Pain Management: Neuropathic Pain

Severe Postherpetic Neuralgia Relieved by Topical Gabapentin

Herpes zoster reactivation, shingles, affects 0.2% of the population and postherpetic neuralgia (PHN) occurs in 10 -15% of patients following an episode of shingles, with the greatest risk in the elderly. A retrospective review involved 23 consecutive patients attending a tertiary complex pain clinic (University Hospital of Wales, Cardiff and Vale University Local Health Board), who were treated with topical gabapentin gel.

Multiple studies have already demonstrated the efficacy of oral gabapentin in treating chronic neuropathic pain, however efficacy is often limited by dose dependent toxicity. Although this patient population was small, these findings support the use of topical gabapentin in the treatment of PHN and potentially other painful neuropathy.

Br J Dermatol. 2014 Dec 18.
Severe postherpetic neuralgia and other neuropathic pain syndromes alleviated by topical gabapentin
Click here to access the abstract of this article.

Topical Analgesics for Neuropathic Pain in the Elderly

Elderly patients exhibit a higher incidence of several neuropathic pain conditions than younger individuals. Systemic treatment of neuropathic pain in the elderly usually requires lower dosing, slower titration, and more monitoring (for efficacy, adverse effects) than in younger patients due to drug factors (altered pharmacokinetics and pharmacodynamics) and patient factors (comorbidities, polypharmacy, frailty). “Despite the availability of several options, treatment of neuropathic pain is not optimal, as medications provide only a partial effect and adverse effects can limit dose escalation, resulting in suboptimal dosing. An often quoted perspective is that less than 50% experience satisfactory pain relief, and side effects are common.”

Summary of perspectives on topical analgesics and relevance to the elderly:

1. Topical analgesics are beneficial in a proportion of those with neuropathic pain, and can produce a degree of analgesia that is comparable with that of oral agents.

2. Topical analgesics are well tolerated, with adverse effects being mainly due to localized skin reactions. Low systemic levels occur following topical administration, and do not contribute to systemic adverse effects or drug interactions.

3. Topical analgesics may be used as alternative analgesics (when systemic analgesics are not tolerated) or as add-on analgesics when an oral agent produces a partial effect (their addition does not increase the side effect burden).

4. Only a limited number of topical analgesics are currently approved, but there is interest in investigational agents that recruit several potential mechanisms of action, and additional options may become available.

5. Topical analgesics have the potential to contribute to improved pain management in the elderly based on their efficacy, adverse effect profile, potential for use as add-on therapies, and potential for oral analgesic-sparing effects with ensuing reduction in adverse effects. 

Drugs Aging. 2014 Dec;31(12):853-62. 
Topical analgesics for neuropathic pain in the elderly: current and future prospects.
Click here to access the PubMed abstract of this article.

Eur J Pain. 2014 Apr;18(4):465-81. 
Topical analgesics for neuropathic pain: preclinical exploration, clinical validation, future development.
Click here to access the PubMed abstract of this article. 

Amitriptyline/Ketamine for Neuropathic Pruritus and pain secondary to herpes zoster. 

Neuropathic pruritus is a complication of herpes zoster which can be either acute or post-infectious when it persists more than 3 months after the rash has healed. In the study, modest control of the pruritus and pain was achieved with continued multimodal therapy and the addition of topical 2% amitriptyline/0.5% ketamine gel. 

J Drugs Dermatol. 2015 Feb;14(2):115-8.
Amitriptyline/Ketamine as therapy for neuropathic pruritus and pain secondary to herpes zoster.
Click here to access the PubMed abstract of this article. 

Topical therapies and combination preparations may have many advantages over systemically administered analgesics, including the ability to provide effective analgesia with reduced systemic drug levels, a factor particularly beneficial to the elderly. Fewer side effects coupled with convenient and painless administration results in improved patient acceptance and compliance, and ease of use may reduce overall treatment costs. Because they are applied directly to the target site, topical administration can provide therapeutic levels in the tissues under the area of application, with minimal serum levels. Lower systemic drug levels potentially lower the risk of organ toxicity. In addition, first pass hepatic metabolism and other variables associated with the gastrointestinal tract are avoided. Topical therapy is a viable solution which often avoids the need for injections when oral dosing is not feasible because the patient is nauseated or unconscious.

Existing commercially-available treatments may have limited effectiveness and produce relatively frequent adverse effects. Patients often convey that different medications will impart distinct analgesic benefits. Presence of side effects such as insomnia, depression, anxiety, and fatigue can diminish the patient's quality of life, and justify a change to a customized therapy.

There is a growing body of evidence on the efficacy and safety of topical agents in a variety of pain disorders, including the most prevalent neuropathic pain conditions. The molecular basis for the usage of peripheral analgesics in neuropathic pain and the available clinical trial evidence for a wide variety of topical agents are reviewed in an excellent article by Oscar A. de Leon-Casasola, MD, Department of Anesthesiology and Critical Care Medicine, Roswell Park Cancer Institute, School of Medicine and Biomedical Studies, State University of New York at Buffalo. Agents “that profoundly reduce neurotransmitter release from nociceptors generating ectopic pulses, such as topical local anesthetics and anticonvulsants, may relieve neuropathic pain. Likewise, increased peripheral sensitivity mediated through the release of prostaglandin E2 and substance P at the peripheral level results in spontaneous discharges that may be inhibited by topical drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs)… Additionally, topical substance P inhibitors and ketamine can reduce the effects of substance P, while sympathetic afferent activation can be modified by the topical administration of a beta-blocker and clonidine. Topical antihistamine may decrease the release of histamine and serotonin, thereby limiting the inflammatory process and hindering vasodilation. Topical opioids can target the opioid receptors present on nociceptive fibers and mast cells. Binding of opioid receptors can inhibit the release of the calcitonin gene-related peptide (CGRP) and substance P from nerves, thereby preventing the feed-forward mechanism of pain that typically results in sensitization at the site of injury (primary hyperalgesia).” Pentoxifylline has effectively provided relief for some neuropathic conditions when applied topically. “Topical tricyclic antidepressants, such as doxepin and amitriptyline, have demonstrated efficacy in a number of neuropathic pain states.”  

Neuropathic pain is often resistant to opioids, so other medication classes - such as tricyclic antidepressants, anticonvulsants, and local anesthetics - are often used. Central sensitization, or pain “wind-up”, may perpetuate chronic neuropathic pain even when ongoing peripheral sensory input is absent. Wind-up is thought to cause allodynia, hyperalgesia, and hyperpathia. Receptors such as NMDA, AMPA, and M-glu have recently been identified for their role in central sensitization and antagonists of these receptors have produced pain relief.  

The analgesic effect of tricyclic antidepressants is independent of their antidepressant activity and generally occurs at low doses with onset of pain relief in one to two weeks. For example, the analgesic effect of topically applied doxepin hydrochloride in chronic human neuropathic pain was described in a randomized, double-blind, placebo-controlled study of 200 adult patients. Fewer side effects were reported compared with oral administration.  

Med Clin North Am. 2007 Jan;91(1):113-24.
Adjuvant analgesics.
Click here to access the PubMed abstract of this article.

J Pain Symptom Manage. 2007 Mar; 33(3):356-64.
Transdermal Lidocaine and Ketamine for Neuropathic Pain: A Study of Effectiveness and Tolerability
Click here to access the PubMed abstract of this article.

Reg Anesth Pain Med 2003 Jul-Aug;28(4):289-93 
Topical amitriptyline in healthy volunteers. 
Click here to access the PubMed abstract of this article.

Pain Clin 2000;12(1):47-50. 
No abstract available. 
 
A phase 2b double-blind, randomized, placebo-controlled clinical trial, involving topical gel candidate ARC-4558 for adults with painful diabetic neuropathy produced effective results in relieving the pain.

Topical Gel to Treat Diabetic Neuropathy Proves Successful in Phase 2
Click here to access the reference. 

Dextromethorphan/Quinidine for Treatment of Diabetic Neuropathic Pain Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. The most frequent form, estimated to affect 50% of diabetic patients, is a distal symmetric polyneuropathy. The associated pain, which affects approximately 25% of DPN patients, can be severe and disabling.

In a 13-week, phase 3, randomized double-blind controlled trial, 379 adults with daily symmetric diabetic peripheral neuropathy (DPN) leg pain of 3 months duration received placebo, dextromethorphan/quinidine (DMQ) 45/30 mg, or DMQ 30/30 mg, administered once daily for 7 days and twice daily thereafter. The results of this study demonstrate that DMQ was more effective than placebo in the treatment of DPN pain at both dose levels studied.

Pain Med. 2012 Feb;13(2):243-54.
Efficacy and safety of dextromethorphan/quinidine at two dosage levels for diabetic neuropathic pain: a double-blind, placebo-controlled, multicenter study.
Click here to access the abstract of this article. 

Topical Glycopyrrolate to Relieve Neuropathic Pain in Lower Extremities 

A patient reported that lower extremity sweating was a reliable predictor of soon-to-increase painful “sparking” and burning pain. A trial of topical 2% glycopyrrolate cream (compounded by a community pharmacist) was instituted, based on reports of its use in Frey syndrome. During an episode where both feet were painful and sweating, 2% glycopyrrolate was applied to the most painful foot, and capsaicin 0.25% to the other. The patient found that treatment with 2% glycopyrrolate better alleviated the neuropathic symptoms compared with capsaicin. This case suggests that hyperhidrosis may be an index symptom for an underlying pathobiological driver of neuropathic pain in patients with painful sweating.

Pain Med. 2012 Mar;13(3):484-5.
The beneficial effect of topical glycopyrrolate in a patient with neuropathic lower extremity pain.
Click here to access the PubMed abstract of this article. 

This study evaluated the effects of a topical gel containing baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) on numbness, tingling, and pain caused by chemotherapy-induced peripheral neuropathy. The study concluded that BAK-PLO was well tolerated without evidence of systemic toxicity and appeared to somewhat improve symptoms of CIPN.

Support Care Cancer. 2011 Jun;19(6):833-41. 
A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA.
Click here to access the PubMed abstract of this article. 

Study subjects with moderate to severe peripheral neuropathic pain found that use of topical 2% amitriptyline/1% ketamine cream was well tolerated and was associated with long-term reduction in perceived pain.

J Pain. 2005 Oct;6(10):644-9.
Topical amitriptyline and ketamine in neuropathic pain syndromes: an open-label study.
Click here to access the PubMed abstract of this article. 

Topical Clonidine for Diabetic Neuropathy

A phase 2b double-blind, randomized, placebo-controlled clinical trial, showed that a topical clonidine 0.1% gel relieved pain in adults with painful diabetic neuropathy and no serious side effects were reported.

http://www.hcplive.com/pain-management/articles/topical_ge_diabetic_neuropathy 

Amitriptyline/Ketamine Topical Cream for Treating Post-Herpetic Neuralgia (PHN) 

Combinations of synergistic drugs can be customized for the patient with chronic pain, and topical or transdermal formulations offer excellent alternatives, sometimes with fewer side effects compared to the same drugs when taken orally. A multicenter, double-blind, randomized, placebo controlled study was conducted to evaluate the efficacy and safety of amitriptyline 4%/ketamine 2% [NP-H] and amitriptyline 2%/ketamine 1% [NP-L] topical creams versus placebo in 251 PHN patients. NP-H was numerically superior to NP-L cream and placebo, and appears to be the optimal concentration for PHN treatment. Less than 5% of subjects who applied NP-H had detectable serum levels of amitriptyline or ketamine.  

This study was presented at the 2007 American Pain Society Annual Meeting, Poster #787 

The following article discusses the use of topical ketamine 0.5% (5 mg/ml) gel, applied as a thin film two to three times daily over the skin where pain was severe. Topical ketamine reduced pain for patients with postherpetic neuralgia with no systemic side effects.

Neurology 2003;60:1391-1392
Topical ketamine treatment of postherpetic neuralgia 
No abstract available. Click here to purchase the full article on line. 

The following randomized, double-blind, placebo-controlled study assessed the analgesic efficacy of topical administration of 3.3% doxepin hydrochloride, 0.025% capsaicin or a combination applied daily for 4 weeks in 200 adult patients with chronic neuropathic pain, and reported that all three preparations significantly reduced overall pain.

Br J Clin Pharmacol 2000 Jun;49(6):574-9
Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study.
Click here to access the PubMed abstract of this article.

To relieve migraine sufferers from pain and reduce the occurrence of migraines, it is important for a clinician to be aware of the four phases and pathophysiology of migraines, drug classes commonly used, various therapeutic approaches and treatment options.

Int J Pharm Compd. 2006 Sept-Oct;10(5):344-350.
Migraine: A General Approach to Prevention and Treatment.
Click here to access the PubMed abstract of this article.

Migraine is associated with a wide-spread metabolic abnormality of mitochondrial oxidative metabolism, leading to the use of riboflavin and coenzyme Q10 as prophylactic therapy for migraine. Riboflavin has the potential of increasing mitochondrial energy efficiency, and riboflavin 400 mg daily was found to be effective for migraine prophylaxis, with decreased attack frequency, fewer headache days, and reduced severity of migraine. Riboflavin 400 mg can be compounded in an extended-release dosage form.

Headache. 2012 Oct;52 Suppl 2:81-7.
CoEnzyme Q10 and riboflavin: the mitochondrial connection.
Click here to access the PubMed abstract of this article.

Vitam Horm. 2004;69:297-312.
Role of magnesium, coenzyme Q10, riboflavin, and vitamin B12 in migraine prophylaxis.
Click here to access the PubMed abstract of this article.

Cephalalgia. 1994 Oct;14(5):328-9.
High-dose riboflavin as a prophylactic treatment of migraine: results of an open pilot study.
Click here to access the PubMed abstract of this article.

