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Seroquel Depot

(Parallellimporterat)
MiljöinformationReceptstatusFörmånsstatus
Cross Pharma AB

Depottablett 400 mg
Avregistreringsdatum: 2016-11-02 (Tillhandahålls ej)

Blisterkartan är märkt både Seroquel Depot och Seroquel XL

Neuroleptikum

Visa information om det parallellimporterade läkemedlet
Aktiv substans:
ATC-kod: N05AH04
För information om det avregistrerade läkemedlet omfattas av Läkemedelsförsäkringen, kontakta Läkemedelsförsäkringen.
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Miljöpåverkan (Läs mer om miljöpåverkan)

Miljöinformationen för kvetiapin är framtagen av företaget AstraZeneca för Seroquel, Seroquel Depot, Seroquel®

Miljörisk: Användning av quetiapin har bedömts medföra försumbar risk för miljöpåverkan.
Nedbrytning: Quetiapin bryts ned långsamt i miljön.
Bioackumulering: Quetiapin har låg potential att bioackumuleras.


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Detaljerad miljöinformation


PEC/PNEC = 5.64 x 10-3 μg/L /10.0 μg/L = 5.64 x 10-4

PEC/PNEC ≤ 0.1 


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 2016, data from IMS Health.

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)

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).


A = 37.6 kg 


R = 0


PEC = 1.5 * 10-6 * 37.6 * (100-0) = 5.64 x 10-3 μg/L 


Metabolism

After oral administration, quetiapine is eliminated almost completely by metabolism, as < 5% of the excreted dose can be recovered in urine and faeces as the parent compound (quetiapine). Approximately 73% of the dose is excreted as metabolites in urine and 21% is excreted in faeces. (Ref. 1)


Ecotoxicity data


Aquatic Toxicity Data

Endpoint

Species

Common Name

Method

Time

Result

Reference

NOEC - Based on Largest Specific Growth Rates

Microcystis aeruginosa

Cyanobacterium (Blue-Green Alga)

US FDA Technical Assistance Document 4.01

21 d

32 mg/L Note 1

2

LOEC - Based on Largest Specific Growth Rates

Microcystis aeruginosa

Cyanobacterium (Blue-Green Alga)

US FDA Technical Assistance Document 4.01

21 d

64 mg/L Note 1

NOEC - Based on Maximum Standing Crops

Microcystis aeruginosa

Cyanobacterium (Blue-Green Alga)

US FDA Technical Assistance Document 4.01

21 d

4.0 mg/L Note 1

LOEC - Based on Maximum Standing Crops

Microcystis aeruginosa

Cyanobacterium (Blue-Green Alga)

US FDA Technical Assistance Document 4.01

21 d

8.0 mg/L Note 1

EC50 - Based on Largest Specific Growth Rates

Pseudokirchneriella subcapitata (formerly known as Selenastrumcapricornutum)

Green Alga

US FDA Technical Assistance Document 4.01

96 h

8.03 mg/L Note 1

3

EC50 - Based on Maximum Standing Crop

Pseudokirchneriella subcapitata (formerly known as Selenastrumcapricornutum)

Green Alga

US FDA Technical Assistance Document 4.01

96 h

3.59 mg/L Note 1

NOEC - Based on Largest Specific Growth Rates

Pseudokirchneriella subcapitata (formerly known as Selenastrum capricornutum)

Green Alga

US FDA Technical Assistance Document 4.01

14 d

2.5 mg/L Note 1

LOEC - Based on Largest Specific Growth Rates

Pseudokirchneriella subcapitata (formerly known as Selenastrum capricornutum)

Green Alga

US FDA Technical Assistance Document 4.01

14 d

5.0 mg/L Note 1

NOEC - Based on Maximum Standing Crops

Pseudokirchneriella subcapitata (formerly known as Selenastrum capricornutum)

Green Alga

US FDA Technical Assistance Document 4.01

14 d

2.5 mg/L Note 1

LOEC - Based on Maximum Standing Crops

Pseudokirchneriella subcapitata (formerly known as Selenastrum capricornutum)

