Brexit
The decision by the UK electorate to leave the European Union will have implications for my project. Even before the vote, I was already assessing the scope for extending the project, and the original comparison between UK and Dutch formularies may well have to be altered if not abandoned.
Amitryptiline
This tricyclic antidepressant has quite varying indications when comparing the Dutch and British formularies, and will be one of the focal points in the area of antidepressants in particular, and psychotropics in general.
Anti-depressants
My comparison will continue in the next few days with anti-depressants. This is a fairly large category, which will probably take me about a week to get through. Again, the comparison is not (at this stage) comparing the clinical efficacy of any compound to another, but a formulary comparison.
Not marketing
I have come across several instances (lurasidone being a case in point) where a manufacturer has registered one or more strengths of their entity, without applying for the strength to be marketed. An enquiry with Takeda, which markets Latuda (lurasidone), as to why 18.5 mg is not available in NL remains open.
Meprobamate
Meprobamate (marketed as Mogadon) was withdrawn from markets in the EU on recommendation from the EMA in 2012. Yet, the drug remains available in the UK, albeit with the comment that it is not recommended.
Anti-psychotics - 3
Dutch regulator complains that the half-dose preparation for one anti-psychotic, needed for use in the elderly, is not on the market. It is. In the UK. See the point of my project now?
Anti-psychotics - 2
Interesting to note that the use of droperidol has been restricted to nausea and vomiting only, and only in the Netherlands is it still being used as an antipsychotic. But even there, it's only through the parenteral route.
Flupentixol is primarily an anti-psychotic, but its license in the UK also includes depression.
Fluspirilene is only marked in NL, as a depot preparation for psychosis and mania.
Flupentixol is primarily an anti-psychotic, but its license in the UK also includes depression.
Fluspirilene is only marked in NL, as a depot preparation for psychosis and mania.
Antipsychotics - clozapine
It is beginning to strike me that the market for psycho-active prescription medicines is broader in NL than in UK. Having covered clozapine this weekend in this comparison, I am surprised by the difference in monitoring requirements. Clozapine (Clozaril in UK and Leponex in NL) can cause serious abnormalities in blood cell counts (agranulocytosis), which is known to be fatal in certain cases. Clozapine is an important substance, as it can be used when other anti-psychotics fail or are not tolerated. One of the main side-effects of many anti-psychotics are extra-piramidal effects (Parkinson-like symptoms, such as tremors). Clozapine does not have this side-effect, but the risk of fatal agranulocytosis makes it impossible for this compound to be first choice.
Benzodiazepines compared
Diazepam
Dosing schedules
Oxazepam
UK has no 5 mg or 25 mg tablets
Alprazolam
UK: no slow-release tablets
Prazepam, Bromazepam, Clorazepate, Valerian, Brotizolam
Not marketed in UK
Clomethiazole, Zaleplon
Not marketed in NL
Temazepam
Capsules not marketed in UK
Lormetazepam
UK: no 2 mg tablets
NL: no 0.5 mg tablets
Flunitrazepam
UK: only available on private prescription
NL: subject to CD-type restriction
Dosing schedules
Oxazepam
UK has no 5 mg or 25 mg tablets
Alprazolam
UK: no slow-release tablets
Prazepam, Bromazepam, Clorazepate, Valerian, Brotizolam
Not marketed in UK
Clomethiazole, Zaleplon
Not marketed in NL
Temazepam
Capsules not marketed in UK
Lormetazepam
UK: no 2 mg tablets
NL: no 0.5 mg tablets
Flunitrazepam
UK: only available on private prescription
NL: subject to CD-type restriction
Benzodiazepines
Having completed the comparisons between the Netherlands and the United Kingdom of indications and dosing of benzodiazepines, a number of differences have surfaced. Most are relatively minor. However, there appear to be a larger number of BZD on the market in Holland than in the UK.
