- Approval Id
- 705946aa043a0727
- Drug Approval Emc Name
- Xetinin XL 500mg prolonged release tablets
- Drug Name
- Xetinin XL 500mg prolonged release tablets
- Company Address
- Morningside House, Unit C Harcourt Way, Meridian Business Park, Leicester, LE19 1WP
- Company Website
- http://www.morningsidehealthcare.com
- Company Telephone
- +44 (0)116 204 5950
- Company Medical Info Direct Line
- +44 (0)116 478 0322
- Company Medical Info Email
- [email protected]
- Company Customer Care Direct Line
- +44 (0)116 204 5950
- Company Stock Availability
- +44 (0)1509 217 705
- Atc Code
- J01FA09
- Legal Category
- Prescription only medicine
- Authorisation Holder
- 7. Marketing authorisation holder Morningside Healthcare Ltd Unit C, Harcourt Way Leicester, LE19 1WP, UK
- Authorisation Number
- 8. Marketing authorisation number(s) PL 20117/0177
- Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation 16/02/2011
- Instruction Authorisation Holder
- 7. Marketing authorisation holder Morningside Healthcare Ltd Unit C, Harcourt Way Leicester, LE19 1WP, UK
- Instruction Authorisation Number
- 8. Marketing authorisation number(s) PL 20117/0177
- Instruction Authorisation Date
- 9. Date of first authorisation/renewal of the authorisation 16/02/2011
- Instruction Composition
- 2. Qualitative and quantitative composition Each film-coated prolonged release tablet contains; Clarithromycin citrate equivalent to clarithromycin 500mg. Excipient with known effect: Each tablet contains 298 mg of lactose monohydrate For the full list of excipients, see section 6.1.
- Instruction Dosage Form
- 3. Pharmaceutical form Prolonged release tablet. Yellow coloured, film coated, oblong shaped, biconvex tablet, with both sides plain.
- Instruction Clinical Particulars
- 4. Clinical particulars 4.1 Therapeutic indications Consideration should be given to official guidance on the appropriate use of antibacterial agents. Xetinin XL 500 mg Tablets are indicated in adults and children 12 years and older. Xetinin XL 500 mg Tablets are indicated for treatment of infections caused by susceptible organisms. Indications include: Lower respiratory tract infections for example, acute and chronic bronchitis, and pneumonia (see section 4.4 and
- Instruction Pharmacology
- 5. Pharmacological properties 5.1 Pharmacodynamic properties General Properties ATC classification Pharmacotherapeutic group: Antibacterial for systemic use, macrolide, ATC code: J01FA09. Mechanism of Action Clarithromycin is an antibiotic belonging to the macrolide antibiotics group. It exerts its antibacterial action by selectively binding to the 50s ribosomal sub-unit of susceptible bacteria preventing translocation of activitate amino acids. It inhibits the intracellular protein synthesis of susceptible bacteria. The 14(R)-hydroxy metabolite of clarithromycin, a product of parent drug metabolism in humans, also has antimicrobial activity. The metabolite is less active than the parent compound for most organisms, including Mycobacterium spp. An exception is Haemophilus influenza where the 14-hydroxy metabolite is two-fold more active than the parent compound. Clarithromycin is usually active against the following organisms in vitro: Gram-positive Bacteria: Staphylococcus aureus (methicillin susceptible); Streptococcus pyogenes (Group A beta-hemolytic streptococci); alpha-hemolytic streptococci (viridans group); Streptococcus (Diplococcus) pneumoniae; Streptococcus agalactiae; Listeria monocytogenes. Gram-negative Bacteria: Haemophilus influenza; Haemophilus parainfluenza; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae; Legionella pneumophila; Bordetella pertussis; Campylobacter jejuni. Mycoplasma: Mycoplasma pneumoniae; Ureaplasma urealyticum. Other Organisms: Chlamydia trachomatis; Mycobacterium avium; Mycobacterium leprae; Mycobacterium kansasii; Mycobacterium chelonae; Mycobacterium fortuitum; Mycobacterium intracellularis; Chlamydia pneumoniae. Anaerobes: Clostridium perfringens; Peptococcus species; Peptostreptococcus species; Propionibacterium acnes. Clarithromycin has bactericidal activity against several bacterial strains. The organisms include Haemophilus influenzae; Streptococcus pneumoniae; Streptococcus pyogenes; Streptococcus agalactiae; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae and Campylobacter spp. Breakpoints The following breakpoints have been established by the European Committee for Antimicrobial Susceptibility Testing (EUCAST). Breakpoints (MIC, mg/L) Microorganism