Wednesday, February 10, 2010

Fentanyl Citrate Sublingual Dosing And Stability

Fentanyl S/L:

- Use: incident pain

- Onset of action: 5-15 minutes

- Peak effect: within 20 minutes

- Duration of action: maximum 45minutes

- Supplied: 100mcg/2ml ampoules (Sublimaze®) – glass ampoules.

* Needs special authorization for Alberta Blue Cross

- Note: decreased saliva production can delay absorption of sublingual fentanyl

- If administered sublingually, the drugs have to remain there for at least 5 minutes.
- Oral bioavailability of fentanyl is negligible and therefore this medication cannot be taken orally.
- Patients are generally unable to keep more than 1.5ml to 2ml under the tongue before it dribbles into the mouth, rendering it inactive.

- Determine the maximum amount of liquid that can be held under the tongue using the cold water technique (pt should be able to feel cold water trickling down throat).

o Max 1.5 ml – 2ml (CHR long term care formulary)

o Max 0.5 ml – 1ml (cold water test)

- Fentanyl must remain under the tongue for at least 5 minutes to be absorbed.

o Oral bioavailability of fentanyl is negligible and therefore this medication cannot be taken orally.

- Any remaining/extra fentanyl in the amp should be drawn up to a syringe and kept in the fridge.

CHR Incident Pain Protocol*

Step 1: Fentanyl 12.5mcg (0.25ml)

Step 2: Fentanyl 25 mcg (0.5ml)

Step 3: Fentanyl 50 mcg (1ml)

Step 4: Fentanyl 100 mcg (2ml)

- Opioid naïve pt: start at Step 1.

- If the pt is opioid tolerant, then start at Step 2.

- If pt unable to tolerate the volume in a single dose then the volume may be given in 2 doses at an interval of 5-10minutes apart. (ie: 2ml – take 1ml twice 5 minutes apart).

- After 10-15 minutes, if the initial dose appears to be insufficient, then the same dose may be repeated up to 2 further doses, at 10-15 minute intervals.

- Consider moving to the next step of the protocol if the maximum number of doses (3) is required to achieve comfort. One may move to the next step of the protocol after one hour of the last dose of fentanyl.

- The Incident Pain Protocol may be used up to q1h.

Side Effects:

Drowsiness, sedation, nausea and vomiting. Respiratory depression is dose dependent, it could potentially occur with an initial fentanyl dose greater than 200mcg IV.

Undiluted fentanyl citrate 50 mcg/mL was tested for stability in polypropylene syringes. The fentanyl citrate injection was filled into polypropylene syringes that were then capped off. The samples were stored for 28 days under refrigeration at 5 °C and at room temperature of 22 °C exposed to light. No change in color or clarity occurred. No loss of fentanyl citrate at either set of storage conditions occurred when evaluated using stability-indicating HPLC analysis.

*Hecq JD, Boitquin LP, Venbeckbergen DF et al. Effect of freezing, long-term storage, and microwave thawing on the stability of ketorolac tromethamine. Ann Pharmacother. 2005; 39:1654-8. [PubMed 16159993]

[Accessed Feb 10/10: Handbook on Injectable Drugs - 15th Ed. (2009)]

Pharmacy On-Call (Calgary Pharmacy) will premix syringes which are stable for 1 week.

*Calgary Health Region Long Term Care Formulary: fentanyl citrate injection.


Friday, February 5, 2010

Drug Interaction: Cyclophosphamide and Allopurinol

*Interaction detected between allopurinol and cyclophosphamide, MAJOR increased toxicity (increase myelosuppression, nausea and vomiting) as per Micromedex Online
(Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically).

Onset: Delayed

Severity: Major

Documentation: Good

Summary: There may be an increase in cyclophosphamide levels and prolongation in half-life of cyclophosphamide (Anon, 1974; Stolbach et al, 1982).


The Boston Collaborative Drug Surveillance Program examined the incidence of bone marrow depression in a series of 160 patients, 95 of whom were controls, during combined allopurinol use with either cyclophosphamide or other cytotoxic drugs (Anon, 1974). Their results indicated that the frequency of bone marrow depression in those patients who received allopurinol and cyclophosphamide was 57.7% as compared to 18.8% in those who did not receive allopurinol. In addition they noted that mortality may be somewhat higher in allopurinol recipient patients.

One study has reported that concomitant allopurinol and cyclophosphamide therapy results in significant elevations of cyclophosphamide cytotoxic metabolites, which may contribute to the increased bone marrow depression observed during concomitant therapy (Witten et al, 1980).

