Cephalexin

6 ADVERSE REACTIONS The following serious events are described in greater detail in the Warning and Precautions section: • Hypersensitivity reactions [see Warning and Precautions ( 5.1 )] • Clostridium difficile-associated diarrhea [see Warnings and Precautions ( 5.2 )] • Direct Coombs' Test Seroconversion [see Warnings and Precautions ( 5.3 )] • Seizure Potential [ see Warnings and Precautions ( 5.4 )] • Effect on Prothrombin Activity [see Warnings and Precautions (5.5)] • Development of Drug-Resistant Bacteria [see Warnings and Precautions (5.6)] The most common adverse reactions associated with cephalexin include diarrhea, nausea, vomiting, dyspepsia and abdominal pain. (6) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC--RX01 (877-272-7901) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical trials, the most frequent adverse reaction was diarrhea. Nausea and vomiting, dyspepsia, gastritis, and abdominal pain have also occurred. As with penicillins and other cephalosporins, transient hepatitis and cholestatic jaundice have been reported. Other reactions have included hypersensitivity reactions, genital and anal pruritus, genital candidiasis, vaginitis and vaginal discharge, dizziness, fatigue, headache, agitation, confusion, hallucinations, arthralgia, arthritis, and joint disorder. Reversible interstitial nephritis has been reported. Eosinophilia, neutropenia, thrombocytopenia, hemolytic anemia, and slight elevations in aspartate transaminase (AST) and alanine transaminase (ALT) have been reported. In addition to the adverse reactions listed above that have been observed in patients treated with cephalexin, the following adverse reactions and other altered laboratory tests have been reported for cephalosporin class antibacterial drugs: Other Adverse Reactions: Fever, colitis, aplastic anemia, hemorrhage, renal dysfunction, and toxic nephropathy. Altered Laboratory Tests: Prolonged prothrombin time, increased blood urea nitrogen (BUN), increased creatinine, elevated alkaline phosphatase, elevated bilirubin, elevated lactate dehydrogenase (LDH), pancytopenia, leukopenia, and agranulocytosis.

4 CONTRAINDICATIONS Cephalexin is contraindicated in patients with known hypersensitivity to cephalexin or other members of the cephalosporin class of antibacterial drugs. Patients with known hypersensitivity to cephalexin or other members of the cephalosporin class of antibacterial drugs. (4)

11 DESCRIPTION Cephalexin oral suspension, USP is a semisynthetic cephalosporin antibacterial drug intended for oral administration. It is 7-(D-α- Amino-α-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid monohydrate. Cephalexin has the molecular formula C 16 H 17 N 3 O 4 S•H 2 O and the molecular weight is 365.41. Cephalexin has the following structural formula: Inactive Ingredients : Colloidal silicon dioxide, FD&C Red # 40, methyl cellulose (15 premium LV), methyl cellulose (4AC premium), sodium benzoate, strawberry flavor, sucrose, xanthan gum. cepha-structure

