Topical & Transdermal Medications
Christian Sinclair, MD
Kansas City Hospice & Palliative Care
October 8, 2008
Medication Routes
• Oral• Intravenous• Rectal• Intraosseous• Intrathecal• Inhaled• Optical• Topical
• Sublingual/Buccal• Subcutaneous• Intravesical• Intramuscular• Epidural• Insuffluation• Intravitreal• Transdermal
Indications for Alternate Route
• Unwilling or unable to swallow meds• Cancers of the head, neck and GI tract• Compromise of the GI tract
– Mucositis– Bowel obstruction
• Intolerable side effects during administration• Treating localized pain• Avoiding systemic side effects• Neonatal/pediatric populations
Topical versus Transdermal
• Topical– Treats at the site of medication placement
– Usually compounded, often non-branded
– Antibiotics for skin infection
– Steroid creams for rashes
• Transdermal– Treats via systemic delivery of the medication
– Usually branded and not compounded
– Hormone replacement, nicotine addiction, Duragesic
Variations
Factors affecting absorption
• Flow increases with– Increased concentration– Increased surface area– Decreasing skin thickness– Lipophillic compounds– Low molecular weights
Available Brand Medications
• Contraceptives/HRT
• Lidocaine
• Clonidine
• Nicotine
• EMLA
• Nitroglycerin
• Methylphenidate
• Estradiol
• Oxybutynin
• Estrogen
• Scopolamine
• Fentanyl
• Testosterone
Compounding Vehicles
• PLO – Pluronic Lecithin Organogel
• Can hold guest molecules which are solubilized in the gel
• DMSO
• Other proprietary gels
Other topical meds in Pubmed• Hormones-estriol and estradiol, DHEA, progesterone,
testosterone• NSAIDs-ketoprofen, diclofenac, piroxicam • SSRIs –fluoxetine, paroxetine • Antipsychotics-haloperidol, prochlorperazine • Levodopa• Morphine• Dexamethasone • Calcium channel blockers-diltiazem, nifedipine • Clonidine with gabapentin and ketamine• Lidocaine, tetracaine
Evidence for Topical Meds
• Poor to Fair
• Animal studies (cats) in small numbers
• Many are single dose studies
• Rare human drug level studies
• Rare human symptom studies
Topical Diclofenac
• OA, lateral epicondylitis
• 2% topical dicoflenac
• n=74, 14
• Improved pain, stiffness, physical function
• J Rheum 1999, Clin J Sport Med 1998
Topical NSAIDs
• Stay mostly in the dermis
• Can reach synovial fluid
• Efficacy ranges from 18-92%
EMLA Cream/Disc
• Typically used in the pediatric population
• 1G for 60 mins before efficacy
• Localized effect
• 5% emulsion preparation
• Combination of lidocaine and prilocaine
• Strong evidence base
• Patch 60 minutes provides 2 hours of relief
Amethocaine
• 1G amethocaine gel 30 mins
• Better results then EMLA in less time
Topical Ketamine
• No to minimal effect – With neuropathic or capsacin induced pain
• Ionotopheresis assisted delivery
• Open label showed long term effectiveness
• Often combined with amitriptyline
Lidocaine Patch
• 5% Lidocaine
• Topical not transdermal
• Indicated for Post-herpetic Neuralgia
• Tried in – CTS, OA, vaccinations, venipuncture
• Also available as lidocaine gel
Topical Opioids
• Opioid receptors on:– Peripheral nerves– Inflammed skin
• Morphine and metabolites not found systemically
• ? Wound healing mechanism– Up-regulate nitric oxide synthase
Topical Opioids
• Skin infiltration of tumor
• Nonmalignant skin ulcers
• Severe oral mucositis
• Knee arthritis
• Tenesmoid pain.
Pain. 1999 Mar;80(1-2):121-5.
Topical Opioids
• Mostly used for pressure ulcer pain• Relief modest for about 7-8 hours• Gel form
– 10 mg of morphine sulfate injection (10mg/ml)– in 8 gm of Intrasite gel– or gel infused dressing
• Also for burn wounds– MISS->Morphine Infused Silver Sulfadiazene
http://www.supportiveoncology.net/journal/articles/0506289.pdf
Topical Methadone
• Methadone 100mg in 10g Stomadhesive powder
• Varied results in wound application
• Analgesic effects of topical methadone: a report of four cases.
Clin J Pain. 2005 Mar-Apr;21(2):190-2.
