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Thursday, December 10, 2009

Opioids In The News Part 1


Opioids In The News Part 1: Does Morphine Stimulate Cancer Growth?



Morphine was first isolated in 1803 by the German pharmacist Friedrich Wilhelm Adam Serturner, who named it 'morphium' after Morpheus, the Greek god of dreams.



Let's take a look at some recent, amazing associations made by the media regarding opioids!



As GeriPal stated:



Over the last week Reuters, ABC news, MSNBC,
BBC News, and more than 75 other outlets reported on how two "two new studies
add to growing evidence that morphine and other opiate-based painkillers may
promote the growth and spread of cancer cells."


Pallimed, on the same topic stated:


The headlines all blared hyperbolic and false
oversimplifications of the impact of the research. Now I am no opioid apologist,
but I do have to recognize that I spend a great deal of my education to
patients, families, staff, and other doctors de-stigmatizing opioids so they may
be used effectively for good pain control while balancing their manageable
risks. So while I nearly always am defending appropriate opioid prescribing, I
also want to recognize if there is potential harm in its use.


GeriPal goes on to state:



All these articles (most stemming from an
initial Reuters report) discussed the recent presentation by a group from the University of Chicago on the mu-opioid antagonist
methylnaltrexone (otherwise known as Relistor or “that new opioid induced
constipation medication”). This work, as presented at a meeting in Boston, revealed that use
methylnaltrexone prevented tumor-cell proliferation and migration in cultured
lung cancer cells.


The most important take home point is that none
of these studies actually looked at opioid use (although many of the news
articles vaguely cite these studies as evidence for morphine’s deleterious
effects on cancer). Even if you want to argue that these were high quality
studies and there is a clear benefit of regional anesthesia, opioids should not
be singled out as the cause.


Their take home message = “There is no clinical evidence that morphine, or any other opioids, cause real harm through stimulating cancer growth.” The evidence will definitely have to be more substantial before we sound the alarms for the general public!



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Friday, October 23, 2009

Medication Pearls For Practice: Methadone In Cancer Pain Overview

METHADONE

History2:

  • Methadone was developed in Germany (it is synthesized from 1,1-diphenylbutane-2-sulfonic acid and dimethylamino-2-chloropropane) in the late 1930s in anticipation of possible shortages of raw opium during the upcoming war and possible blockades by the enemy.
  • The drug was given the trade name Dolophine from the Latin dolor meaning pain (Cf. Dipidolor for piritramide, Dolantin for pethidine, and the "-dol" or "-phine" ending in so many trade and chemical names for analgesics of all types in German, English, French, and other languages) and was not named either in honour of or personally by Adolf Hitler, despite what Tom Cruise and the Church Of Scientology will have you believe.

Class1: Opioid analgesic.

Indications1:

  • Moderate–severe pain (an alternative in cases of intolerance to other strong opioids, morphine poorly-responsive pain)
  • pain relief in severe renal failure
  • cough
  • Also treatment of opioid addiction.

Potential uses1,3:

  • Neuropathic pain (refractory)
  • painful mouth ulcers: It has been used effectively as a mouthwash
  • Restless Leg Syndrome: methadone (5 to 20 mg) have been administered in divided doses, 1 to 2 hours prior to bedtime.3

Pharmacology/Pharmacodynamics1:

  • Methadone is a synthetic strong opioid with mixed properties. Thus, it is a μ-opioid receptor agonist, possibly a -opioid receptor agonist, an NMDA-receptor-channel blocker, and a presynaptic blocker of serotonin re-uptake.1
  • Methadone binds to Mu (μ), Kappa (κ), and Delta (δ) opioid receptors, producing analgesia as well as typical opioid side effects.6 (See Notes section at end of document for opioid receptor information.
  • There is no predictable relationship between methadone plasmalevel and pain relief.
  • Methadone is a racemic mixture; L-methadone is responsible for most of the analgesic effect, whereas D-methadone is antitussive.
  • Methadone is a non-acidic and lipophilic drug which is absorbed well from all routes of administration.
  • Partly because of its lipid-solubility methadone has a high volume of distribution with only about 1% of the drug in the blood.
  • Methadone accumulates in tissues when given repeatedly, creating an extensive reservoir.

Pharmacokinetics1:

  • While methadone can be administered by a number of routes: oral, rectal, intravenous, intramuscular, subcutaneous, epidural, and intrathecal – it is most commonly given orally in either tablets or solution.
  • Oral methadone is readily absorbed and very long-acting.
  • By comparison, its bioavailability is nearly 3 times that of morphine and its half-life is about 10 times greater than morphine.6
  • Bio-availability 80% (range 40–100%) PO.
  • Onset of action <30min PO, 15min IM.
  • Time to peak plasma concentration 4h PO; 1h IM.
  • Plasma halflife 8–75h; longer in older patients; acidifying the urine results in a shorter halflife (20h) and raising the pH with sodium bicarbonate a longer halflife (>40h).

