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Losec®

AstraZeneca

Enterotablett 10 mg
(ljust rosa, 6,5×12 mm, bikonvexa, filmdragerade tabletter, märkta med LOSEC-symbol på ena sidan och 10 mg på den andra)

Syrahämmande medel - protonpumpshämmare

Aktiv substans:
ATC-kod: A02BC01
Läkemedel från AstraZeneca omfattas av Läkemedelsförsäkringen.
  • Vad är miljöinformation?

Miljöinformation

Miljöpåverkan (Läs mer om miljöpåverkan)

Omeprazol

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


Läs mer

Detaljerad miljöinformation

PEC/PNEC = 0.942 µg/L/100 µg/L = 0.0094

PEC/PNEC ≤ 0.1


Environmental Risk Classification

Total sales of esomeprazole and omeprazole are included in the calculation of the Predicted Environmental Concentration (PEC), as a worst case, as esomeprazole is the S-enantiomer of the racemate omeprazole and the toxicity is assumed to be very similar.

Only short-term (acute) toxicity data are availble for omeprazole. Therefore, in the absence of comprehensive environmental data for omeprazole, the more scientifically robust long-term data set for esomeprazole has been used to generate the Predicted No Effect Concentration (PNEC). These data are in accordance with the EU European Medicines Agency (EMA) guideline (ref. 1).


Predicted Environmental Concentration (PEC)

The PEC is based on the 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 2017, data from IQVIA (former IMS Health and Quintiles).

R (%) = removal rate (due to loss by adsorption to sludge particles, by volatilization,

hydrolysis or biodegradation) = 0 if 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) (ref. 2)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (ref. 2)

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


A = 6280.84 kg. This figure is based on sales figures (147.25 kg esomeprazole magnesium + 761.04 kg esomeprazole magnesiumdihydrate + 111.70 kg esomeprazole magnesiumtrihydrate + 260.67 kg esomeprazole sodium + 4905.90 kg omeprazole + 94.28 kg omeprazolmagnesium) 


R = 0


PEC = 1.5 × 10-6 × 6280.84 × (100-0) = 0.942 µg/L

(Note: Whilst esomeprazole and omeprazole are extensively metabolised, little is known about the ecotoxicity of the excreted metabolites. Hence, a total residue approach is taken where no metabolism of parent compound is considered; a worst case assumption.)


Metabolism

After administration, esomeprazole and omeprazole are almost completely metabolised, with <1% found in urine as the parent compound. Approximately 80% of the metabolites are excreted by urine and approximately 20% via faeces. The two main excreted human metabolites are both excreted via urine, and are considerably less pharmacologically active than the parent compounds (ref. 3).


Ecotoxicity data - Esomeprazole

Endpoint

Species

Common Name

Method

Time

Result

Ref.

NOEC - Based on Biomass

Pseudokirchneriella subcapitata (formerly known as Selenastrum capri-cornutum)

Green Alga

OECD 201

72 h

3.9 mg/L

Note 1

4

LOEC - Based on Biomass 

8.4 mg/L

Note 1 

NOEC - Based on Logarithmic Growth Rate 

8.4 mg/L

Note 1

LOEC - Based on Logarithmic Growth Rate

19 mg/L

Note 1

ErC50 - Based on Logarithmic Growth Rate 

85 mg/L

Note 1

EbC50 - Based on Biomass

19 mg/L

Note 1 

NOEC - Overall

Note 2

Daphnia magna

Giant Water Flea

OECD 211

21 d

10 mg/L

Note 3 

5

LOEC - Overall
Note 5

Pimephales promelas

Fathead Minnow

OECD 210

32 d

3.2 mg/L

Note 3

6

NOEC - Overall
Note 5

1.0 mg/L

Note 3

EC50 - Based on Activated Sludge Respiration Inhibition 

-

-

OECD 209

3 h

>100 mg/L

Note 6

7

NOEC - Based on Activated Sludge Respiration Inhibition 

100 mg/L

Note 6

NOEC – Based on overall endpoints

Note 4

Chironomus riparius

Midge

OECD 218

28 d

400 mg/kg

Note 3

8

LOEC – Based on emergence, development rate and sex ratio 

1000 mg/kg dry sediment


Ecotoxicity data - Omeprazole

Endpoint

Species

Common Name

Method

Time

Result

Ref.

EbC50 – Based on Biomass

Note 7

Pseudokirchneriella subcapitata (formerly known as Selenastrum capricornutum)

Green Alga

OECD 201

72 h

30.1 mg/L

Note 1

9

ErC50 – Based on Growth Rate

Note 7

>75.9 mg/L

Note 1

NOEC - Based on Biomass

Note 7

<1.81 mg/L

Note 1

NOEC - Based on Growth Rate

Note 7

1.81 mg/L

Note 1

EC50 - Based on Immobilisation 

Note 7

Daphnia magna

Giant Water Flea

OECD 202

48 h

>100 mg/L

Note 3

10

LC50

Note 7

Danio rerio (formerly known as Brachydanio rerio)

Zebra fish

OECD 203

96 h

41.9 mg/L

Note 1

11

NOEC - Based on Activated Sludge Respiration Inhibition

Note 8

-

-

OECD 209

3 h

100 mg/L

12

EC50 - Based on Activated Sludge Respiration Inhibition

Note 8

>100 mg/L

Note 1: Results are expressed as mean measured concentrations.