Topical antidepressants
• Topical Doxepin combined with capsacin for chronic neuropathic pain
• Doxepin mouthwash improved oral mucosal pain in cancer patients
Transdermal Medications
Testosterone
• Transdermal Patch• Transdermal Cream/Gel
– Testim or Androgel 1% QD
• Injectable, oral, and buccal forms• Indicated for testosterone replacement therapy
– Increased lean body mass, decreased fat mass, increased bone mineral density, increased sexual activity and desire
Transdermal Nicotine
• Approved for nicotine replacement therapy
• Effects of nicotine– Increases glucose, epinephrine– Enhances serotonin and opiate receptors?– Stimulant, but also anxiolytic– Appetite suppressant
• Not indicated in naïve patients
Fentanyl Transdermal Patch
• Well studied
• 92% bioavailable
• Strong mu opioid agonist
• Lipophillic -> High CNS Concentration
• Reservoir and Matrix patches
• Affected by skin thickness and temperature
• Less constipating
Fentanyl Transdermal Patch
Source: Duragesic package insert
Source: Duragesic package insert
Scopolamine Transdermal Patch
• Motion sickness
• Opioid induced nausea
• Smooth muscle spasm
• Parkinson’s
• Drying secretions
• Pyrexia/Sweating
Scopolamine Transdermal Patch
• Belladonna alkaloid (Hyoscine)• Anti-cholinergic• Side effects:
– Drowsiness, dilated pupils, increased HR
• Initial bolus, then 120mcg/d x 3d• Plasma – 4hrs, Peak 24hrs• Post-auricular?• Cost: $8/patch
Transdermal ABHR
• Ativan (lorazepam)– 2 articles
• Benadryl (diphenhydramine)– Case reports
• Haldol (haloperidol)– One study
• Reglan (metoclopramide)– No studies
“Yes, you’re changed; you’ve got new ideas over here,” her friend continued.
“I hope so,” said Isabel; “one should get as many new ideas as possible.”
“Yes; but they shouldn’t interfere with the old ones when the old ones have been the right ones.”
Henry James, Portrait of a Lady
The Future
• More studies
• Med-Tats
• Micro-needles
• Needless jet injectors
• Ionotophoresis
• Phonophoresis
• Liposomal delivery
Review
• Topical vs. Transdermal
• Know the drug
• If it is branded, likely some efficacy
Bibliography
• Carnel SB, Blakesless DB, Oswald SG, Barnes M. Treatment of radiation and chemotherapy-induced stomatitis. Otolaryngol Head Neck Surg. 1990;102:326-30.
• Cerchietti LC, Navigante AH, Bonomi MR et al. Effect of topical morphine for mucositis-associated pain following concomitant chemoradiotherapy for head and neck carcinoma. Cancer. 2002;95:2230-2236.
• Flock P. Pilot study to determine the effectiveness of diamorphine gel to control pressure ulcer pain. J Pain and Symptom Management. 2003;25:547-554.
• Gallagher RE, Arndt DR, Hunt K. Analgesic effects of topical methadone; a report of four cases. Clin J Pain. 2005;21:190-192.
• 5. Kalso E, Tramer MR, Carroll D et al. Pain relief from intra-articular morphine after knee surgery: a qualitative systematic review. Pain. 1997;71:127-34.
Bibliography
• Krajnik M, Zylicz Z, Finlay I et al. Potential uses of topical opioids in palliative care – report of 6 cases. Pain. 1999;80:121-125.
• Picard PR, Tramer MR, McQuay HJ et al. Analgesic efficacy of peripheral opioids (all except intra-articular): a qualitative systematic review of randomized controlled trials. Pain. 1997;72:309-318.
• Poonawala T, Levay-young BK, Hebbel RP, Gupta K. Opioids heal ischemic wounds in the rat. Wound Repair Regen. 2005;13:165-74.
• Porzio G, Marchetti P. Topical morphine in the treatment of painful ulcers. J Pain and Symptom Management. 2005;30:304-305.
Bibliography
• Twillman RK, Long TD, Cathers TA. Treatment of painful skin ulcers with topical opioids. J Pain and Symptom Management. 1999;17:288-292.
• Vernassiere C, Cornet C, Trechot P et al. Study to determine the efficacy of topical morphine on painful chronic skin ulcers. J Wound Care. 2005;14:289-93.
• Zeppetella G, Paul J, Ribeiro MDC. Analgesic efficacy of morphine applied topically to painful ulcers. J Pain and Symptom Management. 2003;25:555-558.
• Zeppetella G, Joel SP, Ribeiro MD. Stability of morphine sulphate and diamorphine hydrochloride in intrasite gel. Palliat Med. 2005;19:131-6.
• Zeppetella G, Ribeiro MDC. Morphine in Intrasite gel applied topically to painful ulcers. J Pain and Symptom Management. 2005;29:118-119.
Topical CCB
• Diltiazem with lidocaine (PLO) for anal fissures
• Also for anal fissures/hemorrhoids– Preparation H (phenylepherine)– 0.2% glyceryl trinitrate
Topical Capsacin• Topical capsaicin preparations of 0.025 and 0.075%
• Postherpetic neuralgia
• Diabetic neuropathy
• Postmastectomy pain syndrome
• Oral neuropathic pain, Trigeminal neuralgia, and TMJ disorders
• Cluster headache (following intranasal application)
• Osteoarthritis
• Dermatological/cutaneous conditions