Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Appendix F
Adverse Events Table
The following is a set of 38 adverse event reports identified in the U.S. Food and Drug Administration’s (FDA’s) Adverse Event Reporting System (FAERS). This dataset describes one or more adverse event experiences resulting from the use of a topical compounded pain creams. Owing to the limited information collected, the data below can give a snapshot of the potential concerns related to insufficient labeling, systemic toxicity, and overall misuse (accidental and intentional) of these medications. See Chapters 4, 6, and 7 for additional discussions on what is known about the safety of compounded topical pain creams.
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
TABLE F-1
Adverse Events Table—Summarized Data
| Patient Demographics/Condition | Drugs Present in Compound | Suspected Cause of Adverse Event (SKRI-1; C-1-5) |
|---|---|---|
| 22y female; patient died after suspected single application of CPCs | Musculoskeletal + bupivicaine compound (no strength noted) No dosage instructions or possible side effects on the prescriptions |
Drug toxicity |
| 14m male; accidental ingestion of grandmother’s CPC (prescribed for diabetic foot pain) | Gabapentin 5%; lidocaine 5%; clonidine 2%; ketamine (nondocumented percentage); baclofen 0.4% | Misuse |
| 18m male; application of father’s CPC (prescribed for neck pain) to treat diaper rash | Ketamine 100 mg; clonidine 2 mg; gabapentin 60 mg; mefenamic acid 10 mg; imipramine 30 mg; and lidocaine 10 mg | Misuse |
| 22m female; cream was prescribed to another family member for an unknown indication, accidental ingestion of CPC | The concomitant medications were ketoprofen, lidocaine, prilocaine, camphor, menthol, ethoxydiglycol, and gabapentin | Misuse |
| 26m male; accidental ingestion of his mother’s CPC | Ketamine 10%, clonidine 0.2%, gabapentin 6%, diclofenac 5%, baclofen 2%, cyclobenzaprine 2%, menthol 1%, nifedipine 2%, and bupivacaine 1% | Misuse |
| 2y female; accidental dermal exposure | Pregabalin 2.5% (w/v), ketamine 10%, gabapentin 8%, and clonidine 0.3% | Misuse |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Physical Response | Publication (If Available) |
|---|---|
| Mother filed report to FDA after discovering her daughter’s body. She suspects her daughter received the CPCs in the mail without a doctor’s visit. According to autopsy report daughter died of toxic effects of ketamine and cyclobenzaprine. | N/A |
| EMTs reported the boy had pinpoint pupils, was only responsive to painful stimulation, and had slow and inadequate respiration. He was put on an endotracheal intubation respirator. After several hours on the respirator he experienced bradycardia (HR 58 bpm). He was admitted to the pediatric ICU and weaned off of respiration and vasoactive support for 2 days before he was discharged. | Lucyk, S. N., L. S Nelson, R. S. Hoffman, M. A. Howland, and M. Su. 2014. Ingestion of compounded ointment leading to significant toxicity in a child. Clinical Toxicology 52(7):801. |
| Within 20 minutes boy was unresponsive and gasping; was admitted to pediatric ICU and put on an endotracheal intubation respirator. Vital signs returned to normal over the next 12 hours. Blood taken returned with a serum clonidine level of 9.2 ng/mL (reference range, 0.5–4.5 ng/mL) and a norketamine level of 41 ng/mL (reporting limit, > 20 ng/mL). He was discharged the next morning. | Sullivan, R. W., M. Ryzewski, M. G. Holland, and J. M. Marraffa. 2013. Compounded ointment results in severe toxicity in a pediatric patient. Pediatric Emergency Care 29(11):1220–1222. |
| In the ED the patient was noted to have intermittent excitation with altered level of consciousness (somnolent condition), followed by periods of apnea, a depressed gag reflex, miosis, and pale, warm, dry skin. An EKG after intubation revealed sinus bradycardia with a rate of 75 BPM, nonspecific Twave inversions, and a firstdegree block with a PR interval of 178 milliseconds with normal QRS and QTc durations. After the patient was transferred to a pediatric ICU her vital signs indicated that the patient was comatose. Fluid resuscitation and “meticulous supportive care” allowed the patient to be extubated after 14 hours and released without incident after 3 days. | Cates, A. L., S. M. Wheatley, and K. D. Katz. 2018. Clonidine overdose in a toddler due to accidental ingestion of a compounding cream. Pediatric Emergency Care 34(4):e79–e81. |
