Naltrexone Cyanocobalamin Topical Cream

Psoriasis Vulgaris, Erythrodermic Psoriasis
Published case studies of low doses of naltrexone (4.5mg nightly) have shown substantial relief from psoriasis vulgaris4 and erythrodermic psoriasis⁵.

VITAMIN B12
Mild to Moderate Plaque Psoriasis
24 patients with mild to moderate plaque psoriasis were enrolled in a 12-week randomized, controlled, single-blind study, followed by a 4-week observational washout period.

Patients were administered either Vitamin B12 ointment containing 0.07% cyanocobalamin with 20% avocado oil (M-treatment) and a glycerol-petrolatum emollient cream (C-treatment) twice daily to the affected skin areas on contralateral sides of their bodies.

After 14 days, there was a statistically highly significant decrease in PASI scores in all M-treated body sides, whereas only small decrease in C-treated sides. The M-treated PASI scores remained lower than the C-treated body scores throughout the study, as well as the washout period.¹

Manifest & Treatment Resistant Psoriasis
A total of 12 patients (8 males and 4 females, 21–86 years old) with manifest and treatment-resistant psoriasis (moderate to severe) were included and treated for 12 weeks.

All patients were assigned to twice-daily treatment with a newly developed topical combination containing plant-based extracts traditionally used in skin disease as black cumin, olive oil, tea tree oil, cocoa butter completed by vitamin A and vitamin B₁₂.

Treatment success was determined by the Psoriasis Area and Severity Index (PASI) score, the body surface area, and the dermatology life index. PASI reduction of >75% in 10 of the 12 treated patients (83%). The remaining two patients showed a PASI reduction of ≤50%. In 5 of the patients PASI reduction was achieved <12 weeks (between week 3–11). ²

Chronic Plaque Psoriasis
In this randomized, prospective clinical trial, the effects of the vitamin D3 analog calcipotriol were evaluated in a trial population of 13 patients (10 men, 3 women) with chronic plaque psoriasis against those of a recently developed vitamin B12 cream containing avocado oil in an intraindividual right/left-side comparison for an observation period of 12 weeks.

There was a more rapid development of beneficial effects with the use of calcipotriol in the initial 8 weeks, although differences in effects were significant only at the time point of therapy week 8 (p < 0.05). After 12 weeks, neither the PASI score nor 20-MHz sonography showed significant differences between the two treatments. While the efficacy of the calcipotriol preparation reached a maximum in the first 4 weeks and then began to subside, the effects of the vitamin B12 cream containing avocado oil remained at a constant level over the whole observation period.⁷

Topical Application

• Topical cyanocobalamin has been clinically studied at a dosing strength of 0.07%.^1,2,7

• Topical naltrexone has been clinically studied at a dosing strength of 1%.³
• Naltrexone and cyanocobalamin may be used in combination or separately and is mostly used as a once daily application to affected areas.

Naltrexone (Oral)

• Naltrexone is most commonly prescribed at doses ranging from 0.5-4.5mg to be taken daily by mouth at bedtime.^3,4
• Each patient will react to LDN at their own individual dosage.
• Pediatric doses are most commonly prescribed at 0.1mg/kg/day.
• Patients should be encouraged to assess the efficacy of LDN for at least 6 months before dismissing it as a clinical utility.
• If clinical efficacy has not been achieved at the typical studied dosage of 4.5mg, some physicians have found benefits for their patients from doses up to 6-12mg.
• If clinical efficacy has been achieved, and patients subsequently complain of a resurgence in symptoms, consider implementing drug holidays, or a complete stoppage of therapy for 2 weeks followed by a re-initiation and reassessment of an efficacious dosage.
• Some patients may benefit from dosing LDN in the morning for several weeks if they experience insomnia and vivid dreams.
• Many physicians report no safety concerns when dosed with short acting opioids (i.e morphine). In this population, patients should separate short acting opioid consumption to 4-6 hours before an LDN dose, or 3-4 hours after an LDN dose.

The most commonly reported adverse effects of naltrexone taken orally include insomnia, vivid dreams, diarrhea, and headaches.

Common adverse effects of parenteral administration of cyanocobalamin include asthenia, headache, paresthesia, congestive heart failure, pulmonary edema, thrombosis, anaphylaxis, and optic atrophy.

Naltrexone
Naltrexone antagonizes the effects of opioid-containing medicines, such as cough and cold remedies, antidiarrheal preparations and opioid analgesics. Therefore, patients taking naltrexone may not benefit from opioid-containing medicines.

No clinical drug interaction studies have been performed with naltrexone to evaluate drug interactions; therefore, prescribers should weigh the risks and benefits of concomitant drug use.

Naltrexone is not a substrate for CYP P450 drug metabolizing enzymes. Therefore, inducers or inhibitors of these enzymes are unlikely to change the clearance of naltrexone.