Continuum (Minneap Minn). 2012 Aug;18(4):796-806.
Nonmedication, alternative, and complementary treatments for migraine.
Click here to access the PubMed abstract of this article.

The goal of acute therapy is to abort or reduce the pain and other symptoms associated with the migraine while minimizing adverse drug effects and ultimately restoring the patient’s ability to function normally. For the acute management of migraine without aura, a double-blind, placebo-controlled trial demonstrated that in 83% of patients, a single dose of sublingual piroxicam 40 mg provided significant analgesic effect within 15 minutes of ingestion, and a further reduction in pain in the 24 hours after drug administration, with excellent tolerability.

J Assoc Physicians India. 2011 Aug;59:494-7.
Sublingual piroxicam in migraine without aura.
Click here to access the PubMed abstract of this article.

Case Report: A 40 year old woman with history of hysterectomy at age 28 and recurrent migraines refractory to treatment with multiple triptans and ergotamine/caffeine suppositories was prescribed a compounded therapy of ketoprofen 12.5mg/riboflavin 100 mg/caffeine citrate 65mg capsules, with directions to take 2 capsules at onset of migraine then two capsules every 4 hours as needed. After 3 weeks, she reported that on four occasions, her migraine was relieved with only the onset dose, and on one other occasion, she required a follow-up dose. She then added progesterone cream (applied twice daily) and three months later reported that she had only two migraines in the three month period, and both were relieved with the Ketoprofen/Riboflavin/Caffeine Capsules.

Int J Pharm Compd. 2007 May-June;11(3):200.
Case Report: Ketoprofen/Riboflavin/Caffeine Capsules and Progesterone Therapy for Recurrent Migraine Pain.
Click here to access the PubMed abstract of this article.

The following article concludes: A fixed combination of indomethacin 25 mg, prochlorperazine dimaleate 4 mg, and caffeine 75 mg is significantly more effective than sumatriptan in the acute treatment of migraine attacks versus sumatriptan 25 mg, both rectal suppositories.

Headache. 2003 Sep;43(8):835-44
Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter, randomized, crossover trial.
Click here to access the PubMed abstract of this article.

The following article concludes: Oral therapy with a combination of LAS (equivalent to 900 mg ASA) and metoclopramide 10 mg was superior to placebo with therapeutic gains of 30% and 31% for the first treated attack, and was comparable to 100 mg sumatriptan.

Funct Neurol. 2000;15 Suppl 3:196-201
The effectiveness of combined oral lysine acetylsalicylate and metoclopramide (Migpriv) in the treatment of migraine attacks. Comparison with placebo and oral sumatriptan.
Click here to access the PubMed abstract of this article.

“Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain associated with a variety of indications, including arthritic conditions, but their usefulness is often limited by dose-dependent adverse events such as gastrointestinal disturbances, cardiovascular events, and renal toxicity. The risk of such effects could be reduced by the use of topical formulations, which offer the potential to deliver analgesic concentrations locally, at the site of inflammation, while minimizing systemic concentrations... Meta-analyses have confirmed the efficacy and safety of these [TOPICAL] preparations. However, it is important to recognize that pharmacokinetics [and] absorption from topical formulations can vary markedly, even between different formulations of the same drug, depending on the agent, the underlying disorder, and the site of application. It is therefore essential to consider the patient, the drug, and the drug delivery mechanism when selecting a topical NSAID preparation.”

Am J Ther. 2012 Feb 22. [Epub ahead of print]
Topical Nonsteroidal Anti-Inflammatory Drugs: The Importance of Drug, Delivery, and Therapeutic Outcome.
Click here to access the PubMed abstract of this article.

To avoid the risks of COX-2 inhibitors, our pharmacy can compound topically applied NSAIDs such as ibuprofen and ketoprofen. Topical NSAIDs have a safety profile which is superior to oral formulations. Topical NSAID administration offers the advantage of local, enhanced delivery to painful sites with a reduced incidence of systemic adverse effects.

Topical preparations can be customized to contain a combination of medications to meet the specific needs of each patient.

This study concluded that topical NSAIDs, when used for treatment of pain resulting from strains, sprains or sports or overuse-type injuries, can provide good levels of pain relief without the systemic adverse events associated with oral NSAIDs.

Cochrane Database Syst Rev. 2010 Jun 16; 6: CD007402.
Topical NSAIDs for acute pain in adults.
Click here to access the PubMed abstract of this article.

"Topical non-steroidal anti-inflammatory drugs have a lower incidence of gastrointestinal adverse effects than the same drugs when they are taken orally. The low incidence of systemic adverse effects for topical NSAIDs probably results from the much lower plasma concentration from similar doses applied topically to those administered orally. Topical application of ibuprofen resulted in measurable tissue concentrations in deep tissue compartments, more than enough to inhibit inflammatory enzymes."

BMJ. 1995 Jul 1;311(6996):22-6
Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study.
Free full text article available at bmj.com:
http://bmj.bmjjournals.com/cgi/content/full/311/6996/22

This study concludes that topical NSAIDs have not been associated with renal failure.

QJM. 1995 Aug;88(8):551-7
Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure.
Click here to access the PubMed abstract of this article.

The following article concludes: "Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions."

BMJ. 1998 Jan 31;316(7128):333-8
Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.
Click here to access the PubMed abstract of this article.

The following article reports "The systemic concentrations of ketoprofen have also been found to be 100 fold lower compared to tissue concentrations below the application site in patients undergoing knee joint surgery. Topically applied ketoprofen thus provides high local concentration below the site of application but lower systemic exposure."

Pharm Res. 1996 Jan;13(1):168-72
Percutaneous absorption of ketoprofen from different anatomical sites in man.
http://www.ncbi.nlm.nih.gov/pubmed/8668669

Sever disease is the most common cause of heel pain in pre-pubertal children. This inflammatory condition is a result of minor repetitive trauma and typically occurs during a growth spurt or at the beginning of a new sport season. A case report described the use of topical ketoprofen 10% gel to relieve pain and inflammation.

Phys Ther. 2006 Mar;86(3):424-33
Ketoprofen gel as an adjunct to physical therapist management of a child with Sever disease.
Click here to access the PubMed abstract of this article.

This study suggests that due to its prompt analgesia, lack of systemic side effects, and convenience, xylocaine pump spray provides a significant improvement in posttraumatic peripheral neuropathy.

Anesth Analg. 2009 Mar;108(3):987-91.
The analgesic effect of a metered-dose 8% lidocaine pump spray in posttraumatic peripheral neuropathy: a pilot study.
Click here to access the PubMed abstract of this article.

A double-blind placebo-controlled crossover trial showed that in patients with Complex Regional Pain Syndrome (CRPS; also known as Reflex Sympathetic Dystrophy), topical application of ketamine 10% cream caused a reduction in allodynia, a most unpleasant aspect of this condition. This study shows promise for the use of topical ketamine as opposed to parenteral and oral forms which often result in undesirable side effects.

