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