Hello all,
As I seem to have experienced a repeat of my anal fissure, I wanted to know a bit more about Diltiazem cream (or Anoheal in the UK) and to fully understand the drug and if recurrence was normal. I also wanted to know if the supply I had in the fridge was still okay, or if I should get some more. Basically I wanted to know the full ins and outs of the drug, so went away and did some research. I feel better informed now, so thought I would share my conclusions with everyone here. The usual caveats apply in that I am not a Doctor or anything, and this is only my own conclusions. Anyhow hope it's useful to someone out there.
Apologies if there are any typos. Feel free to disagree with my findings ;-) Apologies if someone else has posted something similar elsewhere.
Anoheal (Topical diltiazem) - Questions and Answers Questions
1. How does it work?
2. How should it be used?
3. How long should you use it?
4. When will I see improvements?
5. What is the shelf life?
6. What are the side effects?
7. What is the success rate?
Answers in short:
Anoheal works by relaxing the anal sphincter and increasing the amount of blood to help with the healing process. It's applied to the anus as a topical cream. It should be used for at least 8 weeks, with some trials testing for 12. You should see some significant improvement after around 3 weeks of usage. The product should be usable for at least 3 months if stored in the fridge. A small number of people experience headaches (up to 5%) and some (up to 15%) experience anal itching, although this may be controllable with a barrier cream
The long version:
1.
How does it work? Anoheal (Topical diltiazem) is an unlicensed (in the UK) topical treatment for anal fissures. The term
unlicensed simply means the manufactures have not yet provided statistical clinical evidence that the product works and is safe[1]. However a number of trials have been conducted and the empirical evidence highly suggests the product meets this criteria[2]. As of 2012 Anoheal was at phase 3 of testing[11] – phase 4 being the licensed product[12]. However in 2014 it appears development of the product was discontinued[14] although there is no issue obtaining the product via the NHS on prescription.
Diltiazem is a calcium channel blocker and vasodilator[3][15]. The surface lining of blood vessels contain calcium receptors which regulate the contraction and relaxation of the blood cell. A calcium channel blocker blocks calcium from entering the cell and causes the cell to relax[4]. A Vasodilator is an agent that widens the blood vessels causing increased blood flow[5].
Following a tear in the lining of the anal sphincter the body attempts to repair the wound. In order to grow new tissue the a process called Angiogenesis is required. This is a process where new blood vessels form from pre-existing vessels [6]. The increased tone (pressure) of the sphincter, compared to other parts of the body, inhibit this process. The use of diltiazem reduces sphincter tone and increases blood flow allowing the repair process to be more effective[7].
2.
How should it be used? Diltiazem (Anoheal) cream is applied to the opening, and “just inside” the anus twice a day (morning and evening) in the location of the fissure. The usual recommended amount is 2.5cm of cream[7], although other recommendations refer to a “pea-size” as sufficient[8]. It is normally recommended a stool softener is used in conjunction with the product to reduce trauma during bowel movements.
3.
How long should I use it? The normal recommended usage period is 8 weeks[9], although recommendations vary between 6 and 12 weeks[10]. It is important to continue to use the product for the prescribed period of time. Patients sometimes stop using the treatment after symptoms improve only to relapse due to insufficient healing[9].
4.
When will I see improvements? A study comparing a placebo with diltiazem at 4% and 2% strengths showed a significant pain redcution for both strengths at week three[16]. My own personal experience was a relief from pain after about the same period.
5.
What is the shelf life? Most references point to a normal recommended expiry (after opening) of 4 weeks with refrigerated use. However a recent article[13] suggests a much more conservative “in-use stability” of 4 weeks at 25ºC (room temperature) and 6 months if stored below 25ºC. If stored for 4-7 days above 25ºC the product can be returned to the refrigerator with no change to the shelf life (6 months).
A recent supply obtained personally on the NHS in May 2016 had an expiry date of November 2018! The usage guide advised to keep the medicine refrigerated and to not use past the expiry date. In conclusion a 6 month shelf life seems reasonable. In my summary above, I have suggested 3 months.
All references advise to avoid freezing, and to destroy post expiry.
What are the side effects? The main side effect are headaches (1-5%) and anal itching (5-15%)[18]. My personal experience included a mild headache upon first using the product which did not repeat. I also experienced anal itching but have been able to control this with products such as Savalon.
What is the success rate? Numerous clinical trials have been performed. A summary of some of them are as follows:
All trials using 2% diltiazem
Nelson 2012, 200 adults, 6-8 weeks, 18-58 years. 80% healing, 12.5% recurrence[17]
Sanei 2009, 102 adults, 12 weeks, 17-61 years. 67.7% healing, recurrence not reported[17]
Abd Elhady 2009, 160 adults, 8 weeks, 17-70 years, 80% healing, 65% recurrence[17]
Samin 2012, 134 adults, 12 weeks, mean age 46+/- 16, 43% healing, 17.6% recurrence[17]
Suvarna 2012, 200 adults, 6 weeks, 18-65 years, 69% healing, 10% recurrence[17]
References:
[1]
https://www.nice.org.uk/advice/esuom3/ifp/chapter/Licensing-medicines[2]
https://www.nice.org.uk/advice/esuom3/ifp/chapter/Summary-of-possible-benefits-and-harms[3]
https://www.nice.org.uk/advice/esuom3/chapter/Key-points-from-the-evidence[4]
https://www.bhf.org.uk/research-projects/investigations-into-calciumsensing-receptor-mechanisms-in-the-vasculature[5]
https://www.drugs.com/drug-class/vasodilators.html[6]
https://en.wikipedia.org/wiki/Angiogenesis[7]
http://www.stmarksfoundation.org/uploads/docs/patientinformationleaflets/PIL%20Diltiazem.pdf[8]
http://cambridgebowelclinic.co.uk/Conditions/Anal-Fissure[9]
http://www.oxfordpelvicfloor.co.uk/PDFs/rectogesicanoheal.pdf[10]
https://www.nice.org.uk/advice/esuom3/chapter/Overview-for-healthcare-professionals[11]
http://www.biospace.com/News/ventrus-biosciences-inc-unveils-positive-results/260088/source=TopBreaking[12]
http://www.nhs.uk/conditions/medicinesinfo/Pages/Safetyissues.aspx[13]
https://www.sps.nhs.uk/medicines/diltiazem/[14]
http://adisinsight.springer.com/drugs/800019493[15]
https://pubchem.ncbi.nlm.nih.gov/compound/diltiazem#section=Top[16]
http://www.biospace.com/News/ventrus-biosciences-inc-unveils-positive-results/260088/source=TopBreaking[17]
https://www.nice.org.uk/advice/esuom3/chapter/Evidence-review-efficacy[18]
https://www.nice.org.uk/advice/esuom3/chapter/Evidence-review-safety