Pharmacy

Annunziata Lombardi 

Annunziata Lombardi is head of the compounding laboratory producing magistral  preparations at Farmacia Caputo, a family owned pharmacy in Nocera, Italy. She is a  founding member of the medical cannabis committee in 2017, and was a lead contributor to the regional medicinal cannabis reimbursement law. Annunziata has post graduate qualifications and professional interests in clinical pharmacy, pharmaceutical medicine formulation, clinical and traditional compounding, medicine quality control, and  regulatory affairs. Additionally, Annunziata directs a laboratory specialising in cannabinoid analysis, providing her insight to various analytical challenges. 

Training/Education

What training did you receive before  you started dispensing cannabis based medicines?
In 2013, The Italian Ministry of Health  had just passed a new law, and I started  considering the idea of preparing  medical cannabis . Despite scepticism from my family, colleagues and  physicians, I decided to challenge the  status quo and give this new therapy a  try. No formal training was available at  that time to prepare me. I still remember  my first order 10 years ago, receiving  three 5 gram pharmacy containers of  Bedrocan® flos. I was nervous. Now, I  have dispensed over 20,000 cannabis based medicine preparations, most as oil extracts for oromucosal administration. The number continues to  grow annually.

After an initial learning-by-doing phase, I  decided to improve my theoretical and  practical knowledge. I travelled to the  Netherlands to attended the Cannabis  Master Class in Leiden. This training  gave me insights which I have used in my daily laboratory practice. Since then,  I have linked in with experts in this field  with different backgrounds to create a  very fruitful network. In 2016, I was one  of the founders of the IEO (European  Oncology Institute), a cannabis working  group with organisations in Naples,  Milan and Modena.

Dispensing experience  

How long have you dispensed  cannabis-based medicines?
I started preparing and dispensing in  2014 as one of the pioneers in the  Italian market.  

Can you describe a typical patient to  whom you would dispense cannabis based medicines?
There is no typical patient because  cannabis-based medicines can be used  for all age groups and for multiple  pathologies. The Italian National Health  Insurance reimburses cannabis-based  medicines, as magistral prescription  preparations, for a limited number of  medical indications: anorexia/cachexia,  glaucoma, Tourette syndrome, spasms  and pain induced by chemotherapy,  vomit and lack of appetite in chemotherapy patients.

In my experience, the most recurrent  diseases are chronic pain, fibromyalgia  and neurological problems. There is  also a growing demand from patients  suffering from autism, anxiety, and sleep  disorders. 

Thinking about a first interaction with  a patient, how do you start a conversation about the safe and  effective use of cannabis-based medicines?
My role and duty as a pharmacist is to verify that the patient has correctly  understood the instructions given by  his/her physician. I explain the patient  the pharmacokinetic and pharmacodynamics interactions with  other medicines as well. 

How is that different to a follow-up  interactions at the pharmacy?
The follow-up with the patient covers  questions regarding the safety and  efficacy of the therapy. I normally use  the Medicine Use Review process to  interview the patient in a structured and  organised way, and keep records of  their feedback.
Additionally, I ask my patients about the  positive effects in terms of QOL,  symptoms improvement such as pain  relief, or seizure reduction, and the  adequacy of the dosage. Patients also  provide feedback on taste and  intolerances which is potentially used to  develop new formulations, and test new  carriers and excipients.  

Patient considerations

Thinking about a first interaction with  a new patient, how do you start a  conversation about cannabis-based  medicines? 

Assuming that the physician has clearly  explained the basics of the therapy, I  normally focus on the practical side of  administering the medicine.
If the administration route is inhalation, I explain how a vaporiser can be  operated, cleaned, and maintained. If oral administration is chosen, I talk  about the differences between oro mucosal and oral administrations, and  train the patient on the most effective  route.
Dosage is a crucial point as it often  determines the success or failure of a  therapy and the drop-out rate. Patients  are also interested in the reimbursement criteria and process of  the prescriptions, and how to properly  store the medicine. 

Are you aware of patients experiencing interactions with  cannabis-based medicines and other medicines?
Yes. Most side effects are caused by interactions with other medicines  because cannabinoids may modify our  metabolism and influence their  performance.

Administration

Oral dose forms (oil extracts) are an increasingly popular mode of  administration, what advice do you  give patients on safe use?
In Italy, cannabis extracts, for oromocosal dosing, account for 80% of  prescriptions. I train my patients on the  proper dosage to convert the mg of  active substance (THC and CBD)  prescribed by the physician into mL and/or drops of extract. This conversion  is different for every extract, and it is  based on the post-extraction HPLC  analytical results.
In Italy, pharmacists must analyse the  extract for cannabinoid content after  production and state this on the label before dispensing. This helps the  patient know the amount of active  substance taken. 

Vaporisation is an increasingly  popular mode of administration, what  advice do you give patients on safe  use?
I recommend the use a medical device  because it guarantees the quality and  the reproducibility of the therapy.  However, some patient cannot afford a  medical device and opt for another type  of vaporiser. In any case, I ask the  patient to pay attention to two aspects:  (1) the vaporiser temperature, because  naïve patients may experience major  side effects if the temperature is set too  high, (2) the timing of the onset of  action, which can be extremely rapid  with this administration route. 

What do patients say about the  administration of cannabis-based  medicines by vaporisation?
Patients who need an immediate effect  to control tremors, intense pain, and  seizures appreciate the rapid onset of  action provided by inhalation. The main  disadvantages of this route are: it is not  discrete and often cannot be used in  public spaces; the cost of the vaporiser  is high; some patients do not have the  pulmonary power to actively inhale. 

