Unipen

Nafcillin is an antibiotic that fights bacteria. Nafcillin is in the penicillin group of antibiotics.

Nafcillin is used to treat many different types of infections, especially those caused by staphylococcus bacteria ("staph" infections).

Nafcillin may also be used for purposes not listed in this medication guide.

You should not use this medicine if you are allergic to any penicillin antibiotic.

You should not use this medicine if you are allergic to nafcillin or to any other penicillin antibiotic, such as:

• amoxicillin (Amoxil, Augmentin, Moxatag, Trimox);
• ampicillin (Principen, Unasyn);
• dicloxacillin (Dycill, Dynapen);
• oxacillin (Bactocill); or
• penicillin (Bicillin L-A, Pfizerpen, PC Pen VK).

To make sure nafcillin is safe for you, tell your doctor if you have:

• asthma;
• liver disease;
• kidney disease; or
• a history of any type of allergy (especially to a cephalosporin antibiotic such as Omnicef, Cefzil, Ceftin, Keflex, and others).

This medicine is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Nafcillin can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

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

Before taking nafcillin, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to nafcillin or to any of its ingredients
• are allergic to similar antibiotics (penicillins, cephalosporins)
• have a history of other allergies
• are allergic to corn or corn products
• have a history of asthma
• have kidney or liver problems
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant. The FDA categorizes medications based on safety for use during pregnancy.

Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Nafcillin falls into category B. There are no well-done studies that have been done in humans with nafcillin. But in animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

Administration

Administer by IV injection or infusion or by IM injection.1 63

To reduce risk of thrombophlebitis and other adverse local reactions associated with IV administration (particularly in geriatric patients), administer slowly and take care to avoid extravasation.41 62 63

IV route should be used for relatively short periods of time (e.g., 24–48 hours).1 63

For solution and drug compatibility information, see Compatibility under Stability.

IV Injection

Reconstitute vials containing 1 or 2 g of nafcillin by adding 3.4 or 6.8 mL, respectively, of sterile water for injection, bacteriostatic water for injection (with benzyl alcohol or parabens), or 0.9% sodium chloride injection to provide solutions containing 250 mg/mL.1 When dissolved, the appropriate dose of the drug should be further diluted with 15–30 mL of sterile water for injection or sodium chloride injection.1

Inject appropriate dose of diluted solution slowly over 5–10 minutes into the tubing of a free-flowing compatible IV solution.1 (See Solution Compatibility under Stability.)

IV Infusion

Reconstitute vials containing 1 or 2 g of nafcillin by adding 3.4 or 6.8 mL, respectively, of sterile water for injection, bacteriostatic water for injection (with benzyl alcohol or parabens), or 0.9% sodium chloride injection to provide solutions containing 250 mg/mL.1 When dissolved, further dilute with a compatible IV solution (see Solution Compatibility under Stability) according to the manufacturer’s directions.1

Alternatively, ADD-Vantage vials containing 1 or 2 may be reconstituted according to the manufacturer’s directions.

Reconstitute 10-g pharmacy bulk package with 93 mL of sterile water for injection or 0.9% sodium chloride injection to provide a solution containing 100 mg/mL.1 Pharmacy bulk packages of the drug are not intended for direct IV infusion; prior to administration, doses of the drug from the reconstituted pharmacy bulk package must be further diluted in a compatible IV infusion solution (see Solution Compatibility under Stability).

Thaw the commercially available injection (frozen) at room temperature or in a refrigerator; do not force thaw by immersion in a water bath or by exposure to microwave radiation.63 A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature.63 Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact.63 Additives should not be introduced into the injection.63 The injections should not be used in series connections with other plastic containers, since such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from the secondary container is complete.63

For intermittent IV infusion, infuse over a period of at least 30–60 minutes.63

IM Administration

Inject IM deeply into a large muscle (e.g., gluteus maximus),1 avoiding sciatic nerve injury.59

For IM injection, reconstitute vial containing 1 or 2 g of nafcillin by adding 3.4 or 6.8 mL, respectively, of sterile water for injection, bacteriostatic water for injection (with benzyl alcohol or parabens), or 0.9% sodium chloride injection to provide solutions containing 250 mg/mL.1

