Presentation on theme: "Intranasal Medications in Hospice"— Presentation transcript:
1Intranasal Medications in Hospice A Novel method of pain, dyspnea, seizure and anxiety control.
2Disclosures Off Label Medications will be discussed (all the indications are “on label” but the delivery method is “off label”)
3IN medications and off-label use What is “off-label” useUse other than FDA approved specific indications in specific subpopulations by specific route of deliveryIs it OK to use drugs “off-label”Yes – in fact is is expected this will occur and this actually helps advance medical care – supported by FDA, supreme court, standards of care practice, etcWe all do it and its not only legal, it is expected to occur.In fact – about 80% of critically ill children and 40% of adults are treated with “off label” medications (Hospice?)Failure to provide off label can result in malpracticeExample - N-acetylcysteine for Tylenol overdose
4Case 1: Patient with bony metastasis with breakthrough pain A 65 year old female with metastatic breast CA to her spineEvery time she gets up to use the toilet, she suffers severe pain. She also has spontaneous spells of severe pain even at rest (despite baseline opiate therapy).Solution: Prior to movement and/or during spontaneous breakthrough pain she self administers 30 mcg of intranasal sufentanil (30 mcg – 0.6 ml of generic IV sufentanil)Within 5 minutes her pain is improvedAt 15 minutes the patient easily tolerates movement to go to the toilet or conduct other activities.
5Case 2: Episodic breathlessness A 73 y.o. man with metastatic carcinoma tolungs complains of severe dyspnea and cough.RR = 30, O2 saturation 62%, air hunger.Solution: You administer 50 to 150 mcg of intranasal fentanyl – (Fentanyl compounded to 500mcg/ml).In 3 minutes he has improved symptomaticallyAt 7 minutes his RR = 12, O2 saturation = 94%.He self delivers 100 mcg IN fentanyl on an as needed basis for the remainder of his care – using it about 7 times/dayHe dies comfortably within one week, having no further severe dyspnea/air hunger issues.
6Case 3: Neuropathic pain A 59 y.o. man with ALS who suffers extreme neuropathic pain with any contact to his skin.Is already on high doses of opiates to point of sedation and inability to interact with familyFamily cannot touch him due to exacerbation of his painSolution: You administer 50 mg of intranasal ketamine – (100 mg/ml – 0.5 ml total).In 10 minutes he can be touchedHe is able to back off the opiates and be somewhat more alert so he can interact more and touch his loved ones for the last weeks of his life6
7Case 4: Dementia with spells of severe agitation An 86-year old man with dementia, end stage cardiovascular disease suffers intermittent spells of agitation and violent behavior not amendable to pain medication.He is agitated, powerful and dangerous to home assistants and to himself.Solution: You administer 5-10 mg of IN midazolam (titrate) and 10 minutes later he is calm.
8Last case: Seizing patient 55 y.o. with metastatic melanoma – has brain metastasis and seizures.Suffers from recurrent seizures that often progress to status epilepticus.Has been transported to ER multiple times simply to control seizuresRectal diazepam is unsuccessful at controlling the seizure.Solution: Intranasal midazolam is given and within 3 minutes of drug delivery he stops seizing. This is implemented as home therapy and his EMS/ER trips drop off 80%.
9Advantages of IN medications in Hospice Ease of use and convenienceRapidly effective - onset within 3-10 minutesShort acting – no long side effects from drugNo special training is required to deliver the medicationNo shots are needed – Totally PainlessNo needle stick risk, no infection riskPatients (and family) really like this approachWorks even if patient cannot swallow or has N/VSocially acceptable (no rectal drugs)Better than sublingual (faster onset, higher drug levels)Titratable to effect – can re-dose every 5-15 minutesInexpensive –use generic or compounded drug
10Understanding IN delivery: Key concepts First pass metabolismNose brain pathwayBioavailability
11First pass metabolism Nasal Mucosa: No first pass metabolism Gut mucosa: Subject to first pass metabolism
12Nose brain pathway Olfactory mucosa, nerve The olfactory mucosa (smelling area in nose) is in direct contact with the brain and CSF.Medications absorbed across the olfactory mucosa directly enter the CSF.This area is termed the nose brain pathway and offers a rapid, direct route for drug delivery to the brain.BrainCSFHighly vascular nasal mucosa
13BioavailabilityHow much of the administered medication actually ends up in the blood stream.Examples:IV medications are 100% bioavailable.Most oral medications are about 5%-10% bioavailable due to destruction in the gut and liver.Nasal medications vary:Midazolam 75+%Fentanyl and Sufentanil 80+%Naloxone 90+%Lorazepam, ketamine, Romazicon, etc, etc
