Naltrexone

Naltrexone is a drug used to treat opioid overdoses and alcohol and opioid dependence.

Use and indications

Naltrexone is an opioid antagonist which can reverse the effects of opioids (morphine-like drugs) and thus can be used to counteract overdoses. Other indications include the treatment of alcohol and opioid dependence, as well as "off-label" uses for the treatment of various behavioral disorders associated with compulsive behavior.

Naltrexone is administered as film-coated tablets or as an intramuscular injection. The standard dosage for tablets is 50 mg It is available only with a doctor's prescription.

History

Naltrexone was first synthesized in 1963 and described in 1965 as an orally active, long-acting, and highly potent opioid antagonist. It was patented by Endo Laboratories in 1967. In the United States, naltrexone was first approved in 1984. A sustained-release formulation for intramuscular injection was approved by the FDA in 2006 for the treatment of alcohol dependence and in 2010 for the treatment of opioid dependence.

Use and indications

Naltrexone, a pure opioid antagonist at all 4 opioid receptor types. Naltrexone is indicated for the treatment of alcohol dependence and to block the effects of exogenously administered opioids. It markedly attenuates or completely and reversibly blocks the subjectively perceived effects of intravenously administered opioids. When administered concomitantly with morphine, naltrexone blocks physical dependence on morphine, heroin, and other opioids.

The mechanism of action of naltrexone in alcoholism is not clear, but preclinical data suggest involvement of the endogenous opioid system. Naltrexone is thought to act as a competitive antagonist at mc, κ, and δ-receptors in the CNS, with the highest affinity for the μ-receptor. Naltrexone binds competitively to these receptors and can block the action of endogenous opioids (endorphins). Blocking these endorphins suppresses cravings for substances such as alcohol or opioids.

The effect of naltrexone in treating alcohol addiction is described as moderate, reducing the amount and frequency of alcohol consumption. In the treatment of opioid addiction, naltrexone is very effective and has high comliance in patients, requiring subcutaneous administration only 1 time per month. However, one drawback is that use requires complete withdrawal beforehand, whereas current alternatives can be used after a short period of time.

There are studies indicating that naltrexone is useful for reducing behavioral addictions such as gambling or kleptomania, as well as compulsive sexual behavior. In one study, the majority of a group of sex offenders studied reported a sharp decrease in sexual urges and fantasies, which returned to baseline levels after discontinuation of the drug.

Pharmacokinetics

Naltrexone is well absorbed orally but has low bioavailability due to significant first-pass metabolism. This is approximately between 5% and 40%. Plasma protein binding is approximately 40%. Naltrexone is metabolized in the liver and excreted by the kidneys. The unchanged excreted fraction is only 2%. Naltrexone and its metabolites are excreted mainly in the urine. The elimination half-life is approximately 4 hours.

Drug Interactions

Naltrexone is not metabolized by the P450 enzyme system and therefore carries a low risk for interactions. Opioid analgesics used as emergency medications must be dosed higher while taking naltrexone. Taking opioid analgesics concomitantly with naltrexone increases the risk of respiratory depression and should therefore be done only in emergencies.

Contraindications

Naltrexone should not be taken in the following conditions or complaints:

• allergy to naltrexone
• acute hepatitis (liver inflammation) or other severe liver disease
• severe kidney disease
• existing use of opioids
• opioid dependence without having started withdrawal

Side effects

Common side effects of naltrexone include:

• Nausea
• Vomiting
• drowsiness
• anxiety
• headache
• restlessness
• nervousness
• abdominal pain
• Joint pain
• muscle pain and cramps
• weakness
• decreased appetite
• palpitations
• increased heart rate
• ECG changes
• libido disturbances
• thirst
• dizziness
• increased lacrimation
• chest pain
• diarrhea
• constipation
• rash
• delayed ejaculation and erectile dysfunction
• increased energy
• irritability
• increased sweating
• affective disorders
• cold symptoms
• sleep problems
• toothache

Pregnancy and breastfeeding

It is not known whether naltrexone can harm an unborn baby. This medication should be used during pregnancy only if the possible benefit justifies the possible risk.

It is not known whether naltrexone passes into breast milk when administered as an intravenous injection. Naltrexone from tablets passes into breast milk. Therefore, it is not recommended to be taken during breastfeeding.