Nafcillin

Nafcillin may be found in some form under the following brand names:

• Nallpen

• Unipen

Serious side effects have been reported with nafcillin including:

• hypersensitivity (severe allergic reaction). This type of reaction may be serious and possibly fatal. These reactions are more likely to occur in those with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Tell your healthcare provider right away if you start to develop signs or symptoms of a hypersensitivity reaction, which include the following:
  • chest pain
  • swelling of the face, eyes, lips, tongue, arms, or legs
  • difficulty breathing or swallowing
  • fainting
  • rash
• diarrhea. Diarrhea is a common problem caused by antibiotics, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial. If diarrhea is severe or lasts more than 2 or 3 days, contact your doctor, as this may be a sign of an infection of the bowels.
• superinfection: nafcillin should not be used for extended periods. Prolonged use can lead to the growth of dangerous organisms that are resistant to nafcillin. Take this medication for the duration prescribed by your doctor.

Do not take nafcillin if you:

• are allergic to nafcillin or any of its ingredients
• are allergic to penicillins
• are allergic to corn or corn products and are receiving nafcillin that contains dextrose in the solution

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a muscle or as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

In a study of five healthy adults administered a single 500 mg dose of Nafcillin by intravenous injection over seven minutes, the mean plasma concentration of the drug was approximately 30 mcg/mL at 5 minutes after injection. The mean area under the plasma concentration-versus-time curve (AUC) for Nafcillin in this study was 18.06 mcg•h/mL.

The serum half-life of Nafcillin administered by the intravenous route ranged from 33 to 61 minutes as measured in three separate studies.

In contrast to the other penicillinase-resistant penicillins, only about 30% of Nafcillin is excreted as unchanged drug in the urine of normal volunteers, and most within the first six hours. Nafcillin is primarily eliminated by nonrenal routes, namely hepatic inactivation and excretion in the bile.

Nafcillin binds to serum proteins, mainly albumin. The degree of protein binding reported for Nafcillin is 89.9 ± 1.5%. Reported values vary with the method of study and the investigator.

The concurrent administration of probenecid with Nafcillin increases and prolongs plasma concentrations of Nafcillin. Probenecid significantly reduces the total body clearance of Nafcillin with renal clearance being decreased to a greater extent than nonrenal clearance.

The penicillinase-resistant penicillins are widely distributed in various body fluids, including bile, pleural, amniotic and synovial fluids. With normal doses insignificant concentrations are found in the aqueous humor of the eye. High Nafcillin CSF levels have been obtained in the presence of inflamed meninges.

Renal failure does not appreciably affect the serum half-life of Nafcillin; therefore, no modification of the usual Nafcillin dosage is necessary in renal failure with or without hemodialysis. Hemodialysis does not accelerate the rate of clearance of Nafcillin from the blood.

A study which assessed the effects of cirrhosis and extrahepatic biliary obstruction in man demonstrated that the plasma clearance of Nafcillin was significantly decreased in patients with hepatic dysfunction. In these patients with cirrhosis and extrahepatic obstruction, Nafcillin excretion in the urine was significantly increased from about 30 to 50% of the administered dose, suggesting that renal disease superimposed on hepatic disease could further decrease Nafcillin clearance.

Microbiology

Penicillinase-resistant penicillins exert a bactericidal action against penicillin-susceptible microorganisms during the state of active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall. Nafcillin sodium has been shown to be active against most isolates of the following microorganism, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-Positive Bacteria

Staphylococcus aureus (Methicillin susceptible isolates only)

Susceptibility Test Methods

Susceptibility of staphylococcal isolates to Nafcillin may be inferred by testing penicillin and either oxacillin or cefoxitin1. For staphylococcal isolates, penicillin susceptibility implies susceptibility to other beta-lactam agents, (and penicillin resistance implies resistance to penicillinase-labile penicillins). Resistance to oxacillin (or cefoxitin) implies resistance to all other beta-lactam agents, except newer agents with activity against methicillin resistant S. aureus. Routine testing of Nafcillin is not advised.

For Administration by Intravenous Drip

Refer to Directions for Proper Use of a Pharmacy Bulk Package Bottle. Add 93 mL Sterile Water for Injection, USP, or 0.9% Sodium Chloride Injection, USP. The resulting solution will contain 100 mg Nafcillin activity per mL and will require further dilution.

CAUTION: NOT TO BE DISPENSED AS A UNIT.

Directions for Proper Use of Pharmacy Bulk Package

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Do not add supplementary medication to Nafcillin for Injection, USP.