*methadone has an extended terminal half-life, up to 190 hours. This half-life does not match the observed duration of analgesia (6-12 hours) after steady state is reached. This long half-life can lead to increased risk for sedation and respiratory depression, especially in the elderly or with rapid dose adjustments.5

  • Duration of action 4–5h PO and 3–5h IM single dose; 8–12h repeated doses.

Cautions:

In 2006, after a review of deaths and life-threatening adverse events (e.g. respiratory depression, cardiac arrhythmia) associated with unintentional overdose, drug interactions, and prolongation of the QT interval, the FDA in the USA issued a safety warning about the use of methadone. This highlighted the need for:

  • physicians to be fully aware of the pharmacology of methadone
  • close monitoring of the patient when starting methadone, particularly when switching from a high dose of another opioid
  • slow dose titration, and close monitoring of the patient when changing the dose of methadone
  • warning the patient not to exceed the prescribed dose.

Palliativedrugs.comconsiders that cumulation to a variable extent is bound to occur, particularly in elderly patients, and recommends p.r.n. dose titration to minimize the associated risk

Dosage:

  • Dose titration is different from morphine because of the wide interindividual variation in the pharmacokinetics of methadone. Several guidelines exist for switching from morphine to methadone.
  • Because of its long half life, plasma levels of methadone may take up to 10 days to stabilize. There must be a cautious balance between inadequate analgesia due to insufficient dosing and systemic toxicity due to excessive dose during the titration phase.6
  • For detailed dosing guidelines: http://pain-topics.org/pdf/OralMethadoneDosing.pdf
  • http://www.palliativedrugs.com/methadone.html#guidelines
  • From Lexicomp4:

Acute pain (moderate-to-severe):

Opioid-naive: Oral: Initial: 2.5-10 mg every 8-12 hours; more frequent administration may be required during initiation to maintain adequate analgesia. Dosage interval may range from 4-12 hours, since duration of analgesia is relatively short during the first days of therapy, but increases substantially with continued administration.

Chronic pain (opioid-tolerant): Conversion from oral morphine to oral methadone:

  • Daily oral morphine dose <100 mg: Estimated daily oral methadone dose*: 20% to 30% of total daily morphine dose
  • Daily oral morphine dose 100-300 mg: Estimated daily oral methadone dose: 10% to 20% of total daily morphine dose
  • Daily oral morphine dose 300-600 mg: Estimated daily oral methadone dose: 8% to 12% of total daily morphine dose
  • Daily oral morphine dose 600-1000 mg: Estimated daily oral methadone dose: 5% to 10% of total daily morphine dose.
  • Daily oral morphine dose >1000 mg: Estimated daily oral methadone dose: <5% of total daily morphine dose.
  • *in divided doses (commonly q12h, q8h or q6h)
  • Subsequent switching from methadone to other opioids can be difficult. In one series 12/13 patients experienced increased pain±dysphoria.1

Conversion:

Dose Adjustments1,6:

  • Renal and hepatic impairment do not affect methadone clearance.
  • When considering the use of methadone, the difficulty of subsequently switching from methadone to another opioid should also be borne in mind.
  • Methadone is an alternative strong opioid for patients with chronic renal failure who would be at risk of excessive drowsiness±delirium with morphine because of cumulation of morphine-6-glucuronide.2
  • Methadone is poorly removed by haemodialysis.30 However, for moribund patients, alfentanil is probably a better choice.
  • Unlike morphine or meperidine, the metabolism of methadone produces no active or toxic metabolites.
  • Only a minor fraction of methadone is cleared by the kidneys. Except in end-stage renal failure, it is usually unnecessary to adjust the dose of methadone because of renal disease.
  • For patients with severe chronic liver disease, the elimination half-life of methadone increases. However, mean plasma concentrations and dose-adjusted mean plasma concentration do not significantly differ from patients with mild or moderate liver disease (Säwe, 1986), and no dose adjustments are typically required for this degree of hepatic failure (Eap, 2002).

Monitor:

  • sedation
  • confusion
  • respiratory depression

Other Side Effects:

Interactions1:

  • Methadone is principally metabolized by CYP3A4
  • CYP2D6, CYP2C9, CYP2C19 and CYP1A2 may play minor roles
  • MAOIs may prolong and enhance the respiratory depressant effects of methadone.
  • Carbamazepine, phenobarbital, phenytoin and rifampicin increase the metabolism of methadone
  • amitriptyline, cimetidine, ciprofloxacin, fluconazole and SSRIs decrease its metabolism
  • Methadone increases plasma zidovudine concentration.
  • Efavirenz, lopinavir-ritonavir, nelfinavir, nevirapine and ritonavir (all antiretroviral agents) may reduce plasma methadone concentrations.
  • Other medications, especially the benzodiazepines, may act synergistically with methadone, increasing the apparent effect of methadone and likelihood for life threatening adverse events.
  • Certain medications may potentially influence the concentration of methadone indirectly. For example, topiramate is a carbonic anhydrase inhibitor and increases urinary pH alkalinization; Topamax PI 2007). Alkalinization of urine has been shown to increase the half-life of methadone to an average of 42 hours (Baselt 2004). Therefore, when used concomitantly with topiramate, methadone may reach higher plasma levels.
  • Check: http://pain-topics.org/pdf/OralMethadoneDosing.pdf
  • Always check reliable drug interaction sources such as Lexicomp and Micromedex

