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Zovirax®

GlaxoSmithKline

Tablett 400 mg
Avregistreringsdatum: 2020-10-08 (Tillhandahålls ej) (vit, sköldformad, bikonvex, märkt GXCM1)

Antiviralt medel

Aktiv substans:
ATC-kod: J05AB01
För information om det avregistrerade läkemedlet omfattas av Läkemedelsförsäkringen, kontakta Läkemedelsförsäkringen.
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Miljöinformation

Miljöpåverkan

Aciklovir

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


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Detaljerad miljöinformation

Environmental Risk Classification


Predicted Environmental Concentration (PEC)

PEC is calculated according to the following formula:

PEC (μg/L) = (A*109*(100-R)/(365*P*V*D*100) = 1.5*10-6*A(100-R)

PEC = 0.22 μg/L


Where:

A = 1487.5 kg (total sold amount API in Sweden year 2019, data from IQVIA). Total volume of Aciclovir sodium = 14.05 = 12.28 Kg of aciclovir free base.
Total aciclovir = 1,475.22 + 12.28 = 1487.5.

R = 0% removal rate (conservatively, it has been assumed there is no loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)

P = number of inhabitants in Sweden = 9 *106

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Reference 1)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Reference 1)


Predicted No Effect Concentration (PNEC)


Ecotoxicological studies

Green Algae (Selenastrum caprocornutum):

IC50 72h (growth) > 99,000 μg/L (OECD 201) (Reference 3)

NOEC = 99,000 μg/L


Water flea (Daphnia magna):

Acute toxicity

EC50 48 h (immobility) > 1,000,000 μg/L (OECD 202) (Reference 3 )

NOEC = 1,000,000 μg/L


Water flea (Ceriodaphnia dubia):

Chronic toxicity

EC50 7 days (reproduction) > 10,000 μg/L (EPA 1002) (Reference 9)

NOEC = 10,000 μg/L


Fathead Minnow (Juvenilee Pimephales promelas):

Acute toxicity

LC50 96 h (lethality) > 95,000 μg/L (OECD 203) (Reference 3)

NOEC = 95,000 μg/L


Other ecotoxicity data:

Microorganisms in activated sludge

EC50 3 hours (Inhibition) > 1,000,000 μg/L (OECD 209) (Reference 7)


PNEC = 10,000/50 = 200 μg/L


PNEC (μg/L) = lowest NOEC/50, where 50 is the assessment factor applied for two long-term NOECs. NOEC for water flea (= 10,000 ug/L) has been used for this calculation since it is the most sensitive of the three tested species.


Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.22/200 = 1.0 x 10-3, i.e. PEC/PNEC ≤ 1 which justifies the phrase “Use of aciclovir has been considered to result in insignificant environmental risk.”


Degradation

Biotic degradation

Ready degradability:

0.7% degradation in 28 days (TAD 3.11) (Reference 5)

Inherent degradability:

100% primary (loss of parent) degradation in 14 days (OECD 302B) (Reference 8)


Abiotic degradation

Hydrolysis:

Half-life, pH 7 > 1 year (TAD 3.09) (Reference 5)


Photolysis:

Half-life, pH 7 = 3.5 hours (TAD 3.10) (Reference 4)


Justification of chosen degradation phrase:

Aciclovir is not readily biodegradable and is not susceptible to hydrolysis and is therefore expected to persist in the environment. However, this substance is inherently biodegradable. Significant removal of aciclovir is expected to occur in wastewater treatment plants due to biodegradation. This substance has limited water solubility and a low partition coefficient suggests it is unlikely to bioconcentrate in exposed aquatic organisms. (Reference 11).


The phrase “Aciclovir is potentially persistent” is thus chosen.


Bioaccumulation

Partitioning coefficient:

Log Pcalc = -1.55. (Chemaxon) (Reference 10)


Justification of chosen bioaccumulation phrase:

Since log Pow < 4, the substance has low potential for bioaccumulation.


Excretion (metabolism)

In adults the terminal plasma half-life of aciclovir after administrations of intravenous aciclovir is about 2.9 hours. Most of the drug is excreted unchanged by the kidney. Renal clearance of aciclovir is substantially greater than creatinine clearance, indicating that tubular secretion, in addition to glomerular filtration contributes to the renal elimination of the drug. 9-carboxymethoxymethylguanine is the only significant metabolite of aciclovir, and accounts for approximately 10 - 15% of the administered dose recovered from the urine (Reference 2).


PBT/vPvB assessment

Aciclovir does not fulfil the criteria for PBT and/or vBvP.


All three properties, i.e. ‘P’, ‘B’ and ‘T’ are required in order to classify a compound as PBT (Reference 1). Aciclovir does not fulfil the criteria for PBT and/or vBvP based on a log Dow < 4.


Please, also see Safety data sheets on http://www.msds-gsk.com/ExtMSDSlist.asp.


References

  1. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment.

  2. Pharmacokinetic properties: Metabolism and Elimination. Summary of Product Characteristics Zovirax (Aciclovir) Tablets. GlaxoSmithKline, November 2012.

  3. Smith MF. Hydrolysis of 14C-Acyclovir as a Function of pH. Report No. 41609. ABC Laboratories, June 1994.

  4. Gorman M. Determination of Aqueous Photodegradation of 14C-Acyclovir. Report No. 41308. ABC Laboratories, June 1994.

  5. Franklin BB. Aerobioc Biodegradation in Water using 14C-Acyclovir. Report No. 41309. ABC Laboratories, March 1994.

  6. Ziegenfuss MC. Ecotoxicity Evaluation of Acyclovir (CCl22890). Report No. ERL-2001-041. GlaxoSmithKline Environmental Research Laboratory, July 2001.

  7. Koper CM. Acute Toxicity of CCL22890 (Acyclovir) to Activated Sludge Microorganisms. Report No. ERL-2001-047. GlaxoSmithKline Environmental Research Laboratory, October 2001.

  8. Mather JI, Smyth DV and Kent SJ. Aciclovir: Determination of Inherent Biodegradability Using the Zahn-Wellens/EMPA Test. Report No. BL7606/B. Brixham Environmental Laboratories, July 2004.

  9. Young BE and Kent SJ. Acyclovir: Determination of the 3-brood (7 day) Chronic Toxicity of Ceriodaphnia dubia. Report No. BL8144/B. Brixham Environmental Laboratories, April 2006.

  10. Chemaxon /LogD. May 2012. Instant J Chem, ChemAxon Ltd.

  11. GSK. 2014. Environmental Risk Assessment Data Summary – Version 1. https://www.msds-gsk.com/GetEraFile.ashx?fileId=61