| Patient developed hypotension and drowsiness but when given IV fluid his symptoms completely resolved overnight. | Henretig, F., et al. 2014. Toxicity from compounded analgesic creams. Clinical Toxicology 52(7):801–802. |
| Became drowsy, once at the ER she became apneic and was intubated; patient was discharged within 24 hours. | Lange, R. 2017. Apnea in a child following dermal exposure to compounded pain cream. Clinical Toxicology 55(7):733. |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Patient Demographics/Condition | Drugs Present in Compound | Suspected Cause of Adverse Event (SKRI-1; C-1-5) |
|---|---|---|
| 2y male; accidentally smeared his body with CPC | Nifedipine 2%, clonidine 0.2%, 10% ketamine, 5% diclofenac, baclofen 2%, gabapentin 6%, cyclobenzaprine 2%, menthol 1%, and bupivicaine 1% | Misuse |
| 22y female; over application of CPC, followed by wrapping area in plastic wrap | Lidocaine 10% and tetracaine 10% | Misuse |
| 23y male; over application of a CPC | Clonidine 0.2%, gabapentin 6%, imipramine 3%, ketamine 10%, lidocaine 2%, mefenamic acid 1% | Misuse |
| 34y female; intentional ingestion while on methadone | Bupivicaine 90 mg, clonidine 0.9 mg, cyclobenzaprine 90 mg, flurbiprofen 450 mg, and ketamine 450 mg | Misuse |
| 35y male; prescribed cream for relief of chronic pain, over application of CPC | Ketamine 900 mg; baclofen 900 mg; amitriptyline 360 mg; lidocaine 900 mg; and ketoprofen 1,800 mg | Misuse |
| 36y male; used expired CPC on his calf muscles | Neuromax pain cream (ketamine 15%, gabapentin 6%, clonidine 0.2%, prilocaine 7%, baclofen 3%, diclofenac 2%) | Misuse |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Physical Response | Publication (If Available) |
|---|---|
| A call came from a health care facility to Poison Control. Patient was brought in after he smeared three areas on his body with a topical pain cream; he was difficult to awaken with low BP and had very docile behavior. HR 130, BP 69/32, 12 lead EKG, improved with maintenance fluids to 110/59. | N/A |
| Patient had progressive downward course with seizure, decreasing responsiveness, and gradual loss of brainstem reflexes, variability in BP and HR, and elevated intracranial pressure. CT scan showed evolution of severe profound cerebral edema. Patient was declared brain dead and removed from life support at a later date (dates are redacted). She then died. | Unknown |
| Patient presented with HR 46 bpm, BP 180/87, respiratory rate 21 breaths/min., temperature 95.6; he had a decreased level of consciousness with response to painful stimuli, slurred speech, disorientation, mydriasis, and regular bradycardia. The patient spent 2 days in the hospital; at 6 month followup he had made a full recovery. | Pomerleau, A. C., et al. 2014. Dermal exposure to a compounded pain cream resulting in severely elevated clonidine concentration. Journal of Medical Toxicology 10(1):61–64. |
| She was intubated for airway protection when she was brought to the ED. She awoke and was extubated the next day. | Henretig, F., et al. 2014. Toxicity from compounded analgesic creams. Clinical Toxicology 52(7):801–802. |
| Over 2 hours patient lost all brainstem reflexes, and required intubation and mechanical ventilation for 2.5 days. He was discharged neurologically intact after 4 days. | Sigillito, R. J., V. E. Tuckler, K. W. Van Meter, and J. Martinez. 2003. Near fatal accidental transdermal overdose of compounded ketamine, baclofen, amitriptyline, lidocaine and ketoprofen: A case report. Journal of Toxicology and Clinical Toxicology 41(5):672. |
| A short time after application he had an out of body experience, lost feeling in extremities, and passed out. Upon ER presentation he had limited brain stem reflexes but normal MRI; initial tests showed acute ischemic stroke secondary to basilar occlusion. 24 hours after admission patient woke up. | N/A |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Patient Demographics/Condition | Drugs Present in Compound | Suspected Cause of Adverse Event (SKRI-1; C-1-5) |
|---|---|---|
