Nafcillin - Uses, Dose, Side effects

Nafcillin is a narrow spectrum beta-lactamase-resistant penicillin used in the treatment of infections caused by gram-positive organisms resistant to other penicillins.

Nafcillin Uses:

  • Staphylococcal infections:

    • for Treatment of infections caused by susceptible penicillinase-producing staphylococci

  • Off Label Use of Nafcillin in Adults:

    • Catheter-related bloodstream infections;
    • Skin and soft tissue necrotizing infection;
    • Streptococcal skin infections;
    • Surgical site infections
    • Endocarditis caused by susceptible organisms.

Nafcillin Dose in Adults

Nafcillin Dose in the treatment of Catheter-related bloodstream infections (off-label):

  • IV: at 2 g every 4 hours.

Nafcillin Dose in the treatment of Endocarditis caused by Methicillin-susceptible Staphylococcus aureus (MSSA):

  • Native valve endocarditis:

    • 12 g/day iV 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 enough.

  • Prosthetic valve endocarditis:

    • 12 g/day IV 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).

Nafcillin Dose in the treatment of bacterial Meningitis, bacterial caused by Methicillin-susceptible S. aureus:

  • IV:
    • 2 g every 4 hours;
    • consider the addition of rifampin if the organism is susceptible to it and prosthetic material is present.

Nafcillin Dose in the treatment of Osteomyelitis: Methicillin-susceptible S. aureus (MSSA) (off-label dose):

  • IV: at 1.5 to 2 g every 4 to 6 hours or via continuous infusion (IDSA [Berbari 2015])

Nafcillin Dose in the treatment of Prosthetic joint infections: Methicillin-susceptible S. aureus (MSSA):

  • 5 to 2 g every 4 to 6 hours (IDSA [Osmon 2013])

Nafcillin Dose in the treatment of Skin and soft tissue infections:

  • 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:
      • at 1 to 2 g every 4 hours;
      • continue until further debridement is not necessary, the patient has clinically improved, and patient remains afebrile for 48 to 72 hours

Nafcillin Dose in the treatment of Streptococcal skin infections (off-label):

  • IV: at 1 to 2 g every 4 to 6 hours (IDSA [Stevens 2014])

Nafcillin Dose in the treatment of Surgical site infections (trunk or extremity away from axilla or perineum):

  • IV: 2 g every 6 hours (IDSA [Stevens 2014])

Nafcillin Dose in Childrens

Nafcillin General dosing in susceptible infections:

  • Mild to moderate infections: IM, IV:

    • 100 to 150 mg/kg/day in divided doses every 6 hours;
    • maximum daily dose: 4 g/day

  • Severe infections: IM, IV:

    • at 150 to 200 mg/kg per day in divided doses every 4 to 6 hours;
    • maximum daily dose: 12 g/day

Nafcillin Dose in the treatment of Endocarditis:

  • Children and Adolescents:

    • Intravenous:
      • 200 mg/kg/day in divided doses every 4 to 6 hours;
      • maximum daily dose: 12 g/day;
      • treat for at least 4 weeks;
      • longer durations may be necessary;
      • It may be used in combination with gentamicin for some resistant organisms.

Nafcillin Dose in the treatment of Meningitis:

  • IV:
    • at 200 mg/kg/day in divided doses every 6 hours;
    • maximum daily dose: 12 g/day.

Nafcillin Dose in the treatment of Skin and soft tissue infections:

 

  • Methicillin-susceptible Staphylococcus aureus (MSSA):
    • 100 to 150 mg/kg/day intravenous in divided doses every 6 hours;
    • The maximum daily dose: 12 g/day

  • Necrotizing infection due to MSSA:

    • 200 mg/kg/day intravenous in divided doses every 6 hours;
    • maximum daily dose: 12 g/day;
    • continue until further debridement is not necessary,
    • patient has clinically improved,
    • and patient stays afebrile for 48 to 72 hours

Nafcillin Dose in the treatment of Streptococcal skin infections:

  • IV: at 200 mg/kg/day in divided doses every 6 hours;
  • maximum daily dose: 12 g/day

Pregnancy Risk Factor B

  • Animal reproduction studies have not shown any adverse events.
  • Limited information is available on nafcillin usage during pregnancy.
  • Penicillins used by mothers during pregnancy have not been linked to an increase in birth defects.