* IMPORTANT: This chemical stability information in no way indicates that it would be acceptable practice to use this product well after the preparation time. Good professional practice suggests that a product should be used as soon after preparation as feasible.

Only those solutions listed above should be used for the intravenous infusion of Nafcillin sodium, USP. The concentration of the antibiotic should fall within the range specified. The drug concentration and the rate and volume of the infusion should be adjusted so that the total dose of Nafcillin is administered before the drug loses its stability in the solution in use.

There is no clinical experience available on the use of this agent in neonates or infants for this route of administration.

This route of administration should be used for relatively short-term therapy (24 to 48 hours) because of the occasional occurrence of thrombophlebitis particularly in elderly patients.

If another agent is used in conjunction with Nafcillin therapy, it should not be physically mixed with Nafcillin but should be administered separately.

Plasma clearance is significantly decreased and excretion in urine was significantly increased from approximately 30% to 50% in patients with biliary obstruction and cirrhosis.

Catheter-related bloodstream infections (off-label use): IV: 2 g every 4 hours (IDSA [Mermel 2009])

Endocarditis: Methicillin-susceptible Staphylococcus aureus (MSSA) (off-label dose): IV:

Native valve: 12 g/day in 4 or 6 divided doses (ie, 2 g every 4 hours or 3 g every 6 hours) for 6 weeks. Note: Duration intended for complicated right-sided infective endocarditis (IE) or left-sided IE. For uncomplicated right-sided IE, 2 weeks of therapy may be adequate (AHA [Baddour 2015]).

Prosthetic valve: 12 g/day in 6 divided doses (ie, 2 g every 4 hours) for ≥6 weeks (use with rifampin for entire course and gentamicin for first 2 weeks) (AHA [Baddour 2015])

Osteomyelitis: Methicillin-susceptible S. aureus (MSSA) (off-label dose): IV: 1.5 to 2 g every 4 to 6 hours or via continuous infusion (IDSA [Berbari 2015])

Prosthetic joint infections: Methicillin-susceptible S. aureus (MSSA) (off-label dose): 1.5 to 2 g every 4 to 6 hours (IDSA [Osmon 2013])

Skin and soft tissue infections (IDSA [Stevens 2014]):

Due to methicillin-susceptible Staphylococcus aureus (MSSA) (off-label dose): IV: 1 to 2 g every 4 hours for 7 to 14 days

Necrotizing infection due to MSSA (off-label use): IV: 1 to 2 g every 4 hours; continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours

Streptococcal skin infections (off-label use): IV: 1 to 2 g every 4 to 6 hours (IDSA [Stevens 2014])

Surgical site infections (trunk or extremity [away from axilla or perineum]) (off-label use): IV: 2 g every 6 hours (IDSA [Stevens 2014])

Mild-to-moderate infections: IM, IV: 100 to 150 mg/kg/day in divided doses every 6 hours (maximum dose: 4,000 mg daily) (Red Book [AAP 2015])

Severe infections: IM, IV: 150 to 200 mg/kg/day in divided doses every 4 to 6 hours (Red Book [AAP 2015]); for life-threatening infection (eg, meningitis), 200 mg/kg/day in divided doses every 6 hours (maximum dose: 12 g daily) (Tunkel 2004)

Skin and soft tissue infections (IDSA [Stevens 2014]):

Due to methicillin-susceptible Staphylococcus aureus (MSSA): IV: 100 to 150 mg/kg/day in divided doses every 6 hours for 7 to 14 days

Necrotizing infection due to MSSA (off-label use): IV: 200 mg/kg/day in divided doses every 6 hours; continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours

Streptococcal skin infections (off-label use): IV: 200 mg/kg/day in divided doses every 6 hours (IDSA [Stevens 2014])

IM: Administer as a deep intragluteal injection; rotate injection sites.

IV: Infuse over 30 to 60 minutes. Vesicant; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave needle/cannula in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote; remove needle/cannula (if not using IV hyaluronidase antidote), apply dry cold compresses (Hurst 2004); elevate extremity.

Hyaluronidase: Intradermal or SubQ: Inject a total of 1 mL (15 units/mL) as five separate 0.2 mL injections (using a 25-gauge needle) into area of extravasation at the leading edge in a clockwise manner (MacCara 1983; Zenk 1981).

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, or diarrhea. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), muscle weakness, muscle pain, joint pain, abdominal pain, bruising, bleeding, severe dizziness, passing out, chills, pharyngitis, severe loss of strength and energy, twitching, seizure, burning or numbness feeling, severe injection site pain, redness, burning, edema, or irritation, or signs of Clostridium difficile (C. diff)-associated diarrhea (stomach pain or cramps, very loose or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.