UNIPEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UNIPEN (UNIPEN).
Unipen (nafcillin) is a penicillinase-resistant penicillin that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), blocking transpeptidation and autolysin inhibition.
| Metabolism | Hepatic metabolism, primarily via hydrolysis and conjugation; minor renal elimination. |
| Excretion | Renal: 70-90% unchanged via tubular secretion and glomerular filtration; biliary: minor (<10%); fecal: minimal. |
| Half-life | 0.5-1 hour in normal renal function; prolonged to 7-10 hours in anuria or severe renal impairment. |
| Protein binding | 20-40% bound to serum albumin and other plasma proteins. |
| Volume of Distribution | 0.2-0.3 L/kg; low Vd indicates limited tissue penetration, predominantly extracellular fluid. |
| Bioavailability | Oral: 30-50% due to acid lability and first-pass metabolism; IM: 70-90%. |
| Onset of Action | IV: immediate; IM: 15-30 minutes; oral: 30-60 minutes. |
| Duration of Action | 4-6 hours; may be extended in renal impairment. |
| Molecular Weight | 436.48 Da |
500 mg to 2 g orally or intravenously every 4 to 6 hours; maximum 12 g/day IV for serious infections.
| Dosage form | INJECTABLE |
| Renal impairment | For CrCl <10 mL/min: administer every 8 to 12 hours; for CrCl 10-50 mL/min: no adjustment needed; for hemodialysis: dose after dialysis. |
| Liver impairment | No specific adjustment recommended; use with caution in severe hepatic impairment due to potential increased toxicity. |
| Pediatric use | Neonates: 25-50 mg/kg/day divided every 8-12 hours (weight <2 kg) or every 6-8 hours (weight >2 kg); Infants and children: 50-100 mg/kg/day divided every 6 hours; maximum 12 g/day. |
| Geriatric use | No specific dose adjustment required; monitor renal function and adjust based on creatinine clearance to avoid accumulation. |
| 1st trimester | Limited human data; animal studies not suggestive of harm. Use only if clearly needed. |
| 2nd trimester | Limited human data; generally considered safe when penicillin allergy is absent. |
| 3rd trimester | Limited human data; risk of neonatal sensitization or diarrhea theoretically possible but not reported. |
Clinical note
Comprehensive clinical and safety monograph for UNIPEN (UNIPEN).
| Placental transfer | Nafcillin crosses the placenta in therapeutic concentrations. Studies show cord blood levels approximately 10–50% of maternal serum levels. |
| Breastfeeding | Nafcillin is excreted into breast milk in small amounts. It is generally considered compatible with breastfeeding due to low oral bioavailability and lack of adverse effects in infants. Monitor for potential rash or diarrhea. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to nafcillin or any penicillinHistory of immediate hypersensitivity reaction (e.g., anaphylaxis) to beta-lactam antibiotics
| Precautions | Hypersensitivity reactions: Risk of anaphylaxis and severe skin reactions., Clostridioides difficile-associated diarrhea: Consider if diarrhea occurs., Serum potassium monitoring: Nafcillin can cause hypokalemia with high doses., Hematologic effects: Neutropenia, thrombocytopenia, and agranulocytosis with prolonged therapy., Drug-induced liver injury: Elevated transaminases and cholestatic hepatitis. |
| Food/Dietary | No specific food interactions. Take with food to reduce gastrointestinal upset if oral use; however, oral nafcillin is not recommended due to poor absorption. Avoid alcohol during therapy. |
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| Lactation Rating |
| L2 |
| Teratogenic Risk | Nafcillin is FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; no adequate human studies. Avoid in first trimester unless benefits outweigh risks. Second and third trimester: Use with caution due to limited data. |
| Fetal Monitoring | Monitor for maternal hypersensitivity reactions, renal function, and signs of hepatotoxicity. No specific fetal monitoring required beyond routine antenatal care. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility. |
| Clinical Pearls | UNIPEN (nafcillin) is a penicillinase-resistant penicillin. Administer via IV or IM only; oral absorption is unreliable. Do not mix with aminoglycosides in the same IV line due to inactivation. Monitor liver function tests as nafcillin can cause transient elevations. Use with caution in neonates due to risk of kernicterus. |
| Patient Advice | This medication must be given by injection or IV, not by mouth. · Report any signs of allergic reaction such as rash, itching, or difficulty breathing immediately. · Complete the full course of therapy even if you feel better. · Inform your healthcare provider about all medications you are taking, especially blood thinners. · Liver function tests may be monitored during treatment. |