Diazepam
ATC: N05BA01
DDD: 10 mg
ICD-10: F10, F41, G40, G47, O14, O15
Tmax: 30-90 minutes
Half-life: 20-48 hours, metabolite N-desmethyldiazepam 42-100 h
Contra-indications: myasthenia gravis, respiratory and hepatic failure, sleep apnea
Not to be used alone in depression or in psychotic illness
NL: Tablets 2, 5 and 10 mg
Rectal tubes: 2 mg/ml and 4 mg/ml (both 2.5 ml)
Injection: 5 mg/ml, 2 ml amp
UK: CD4-1
Tablets: 2 and 5 and 10 mg
Oral solution: 2 mg / 5 ml and 5mg/5ml
Injection: 5 mg/ml, 2 ml amp
Rectal tubes: 2 mg /ml (1.25 and 2.5 ml) and 4 mg/ml (2.5 ml)
DDD: 10 mg
ICD-10: F10, F41, G40, G47, O14, O15
Tmax: 30-90 minutes
Half-life: 20-48 hours, metabolite N-desmethyldiazepam 42-100 h
Contra-indications: myasthenia gravis, respiratory and hepatic failure, sleep apnea
Not to be used alone in depression or in psychotic illness
NL: Tablets 2, 5 and 10 mg
Rectal tubes: 2 mg/ml and 4 mg/ml (both 2.5 ml)
Injection: 5 mg/ml, 2 ml amp
UK: CD4-1
Tablets: 2 and 5 and 10 mg
Oral solution: 2 mg / 5 ml and 5mg/5ml
Injection: 5 mg/ml, 2 ml amp
Rectal tubes: 2 mg /ml (1.25 and 2.5 ml) and 4 mg/ml (2.5 ml)
Diazepam
| ||
Indication
|
Netherlands
|
UK
|
Anxiety
|
Oral
2.5 mg 2-3 dd, up to 30 mg
|
Oral
2 mg 3dd, up to max daily dose 15-30 mg, elderly half dose
|
IM/IV
0.1-0.2 mg/kg, 8 hourly
|
IM :
10 mg over 2 mins, repeated (if necessary) after at least 4h
| |
PR
5-10 mg 2-3dd, 60 mg max
| ||
Insomnia
|
Oral
2.5 – 20 mg
|
Oral
5 – 15 mg
|
Status epilepticus
|
PR
Adult 10-20 mg
Child over 3: 10mg
Child 1-3: 5 mg
Child <1: 0.5 mg/kg
|
PR
Adult & child over 12: 10-20 mg, elderly 10 mg
Neonate: 1.25-2.5 mg Child 1-12 months: 5 mg Child 1-2 years: 5 mg Child 2-12 years: 5-10 mg |
IV/IM
Adult 0.15-0.25 mg/kg
|
IV/IM
10 mg over 2 mins, repeat once after 10 mins
Child under 12: 0.3-0.4 mg/kg, max 10 mg | |
Muscular spasms
|
Oral
15 mg / day 2-4 doses, up to 60mg
| |
IV/IM
2-20 mg
|
IV
5-10 mg
Child 1-12 months: 0.1 mg/kg
| |
PR
10-20 mg 2-3 dd
Child: 0.04-0.2 mg/ kg
Max 0.6 mg/kg/8 h
|
PR
0.5 mg/kg, elderly half dose | |
Upper motoric nerves
|
15 mg / day 2-4 doses, max 60 mg
| |
Febrile convulsions
|
PR
0.25 – 0.5 mg/kg
Adult: 20mg, repeat after 10 mins, half dose in elderly
Child: 10-15 kg: 5 mg
Child: > 15 kg: 10 mg
|
PR
Adult & child over 12: 10-20 mg, elderly 10 mg
Neonate: 1.25-2.5 mg Child 1-12 months: 5 mg Child 1-2 years: 5 mg Child 2-12 years: 5-10 mg |
IV
0.2-0.5 mg/kg
|
IV/IM
10 mg over 2 mins, repeat once after 10 mins
Child under 12: 0.3-0.4 mg/kg, max 10 mg | |
Tetanus
|
PR
0.25 – 0.5 mg/kg
Adult: 20mg, repeat after 10 mins, half dose in elderly
Child: 10-15 kg: 5 mg
Child: > 15 kg: 10 mg
| |
IV
0.1 – 0.3 mg/kg every 1-4 h, max 4 mg/kg/day
| ||
Alcohol withdrawal
|
Oral
5-20 mg, repeat once after 2-4 h, 10 mg 3-4 dd, reduce 5 mg 3-4 dd
Hospital: 10 mg hourly till asymptomatic, up to 80 mg | |
IV
0.1-0.2 mg/kg, every 8h
|
IM : 10 mg over 2 mins, repeated (if necessary) after at least 4h
| |
PR
20 mg 3dd for 24 hours, then 10 mg 3 dd
| ||
(Pre) Eclampsia, post partum
|
IV
10-20 mg
|
Oxazepam
ATC: N05BA04
DDD: 50 mg oral
ICD-10: F41, G47, F10
Tmax: 2-3 h
Half life: 4-15 h
Contra-indications: myasthenia gravis, liver and respiratory failure and sleep apnea
Dose
Anxiety: 10 mg 3-4dd in mild cases, 50 mg in severe cases, up to 100-300 mg daily