Patient Handout:

  • Great patient information (print page 4-5 of the document)

http://pain-topics.org/pdf/MethadoneHandout.pdf

Advantages:

  • Inexpensive
  • can use in patients with morphine allergy
  • ok with renal patients
  • generally less constipating
  • more effective for neuropathic pain in comparison with other opioids
  • suited for the management of difficult pain syndromes, particularly where activation of the NMDA recptors has resulted in CNS sensitization - hyperanalgesia and allodynia {Note: Without the d-isomer [racemic d- & l-isomer used in North America ] less impressive results may be observed.}

Interesting…

Sources/References:

  1. http://www.palliativedrugs.com/methadone.html
  2. http://en.wikipedia.org/wiki/Methadone
  3. Micromedex Online
  4. Lexicomp Online
  5. http://www.eperc.mcw.edu/FastFactPDF/Concept%20075.pdf
  6. http://pain-topics.org/pdf/OralMethadoneDosing.pdf
  7. Pallium Palliative Handbook 2008 www.pallium.ca

inical Effects

*NOTES:

Receptor > Clinical Effects:

  • Mu (μ): Analgesia, Euphoria, Respiratory depression, Physical dependence, Miosis, Decreased gastric motility
  • Kappa (κ ): Analgesia, Sedation, Respiratory depression
  • Delta (δ): Analgesia, Dysphoria, Hallucinations

*Adapted from: Warfield and Fausett, 2002

*(one pt - I.R. – took 90 mg qid + 60 mg q2h for over 700 mg/day – max we’ve seen)

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Thursday, October 8, 2009

Medications In The Pipeline: Intranasal Fentanyl Spray Versus Oral Transmucosal Fentanyl Citrate

A comparison of intranasal fentanyl spray with oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised, crossover trial

Current Medical Research and Opinion, 10/08/09

“Mercadante S et al. – In this open–label, randomised, crossover trial, significantly more patients attained faster ‘meaningful’ pain relief with intranasal fentanyl spray (INFS) than oral transmucosal fentanyl citrate (OTFC), and more patients preferred INFS to OTFC.”

Results:

Among the intention-to-treat population (n ¼ 139):
• median time to onset of ‘meaningful’ pain relief was 11 minutes with INFS versus 16 minutes with OTFC; 65.7% of patients attained faster time to ‘meaningful’ pain-relief onset with INFS ( p50.001). PID was statistically significantly greater for INFS than OTFC from 5 minutes post-dosing.
• Significantly more INFS-treated breakthrough pain episodes achieved clinically important pain relief (_33% and _50% PI reduction) up to 30 minutes post-dosing.
• The proportions of episodes treated with INFS and OTFC achieving a PI reduction of _33% at 5 minutes were 25.3% versus 6.8% ( p50.001), and at 10 minutes were 51.0% versus 23.6% ( p50.001), respectively
• The proportions of episodes treated with INFS and OTFC achieving a _50% PI reduction at 5 minutes were 12.8% versus 2.1% ( p50.001), and at 10 minutes were 36.9% versus 9.7% ( p50.001), respectively.
• Both treatments were well tolerated. In the safety population (n ¼ 139), 56.8% (n ¼ 79) of patients experienced _1 AE during the trial. The only AE that occurred in _5% of patients in either treatment group was nausea. Among those patients who experienced serious AEs (13.7%, n ¼ 19), none were considered to be related to either study medication.
• There was a weak correlation between effective INFS doses and background opioid doses.

Treatment administration:
• Up to four episodes of BTP per day were treated with study medication, intranasal fentanyl spray (INFS), as described below.
• Intranasal fentanyl spray has recently received marketing authorization from the Committee for Medicinal Products for Human Use and will be launched under the trade name Instanyl (Nycomed, Denmark).
• Doses of 50, 100 and 200 mg fentanyl (using INFS solutions of 0.5 mg/ml, 1.0 mg/ml and 2.0 mg/ml, respectively) were taken as a single dose in one nostril. A second INFS dose was permitted 10 minutes after the first, if required, taken in the other nostril. Rescue analgesics were permitted 10 minutes after the second INFS administration if pain relief was still insufficient.
• The comparator medication, oral transmucosal fentanyl citrate (OTFC) (Actiq, Cephalon, USA), was used at six doses: 200, 400, 600, 800, 1200 or 1600 mg in the form of single compressed lozenges with integral oromucosal applicators. One lozenge equalled one dose. OTFC was administered according to manufacturer’s recommendations (15 minutes in the oral cavity between cheek and gum). A second OTFC dose was permitted 30 minutes after the first, if required. Rescue analgesics were allowed, as needed, 45 minutes (if a second OTFC dose was not taken) or 60 minutes (if a second OTFC dose was taken) after start of administration.

