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Magistraal bereide ketamine cremes voor neuropathische pijnen

magistrale_bereiding.jpgHet internet is een boeiende bron van allerlei ervaringen op allerlei gebied, en dus ook op het gebied van cremes die je kan inzetten bij neuropathische pijnen. Hier een tweetal voorbeelden uit weblogs. Onze focus hier ligt op ketamine en de invloed van ketamine creme.

In ons Instituut voor Neuropthische Pijn (INP) hebben we na jaren ontwikkelingswrk een aantal speciale pijnstillende cremes geproduceerd, waaronder de ketamine 10% creme in INP basis. Deze 10% ketamine INP creme bevat een speciaal ontwikkelde basis creme waarin 10% rademisch ketamine is opgelost. De basis bevat op haar beurt 1.5% PEA, en deze PEA creme versterkt de ontstekingsremmende en pijnstillende werking van de ketamine.

Onze creme is gebleken uitermate effectief te zijn, en vrij van problematische biwjerkingen. De cremes in deze verhalen zijn echter gebaseerd op het zogenaamde PLO gel, een gel waarmee wij ook begonnen zijn, maar dat bleek snel niet optimaal te zijn. Momenteel maken we gebruik van een goed smeerbare creme.   

In het stuk hieronder is ook sprake van klachten van patienten over een dunne, waterige en brekende creme, terwijl de apotheker beklemtoonde dat de formulering volgens hem juist was. Dat probleem hebben we met onze cremes opgelost, terwijl de werking ervan superieur is. 

Ketamine 10% gel

1. I just got the cream that my PM had compounded at the pharmacy. It is a Ketamine 10% cream with PLO gel.

2. My daughter was prescribed a cream that has a mix of 10% ketoprofen,5% ketamine, 5% gabepentin, 5% lidocaine, in a lipophylic base. I remembered a thread a while back that people had responded to about creams and how important bases were so when I had the pharmacist create this, I had him make the smallest dose for the prescription and then we could tweak it as necessary. We applied it after warming the foot–usually moist heat and massaged it in for up to four minutes, moistening it as it became tacky. The pharmacists said this was the best way to ensure its absorption. She felt some relief with the cream for breakthrough pain.

Het toevoegen van ketoprofen is zinloos, NSAID’s werken bij neuropathische pijnen niet. De combinatie ketamine en gabapentine is logisch gezien de werkingsmechanismen en de lidocaine geeft een toegevoegd direct effect.

3. To make this short, he prescribed a combination pharmacutical lotion that works so well on the skin pain I have. I thought you all might like the formula.Here goes: KETO10/FLEX1/LIDO10/KETAMIN2.5. The pharmacist mixed it into an approx 8 oz container.  I don’t have regular insurance, so my cost was $55.00. A bargin considering the fact that within one minute after I rub a little on my toes, foot and leg, the breakthrough doesn’t exist; it is GONE. On top of that, it has lasted for over 24 hrs on several ocassions.

4. I use a Ketamine gel 3 times a day. It’s 15% Ketamiine, 10% Lidocaine and 2% Clonidine. I rub it in gently and then wrap my finger (what’s left of it) with Saran Wrap so that none of it evaporates. It does help. but it’s no magic bullet.

5. I use a cream that is 10% ketamine hydrochloride with some other ingredients… I typically use it on the entire top of one foot, about 1/3 of one calf, on one upper arm, and about 75% of my back. I am allowed to use it 4 times a day.I don’t use it right after getting out of the shower, or when my skin temp is really warm, as it seems to work a lot more then… I have had my tongue feel numb before from doing this but have had no other problems.Oh… and one time, my massage therapist was putting it on for me after a session. It was the first time she applied it. She was expecting a thicker cream. It is almost a watery liquid. When she went to pour a small amount onto my back, a lot came out, and so she just rubbed it in. Again, I think my skin was warm from the massage…. I did get a light-headed feeling for about half an hour. This was using about 3 times the normal amount. I did not feel really impared…

6. I use a cream that is a little bit like yours. Here is what mine is.2% amitriptyline hydrochloride 2% bupivacaine hydrochloride (local anesthetic) 5% gabapentin, 5% ketaprofen (the NSAID Orudis)10% ketamine hydrochloride2% lidocaine”in lipoderm base” the “base” pharmacist uses makes ALL the difference in how the cream works.

The cream was thin, watery – hard to apply. I called the pharmacy and asked to be sure that it was even the right prescription. The druggest said he had trouble mixing it and worried about it being to thin. He said he would order in a different base for my refill. So… when I ordered it again, it was thicker, a little bit greasy, but it worked a lot better. Still it was not nearly the strength of pain relief as the very first little jar I got from the expensive place.Then, my employer changed insurance carriers. Their mail order pharmacy did compounding but did not use ketamine. Now I had to try to find a new compounding pharmacy that would do something with ketamine.

FINALLY found one. I talked to the pharmacist, and he said he had made up a cream for his uncle who had terrible shingles, used several bases till he found one that allowed the medications to “glide through the skin” taking the medication right through the skin layers to the nerves. He said the less expensive bases do not allow for the medications to glide through the skin as easily. He took the time to look up RSD (website I gave him) and called me back the next day. I thought that was GREAT!! That way, he knew what I had, and needed it for. Now he understood for RSD, you need the medication to go deep into the tissue to get to the nerves – unlike a base you would use for a dermatology reason, where you would want the base to let the medication stay on the skin surface to treat acne for example. Like his uncle did for his shingles. He thought he knew just what I would need – but would need to order it. Did I mind waiting a couple extra days? Not a problem!! I would gladly wait a couple extra days!When I got the cream from this pharmacist – I was amazed at the difference. It worked really well. Then, my RSD ramped up a few notches – spread all the way down my back. I talked it over with my doctor and we increased the ketamine from 5% to 10% (like in the script I gave above). WOW what a difference. It still does not make my pain “GONE” like yours does Michael… I wish it did… as I do not take any pain meds and wish something would make the pain gone!! But, this cream does take a great deal of the edge off.

I have noticed that this stronger cream does make my tongue numb and I feel a bit woozy if I put to much on my body. The first day I used it where I would normally… my entire back, shoulders, upper arms, neck and lower face, and my foot… and went off to work… a couple hours later I started feeling a bit odd and I asked a co-worker if I looked stoned, as I felt like it. The next time I used it, I just put it all over my back… didn’t get the woozy stoned feeling, but my tongue did get numb. Next time I go back to the doctor, I will ask for the lower strength cream for most areas, and just get this stronger one for the worst areas.I would hate to get a DUI because of ketamine cream. Not sure this can happen, but would hate to be denying myself pain meds because of safe driving only to get a DUI because of the cream. Anyway, if you have tried a cream like this, and it has not worked — try asking the pharmacist if he can try a different base for you. It may well be the answer to having it work for you. I have 4 different creams with all the exact same meds – just four different bases — and they all work at different levels — with one not working at all and one working really well and the other two falling in between.

My compounding pharmacy provides Ketamine 10% and Lidocaine 10% patch.Looks like a very large bandaid, doesn’t hurt to take it off either. I’ve tried to go without it but the sensitivity is too bad. The numbness last for awhile after you take it off while bathing, so that is nice.

Cremes in ons instituut

In ons instituut ontwikkelen we cremes, op basis van inzichten in de farmacokinetiek van de substantie die we in de creme formulering brengen, en op basis van de fysisch chemische eigenschappen van het vehiculum. Zo hebben we o.a. een racemische ketamine creme ontwikkeld. Racemisch, omdat uit onderzoek gebleken is dat de halfwaarde tijd van de S ketamine enantiomeer langer is in aanwezigheid van de R isomeer. [1]

Het succes van een topicale cream is namelijk afhankelijk van de concentratie van de analgetische stof, de samenstelling ervan en de samenstelling van het vehikel. Al deze aspecten verdienen aandacht, om de pijnstillende werking optimaal te laten zijn. We hebben in ons instituut een ontwikkelteam, waarbij we samen met een gekwalificeerde apotheker nieuwe prototypes van pijnstillende cremes toetsen.

Juli 2010, Jan M. Keppel Hesselink, MD, PhD

Referentie

[1] Ihmsen H, Geisslinger G, Schüttler J. | Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine. | Clin Pharmacol Ther. | 2001 Nov;70(5):431-8.

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