Note 2: The population relevant endpoints measured were survival, fecundity and adult length.

Note 3: Concentrations were confirmed by analysis, and results expressed as nominal.

Note 4: The population relevant endpoints measured were total number of emerged adult insects, sex ratio and replicate mean plus individual emergence times (development rates).

Note 5: The population relevant endpoints measured were hatch, survival, length and dry weight.

Note 6: Results are expressed as nominal concentrations.

Note 7: Data from studies on omeprazole sodium.

Note 8: Data from studies on omeprazole.


PNEC (Predicted No Effect Concentration)

Long-term tests of esomeprazole have been undertaken for species from three trophic levels, based on internationally accepted guidelines. The most sensitive species of these is the fathead minnow. Therefore, the PNEC is based on the results from the fathead minnow early life stage test, and an assessment factor of 10 is applied, in accordance with ECHA guidance (ref. 13).


PNEC = 1000/10 µg/L = 100 µg/L


Environmental risk classification (PEC/PNEC ratio)


PEC/PNEC = 0.942 µg/L/100 µg/L = 0.0094,

i.e. PEC/PNEC ≤ 0.1 which justifies the phrase “Use of omeprazole has been considered to result in insignificant environmental risk”.


In Swedish: ”Användning av omeprazol har bedömts medföra försumbar risk för miljöpåverkan” under the heading ”Miljörisk”.


Environmental Fate Data – Omeprazole

Endpoint

Method

Test Substance Concentration

Time

Result

Ref.

Half-life

Note 9

Unknown

In aqueous solution

-

T1/2 @20 oC:

pH 4 = 15 mins

pH 7 = 30 h

pH 9 = > week

14

T1/2 =10 h @ 37 oC, pH 7

Note 9: This study predates current ERA regulatory requirements and may not have been undertaken to standardised test guidelines.


Physical Chemistry Data- Omeprazole

Endpoint

Method

Test Substance Conditions

Result

Ref.

Distribution Coefficient Octanol Water

Unknown

-

Log D (experimental) = 2.24

14

Solubility Water 

Note 9

Unknown

22 oC

130 mg/L

Dissociation Constant

Note 9

Unknown

-

pKa(1) = 4 (Pyridinium ion)

Dissociation Constant

pKa(2) = 8.8 (Benzimidazole ion)

Note 9: This study predates current ERA regulatory requirements and may not have been undertaken to standardised test guidelines.


Biodegradation

Omeprazole was found not to be readily biodegradable in biodegradability studies. The substance has hence been assigned the phrase: “Omeprazol is potentially persistent”.


In Swedish: ”Omeprazol är potentiellt persistent” under the heading ”Nedbrytning”.


Bioaccumulation

Since Log D < 4, Omeprazole has low potential to bioaccumulate and the phrase “Omeprazole has low potential for bioaccumulation” is assigned.


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


References

  1. Committee for Medicinal Products for Human Use (CHMP); Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use. 1 June 2006, Ref EMEA/CPMP/SWP/4447/00.


  2. [ECHA] European Chemicals Agency. Guidance on Information Requirements and Chemical Safety Assessment. Chapter R.16: Environmental exposure assessment (version 3.0). February 2016.


  3. AstraZeneca, access September 2019.

    <https://www.astrazeneca.com/content/dam/az/our-company/Sustainability/2017/esomeprazole%20and%20omeprazole.pdf>


  4. Esomeprazole Na: Toxicity to the green alga Selenastrum capricornutum.

    Brixham Environmental Laboratory, AstraZeneca, UK, Report BL8021

    March 2005


  5. Esomeprazole sodium: Chronic toxicity to Daphnia magna.

    Brixham Environmental Laboratory, AstraZeneca, UK, Report BL8555

    February 2008


  6. Esomeprazole Sodium: Determination of Effects on the Early-Life Stage of Fathead Minnow (Pimephales promelas).

    Brixham Environmental Laboratory, AstraZeneca, UK, Report BL8452

    July 2007


  7. Esomeprazole sodium: Effect on the Respiration Rate of Activated Sludge.

    Brixham Environmental Laboratory, AstraZeneca, UK, Report BR0162

    March 2010


  8. [14C]Esomeprazole sodium: Effects in sediment on emergence of the midge, Chironomus riparius

    Brixham Environmental Laboratory, AstraZeneca, UK, Report BL8557

    March 2008


  9. H 168/68 Na salt: acute Toxicity to Pseudokirchneriella sucapitata. Document No. T3355, Corning Hazelton, Harrogate, England. June 1996.


  10. H 168/68 Na salt: acute Toxicity to Daphnia Magna. Document No. T3353, Corning Hazelton, Harrogate, England. June 1996.


  11. H 168/68 Na salt: acute Toxicity to Brachydanio rerio. Document No. T3354, Corning Hazelton, Harrogate, England. June 1996.


  12. IVL Swedish Environmental Research Institute Commissioned Report; Investigation of the ‘ready biodegradability’ of A001 drug substance, Report BD3984. June 1991.


  13. [ECHA] European Chemicals Agency. Guidance on Information Requirements and Chemical Safety Assessment. Chapter R.10: Characterisation of dose [concentration]-response for environment. May 2008.


  14. Marketing. S1-03 (pre-CTD) Physicochemical Data, APCD 23075, Omeprazole pwd. August 1985.