Pain. 2009 Nov;146(1-2):18-25.
Reduction of allodynia in patients with complex regional pain syndrome: A double-blind placebo-controlled trial of topical ketamine.
Click here to access the PubMed abstract of this article.

“Lidocaine lollipop is a promising form of local oropharyngeal anesthesia for EGD. Its use resulted in sparing the use of intravenous sedation. It is well tolerated and safe and may be particularly important in the elderly, patients with comorbidities, and office-based endoscopy. “

Gastrointest Endosc. 2007 Oct;66(4):786-93.
Lidocaine lollipop as single-agent anesthesia in upper GI endoscopy.
Click here to access the PubMed abstract of this article.

Topical piroxicam 0.5% gel was associated with fewer inflammatory side effects than was EMLA cream, because of its anti-inflammatory effect after the procedure.

Lasers Med Sci. 2008 Aug 21. [Epub ahead of print]
A clinical comparison of topical piroxicam and EMLA cream for pain relief and inflammation in laser hair removal.
Click here to access the PubMed abstract of this article.

The following article concludes: "LAT gel (4% lidocaine, 1:2000 adrenaline, 0.5% tetracaine) worked as well as TAC gel (0.5% tetracaine, 1:2000 adrenaline, 11.8% cocaine) for topical anesthesia in facial and scalp lacerations. Considering the advantages of a noncontrolled substance and less expense, LAT gel appears to be better suited than TAC gel for topical anesthesia in laceration repair in children."

Pediatrics 1995 Feb;95(2):255-8
Lidocaine adrenaline tetracaine gel versus tetracaine adrenaline cocaine gel for topical anesthesia in linear scalp and facial lacerations in children aged 5 to 17 years.
Click here to access the PubMed abstract of this article.

The following article reported that a triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine ("BLT") applied prior to treatment with a 532-nm KTP laser resulted in significantly lower pain scores than with 3 other topical anesthetics at 15, 30, 45, and 60 minutes after application.

Cosmetic Dermatology 2003 Apr;16(4):35-7
Topical Triple-Anesthetic Gel Compared With 3 Topical Anesthetics

The discovery of peripheral opioid receptors has become the scientific basis for topical use of opioids in malignant and nonmalignant ulcers and oropharyngeal mucositis. A systematic review assessed the quality of published literature and examined whether topical opioids are effective in controlling pain in palliative care settings. Eighteen studies favored topical opioids in pain relief, but time to onset and duration of analgesia varied widely, perhaps due to variances in formulations. “N-of-1 trials should be encouraged for specific clinical circumstances.”

J Pain Symptom Manage. 2009 May;37(5):913-7.
Effectiveness of topical administration of opioids in palliative care: a systematic review.
Click here to access the PubMed abstract of this article.

B&O Suppositories

B&O Suppositories are used for relief of moderate to severe pain associated with rectal or bladder spasms that may occur postoperatively or secondary to cancer. Periodically, these have been on back order. When medications are not commercially available, call our compounding pharmacy.

At Columbia- New York Presbyterian Hospital, physicians examined whether acetaminophen with codeine administered per rectum is an effective alternative for pain control compared with oral administration after an adenotonsillectomy. Equivalent postoperative pain control was achieved with suppositories and oral medication, with few side effects and good tolerance. Furthermore, many parents preferred the suppositories to oral medication in maintaining postoperative pain control because of ease of administration.

Laryngoscope 2006 Aug;116(8):1485-8
Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients.
Click here to access the PubMed abstract of this article.

The use of topical morphine gel is reported in two children with epidermolysis bullosa, where acute inflammatory pain is a major symptom and where effective analgesia is a major clinical problem.

Arch Dis Child. 2004 Jul;89(7):679-81
Peripheral opioids in inflammatory pain.
Click here to access the PubMed abstract of this article.

Morphine sulfate 10 mg in Intrasite gel was applied topically to skin ulcers of hospice inpatients. The topical morphine was not absorbed in the majority of patients, suggesting any analgesic effect was mediated locally rather than systemically.

J Pain Symptom Manage. 2004 May;27(5):434-9
The bioavailability of morphine applied topically to cutaneous ulcers.
Click here to access the PubMed abstract of this article.

Iontophoresis and phonophoresis are technologies that are capable of enhancing drug penetration through the skin. Phonophoresis uses ultrasonic waves to transmit molecules of drug through the skin, as opposed to iontophoresis, which uses low level electric current. Both techniques are used to treat inflammatory conditions such as arthritis, plantar fasciitis, tendonitis, bursitis, and carpal tunnel syndrome.

Iontophoresis: Many ionic drugs are available including several antivirals, various antibiotics, and other specific drugs. Iontophoresis of ionized drugs provided a 20-60 fold increase in penetration over topical application.

Examples of successful applications of iontophoresis include:

• treatment of inflammation/pain of muscles and tendons, including the Achilles tendon
• rapid, noninvasive local anesthesia, particularly for children
• relief of heel pain from bone spurs
• controlling the pain of tennis elbow
• relief of pain from rheumatoid arthritis of the knee
• relief of pain associated with plantar fasciitis
• improvement of jaw function in patients with temporomandibular joint (TMJ) disorders
• management of hip pain in patients with sickle cell disorders (SCD)
• an alternative to steroid injections for therapy of Carpal Tunnel Syndrome
• treatment for scar and tendon adhesions

Phonophoresis (or sonophoresis) combines ultrasound with topical drug therapy to achieve therapeutic drug concentrations at target sites below the skin. A cream or gel containing medications such as corticosteroids, local anesthetics, electrolytes, or antibiotics is applied to the treatment area and then massaged with a transducer head. The technique has been widely used in sports medicine since the 1960s by podiatrists, orthopedists, and physical therapists.

The method of preparation and quality of ingredients used for solutions or gels for iontophoresis or phonophoresis are critical to the success of the therapy and minimizing side effects.

Am J Sports Med. 1997 May-Jun;25(3):312-6
Treatment of plantar fasciitis by iontophoresis of 0.4% dexamethasone. A randomized, double-blind, placebo-controlled study.
Click here to access the PubMed abstract of this article.

All formulations are customized per prescription to meet the unique needs of each patient. Please call us to discuss the dosage form, medication, and strength which are most appropriate for your patient.

• Ketoprofen topical or transdermal gel
• Ketamine transdermal gel
• Ketamine/Ketoprofen/Gabapentin transdermal gel
• Lidocaine/Prilocaine topical gel
• Triple-Anesthetic gel - benzocaine/lidocaine/tetracaine (“BLT”)
• Gabapentin/Clonidine in PLO (Pluronic Lecithin Organogel)
• Piroxicam tablet triturates
• Ibuprofen suppositories
• Ketoprofen/Cyclobenzaprine topical gel

Pain Management: Neuropathic Pain

Severe Postherpetic Neuralgia Relieved by Topical Gabapentin

Herpes zoster reactivation, shingles, affects 0.2% of the population and postherpetic neuralgia (PHN) occurs in 10 -15% of patients following an episode of shingles, with the greatest risk in the elderly. A retrospective review involved 23 consecutive patients attending a tertiary complex pain clinic (University Hospital of Wales, Cardiff and Vale University Local Health Board), who were treated with topical gabapentin gel.

Multiple studies have already demonstrated the efficacy of oral gabapentin in treating chronic neuropathic pain, however efficacy is often limited by dose dependent toxicity. Although this patient population was small, these findings support the use of topical gabapentin in the treatment of PHN and potentially other painful neuropathy.

Br J Dermatol. 2014 Dec 18.
Severe postherpetic neuralgia and other neuropathic pain syndromes alleviated by topical gabapentin
Click here to access the abstract of this article.

Topical Analgesics for Neuropathic Pain in the Elderly

Elderly patients exhibit a higher incidence of several neuropathic pain conditions than younger individuals. Systemic treatment of neuropathic pain in the elderly usually requires lower dosing, slower titration, and more monitoring (for efficacy, adverse effects) than in younger patients due to drug factors (altered pharmacokinetics and pharmacodynamics) and patient factors (comorbidities, polypharmacy, frailty). “Despite the availability of several options, treatment of neuropathic pain is not optimal, as medications provide only a partial effect and adverse effects can limit dose escalation, resulting in suboptimal dosing. An often quoted perspective is that less than 50% experience satisfactory pain relief, and side effects are common.”

Summary of perspectives on topical analgesics and relevance to the elderly:

1. Topical analgesics are beneficial in a proportion of those with neuropathic pain, and can produce a degree of analgesia that is comparable with that of oral agents.

2. Topical analgesics are well tolerated, with adverse effects being mainly due to localized skin reactions. Low systemic levels occur following topical administration, and do not contribute to systemic adverse effects or drug interactions.

3. Topical analgesics may be used as alternative analgesics (when systemic analgesics are not tolerated) or as add-on analgesics when an oral agent produces a partial effect (their addition does not increase the side effect burden).

4. Only a limited number of topical analgesics are currently approved, but there is interest in investigational agents that recruit several potential mechanisms of action, and additional options may become available.

5. Topical analgesics have the potential to contribute to improved pain management in the elderly based on their efficacy, adverse effect profile, potential for use as add-on therapies, and potential for oral analgesic-sparing effects with ensuing reduction in adverse effects. 

Drugs Aging. 2014 Dec;31(12):853-62. 
Topical analgesics for neuropathic pain in the elderly: current and future prospects.
Click here to access the PubMed abstract of this article.

Eur J Pain. 2014 Apr;18(4):465-81. 
Topical analgesics for neuropathic pain: preclinical exploration, clinical validation, future development.
Click here to access the PubMed abstract of this article. 

Amitriptyline/Ketamine for Neuropathic Pruritus and pain secondary to herpes zoster. 

Neuropathic pruritus is a complication of herpes zoster which can be either acute or post-infectious when it persists more than 3 months after the rash has healed. In the study, modest control of the pruritus and pain was achieved with continued multimodal therapy and the addition of topical 2% amitriptyline/0.5% ketamine gel. 

J Drugs Dermatol. 2015 Feb;14(2):115-8.
Amitriptyline/Ketamine as therapy for neuropathic pruritus and pain secondary to herpes zoster.
Click here to access the PubMed abstract of this article. 

Topical therapies and combination preparations may have many advantages over systemically administered analgesics, including the ability to provide effective analgesia with reduced systemic drug levels, a factor particularly beneficial to the elderly. Fewer side effects coupled with convenient and painless administration results in improved patient acceptance and compliance, and ease of use may reduce overall treatment costs. Because they are applied directly to the target site, topical administration can provide therapeutic levels in the tissues under the area of application, with minimal serum levels. Lower systemic drug levels potentially lower the risk of organ toxicity. In addition, first pass hepatic metabolism and other variables associated with the gastrointestinal tract are avoided. Topical therapy is a viable solution which often avoids the need for injections when oral dosing is not feasible because the patient is nauseated or unconscious.

Existing commercially-available treatments may have limited effectiveness and produce relatively frequent adverse effects. Patients often convey that different medications will impart distinct analgesic benefits. Presence of side effects such as insomnia, depression, anxiety, and fatigue can diminish the patient's quality of life, and justify a change to a customized therapy.

There is a growing body of evidence on the efficacy and safety of topical agents in a variety of pain disorders, including the most prevalent neuropathic pain conditions. The molecular basis for the usage of peripheral analgesics in neuropathic pain and the available clinical trial evidence for a wide variety of topical agents are reviewed in an excellent article by Oscar A. de Leon-Casasola, MD, Department of Anesthesiology and Critical Care Medicine, Roswell Park Cancer Institute, School of Medicine and Biomedical Studies, State University of New York at Buffalo. Agents “that profoundly reduce neurotransmitter release from nociceptors generating ectopic pulses, such as topical local anesthetics and anticonvulsants, may relieve neuropathic pain. Likewise, increased peripheral sensitivity mediated through the release of prostaglandin E2 and substance P at the peripheral level results in spontaneous discharges that may be inhibited by topical drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs)… Additionally, topical substance P inhibitors and ketamine can reduce the effects of substance P, while sympathetic afferent activation can be modified by the topical administration of a beta-blocker and clonidine. Topical antihistamine may decrease the release of histamine and serotonin, thereby limiting the inflammatory process and hindering vasodilation. Topical opioids can target the opioid receptors present on nociceptive fibers and mast cells. Binding of opioid receptors can inhibit the release of the calcitonin gene-related peptide (CGRP) and substance P from nerves, thereby preventing the feed-forward mechanism of pain that typically results in sensitization at the site of injury (primary hyperalgesia).” Pentoxifylline has effectively provided relief for some neuropathic conditions when applied topically. “Topical tricyclic antidepressants, such as doxepin and amitriptyline, have demonstrated efficacy in a number of neuropathic pain states.”  

Neuropathic pain is often resistant to opioids, so other medication classes - such as tricyclic antidepressants, anticonvulsants, and local anesthetics - are often used. Central sensitization, or pain “wind-up”, may perpetuate chronic neuropathic pain even when ongoing peripheral sensory input is absent. Wind-up is thought to cause allodynia, hyperalgesia, and hyperpathia. Receptors such as NMDA, AMPA, and M-glu have recently been identified for their role in central sensitization and antagonists of these receptors have produced pain relief.  

The analgesic effect of tricyclic antidepressants is independent of their antidepressant activity and generally occurs at low doses with onset of pain relief in one to two weeks. For example, the analgesic effect of topically applied doxepin hydrochloride in chronic human neuropathic pain was described in a randomized, double-blind, placebo-controlled study of 200 adult patients. Fewer side effects were reported compared with oral administration.  

Med Clin North Am. 2007 Jan;91(1):113-24.
Adjuvant analgesics.
Click here to access the PubMed abstract of this article.

J Pain Symptom Manage. 2007 Mar; 33(3):356-64.
Transdermal Lidocaine and Ketamine for Neuropathic Pain: A Study of Effectiveness and Tolerability
Click here to access the PubMed abstract of this article.

Reg Anesth Pain Med 2003 Jul-Aug;28(4):289-93 
Topical amitriptyline in healthy volunteers. 
Click here to access the PubMed abstract of this article.

Pain Clin 2000;12(1):47-50. 
No abstract available. 
 
A phase 2b double-blind, randomized, placebo-controlled clinical trial, involving topical gel candidate ARC-4558 for adults with painful diabetic neuropathy produced effective results in relieving the pain.

Topical Gel to Treat Diabetic Neuropathy Proves Successful in Phase 2
Click here to access the reference. 

Dextromethorphan/Quinidine for Treatment of Diabetic Neuropathic Pain Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. The most frequent form, estimated to affect 50% of diabetic patients, is a distal symmetric polyneuropathy. The associated pain, which affects approximately 25% of DPN patients, can be severe and disabling.

In a 13-week, phase 3, randomized double-blind controlled trial, 379 adults with daily symmetric diabetic peripheral neuropathy (DPN) leg pain of 3 months duration received placebo, dextromethorphan/quinidine (DMQ) 45/30 mg, or DMQ 30/30 mg, administered once daily for 7 days and twice daily thereafter. The results of this study demonstrate that DMQ was more effective than placebo in the treatment of DPN pain at both dose levels studied.

Pain Med. 2012 Feb;13(2):243-54.
Efficacy and safety of dextromethorphan/quinidine at two dosage levels for diabetic neuropathic pain: a double-blind, placebo-controlled, multicenter study.
Click here to access the abstract of this article. 

Topical Glycopyrrolate to Relieve Neuropathic Pain in Lower Extremities 

A patient reported that lower extremity sweating was a reliable predictor of soon-to-increase painful “sparking” and burning pain. A trial of topical 2% glycopyrrolate cream (compounded by a community pharmacist) was instituted, based on reports of its use in Frey syndrome. During an episode where both feet were painful and sweating, 2% glycopyrrolate was applied to the most painful foot, and capsaicin 0.25% to the other. The patient found that treatment with 2% glycopyrrolate better alleviated the neuropathic symptoms compared with capsaicin. This case suggests that hyperhidrosis may be an index symptom for an underlying pathobiological driver of neuropathic pain in patients with painful sweating.

Pain Med. 2012 Mar;13(3):484-5.
The beneficial effect of topical glycopyrrolate in a patient with neuropathic lower extremity pain.
Click here to access the PubMed abstract of this article. 

This study evaluated the effects of a topical gel containing baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) on numbness, tingling, and pain caused by chemotherapy-induced peripheral neuropathy. The study concluded that BAK-PLO was well tolerated without evidence of systemic toxicity and appeared to somewhat improve symptoms of CIPN.

Support Care Cancer. 2011 Jun;19(6):833-41. 
A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA.
Click here to access the PubMed abstract of this article. 

Study subjects with moderate to severe peripheral neuropathic pain found that use of topical 2% amitriptyline/1% ketamine cream was well tolerated and was associated with long-term reduction in perceived pain.

J Pain. 2005 Oct;6(10):644-9.
Topical amitriptyline and ketamine in neuropathic pain syndromes: an open-label study.
Click here to access the PubMed abstract of this article. 

Topical Clonidine for Diabetic Neuropathy

A phase 2b double-blind, randomized, placebo-controlled clinical trial, showed that a topical clonidine 0.1% gel relieved pain in adults with painful diabetic neuropathy and no serious side effects were reported.

http://www.hcplive.com/pain-management/articles/topical_ge_diabetic_neuropathy 

Amitriptyline/Ketamine Topical Cream for Treating Post-Herpetic Neuralgia (PHN) 

Combinations of synergistic drugs can be customized for the patient with chronic pain, and topical or transdermal formulations offer excellent alternatives, sometimes with fewer side effects compared to the same drugs when taken orally. A multicenter, double-blind, randomized, placebo controlled study was conducted to evaluate the efficacy and safety of amitriptyline 4%/ketamine 2% [NP-H] and amitriptyline 2%/ketamine 1% [NP-L] topical creams versus placebo in 251 PHN patients. NP-H was numerically superior to NP-L cream and placebo, and appears to be the optimal concentration for PHN treatment. Less than 5% of subjects who applied NP-H had detectable serum levels of amitriptyline or ketamine.  

This study was presented at the 2007 American Pain Society Annual Meeting, Poster #787 

The following article discusses the use of topical ketamine 0.5% (5 mg/ml) gel, applied as a thin film two to three times daily over the skin where pain was severe. Topical ketamine reduced pain for patients with postherpetic neuralgia with no systemic side effects.

Neurology 2003;60:1391-1392
Topical ketamine treatment of postherpetic neuralgia 
No abstract available. Click here to purchase the full article on line. 

The following randomized, double-blind, placebo-controlled study assessed the analgesic efficacy of topical administration of 3.3% doxepin hydrochloride, 0.025% capsaicin or a combination applied daily for 4 weeks in 200 adult patients with chronic neuropathic pain, and reported that all three preparations significantly reduced overall pain.

Br J Clin Pharmacol 2000 Jun;49(6):574-9
Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study.
Click here to access the PubMed abstract of this article.

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To relieve migraine sufferers from pain and reduce the occurrence of migraines, it is important for a clinician to be aware of the four phases and pathophysiology of migraines, drug classes commonly used, various therapeutic approaches and treatment options.

Int J Pharm Compd. 2006 Sept-Oct;10(5):344-350.
Migraine: A General Approach to Prevention and Treatment.
Click here to access the PubMed abstract of this article.

Migraine is associated with a wide-spread metabolic abnormality of mitochondrial oxidative metabolism, leading to the use of riboflavin and coenzyme Q10 as prophylactic therapy for migraine. Riboflavin has the potential of increasing mitochondrial energy efficiency, and riboflavin 400 mg daily was found to be effective for migraine prophylaxis, with decreased attack frequency, fewer headache days, and reduced severity of migraine. Riboflavin 400 mg can be compounded in an extended-release dosage form.

Headache. 2012 Oct;52 Suppl 2:81-7.
CoEnzyme Q10 and riboflavin: the mitochondrial connection.
Click here to access the PubMed abstract of this article.

Vitam Horm. 2004;69:297-312.
Role of magnesium, coenzyme Q10, riboflavin, and vitamin B12 in migraine prophylaxis.
Click here to access the PubMed abstract of this article.

Cephalalgia. 1994 Oct;14(5):328-9.
High-dose riboflavin as a prophylactic treatment of migraine: results of an open pilot study.
Click here to access the PubMed abstract of this article.

Continuum (Minneap Minn). 2012 Aug;18(4):796-806.
Nonmedication, alternative, and complementary treatments for migraine.
Click here to access the PubMed abstract of this article.

The goal of acute therapy is to abort or reduce the pain and other symptoms associated with the migraine while minimizing adverse drug effects and ultimately restoring the patient’s ability to function normally. For the acute management of migraine without aura, a double-blind, placebo-controlled trial demonstrated that in 83% of patients, a single dose of sublingual piroxicam 40 mg provided significant analgesic effect within 15 minutes of ingestion, and a further reduction in pain in the 24 hours after drug administration, with excellent tolerability.

J Assoc Physicians India. 2011 Aug;59:494-7.
Sublingual piroxicam in migraine without aura.
Click here to access the PubMed abstract of this article.

Case Report: A 40 year old woman with history of hysterectomy at age 28 and recurrent migraines refractory to treatment with multiple triptans and ergotamine/caffeine suppositories was prescribed a compounded therapy of ketoprofen 12.5mg/riboflavin 100 mg/caffeine citrate 65mg capsules, with directions to take 2 capsules at onset of migraine then two capsules every 4 hours as needed. After 3 weeks, she reported that on four occasions, her migraine was relieved with only the onset dose, and on one other occasion, she required a follow-up dose. She then added progesterone cream (applied twice daily) and three months later reported that she had only two migraines in the three month period, and both were relieved with the Ketoprofen/Riboflavin/Caffeine Capsules.

Int J Pharm Compd. 2007 May-June;11(3):200.
Case Report: Ketoprofen/Riboflavin/Caffeine Capsules and Progesterone Therapy for Recurrent Migraine Pain.
Click here to access the PubMed abstract of this article.

The following article concludes: A fixed combination of indomethacin 25 mg, prochlorperazine dimaleate 4 mg, and caffeine 75 mg is significantly more effective than sumatriptan in the acute treatment of migraine attacks versus sumatriptan 25 mg, both rectal suppositories.

Headache. 2003 Sep;43(8):835-44
Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter, randomized, crossover trial.
Click here to access the PubMed abstract of this article.

The following article concludes: Oral therapy with a combination of LAS (equivalent to 900 mg ASA) and metoclopramide 10 mg was superior to placebo with therapeutic gains of 30% and 31% for the first treated attack, and was comparable to 100 mg sumatriptan.

Funct Neurol. 2000;15 Suppl 3:196-201
The effectiveness of combined oral lysine acetylsalicylate and metoclopramide (Migpriv) in the treatment of migraine attacks. Comparison with placebo and oral sumatriptan.
Click here to access the PubMed abstract of this article.

©Storey Marketing. Used with permission. All rights reserved.

“Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain associated with a variety of indications, including arthritic conditions, but their usefulness is often limited by dose-dependent adverse events such as gastrointestinal disturbances, cardiovascular events, and renal toxicity. The risk of such effects could be reduced by the use of topical formulations, which offer the potential to deliver analgesic concentrations locally, at the site of inflammation, while minimizing systemic concentrations... Meta-analyses have confirmed the efficacy and safety of these [TOPICAL] preparations. However, it is important to recognize that pharmacokinetics [and] absorption from topical formulations can vary markedly, even between different formulations of the same drug, depending on the agent, the underlying disorder, and the site of application. It is therefore essential to consider the patient, the drug, and the drug delivery mechanism when selecting a topical NSAID preparation.”

Am J Ther. 2012 Feb 22. [Epub ahead of print]
Topical Nonsteroidal Anti-Inflammatory Drugs: The Importance of Drug, Delivery, and Therapeutic Outcome.
Click here to access the PubMed abstract of this article.

To avoid the risks of COX-2 inhibitors, our pharmacy can compound topically applied NSAIDs such as ibuprofen and ketoprofen. Topical NSAIDs have a safety profile which is superior to oral formulations. Topical NSAID administration offers the advantage of local, enhanced delivery to painful sites with a reduced incidence of systemic adverse effects.

Topical preparations can be customized to contain a combination of medications to meet the specific needs of each patient.

This study concluded that topical NSAIDs, when used for treatment of pain resulting from strains, sprains or sports or overuse-type injuries, can provide good levels of pain relief without the systemic adverse events associated with oral NSAIDs.

Cochrane Database Syst Rev. 2010 Jun 16; 6: CD007402.
Topical NSAIDs for acute pain in adults.
Click here to access the PubMed abstract of this article.

"Topical non-steroidal anti-inflammatory drugs have a lower incidence of gastrointestinal adverse effects than the same drugs when they are taken orally. The low incidence of systemic adverse effects for topical NSAIDs probably results from the much lower plasma concentration from similar doses applied topically to those administered orally. Topical application of ibuprofen resulted in measurable tissue concentrations in deep tissue compartments, more than enough to inhibit inflammatory enzymes."

BMJ. 1995 Jul 1;311(6996):22-6
Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study.
Free full text article available at bmj.com:
http://bmj.bmjjournals.com/cgi/content/full/311/6996/22

This study concludes that topical NSAIDs have not been associated with renal failure.

QJM. 1995 Aug;88(8):551-7
Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure.
Click here to access the PubMed abstract of this article.

The following article concludes: "Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions."

BMJ. 1998 Jan 31;316(7128):333-8
Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.
Click here to access the PubMed abstract of this article.

The following article reports "The systemic concentrations of ketoprofen have also been found to be 100 fold lower compared to tissue concentrations below the application site in patients undergoing knee joint surgery. Topically applied ketoprofen thus provides high local concentration below the site of application but lower systemic exposure."

Pharm Res. 1996 Jan;13(1):168-72
Percutaneous absorption of ketoprofen from different anatomical sites in man.
http://www.ncbi.nlm.nih.gov/pubmed/8668669

Sever disease is the most common cause of heel pain in pre-pubertal children. This inflammatory condition is a result of minor repetitive trauma and typically occurs during a growth spurt or at the beginning of a new sport season. A case report described the use of topical ketoprofen 10% gel to relieve pain and inflammation.

Phys Ther. 2006 Mar;86(3):424-33
Ketoprofen gel as an adjunct to physical therapist management of a child with Sever disease.
Click here to access the PubMed abstract of this article.

©Storey Marketing. Used with permission. All rights reserved.

This study suggests that due to its prompt analgesia, lack of systemic side effects, and convenience, xylocaine pump spray provides a significant improvement in posttraumatic peripheral neuropathy.

Anesth Analg. 2009 Mar;108(3):987-91.
The analgesic effect of a metered-dose 8% lidocaine pump spray in posttraumatic peripheral neuropathy: a pilot study.
Click here to access the PubMed abstract of this article.

A double-blind placebo-controlled crossover trial showed that in patients with Complex Regional Pain Syndrome (CRPS; also known as Reflex Sympathetic Dystrophy), topical application of ketamine 10% cream caused a reduction in allodynia, a most unpleasant aspect of this condition. This study shows promise for the use of topical ketamine as opposed to parenteral and oral forms which often result in undesirable side effects.