| 58y female; prescribed for chronic neck pain and oral ulcers, purposeful overdose and misuse of CPC | Topical medication for chronic neck pain: amitriptyline 3%, baclofen 0.5%, diclofenac 3%, and lidocaine 5% 3 to 4 times daily as needed; and a topical lidocaine gel for oral ulcers | Misuse |
| 85y male; prescribed for severe intractable pruritus secondary to atopic dermatitis, over application of CPC | 10% ketamine, 5% amitriptyline, and 5% lidocaine (KAL) compounded in a Lipoderm base | Misuse |
| Adult (age unknown) female; accidental over application of CPC | Ketamine 3%, aloe 0.5%, amitriptyline 2%, baclofen 1%, estriol 0.1%, gabapentin 2%, lidocaine 2% | Misuse |
| 14y female; CPC prescribed for knee pain acerbated by running | 5F diclofenac3, gabapentin, lidocaine | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 29y female; prescribed for oral mucosa for dental pain | Pentoxifylline 3%, diclofenac 3%, bupivacaine 1%, gabapentin 6%, baclofen 2%, ibuprofen 3%, ketamine 10% | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Physical Response | Publication (If Available) |
|---|---|
| She was using the cream twice as often as instructed on her neck and in her mouth since she had run out of the lidocaine gel prescribed for her oral ulcers. She presented with acute onset altered mental status from serotonin syndrome. 5 days after she stopped using the cream she returned to cognitive baseline. Serum nortriptyline/amitriptyline level that was drawn at 6 am on the second day was found elevated at 288 ng/mL (amitriptyline 231 ng/mL). | Ellison, C. 2017. Staying topical: An unusual case of serotonin syndrome. Journal of Clinical Psychopharmacology 37(5):633–635. |
| A highly functioning man in his 80s with a history of Parkinson’s disease presented to the ED with slurred speech, ataxia, and altered mental status (resulting in confirmation of toxic encephalopathy). Four days prior to presentation, his dermatologist prescribed several new medications to manage severe intractable pruritus secondary to atopic dermatitis. Over the ensuing 2 weeks on the inpatient service, the patients’ mental status improved to baseline, and he was discharged on hospital day 17. | Cardis, M. 2016. Safety of topical neuromodulators for the treatment of pruritus. JAMA Dermatology 152(12):1390–1391. |
| Patient was instructed to apply CPC to vulvar area 3 times daily, but accidentally applied full 3 ml syringe intravaginally prior to reading the instructions. She was instructed to go to the ER but declined. She said she never felt anything other than a little sedated. | N/A |
| Area of application became swollen, formed hives, and extremely painful. | N/A |
| Presented to the ER with seizurelike activity (rhythmic shaking of her arms and legs), testing revealed a nonanion gap metabolic acidosis, and EEG demonstrated nonspecific findings consistent with toxic metabolic encephalopathy. A comprehensive urine drug screen demonstrated the presence of propofol, caffeine, topiramate, doxepin, ibuprofen, lidocaine, baclofen, and ketamine. Observed uneventfully and released on day 4. | Swartzentruber, G. S., et al. 2014. Inappropriate application of compounded topical pain medication cream leading to significant neurotoxicity. Clinical Toxicology 52(7):692–693. |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Patient Demographics/Condition | Drugs Present in Compound | Suspected Cause of Adverse Event (SKRI-1; C-1-5) |
|---|---|---|
| 33y female; prescribed for SI joint area pain | Ketoprofen 10%, baclofen 5%, gabapentin 5%, Keta 5% | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 37y female; CPC used to numb area prior to a skin treatment | Benzocaine 20%, lidocaine 6%, tetracaine 4% | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 37y female; prescribed CPC for shoulder pain | Compounded cream bupi/clon/doxe/gaba/pent (1K) 1/0.2/5/6/3% | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 39y male | Amantadine 10%, ibuprofen 20%, dexamethasone 0.4%, lidocaine 1% | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 44y female; applied CPC cream in gynecologist office to numb reddened, broken, inflamed skin | Benzocaine, tetracaine, lidocaine (no strengths given) | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Physical Response | Publication (If Available) |
|---|---|