Susceptible (≤) Resistant (>) Staphylococcus spp. 1 mg/L 2 mg/L Streptococcus A, B, C and G 0.25 mg/L 0.5 mg/L Streptococcus pneumonia 0.25 mg/L 0.5 mg/L Viridans group streptococcus IE IE Haemophilus spp. 1 mg/L 32 mg/L Moraxella catarrhalis 0.25 mg/L 0.5 mg/L 1 Helicobacter pylori 0.25 mg/L1 0.5 mg/L 1 The breakpoints are based on epidemiological cut-off values (ECOFFs), which distinguish wild-type isolates from those with reduces susceptibility. “IE" indicates that there is insufficient evidence that the species in question is a good target for therapy with the drug. 5.2 Pharmacokinetic properties The kinetics of orally administered extended-release clarithromycin have been studied in adult humans and compared with clarithromycin 250mg and 500mg immediate release tablets. The extent of absorption was found to be equivalent when equal total daily doses were administered. The absolute bioavailability is approximately 50%. Little or no unpredicted accumulation was found and the metabolic disposition did not change in any species following multiple dosing. Based upon the finding of equivalent absorption the following in vitro and in vivo data are applicable to the extended -release formulation. In vitro: Results of in vitro studies showed that the protein binding of clarithromycin in human plasma averaged about 70 % at concentrations of 0.45 - 4.5μg/mL A decrease in binding to 41% at 45.0μg/mL suggested that the binding sites might become saturated, but this only occurred at concentrations far in excess of therapeutic drug levels. In vivo: Clarithromycin levels in all tissues, except the central nervous system, were several times higher than the circulating drug levels. The highest concentrations were found in the liver and lung tissue, where the tissue to plasma ratios reached 10 to 20. The pharmacokinetic behaviour of clarithromycin is non-linear. In fed patients given 500mg clarithromycin extended-release daily, the peak steady state plasma concentration of clarithromycin and 14 hydroxy clarithromycin were 1.3 and 0.48μg/mL, respectively. When the dosage was increased to 1000mg daily, these steady-state values were 2.4μg/mL and 0.67μg/mL respectively. Elimination half-lives of the parent drug and metabolite were approximately 5.3 and 7.7 hours respectively. The apparent half-lives of both clarithromycin and its hydroxylated metabolite tended to be longer at higher doses. Urinary excretion accounted for approximately 40% of the clarithromycin dose. Faecal elimination accounts for approximately 30%. 5.3 Preclinical safety data In repeated dose studies, clarithromycin toxicity was related to dose and duration of treatment. The primary target organ was the liver in all species, with hepatic lesions seen after 14 days in dogs and monkeys. Systemic exposure levels associated with this toxicity are not known but toxic mg/kg doses were higher than the dose recommended for patient treatment. Fertility, Reproduction and Teratogenicity Studies performed in rats at oral doses up to 500 mg/kg/day (highest dose associated with overt renal toxicity) demonstrated no evidence for clarithromycin-related adverse effects on male fertility. This dose corresponds to a human equivalent dose (HED) of approximately 5 times the maximum recommended human dose (MRHD) on a mg/m2 basis for a 60-kg individual. Fertility and reproduction studies in female rats have shown that a daily dosage of 150mg/kg/day (highest dose tested) caused no adverse effects on the oestrus cycle, fertility, parturition and number and viability of offspring. Oral teratogenicity studies in rats (Wistar and Sprague-Dawley), rabbits (New Zealand White) and cynomolgous monkeys failed to demonstrate any teratogenicity from clarithromycin at the highest doses tested up to 1.5, 2.4 and 1.5 times the MRHD on a mg/m2 basis in the respective species. However, a similar study in Sprague-Dawley rats indicated a low (6%) incidence of cardiovascular abnormalities which appeared to be due to spontaneous expression of genetic changes. Two mouse studies revealed a variable incidence (3-30%) of cleft palate at ~5 times the MRHD on a mg/m2 basis for a 60-kg individual. Embryonic loss was seen in monkeys but only at dose levels which were clearly toxic to the mothers. No evidence of mutagenic potential of clarithromycin was seen during a range of in vitro and in vivo tests. No other toxicological findings considered to be of relevance to the dose level recommended for patient treatment have been reported.