Pain. 2009 Nov;146(1-2):18-25.
Reduction of allodynia in patients with complex regional pain syndrome: A double-blind placebo-controlled trial of topical ketamine.
Click here to access the PubMed abstract of this article.

“Lidocaine lollipop is a promising form of local oropharyngeal anesthesia for EGD. Its use resulted in sparing the use of intravenous sedation. It is well tolerated and safe and may be particularly important in the elderly, patients with comorbidities, and office-based endoscopy. “

Gastrointest Endosc. 2007 Oct;66(4):786-93.
Lidocaine lollipop as single-agent anesthesia in upper GI endoscopy.
Click here to access the PubMed abstract of this article.

Topical piroxicam 0.5% gel was associated with fewer inflammatory side effects than was EMLA cream, because of its anti-inflammatory effect after the procedure.

Lasers Med Sci. 2008 Aug 21. [Epub ahead of print]
A clinical comparison of topical piroxicam and EMLA cream for pain relief and inflammation in laser hair removal.
Click here to access the PubMed abstract of this article.

The following article concludes: "LAT gel (4% lidocaine, 1:2000 adrenaline, 0.5% tetracaine) worked as well as TAC gel (0.5% tetracaine, 1:2000 adrenaline, 11.8% cocaine) for topical anesthesia in facial and scalp lacerations. Considering the advantages of a noncontrolled substance and less expense, LAT gel appears to be better suited than TAC gel for topical anesthesia in laceration repair in children."

Pediatrics 1995 Feb;95(2):255-8
Lidocaine adrenaline tetracaine gel versus tetracaine adrenaline cocaine gel for topical anesthesia in linear scalp and facial lacerations in children aged 5 to 17 years.
Click here to access the PubMed abstract of this article.

The following article reported that a triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine ("BLT") applied prior to treatment with a 532-nm KTP laser resulted in significantly lower pain scores than with 3 other topical anesthetics at 15, 30, 45, and 60 minutes after application.

Cosmetic Dermatology 2003 Apr;16(4):35-7
Topical Triple-Anesthetic Gel Compared With 3 Topical Anesthetics

©Storey Marketing. Used with permission. All rights reserved.

The discovery of peripheral opioid receptors has become the scientific basis for topical use of opioids in malignant and nonmalignant ulcers and oropharyngeal mucositis. A systematic review assessed the quality of published literature and examined whether topical opioids are effective in controlling pain in palliative care settings. Eighteen studies favored topical opioids in pain relief, but time to onset and duration of analgesia varied widely, perhaps due to variances in formulations. “N-of-1 trials should be encouraged for specific clinical circumstances.”

J Pain Symptom Manage. 2009 May;37(5):913-7.
Effectiveness of topical administration of opioids in palliative care: a systematic review.
Click here to access the PubMed abstract of this article.

B&O Suppositories

B&O Suppositories are used for relief of moderate to severe pain associated with rectal or bladder spasms that may occur postoperatively or secondary to cancer. Periodically, these have been on back order. When medications are not commercially available, call our compounding pharmacy.

At Columbia- New York Presbyterian Hospital, physicians examined whether acetaminophen with codeine administered per rectum is an effective alternative for pain control compared with oral administration after an adenotonsillectomy. Equivalent postoperative pain control was achieved with suppositories and oral medication, with few side effects and good tolerance. Furthermore, many parents preferred the suppositories to oral medication in maintaining postoperative pain control because of ease of administration.

Laryngoscope 2006 Aug;116(8):1485-8
Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients.
Click here to access the PubMed abstract of this article.

The use of topical morphine gel is reported in two children with epidermolysis bullosa, where acute inflammatory pain is a major symptom and where effective analgesia is a major clinical problem.

Arch Dis Child. 2004 Jul;89(7):679-81
Peripheral opioids in inflammatory pain.
Click here to access the PubMed abstract of this article.

Morphine sulfate 10 mg in Intrasite gel was applied topically to skin ulcers of hospice inpatients. The topical morphine was not absorbed in the majority of patients, suggesting any analgesic effect was mediated locally rather than systemically.

J Pain Symptom Manage. 2004 May;27(5):434-9
The bioavailability of morphine applied topically to cutaneous ulcers.
Click here to access the PubMed abstract of this article.

©Storey Marketing. Used with permission. All rights reserved.

Iontophoresis and phonophoresis are technologies that are capable of enhancing drug penetration through the skin. Phonophoresis uses ultrasonic waves to transmit molecules of drug through the skin, as opposed to iontophoresis, which uses low level electric current. Both techniques are used to treat inflammatory conditions such as arthritis, plantar fasciitis, tendonitis, bursitis, and carpal tunnel syndrome.

Iontophoresis: Many ionic drugs are available including several antivirals, various antibiotics, and other specific drugs. Iontophoresis of ionized drugs provided a 20-60 fold increase in penetration over topical application.

Examples of successful applications of iontophoresis include:

• treatment of inflammation/pain of muscles and tendons, including the Achilles tendon
• rapid, noninvasive local anesthesia, particularly for children
• relief of heel pain from bone spurs
• controlling the pain of tennis elbow
• relief of pain from rheumatoid arthritis of the knee
• relief of pain associated with plantar fasciitis
• improvement of jaw function in patients with temporomandibular joint (TMJ) disorders
• management of hip pain in patients with sickle cell disorders (SCD)
• an alternative to steroid injections for therapy of Carpal Tunnel Syndrome
• treatment for scar and tendon adhesions

Phonophoresis (or sonophoresis) combines ultrasound with topical drug therapy to achieve therapeutic drug concentrations at target sites below the skin. A cream or gel containing medications such as corticosteroids, local anesthetics, electrolytes, or antibiotics is applied to the treatment area and then massaged with a transducer head. The technique has been widely used in sports medicine since the 1960s by podiatrists, orthopedists, and physical therapists.

The method of preparation and quality of ingredients used for solutions or gels for iontophoresis or phonophoresis are critical to the success of the therapy and minimizing side effects.

Am J Sports Med. 1997 May-Jun;25(3):312-6
Treatment of plantar fasciitis by iontophoresis of 0.4% dexamethasone. A randomized, double-blind, placebo-controlled study.
Click here to access the PubMed abstract of this article.

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All formulations are customized per prescription to meet the unique needs of each patient. Please call us to discuss the dosage form, medication, and strength which are most appropriate for your patient.

• Ketoprofen topical or transdermal gel
• Ketamine transdermal gel
• Ketamine/Ketoprofen/Gabapentin transdermal gel
• Lidocaine/Prilocaine topical gel
• Triple-Anesthetic gel - benzocaine/lidocaine/tetracaine (“BLT”)
• Gabapentin/Clonidine in PLO (Pluronic Lecithin Organogel)
• Piroxicam tablet triturates
• Ibuprofen suppositories
• Ketoprofen/Cyclobenzaprine topical gel

©Storey Marketing. Used with permission. All rights reserved.