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Medication Pearls For Practice: Methadone And Sleep Apnea

"Medication Pearls For Practice" is a new column to be a regular feature here at Onco-PRN. With my role in the Pain and Paliative Care Clinic, expect a lot of pain and symtom control related medication topics. Of course, oncology medications will also be featured.

In this post, key points taken from the Pharmacist's Letter are in bold and italicized.

From: Canadian Pharmacist's Letter 2008; 15(10):241007

Medications that Can Exacerbate Sleep Apnea

“A number of medications, especially CNS depressants such as opioids, benzodiazepines, and muscle relaxants can potentially exacerbate sleep apnea.

*Recently, central sleep apnea has been reported with chronic opioid use and up to 30% of stable methadone maintenance treatment patients have central sleep apnea. In one study (n=50), patients on methadone maintenance therapy were found to have significantly less rapid eye movement (REM) sleep. Central sleep apnea occurred more often in non-REM sleep in methadone maintenance therapy patients. In contrast, respiratory disturbances occur more often during REM sleep with obstructive apnea. These patients had normal resting cardiac function.

*In another study (n=140), the association of methadone, non-methadone opioids, and benzodiazepines with sleep apnea was examined. In the study, patients taking methadone and benzodiazepines concomitantly were found to have a significantly higher rate of central sleep apnea. In the 33% of patients taking methadone, the median daily dosage of morphine equivalents was 187.5 mg/day. The median daily dosage of sustained-release opioids other than methadone in morphine equivalents was 187.5 mg/day. In 36% of patients taking benzodiazepines, the median daily dosage in diazepam equivalents was 15 mg/day. Results of the study showed that 75% of the patients had apnea/hypopnea episodes during sleep. Thirty-nine percent had obstructive sleep apnea, 4% had sleep apnea of an indeterminate type, 24% had central sleep apnea, and 8% had both central and obstructive sleep apnea. Increased dosage of methadone was associated with a higher incidence of central sleep apnea. In contrast, equivalent doses of non-methadone opioids were not found to be associated with increased risk for sleep apnea. The combination of methadone and benzodiazepine also caused significantly more sleep apnea. There are data suggesting that benzodiazepines could possibly inhibit methadone metabolism, prolonging its effect; therefore, this combination should be used cautiously.

In both of these studies presentation of central sleep apnea was atypical compared to those with chronic heart failure (no Cheyne-Stokes respiration, no crescendo-decrescendo pattern of tidal volume).

The cause of central sleep apnea associated with chronic opioid use is likely multifactorial, involving the change of sleep architecture (REM, non-REM, sleep stages, etc) and respiratory depression effect.

Patients with sleep apnea are more likely to experience exacerbation of symptoms when treated with opioids. It is especially important to use caution when titrating opioid analgesic doses in this patient population. The use of patient controlled analgesia (PCA) should be monitored closely in this patient population.”

Feel free to comment below and if you would like to contribute to this featured column topic, "Medication Pearls For Practice", email me at: chrisral@albertahealthservices.ca

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Thursday, October 1, 2009

Continuing Education And Certificate Programs

There are some great CEU programs out there. I wanted to highlight just a sampling of these.

Projects In Knowledge have some great individual CEUs, as well as various certificate programs. You can do individual courses or complete them all to obtain the certificate. All are free, but you need to register.

1. The Advanced Certificate Program: Lung Cancer Management
Curriculum I courses present a basic overview of management strategies for optimal personalized care of lung cancer patients. Curriculum II presents more-advanced courses that build on scientific advances and the topics covered in Curriculum I.

2. The Advanced Certificate Program: Breast Cancer Management
Curriculum I courses present a basic overview of management strategies for optimal personalized care of breast cancer patients. Curriculum II presents more advanced courses that build on new scientific developments and the topics covered in Curriculum I.

3. The Certificate Program in Advanced/Metastatic Colorectal Cancer features the very latest information about:
- Colorectal Cancer Diagnosis
- Colorectal Cancer Treatment
- Colorectal Cancer Disease Management

4. The Advanced Certificate Program in Hepatocellular Carcinoma

5. Caring for Oncology Patients: Tips and Tools for Managing Targeted Therapy
"The curriculum offered in this CME/CE program promises to be a timely and continuously updated source of practical information that can be immediately used in treating, monitoring, and managing side effects in cancer patients receiving targeted therapy."


Other CEUs to be had include:
- PainEDU CE Course:
"Interactive case-based learning modules address a range of topics in pain assessment and pain management. Articles and treatment recommendations explore a balanced approach to care with the patients who are prescribed opioids. Update your clinical skills, test your knowledge, and enhance your approach to care!"

- CaPHO's "HOPE" series of CE features topics such as: CINV, Epigenetics, and Molecular Biology of Cancer and Promise of Targeted Therapy.

