Naltrexone

After oral administration, naltrexone is rapidly and completely absorbed from the gastrointestinal tract. After absorption, naltrexone undergoes substantial first-pass metabolism, producing 6-b-naltrexol as the major metabolite. The plasma half-life of naltrexone is approximately 4 hours, with a mean blood level of 8.55 ng/ml. The plasma half-life of 6-b-naltrexol is approximately 13 hours. Plasma protein binding of naltrexone is approximately 21%. Excretion is primarily by the kidney. Within 48 hours, approximately 60 % of a perorally administered dose is excreted in the urine as 6-b-naltrexol, hydroxy-methoxy-naltrexol and naltrexone.

Alcohol dependence: Naltrexone is approved for alcohol relapse prevention in many European countries (+USA). Approval is granted to reduce the risk of relapse, support abstinence and reduce craving for alcohol (craving) as part of a comprehensive therapy.

Other: Off-label, naltrexone is used successfully in the treatment of self-injurious behavior in dissociative disorders and borderline personality disorder. Naltrexone also appears to be useful for self-injurious behavior in the context of autism and developmental mental disorders. Thus, trichotillomania is an indication for naltrexone (Sani G et al. 2019).

Low-dose naltrexone (1.5-3.0-4.0 mg/day - nightly application) has been used successfully in individual cases of Hailey-Hailey M. (Albers LN et al. 2017; Ibrahim O et al. 2017).

Other possible dermatological indications include pruritus in atopic dermatitis and cholestasis, prurigo nodularis (Ekelem C et al. 2019), lichen planus follicularis (Strazzulla LC et al. 2017), and psoriasis (Weinstock LB et al. 2020).

Naltrexone does not appear to have teratogenic effects. Nevertheless, it should only be used in pregnancy if it is essential. In newborns, the active substance can lead to withdrawal symptoms.

As it is unclear whether naltrexone passes into breast milk, it should only be used in nursing mothers after careful consideration of the benefits and risks.

The initial dose of naltrexone hydrochloride should be 25 mg for patients who were opioid dependent; then 50 mg naltrexone hydrochloride) the next day. To support abstinence in alcohol dependence, the recommended dose is 50 mg per day. If the course of therapy is monitored, the dosage may also be adjusted as follows: 100 mg naltrexone hydrochloride on Monday and Wednesday, 150 mg naltrexone hydrochloride on Friday. Opioid blockade may be reduced with higher dosing at longer intervals.

Low-dose dosing: 1.5-4.0mg/day.

Adverse reactions(very common (≥ 1/10), common (≥ 1/100 to < 1/10), occasional (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known: frequency cannot be estimated based on available data).

• Infections: occasionally: herpes simplex labialis,
• Blood and lymphatic disorders: occasionally: lymphadenopathy, rarely: idiopathic thrombocytopenic purpura.
• Metabolic and nutritional disorders: frequent: decreased appetite
• Psychiatric disorders: very common: sleep disturbances, anxiety, nervousness; common: mood disturbances, irritability; occasional: agitation, confusion, hallucinations, depression, paranoia, disorientation, nightmares, libido disturbance, abnormal dreams; rare: suicidal ideation, attempted suicide.
• Nervous system disorders: very common: headache, restlessness; common: dizziness; occasional: tremor, somnolence.
• Eye disorders: frequent: increased lacrimation; occasional: visual disturbance, eye irritation, photophobia, swelling of the eye, painful eye or asthenopia
• Ear and labyrinth disorders; occasional: ear discomfort, ear pain, tinnitus, dizziness
• Cardiac disorders: frequent: tachycardia, palpitations, ECG changes, vascular disorders; occasional: blood pressure fluctuations, flushing
• Respiratory, thoracic, and mediastinal disorders: frequent: thoracic pain; occasional: nasal congestion, nasal symptoms, rhinorrhea, sneezing, oropharyngeal pain, increased sputum secretion, sinus disease, dyspnea, dysphonia, cough,
• Gastrointestinal disorders: very common: abdominal pain, nausea and/or vomiting; common: diarrhea, constipation; ulcer, dry mouth;
• Liver and biliary disorders: occasionally: hepatic dysfunction, bilirubin increase, hepatitis transaminase increase.
• Skin and subcutaneous tissue disorders: frequent: exanthema; occasional: seborrhoea, pruritus, acne, alopecia; occasional: hyperhidrosis.
• Musculoskeletal, connective tissue and bone disorders: very common: joint and muscle pain; very rare: rhabdomyolysis
• Kidney and urinary tract disorders: occasionally: pollakiuria, dysuria
• Naltrexone not only abolishes the side effects of opioids but also their desirable effects (e.g. analgesia).

Monopreparations: Adepend® (D), Dependex® (A), Ethylex® (A), Naltrexin® (A, CH), Nemexin® (D, A), Revia® (A) and generics (D, A)

Naltrexone as well as naloxone are derived from the morphine derivative oxymorphone and differ from it only by the replacement of a methyl group at the N-atom of the piperidine ring by a larger substituent.

A new substance that cannot cross the blood-brain barrier is methylnaltrexone.

1. Albers LN et al (2017) Treatment of Hailey-Hailey Disease With Low-Dose Naltrexone. JAMA Dermatol 153:1018-1020.
2. Ekelem C et al (2019) Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions: A Systematic Review. JAMA Dermatol 155:229-236.
3. Ibrahim O et al (2017) Low-dose naltrexone treatment of familial benign pemphigus (Hailey-Hailey disease). JAMA Dermatol 153:1015-1017.
4. Lee B et al (2019) The uses of naltrexone in dermatologic conditions. J Am Acad Dermatol 80:1746-1752.
5. Panchagnula R et al (2005) Transdermal delivery of naloxone: skin permeation, pharmacokinetic, irritancy and stability studies. Int J Pharm 293:213-223.
6. Sani G et al. (2019) Drug treatment of trichotillomania (hair-pulling disorder), excoriation (skin-picking) disorder, and nail-biting (onychophagia). Curr Neuropharmacol 17:775-786.
7. Strazzulla LC et al (2017) Novel Treatment Using Low-Dose Naltrexone for Lichen Planopilaris. J Drugs Dermatol 16:1140-1142.
8. Summerfield JA (1980) Naloxone modulates the perception of itch in man. Br J Clin Pharmacol 10:180-183.
9. Weinstock LB et al (2020) Low-dose naltrexone therapy for psoriasis. Int J Pharm Compd 24:94-96.