2 DOSAGE & ADMINISTRATION Adults and patients at least 15 years of age The usual dose is 250 mg every 6 hours, but a dose of 500 mg every 12 hours may be administered ( 2.1 ). Pediatric patients (over 1 year of age) Otitis media: 75 to 100 mg/kg in equally divided doses every 6 hours ( 2.2 ) All other indications: 25 to 50 mg/kg given in equally divided doses ( 2.2 ) In severe infections: 50 to 100 mg/kg may be administered in equally divided doses ( 2.2 ) • Duration of therapy ranges from 7 to 14 days depending on the infection type and severity. (2) • Dosage adjustment is required in patients with severe and end stage renal disease (ESRD) defined as creatinine clearance below 30 mL/min. (2.3) 2.1 Adults and Pediatric Patients at Least 15 Years of Age The usual dose of oral cephalexin is 250 mg every 6 hours, but a dose of 500 mg every 12 hours may be administered. Treatment is administered for 7 to 14 days. For more severe infections larger doses of oral cephalexin may be needed, up to 4 grams daily in two to four equally divided doses. 2.2 Pediatric Patients (over 1 year of age) The recommended total daily dose of oral cephalexin for pediatric patients is 25 to 50 mg/kg given in equally divided doses for 7 to 14 days. In the treatment of β-hemolytic streptococcal infections, duration of at least 10 days is recommended. In severe infections, a total daily dose of 50 to 100 mg/kg may be administered in equally divided doses. For the treatment of otitis media, the recommended daily dose is 75 to 100 mg/kg given in equally divided doses. Weight 10 kg (22 lb) 20 kg (44 lb) 40 kg (88 lb) Cephalexin Suspension 125mg/5mL ½ to 1 tsp q.i.d. 1 to 2 tsp q.i.d. 2 to 4 tsp q.i.d. 250mg/5mL ¼ to ½ tsp q.i.d. ½ to 1 tsp q.i.d. 1 to 2 tsp q.i.d. Weight 10 kg (22 lb) 20 kg (44 lb) 40 kg (88 lb) 125mg/5mL 1 to 2 tsp b.i.d. 2 to 4 tsp b.i.d. 4 to 8 tsp b.i.d. 250mg/5mL ½ to 1 tsp b.i.d 1 to 2 tsp b.i.d. 2 to 4 tsp b.i.d. Directions for Mixing 125 mg per 5 mL (100 mL when mixed): Prepare suspension time at dispensing. Add to the bottle a total of 67 mL of water. For ease in preparation, tap bottle to loosen powder, add the water in 2 portions, shaking well after each addition. The resulting suspension will contain cephalexin monohydrate equivalent to 125 mg cephalexin in each 5 mL (teaspoonful). 125 mg per 5 mL (200 mL when mixed): Prepare suspension time at dispensing. Add to the bottle a total of 134 mL of water. For ease in preparation, tap bottle to loosen powder, add the water in 2 portions, shaking well after each addition. The resulting suspension will contain cephalexin monohydrate equivalent to 125 mg cephalexin in each 5 mL (teaspoonful). 250 mg per 5 mL (100 mL when mixed): Prepare suspension time at dispensing. Add to the bottle a total of 67 mL of water. For ease in preparation, tap bottle to loosen powder, add the water in 2 portions, shaking well after each addition. The resulting suspension will contain cephalexin monohydrate equivalent to 250 mg cephalexin in each 5 mL (teaspoonful). 250 mg per 5 mL (200 mL when mixed): Prepare suspension time at dispensing. Add to the bottle a total of 134 mL of water. For ease in preparation, tap bottle to loosen powder, add the water in 2 portions, shaking well after each addition. The resulting suspension will contain cephalexin monohydrate equivalent to 250 mg cephalexin in each 5 mL (teaspoonful). *After mixing, store in refrigerator. May be kept for 14 days without significant loss of potency. 2.3 Dosage Adjustments in Adult and Pediatric Patients at Least 15 Years of Age with Renal Impairment Administer the following dosing regimens for cephalexin to patients with impaired renal function [ see Warnings and Precautions ( 5.4 ) and Use in Specific Populations ( 8.6 ) ]. Table 1. Recommended Dose Regimen for Patients with Renal Impairment Renal function Dose regimen recommendation Creatinine clearance ≥60 mL/min No dose adjustment Creatinine clearance 30 to 59 mL/min No dose adjustment; maximum daily dose should not exceed 1 g Creatinine clearance 15 to 29 mL/min 250 mg, every 8 hours or every 12 hours Creatinine clearance 5 to 14 mL/min not yet on dialysis* 250 mg, every 24 hours Creatinine clearance 1 to 4 mL/min not yet on dialysis* 250 mg, every 48 hours or every 60 hours *There is insufficient information to make dose adjustment recommendations in patients on hemodialysis.

