Nafcillin

Nafcillin belongs to the pharmacological class of Beta-Lactam Antibiotics.

Nafcillin has been approved to relieve symptoms and also for the treatment and maintenance of bloodstream infection, endocarditis treatment, meningitis, bacteria, osteomyelitis and disciti, pneumonia, prosthetic joint infection, and skin and soft tissue infection.

Nafcillin Sodium is rapidly excreted in the form of an unchanged drug in the urine by glomerular filtration as well as active tubular secretion.

The common side effects involving the use of Nafcillin are diarrhea, nausea, dizziness, oral thrush, vomiting, headache, and vaginal yeast infection.

Nafcillin is available in the form of an Injectable solution, Powder for injection.

Nafcillin is available in the U.S., European Union, India, China, and Canada.

Nafcillin belongs to the pharmacological class of Beta-Lactam Antibiotics.

Nafcillin binds to and inhibits penicillin-binding proteins (PBPs). Nafcillin binds to specific penicillin-binding proteins (PBPs), which are located inside the bacterial cell wall. Nafcillin is said to inhibit the third and last stage of bacterial cell wall synthesis. Hence, the Cell lysis is then mediated by the bacterial cell wall autolytic enzymes such as autolysins.

Nafcillin has been approved to relieve symptoms and also for the treatment and maintenance of bloodstream infection, endocarditis, treatment, meningitis, bacteria, osteomyelitis and/or disciti , pneumonia, prosthetic joint infection, skin, and soft tissue infection.

The duration of action of Nafcillin is 6-8 hours.

Nafcillin is available in the form of an Injectable solution, Powder for injection.

Nafcillin can be used in the following treatment:

• Bloodstream infection
• Endocarditis, treatment
• Meningitis, bacterial
• Osteomyelitis and/or discitis
• Pneumonia
• Prosthetic joint infection
• Skin and soft tissue infection

Nafcillin can help to relieve symptoms and also for the treatment and maintenance of bloodstream infection, endocarditis, treatment, meningitis, bacteria, osteomyelitis and/or disciti , pneumonia, prosthetic joint infection, skin and soft tissue infection.

Nafcillin is approved for use in the following clinical indications:

• Bloodstream infection
• Endocarditis, treatment
• Meningitis, bacterial
• Osteomyelitis and/or discitis
• Pneumonia
• Prosthetic joint infection
• Skin and soft tissue infection

Injectable solution: To be administered by the registered medical practitioner

Powder for injection: To be reconstituted and administered by the registered medical practitioner.

• Bloodstream infection

Pathogen-directed therapy for methicillin-susceptible staphylococci (off label):Intravenous: 2 g every 4 hours; treat uncomplicated bacteremia for ≥14 days starting from the day of first negatIntravenouse blood culture

• Endocarditis, treatment

Pathogen-directed therapy for methicillin-susceptible staphylococci (off-label):

Native valve: Intravenous: 12 g/day in 4 or 6 divided doses (i.e., 2 g every 4 hours or 3 g every 6 hours) for six weeks.

Prosthetic valve: Intravenous: 12 g/day in 6 divided doses (i.e., 2 g every 4 hours) for ≥ six weeks; use with rifampin for the entire duration of therapy and gentamicin for first two weeks

• Meningitis, bacterial

Pathogen-directed therapy for methicillin-susceptible staphylococci (off-label): Intravenous: 2 g every 4 hours; consider the addition of rifampin if the organism is susceptible and prosthetic material is present. The treatment duration is 10 to 14 days.

• Osteomyelitis and/or discitis

Pathogen-directed therapy for methicillin-susceptible staphylococci (off-label): Intravenous: 1.5 to 2 g every 4 to 6 hours or via continuous infusion for ≥6 weeks

• Pneumonia

Pathogen-directed therapy for methicillin-susceptible S. aureus (off-label): Intravenous: 2 g every 4 hours. The minimum duration is generally five days for community-acquired pneumonia and seven days for hospital-acquired or ventilator-associated pneumonia.