14Optimizing Bioavailability of IN drugs CriticalConceptMinimize volume - Maximize concentration0.2 to 0.4 ml per nostril ideal, 1 ml is maximumMost potent (highly concentrated) drug should be usedMaximize total absorptive mucosal surface areaUse BOTH nostrils (doubles your absorptive surface area)Use a delivery system that maximizes mucosal coverage and minimizes run-off.Atomized particles across broad surface areaBeware of abnormal nasal mucosal characteristicsMucous, blood and vasoconstrictors reduce absorptionSuction nose or consider alternate delivery route if present
15Potential indications for intranasal medications in Hospice: Breakthrough pain control – Opiates, ketamineThis will be the main focusEpisodic breathlessness – OpiatesMinor commentsSedation- Benzodiazepines, ketamine, dexmedetomidineSeizure Therapy – Benzodiazepines
16Intranasal Opiates for pain: Literature support Mercadante, Current Med Res Opinion 2009Compared IN Fentanyl (compounded) to OTFC (Actiq) for cancer breakthrough painProspective, Randomized, crossover trialResults: (see next slide)IN fentanyl worked fasterMore patients achieved meaningful pain control77% preferred nasal to Actiq lollipops
17Mercadante 2009 Intranasal vs buccal: 33% pain reductionMercadante 2009Intranasal vs buccal:Meaningful pain reduction 11 minutes vs 16 minutesPreferred by 77%Much faster onset of pain control on VAS for 33% and 50% drop in pain scores50% pain reduction
18Intranasal Opiates for pain : Literature support Kress, Clinical Therapeutics 2009Compared IN Fentanyl (compounded) to placebo plus standard therapy for cancer breakthrough painProspective, Blinded, Randomized, crossover trialResults: (see next slide)IN fentanyl showed significant pain reduction by 5 minutesMore INF patients achieved meaningful pain controlOnly 14% of INF used rescue drug, while 45% of control group used rescue drug
19Kress, 2009 Intranasal Fentanyl vs standard therapy: Much faster onset of pain control on VASWell toleratedImpression of pain control “good to very good” in 75% vs 31%
20Intranasal Opiates for pain : Literature support Good, Palliative Med 2009Investigated efficacy of generic IN sufentanil for cancer breakthrough pain(Sufentanil is 10 times as potent as fentanyl)Prospective trialResults: (see next slide)IN sufentanil worked fast and was safe at home94% preferred IN sufentanil to prior methods
23Intranasal Opiates for dyspnea: Literature support Sitte, Intranasal fentanyl for episodic breathlessness, J Pain & Symptom Management 2008Case series describing their experience with IN fentanyl for breathlessnessTheir pharmacy compounds the drug for themHave used in over 200 patients successfullyHave not seen patients overuse or significant side effects
24Intranasal Ketamine for pain: Why ketamine?NMDA receptor blocker – different site than opiatesDoses times less than anesthetic dose are all that is needed for pain control (analgesia)Side effects are dose dependent – so rare side effectsAlternative option to opiates, ideal for neuropathic pain (common in cancer, radiation injury to nerves, MS, ALS, etc)24
25Intranasal Ketamine for pain: Literature support Carr, Pain 2004Compared IN Ketamine (generic 100 mg/ml) to placebo for breakthrough painProspective, Randomized, crossover trial1 atomized spray (10 mg) q 90 sec to 5 doses maxResults: (see next slide)VAS drop in pain 26.5 mm vs 8 mmOnset of pain relief 10 minutesNo side effects at this dose25
26Carr 2004 Intranasal Ketamine: Meaningful pain reduction in 10 minutes Low doseNo side effectsAlternative therapy when opiate failing26
27Intranasal Ketamine for pain: Literature support US Army IN ketamine dataCompared IN ketamine to IV morphine for severe painIN ketamine (50 mg) as fast and as good as IV morphine (7.5 mg) w/o side effects.27
28IN Midazolam for adult sedation Hundreds of articles showing efficacy in sedation in children and in some adult studies outside the hospice setting.No actual published literature in hospiceMany discussions demonstrating sublingual benzodiazepines work – so nasal should work as well or better (see
29IN Midazolam for adult sedation Hollenhorst, AJR 2001: IN midazolam for MR imaging in adultsResulted in “sizable reduction in MR imaging related anxiety and improved MR image quality”Tschirch,Eur Radiology 2007: IN midazolam prior to MRI in adults97% success rate in anxiolysisManley, Brit Dental 2008: IN midazolam prior to dental therapy in agitated, mentally disabled adults93% success rate in sedation prior to oral procedures
30IN Midazolam for adult seizures Scheepers, Seizure 2000: Is intranasal midazolam an effective rescue medication in adolescents and adults with severe epilepsy?84 adult seizures treated, 79 successfullyMuch preferred to rectal and more effectiveOther: Numerous studies demonstrate successful, safe home, EMS and ER therapy for seizures.This is now standard of care in Australia/NZ and becoming very common in USA
31Contact and Educational Information Educational web site(s) with extensive literature on this topic: