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Lofexidine

Lofexidine (Britlofex) is an alpha2-adrenergic receptor agonist commonly used to alleviate some of the physical symptoms of opiate withdrawal by decreasing the release of norepinephine and epinephrine. It helps to lessen physical withdrawal symptoms such as chills, sweating and cramps, but will not eliminate the symptoms. It will not stop cravings either.[1] Lofexidine effects blood pressure less than clonidine[2], so is safer for detox outside of an inpatient setting I.E. home detox. [3][4]

Contents




[top]Introduction to Lofexidine



[top]Using Lofexidine


THe initial dosage should be 0.8mg per day in divided doses. The dosage may be increased by increments of 0.4 to 0.8mg per day up to a max of 2.4mg daily. Max single dose should not exceed 0.8mg. [5]The amount required will depend on a number of factors. For example, those who are undergoing an acute detox (cold turkey) will need a higher dose than those commencing lofexidine treatment at the end of a taper. The typical duration of treatment for a detox without opiate substitution is 7-10 days, however some user made guides recommend is use for a longer duration, especially with "cold turkey" or steep taper detoxes [6] It is recommended to gradually reduce the dose, rather than stopping suddenly, to avoid the risk of rebound hypertension, which not only could be unpleasant, but potentially harmful to health

[top]Ways of Administration


Lofexidine is administered orally, as the hydrochloride salt and is available as 0.2mg tablets.

[top]Effects of Lofexidine

[top]Combinations with Lofexidine

Naltrexone may be used in combination with lofexidine as part of an inpatient detoxification treatment. In one study, lofexidine was compared to a combination of lofexidine and nalrexone for detox purposes. Withdrawal symptoms were significantly less severe on days 47, and 913, in the naltrexone/lofexidine combination group than lofexidine alone[7] Lofexidine in combination with naltrexone also reduced post detox relapses and reduced the effect of cravings caused by stress, stress-induced opiate craving, and negative emotions [8]
Naloxone has also been used, with similar results. Overall abstenance rates were not different for naloxone/lofexidine versus lofexidine alone, but reported/subjective withdrawal symptoms were lower for the combination group[9]

Lofexidine may also be user in conjunction with opiates as part of a taper [10] however when used as part of a slow taper is not shown to significantly increase success rates, and appears to be more useful for quick tapers or cold turkey detoxes. Useful guides to utilising lofexidine in methadone/buprenorphine tapers can be found in the thread: http://www.drugs-forum.com/forum/showthread.php?t=76991


According to NHS guidlines, the following medications may also be prescribed to offer further symptomatic relief, for no longer than 21 days[11]:
  • Diazepam: For agitation
  • Zopiclone: For insomnia
  • Buscopan: For stomach cramps
  • Ibuprofen: For analgesia
  • Loperamide: For diarrhoea

[top]Different Uses for Lofexidine



[top]Pharmacology of Lofexidine

During opiate withdrawal, levels of catacholeamines like adrenaline and noradrenaline are significantly elevated, and are responsible for some of the physical effects of opiate withdrawal. Lofexidine stimulates receptors in the brain that monitor the levels of adrenaline and noradrenaline in the blood. The brain believes that catecholamine levels are higher than they really are, causing signals to be sent to the adrenal medulla, which is part of the adrenal glands that sit above the kidneys. The signals cause the adrenal glands to lower catecholamine production, which lowers the amount in the bloodstream. This lowers the heart rate and blood pressure, offering some relief from the physical withdrawal symptoms

Lofexidine is a structural analogue of clonidine. It is an imidazoline with a high affinity for α2-adrenergic receptor subtypes. This makes it less likely to cause hypotension than non-selective α2-adrenergic agonists [12]
When taken orally lofexidine has a very high bioavailability, in the range of around 90%. Average time to peak plasma concentration is 3 hours, but can vary from 2-5. Half life is approximately 11 hours, meaning that a steady state for plasma concentration is reached after approx 2 days (55hours)[13][14]
There are few studies available on the metabolism and excretion of lofexidine, but one study using radiolabeled C14 showed "significant
hepatic metabolism [glucuronidation] with four metabolites detected. The glucuronide metabolites accounted for 50% of those identified. Approximately 10% of the drug appears unchanged in the urine."[15]The main metabolite found was 2,6-dichlorophenol, which was excreted in urine as "two O-glucuronic acid conjugates" [16]


[top]Chemistry of Lofexidine

IUPAC name: 2-[1-(2,6-dichlorophenoxy)ethyl]-4,5-dihydro-1H-imidazole
CAS number 31036-80-3
Molar mass: 259.132 g/mol


[top]The Dangers of Lofexidine

Lofexidine should be used with caution if you suffer from severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease or chronic renal failure and in patients with bradycardia or hypotension.[17]
Lofexidine should not be taken if you are pregnant or breast feeding or have underlying psychosis or mental health[18]

Lofexidine can cause hypotension and bradycardia, though not as severely as clonidine, so caution should be taken when standing up quickly, getting out of a hot bath, or any situation in which you are chaning posture quickly. If you feel dizzy, light headed or faint, do not drive or operate machinery.