• Prosthetic joint infection

Pathogen-directed therapy for methicillin-susceptible staphylococci (off-label): Intravenous: 1.5 to 2 g every 4 to 6 hours; duration ranges from 2 to 6 weeks depending on prosthesis management,

• Skin and soft tissue infection

Cellulitis (nonpurulent) in patients without risk for methicillin-resistant S. aureus: Intravenous: 1 to 2 g every 4 hours. The total duration of therapy is ≥5 days.

Necrotizing infection due to methicillin-susceptible S. aureus (MSSA) (off-label): Intravenous: 1 to 2 g every 4 hours; continue until further debridement is not necessary

Surgical site incisional infection (trunk or extremity, not involving axilla or perineum) (off-label): Intravenous: 2 g every 6 hours; duration is dependent upon severity.

The injectable solution , Powder for injection

• Dosage Adjustments in Kidney Patients:

The renal dosing recommendations are based on the best available evidence and clinical expertise.

CrCl ≥10 mL/minute: No dosage adjustment is necessary.

CrCl <10 mL/minute: No specific dosage adjustment is recommended

• Dosage Adjustments in Pediatric Patients:

150 to 200 mg/kg/day infused continuously over 24 hours; maximum daily dose.

Avoid high-acid foods like citrus fruits and juices like orange and grapefruit, soda, and chocolates.

Alcohol intake might lead to nausea, vomiting, and headache

Mult Intravenous vitamins and antacids contain minerals, primarily magnesium, calcium, aluminum, iron, or zinc, which bind to the antibiotic and refrain it from working. Spacing them at least for 2 hours after Nafcillin administration is recommended.

Nafcillin may is contraindicated under the following conditions:

• Patients with known hypersensitivity to penicillins.

The physician should closely monitor the patients and keep pharmacovigilance as follows:

Serious and occasionally fatal hypersensitivity(anaphylactic) reactions had been reported in patients receIntravenousing therapy with penicillins. These reactions are foudnt to be more likely to occur in persons with a history of sensitIntravenousity to multiple allergens. Cross-sensitivity of patients to penicillins and cephalosporins has been reported. Before initiating therapy with Nafcillin for Injection, careful inquiry should be made concerning previous the hypersensitivity reactions to penicillins, cephalosporins, and other allergens. If an allergic reaction occurs, the antibiotic should be discontinued. The usual agents (antihistamines, pressor amines, and corticosteroids) should be readily available.

Antibiotic-associated pseudomembranous colitis has been reported with nearly all antibacterial agents, including Nafcillin, and might range in severity from mild to life-threatening. It is important to consider this diagnosis if significant diarrhea or colitis occurs during therapy. Mild cases usually respond to the drug discontinuation alone. However, in moderate to severe cases, management with fluids as well as electrolytes, protein supplementation, and treatment with an oral antibacterial drug effective against Clostridium difficile (e.g., oral vancomycin) should be considered.

Usage of alcohol should be avoided while on Nafcillin medication, as alcohol can worsen the effects of any underlying disease condition, including conditions such as dizziness, blurred vision, etc.

Caution should be exercised when Nafcillin for Injection is administered to nursing mothers. It is excreted in low concentrations in milk.

Category B

Reproduction studies had been performed in the mouse with oral doses which is up to 20 times the human dose as well as orally in the rat at doses up to 40 times the human dose, and had revealed no evidence of the impaired fertility or harm to the rodent fetus due to nafcillin. There are, however,found to be no adequate or well-controlled studies on pregnant women. As the animal reproduction studies do not always predictive of the human response, nafcillin should be used during pregnancy only if it is clearly needed.

No sufficient scientific evidence is traceable regarding the use and safety of Nafcillin in concurrent use with any particular food.