Green Alga

US FDA Technical Assistance Document 4.01

14 d

5.0 mg/L Note 1

LC50

Daphnia magna

Giant Water Flea

US FDA Technical Assistance Document 4.09

21 d

> 32 mg/L Note 1

4

NOEC - Based on Reproduction & Length

Daphnia magna

Giant Water Flea

US FDA Technical Assistance Document 4.09

21 d

18 mg/L Note 1

LOEC - Based on Reproduction & Length

Daphnia magna

Giant Water Flea

US FDA Technical Assistance Document 4.09

21 d

32 mg/L Note 1

EC50 - Based on Emergence

Chironomus riparius

Midge

OECD 218

28 d

465 mg/kg dry sediment

5

NOEC - Based on Emergence

Chironomus riparius

Midge

OECD 218

28 d

125 mg/kg dry sediment

LOEC - Based on Emergence

Chironomus riparius

Midge

OECD 218

28 d

250 mg/kg dry sediment

LC50

Lepomis macrochirus

Bluegill Sunfish

US FDA Technical Assistance Document 4.11

96 h

19.3 mg/L Note 1

6

NOEC - Based on Symptoms of Toxicity

Lepomis macrochirus

Bluegill Sunfish

US FDA Technical Assistance Document 4.11

96 h

1.8 mg/L Note 1

LC50

Oncorhynchus mykiss

Rainbow Trout

US FDA Technical Assistance Document 4.11

96 h

22.0 mg/L Note 1

7

NOEC - Based on Symptoms of Toxicity

Oncorhynchus mykiss

Rainbow Trout

US FDA Technical Assistance Document 4.11

96 h

1.0 mg/L Note 1

NOEC - Based on Overall Endpoints Note 2

Pimephales promelas

Fathead Minnow

OECD 210

32 d

0.1 mg/L Note 1

8

LOEC - Based on Overall Endpoints Note 2

Pimephales promelas

Fathead Minnow

OECD 210

32 d

0.32 mg/L Note 1

EC50 - Based on Respiration Inhibition

-

-

OECD 209

3 h

>100 mg/L

Note 3

9

Note 1: Concentrations were confirmed by analysis, and results expressed as nominal.

Note 2: The relevant endpoints measured were hatch, survival, length, wet and dry weight.

Note 3: Results are expressed as nominal concentrations.


PNEC (Predicted No Effect Concentration)

Long-term tests have been undertaken for species from three trophic levels, based on internationally accepted guidelines. Therefore, the PNEC is based on the results from the chronic toxicity to fathead minnow (Pimephales promelas), the most sensitive species, and an assessment factor of 10 is applied, in accordance with ECHA guidance (ref. 8).


PNEC = 100 µg /L/10 = 10 µg/L


Environmental risk classification (PEC/PNEC ratio)


PEC/PNEC = 5.64 x 10-3 μg/L /10.0 μg/L = 5.64 x 10-4 

PEC/PNEC ≤ 0.1 which justifies the phrase

“Use of Quetiapin has been considered to result in insignificant environmental risk.”


In Swedish: “ Användning av Quetiapin har bedömts medföra försumbar risk för miljöpåverkan.”.


Environmental Fate Data

Endpoint

Method

Test Substance Concentration

Time

Result

Reference

Percentage Aerobic Biodegradation

OECD 301F

100 mg/L

28 d

0 % ThOD

10

Percentage Carbon Removal

OECD 301F

100 mg/L

28 d

10 %

Percentage Compound Removal

OECD 301F

100 mg/L

28 d

24 %

Percentage Anaerobic Biodegradation

DoE Modified According to ISO/CD 11734

50 & 100 mg Carbon/L

57 d

0 %

11

Percentage Compound Removal

DoE Modified According to ISO/CD 11734

50 & 100 mg Carbon/L

57 d

52 %

Dissipation Half-life

OECD 308

-

-

T1/2 = 5.2 d (in aqueous phase over high organic matter sediment)

12

Dissipation Half-life

OECD 308

-

-

T1/2 = 18 d (in aqueous phase over low organic matter sediment)