UK: 15-30 mg, but 10-20 mg in elderly or infirm
Anxiety with depression: 10-20 mg 3-4dd, also for alcohol withdrawal (not more than 1 week)
Child under 6: 10-30 mg per day in divided doses
Child 6-12 years: 10-40 mg
Insomnia: 15-30 mg
NL: 5, 10, 25, 50 mg tablets (Seresta)
UK: CD4-1. 10 and 15 mg tablets (non-propr)
DDD: 50 mg oral
ICD-10: F41, G47, F10
Tmax: 2-3 h
Half life: 4-15 h
Contra-indications: myasthenia gravis, liver and respiratory failure and sleep apnea
Dose
Anxiety: 10 mg 3-4dd in mild cases, 50 mg in severe cases, up to 100-300 mg daily
UK: 15-30 mg, but 10-20 mg in elderly or infirm
Anxiety with depression: 10-20 mg 3-4dd, also for alcohol withdrawal (not more than 1 week)
Child under 6: 10-30 mg per day in divided doses
Child 6-12 years: 10-40 mg
Insomnia: 15-30 mg
NL: 5, 10, 25, 50 mg tablets (Seresta)
UK: CD4-1. 10 and 15 mg tablets (non-propr)
Alprazolam
ATC: N05BA12
DDD: 1 mg oral
ICD-10: F41
Tmax (tablets): 1-2 h, Retard tablets 5 - 11 h
Half-life: 12-15 h, elderly 16 h
Contra-indications: Myasthenia gravis, respiratory and hepatic failure, sleep apnea
Dose: Start on 0.25 - 0.5 mg 3 dd, then 0.5 - 3 mg daily in divided doses
Retard tablet: Start 1 mg 1-2 dd, then 0.5 - 3 mg daily in divided doses
NL: 0.25 and 0.5 mg tablets, Retard tablets 0.5, 1 and 2 mg (Xanax)
UK: CD4-1, not NHS
0.25 and 0.5 mg tablets, Xanax
DDD: 1 mg oral
ICD-10: F41
Tmax (tablets): 1-2 h, Retard tablets 5 - 11 h
Half-life: 12-15 h, elderly 16 h
Contra-indications: Myasthenia gravis, respiratory and hepatic failure, sleep apnea
Dose: Start on 0.25 - 0.5 mg 3 dd, then 0.5 - 3 mg daily in divided doses
Retard tablet: Start 1 mg 1-2 dd, then 0.5 - 3 mg daily in divided doses
NL: 0.25 and 0.5 mg tablets, Retard tablets 0.5, 1 and 2 mg (Xanax)
UK: CD4-1, not NHS
0.25 and 0.5 mg tablets, Xanax
Prazepam
ATC: N05BA11
DDD: 30 mg
ICD-10: F41
First pass effect to N-desmethyldiazepam, tmax 6 h
Half -life: 42-100 hours, metabolite
Contra-indications: myasthenia gravis, respiratory and hepatic failure
Dose: 10 - 60 mg, usually 30 mg, for no longer than 8 to 12 weeks, decrease out slowly
Elderly, hepatic, renal and respiratory failure: start at 10-15 mg
NL: 10 mg tablets (Reapam)
UK: Not marketed
DDD: 30 mg
ICD-10: F41
First pass effect to N-desmethyldiazepam, tmax 6 h
Half -life: 42-100 hours, metabolite
Contra-indications: myasthenia gravis, respiratory and hepatic failure
Dose: 10 - 60 mg, usually 30 mg, for no longer than 8 to 12 weeks, decrease out slowly
Elderly, hepatic, renal and respiratory failure: start at 10-15 mg
NL: 10 mg tablets (Reapam)
UK: Not marketed
Bromazepam
ATC: N05BA08
DDD: 10 mg oral
ICD-10: F41
Tmax: 1-2 h
Half life: 15 - 22 h
CI: myasthenia gravis, respiratory and hepatic failure, sleep apnea
Dose: 1.5 - 3 mg, 3 dd, in severe anxiety 6 - 12 mg 2-3 dd; for not longer than 2 weeks
UK: Not marketed
NL: 1.5, 3 and 6 mg tablets
DDD: 10 mg oral
ICD-10: F41
Tmax: 1-2 h
Half life: 15 - 22 h
CI: myasthenia gravis, respiratory and hepatic failure, sleep apnea
Dose: 1.5 - 3 mg, 3 dd, in severe anxiety 6 - 12 mg 2-3 dd; for not longer than 2 weeks
UK: Not marketed
NL: 1.5, 3 and 6 mg tablets
Lorazepam
ATC: N05BA06
DDD: 2.5 mg oral, parenteral and sub-lingual
ICD-10: F41, G41, G47
Tmax 2 h, half-life 12 to 16 hours
