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Clarithromycin Krka

MiljöinformationReceptstatusFörmånsstatus
KRKA

Filmdragerad tablett 250 mg
(Ovala, bikonvexa, aningen brungula filmdragerade tabletter, längd 15-15,2 mm och bredd 8 mm.)

Antibakteriella medel för systemiskt bruk, makrolider

Aktiv substans:
ATC-kod: J01FA09
Läkemedel från KRKA omfattas av Läkemedelsförsäkringen.
  • Vad är miljöinformation?

Miljöpåverkan (Läs mer om miljöpåverkan)

Miljöinformationen för klaritromycin är framtagen av företaget AstraZeneca för Nexium® HP

Miljörisk: Användning av klaritromycin har bedömts medföra låg risk för miljöpåverkan.
Nedbrytning: Klaritromycin är potentiellt persistent.
Bioackumulering: Klaritromycin har låg potential att bioackumuleras.


Läs mer

Detaljerad miljöinformation

PEC/PNEC = 0.031 µg/L/ 0.26 µg/L = 0.12


0.1 < PEC/PNEC ≤ 1


Environmental Risk Classification


Predicted Environmental Concentration (PEC)


PEC is based on following data:


PEC (µg/L) = (A*109*(100-R))/(365*P*V*D*100)


PEC (µg/L) = 1.5*10-6*A*(100-R)


A (kg/year) = total sold amount API in Sweden year 2011, = 205.39 kg (data from Quintiles IMS)


R (%) = removal rate (due to loss by adsorption to sludge particles, volatilization, hydrolysis or biodegradation) = 0 (no data is available).


P = number of inhabitants in Sweden = 9 *106


V (L/day) = volume of wastewater per capita and day = 200 (ECHA default)


D = factor for dilution of waste water by surface water flow = 10 (ECHA default)

(Note: The factor 109 converts the quantity used from kg to μg).


PEC = 1.5 * 10-6 * 205.39 * (100-0) = 0.031 µg/L


Metabolism

Reported observations suggest that the metabolism of clarithromycin is saturable and that elimination may be dose-dependent (Ref 2). Following administration of a single 250 mg dose approximately 18 and 4% of clarithromycin were recovered in the urine and faeces, respectively. Following administration of a single 1200 mg dose the recovery of unchanged clarithromycin increased by 75%.


Ecotoxicity data

Study Type

Method

Result

Ref

Toxicity to green alga, Pseudokirchneriella subcapitata, growth inhibition test

OECD 201 Note 1

72 hour NOEC(growth rate) = 0.0031 mg/L

72 hour EC50(growth rate) = 0.011 mg/L

3

ISO 8692 (1989) Note 1

72 hour EC50(growth rate) = 0.002 mg/L

4

Toxicity to green alga, Desmodesmus subspicatus, growth inhibition test

ISO 8692 (1989)

72 hour NOEC(growth rate) = 0.025 mg/L

72 hour EC50(growth rate) = 0.037 mg/L

5

Toxicity to cyanobacteria, Anabaena flos-aquae, growth inhibition test

OECD201

72 hour NOEC(growth rate) = 0.0026 mg/L

72 hour EC50(growth rate) = 0.012 mg/L

Acute toxicity to the Giant Water Flea, Daphnia magna

ISO 6341 (1996) Note 1

48 hour EC50(Immobilisation) >2.1 mg/L

24 hour EC50(Immobilisation) =25.7 mg/L

6

Acute toxicity to the Water Flea, Ceriodaphnia dubia 

EPA 600-4-90-027F 

24 hour EC50(Immobilisation) =18.7 mg/L

Acute toxicity to the freshwater Rotifer, Brachionus calyciflorus

ASTM E1440-91 Note 1

24 hour LC50(mortality) = 35.46 mg/L

Acute toxicity to the Beavertail Fairy Shrimp, Thamnocephalus platyurus 

MicroBio-Test Procedure

24 hour LC50(mortality) = 33.64 mg/L

Acute toxicity to Japanese Ricefish, Oryzias latipes

Not standard method

96 hour LC50(mortality) >100 mg/L

7

Acute toxicity to Zebra fish, Danio rerio

ISO 7346 (1996)

96 hour NOEC(mortality) =1000 mg/L

96 hour LC50(mortality) >1000 mg/L

6

Toxicity testing to the aquatic macrophyte, Lemna minor

OECD 221

7 day NOEC(frond, area) >1.9 mg/L

7 day NOEC(dry weight) = 0.80 mg/L

5

Reproductive toxicity to the Giant Water Flea, Daphnia magna

OECD 211 Note 1

21 day EC50(Reproduction) = 0.040 mg/L

21 day NOEC(Reproduction) =0.0031 mg/L

3

21 day NOEC(Reproduction) >2.1 mg/L

5

Reproductive toxicity to the Water Flea, Ceriodaphnia dubia 

ISO/CD 20665 Note 1

7 day EC50(Reproduction) = 8.16 mg/L

6

Reproductive toxicity to the freshwater Rotifer, Brachionus calyciflorus

ISO/CD 20666 (2001)Note 1

48 hour EC50(Population Growth Inhibition) = 12.21 mg/L

Note 1: Results are expressed as nominal concentrations


PNEC (Predicted No Effect Concentration)


Long-term tests have been undertaken for species from two trophic levels, algae and invertebrates, based on internationally accepted guidelines. In accordance with the Fass guideline an assessment factor of 10 is applied to the NOECgrowth rate for the cyanobacteria (Anabaena flos-aquae), since cyanobacteria are considered a particularly sensitive species to antibiotics, to derive the PNEC.