- Advancing the Safe and Appropriate Use of Oral Chemotherapy Agents: An Interdisciplinary Educational Series for Healthcare Professionals

- http://www.oncologyeducation.ca/ - have to register


Feel free to post other CEUs you find in the comments.

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Tuesday, September 15, 2009

Onco P.R.N. Has Been Linked!

A great list of various Palliative Medicine blogs...Onco P.R.N. included!
http://www.pallimed.org/2009/09/updated-list-of-hospice-palliative.html

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Why You Should Comment On Blogs And How To

From an excellent Palliative Medicine blog, this article discusses why uou should post comments and is applicable to this blog as well:
http://www.pallimed.org/2009/08/why-you-should-comment-on-blogs-and-how.html

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Pain And Symptom Medication Info - Ketamine For Mucositis Pain

From MDLinx:

Ketamine mouthwash for mucositis pain
Journal of Palliative Medicine, 09/01/09

Ryan AJ et al. – Ketamine swish and expectorate may be a viable treatment option in refractory mucositis pain.

Methods
A retrospective chart audit was preformed on eight patients who received ketamine mouthwash (20mg/5mL) for refractory mucositis pain.

Results
All eight patients had mucositis pain refractory to a mucositis mixture (lidocaine, magnesium/aluminum hydroxide, and diphenhydramine) and opioids.
An improvement in mucositis pain was seen in over half (5/8) of the patients.
Four of eight patients had adverse effects that could have been associated with the ketamine mouthwash; all side effects were transient and subsided when the ketamine mouthwash was stopped.

The following articles discuss management of oral mucositis:

http://www.supportiveoncology.net/journal/articles/0502s113.pdf

http://www3.interscience.wiley.com/cgi-bin/fulltext/114078093/PDFSTART

If you have any other articles or information, please share below in the comments or email me at: chrisral@cancerboard.ab.ca

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Pain And Symptom Control Medication Highlights - Intranasal Fentanyl

Efficacy and tolerability of intranasal fentanyl spray 50 to 200 microg for breakthrough pain in patients with cancer: A phase III, multinational, randomized, double-blind, placebo-controlled, crossover trial with a 10-month, open-label extension treatment period

Clinical Therapeutics, 08/26/09

Kress HG et al. – Intranasal fentanyl spray (INFS), at 50, 100, and 200 micrograms, was associated with an onset of activity at 10 min and effective tx of breakthrough pain compared with placebo.

Methods
Phase III, double-blind, randomized, placebo-controlled, crossover trial 120 adults with cancer receiving a stable dose of long-term opioid tx for the control of background pain. Patients were treated at home with 50, 100, or 200 micrograms of INFS or placebo for 3 weeks, followed by a 10-month, phase when they received their effective dose of INFS.

Results
The pain intensity difference at 10 minutes (PID10) with INFS was 2-fold that with placebo.
The mean response rate with all 3 doses of INFS was 51.1% vs. 20.9% with placebo.
The prevalence of AEs was 19.8% (nausea [4.5%] and vertigo [1.8%]).

Of course, Onsolis (Fentanyl Buccal Film) was approved by the FDA back in July “for the management of breakthrough pain in patients with cancer aged 18 years and older who receive around-the-clock opioid therapy and are able to safely use high doses of additional opioid agents.”

"Onsolis can provide strong pain relief to patients who are opioid tolerant. But for patients who are not opioid tolerant, it can lead to overdose, sudden serious breathing difficulties and death," said Bob Rappaport, MD, director, Division of Anesthesia, Analgesia and Rheumatology Products in the FDA's Center for Drug Evaluation and Research, in an agency news release. "For this reason, Onsolis should be prescribed only under the safeguards provided by the FDA-required [risk evaluation and mitigation strategy] and by health care professionals knowledgeable about Onsolis and the use of potent opioid medications."

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Wednesday, August 26, 2009

Long-term Tamoxifen Use Linked To Second Breast Cancer



{Tamoxifen 3D - photo left}
Long-term tamoxifen use linked to second breast cancer:
http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20090825/tamoxifen_risk_090825/20090825?hub=Health
From The Canadian Press, “A new study suggests long-term use of tamoxifen is linked to an increased risk of a second type of breast cancer…another rare subtype of the disease increased by more than 400 per cent.”


Adjuvant Hormonal Therapy for Breast Cancer and Risk of Hormone Receptor–Specific Subtypes of Contralateral Breast Cancer
http://cancerres.aacrjournals.org/cgi/content/abstract/0008-5472.CAN-09-1355v1

From Cancer Res 2009;69(17):6865–70, “Compared with the breast cancer risk women in the general population have, breast cancer survivors have a substantially higher risk of developing a second primary contralateral breast cancer. Adjuvant hormonal therapy reduces this risk, but preliminary data indicate that it may also increase risk of hormone receptor–negative contralateral tumors…Compared with women not treated with hormonal therapy, users of adjuvant tamoxifen for 5 years had a reduced risk of ER+ contralateral breast cancer [odds ratio, 0.4; 95% confidence interval (CI), 0.3–0.7], but a 4.4-fold (95% CI, 1.03–19.0) increased risk of ER- contralateral breast cancer. Tamoxifen use for <5>

From U.S. News (HealthBuzz):
http://health.usnews.com/articles/health/2009/08/26/health-buzz-rare-risk-of-cancer-after-taking-tamoxifen-and-other-health-news.html
“The study's lead author (Dr. Christopher Li ) told HealthDay News he does not think women should be afraid to take the drug, stating that its benefits outweigh its risks. Tamoxifen is customarily given only for five years because there's no evidence that longer-term use has additional benefits.”