Use of Nafcillin while breastfeeding

  • Breast milk is free from penicillins.
  • The drug manufacturer suggests that nursing mothers exercise caution when using nafcillin.
  • Modification of the bowel flora could also be a non-dose-related effect.

Nafcillin Dose in Kidney Disease:

  • No dosage adjustment necessary;
  • use with caution in patients with concomitant hepatic impairment.
  • Poorly dialyzed.
  • No supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD).

Nafcillin Dose in Liver disease:

  • There are no dosage adjustments provided in the drug manufacturer's labeling.
  • Nafcillin primarily undergoes hepatic metabolism;
  • dosage adjustment may be necessary, particularly in the setting of concomitant renal impairment.

Side effects of Nafcillin:

  • Cardiovascular:

    • Local Thrombophlebitis

  • Central Nervous System:

    • Neurotoxicity (High Doses)

  • Gastrointestinal:

    • Cholestasis
    • Clostridioides (Formerly Clostridium) Difficile-Associated Diarrhea

  • Hematologic & Oncologic:

    • Agranulocytosis
    • Bone Marrow Depression
    • Neutropenia

  • Hepatic:

    • Increased Serum Transaminases

  • Hypersensitivity:

    • Anaphylaxis

  • Local:

    • Inflammation At Injection Site
    • Injection Site Phlebitis
    • Local Skin Exfoliation (At Injection Site)
    • Pain At Injection Site
    • Swelling At Injection Site

  • Renal:

    • Interstitial Nephritis
    • Renal Tubular Disease

Contraindications to Nafcillin:

  • Hypersensitivity/ hyperresponsiveness of nafcillin or other penicillins or any component in the formulation
  • Limited documentation exists on cross-reactivity between beta-lactams (eg penicillins or cephalosporins), which can cause allergenic reactions.
  • Cross-sensitivity is possible due to similarities in chemical structure or mechanism of action.

Warnings and precautions

  • Anaphylactic and hypersensitivity reactions

    • Patients on penicillin therapy have had severe, sometimes fatal, hypersensitivity/ hyperresponsiveness reactions (anaphylactic) observed.
    • This is especially true if they have a history beta-lactam hypersensitivity and/or sensitivity to multiple allergens.
    • Patients with severe allergies or asthma should be cautious.
    • If an allergic reaction occurs, discontinue the treatment and initiate appropriate/appropriate therapy.

  • Extravasation:

    • Avoid IV Infusions Extravasation
    • Before and during infusion, ensure that the catheter or needle is properly positioned.

  • Hepatic effects

    • High doses of alcohol can lead to liver transaminases elevation and/or cholestasis.
    • Patients with a worsening of hepatic function should be evaluated.

  • Neurotoxic effects

    • Neurotoxicity has been linked to large intraventricular or IV doses.
    • Patients with renal or hepatic dysfunction should exercise caution.

  • Superinfection

    • Long-term use may result in fungal or bacterial superinfection, including pseudomembranous colitis and C.difficile-associated diarrhoea (CDAD); CDAD was noted after more than two months of post-antibiotic treatment.

  • Heart failure:

    • It may contain significant amounts of sodium.
    • Use caution in the event of heart failure

  • Hepatic and renal impairment

    • Patients with concomitant renal and hepatic impairments should be used with caution.

Nafcillin: Drug Interaction

Risk Factor C (Monitor therapy)

Acemetacin

Could raise the serum level of penicillins.

BCG Vaccine (Immunization)

Antibiotics may reduce the BCG vaccine's therapeutic effect (Immunization).

Benzhydrocodone

CYP3A4 Inducers (Moderate) may lower the level of benzhydrocodone in the blood. More specifically, hydrocodone serum concentrations might be decreased.

CloZAPine

CloZAPine's serum levels may be lowered by moderate CYP3A4 inducers.

Codeine

The active metabolite(s) of codeine's serum concentrations may be lowered by CYP3A4 Inducers (Moderate).

CycloSPORINE (Systemic)

Nafcillin may speed up CycloSPORINE metabolism (Systemic).

CYP3A4 Substrates (High risk with Inducers)

The serum concentration of CYP3A4 Substrates may drop when taking CYP3A4 Inducers (Moderate) (High risk with Inducers). Apixaban and Rivaroxaban are exceptions.

Doravirine

The serum concentration of doravirine may drop in response to CYP3A4 Inducers (Moderate).

Estriol (Systemic)

Estriol serum levels may be decreased by moderately potent CYP3A4 inducers (Systemic).

Estriol (Topical)

Estriol serum levels may be decreased by moderately potent CYP3A4 inducers (Topical).

FentaNYL

The serum concentration of FentaNYL may drop in response to CYP3A4 Inducers (Moderate).

Glecaprevir and Pibrentasvir

Glecaprevir and Pibrentasvir's serum concentrations may be affected by CYP3A4 Inducers (Moderate).

HYDROcodone

The serum levels of HYDROcodone may drop in response to CYP3A4 Inducers (Moderate).

Ibrutinib

Ibrutinib's serum levels may be decreased by CYP3A4 Inducers (Moderate).

Ifosfamide

The active metabolite(s) of ifosfamide may be present in lower serum quantities when CYP3A4 Inducers (Moderate) are present. The active metabolite(s) of ifosfamide may be present in higher serum concentrations when CYP3A4 Inducers (Moderate) are used.

Lactobacillus and Estriol

The therapeutic effects of Lactobacillus and Estriol may be reduced by antibiotics.

Methotrexate

Penicillins may raise the level of methotrexate in the serum.

Mirodenafil

The serum concentration of Mirodenafil may be decreased by CYP3A4 Inducers (Moderate).

Mycophenolate

The serum levels of the active metabolite(s) of mycophenolate may drop when penicillins are used. Enterohepatic recirculation appears to be hindered, which has this impact.

Naldemedine

The serum concentration of naldemedine may drop in response to CYP3A4 Inducers (Moderate).

NiMODipine

NiMODipine's serum levels may be decreased by CYP3A4 Inducers (Moderate).

Pexidartinib

Pexidartinib's serum levels may be decreased by CYP3A4 Inducers (Moderate).

Pitolisant

Pitolisant's serum levels may drop when taken with CYP3A4 Inducers (Moderate).

Probenecid

May increase the serum concentration of Penicillins.

Rolapitant

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant.

Upadacitinib

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Upadacitinib.

Zolpidem

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zolpidem.

Risk Factor D (Consider therapy modification)

Brigatinib

The serum concentration of Brigatinib may fall in response to CYP3A4 Inducers (Moderate). Management: Whenever possible, avoid taking brigatinib at the same time as mild CYP3A4 inducers. After seven days of treatment with the current brigatinib dose, increase the daily dose in increments of 30 mg, 

Clarithromycin

The active metabolite(s) of clarithromycin may be present in higher serum quantities when CYP3A4 Inducers (Moderate) are present. It is possible for CYP3A4 Inducers (Moderate) to lower the level of clarithromycin in the blood. If a patient is receiving a CYP3A inducer, other antimicrobial therapy should be considered. Drugs that speed up the conversion of 14-hydroxyclarithromycin from clarithromycin may change the clinical action of clarithromycin and reduce its effectiveness.

Daclatasvir

Daclatasvir's serum levels may be lowered by moderate CYP3A4 inducers. Treatment: If daclatasvir is used with a moderate CYP3A4 inducer, increase the dose to 90 mg once daily.

Erdafitinib

Erdafitinib's serum levels may be decreased by CYP3A4 Inducers (Moderate). Management: Erdafitinib dosage adjustments may be necessary. For information, see the entire monograph.

Estrogen Derivatives (Contraceptive)

Estrogen derivatives' metabolism may be accelerated by nafcillin (Contraceptive). Treatment: It is advised to use an alternative, nonhormonal method of contraception while using nafcillin.

GuanFACINE

GuanFACINE serum levels may be decreased by CYP3A4 Inducers (Moderate). Treatment: When starting guanfacine in a patient receiving a moderate CYP3A4 inducer, increase the guanfacine dose by up to a factor of two. If a patient is currently receiving guanfacine and a moderate CYP3A4 inducer is started, gradually increase the guanfacine dose over the course of 1 to 2 weeks.

Lefamulin

Lefamulin's serum levels may be decreased by CYP3A4 Inducers (Moderate). Management: Unless the advantages outweigh the hazards, avoid using lefamulin concurrently with mild CYP3A4 inducers.

Lefamulin (Intravenous)

Lefamulin serum levels may be decreased by moderate CYP3A4 inducers (Intravenous). Management: Lefamulin (intravenous) should not be used concurrently with moderate CYP3A4 inducers unless the advantages outweigh the dangers.

Lorlatinib

The hepatotoxic impact of lorlatinib may be enhanced by CYP3A4 Inducers (Moderate). Lorlatinib's serum levels may be decreased by CYP3A4 Inducers (Moderate). Avoid using lorlatinib in combination with mild CYP3A4 inducers. If such a mixture must be used, AST, ALT, and bilirubin levels should be checked within 48 hours after beginning the mixture and at least three times during the first week of use.

Lurasidone

Lurasidone's serum levels may be reduced by moderate CYP3A4 inducers. Management: If provided with moderate CYP3A4 inducers for seven or more days, watch for any diminished effects of the lurasidone and consider raising the dose.

Meperidine

Meperidine's serum levels may drop if you take CYP3A4 Inducers (Moderate). When using mild CYP3A4 inducers concurrently, the dose of meperidine may need to be increased. Keep an eye out for the effects of opioid withdrawal.

NIFEdipine

Nafcillin may lower NIFEdipine's serum levels.

Palbociclib

Palbociclib's serum levels may be decreased by moderate CYP3A4 inducers. Management: The Canadian label advises against using mild CYP3A4 inducers, however the US label makes no particular advice on their use.

Perampanel

The serum concentration of Perampanel may be decreased by CYP3A4 Inducers (Moderate). When using perampanel alongside strong and moderate CYP3A4 inducers, the beginning dose should be increased to 4 mg/day.

Sodium Picosulfate

Antibiotics may reduce Sodium Picosulfate's therapeutic impact. Management: If a patient previously used or is currently using an antibiotic, think about utilising an alternative product for bowel cleansing prior to a colonoscopy.

Tetracyclines

May reduce penicillins' therapeutic efficacy.

Typhoid Vaccine

The Typhoid Vaccine's therapeutic benefits may be reduced by antibiotics. The only strain impacted is the live attenuated Ty21a strain. Treatment: Patients receiving systemic antibacterial drugs should refrain from receiving the live attenuated typhoid vaccination (Ty21a). It is recommended to wait at least 3 days following the last dose of antibacterial medication before administering this vaccine.

Vitamin K Antagonists (eg, warfarin)

The anticoagulant impact of Vitamin K antagonists may be lessened by nafcillin. Management: Take into account using a different antibiotic. When starting or increasing the dosage of nafcillin, keep an eye out for increased or decreased therapeutic effects and the need to change the dose of oral anticoagulants.

Risk Factor X (Avoid combination)

Abemaciclib

Abemaciclib's serum levels may be reduced by moderate CYP3A4 inducers.

Antihepaciviral Combination Products

Antihepaciviral Combination Products' serum concentration may be decreased by CYP3A4 Inducers (Moderate).

Asunaprevir

Asunaprevir's serum levels may be decreased by CYP3A4 Inducers (Moderate).

Axitinib

Axitinib's serum levels may be decreased by CYP3A4 Inducers (Moderate).

BCG (Intravesical)

Antibiotics may lessen BCG's therapeutic effects (Intravesical).

Bedaquiline

Bedaquiline's serum levels may be lowered by moderately potent CYP3A4 inducers.

Bosutinib

Bosutinib's serum levels may be decreased by CYP3A4 Inducers (Moderate).

Cholera Vaccine

The therapeutic benefit of the cholera vaccine may be reduced by antibiotic use. Management: Cholera vaccine should not be administered to individuals taking systemic antibiotics or within 14 days after taking oral or parenteral antibiotics.

Cobimetinib

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib.

Dasabuvir

Dasabuvir's serum levels may be decreased by moderate CYP3A4 inducers.

Deflazacort

CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort.

Elbasvir

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elbasvir.

Encorafenib

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Encorafenib.

Entrectinib

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Entrectinib.

Fedratinib

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fedratinib.

Flibanserin

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin.

Grazoprevir

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Grazoprevir.

Neratinib

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib.

Nisoldipine

The serum concentration of nisoldipine may fall in response to CYP3A4 Inducers (Moderate).

Olaparib

Olaparib's serum levels may be decreased by CYP3A4 Inducers (Moderate).

Pimavanserin

Pimavanserin's serum levels may be decreased by moderate CYP3A4 inducers.

Pretomanid

Pretomanid's serum levels may be decreased by CYP3A4 Inducers (Moderate).

Ranolazine

Ranolazine's serum levels may be reduced by moderate CYP3A4 inducers.

Simeprevir

Simeprevir's serum levels may be decreased by CYP3A4 Inducers (Moderate).

Sonidegib

Sonidegib's serum levels may be decreased by CYP3A4 Inducers (Moderate).

Velpatasvir

CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir.

Venetoclax

Venetoclax serum levels may be decreased by CYP3A4 Inducers (Moderate).

Monitoring parameters:

  • Baseline and periodic CBC with differential,
  • urinalysis,
  • BUN, serum creatinine;
  • should do baseline and periodic serum bilirubin, AST, ALT, alkaline phosphatase and gamma glutamyl transferase (especially when using high doses);
  • observe for signs and symptoms of anaphylaxis during administration of first dose.
  • Monitor infusion site.

How to administer Nafcillin?

  • IM:

    • Administer as a deep intragluteal injection;
    • rotate injection sites.

  • IV:

    • Infuse over 30 to 60 minutes.
    • Vesicant
    • Avoid extravasation.

Extravasation management:

  • Extravasation should be stopped immediately, and the needle or cannula should be left in place.
  • Aspirate extravasated solution slowly without flushing the line;
  • initiate hyaluronidase antidote;
  • remove needle/cannula in case of not using IV hyaluronidase antidote),
  • apply dry cold compressions.
  • elevate extremity.

Hyaluronidase:

  • Intradermal or SubQ:
    • Use a 25-gauge needle to provide 5 sequential 0.2 to 0.3 mL injections totaling 1 to 1.7 mL (15 units/mL) clockwise into the extravasation area at the leading edge.

Mechanism of action of Nafcillin:

  • Interferes during active multiplication with the bacterial cell wall synthesis, leading to cell wall destruction and bactericidal activity.
  • It can be inactivated by staphylococcal penicillinase.

Distribution:

  • Widely distributed; CSF penetration is poor but enhanced by meningeal inflammation

Protein binding:

  • ~90%; primarily to albumin

Metabolism:

  • Primarily hepatic; undergoes enterohepatic recirculation

Half-life elimination:

  • Neonates <3 weeks: 2.2 to 5.5 hours; 4 to 9 weeks: 1.2 to 2.3 hours
  • Infants and Children 1 month to 14 years: 0.75 to 1.9 hours
  • Adults: Normal renal/hepatic function: 33 to 61 minutes

Time to peak serum concentrations:

  • IM: 30 to 60 minutes

Excretion:

  • Primarily feces; urine (~30% as unchanged drug)

Nafcillin Brand Names (International):

Nafcil Nallpen

Nafcillin Brand Names in Pakistan:

No Brands Available in Pakistan.

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