Sulfadoxine+ Pyrimethamine

# Sulfadoxine+ pyrimethamine ## Overview - **Classification**: Antimalarial, Folic Acid Antagonist (Sulfonamide + Dihydrofolate Reductase Inhibitor) - **Mechanism**: Blocks two sequential steps in parasitic folate synthesis. Sulfadoxine inhibits dihydropteroate synthase; Pyrimethamine inhibits dihydrofolate reductase. ## Primary Indications 1. **Intermittent Presumptive Treatment in Pregnancy (IPTp)** - Prevention of malaria in pregnant women, particularly in endemic areas. 2. **Intermittent Presumptive Treatment in Infants/Children (IPTi/IPTc)** - Prevention of malaria in infants/children in specific endemic settings. 3. **Malaria Treatment** - Treatment of uncomplicated *P. falciparum* malaria, but resistance is widespread in many regions. ## Adult Dosing ### Standard Dosing **Intermittent Presumptive Treatment in Pregnancy (IPTp)** - **Dose**: **3 tablets** of **500 mg sulfadoxine / 25 mg pyrimethamine** (total **1500 mg sulfadoxine / 75 mg pyrimethamine**). - **Frequency**: Once per month. - **Route**: Oral - **Duration**: Starting in the second trimester (after 16 weeks gestation) until delivery. Administer at least 3 doses, each 1 month apart. **Malaria Treatment (Uncomplicated *P. falciparum*)** - *Use limited by widespread resistance* - **Dose**: **3 tablets** of **500 mg sulfadoxine / 25 mg pyrimethamine** (total **1500 mg sulfadoxine / 75 mg pyrimethamine**). - **Frequency**: Single dose. - **Route**: Oral ### Dose Adjustments - **Renal Impairment**: Not recommended in severe impairment (CrCl < 30 mL/min). Use with caution in moderate impairment. - **Hepatic Impairment**: Use with caution. Not recommended in severe hepatic disease. - **Elderly Patients**: Use with caution due to potential decreased renal/hepatic function and increased sensitivity to adverse effects. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: Not recommended. - **Special Notes**: Sulfonamides may displace bilirubin, increasing risk of kernicterus in neonates. ### Infants (1-12 months) **Intermittent Presumptive Treatment in Infants (IPTi)** - **Dose**: **1/2 tablet** of **500 mg sulfadoxine / 25 mg pyrimethamine** (total **250 mg sulfadoxine / 12.5 mg pyrimethamine**). - **Frequency**: Given with routine EPI vaccination visits (e.g., at 10 weeks, 14 weeks, 9 months). - **Maximum**: **250 mg sulfadoxine / 12.5 mg pyrimethamine** per dose. **Malaria Treatment (Uncomplicated *P. falciparum*)** - **Dose**: **1/2 tablet** of **500 mg sulfadoxine / 25 mg pyrimethamine** (total **250 mg sulfadoxine / 12.5 mg pyrimethamine**). - **Frequency**: Single dose. - **Maximum**: **250 mg sulfadoxine / 12.5 mg pyrimethamine** per dose. ### Children (1-12 years) **Malaria Treatment (Uncomplicated *P. falciparum*)** - **Dose**: - **1-3 years (approx. <15 kg)**: **1 tablet** (500 mg sulfadoxine / 25 mg pyrimethamine). - **4-8 years (approx. 15-30 kg)**: **2 tablets** (1000 mg sulfadoxine / 50 mg pyrimethamine). - **9-12 years (approx. 31-45 kg)**: **2-3 tablets** (1000-1500 mg sulfadoxine / 50-75 mg pyrimethamine). - **Frequency**: Single dose. - **Maximum**: **3 tablets** (**1500 mg sulfadoxine / 75 mg pyrimethamine**) per dose. ### Adolescents (13-18 years) - **Dose**: Follows **adult dosing** guidelines based on weight. - **Maximum**: **3 tablets** (**1500 mg sulfadoxine / 75 mg pyrimethamine**) per dose. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to sulfadoxine, pyrimethamine, or other sulfonamides. - **Absolute**: Documented megaloblastic anemia due to folate deficiency. - **Absolute**: Infants < 2 months of age (risk of kernicterus). - **Absolute**: Severe renal or hepatic impairment. - **Absolute**: Porphyria. - **Relative**: History of blood dyscrasias. ### Common Adverse Effects - **Very Common (>10%)**: Nausea, vomiting, abdominal pain. - **Common (1-10%)**: Rash, pruritus, headache, dizziness, loss of appetite. - **Serious but Rare**: Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), agranulocytosis, aplastic anemia, hepatic necrosis, crystalluria. ### Key Drug Interactions - **Folic acid antagonists (e.g., Methotrexate, Trimethoprim)**: Increased risk of bone marrow suppression (myelosuppression). Avoid co-administration or monitor CBC closely. - **Warfarin**: May enhance anticoagulant effect of warfarin. Monitor INR frequently. - **Phenytoin**: May increase phenytoin concentrations. Monitor phenytoin levels. - **Sulfonylureas**: May enhance hypoglycemic effect. Monitor blood glucose. ## Monitoring & Follow-up - **Before Treatment**: Assess for sulfa allergy, pre-existing folate deficiency, severe renal/hepatic disease. - **During Treatment**: Monitor for signs of hypersensitivity (skin rash), GI upset. - For prolonged use or high doses: Baseline and periodic **complete blood count (CBC)**, renal and hepatic function tests. - **Clinical Signs**: Watch for severe skin rash, fever, sore throat, signs of unusual bleeding/bruising (possible myelosuppression). ## Clinical Pearls - 💡 **IPTp Efficacy**: SP is a cornerstone for preventing malaria in pregnant women, leading to reduced maternal anemia and improved birth outcomes. - 💡 **Folate Supplementation**: Advise taking SP on a day separate from daily iron/folate supplements, as high-dose folate can reduce SP's efficacy. Routine low-dose folate is generally safe. - 💡 **Hydration**: Encourage adequate fluid intake to help prevent crystalluria, particularly with higher doses. - 💡 **Taste**: Pediatric formulations or administration advice may be needed due to the potentially bitter taste. - 💡 **Resistance**: Due to widespread *P. falciparum* resistance, SP is often ineffective for malaria *treatment* in many areas. Adhere strictly to local treatment guidelines. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.