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Monday, August 17, 2009

Aspirin Use After Colorectal Cancer Diagnosis Associated With Improved Survival

New Study Finds Risks With Plavix-Aspirin Combination


A study published in JAMA August 12th, 2009 concludes:

Regular aspirin use after the diagnosis of colorectal cancer is associated with lower risk of colorectal cancer–specific and overall mortality, especially among individuals with tumors that overexpress COX-2.

The researchers explained:
"These results suggest that aspirin may influence the biology of established colorectal tumors in addition to preventing their occurrence. Our data also highlight the potential for using COX-2 or related markers to tailor aspirin use among patients with newly diagnosed colorectal cancer. Nonetheless, because our data are observational, routine use of aspirin or related agents as cancer therapy cannot be recommended, especially in light of concerns over their related toxicities, such as gastrointestinal bleeding."

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PharmQD: Pharmacist Social Network With Continuing Education and more

This is the link to the CE portion and they are grouped by topic - a lot of FREE ones, but some have associated costs:
http://www.pharmqd.com/ce

PharmQD promotes:

"Become a member of our interactive community. Collaborate and network with
your colleagues and trusted peers. Membership is free!"

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FDA issues final rules to help patients access investigational drugs

As HemOnctoday reported August 13th/09:
The FDA has published two new final rules explaining how critically ill patients can get access to investigational therapies when they are ineligible for clinical trials and do not have other treatment options.

The first rule, “Expanded access to investigational drugs for treatment use,”
clarifies procedures and standards with the aim of making investigational drugs
more widely available. It clarifies existing regulations and adds new types of
expanded access for treatment use. Under the final rule, expanded access to
investigational drugs for treatment use will be available to:

- Individual patients, including in emergencies.

- Intermediate-size patient populations.

- Larger populations under a treatment protocol or treatment investigational
new drug application (IND).

The second rule, “Charging for investigational drugs under an investigational
new drug application,” spells out the specific circumstances and costs for which
a manufacturer can charge patients for an investigational drug. The rule revises
the charging regulation to:

- Clarify the circumstances under which charging for an investigational drug
in a clinical trial is appropriate.

- Set forth criteria for charging for an investigational drug for the
different types of expanded access for treatment use described in FDA’s final
rule on expanded access for treatment use of investigational drugs.

- Clarify what costs can be recovered.

The agency has also launched a website for patients and physicians seeking more information about their options with regard to these investigational drugs. It includes information on treatment with an FDA-approved drug, treatment with an investigational drug as part of a clinical trial or obtaining access to an investigational drug outside of a clinical trial.
“With these initiatives, patients will have the information they need to help them decide whether to seek investigational products,” Margaret A. Hamburg, MD, commissioner of food and drugs, said in a press release. “For patients seeking expanded access to investigational drugs and biologics, the new rules make the process easier to understand.”

This is the direct link to the FDA post:
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm176526.htm

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Thursday, August 6, 2009

A Glimpse At The History Of The Pharmacist Profession


















{Photo: The Sibiu Pharmacy Museum in Sibiu, in the Transylvania region of Romania, is housed in a 1569 Gothic townhouse where the oldest pharmacy in Romania operated for over 150 years. The pharmacy was known as La Ursul Negru (The Black Bear), and likely looked nothing like this. While the museum has a vast collection of chemistry instruments ranging from the 15th century to the 19th, this beautiful pharmacy reconstruction dates from the 18th century.}

While not quite specific to the realm of oncology pharmacy I thought pharmacists from all fields would enjoy a look back at the roots of our profession. I stumbled upon this intriguing piece on pharmacist history whilst searching for something in WIkipedia. The last statment below is very interesting and amusing indeed.

In Japan, at the end of the Asuka period (538-710) and
the early Nara period (710-794), the
men who fulfilled roles similar to those of modern pharamacists were highly
respected. The place of pharmacists in society was expressly defined in the Taihō Code (701) and re-stated in the Yōrō Code (718). Ranked
positions in the pre-Heian Imperial court were
established; and this organizational structure remained largely intact until the Meiji Restoration
(1868). In this highly stable hierarchy, the pharmacists -- and even pharmacist
assistants -- were assigned status superior to all others in health-related
fields such as physicians and acupuncturists. In the Imperial household, the pharmacist was even ranked above the two personal physicians of the Emperor.

