Cephalexin (Cefalexin)

Cephalexin belongs to the pharmacological class of first-generation cephalosporin antibiotics.

Cephalexin has been approved to relieve symptoms and also for the treatment and maintenance of endocarditis, prophylaxis (Off Label), mastitis, lactational,prosthetic joint infection ,skin and soft tissue infection ,streptococcal pharyngitis, group A ,urinary tract infection.

Cephalexin is well absorbed in the Gastrointestinal tract with 100 % oral bioavailability. The volume of distribution of cephalexin is found to be 5.2-5.8 liters. Cephalexin is not metabolized in the liver. Cephalexin is excreted unchanged in the urine.In 6 hours after the administered almost 60% of the drug gets excreted.

The common side effects involving the use of Cephalexin are nausea, vomiting, gas, weakness, tiredness,itching, diarrhea, headache ,upset stomach etc.

Cephalexin is available in the form of Capsules, Tablets and Powder for suspension.

Cephalexin is approved in the U.S., U.K., Germany, Japan, Malaysia, India, and China.

Cephalexin belongs to the pharmacological class of first-generation cephalosporin antibiotics.

Cephalexin is a cephalosporin antibiotic, a class of β-lactam antibiotics similar to penicillins, which binds to and inhibits penicillin-binding proteins (PBPs). Cephalexin binds to specific penicillin-binding proteins (PBPs) which are located inside the bacterial cell wall. Cephalexin inhibits 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.

Cephalexin has been approved to relieve symptoms and also for the treatment and maintenance of endocarditis, prophylaxis (Off Label) ,mastitis, lactational ,prosthetic joint infection ,skin and soft tissue infection ,streptococcal pharyngitis, group A ,urinary tract infection

Following an oral of Cephalexin , the mean T1/2 was found to be 0.5-1.2hours .

Cephalexin is available in the form of Capsules, Tablets and Powder for suspension.

Cephalexin can be used in the following treatment:

● Endocarditis, prophylaxis (Off Label)

● Mastitis, lactation

● Prosthetic joint infection

● Skin and soft tissue infection

● Streptococcal pharyngitis, group A

● Urinary tract infection

Cephalexin can help to relieve symptoms and also for the treatment and maintenance of endocarditis, prophylaxis (Off Label) ,mastitis, lactational ,prosthetic joint infection ,skin and soft tissue infection ,streptococcal pharyngitis, group A ,urinary tract infection.

Cephalexin is approved for use in the following clinical indications:

● Endocarditis, prophylaxis (Off Label)

● Mastitis, lactational

● Prosthetic joint infection

● Skin and soft tissue infection

● Streptococcal pharyngitis, group A

● Urinary tract infection

Capsules, Tablet : To be taken as a whole with water

Powder for suspension: To be mixed with water an taken as a whole

Endocarditis, prophylaxis (OFF LABEL)

2 g 30 to 60 minutes prior to procedure; if inadvertently not given prior to the procedure, may be administered up to 2 hours after the procedure.

Mastitis, lactational

500 mg 4 times daily for 10 to 14 days; shorter courses (eg, 5 to 7 days) may be considered for patients with rapid clinical resolution.

Prosthetic joint infection

Staphylococci (methicillin-susceptible): 500 mg every 6 to 8 hours or 1 g every 8 to 12 hours. For the first 3 to 6 months of therapy, combine with rifampin

Streptococci, beta-hemolytic (alternative agent): 500 mg every 6 to 8 hours

Cutibacterium spp (alternative agent): 500 mg every 6 to 8 hours

Skin and soft tissue infection

Cellulitis (nonpurulent)/erysipelas, mild: Oral: 500 mg 4 times daily for at least 5 days (duration should be extended up to 14 days if not resolved/slow response)

Impetigo or ecthyma: Oral: 250 to 500 mg 4 times daily for 7 days (Ref).

Streptococcal pharyngitis, group A

500 mg twice daily for 10 days

Urinary tract infection

Asymptomatic bacteriuria (≥105 CFU per mL) in pregnancy: 250 to 500 mg every 6 hours for 4 to 7 days.

Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection):250 to 500 mg every 6 hours for 5 to 7 days.