- Instruction Pharmaceutical Particulars
- 6. Pharmaceutical particulars 6.1 List of excipients Tablet core • Lactose Monohydrate • Hypromellose • Hypromellose Phthalate • Talc • Magnesium Stearate Film Coat • Hypromellose • Lactose Monohydrate • Macrogol • Quinoline Yellow Aluminium Lake (E104) • Talc • Titanium Dioxide (E171) 6.2 Incompatibilities None known. 6.3 Shelf life 3 years 6.4 Special precautions for storage This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container Blister pack of Clear PVC/PVDC lidded with aluminium foil for blister pack of 7, 10, 14, 20, 28, 30, 56, 60, 84, 90, 100 and 112 film coated tablets. Not all pack sizes may be marketed 6.6 Special precautions for disposal and other handling No special requirements
- Instruction Content
- ## Composition
2. Qualitative and quantitative composition Each film-coated prolonged release tablet contains; Clarithromycin citrate equivalent to clarithromycin 500mg. Excipient with known effect: Each tablet contains 298 mg of lactose monohydrate For the full list of excipients, see section 6.1.
## Pharmaceutical Form
3. Pharmaceutical form Prolonged release tablet. Yellow coloured, film coated, oblong shaped, biconvex tablet, with both sides plain.
## Clinical Particulars
4. Clinical particulars 4.1 Therapeutic indications Consideration should be given to official guidance on the appropriate use of antibacterial agents. Xetinin XL 500 mg Tablets are indicated in adults and children 12 years and older. Xetinin XL 500 mg Tablets are indicated for treatment of infections caused by susceptible organisms. Indications include: Lower respiratory tract infections for example, acute and chronic bronchitis, and pneumonia (see section 4.4 and
## Pharmacological Properties
5. Pharmacological properties 5.1 Pharmacodynamic properties General Properties ATC classification Pharmacotherapeutic group: Antibacterial for systemic use, macrolide, ATC code: J01FA09. Mechanism of Action Clarithromycin is an antibiotic belonging to the macrolide antibiotics group. It exerts its antibacterial action by selectively binding to the 50s ribosomal sub-unit of susceptible bacteria preventing translocation of activitate amino acids. It inhibits the intracellular protein synthesis of susceptible bacteria. The 14(R)-hydroxy metabolite of clarithromycin, a product of parent drug metabolism in humans, also has antimicrobial activity. The metabolite is less active than the parent compound for most organisms, including Mycobacterium spp. An exception is Haemophilus influenza where the 14-hydroxy metabolite is two-fold more active than the parent compound. Clarithromycin is usually active against the following organisms in vitro: Gram-positive Bacteria: Staphylococcus aureus (methicillin susceptible); Streptococcus pyogenes (Group A beta-hemolytic streptococci); alpha-hemolytic streptococci (viridans group); Streptococcus (Diplococcus) pneumoniae; Streptococcus agalactiae; Listeria monocytogenes. Gram-negative Bacteria: Haemophilus influenza; Haemophilus parainfluenza; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae; Legionella pneumophila; Bordetella pertussis; Campylobacter jejuni. Mycoplasma: Mycoplasma pneumoniae; Ureaplasma urealyticum. Other Organisms: Chlamydia trachomatis; Mycobacterium avium; Mycobacterium leprae; Mycobacterium kansasii; Mycobacterium chelonae; Mycobacterium fortuitum; Mycobacterium intracellularis; Chlamydia pneumoniae. Anaerobes: Clostridium perfringens; Peptococcus species; Peptostreptococcus species; Propionibacterium acnes. Clarithromycin has bactericidal activity against several bacterial strains. The organisms include Haemophilus influenzae; Streptococcus pneumoniae; Streptococcus pyogenes; Streptococcus agalactiae; Moraxella (Branhamella) catarrhalis; Neisseria gonorrhoeae and Campylobacter spp. Breakpoints The following breakpoints have been established by the European Committee for Antimicrobial Susceptibility Testing (EUCAST). Breakpoints (MIC, mg/L) Microorganism Susceptible (≤) Resistant (>) Staphylococcus spp. 1 mg/L 2 mg/L Streptococcus A, B, C and G 0.25 mg/L 0.5 mg/L Streptococcus pneumonia 0.25 mg/L 0.5 mg/L Viridans group streptococcus IE IE Haemophilus spp. 1 mg/L 32 mg/L Moraxella catarrhalis 0.25 mg/L 0.5 mg/L 1 Helicobacter pylori 0.25 mg/L1 0.5 mg/L 1 The breakpoints are based on epidemiological cut-off values (ECOFFs), which distinguish wild-type isolates from those with reduces susceptibility. “IE" indicates that there is insufficient evidence that the species in question is a good target for therapy with the drug. 5.2 Pharmacokinetic properties The kinetics of orally administered extended-release