| After first application patient could not straighten leg, could not walk, and experienced very painful nerve twitching on the inner part of right leg. The twitching lasted about 1.5 days, completely resolved on day 3. | N/A |
| About 10–20 minutes after application patient felt burning on leg and then chest tightening and difficulty breathing. Fingers and hands turned blue and patient became chilled. | N/A |
| After first week pain subsided; however, rash appeared. Patient talked with pharmacists who said the rash may be due to DMSO in the cream. | N/A |
| Patient experienced a bruiselike purple discoloration to the skin in the maxillary region of the body, which tingled and burned. When patient attempted to selfmedicate with aloe vera, further irritation occurred. | N/A |
| Within 5 minutes of application patient experienced tachycardia, diaphoresis, and chest pressure; after 15 minutes, abnormal involuntary movements with spasms including neck and jaw. Observed in doctor’s office for more than 2 hours then transferred to the ER where benzodiazepine was given IV and symptoms alleviated but returned the next day and progressively worsened. Out of work for 6 months, still has occasional twitches and spasms, but mostly resolved 2 years later. | N/A |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Patient Demographics/Condition | Drugs Present in Compound | Suspected Cause of Adverse Event (SKRI-1; C-1-5) |
|---|---|---|
| 48y male; prescribed CPC for frozen shoulder | Baclofen 2%, cyclobenzaprine 2%, diclofenac 3%, gabapentin 6%, bupivacaine 2% in a Versapro cream base | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 49y female; prescribed CPC for chronic pain in ankles, knees, wrists, hands, shoulder, and neck | Diclofenac 5%, baclofen 2%, cyclobenzaprine 2%, bupivacaine 1%, lidocaine 5%, prilocaine 2.5%, imipramine 3% | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 50y female; prescribed cream for tarsal tunnel syndrome in both feet | Concentrations/ingredients are unknown, compound was called Jonas Neuropathy Cream #3 | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 54y male; applied anesthetic CPC prior to ablative laser therapy | 23% lidocaine and 7% tetracaine mixed in ointment base | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 57y female; used CPC numbing cream prior to skin tag removal procedure | Lidocaine and benzocaine (strength not given) | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Physical Response | Publication (If Available) |
|---|---|
| Patient applied 1–2 grams of pain cream to shoulder for 10 days, four times per day, then noticed rash/hives develop on shoulder. Hives spread from shoulder to top of neck down to wrist on right side. | N/A |
| After application pain in shoulder increased, face became flushed, red, and swollen, felt disoriented, and she had trouble breathing. Event abated after use stopped. | N/A |
| After 1 week of applying CPC three times per day, resulted in dizziness, nausea, vomiting, and inability to get out of bed. After she stopped using the cream her symptoms have improved but she is still in pain and unable to work. | Unknown |
| Immediately after application of cream the patient developed a diffuse eruption of vesicles and bullae (ranging in size from 1 to 15 mm) on a welldemarcated erythematous base. The lesions resolved after less than 1 week with gentle skin care. Patient developed postinflammatory hyperpigmentation, which faded over 2 months. | Alok, V., and R. Markus. 2011. Immediate vesicular eruption caused by topical 23% lidocaine 7% tetracaine ointment in a patient scheduled for laser therapy: A new adverse drug reaction. Journal of Cosmetic Dermatology 10:307–310. |
| Patient experienced red ulcerating nodules and was very itchy where cream was applied for about 1 week. Full recovery in about 1 month. | N/A |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Patient Demographics/Condition | Drugs Present in Compound | Suspected Cause of Adverse Event (SKRI-1; C-1-5) |
|---|---|---|
| 58y male; prescribed CPC for tennis elbow | Diclofenac 3%, baclofen 2%, cyclobenzaprine 2%, lidocaine 2% | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| Late 50s/early 60s female; prescribed CPC for joint damage | Ingredient amounts were not listed on label, ketoprofen, lidocaine, and hydrocodone in a VanPen base | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; suboptimal compounded preparations) Inadequate labeling |