Of course, as Bob Dylan sang: "The Times They Are A-Changing."

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Wednesday, August 5, 2009

FDA Approves Bevacizumab To Treat Advanced Renal Cell Carcinoma

Pharmaceutical Company Genentech Announces Earnings


As Reported by The Associated Press. 2009 Aug 2:

Avastin (bevacizumab) received approval from the Food and Drug Administration
(FDA) for a new indication to treat advanced renal cell carcinoma. This is the
most common form of kidney cancer. The FDA approval adds kidney cancer
indication to the 5 others for this drug, which include treatment of breast,
colon, and lung cancers. Bevacizumab, a targeted therapy for cancer, is an
angiogenesis inhibitor. Genentech, the manufacturer of Avastin, announced
approval for the new indication on August 2.


From Medscape, Aug 4:

The US Food and Drug Administration (FDA) has approved a new indication for
bevacizumab intravenous infusion (Avastin, Genentech, Inc) for the treatment of
metastatic renal cell carcinoma. The recommended dose is 10 mg/kg every 2 weeks
in combination with interferon α-2a (9 MIU subcutaneously 3 times weekly).

Bevacizumab is a monoclonal antibody that works by binding to vascular
endothelial growth factor and preventing its role in angiogenesis, which
deprives tumors of blood, oxygen, and other nutrients necessary to support their
growth and metastasis.

Approval of the indication was based on data from a global, randomized,
double-blind, placebo-controlled phase 3 study — the Avastin in Renal (AVOREN)
study — of 649 patients with newly diagnosed metastatic renal cell carcinoma,
showing that the addition of bevacizumab to interferon α-2a significantly
increased progression-free survival by 67% compared with interferon α-2a alone
(10.2 months vs 5.4 months; hazard ratio [HR], 0.60; 95% confidence interval
[CI], 0.49 – 0.72).

Results also showed that the combination therapy significantly
decreased tumor size by 30% compared with 12% for interferon α-2a alone.
However, no improvements were observed in median overall survival on the final
analysis after 444 deaths (survival, 23 months vs 21 months; HR, 0.86; 95% CI,
0.72 – 1.04).

Adverse events reported in the study were consistent with the safety
profiles for bevacizumab and interferon α-2a, with fatigue (13%), weakness
(10%), proteinuria (7%), hypertension (6%), and bleeding (3%) most often
reported.

Bevacizumab previously was approved for the treatment of metastatic
colorectal cancer, nonsquamous non-small cell lung cancer, metastatic breast
cancer, and glioblastoma.

Read more...

Thursday, July 2, 2009

Researchers Question Cost-Effectiveness Of Cancer Drugs





"The widespread use of expensive cancer drugs to prolong patients’ lives by just
weeks or months was called into question by an article published Monday in the
Journal of the National Cancer Institute. Crunching data from published
studies, the authors found that treating a lung-cancer patient with Erbitux, a
drug that costs $80,000 for an 18-week regimen, prolongs survival by only
1.2 months. Based on that estimate, extending the lives of the 550,000
Americans who die of cancer annually by one year would then cost $440 billion,
they extrapolated. How to control escalating spending on end-of-life care is one
of the thorniest questions facing lawmakers working on the overhaul of the U.S.
health-care system. Some countries, like the United Kingdom, agree to pay
for expensive drugs only if they meet a certain threshold of efficacy, but no
such rationing exists in the U.S."
"June 29 (Bloomberg) -- Eli Lilly & Co.’s tumor-fighter Erbitux doesn’t prolong lung cancer patients’ lives enough to justify its $80,000 cost, U.S. scientists said in commentary published today. Erbitux added to other cancer drugs extends survival about 1.2 months more than chemotherapy alone, making the price too high for a “marginal benefit,” commentary in the Journal of the National Cancer Institute said. Erbitux, which Lilly markets with Bristol-Myers Squibb Co., generated $1.3 billion last year as treatment approved for other malignancies."
{Click on links (titles) for more information.}
{Thanks to Lynne Nakashima of the BC Cancer Agency for the above links}

Read more...

Navigating The Waters Of This Website/Blog

Replica Slave Ship The Zong Sails Up The Thames






My introductory post {Click here} last month highlighted what I'd like this website to evolve into.

This post will highlight some of the ways to get the most use out of the website/blog.

  • The "search" feature (located in the upper right-hand portion of the main page) allows you to search the website's contents, as well as the ability to search the web.
  • Articles are posted to the blog chronologically, with most recent displaying first.
  • You can search the archives of the blog (heading on the left about half way down), which are sorted again by date.
  • You can also search the site by "Labels" which is another heading on the left hand side. "Labels" are basically topics/subjects that I will assign to each post.
  • There are also oncology and pharmacy related "real-time" updates from OncologySTAT and Medscape, on the right-hand side of the website and some towards the bottom as well.
  • There is a link to my online bookmarks (located on the menu bar under the front page heading) via the "delicious" website, which feature useful websites that are pharmacy, oncology and pain & symptom control related (Click on "Favourites" on the Right hand side of that web site to get most commonly used bookmarks).
  • Also featured on the menu bar is the continuing education main link, and a link to the Onco-PRN online message board. On this separate web site there are various subjects to facilitate discussions and ask questions to other readers.
  • Finally, I have a "blog list", on the right-hand side as well, which features some blogs related to our field.