*At our centre and in this individual case, patient was on allopurinol 100 mg daily continuously for management of gout. The patient was to start FEC. After discussing with treating physician, there was insufficient time to temporarily discontinue allopurinol without delaying treatment. Therefore, it was decided to monitor CBCs carefully - that is, weekly (at least for the first cycle). It will then be decided if allopurinol will be held at all next cycle.

One possible recommendation would be to hold allopurinol for 5 days before and 2 days after chemotherapy treatment. This is based on half-life of active metabolite of allopurinol, oxypurinol, being 18-30 hours and cyclophosphamide's 3-12 hours.


Targeted Therapy Online Learning

1. OnTarget: Common Side Effects Of Targeted Therapy

"To Build Confidence and Skill in the Prevention and Management of Common Side Effects of Targeted Oncology Therapy"

- Oct. 2009
- The Canadian Council on Continuing Education in Pharmacy has awarded this program 10 CEUs.
- Exp: Aug. 19 2012

"Who created this Resource Guide

A committee of practicing oncology pharmacists, experienced in hospital and community pharmacy practice, in conjunction with an expert review panel and in collaboration with the Groupe d’étude en oncologie du Québec, developed this Resource Guide."
2.Caring for Oncology Patients: Tips and Tools for Managing Targeted Therapy
- An Ongoing Online CME/CE Curriculum
- This is a series of CEU modules from Projects In Knowldge.
- Currently, they have 12 different modules in the curriculum.
Note: CE Information: Pharmacists

Projects In Knowledge® is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.
- They can be used as accredited CEUs for Alberta pharmacists.


Wednesday, February 3, 2010

"MIB","MAB" & "NIB" News

*As per Medscape:

February 2, 2009 — Trastuzumab (Herceptin, Roche) has been approved for use in the treatment of HER2-positive gastric cancer by the European Commission. This is the first approval in the world for this label extension for trastuzumab, which is already marketed for use in the treatment of HER2-positive breast cancer.
*As per OncoSTAT:
A new drug has been found to slow the progression of advanced kidney cancer. The drug, pazopanib, was tested in a phase III study among 435 patients...Pazopanib targets multiple pathways involved in cancer cell growth and is an angiogenesis inhibitor. The drug is administered orally. Using supportive evidence from this study, the Food and Drug Administration approved pazopanib in October 2009 for the treatment of advanced renal cell carcinoma. The research results were published in the January 25 online issue of the Journal of Clinical Oncology.

*Also from OncoSTAT:
CORONADO, Calif. (EGMN) - Smokers with metastatic non-small cell lung cancer were able to tolerate much higher doses of the targeted therapy erlotinib than were their nonsmoking counterparts in a small, ongoing phase II clinical trial.

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About Onco-PRN

Welcome and thanks for visiting Onco-P.R.N. - The oncology website with a focus on all things oncology pharmacy/pain/palliative care-related. It is intended to be an information resource for those pharmacist and relevant health care professionals involved in whatever fashion with cancer and palliative care. Stay tuned for the latest and greatest links and information with respect to: oncology medications, continuing education, pharmaceutical care initiatives, pain and symptom control, supportive care topics, and whatever else that might fit into the theme.

*Note: This website is not affiliated with Alberta Health Services (AHS) or CAPhO and the opinions expressed herewithin are that of the author(s).

Pharmacy History

"The earliest known compilation of medicinal substances was ARIANA the Sushruta Samhita, an Indian Ayurvedic treatise attributed to Sushruta in the 6th century BC. However, the earliest text as preserved dates to the 3rd or 4th century AD.
Many Sumerian (late 6th millennium BC - early 2nd millennium BC) cuneiform clay tablets record prescriptions for medicine.[3]

Ancient Egyptian pharmacological knowledge was recorded in various papyri such as the Ebers Papyrus of 1550 BC, and the Edwin Smith Papyrus of the 16th century BC.

The earliest known Chinese manual on materia medica is the Shennong Bencao Jing (The Divine Farmer's Herb-Root Classic), dating back to the 1st century AD. It was compiled during the Han dynasty and was attributed to the mythical Shennong. Earlier literature included lists of prescriptions for specific ailments, exemplified by a manuscript "Recipes for 52 Ailments", found in the Mawangdui tomb, sealed in 168 BC. Further details on Chinese pharmacy can be found in the Pharmacy in China article."

From Wikipedia:

Journal of Palliative Medicine - Table of Contents

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