Cefalexin 250mg Capsules

Document: spc-doc_PL 30684-0207 change

SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each capsule contains, as the active ingredient, Cefalexin monohydrate equivalent to 250mg of Cefalexin base.

For a full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Capsule, hard

Green coloured opaque cap and opaque white coloured body, size “2” hard gelatin capsules imprinted with black “CEF” on cap & “250” on body, filled with white to off white granular powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Cefalexin is a semi-synthetic cephalosporin antibiotic for oral administration.

Cefalexin is indicated for the treatment of the following infections when caused by susceptible organisms (see also sections 4.4 and 5.1).

Upper respiratory tract infections Otitis media

Exacerbation of chronic bronchitis

Community-acquired pneumonia

Uncomplicated upper and lower urinary tract infections

Acute prostatitis

Skin and soft tissue infections

Bone and joint infections

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration Posology

The recommended dose for adults is 1-4 g daily in divided doses. Most infections will respond to a dosage of 500 mg every 8 hours. For skin and soft tissue infections, streptococcal pharyngitis, and mild, uncomplicated urinary tract infections, the usual dosage is 250 mg every 6 hours, or 500 mg every 12 hours.

For more severe infections or those caused by less susceptible organisms, larger doses may be needed. If daily doses of Cefalexin greater than 4 g are required, parenteral cephalosporins, in appropriate doses, should be considered.

Patients with impaired renal function

Reduce dosage if renal function is markedly impaired (see section 4.4).

Elderly patients

The recommended dose for adults should be used in elderly patients except those with impaired renal function (see section 4.4).

Children

The usual recommended daily dosage for children is 25-50 mg/kg body weight (10-20 mg/lb body weight) in divided doses. For skin and soft tissue infections, streptococcal pharyngitis, and mild, uncomplicated urinary tract infections, the total daily dose may be divided and administered every 12 hours. For most infections the following schedule is suggested:

Children under 5 years: 125 mg every 8 hours.

Children 5 years and over: 250 mg every 8 hours.

In severe infections, the dosage may be doubled. In the therapy of otitis media, clinical studies have shown that a dosage of 75 to 100 mg/kg/day in 4 divided doses is required.

In the treatment of beta-haemolytic streptococcal infections, a therapeutic dose should be administered for at least 10 days.

Method of administration

Cefalexin is administered orally.

4.3 Contraindications

Cefalexin is contra-indicated in patients with known allergy to the cephalosporin group of antibiotics or to any of the excipients.

4.4 Special warnings and precautions for use

Before instituting therapy with Cefalexin, every effort should be made to determine whether the patient has had previous hypersensitivity reactions to the cephalosporins, penicillins or other drugs. Cefalexin should be given cautiously to penicillin-sensitive patients. There is some clinical and laboratory evidence of partial cross-allergenicity of the penicillins and cephalosporins. Patients have had severe reactions (including anaphylaxis) to both drugs.

Pseudomembranous colitis has been reported with virtually all broad-spectrum antibiotics, including macrolides, semi-synthetic penicillins, and cephalosporins. It is important, therefore, to consider its diagnosis in patients who develop diarrhoea in association with the use of antibiotics. Such colitis may range in severity from mild to life-threatening. Mild cases of pseudomembranous colitis usually respond to drug discontinuance alone. In moderate to severe cases, appropriate measures should be taken.

If an allergic reaction to Cefalexin occurs, the drug should be discontinued and the patient treated with the appropriate agents.

Prolonged use of Cefalexin may result in the overgrowth of non-susceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

Cefalexin should be administered with caution in the presence of markedly impaired renal function. Careful clinical and laboratory studies should be made because safe dosage may be lower than that usually recommended.

Positive direct Coombs' tests have been reported during treatment with the cephalosporin antibiotics. In haematological studies, or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side, or in Coombs' testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognised that a positive Coombs' test may be due to the drug.

A false positive reaction for glucose in the urine may occur with Benedict's or Fehling's solutions, or with copper sulphate test tablets.

Cefalexin capsules contains colouring agents Brilliant Blue FCF (E133) and Sunset yellow FCF (E110), which may cause allergic reactions.