| 63y male; prescribed CPC for pain from degenerative disk disease in his neck | Compounded cream #180 GM keta/bupi/dicl/doxe/gaba/pent (7) 10/1/3/3/6/5 | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 65y female; prescribed CPC for rectal pain (included rectal tenesmus, burning and nerve pain) | XYREM (500 mg/ml solution) sodium oxybate, baclofen, | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 66y female; CPC prescribed for pain in foot | Baclofen 2%, diclofenac 5%, gabapentin 6%, tetracaine 3% | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Physical Response | Publication (If Available) |
|---|---|
| He only used the cream three times before he experienced an irregular heartbeat. The tachycardia continued for about 10.5 hours. | N/A |
| After three applications pain became worse and spread to other joints. Patient experienced edema in lower legs and knees, with stasis pigmentation, coldness in her legs, and abnormal sensations in her hands. These symptoms persist to a lesser extent after she stopped using the cream. | N/A |
| After using the cream for more than 2 weeks patient described the skin on his neck becoming bright red and dried out as though sunburned. | N/A |
| After application of the cream she developed a rash that spread and she reported urinating blood. | N/A |
| After 3 days of use patient started seeing small blood like blisters. On the fourth day it has progressed to a rash full of blisters and she stopped using the cream. Severe swelling with hives, deep blisters, and darkening (blackening) of toes and side of outer foot. Condition improved after patient stopped applying the cream but she is still having some swelling, peeling, and itching 1 month later. | N/A |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Patient Demographics/Condition | Drugs Present in Compound | Suspected Cause of Adverse Event (SKRI-1; C-1-5) |
|---|---|---|
| 66y male; CPC prescribed for nerve pain in feet | BENZ20%LIDO6%TETR4%PLO (K) | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 66y male; prescribed for CPC for tendonitis of left foot to be applied four times/day | 120 Gm CMP DBCT Lipoderm | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 70y female; prescribed for idiopathic itching, rash, shingles, and neuralgia | Compounded cream (gabapentin/lidocaine/clonidine/ketamine topical cream, percentages or mg of each API not given), patient was also taking the following oral medications: neurontin (gabapentin) 100 mg per day increased to 200 mg, and ibuprofen 200 mg. During this time the patient was also taking paracetamol (Norco 5/325 mg), cephalexin monohydrate (Keflex 250 mg), and using Neosporin (bacitracin zin, neomycin sulfate, polymixin b sulfate, 800 mg) daily | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 72y female; condition unknown | Emla cream—topiramate 2.5%, meloxicam 0.09%, in a base of Lidocaine 2.5%, Prilocaine 2.5% | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Physical Response | Publication (If Available) |
|---|---|
| Patient experienced chemical burns to foot skin. | N/A |
| After 6 days the patient noticed his foot skin looked like it had undergone a bad chemical burn but without pain, areas ranged from red to purple with some blistering and peeling. | N/A |
| The patient began taking gabapentin (Neurontin), ibuprofen, and applying the compounded cream 2–4 times per day for postherpetic neuralgia. She doubled the amount of Neurontin at the advice of her pharmacist and initially it worked but left her feeling dizzy and weak. The pain relief did not last and she developed abdominal pain. The outcome of these events was not recovered. | N/A |
| Allergic response to lidocaine, leg skin redness and blistering; patient was advised to stop using the cream. | N/A |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Patient Demographics/Condition | Drugs Present in Compound | Suspected Cause of Adverse Event (SKRI-1; C-1-5) |
|---|---|---|
| 74y female; prescribed cream to be applied perivaginally for chronic pelvis neuritis with vaginal pruritus; patient had 2year history of Alzheimer’s dementia | 6% gabapentin, 10% ketamine, 10% ketoprofen, 3% lidocaine, and 0.6% clonidine | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
| 75y male; prescribed cream containing gabapentin for pain after a lumbar discectomy procedure, to be applied to his entire back and left lower extremity three times daily | 10% ketamine, 3% imipramine, 2% lidocaine, 1% mefenamic acid, 0.2% clonidine, gabapentin (unknown dose) | Reaction due to unknown cause (e.g., allergy to the API or excipient; drug–drug interactions; systemic toxicity; suboptimal compounded preparations) |
NOTE: API = active pharmaceutical ingredient; BP = blood pressure; bpm = beats per minute; CPC = compounded pain cream; CT = computed tomography; DMSO = dimethyl sulfoxide; ED = emergency department; EEG = electroencephalogram; EKG = electrocardiogram; EMT = emergency medical technician; ER = emergency room; FDA = U.S. Food and Drug Administration; HR = heart rate; ICU = intensive care unit; IV = intravenous; intravenously; KAL = ketamine, amitriptyline, and lidocaine; MRI = magnetic resonance imaging; PR = a PR interval in electrocardiography is the measure of time in milliseconds between the onset of atrial depolarization and the onset of ventricular depolarization; QRS = a QRS complex is the combination of three of the graphical deflections seen on a typical electrocardiogram (the Q, R, and S waves); QTc = corrected QT interval; a QT interval is a measurement made on a electrocardiogram used to assess some of the electrical properties of the heart; SI = sacroiliac.
Considerations for data extracted from the FAERS database:
These adverse event reports were identified in the FAERS database by the study sponsor, FDA. FDA identified 38 adverse events reports that relate to the use of a compounded topical drug by reading through report descriptions of all entries marked as compounded. It is important to note that there may be other FAERS cases related to the use of a compounded topical drugs, but if the necessary indication box for compounded mediations was not checked during the data entry process, then those cases would not be represented in the full dataset.
For full submitted data please see the Public Access File for the Committee on the Assessment of the Available Scientific Data Regarding the Safety and Effectiveness of Ingredients Used in Compounded Topical Pain Creams at the National Academies website at https://www8.nationalacademies.org/pa/managerequest.aspx?key=HMDHSP1818 (accessed April 9, 2020).
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
| Physical Response | Publication (If Available) |
|---|---|
| Within the first 2 weeks of cream use, her behavior became increasingly erratic prompting a visit to primary care. Believing that her unusual behavior and altered mental status was a consequence of dementia, both risperidone and lorazepam were prescribed. Six days later, she applied the cream over her upper body, arms, perineum, and vulva. She soon became markedly agitated, expressing homicidal ideation toward her husband by burning down the house, and suicidal ideation. | Soumoff, A. A., D. L. Cook, and C. C. Clark. 2018. Delirium following topical application of compounded creams containing multiple analgesic medications in geriatric patients: Two new cases. Psychosomatics 59(1):81–89. |
| From onset of cream use, he had an altered mental status and delirium. He became increasingly angry and paranoid with decreased need for sleep. During hospital week 1, despite discontinuation of the cream, he frequently became hostile and combative. Over the last few days of his 13day hospitalization, his mental status and behavior returned to baseline with no cognitive deficits. | Soumoff, A. A., D. L. Cook, and C. C. Clark. 2018. Delirium following topical application of compounded creams containing multiple analgesic medications in geriatric patients: Two new cases. Psychosomatics 59:81–89. |
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
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Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
Suggested Citation:"Appendix F: Adverse Events Table." National Academies of Sciences, Engineering, and Medicine. 2020. Compounded Topical Pain Creams: Review of Select Ingredients for Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. doi: 10.17226/25689.
×