Dosage

Available as nafcillin sodium; dosage expressed in terms of nafcillin.1 63

Duration of treatment depends on type and severity of infection and should be determined by clinical and bacteriologic response of the patient.46 49 59 71 In severe staphylococcal infections, duration usually is ≥2 weeks;59 more prolonged therapy is necessary for treatment of osteomyelitis, endocarditis, or other metastatic infections.46 52 53 55 56 59 71

Pediatric Patients

Neonates <1 week of age: AAP and others recommend 25 mg/kg every 12 hours for those weighing ≤2 kg and 25 mg/kg every 8 hours for those weighing >2 kg.67 72 The higher dosages are recommended for meningitis.67

Neonates 1–4 weeks of age: AAP and others recommend 25 mg/kg every 12 hours for those weighing <1.2 kg; 25 mg/kg every 8 hours for those weighing 1.2–2 kg; and 25–35 mg/kg every 6 hours for those weighing >2 kg.67 72 The higher dosages are recommended for meningitis.67

10 mg/kg twice daily recommended by manufacturer.1

Neonates <1 week of age: AAP and others recommend 25 mg/kg every 12 hours for those weighing ≤2 kg and 25 mg/kg every 8 hours for those weighing >2 kg.67 72 The higher dosages are recommended for meningitis.67

Neonates 1–4 weeks of age: AAP and others recommend 25 mg/kg every 12 hours for those weighing <1.2 kg; 25 mg/kg every 8 hours for those weighing 1.2 to 2 kg; and 25–35 mg/kg every 6 hours for those weighing >2 kg.67 72 The higher dosages are recommended for meningitis.67

Children weighing ≥40 kg: manufacturer recommends 500 mg every 4 hours for mild to moderate infections and 1 g every 4 hours for severe infections.1

Children ≥1 month of age: AAP recommends 50–100 mg/kg daily in 4 divided doses for mild to moderate infections or 100–150 mg/kg daily in 4 divided doses for severe infections.67

Children weighing <40 kg: manufacturer recommends 25 mg/kg twice daily.1

Children weighing ≥40 kg: manufacturer recommends 500 mg every 4–6 hours for mild to moderate infections and 1 g every 4 hours for severe infections.1

Children ≥1 month of age: AAP recommends 50–100 mg/kg daily in 4 divided doses for mild to moderate infections or 100–150 mg/kg daily in 4 divided doses for severe infections.67

AHA recommends 200 mg/kg daily given in divided doses every 4–6 hours for 6 weeks (maximum 12 g daily).69

In addition, during the first 3–5 days of nafcillin therapy, IM or IV gentamicin (3 mg/kg daily given in divided doses every 8 hours; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL) may be given concomitantly if the causative organism is susceptible to the drug.69

AHA recommends 200 mg/kg daily given in divided doses every 4–6 hours for 6 weeks or longer (maximum 12 g daily).

Used in conjunction with oral rifampin (20 mg/kg daily given in divided doses every 8 hours for 6 weeks or longer) and IM or IV gentamicin (3 mg/kg daily given in divided doses every 8 hours during the first 2 weeks of nafcillin therapy; dosage adjusted to achieve peak serum gentamicin concentrations approximately 3 mcg/mL and trough concentrations <1 mcg/mL).69

Adults

500 mg every 4 hours; severe infections may require 1 g every 4 hours.1

500 mg every 4–6 hours; severe infections may require 1 g every 4 hours.1

1–2 g every 4 hours.44 50 51 52 54

When used for treatment of acute or chronic osteomyelitis caused by susceptible penicillinase-producing staphylococci, parenteral therapy usually given for 3–8 weeks;44 50 51 52 53 54 56 58 71 follow-up with an oral penicillinase-resistant penicillin generally is recommended for treatment of chronic osteomyelitis.47 53 55 71

AHA recommends 2 g every 4 hours for 4–6 weeks.54

Although benefits of concomitant aminoglycosides have not been clearly established, AHA states that IM or IV gentamicin (1 mg/kg every 8 hours) may be given concomitantly during the first 3–5 days of nafcillin therapy.54

AHA recommends 2 g every 4 hours for ≥6 weeks in conjunction with oral rifampin (300 mg every 8 hours for 6 weeks or longer) and IM or IV gentamicin (1 mg/kg every 8 hours during the first 2 weeks of nafcillin therapy).54 (See Staphylococci Resistant to Penicillinase-resistant Penicillins under Cautions.)

