantiomer |
Phenothiazines
| Anti-malarial agents may increase the serum concentration |
Fesoterodine
| Serum concentrations of the active metabolite may be increased |
Nebivolol
| Serum concentration may be increased |
Zidovudine, abacavir, lamivudine
| Increased risk of bone marrow suppression |
Tamoxifen
| Metabolism of Tamoxifen to the active metabolites may be decreased |
Lorazepam
| Increases risk of elevated liver function tests |
Codeine
| CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine, diminishing its therapeutic effect |
Tramadol
| CYP2D6 inhibitors may prevent the metabolic conversion to the active metabolite, diminishing its therapeutic effect |
Antacids
| Reduce the absorption of pyrimethamine (decreased bioavailability) |