Contra-indications: Myasthenia gravis, respiratory or hepatic insuffiency, sleep apnea
Dose:
NL: Anxiety: 0.5 mg 2-3 dd, increased to 1 mg 2-3 dd
Severe anxiety: 1.25 - 2.5 mg 2-3 dd
IV/IM: 2-4 mg, repeat after 2h if necessary
Sleep: 1-2 mg at night
UK: 1-4 mg daily in divided doses; elderly half doses
Insomnia: 1-2 mg at bedtime
IM/IV: 25-30 mcg/kg (1.5-2.5mg) every 6 hours
NL: 0.5, 1 and 2.5 mg tablets (Temesta)
Injection: 4 mg / ml
UK: CD4-1
1 and 2.5 mg tablets
Injection: 4 mg / ml (Ativan)
Also for status epilepticus
DDD: 2.5 mg oral, parenteral and sub-lingual
ICD-10: F41, G41, G47
Tmax 2 h, half-life 12 to 16 hours
Contra-indications: Myasthenia gravis, respiratory or hepatic insuffiency, sleep apnea
Dose:
NL: Anxiety: 0.5 mg 2-3 dd, increased to 1 mg 2-3 dd
Severe anxiety: 1.25 - 2.5 mg 2-3 dd
IV/IM: 2-4 mg, repeat after 2h if necessary
Sleep: 1-2 mg at night
UK: 1-4 mg daily in divided doses; elderly half doses
Insomnia: 1-2 mg at bedtime
IM/IV: 25-30 mcg/kg (1.5-2.5mg) every 6 hours
NL: 0.5, 1 and 2.5 mg tablets (Temesta)
Injection: 4 mg / ml
UK: CD4-1
1 and 2.5 mg tablets
Injection: 4 mg / ml (Ativan)
Also for status epilepticus
Clorazepate
ATC: N05BA05
DDD: 20 mg oral
ICD-10: F41, F10
Metabolised to active metabolite N-desmethyldiazepam
Tmax 45 minutes, half-life 2-3 hours
Metabolite half-life: 42 to 96 hours
Contra-indications: Myasthenia gravis, respiratory and hepatic insuffiency, sleep apnea
Dose
Anxiety: 5 mg 3 dd, up to 50 mg 3dd, up to 300 mg in a day
Alcohol withdrawal: 200 to 300 mg in divided doses, IM 20-40 mg every 2 h
UK: Not marketed
NL: Tranxene
5 and 10 mg caps
Film-coated tabs 20 mg MB (can be quartered), and 50 mg
DDD: 20 mg oral
ICD-10: F41, F10
Metabolised to active metabolite N-desmethyldiazepam
Tmax 45 minutes, half-life 2-3 hours
Metabolite half-life: 42 to 96 hours
Contra-indications: Myasthenia gravis, respiratory and hepatic insuffiency, sleep apnea
Dose
Anxiety: 5 mg 3 dd, up to 50 mg 3dd, up to 300 mg in a day
Alcohol withdrawal: 200 to 300 mg in divided doses, IM 20-40 mg every 2 h
UK: Not marketed
NL: Tranxene
5 and 10 mg caps
Film-coated tabs 20 mg MB (can be quartered), and 50 mg
Clobazam
ATC: N05BA09
DDD: 20 mg oral
ICD-10: F41, G40
tmax: 0.5 - 4 h
Half life: 18-30 h, metabolites 50 h
Renal and liver insufficiency, myasthenia gravis
Dose:
Anxiety: 10 mg 2-3dd, or 20 mg at night, up to 60 mg, not longer than 8 - 12 weeks
Epilepsy:
NL: start 5-15 mg, up to 80 mg
child 5 mg / day, 0.3-1 mg / kg / day
UK: 20-30 mg daily, up to 60 mg
child 5 mg / day, 0.3-1 mg / kg / day
NL: 5, 10, 20 mg tabs (Frisium 10, 20 mg)
UK: CD4-1
10 mg tabs (Frisium, NHS only for epilepsy)
suspension 5 mg / 5ml
DDD: 20 mg oral
ICD-10: F41, G40
tmax: 0.5 - 4 h
Half life: 18-30 h, metabolites 50 h
Renal and liver insufficiency, myasthenia gravis
Dose:
Anxiety: 10 mg 2-3dd, or 20 mg at night, up to 60 mg, not longer than 8 - 12 weeks
Epilepsy:
NL: start 5-15 mg, up to 80 mg
child 5 mg / day, 0.3-1 mg / kg / day
UK: 20-30 mg daily, up to 60 mg
child 5 mg / day, 0.3-1 mg / kg / day
NL: 5, 10, 20 mg tabs (Frisium 10, 20 mg)
UK: CD4-1
10 mg tabs (Frisium, NHS only for epilepsy)
suspension 5 mg / 5ml
Chlordiazepoxide
ATC: N05BA02
DDD: 30 mg oral, 50 mg parenteral
ICD-10: F41, F10
Half life: 9 h, metabolites 40-50 h
Liver / renal impairment
Dose:
NL: Anxiety: 5 - 10 mg, 3-4 dd, up to 20 - 25 mg
UK: 10 mg 3dd, up to 60-100 mg in divided doses; elderly half dose
Alcohol detox (UK only) 10-50 mg 4 dd, reduce over 7-10 days
NL: 5, 10 and 25 mg tablets
UK: CD4-1
5 mg tablets and 5 mg caps. Librium non-NHS
DDD: 30 mg oral, 50 mg parenteral
ICD-10: F41, F10
Half life: 9 h, metabolites 40-50 h
Liver / renal impairment
Dose:
NL: Anxiety: 5 - 10 mg, 3-4 dd, up to 20 - 25 mg
UK: 10 mg 3dd, up to 60-100 mg in divided doses; elderly half dose
Alcohol detox (UK only) 10-50 mg 4 dd, reduce over 7-10 days
NL: 5, 10 and 25 mg tablets
UK: CD4-1
5 mg tablets and 5 mg caps. Librium non-NHS
Valerian
ATC: N05CM09
DDD: -
ICD-10: G47
UK: not marketed
NL: Nerviplant 500 mg tabs
Tendo tincture
Valdispert 45 mg coated tabs
Dose:
Valdispert:
Insomnia, 1 at night
Anxiety: 1-3 tabs 3 x daily
Nerviplant:
Anxiety: 1-3 tabs up to 4 x daily
Not held to have great efficacy
DDD: -
ICD-10: G47
UK: not marketed
NL: Nerviplant 500 mg tabs
Tendo tincture
Valdispert 45 mg coated tabs
Dose:
Valdispert:
Insomnia, 1 at night
Anxiety: 1-3 tabs 3 x daily
Nerviplant:
Anxiety: 1-3 tabs up to 4 x daily
Not held to have great efficacy
Clomethiazole
ATC: N05CM02
DDD: 1.5 g oral / parenteral
ICD-10: G47, F10.3
Dose: 1 to 2 capsules, insomnia in the elderly
Contra-indications: hepatic, renal and respiratory insufficiency
Alcohol withdrawal treatment: not longer than 9 days
NL: Not marketed
UK: 192 mg capsules
157.5 mg / 5ml oral solution
DDD: 1.5 g oral / parenteral
ICD-10: G47, F10.3
Dose: 1 to 2 capsules, insomnia in the elderly
Contra-indications: hepatic, renal and respiratory insufficiency
Alcohol withdrawal treatment: not longer than 9 days
NL: Not marketed
UK: 192 mg capsules
157.5 mg / 5ml oral solution
Zaleplon
ATC: N05CF03
DDD: 10 mg oral
ICD-10: G47
Half-life: 1 hour
Dose: 10 mg (elderly 5 mg) at night (up to 2 weeks)
Contra-indications: hepatic, renal and respiratory insufficiency; myasthenia gravis and sleep apnea
NL: not marketed
UK: CD4-1
Sonata, 5 and 10 mg capsules
DDD: 10 mg oral
ICD-10: G47
Half-life: 1 hour
Dose: 10 mg (elderly 5 mg) at night (up to 2 weeks)
Contra-indications: hepatic, renal and respiratory insufficiency; myasthenia gravis and sleep apnea
NL: not marketed
UK: CD4-1
Sonata, 5 and 10 mg capsules
Zopiclone
ATC: N05CF01
DDD: 7.5 mg oral
ICD-10: G47
Max level after 45 to 120 minutes
Half life: 5 hours, elderly 7 hours, in liver cirrhosis 10 hours
Dose: 7.5 mg at night, for 2 weeks, max 4 weeks
Start on 3.75 mg in the elderly and with liver and renal insuffiency
Contra-indications: myasthenia gravis, liver and renal insufficiency, sleep apnea
Interactions around CYP3A4 metabolism
UK: CD 4-1. Zimovane 3.75 and 7.5 mg
NL: Imovane 3.75 and 7.5 mg
DDD: 7.5 mg oral
ICD-10: G47
Max level after 45 to 120 minutes
Half life: 5 hours, elderly 7 hours, in liver cirrhosis 10 hours
Dose: 7.5 mg at night, for 2 weeks, max 4 weeks
Start on 3.75 mg in the elderly and with liver and renal insuffiency
Contra-indications: myasthenia gravis, liver and renal insufficiency, sleep apnea
Interactions around CYP3A4 metabolism
UK: CD 4-1. Zimovane 3.75 and 7.5 mg
NL: Imovane 3.75 and 7.5 mg
Zolpidem
ATC: N05CF02
DDD: 10 mg oral
ICD-10: G47
Dose: 10 mg at night (up to 4 weeks), elderly 5 mg
Max level after ½ to 3 hours
Contra-indications: myasthenia gravis, sleep apnea, respiratory, hepatic and renal insufficiency
Interactions related to CYP3A4 metabolism
NL: Stilnoct and non-proprietary, 5 and 10 mg tablets
UK: CD 4-1; Stilnoct and non-proprietary 5 and 10 mg tablets
DDD: 10 mg oral
ICD-10: G47
Dose: 10 mg at night (up to 4 weeks), elderly 5 mg
Max level after ½ to 3 hours
Contra-indications: myasthenia gravis, sleep apnea, respiratory, hepatic and renal insufficiency
Interactions related to CYP3A4 metabolism
NL: Stilnoct and non-proprietary, 5 and 10 mg tablets
UK: CD 4-1; Stilnoct and non-proprietary 5 and 10 mg tablets
Temazepam
ATC: N05CD07
DDD: 20 mg oral
ICD-10: G47
Dose: 10 - 20 mg, exceptionally 30 - 40 mg
Conscious sedation (dental procedures): 15 - 30 mg
Contra-indications: hepatic and renal failure, myasthenia gravis
Max level after 50 minutes
Half life: 7 - 11 hours
NL: Capsules 10 and 20 mg, Normison;
Tablets 10 and 20mg
Oral solution: 30 mg/ml
UK (CD 3): Tablets 10 mg and 20 mg
Oral solution: 10 mg / 5ml
DDD: 20 mg oral
ICD-10: G47
Dose: 10 - 20 mg, exceptionally 30 - 40 mg
Conscious sedation (dental procedures): 15 - 30 mg
Contra-indications: hepatic and renal failure, myasthenia gravis
Max level after 50 minutes
Half life: 7 - 11 hours
NL: Capsules 10 and 20 mg, Normison;
Tablets 10 and 20mg
Oral solution: 30 mg/ml
UK (CD 3): Tablets 10 mg and 20 mg
Oral solution: 10 mg / 5ml
Nitrazepam
ATC: N05CD02
DDD: 5 mg oral
ICD-10: G47, G40.4
Dose: 2.5 - 5, or 5 - 10 mg at night
Max level after 2 hours
Half life: 30 hours
Contra-indications: hepatic or renal failure, myasthenia gravis
NL: non-proprietary 5 mg tablets
UK: CD 4-1
Non-proprietary 5 mg tablets
Non-proprietary liquid 2.5 mg / 5 ml
DDD: 5 mg oral
ICD-10: G47, G40.4
Dose: 2.5 - 5, or 5 - 10 mg at night
Max level after 2 hours
Half life: 30 hours
Contra-indications: hepatic or renal failure, myasthenia gravis
NL: non-proprietary 5 mg tablets
UK: CD 4-1
Non-proprietary 5 mg tablets
Non-proprietary liquid 2.5 mg / 5 ml
Midazolam
ATC: N05CD08
DDD: 15 mg oral and parenteral
ICD-10: G47, G41
Dose:
NL: oral 7.5 - 15 mg at night
UK: buccal: 10 mg, repeated after 10 minutes (unlicensed)
Parenteral: according to dosage schedules for various forms of sedation
Contra-indications: hepatic and renal failure, myasthenia gravis
Interactions: through CYP3A4
Max level (oral) after 30 to 90 minutes
Half life:
Adults 2 - 3½ hours
Child aged 3-10: 1 - 1½ hours
Neonates: 6 - 12 hours
Metabolites: 0.8 - 1 hour
Elderly: 3 times longer
Long-term sedation in ITU: up to 6 x longer
NL: Dormicum 7.5 and 15 mg tablets
Injection: 1 mg/ml, 5 and 50 ml
2 mg/ml, 50 ml
5 mg/ml, 1, 3 and 10 ml
Nasal spray (not licensed) 2.5mg and 0.5mg per dose
UK: CD3
oromucosal solution 5mg/ml, 0.5, 1ml, 1.5 and 2 ml prefilled syringes
injection: 1 mg/ml, 2ml, 5 ml, 50 ml; 2 mg/ml, 5 ml; 5 mg/ml 2ml and 10 ml
Hypnovel: 5 mg/ml, 2ml
DDD: 15 mg oral and parenteral
ICD-10: G47, G41
Dose:
NL: oral 7.5 - 15 mg at night
UK: buccal: 10 mg, repeated after 10 minutes (unlicensed)
Parenteral: according to dosage schedules for various forms of sedation
Contra-indications: hepatic and renal failure, myasthenia gravis
Interactions: through CYP3A4
Max level (oral) after 30 to 90 minutes
Half life:
Adults 2 - 3½ hours
Child aged 3-10: 1 - 1½ hours