PNEC = 2.6 µg /L / 50 = 0.26 µg/L


Environmental risk classification (PEC/PNEC ratio)


The PEC/PNEC ratio is calculated as= 0.031 /0.26 = 0.12


Since the PEC to PNEC ratio is 1 ≤ 0.1 the phrase ‘Use of Clarithromycin has been considered to result in low environmental risk’ has been assigned.


In Swedish: “ Användning av Klaritromycin har bedömts medföra låg risk för miljöpåverkan”.


Environmental Fate Data

Endpoint

Method

Test Substance Concentration

Time

Result

Ref

Percentage Biodegradation


OECD 301D

0.003 mg/L

28 d

0 % ThOD

8

2.43 mg/L

0 % ThOD

ThOD – Theoretical Oxygen Demand


Biotic degradation

Based on the data above (considering that no other data is available), the phrase ‘Clarithromycin is potentially persistent ’ is chosen.


In Swedish:

Klaritromycin är potentiellt persistent.


Physical Chemistry Data

Endpoint

Method

Test Conditions

Result

Ref

Water solubility

Predicted - ALOGPS

-

0.217 mg/mL

9

Solubility in test media, verified by chemical analysis

pH 7.8, room temperature

~2 mg/L

5

Octanol-water Partition Coefficient

Potentiometric Method

25oC

Log P = 3.16

10

Predictied

Log D = 1.57

Dissociation Constant

Potentiometric Method

25oC

pKa = 8.99

11


Bioaccumulation


Since Log P < 4, the substance has been assigned the phrase: ‘Clarithromycin has low potential for bioaccumulation’.


In Swedish: “Klaritromycin har låg potential att bioackumuleras” under the heading “Bioackumulering”.


References

  1. ECHA, European Chemicals Agency. May 2008 Guidance on information requirements and chemical safety assessment. Chapter R.10: Characterisation of dose [concentration]-response for environment. https://echa.europa.eu/documents/10162/13632/information_requirements_r10_en.pdf/bb902be7-a503-4ab7-9036-d866b8ddce69 

  2. Clinical Pharmacokinetics of Clarithromycin. Rodvold, KA. Clin Pharmacokinet 1999 Nov; 37 (5): 385-398

  3. Effects of Anti-bacterial Agents, Levofloxacin and Clarithromycin, on Aquatic Organisms. Yamashita N.; Yasojima N.; Nakada N.; Miyajima K.; Komori K.; Suzuki Y.; Tanaka H. Water Sci. Technol. 2006 v53 n11 p65-72

  4. Growth-Inhibiting Effects of 12 Antibacterial Agents and Their Mixtures on the Freshwater Microalga Pseudokirchneriella subcapitata. Yang L.H.; Ying G.G.; Su H.C.; Stauber J.L.; Adams M.S.; Binet M.T. Environ. Toxicol. Chem. 2008 v27 n5 p1201-1208

  5. Aquatic toxicity of the macrolide antibiotic clarithromycin and its metabolites. Baumann M., Weiss K., Maletzkib D., Schüssler W., Schudoma D., Kopf W. and Kühnen U. Chemosphere 120 (2015) 192–198

  6. Toxic and Genotoxic Evaluation of Six Antibiotics on Non-target Organisms. Isidori M.; Lavorgna M.; Nardelli A.; Pascarella L.; Parnella A. Sci. Total Environ. 2005 v346 n1 p87-98

  7. Acute Toxicity of Pharmaceutical and Personal Care Products on Freshwater Crustacean (Thamnocepalus platyurus) and Fish (Oryzias latipes). Kim Joon-Woo ; Ishibashi H.; Yamauchi R.; Ichikawa N.; Takao Y.; Hirano M.; Koga M.; Arizono K. J. Toxicol. Sci. 2009 v34 n2 p227-232

  8. Assessment of Degration of 18 Antiobiotics in the Closed Bottle Test. Alexy R.; Kumpel T.; Kummerer K. Chemosphere 2004 v57 p505-512

  9. Drug bank. Clarithromycin, available at http://www.drugbank.ca/drugs/DB01211 accessed on 5 May 2017 

  10. PhysProp Database. Syracuse Research Corporation

  11. Quantitative Structure-Activity Relationships Among Macrolide Antibacterial Agents: In Vitro & In Vivo Potency Against Pasteurella multocida. McFarland J.W.; Berger C.M.; Froshauer S.A.; Hayashi S.F.; Hecker S.J.; Jaynes B.H.; Jefson M.R.; Kamicker B.J.; Lipinski C.A.; Lundy K.M.; Reese C.P.; Vu C.B. J. Med. Chem. 1997 v40 n9 p1340-1346