1 INDICATIONS & USAGE Cephalexin is a cephalosporin antibacterial drug indicated for the treatment of the following infections caused by susceptible isolates of designated bacteria: • Respiratory tract infection ( 1.1 ) • Otitis media ( 1.2 ) • Skin and skin structure infections ( 1.3 ) • Bone infections ( 1.4 ) • Genitourinary tract infections ( 1.5 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin and other antibacterial drugs, cephalexin should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. ( 1.6 ) 1.1 Respiratory Tract Infections Cephalexin is indicated for the treatment of respiratory tract infections caused by susceptible isolates of Streptococcus pneumoniae and Streptococcus pyogenes . 1.2 Otitis Media Cephalexin is indicated for the treatment of otitis media caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes, and Moraxella catarrhalis. 1.3 Skin and Skin Structure Infections Cephalexin is indicated for the treatment of skin and skin structure infections caused by susceptible isolates of the following Gram-positive bacteria: Staphylococcus aureus and Streptococcus pyogenes. 1.4 Bone Infections Cephalexin is indicated for the treatment of bone infections caused by susceptible isolates of Staphylococcus aureus and Proteus mirabilis. 1.5 Genitourinary Tract Infections Cephalexin is indicated for the treatment of genitourinary tract infections, including acute prostatitis, caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. 1.6 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin and other antibacterial drugs, cephalexin should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information is available, this information should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

10 OVERDOSAGE Symptoms of oral overdose may include nausea, vomiting, epigastric distress, diarrhea, and hematuria. In the event of an overdose, institute general supportive measures. Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of cephalexin.

7 DRUG INTERACTIONS • Metformin: increased metformin concentrations. Monitor for hypoglycemia. (7.1) • Probenecid - The renal excretion of cephalexin is inhibited by probenecid. Co-administration of probenecid with cephalexin is not recommended. (7.2) • Administration of cephalexin may result in a false-positive reaction for glucose in the urine. (7.3) 7.1 Metformin Administration of cephalexin with metformin results in increased plasma metformin concentrations and decreased renal clearance of metformin. Careful patient monitoring and dose adjustment of metformin is recommended in patients concomitantly taking cephalexin and metformin [ see Clinical Pharmacology (12.2) ]. 7.2 Probenecid The renal excretion of cephalexin is inhibited by probenecid. Co-administration of probenecid with cephalexin is not recommended. 7.3 Interaction with Laboratory or Diagnostic Testing A false-positive reaction may occur when testing for the presence of glucose in the urine using Benedict's solution or Fehling's solution.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Cephalexin is a cephalosporin antibacterial drug [ see Microbiology (12.4) ]. 12.3 Pharmacokinetics Absorption: Cephalexin is acid stable and may be given without regard to meals. Following doses of 250 mg, 500 mg, and 1 g, average peak serum levels of approximately 9, 18, and 32 mcg/mL, respectively, were obtained at 1 hour. Serum levels were detectable 6 hours after administration (at a level of detection of 0.2 mcg/mL). Distribution: Cephalexin is approximately 10% to 15% bound to plasma proteins. Excretion: Cephalexin is excreted in the urine by glomerular filtration and tubular secretion. Studies showed that over 90% of the drug was excreted unchanged in the urine within 8 hours. During this period, peak urine concentrations following the 250 mg, 500 mg, and 1 g doses were approximately 1,000, 2,200, and 5,000 mcg/mL respectively. Drug Interactions: In healthy subjects given single 500 mg doses of cephalexin and metformin, plasma metformin mean C max and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%. No information is available about the interaction of cephalexin and metformin following multiple doses of either drug. 12.4 Microbiology Mechanism of Action Cephalexin is a bactericidal agent that acts by the inhibition of bacterial cell-wall synthesis. Resistance Methicillin-resistant staphylococci and most isolates of enterococci are resistant to cephalexin. Cephalexin is not active against most isolates of Enterobacter spp., Morganella morganii, and Proteus vulgaris . Cephalexin has no activity against Pseudomonas spp. , or Acinetobacter calcoaceticus. Penicillin-resistant Streptococcus pneumoniae is usually cross-resistant to beta-lactam antibacterial drugs. Antimicrobial Activity Cephalexin has been shown to be active against most isolates of the following bacteria both in vitro and in clinical infections [ see Indications and Usage (1) ]. Gram-positive bacteria Staphylococcus aureus (methicillin-susceptible isolates only) Streptococcus pneumoniae (penicillin-susceptible isolates) Streptococcus pyogenes Gram-negative bacteria Escherichia coli Haemophilus influenzae Klebsiella pneumoniae Moraxella catarrhalis Proteus mirabilis SusceptibilityTesting For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC .

12.1 Mechanism of Action Cephalexin is a cephalosporin antibacterial drug [ see Microbiology (12.4) ].

12.3 Pharmacokinetics Absorption: Cephalexin is acid stable and may be given without regard to meals. Following doses of 250 mg, 500 mg, and 1 g, average peak serum levels of approximately 9, 18, and 32 mcg/mL, respectively, were obtained at 1 hour. Serum levels were detectable 6 hours after administration (at a level of detection of 0.2 mcg/mL). Distribution: Cephalexin is approximately 10% to 15% bound to plasma proteins. Excretion: Cephalexin is excreted in the urine by glomerular filtration and tubular secretion. Studies showed that over 90% of the drug was excreted unchanged in the urine within 8 hours. During this period, peak urine concentrations following the 250 mg, 500 mg, and 1 g doses were approximately 1,000, 2,200, and 5,000 mcg/mL respectively. Drug Interactions: In healthy subjects given single 500 mg doses of cephalexin and metformin, plasma metformin mean C max and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%. No information is available about the interaction of cephalexin and metformin following multiple doses of either drug.

20220707

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3 DOSAGE FORMS & STRENGTHS Cephalexin For Oral Suspension USP 125 mg/5mL and 250 mg/5mL For oral suspension: 125mg/5mL and 250mg/5mL (3)

Cephalexin Cephalexin CEPHALEXIN CEPHALEXIN ANHYDROUS SUCROSE METHYLCELLULOSE (15 MPA.S) METHYLCELLULOSE (400 MPA.S) SODIUM BENZOATE XANTHAN GUM SILICON DIOXIDE STRAWBERRY FD&C RED NO. 40 Pale Yellow Cephalexin Cephalexin CEPHALEXIN CEPHALEXIN ANHYDROUS SUCROSE METHYLCELLULOSE (15 MPA.S) METHYLCELLULOSE (400 MPA.S) SODIUM BENZOATE XANTHAN GUM SILICON DIOXIDE STRAWBERRY FD&C RED NO. 40 Pale Yellow

13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility Lifetime studies in animals have not been performed to evaluate the carcinogenic potential of cephalexin. Tests to determine the mutagenic potential of cephalexin have not been performed. In male and female rats, fertility and reproductive performance were not affected by cephalexin oral doses up to 1.5 times the highest recommended human dose based upon body surface area.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility Lifetime studies in animals have not been performed to evaluate the carcinogenic potential of cephalexin. Tests to determine the mutagenic potential of cephalexin have not been performed. In male and female rats, fertility and reproductive performance were not affected by cephalexin oral doses up to 1.5 times the highest recommended human dose based upon body surface area.