2 g every 4 hours.74

Special Populations

Hepatic Impairment

Dosage adjustments not required unless renal function also impaired.18 27 33 57 60 63 70

Renal Impairment

Modification of dosage generally is unnecessary in patients with renal impairment alone; modification of dosage may be necessary in those with both severe renal impairment and hepatic impairment.18 27 33 57 60 63 70

Specific Drugs

• Based on spectrum of activity, classified as a penicillinase-resistant penicillin.4 5 8 59 70

• Usually bactericidal.1

• Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.1

• Spectrum of activity includes many gram-positive aerobic cocci , some gram-positive bacilli, and a few gram-negative aerobic cocci; generally inactive against gram-negative bacilli and anaerobic bacteria.a Inactive against mycobacteria, Mycoplasma, Rickettsia, fungi, and viruses.a

• Gram-positive aerobes: active in vitro against penicillinase-producing and nonpenicillinase-producing Staphylococcus aureus and S. epidermidis, S. pyogenes (group A β-hemolytic streptococci), S. agalactiae (group B streptococci), groups C and G streptococci, S. pneumoniae, and some viridans streptococci.a Enterococci (including E. faecalis) usually resistant.a

• Like other penicillinase-resistant penicillins, nafcillin is resistant to inactivation by most staphylococcal penicillinases and is active against many penicillinase-producing strains of S. aureus and S. epidermidis resistant to natural penicillins, aminopenicillins, and extended-spectrum penicillins.8 10 59 70

• Staphylococci resistant to penicillinase-resistant penicillins (referred to as oxacillin-resistant [methicillin-resistant] staphylococci) are being reported with increasing frequency.a Complete cross-resistance occurs among the penicillinase-resistant penicillins (dicloxacillin, nafcillin, oxacillin).a

Applies to nafcillin: injectable powder for injection, intravenous solution, oral capsule

Gastrointestinal

Gastrointestinal side effects have included nausea, vomiting, diarrhea, stomatitis, black or hairy tongue, gastrointestinal irritation, and pseudomembranous colitis.[Ref]

Local

Local side effects have included pain, swelling, phlebitis, thrombophlebitis, and skin sloughing after intravenous administration. Intramuscular injections may cause pain at the injection site. Extravasation may result in severe chemical irritation. Subcutaneous extravasation has been associated with severe tissue necrosis.[Ref]

Hypersensitivity

Hypersensitivity reactions have included urticaria, pruritus, angioneurotic edema, laryngeal edema, laryngospasm, bronchospasm, hypotension, vascular collapse, anaphylaxis, serum sickness-like reactions, fever, and death.[Ref]

Hematologic

Hematologic side effects have included agranulocytosis, neutropenia, bone marrow depression, and platelet dysfunction. These reactions are usually reversible upon discontinuation of nafcillin (the active ingredient contained in Unipen) [Ref]

At least three cases of platelet dysfunction with prolonged bleeding times have been reported with nafcillin therapy. All cases resolved following discontinuation of nafcillin.[Ref]

Renal

Renal side effects have included renal tubular damage and interstitial nephritis. Symptoms may include rash, fever, eosinophilia, hematuria, proteinuria, and renal insufficiency.[Ref]

Hepatic

Hepatic adverse effects are rare, but cases of hepatotoxicity associated with nafcillin (the active ingredient contained in Unipen) therapy have been reported.[Ref]

Nervous system

Nervous system side effects have included neurotoxicity with high intravenous or intraventricular doses, especially in patients with both hepatic and renal impairment.[Ref]

Some side effects of Unipen may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.