4.5 Interaction with other medicinal products and other forms of interaction

As with other beta-lactam drugs, renal excretion of Cefalexin is inhibited by probenecid.

In a single study of 12 healthy subjects given single 500 mg doses of Cefalexin and metformin, plasma metformin C_max and AUC increased by an average of 34% and 24%, respectively, and metformin renal clearance decreased by an average of 14%. No side effects were reported in 12 healthy subjects in this study. No information is available about the interaction of Cefalexin and metformin following multiple dose administration. The clinical significance of this study is unclear, particularly as no cases of “lactic acidosis” have been reported in association with concomitant metformin and Cefalexin treatment.

4.6 Pregnancy and lactation

Pregnancy

Although laboratory and clinical studies have shown no evidence of teratogenicity, caution should be exercised when prescribing for the pregnant patient.

Lactation

The excretion of Cefalexin in human breast milk increased up to 4 hours following a 500 mg dose. The drug reached a maximum level of 4 micrograms/ml, then decreased gradually and had disappeared 8 hours after administration. Caution should be exercised when Cefalexin is administered to a nursing woman.

4.7 Effects on ability to drive and use machines

When performing these activities the possible occurrence of the adverse reactions dizziness, fatigue and confusion should be taken into account.

4.8 Undesirable effects

Adverse events that have been reported in Cefalexin trials are categorised below, according to system organ class and frequency.

Frequencies are defined as:

• very common (> 1/10);

• common (> 1/100 to <1/10);

• uncommon (> 1/1000 to <1/100);

• rare (> 1/10000 to <1/1000) and

• very rare (<1/10000).

Undesirable effects for Cefalexin occur at a frequency of 3-6%.

Infections and infestations Rare	Genital and anal pruritus, vaginitis.
Frequency not stated	Vaginal candidiasis.
Blood and lymphatic disorders Uncommon	Eosinophilia.
Rare	Neutropenia, thrombocytopenia, haemolytic anaemia.
Immune system disorders Rare	Anaphylactic reaction.
Psychiatric disorders Frequency not stated	Hallucinations, agitation, confusion.
Central and peripheral nervous system disorders Rare	Headache, dizziness.


Gastrointestinal disorders Common	Diarrhoea, nausea.
Rare	Abdominal pain, vomiting, dyspepsia, pseudomembranous colitis.
Hepatobiliary disorders Rare	Hepatitis, cholestatic icterus.
Dermatological disorders Uncommon	Rash, urticaria, pruritus.
Rare	Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis (Lyell’s syndrome), angioedema.
Musculoskeletal, connective tissue and bone disorders Frequency not stated	Arthralgia, arthritis.
Renal and urinary tract disorders Rare	Reversible interstitial nephritis.
General symptoms and problems at site of application Rare	Tiredness.
Frequency not stated	Fever.
Investigations Uncommon	Increase in AST and ALT (reversible).
Frequency not stated	Positive direct Coombs test. False positive reaction for some tests of glucose in the urine (see section 4.4).

4.9 Overdose

Symptoms of oral overdose may include nausea, vomiting, epigastric distress, diarrhoea, and haematuria.

In the event of severe overdosage, general supportive care is recommended, including close clinical and laboratory monitoring of haematological, renal and hepatic functions, and coagulation status until the patient is stable. Forced diuresis, peritoneal dialysis, haemodialysis, or charcoal haemoperfusion have not been established as beneficial for an overdose of Cefalexin. It would be extremely unlikely that one of these procedures would be indicated.

Unless 5 to 10 times the normal total daily dose has been ingested, gastro-intestinal decontamination should not be necessary.

There have been reports of haematuria, without impairment of renal function, in children accidentally ingesting more than 3.5 g of Cefalexin in a day. Treatment has been supportive (fluids) and no sequelae have been reported.

5 PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: First generation cephalosporin. ATC code:

J01DB01

Mode of Action

Cefalexin is an antibacterial agent of the cephalosporin class. Like other cephalosporins cefalexin exerts antibacterial activity by binding to and inhibiting the action of penicillin-binding proteins involved in the synthesis of bacterial cell walls. This leads to bacterial cell lysis and cell death.