ANDA210221

Cephalexin

Cephalexin

67877-545

HUMAN PRESCRIPTION DRUG

ORAL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 67877-544-88 Cephalexin for Oral Suspension, USP 125 mg per 5 mL when reconstituted according to directions. Usual Pediatric Dose: 25 to 50 mg per kg a day in four divided doses. For more severe infection, dose may be doubled. See accompanying literature. Rx only For Oral Use only 100 mL (when mixed) Ascend Laboratories, LLC NDC 67877-545-88 Cephalexin for Oral Suspension, USP 250 mg per 5 mL when reconstituted according to directions. Usual Pediatric Dose: 25 to 50 mg per kg a day in four divided doses. For more severe infection, dose may be doubled. See accompanying literature. Rx only For Oral Use only 100 mL (when mixed) Ascend Laboratories, LLC cepha-125mg-5ml-100ml cepha-250mg-5ml-100ml

17 PATIENT COUNSELING INFORMATION Advise patients that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment. Ask the patient about any previous hypersensitivity reactions to cephalexin, other beta-lactams (including cephalosporins) or other allergens (5.1) Advise patients that diarrhea is a common problem caused by antibacterial drugs and usually resolves when the drug is discontinued. Sometimes, frequent watery or bloody diarrhea may occur and may be a sign of a more serious intestinal infection. If severe watery or bloody diarrhea develops, advise patients to contact their healthcare provider. Counsel patients that antibacterial drugs including cephalexin, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cephalexin is prescribed to treat a bacterial infection, tell patients that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cephalexin or other antibacterial drugs in the future. Manufactured by : Alkem Laboratories Ltd., INDIA. Distributed by: Ascend Laboratories, LLC Parsippany, NJ 07054 Revised: November, 2021 PT 2851-01

8.5 Geriatric Use Of the 701 subjects in 3 published clinical studies of cephalexin, 433 (62%) were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. This drug is substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection [ see Warnings and Precautions (5.4) ].

8.3 Nursing Mothers Cephalexin is excreted in human milk. Caution should be exercised when cephalexin is administered to a nursing woman.

8.4 Pediatric Use The safety and effectiveness of cephalexin in pediatric patients was established in clinical trials for the dosages described in the dosage and administration section [ see Dosage and Administration (2.2) ].

8.1 Pregnancy Pregnancy Category B There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Reproduction studies have been performed on mice and rats using oral doses of cephalexin monohydrate 0.6 and 1.5 times the maximum daily human dose (66 mg/kg/day) based upon body surface area basis, and have revealed no evidence of impaired fertility or harm to the fetus.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category B There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Reproduction studies have been performed on mice and rats using oral doses of cephalexin monohydrate 0.6 and 1.5 times the maximum daily human dose (66 mg/kg/day) based upon body surface area basis, and have revealed no evidence of impaired fertility or harm to the fetus. 8.3 Nursing Mothers Cephalexin is excreted in human milk. Caution should be exercised when cephalexin is administered to a nursing woman. 8.4 Pediatric Use The safety and effectiveness of cephalexin in pediatric patients was established in clinical trials for the dosages described in the dosage and administration section [ see Dosage and Administration (2.2) ]. 8.5 Geriatric Use Of the 701 subjects in 3 published clinical studies of cephalexin, 433 (62%) were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. This drug is substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection [ see Warnings and Precautions (5.4) ]. 8.6 Renal Impairment Cephalexin should be administered with caution in the presence of impaired renal function (creatinine clearance < 30 mL/min, with or without dialysis). Under such conditions, careful clinical observation and laboratory studies renal function monitoring should be conducted because safe dosage may be lower than that usually recommended [see Dosage and Administration (2.3)].

16 HOW SUPPLIED/STORAGE AND HANDLING Cephalexin for oral suspension* USP (a strawberry flavored formula) is supplied as follows: 125 mg/5 mL: Bottles of 100 mL (NDC 67877-544-88) Bottles of 200 mL (NDC 67877-544-68) 250 mg/5 mL: Bottles of 100 mL (NDC 67877-545-88) Bottles of 200 mL (NDC 67877-545-68) Directions for mixing are included on the label. Store at 20 o to 25 o C (68 o to 77 o F) [See USP Controlled Room Temperature]. Shake well before using. Keep tightly closed. *After mixing, store in refrigerator. May be kept for 14 days without significant loss of potency.