Vitamin B12
Chloramphenicol (moderate), colchicine/omeprazole/ ascorbic acid/aminosalicyclic acid (minor)

Absorption. Naltrexone is almost completely absorbed (96%), but its oral bioavailability ranges between 5% and 40% due to first-pass metabolism.

Distribution. In vitro data demonstrate that naltrexone plasma protein binding is low (21%).

Metabolism. Naltrexone’s half-life is 4 hours and it is extensively metabolized (>98%) in humans—the major metabolite being 6-β-naltrexol with a half-life of 13 hours and antagonist action on opioid receptors.

The cytochrome P450 system is not involved in naltrexone metabolism. Two other minor metabolites are 2-hydroxy-3-methoxy-6β-naltrexol and 2-hydroxy-3-methoxy-naltrexone. Naltrexone and its metabolites are also conjugated to form glucuronide products.

Significantly less 6β-naltrexol is generated following subcutaneous administration of naltrexone compared to administration of oral naltrexone due to a reduction in first-pass hepatic metabolism.

Elimination. Glomerular filtration is the predominant mode of renal elimination for a small fraction of unmetabolized naltrexone, while 6-β-naltrexol is additionally secreted.

Pregnancy
Safety and effectiveness have not been clinically studied in this population. Therefore, this compound should not be used in pregnant women.

Lactation
It is not known whether it is safe for breastfeeding mothers. Therefore, this compound should not be used in lactating women who are breastfeeding.

Children
Studies with children 8-17 years old were given low dose naltrexone at 0.1mg/kg for 8 weeks to treat Crohn’s disease. Oral LDN was well tolerated without serious adverse events in this patient population.

Interference with Laboratory Tests
Naltrexone may be cross-reactive with certain immunoassay methods for the detection of drugs of abuse (specifically opioids) in urine.

Unintended Opiate Withdrawal
To prevent occurrence of an acute abstinence syndrome (withdrawal) in patients dependent on opioids, or exacerbation of a pre-existing subclinical abstinence syndrome, opioid-dependent patients, including those being treated for alcohol dependence, patients should be opioid-free from longer acting opioids for a minimum of 7–10 days before starting naltrexone treatment. Since the absence of an opioid drug in the urine is often not sufficient proof that a patient is opioid-free, a naloxone challenge test may be employed if the prescribing physician feels there is a risk of precipitating a withdrawal reaction following administration of naltrexone. Patients treated for alcohol dependence with naltrexone should be assessed for underlying opioid dependence and for any recent use of opioids prior to initiation of treatment with naltrexone. Precipitated opioid withdrawal has been observed in alcohol-dependent patients in circumstances where the prescriber had been unaware of the additional use of opioids or dependence on opioids.

Surgery
When Reversal of Naltrexone is Required for SurgerY, patients taking naltrexone should be encouraged to stop their medication by at least 24 hours before a scheduled or elective surgery.

• Patients receiving opioid analgesics
• Patients with current physiologic opioid dependence
• Patients in acute opiate withdrawal
• Any individual suspected of opioid abuse, and who has failed the naloxone challenge test or has a positive urine screen for opioids.
• Hypersensitivity to cobalt, vitamin B12, or any component of the product.

• Keep out of reach from children.
• Store in a cool and dry place. Avoid exposure to direct sunlight.

1. Del Duca E, Farnetani F, De Carvalho N, Bottoni U, Pellacani G, Nisticò SP. Superiority of a vitamin B12-containing emollient compared to a standard emollient in the maintenance treatment of mild-to-moderate plaque psoriasis. Int J Immunopathol Pharmacol. 2017; 30(4):439‐444.
2. Michalsen A, Eddin O, Salama A. A case series of the effects of a novel composition of a traditional natural preparation for the treatment of psoriasis. J Traditional and Complementary Medicine. 2016 Oct; 6(4) 395-398.
3. Bigliardi Pl, Stammer H, Jost G, Rufli T, Buchner S, et al. Treatment of pruritus with topically applied opiate receptor antagonist. J Am Aca Dermatol. 2007; 56: 979-988.
4. Bridgman AC, Kirchhof MG. Treatment of psoriasis vulgaris using low-dose naltrexone. JAAD Case Rep. 2018;4(8):827‐829. Published 2018 Sep 18.
5. Beltran Monasterio EP. Low-dose Naltrexone: An Alternative Treatment for Erythrodermic Psoriasis. Cureus. 2019;11(1):e3943. Published 2019 Jan 23. doi:10.7759/cureus.3943
6. Ip K, Song G, Banov D, Bassani AS, Valdez BC. In vitro evaluation of Naltrexone HCl 1% Topical Cream in XemaTop™ for psoriasis. Arch Dermatol Res. 2020;312(2):145‐154
7. Stücker M, Memmel U, Hoffmann M, Hartung J, Altmeyer P. Vitamin B(12) cream containing avocado oil in the therapy of plaque psoriasis. Dermatology. 2001;203(2):141-7. doi: 10.1159/000051729. PMID: 11586013.

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