What special considerations should  pharmacists be aware of for patients  taking oral dose forms?
Pharmacists must inform the patient that  the onset of the oral dose form is slow  and can take up to 3 hours. The patient  must be aware of that and wait for the effect and not take additional medicine.

Safety

Are you aware of any patients that  have experienced interactions of  cannabis-based medicines with other  medicines? If yes, please describe the  major interactions.
Typical interactions take place with  neuroleptic medicines and lead to, for  example, increase in appetite,  dizziness, tachycardia, fatigue. 

What are the actual and potential complications with cannabis-based  medicines?
Oil extracts as well as inhalable  preparations are not tolerated by every  patient. New pharmaceutical forms with  improved bioavailability and usability, such as water-soluble solutions, dry  inhalable powders, sublingual tablets,  oral powders, and so forth, must be  developed in the future to access a  wider patient base.
Another critical aspect of this therapy is  the variability of the different Cannabis  strains [cultivars]. Current studies have not identified a clear correlation  between strain, type and quantity of  cannabinoids, pharmaceutical form, and  dosage and their effect on specific  medical indications. A structured and  large data collection using AI are  needed to make sense of this complexity and exploit this vast  pharmacological treasure.

What is the role of the pharmacy  profession in ensuring patient safety  with the use of these medicines?
For Italy it might be a bit different than  that of colleagues from other countries.  Here, we give a lot of importance to the  personalisation of this medicine. Doing  an extraction in the pharmacy rather  than buying standardised extracts from  the industry gives us full potential for  customisation by choosing different Cannabis strains [cultivars], oil carriers,  extraction methods, and concentrations. In this case the pharmacist role is to  make a high-quality product using a  safe and reproducible extraction  process. In Italy we have defined some  limits and parameters to control the  quality and acceptability of compounded cannabis extracts.  

Do you encounter diversion, misuse,  or abuse of cannabis-based medicines?
Yes, but I consider this phenomenon  limited to a very few cases. The  average quantity of cannabis per patient in Italy is relatively low. Indeed,  most Italian patients are using oral  extracts rather than inhaling or smoking,  which reduces the risk for abuse to a  minimum. 

How do you identify this issue in your  practice?
When I receive prescriptions with very  high dosage for inhalation in young  patients or the patient finishes the  medicine earlier than expected and comes back with a new prescription, I  normally become suspicious.
I call first the patient and try to understand why he/she increased the  dosage and ran out of medicine. After  that I may call the physician to cross check this information.

Medicine type/dose forms

How is cannabis-based medicines  different to storing and dispensing  other medicines (for both herbal  material and for oral dose forms)?
I store cannabis in a separate area with  restricted and recorded access.  Dispensing requires a magistral  prescription because it is an off-label  medicine. Moreover it is classified as  doping and narcotic which makes it  even more complicated. 

Are there any special considerations  you make when dispensing cannabis based medicines (i.e. oil extracts)?
I make sure that the patient has clearly  understood the therapeutic plan  prescribed by the physician, and I  check potential interactions with other  medicines. With oil extracts I pay  particular attention to the titration plan, and the use of pipette or graduated  syringe for the correct administration  under the tongue. 

Are there any special considerations  you make when dispensing a herbal medicine (as cannabis flos)?
I pay attention to the vaporiser and train  the patient on the use and setting of the  device. I prepare single doses weighted, milled (in some case whole  flower), packed and labelled individually  in aluminium bags. These are ready-to use and the patient takes a known and  precise quantity. 

Therapeutic regimen

What are the key benefits of using  cannabis-based medicines?
Almost no severe side effects. It  improves several medical conditions  where alternative medicines have low  efficacy or lead to important side  effects. Cannabis represents a new  frontier in medicine acting on modulating the endocannabinoid  system. 

What are the key risks of using  cannabis-based medicines?
I do not see major risks using oil  extracts and only a minor risk for abuse using flos. The bigger risk to make the  wrong choice in terms of strain [cultivar]  and dosage leading to poor results and  a high drop-out rate.

What do you think are pharmacy  practices that improve patient outcomes?
Correct and relevant information to the  patient. Collect feedback from all  patients and identify trends and  correlations between strain, dosage,  pharmaceutical form and concentration. Train physicians on cannabis magistral  prescriptions because the level of  clinical expertise is still relatively low.

How closely do pharmacists work with the prescribing doctor?
They have an extremely close relationship. There is an ongoing  interaction between the doctor, the  pharmacist and the patient to adjust the  therapy. In the context of cannabis based medicines, the pharmacist has  rediscovered their  dimension and vocation and is  recognised by doctors and patients as  in the triangle  Doctor-Pharmacist-Patient.

Final remarks

Do you have any good advice (tips) for pharmacists starting out?

• Be passionate about what you do. This is an exciting professional opportunity and it is nothing like dispensing finished drugs
• Be convinced that you are part the cannabis-based medicines revolution and this is just the beginning.
• Go to cannabis conferences and trainings in your country and abroad if you have the chance.
• Read scientific literature. There is lot of academic and clinical research going on.
• Collect feedback and data.
• Look for other professionals who share your interest. Do not stop at pharmacists but look for physicians, scientists, patients  and anybody who can help you enrich your knowledge.
• Build-up strong and solid relationships with physicians and patients.