Percentage Hydrolysis

US FDA Technical Assistance Document 3.09

-

5 d

< 10 % @ pH 5,7, & 9, 50C

13

Hydrolysis Half-life

US FDA Technical Assistance Document 3.09

-

-

≥ 1 yr @ 25C

Partition Coefficient Octanol Water

FDA Technical Assistance Handbook 3.02

-

-

LogP = 0.5

14

Partition Coefficient Octanol Water (Buffer)

FDA Technical Assistance Handbook 3.02

-

-

LogDow = 1.4 @ pH 5

Partition Coefficient Octanol Water (Buffer)

FDA Technical Assistance Handbook 3.02

-

-

LogDow = 2.7 @ pH 7

Partition Coefficient Octanol Water (Buffer)

FDA Technical Assistance Handbook 3.02

-

-

LogDow = 2.6 @ pH 9


Biodegradation


Aerobic biodegradation (OECD 301F) (ref. 10)

A ready biodegradation test of quetiapine fumarate was undertaken by using aerobic microorganisms from a sewage treatment works to investigate their potential to readily degrade the substance. The test ended after 28 days. The results showed that quetiapine fumarate is not readily biodegradable (BOD28/ThOD <0.6).


Anaerobic degradation (UK Department of the Environment ISO/CD 11734) (Ref. 11)

Primary anaerobic digested sludge was obtained from a sewage treatment works, to determine the anaerobic biodegradability of quetiapine fumarate. The day 57 results show that quetiapine, in the presence of anaerobic slugde remains only to 48 %, and to 81 % in absence of anaerobic sludge. Some degree of elimination was observed, probably attributable to the adsorption processes. The conclusion is that quetiapine fumarate is not anaerobically biodegradable under the conditions of the test.


Aerobic transformation in aquatic sediment systems

The degradation of quetiapine fumarate in aquatic sediment systems was assessed according to the OECD 308 Test Guideline (Ref. 12). Two different sediments were used, one with high and one with low organic matter content over the 100 d test period.


Dissipation half-life = 5.2 days in water (sediment with high organic matter)

Dissipation half-life = 18 days in water (sediment with low organic matter)


In conclusion, in both the high and low organic matter test vessels, quetiapine fumarate was rapidly dissipated from the water phase. In the sediment there was evidence to show that quetiapine fumarate was degraded, but there was insufficient analytical data to quantify the rate. Overall, the evidence from this study suggests that quetiapine fumarate will not be persistent in the environment. 


Based on the information from all three studies above, the statement ‘The medicine is slowly degraded in the environment’ is justified under the heading ‘Degradation’.

In Swedish: “Läkemedlet bryts ned långsamt i miljön” under the heading “Nedbrytning”.


Bioaccumulation

Since Log P < 4 at pH 7, the substance has been assigned the phrase: ‘Quetiapin has low potential for bioaccumulation’.


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


Physical Chemistry Data

Endpoint

Method

Test Conditions

Result

Reference

Solubility Water

US FDA Technical Assistance Handbook 3.01

16 d @ pH 5

10800 mg/L

15

Solubility Water

US FDA Technical Assistance Handbook 3.01

20 d @ pH 7

1600 mg/L

Solubility Water

US FDA Technical Assistance Handbook 3.01

6 d @ pH 9

360 mg/L

Dissociation Constant

Not-specified

-

pKa = 6.83

16

Dissociation Constant

Not-specified

-

pKa = 3.32

Sewage Adsorption Coefficient

OPPTS 835.1110

0.2 mg/L

Kd = 335

Koc = 905 L/Kg*

17

Soil Adsorption Coefficient

US FDA Technical Assistance Document 3.08

25 mg/L

Koc = 220000 in Nebo Soil

18

Soil Adsorption Coefficient

US FDA Technical Assistance Document 3.08

25 mg/L

Koc = 1400 in Kenny Hill Soil

Soil Adsorption Coefficient

US FDA Technical Assistance Document 3.08

25 mg/L

Koc = 8000 in East Jubilee Soil

Soil Adsorption Coefficient

US FDA Technical Assistance Document 3.08

25 mg/L

Kd = 3633 in Nebo Soil

Soil Adsorption Coefficient

US FDA Technical Assistance Document 3.08

25 mg/L

Kd = 45 in Kenny Hill Soil

Soil Adsorption Coefficient

US FDA Technical Assistance Document 3.08

25 mg/L

Kd = 177 in East Jubilee Soil

*  Calculated Koc = Kd(ads) / 0.37


From the results on the three soils tested, it is evident that the Kd may vary in different soils. However, the data suggests that quetiapine fumarate will be essentially immobile.