Cystitis, prophylaxis for recurrent infection:125 to 250 mg once daily

Capsule , Tablet , Powder for suspension.

• Dosage Adjustments in Kidney Patients:

Cephalexin should be administered cautiously in the presence of the impaired renal function i.e.creatinine clearance < 30 mL/min, with or without dialysis.

• Dosage Adjustments in Pediatric Patients:

It is recommended that the total daily dose of oral Cephalexin for pediatric patients is about 25 to 50 mg/kg given in equally divided doses for seven to fourteen days.

In the treatment of β-hemolytic streptococcal infections, a duration of at least ten days is recommended. In the severe infections, a total daily dose of about 50 to 100 mg/kg might be administered in divided doses equally .

For the treatment of otitis media, the recommended daily dose is about 75 to 100 mg/kg given in equally divided doses.

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

Multivitamins and antacids contain minerals primarily magnesium calcium aluminum iron or zinc which binds to the antibiotic and refrain it from working. Spacing them at least for 2 hours after Cephalexin administration is recommended.

Cephalexin may be contraindicated under the following conditions:

• Patients with known hypersensitivity to cephalosporins.

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

• Hypersensitivity Reactions

Allergic reactions such as rash, urticaria, angioedema, anaphylaxis, erythema multiforme, Stevens-Johnson syndrome/ toxic epidermal necrolysis had been reported with the use of Cephalexin. It is advised that before therapy with Cephalexin is to be instituted, inquire whether the patient has a history of hypersensitivity reactions to Cephalexin, cephalosporins, penicillins, or other drugs. Cross-hypersensitivity among beta-lactam antibacterial drugs might occur in up to 10% of patients having a history of penicillin allergy.

If an allergic reaction to Cephalexin occurs, it is advised to discontinue the drug and institute appropriate treatment.

• Clostridium difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) had been reported with use of nearly all antibacterial agents, including Cephalexin, and might range in severity from mild diarrhea to a fatal colitis. Treatment with antibacterial agents is said to alter the normal flora of the colon in turn leading to overgrowth of C. difficile. C. difficile also produces toxins A and B, which contribute to the development of Clostridium difficile-associated diarrhea Hyper Toxin-producing strains of C. difficile caused increased morbidity as well as mortality, as these infections can be refractory to antimicrobial therapy and might require colectomy. Clostridium difficile-associated diarrhea must be considered in all patients who are present with diarrhea following antibiotic use. A careful medical history is necessary since Clostridium difficile-associated diarrhea had been reported to occur over 2 months after the administration of antibacterial agents.

• Direct Coombs’ Test Seroconversion

Positive direct Coombs' tests had been reported during treatment with the cephalosporin antibacterial drugs which including cephalexin. Acute intravascular hemolysis induced by cephalexin therapy had been reported. If anemia is developed during or after cephalexin therapy, a diagnostic work-up should be performed for drug-induced hemolytic anemia, and it is advised to discontinue cephalexin as well as institute appropriate therapy.

• Seizure Potential

Several cephalosporins had been implicated in triggering seizures, particularly in the patients with renal impairment when the dosage had not been reduced. If seizures occur, it is advised to discontinue Cephalexin. Anticonvulsant therapy can be given if it is clinically indicated.

• Prolonged Prothrombin Time

Cephalosporins might be associated with prolonged prothrombin time. The patients who are at risk include patients with renal or hepatic impairment, or poor nutritional state, as well as patients who are receiving a protracted course of antibacterial therapy, as well as patients receiving anticoagulant therapy. It is advised to monitor prothrombin time in patients at risk and manage as indicated.

• Development of Drug-Resistant Bacteria

It is found that prescribing Cephalexin in the absence of a proven or strongly suspected bacterial infection will not provide benefit to the patient as well as increase the risk of the development of drug-resistant bacteria.

Prolonged use of Cephalexin might result in the overgrowth of nonsusceptible organisms. Careful observation of the patient is found to be essential. If superinfection occurs during therapy, the appropriate measures should be taken.

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

Cephalexin is found to be excreted in human milk. Hence ,caution should be exercised when Cephalexin is administered to a nursing woman.

Pregnancy Category B

There are found to be no adequate and well-controlled studies in the pregnant women. As animal reproduction studies are not always found to be predictive of human response, cephalexin should be used during pregnancy only if it is clearly indicated.