As Lofexidine may cause drowsiness and sedation, interactions may occur when taken in combination with
alcohol, sedatives, anti-hypertensive agents and tricyclic antidepressants. Particular risk arises when pharmacokinetic and pharmacodynamic interactions may occur e.g. concurrent use of alcohol or sedatives.[19]

Overdosage may cause hypotension, bradycardia and sedation.[20]

[top]Summary of side effects

BritLofex tablets may sometimes cause the following:
dry mouth or throat
dry nose
sleepiness
light-headedness or dizzyness upon standing
slow heart beat
[21]


[top]Legal Status of Lofexidine

Not controlled. Prescription only medicine

[top]USA

Lofexidine has not yet been approved by the FDA for use in the USA, however it is undergoing phase III trials [22]

[top]EU

[top]UK

Lofexidine has been used in an estimated 20 000[23] detoxifications over 13 years in the UK, where it is marketed by Britannia Pharmaceuticals as Britlofex. It is a prescription only medication and is approved for home and inpatient detox

[top]Ireland



[top]Popularity of lofexidine over time

[top]The Latest Lofexidine Threads

  Article / Page Starter Last Post Comments Views
gman2858
17-04-2014 09:07
by Nefret Go to last post
7 203
pharmaboy
17-04-2014 07:33
by Nefret Go to last post
24 22,412
BiffdaBearKiller
17-04-2014 06:33
by trdofbeingtrd Go to last post
81 2,431
DoctorHermit
17-04-2014 06:26
by TheBigBadWolf Go to last post
1 34
junkiegirl110
17-04-2014 04:36
by D0pe Go to last post
4 172
had enough
17-04-2014 03:37
by had enough Go to last post
82 4,447
JasonO
17-04-2014 03:02
by JasonO Go to last post
18 617
shotz
16-04-2014 23:07
by vervain Go to last post
4 106


[top]References

  1. ^ http://www.patient.co.uk/medicine/Lofexidine.htm
  2. ^ http://www.ncbi.nlm.nih.gov/pubmed/6890374
  3. ^ http://www.drugs-forum.com/forum/local_links.php?action=jump&catid=133&id=4559
  4. ^ http://www.sciencedirect.com/science/article/pii/S0376871698000404
  5. ^ http://www.medicines.org.uk/emc/medicine/7119/SPC/BritLofex+Tablets+0.2mg/#POSOLOGY
  6. ^ http://www.drugs-forum.com/forum/showthread.php?t=76991
  7. ^ http://www.sciencedirect.com/science/article/pii/S0376871699001167
  8. ^ http://www.drugs-forum.com/forum/showthread.php?t=91820
  9. ^ Bearn J, Bennet J, Martin T, Gossop M, Strang J The impact of naloxone/lofexidine combination
    treatment of the opiate withdrawal syndrome. Addiction Biology 2001; 6(2): 147-156
  10. ^ http://www.drugs-forum.com/forum/showthread.php?t=76991&highlight=lofexidine
  11. ^ http://www.nhft.nhs.uk/mediaFiles/downloads/30503881/MMG025.pdf.pdf
  12. ^ Cox, S. and Alcorn, A. (1995) Lofexidine and opioid withdrawal. Lancet, 345, 13851386.
  13. ^ http://www.ncbi.nlm.nih.gov/pubmed/18393298
  14. ^ http://www.medicines.org.uk/emc/medicine/7119/SPC/BritLofex+Tablets+0.2mg/#PHARMACOKINETIC_PROPS
  15. ^ http://www.nacd.ie/publications/LofexidineReport.pdf
  16. ^ http://www.ncbi.nlm.nih.gov/pubmed/6880242
  17. ^ http://www.medicines.org.uk/emc/medicine/7119/SPC/BritLofex+Tablets+0.2mg/#INTERACTIONS
  18. ^ http://www.nhft.nhs.uk/mediaFiles/downloads/30503881/MMG025.pdf.pdf
  19. ^ http://alcalc.oxfordjournals.org/content/36/5/426.full
  20. ^ http://www.drugbank.ca/drugs/DB04948
  21. ^ http://www.drugs-forum.com/forum/showthread.php?t=92535
  22. ^ http://www.solsticeneuro.com/docs/USW%20RELEASE%20-%20FINAL%20REV%2010.10.pdf
  23. ^ Strang, J., Bearn, J. and Gossop, M. (1999) Lofexidine for opiate detoxification: review of recent randomised and open controlled trials. American Journal on Addictions 8, 337348.


Contributors: Alfa, Docta, davestate Gold member
Created by davestate Gold member, 12-04-2012 at 21:37
Last edited by Docta, 13-04-2012 at 08:33
Last comment by Docta on 13-04-2012 at 10:38
3 Comments, 9,564 Views

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