clarithromycin have been studied in adult humans and compared with clarithromycin 250mg and 500mg immediate release tablets. The extent of absorption was found to be equivalent when equal total daily doses were administered. The absolute bioavailability is approximately 50%. Little or no unpredicted accumulation was found and the metabolic disposition did not change in any species following multiple dosing. Based upon the finding of equivalent absorption the following in vitro and in vivo data are applicable to the extended -release formulation. In vitro: Results of in vitro studies showed that the protein binding of clarithromycin in human plasma averaged about 70 % at concentrations of 0.45 - 4.5μg/mL A decrease in binding to 41% at 45.0μg/mL suggested that the binding sites might become saturated, but this only occurred at concentrations far in excess of therapeutic drug levels. In vivo: Clarithromycin levels in all tissues, except the central nervous system, were several times higher than the circulating drug levels. The highest concentrations were found in the liver and lung tissue, where the tissue to plasma ratios reached 10 to 20. The pharmacokinetic behaviour of clarithromycin is non-linear. In fed patients given 500mg clarithromycin extended-release daily, the peak steady state plasma concentration of clarithromycin and 14 hydroxy clarithromycin were 1.3 and 0.48μg/mL, respectively. When the dosage was increased to 1000mg daily, these steady-state values were 2.4μg/mL and 0.67μg/mL respectively. Elimination half-lives of the parent drug and metabolite were approximately 5.3 and 7.7 hours respectively. The apparent half-lives of both clarithromycin and its hydroxylated metabolite tended to be longer at higher doses. Urinary excretion accounted for approximately 40% of the clarithromycin dose. Faecal elimination accounts for approximately 30%. 5.3 Preclinical safety data In repeated dose studies, clarithromycin toxicity was related to dose and duration of treatment. The primary target organ was the liver in all species, with hepatic lesions seen after 14 days in dogs and monkeys. Systemic exposure levels associated with this toxicity are not known but toxic mg/kg doses were higher than the dose recommended for patient treatment. Fertility, Reproduction and Teratogenicity Studies performed in rats at oral doses up to 500 mg/kg/day (highest dose associated with overt renal toxicity) demonstrated no evidence for clarithromycin-related adverse effects on male fertility. This dose corresponds to a human equivalent dose (HED) of approximately 5 times the maximum recommended human dose (MRHD) on a mg/m2 basis for a 60-kg individual. Fertility and reproduction studies in female rats have shown that a daily dosage of 150mg/kg/day (highest dose tested) caused no adverse effects on the oestrus cycle, fertility, parturition and number and viability of offspring. Oral teratogenicity studies in rats (Wistar and Sprague-Dawley), rabbits (New Zealand White) and cynomolgous monkeys failed to demonstrate any teratogenicity from clarithromycin at the highest doses tested up to 1.5, 2.4 and 1.5 times the MRHD on a mg/m2 basis in the respective species. However, a similar study in Sprague-Dawley rats indicated a low (6%) incidence of cardiovascular abnormalities which appeared to be due to spontaneous expression of genetic changes. Two mouse studies revealed a variable incidence (3-30%) of cleft palate at ~5 times the MRHD on a mg/m2 basis for a 60-kg individual. Embryonic loss was seen in monkeys but only at dose levels which were clearly toxic to the mothers. No evidence of mutagenic potential of clarithromycin was seen during a range of in vitro and in vivo tests. No other toxicological findings considered to be of relevance to the dose level recommended for patient treatment have been reported.
## Pharmaceutical Particulars
6. Pharmaceutical particulars 6.1 List of excipients Tablet core • Lactose Monohydrate • Hypromellose • Hypromellose Phthalate • Talc • Magnesium Stearate Film Coat • Hypromellose • Lactose Monohydrate • Macrogol • Quinoline Yellow Aluminium Lake (E104) • Talc • Titanium Dioxide (E171) 6.2 Incompatibilities None known. 6.3 Shelf life 3 years 6.4 Special precautions for storage This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container Blister pack of Clear PVC/PVDC lidded with aluminium foil for blister pack of 7, 10, 14, 20, 28, 30, 56, 60, 84, 90, 100 and 112 film coated tablets. Not all pack sizes may be marketed 6.6 Special precautions for disposal and other handling No special requirements
- Company Detail Path
- /organization/morningside-healthcare-ltd