Reproduction studies had been performed on mice and rats using oral doses of cephalexin monohydrate which were 0.6 and 1.5 times the maximum daily human dose (66 mg/kg/day) based upon the body surface area, and had revealed no evidence of impaired fertility/ or harm to the fetus.

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

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

Common

• Stomach upset
• Abdominal pain
• Itching
• Swelling
• Rash
• Joint pain
• Vaginal itching or discharge
• Diarrhea
• Dizziness
• Tiredness
• Headache
• Nausea
• Vomiting

Rare

• Red skin lesions
• Irritated eyes
• Abdominal or stomach pain
• Blistering, peeling, or loosening of the skin
• Chills
• Clay-colored stools
• Cough
• Dark urine
• Diarrhea
• Joint or muscle pain
• Light-colored stools
• Upper right abdominal or stomach pain
• Vomiting of blood
• Dizziness
• Fever
• General tiredness and weakness
• Headache
• Itching or rash
• Sore throat
• Unpleasant breath odor
• Yellow eyes or skin
• Loss of appetite
• Nausea and vomiting
• Unusual tiredness or weakness

The clinically relevant drug interactions of Cephalexin is briefly summarized here:

Probenecid — As with other β-lactams, it is found that the renal excretion of cephalexin is inhibited by probenecid.

The following are the side effects involving Cephalexin :

● Stomach upset

● Abdominal pain

● Itching

● Swelling

● Rash

● Joint pain

● Vaginal itching or discharge

● Diarrhea

● Dizziness

● Tiredness

● Headache

● Nausea

● Vomiting

• Pregnancy

Pregnancy Category B

There are found to be no adequate and well-controlled studies in the pregnant women. As animal reproduction studies are not always found to be predictive of human response, cephalexin should be used during pregnancy only if it is clearly indicated.

Reproduction studies had been performed on mice and rats using oral doses of cephalexin monohydrate which were 0.6 and 1.5 times the maximum daily human dose (66 mg/kg/day) based upon the body surface area, and had revealed no evidence of impaired fertility/ or harm to the fetus.

• Lactation

Cephalexin is found to be excreted in human milk. Hence ,caution should be exercised when Cephalexin is administered to a nursing woman..

• Pediatric

In these trials, pediatric patients might have received Cephalexin capsules/ or Cephalexin for Oral Suspension. Cephalexin capsules should only be given in children as well as adolescents who are capable of ingesting the capsule.

• Geriatric

Out of the 701 subjects in three published the clinical studies of cephalexin, 433 (62%) were 65 and over.There was found to be no overall differences in safety as well as effectiveness were observed between these subjects and younger subjects, as well as other reported clinical experience had not identified differences in responses between the elderly as well as younger patients.

Physicians should be knowledgeable and vigilant about the treatment and identification of overdosage of Cephalexin.

Symptoms of oral overdose might include nausea, vomiting, epigastric distress, diarrhea, and hematuria.

Pharmacodynamics

Cephalexin (also called Cephalexin) is a first generation cephalosporin antibiotic.It is one of the most widely prescribed antibiotics, often used for the treatment of superficial infections that result as complications of minor wounds or lacerations. It is effective against most gram-positive bacteria through its inhibition of the cross linking reaction between N-acetyl muramic acid and N-acetylglucosamine in the cell wall, leading to cell lysis.

Pharmacokinetics

• Absorption:

Cephalexin is said to be an acid stable and might be given without regard to meals. Following doses of 250 mg, 500 mg, as well as 1 g, average peak serum levels were found to be of approximately about 9, 18, and 32 mcg/mL, respectively, were obtained at one hour. Serum levels were detectable six hours after administration .

• Distribution:

Cephalexin is found to be approximately 10% to 15% bound to plasma proteins.

• Metabolism:

Cephalexin is not metabolized in the body

• Excretion:

Cephalexin is found to be excreted in the urine by the glomerular filtration and tubular secretion. The Studies showed that over 90% of the drug had been excreted unchanged in the urine within eight hours. During this period, peak urine concentrations following the 250 mg, 500 mg, as well as 1 g doses were approximately about 1000, 2200, and 5000 mcg/mL respectively.

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