Mechanisms of resistance

Bacterial resistance to cefalexin may be due to one or more of the following mechanisms:

• Hydrolysis by extended-spectrum beta-lactamases and / or by chromosomally-encoded (AmpC) enzymes that may be induced or de-repressed in certain aerobic gram-negative bacterial species.

• Reduced affinity of pencillin-binding proteins.

• Reduced permeability of the outer membrane of certain gram-negative organisms restricting access to penicillin-binding proteins

• drug efflux pumps

More than one of these mechanisms of resistance may co-exist in a single bacterial cell. Depending on the mechanism(s) present, bacteria may express cross-resistance to several or all other beta-lactams and/ or antibacterial drugs of other classes.

Breakpoints

Minimum inhibitory concentration (MIC) breakpoints established by the British Society of Antimicrobial Chemotherapy for beta-haemolytic Streptococci and Streptococcus pneumoniae are: susceptible < 2mg /L, resistant >2.5mg /L.

Susceptibility

The prevalence of resistance may vary geographically and over time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Commonly susceptible species

Aerobes, Gram positive:

Staphylococcus aureus (methicillin susceptible)

Streptococcus agalactiae Streptococcus pneumoniae

Streptococcus pyogenes

Aerobes, Gram negative:

Escherichia coli Haemophilus influenzae Moraxella catarrhalis

Anaerobes:

Peptostreptococcus species

Species for which resistance may be a problem

Citrobacter species Enterobacter species Morganella morganii.

5.2 Pharmacokinetic properties

Cefalexin is acid stable and may be given without regard to meals. It is rapidly absorbed after oral administration. Following doses of 250 mg, 500 mg, and 1 g, average peak serum levels of approximately 9, 18, and 32 mg/l, respectively, were obtained at 1 hour. Measurable levels were present 6 hours after administration. Cefalexin 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 mg/l, respectively.

Cefalexin is almost completely absorbed from the gastro-intestinal tract, and 75-100% is rapidly excreted in active form in the urine. Absorption is slightly reduced if the drug is administered with food. The half-life is approximately 60 minutes in patients with normal renal function. Haemodialysis and peritoneal dialysis will remove cefalexin from the blood.

Peak blood levels are achieved one hour after administration, and therapeutic levels are maintained for 6-8 hours. Approximately 80% of the active drug is excreted in the urine within 6 hours. No accumulation is seen with dosages above the therapeutic maximum of 4 g/day.

The half-life may be increased in neonates due to their renal immaturity, but there is no accumulation when given at up to 50 mg/kg/day.

5.3 Preclinical safety data

The daily oral administration of Cefalexin to rats in doses of 250 or 500 mg/kg prior to and during pregnancy, or to rats and mice during the period of organogenesis only, had no adverse effect on fertility, foetal viability, foetal weight, or litter size.

Cefalexin showed no enhanced toxicity in weanling and newborn rats as compared with adult animals.

The oral LD₅₀ of Cefalexin in rats is 5,000 mg/kg.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients Capsule contents

Cellulose Microcrystalline Croscarmellose Sodium Magnesium Stearate

Capsule shell Brilliant Blue FCF (E133) Sunset yellow FCF (E110) Titanium dioxide Gelatin

Sodium lauril sulfate

Black printing ink (SW-9008 & SW-9009)

Shellac

Dehydrated Alcohol Isopropyl Alcohol Butyl Alcohol Propylene Glycol Purified Water Strong Ammonia Solution Potassium Hydroxide Black Iron Oxide (E172)

6.2 Incompatibilities

Not applicable

6.3 Shelf life

24 months

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

Keep containers tightly closed.

6.5 Nature and contents of container

The products are filled into HDPE bottles of 20 or 100 capsules, or blister packs of 28 or 100 capsules consisting of PVC/Aclar Blister film.

Not all pack sizes may be marketed

6.6 Special precautions for disposal

Any unused product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Dawa Limited 5 Sandridge Close Harrow Middlesex HA1 1XD UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 30684/0207

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

12/08/2009

10 DATE OF REVISION OF THE TEXT

20/12/2011