Again, I also recommend you sign up as a "Follower" by clicking on the relevant link on the left side. The process is easy and you can even use an existing google or yahoo account, amongst others. This will help establish a network of oncology pharmacists (or others with an interest in this area).

Please post comments below (or email me at christopher.ralph@albertahealthservices.ca ) for suggestions on information or links you would like to share or for me to post, or comments in general.

Read more...

Friday, June 5, 2009

SSRIs and Tamoxifen: Does the Combination Increase Recurrence?

Prozac Linked to Suicide Attempts and Violence




As recently reported by CTV: {excerpts from the article; data presented at ASCO May 31/09}

ORLANDO, Fla. — Breast cancer survivors risk having their disease come back if
they use certain antidepressants while also taking the cancer prevention drug
tamoxifen, worrisome new research shows...The new study, reported Saturday at a
cancer conference in Florida (ASCO), is the largest to look at the issue. It found that
using these interfering drugs -- including Prozac, Paxil or Zoloft -- can
virtually wipe out the benefit tamoxifen provides...Breast cancer recurred in
about seven per cent of women on tamoxifen alone, and in 14 per cent of women
also taking other drugs that could interfere -- mainly the antidepressants Paxil
and Prozac, and, to a lesser extent, Zoloft...No greater breast cancer risk was
seen in women taking the antidepressants Celexa, Lexapro or Luvox with
tamoxifen, and there are reasons to think that other antidepressants may be safe
as well, Epstein said..."This is a very controversial area," said Dr. Claudine
Isaacs, a breast specialist at Georgetown University's Lombardi Comprehensive
Cancer Center. "Until these data are absolutely clear, I would avoid drugs that
impact on tamoxifen metabolism."


From OncocologySTAT:
"SRIs, however, can also inhibit the 2D6 enzyme that converts tamoxifen to its
main active metabolite, endoxifen, thus possibly decreasing its efficacy."


Massachusetts General Hospital Centre For Women's Health posted an article in June '08 regarding interactions between tamoxifen and antidepressants. I discovered this post when searching for solutions after detecting the interaction via Micromedex/Lexicomp.
{Click here for link to article}.

The following table from the above mentioned article provides some guidance when faced with such a dilemma:

CPY2D6 Inhibitors

Strong Inhibitors (Should be avoided if
possible):

Paroxetine
Fluoxetine
Bupropion
Duloxetine

Moderate Inhibitors:
Sertraline
Citalopram/Escitalopram
Doxepin

Weak Inhibitors (Use not restricted by treatment with
tamoxifen):

Venlafaxine
Desvenlafaxine


If antidepressants are indicated in the treatment of a woman currently
taking tamoxifen, the following treatment recommendations have been made:
*If possible, avoid antidepressants, including fluoxetine and paroxetine, that are
strong inhibitors of the CPY2D6 enzyme (see the list of inhibitors above)
*If the antidepressant is being used solely for the management of hot
flushes, other agents, such as gabapentin, may be used instead
*If it is not possible to avoid these antidepressants, another option for postmenopausal women
only would be to switch from tamoxifen to an aromatase inhibitor, if medically
appropriate


Please post your comments below or email me at: chrisral@cancerboard.ab.ca

* Thanks to Scott Edwards, PharmD for the link to the CTV News article.

Read more...

Monday, June 1, 2009

Introducing...The Information Resource Blog For Oncology Professionals

At The Chemists



Welcome and thanks for visiting Onco-P.R.N. - The oncology blog 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 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.

I am a clinical pharmacist at the Tom Baker Cancer Centre in Calgary, Alberta, Canada. I currently practice in our outpatient Pain and Symptom Control Clinic, am also a member of our provincial IV committee, as well as spending time in rotation whether it be in the dispensary or the processing or checking IV regimens and orders.

Please post comments below (or email me at cral66@gmail.com ) for suggestions on information or links you would like to share or for me to post, or comments in general.

It is also recommended you sign up as a "Follower" by clicking on the relevant link on the left side (It is the sixth heading from the top). The process is easy and you can even use an existing google or yahoo account, amongst others. This will help establish a network of oncology pharmacists (or others with an interest in this area).

I'll end off my inaugural post with a link to an article discussing how a commonly used chemotherapeutic agent can erase finger prints! {Click on the link below.}
"Cancer drug erases fingerprints." {from BBC News}
I wonder if some criminal minds reading this might be already formulating ideas on how to make use of this!

Read more...
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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: http://en.wikipedia.org/wiki/Pharmacy#History_of_pharmacy

Journal of Palliative Medicine - Table of Contents

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