PHENY-PAS-TEBAMIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PHENY-PAS-TEBAMIN (PHENY-PAS-TEBAMIN).
Phenyl-PAS-Tebamin is a combination of p-aminosalicylic acid (PAS) and phenyl aminosalicylate. PAS inhibits folic acid synthesis in Mycobacterium tuberculosis by competing with p-aminobenzoic acid (PABA) for the enzyme dihydropteroate synthase, thereby blocking the conversion of PABA to dihydrofolate. The phenyl ester may enhance gastrointestinal absorption and tolerability.
| Metabolism | Primarily hepatic metabolism via acetylation (N-acetyltransferase 2, NAT2) and conjugation. Phenyl-PAS-Tebamin is metabolized to PAS and phenyl aminosalicylate, which are further acetylated and glucuronidated. |
| Excretion | Renal: 85-90% (mostly as inactive metabolites, with <5% as p-aminosalicylic acid and <1% as phenyl-p-aminosalicylate); Biliary/Fecal: 5-10%. |
| Half-life | Terminal elimination half-life for p-aminosalicylic acid is approximately 0.75-1 hour; for phenyl-p-aminosalicylate, half-life is longer, around 2-3 hours, allowing twice-daily dosing for improved compliance. |
| Protein binding | p-Aminosalicylic acid: 50-60% (primarily to albumin); phenyl-p-aminosalicylate: 80-90% (primarily to albumin). |
| Volume of Distribution | p-Aminosalicylic acid: 0.3-0.5 L/kg; phenyl-p-aminosalicylate: 0.5-0.8 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral: 85-95% (as phenyl-p-aminosalicylate, with rapid hydrolysis to p-aminosalicylic acid in the gut and liver). |
| Onset of Action | Oral: 30-60 minutes (bacteriostatic effect against Mycobacterium tuberculosis). |
| Duration of Action | Oral: 8-12 hours (bacteriostatic concentrations maintained with twice-daily dosing). |
8-12 g/day orally in 3-4 divided doses (4 g every 8-12 hours) as p-aminosalicylic acid; administered as granules or tablets.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-50 mL/min: 50% of normal dose; CrCl <10 mL/min: avoid use or 25% of normal dose. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | 200-300 mg/kg/day orally in 3-4 divided doses; maximum 12 g/day. |
| Geriatric use | Initiate at lower end of dosing range (4-8 g/day) due to reduced renal function; monitor for gastrointestinal intolerance and hepatotoxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PHENY-PAS-TEBAMIN (PHENY-PAS-TEBAMIN).
| Breastfeeding | Phenytoin is excreted into breast milk with M/P ratio approximately 0.45. Infant plasma levels are typically subtherapeutic. Monitor infant for sedation, poor feeding, and allergic reactions. Benefit of breastfeeding may outweigh risk if maternal levels are in therapeutic range. |
| Teratogenic Risk | Phenytoin (component of Phenyl-Pas-Tebamin) is associated with fetal hydantoin syndrome, including craniofacial anomalies, growth retardation, and cognitive deficits. First trimester exposure increases risk of neural tube defects due to folate antagonism. Third trimester use may cause neonatal hemorrhage due to vitamin K deficiency. All trimesters: risk of major congenital malformations approximately 2-3x baseline. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to p-aminosalicylic acid or any component","Severe hepatic impairment","Severe renal impairment (consider dose adjustment)"]
| Precautions | ["May cause hepatotoxicity, especially in patients with pre-existing liver disease","Monitor liver function tests regularly","May cause gastrointestinal intolerance (nausea, vomiting, diarrhea)","May interfere with thyroid function tests","Risk of hypersensitivity reactions including rash and fever"] |
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| Fetal Monitoring | Monitor maternal serum phenytoin levels regularly (target 10-20 mcg/mL). Fetal ultrasound for anomaly detection. Neonatal vitamin K prophylaxis. Assess infant for withdrawal symptoms or toxicity. Periodic liver function tests and CBC in mother. |
| Fertility Effects | Phenytoin has minimal direct effects on fertility but may cause menstrual irregularities and ovulatory dysfunction due to enzyme induction affecting hormone metabolism. No established impact on spermatogenesis. |