The Kd values are not proportional to the carbon content, so the Koc is not likely to be a reliable predictor of adsorption to soil. It is more likely that the adsorption is dependent on pH, with higher adsorption in more acidic soils. There is also evidence to suggest that the adsorption of quetiapine fumarate is irreversible, especially in more acidic soils.


References

  1. Investigator’s Brochure Seroquel (Quetiapine fumarate; ICI 204,636 fumarate). AstraZeneca. 10th edition, September 2005.


  2. Seroquel: Toxicity to the blue-green alga Microcystis aeruginosa. BL5018/B. Brixham Environmental Laboratory, Brixham, UK. February 1994.


  3. Seroquel: Toxicity to the green alga Selenastrum capricornutum. BL5017/B. Brixham Environmental Laboratory, Brixham, UK. February 1994.


  4. Seroquel: Chronic toxicity to Daphnia magna. BL5232/B. Brixham Environmental Laboratory, Brixham, UK. September 1994.


  5. Quetiapine fumarate Toxicity to the sediment-dwelling phase of the midge

    Chironomus riparius. Report No. VKS0391/073509. Sponsors reference number: 06-0052/A. Huntingdon Life Sciences Ltd. UK. December 2007.


  6. Seroquel: Acute toxicity to bluegill sunfish Lepomis macrochirus. BL5085/B. Brixham Environmental Laboratory, Brixham, UK. February 1994.


  7. Seroquel: Acute toxicity to rainbow trout Oncorhynchus mykiss. BL5084/B. Brixham Environmental Laboratory, Brixham, UK. February 1994.


  8. Quetiapine fumarate: Determination of effects on the early-life stage of the fathead minnow (Pimephales promelas). BL8351/B. Brixham Environmental Laboratory, Brixham, UK. August 2006.


  9. Quetiapine fumarate: Effect on the respiration rate of activated sludge. Report No. BL8333/B. Brixham Environmental Laboratory, Brixham, UK. June 2006.


  10. Seroquel: Determination of 28 day ready biodegradability. Report No. BL5078/B. Brixham Environmental Laboratory, Brixham, UK. February 1994.


  11. Seroquel: Determination of anaerobic biodegradability. Report No. BL5077/B. Brixham Environmental Laboratory, Brixham, UK. February 1994.


  12. Quetiapine fumarate: Aerobic transformation in aquatic sediment systems. BL8364/B. Brixham Environmental Laboratory, Brixham, UK. August 2007.


  13. Data generated in the US to support the environmental assessment report for ICI 204,636. Pharmaceutical research & development Report no. SP2900/B. BD4185 Zeneca Pharmaceuticals Group, Wilmington, USA. 29 March 1995.


  14. ICI 204,636 log partition coefficient measurements in partial fulfillment of FDA

    environmental assessment requirements. Pharmaceutical research & development Report No. SP3011/B. BD4119. Zeneca Pharmaceuticals, Wilmington, USA. 3 October 1995.


  15. ICI 204,636 solubility measurements in partial fulfillment of FDA environmental assessment requirements. Pharmaceutical research & development report no. SP3010/B. BD4118. Zeneca Pharmaceuticals, Wilmington, USA. 22 September 1995.


  16. Clinical, S1-03, General Properties, Quetiapine, ZD5077. Report no. BD4184


  17. Quetiapine fumarate: Adsorption and desorption to sludge. Report No. BL8343/B. Brixham Environmental Laboratory, Brixham, UK. August 2006.


  18. Seroquel: Soil sorption and adsorption. Report no. BL5062/B. Brixham Environmental Laboratory, Brixham, UK. February 1994.