The adverse reactions related to Nafcillin can be categorized as follows:

Common

• Allergic reactions
• Nausea
• Vomiting
• Diarrhea
• Stomatitis
• Black or hairy tongue
• Gastrointestinal irritation

Rare

• Hepatotoxicity
• Agranulocytosis
• Neutropenia
• Hematuria
• Proteinuria
• Renal tubular damage
• Interstitial nephritis
• Nephrotoxicity
• Neurotoxic reactions
• Neurotoxicity
• Elevated liver transaminases
• Cholestasis
• Bone marrow depression
• Eosinophilia
• Platelet dysfunction
• Anaphylactic shock resulting in death

The clinically relevant drug interactions of Nafcillin are briefly summarized here:

• Tetracycline, is found to be a bacteriostatic antibiotic, might antagonize the bactericidal effect of penicillin, and concurrent use of nafcillin and tetracycline should be avoided.
• Nafcillin in high dosage regimens, i.e., 2 grams fro every 4 hours, had been reported to decrease the effects of warfarin. When nafcillin+warfarin are used concomitantly, the prothrombin time should be closely monitored, as well as the dose of warfarin should be adjusted as necessary. This effect might persist for up to 30 days after nafcillin had been discontinued.
• Nafcillin, when administered concomitantly with cyclosporine, had been reported to be resulted in subtherapeutic the cyclosporine levels. The nafcillin-cyclosporine interaction hd been documented in a patient during two separate courses of the therapy. When cyclosporine and nafcillin are used concomitantly in the organ transplant patients, the cyclosporine levels should be monitored.

The following are the side effects involving Nafcillin:

• Diarrhea
• Skin rash
• Nausea
• Vomiting
• Black or "hairy" tongue
• Tenderness or irritation around the IV needle

• Pregnancy

Reproduction studies had been performed in the mouse with oral doses which is up to 20 times the human dose as well as orally in the rat at doses up to 40 times the human dose, and had revealed no evidence of the impaired fertility or harm to the rodent fetus due to nafcillin. There are, however,found to be no adequate or well-controlled studies on pregnant women. As the animal reproduction studies do not always predictive of the human response, nafcillin should be used during pregnancy only if it is clearly needed.

• Lactation

Caution should be exercised when Nafcillin for Injection is administered to nursing mothers. It is excreted in low concentrations in milk.

• Pediatric

The liver/biliary tract is said to be the principal route of nafcillin elimination. Because of immature hepatic as well as renal function in pediatric patients, nafcillin excretion might be impaired, with the abnormally high serum levels resulting. Serum levels should be monitored, as well as the dosage adjusted appropriately. There are no approved pediatric patient dosage regimens for the intravenous nafcillin. Safety as well as effectiveness in pediatric patients had not been established. The potential for toxic effects in the pediatric patients from chemicals that might leach from the single-dose premixed intravenous preparation in the plastic containers has not been determined.

• Geriatric

Clinical studies of Nafcillin injection did not include a sufficient number of subjects who were aged 65 and over to determine whether they responded differently from the younger subjects. Other reported clinical experiences had not identified differences in responses between the older and younger patients. In general, dose selection for an older patient should be made cautiously, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased renal, hepatic, or cardiac function as well as of concomitant disease or other drug therapy.

Physicians should be knowledgeable as well asvigilant about the treatment and identification of overdosage of Nafcillin.

Neurotoxic reactions similar to those observed with penicillin G might arise with intravenous doses of nafcillin, especially in the patients with concomitant hepatic insufficiency as well as renal dysfunction. In the case of over dosage, it is advised to discontinue nafcillin, treat symptomatically, and institute supportive measures when required.

Pharmacodynamics

Nafcillin is a semisynthetic antibiotic substance derived from 6-amino-penicillanic acid. The drugs in this class are the highly resistant to inactivation by staphylococcal penicillinase and are also active against penicillinase-producing and non-penicillinase-producing strains of Staphylococcus species.

Pharmacokinetics

• Absorption

Following intravenous administration of 500mg nafcillin, the mean plasma concentration was approximately 30 µg/mL. This value was reached after 5 minutes of injection.

• Volume of distribution

Nafcillin is reported to be widely distributed in the various body fluids, including bile, pleural, amniotic, and synovial fluids.

• Metabolism

Hepatic metabolism accounts for less than 30% of the biotransformation of most penicillins.

• Route of elimination

Nafcillin is primarily eliminated by non-renal routes, namely hepatic inactivation and excretion in the bile.

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