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Iktorivil®

Roche

Tablett 0,5 mg
(8 mm, beige, plana, på ena sidan enkel brytskåra, på andra sidan märkta ROCHE 0,5)

narkotikaindikation Risk för tillvänjning föreligger.
Iakttag försiktighet vid förskrivning av detta läkemedel.

Särskild receptblankett krävs

Antiepileptikum

Aktiv substans:
ATC-kod: N03AE01
Utbytbarhet: Ej utbytbar
Läkemedel från Roche omfattas av Läkemedelsförsäkringen.
  • Vad är miljöinformation?

Miljöinformation

Miljöpåverkan

Klonazepam

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


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Detaljerad miljöinformation

Identification and characterisation

CAS number: 1622-61-3 [1]

Molecular weight: 315.7 [1]

Brand name: Iktorivil [1]


Physico-chemical properties

Aqueous solubility: <100 mg/l (20 °C) (method not specified) [1]

Dissociation constant, pKa: pKa = 1.5 [1], pKb = 10.5 [1]

Melting point: 236.5–238.5 °C (method not specified) [1]

Vapour pressure: 9.76*E–09 Pa (25 °C) QSAR

Boiling point: ND

KH: 8.6*E–13 atm*m3/mol QSAR


QSAR = QSAR-modelled (EPISuite, SPARC, ACD Solaris)


Predicted Environmental Concentration (PEC)

PEC is calculated according to the formula:

PEC (μg/L) = (A x 1'000'000'000 x (100-R)) / (365 x P x V x D x 100) = 1.5 x 10-6 x A x (100 - R) = 0.00093 μg/L


Where:

A Sold quantity = 6.20736272 kg/y (total sold amount API in Sweden year 2017, data from IQVIA)

R Removal rate = 0 % Default [2]

P Population of Sweden = 9000000

V Volume of Wastewater = 200 l/day Default [2]

D Factor for Dilution = 10 Default [2]


Predicted No Effect Concentration (PNEC)


Ecotoxicological Studies

Green alga (Desmodesmus subspicatus): [4]

72 h ErC50 (growth rate) >240 mg/l loading rate (OECD 201)

72 h ErC50 (growth rate) >15.4 mg/l (solubility limit in algal medium, estimated) (OECD 201)

72 h NOEC = 2.46 mg/l loading rate (OECD 201)

(With respect to algal growth rate inhibition the following effects as compared to the untreated controls were observed at the respective loading rates: 240 mg/l (49%), 96 mg/l (46%), 38.4 mg/l (38%), 15.4 mg/l (34%) and 6.14 mg/l (16%). No significant effects were observed at 2.46 mg/l. Since no significant increase of toxicity occurred at concentrations >15.4 mg/l, this concentration can estimated to be the solubility limit in algal medium)


Water-flea (Daphnia magna): [5]

48 h EC50 = 30.3 mg/l mean measured concentration(FDA Technical Assistance Document 4.08)

(the nominal concentrations were 5.4, 9.1, 15.1, 25.2, 42.0 and 70.0 mg/l, The respective analytically determined mean measured concentrations were 4.04, 7.08, 11.7, 19.1, 31.4 and 48.8 mg/l, respectively)


Rainbow trout (Oncorhynchus mykiss): [7]

96 h LC50 >1000 mg/l (applied as an emulsion) (OECD 203)

96 h NOEC = 1000 mg/l (applied as an emulsion) (OECD 203)


Micro-organisms: [6]

NOEC (microbial growth) = 4.2 mg/l (FDA Technical Assistance Document 4.02)

(various pure cultures of bacteria, fungi, and cyanobacteria)


PNEC Derivation

The PNEC is based on the following data:

PNEC (mg/l) = lowest EC50/1000, where 1000 is the assessment factor used. An estimated solubility limit of 15400μ g/l in algal medium has been used for this calculation.

PNEC = 15400 / 1000 = 15.4 μg/l


Environmental Risk Classification (PEC/PNEC Ratio)

PEC Predicted Environmental Concentration = 0.00093 μg/L

PNEC Predicted No Effect Concentration = 15.4 μg/L

Ratio PEC/PNEC = 0.00006


PEC/PNEC = 0.00093/15.4 = 0.00006 for Clonazepam which justifies the phrase 'Use of Clonazepam has been considered to result in insignificant environmental risk.'


Degradation


Biotic Degradation

Ready biodegradability: ND


Inherent biodegradability: [7]

0% after 21 days of incubation BOD/ThOD (OECD 302 C)


Other degradation information: ND


Abiotic Degradation

Photodegradation: light sensitive [1]

Hydrolysis: ND


Clonazepam was not inherently biodegradable in a standard test. This justifies the phrase 'Clonazepam is potentially persistent.'


Bioaccumulation/Adsorption


logPOW 2.53 QSAR

logDOW 2.41 (25 °C, pH 7.4) (method not specified) [1]


KOC 283 l/kg QSAR

BCF <20 QSAR


Clonazepam has low potential for bioaccumulation.


Excretion/metabolism


The elimination half-life of Clonazepam is between 20 and 60 hours (mean 30 hours). Within 4–10 days 50–70% of are excreted in the urine and 10–30% in the faeces, almost exclusively in the form of free or conjugated metabolites. Less than 0.5% appears as unchanged clonazepam in the urine. [3]


References


1. F. Hoffmann-La Roche Ltd (2018): Safety Data Sheet for Clonazepam, 31.01.2018; https://www.roche.com/sustainability/what_we_do/for_communities_and_environment/environment/safety_data_sheetsrow. htm.

2. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment. http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm.

3. electronic Medicines Compendium (eMC). 2017. https://www.medicines.org.uk/emc/.

4. BMG Engineering Ltd, on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (2007). Clonazepam: Fresh water growth inhibition test with Desmodesmus subspicatus. BMG study no. 1226-07.

5. Toxikon Environmental Sciences, on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (1992). Clonazepam: Acute toxicity to the water flea Daphnia magna under static test conditions. Toxikon study no. J9108014b.

6. ABC Laboratories, Inc., on behalf of F. Hoffmann-La Roche Ltd, Basel, Switzerland (1992). Microbial inhibition with Clonazepam. ABC study no. 40067.

7. Roche internal ecotox report. 1981.