Neonates: 6 - 12 hours
Metabolites: 0.8 - 1 hour
Elderly: 3 times longer
Long-term sedation in ITU: up to 6 x longer
NL: Dormicum 7.5 and 15 mg tablets
Injection: 1 mg/ml, 5 and 50 ml
2 mg/ml, 50 ml
5 mg/ml, 1, 3 and 10 ml
Nasal spray (not licensed) 2.5mg and 0.5mg per dose
UK: CD3
oromucosal solution 5mg/ml, 0.5, 1ml, 1.5 and 2 ml prefilled syringes
injection: 1 mg/ml, 2ml, 5 ml, 50 ml; 2 mg/ml, 5 ml; 5 mg/ml 2ml and 10 ml
Hypnovel: 5 mg/ml, 2ml
|
|
Midazolam - parenteral
|
|
|
Indication
|
UK
|
NL
|
|
Conscious sedation
|
IV 2-2.5 mg increase in steps of 1 mg to total of 3.5-5 mg, max 7.5
mg
Elderly: 0.5-1mg, steps 0.5-1mg, max 3.5 mg |
IV 2-2.5 mg increase in steps of 1 mg to total of 3.5-5 mg, max 7.5
mg
Elderly: 0.5-1mg, steps 0.5-1mg, max 3.5 mg |
|
Sedative in combined anaesthesia
|
IV 30-100 mcg/kg repeated as necessary of 30-100 mcg/kg/h by
continuous infusion
|
IV 30-100 mcg/kg repeated as necessary of 30-100 mcg/kg/h by
continuous infusion
|
|
Premedication
|
IM 70-100 mcg/kg (elderly 25-50 mcg/kg)
IV 1-2 mg (elderly 0.5 mg( |
IM 70-100 mcg/kg (elderly 25-50 mcg/kg)
IV 1-2 mg (elderly 0.5 mg( |
|
Induction
|
150-200 mcg/kg (elderly 50-150 mcg/kg) in divided doses of max 5 mg
every 2 minutes, max 600 mcg/kg
|
150-200 mcg/kg (elderly 50-150 mcg/kg) in divided doses of max 5 mg
every 2 minutes, max 600 mcg/kg
|
|
Sedation in ITU
|
30-300 mcg/kg in steps of
1-2.5 mg every 2 minutes, then 30-200 mcg/kg/h
|
30-300 mcg/kg in steps of
1-2.5 mg every 2 minutes, then 30-200 mcg/kg/h
|
Melatonin
ATC: N05CH01
DDD: 2 mg
ICD-10: G47
Dose: 2 mg, 1-2 hours before sleep, not longer than 3 weeks
Half life: 3½ to 4 hours
Hepatically cleared
NL / UK: Circadin, modified release
DDD: 2 mg
ICD-10: G47
Dose: 2 mg, 1-2 hours before sleep, not longer than 3 weeks
Half life: 3½ to 4 hours
Hepatically cleared
NL / UK: Circadin, modified release
Lormetazepam
ATC: N05CD06
DDD: 1 mg po
ICD-10: G47
Dose: 1 - 2 mg, elderly and resp/hep/renally impairment 0.5 - 1mg
UK: 0.5-1.5 mg (elderly only 0.5mg)
Max level after 2 hours
Half-life: 10 - 12 hours
NL: 1 and 2 mg tablets (Noctamid)
UK: CD4-1. Tablets 0.5 and 1 mg
DDD: 1 mg po
ICD-10: G47
Dose: 1 - 2 mg, elderly and resp/hep/renally impairment 0.5 - 1mg
UK: 0.5-1.5 mg (elderly only 0.5mg)
Max level after 2 hours
Half-life: 10 - 12 hours
NL: 1 and 2 mg tablets (Noctamid)
UK: CD4-1. Tablets 0.5 and 1 mg
Loprazolam
ATC: N05CD11
DDD: 1 mg po
ICD-10: G47
Tmax: 1 hour
Half-life: 6-8 hours
Contra-indications: hepatic and respiratory insufficiency; myasthenia gravis
Dose: 0.5 - 1 mg, up to 2 mg; elderly 0.5 or 1 mg
UK: CD4-1. Non proprietary, 1 mg tablets
NL: Dormonoct 1 mg tablets, additional indication as pre-med for procedure, taken the night before
DDD: 1 mg po
ICD-10: G47
Tmax: 1 hour
Half-life: 6-8 hours
Contra-indications: hepatic and respiratory insufficiency; myasthenia gravis
Dose: 0.5 - 1 mg, up to 2 mg; elderly 0.5 or 1 mg
UK: CD4-1. Non proprietary, 1 mg tablets
NL: Dormonoct 1 mg tablets, additional indication as pre-med for procedure, taken the night before
Flurazepam
ATC: N05CD01
DDD: 30 mg po
ICD-10: G47
Dose: 15-30 mg, max 60 mg
First pass effect yields active metabolites
Half-life: 47 - 100 h (active metabolites)
Contra-indications: renal, hepatic and respiratory insufficiency; myasthenia gravis
Long half-life renders this benzodiazepine less suitable as a hypnotic
UK: CD4-1, Dalmane, not NHS
NL: non-proprietary
DDD: 30 mg po
ICD-10: G47
Dose: 15-30 mg, max 60 mg
First pass effect yields active metabolites
Half-life: 47 - 100 h (active metabolites)
Contra-indications: renal, hepatic and respiratory insufficiency; myasthenia gravis
Long half-life renders this benzodiazepine less suitable as a hypnotic
UK: CD4-1, Dalmane, not NHS
NL: non-proprietary
Brotizolam
ATC: N05CD09
DDD: 0.25 mg
ICD-10: G47
Max level after 60 to 100 minutes
Half-life: 3-8 hours
Contra-indication: renal and hepatic impairment
Dose: 0.125 - 0.25 mg
NL: Lendormin tablets
UK: not marketed
DDD: 0.25 mg
ICD-10: G47
Max level after 60 to 100 minutes
Half-life: 3-8 hours
Contra-indication: renal and hepatic impairment
Dose: 0.125 - 0.25 mg
NL: Lendormin tablets
UK: not marketed
Chloral hydrate
ATC: N05CC01.
DDD: 1000 mg po / pr
ICD-10: G47
Half-life: 8 h
Contra-indications: hepatic and renal impairment
Adverse effects: G/I disturbances
Oral liquid
NL (FNA product): 500 mg / 5ml
UK: 500 mg / 5ml and 200 mg/5ml
Welldorm: 143.3 mg / 5 ml
Tablets:
UK: Welldorm, (cloral betaine) 707 mg = 414 mg chloral hydrate
Dose 1-2 tablets at bedtime, max 5 tabs (2000 mg) daily
Rectal
NL: FNA product
Enema 150 mg/ml; 100 ml.
Suppository 300 mg, 500 mg, 750 mg, 1000 mg.
Dose:
NL: 250 - 1000 mg, max 2000 mg
UK: 500 - 2000 mg, child 30-50 mg/kg, max 1000 mg
DDD: 1000 mg po / pr
ICD-10: G47
Half-life: 8 h
Contra-indications: hepatic and renal impairment
Adverse effects: G/I disturbances
Oral liquid
NL (FNA product): 500 mg / 5ml
UK: 500 mg / 5ml and 200 mg/5ml
Welldorm: 143.3 mg / 5 ml
Tablets:
UK: Welldorm, (cloral betaine) 707 mg = 414 mg chloral hydrate
Dose 1-2 tablets at bedtime, max 5 tabs (2000 mg) daily
Rectal
NL: FNA product
Enema 150 mg/ml; 100 ml.
Suppository 300 mg, 500 mg, 750 mg, 1000 mg.
Dose:
NL: 250 - 1000 mg, max 2000 mg
UK: 500 - 2000 mg, child 30-50 mg/kg, max 1000 mg
Flunitrazepam
ATC: N05CD03
DDD: 1 mg po / parenteral
ICD-10: G47
Dose: 0.5 - 1 mg, max 2 mg
Max level after 25 to 115 minutes
Half life: 16 - 35 h, active metabolites 23 - 33 h
Hepatically cleared
Contra-indications: myasthenia gravis, respiratory insufficiency
UK: only available on private prescription, not listed in the BNF.
NL: Rohypnol, subject to the Opiumwet [Controlled Drugs Act], 1 mg and 2 mg tablets
DDD: 1 mg po / parenteral
ICD-10: G47
Dose: 0.5 - 1 mg, max 2 mg
Max level after 25 to 115 minutes
Half life: 16 - 35 h, active metabolites 23 - 33 h
Hepatically cleared
Contra-indications: myasthenia gravis, respiratory insufficiency
UK: only available on private prescription, not listed in the BNF.
NL: Rohypnol, subject to the Opiumwet [Controlled Drugs Act], 1 mg and 2 mg tablets
Pills, potions and poisons
Comparing formularies, the British National Formulary (BNF) and the Dutch Farmacotherapeutisch Kompas. Using the ATC-code (Anatomical Therapeutical Chemical) for the drug, accompanying DDD (Defined Daily Dose) and International Classification of Disease (10th edition), I attempt to find similarities and differences. I'm updating my knowledge on the subject, after suspending activities in the profession for some time.
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