Naloxone

After intravenous injection, naloxone takes effect within one to two minutes, as it is rapidly distributed throughout the body via the bloodstream. It also crosses the blood-brain barrier quickly - eight to ten times faster than morphine. This contributes to its prompt onset of action. The duration of action of naloxone depends on the site of application and the dose, but the duration of action is comparatively short because the concentration in the cerebrospinal fluid falls rapidly and the active substance is broken down in the liver. The duration of action is about one to four hours, with a half-life of only about 70 minutes. Only in newborns is it reached after 2.5 to 3.5 hours. Naloxone is excreted renally, mainly in the form of its metabolite naloxone glucuronide.

The most common form of administration of naloxone is intravenous. The active substance is also administered as a nasal spray or injected subcutaneously/ intramuscularly.

Naloxone it is used as an antidote in opioid intoxication. Naloxone can also be administered in cases of analgesic-induced respiratory depression (e.g. after the administration of opioid analgesics).

In combination with oxycodone, naloxone is also processed into sustained-release tablets - in this case, the active ingredient has the task of reversing the side effects of the opioid in the intestine (constipation).

In combination with the opioid painkiller tilidine, naloxone prevents the misuse of tilidine as a narcotic, as naloxone would cancel out the effect of tilidine if administered intravenously. To treat opioid dependence, naloxone is combined with buprenorphine and then administered sublingually, transdermally or perorally.

Naloxone 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 naloxone passes into breast milk, it should only be used in nursing mothers after careful consideration of the benefits and risks.

Since naloxone competitively blocks the receptors and its half-life is also comparatively short, it is important that the active substance is administered in a sufficiently high dose. Otherwise, a displacement reaction at the receptor by the opioids would occur.

For respiratory depression and central nervous depression:

• Adults: 0.1-0.2 mg intravenously every two to three minutes.
• Children: 0.01-0.02 mg/kg body weight intravenously every two to three minutes.

For opioid overdose or intoxication

• Adults: 0.4-2.0 mg intravenously, after 3 minutes a further administration of 0.4 mg every two to three minutes if necessary (Important: If a total of 10 mg has not achieved the desired effect, the diagnosis should be questioned!)
• Children: 0.01 mg/kg body weight intravenously or intramuscularly, after three minutes a further administration if necessary.
• Newborns: If the mother received opioids, the newborn may be treated with naloxone to reverse their effect. The recommended dose is then 0.01 mg/kg body weight, with a repeat after three to five minutes if necessary.
• Overdose: An overdose is usually well tolerated.Caveat: Naloxone always also rapidly abolishes the analgesic effect of opioids. This can lead to an acute withdrawal syndrome in dependent individuals.

Dizziness, lightheadedness, tremor, hypertension, sweating, nausea and vomiting. The side effects are listed below according to their frequency.

Very common: nausea

Frequent: dizziness, headache, tachycardia, hypotension, hypertension, vomiting, postoperative pain.

Occasional: tremor, sweating, arrhythmias, bradycardia, diarrhea, dry mouth, hyperventilation, local irritation of the vascular wall, local inflammation.

Rare:seizures, nervousness, ventricular fibrillation, cardiac arrest.

Very rare: allergic reactions, anaphylactic shock, pulmonary edema, erythema multiforme.

Naloxone cancels not only the side effects of opioids but also their desirable effects (e.g. analgesia).

The interactions of naloxone are limited and at the usual dosage there are no interactions between naloxone and barbiturates or sedatives. The effects of naloxone may be delayed with concomitant consumption of alcohol, but this does not apply to all patients.

Hypersensitivity to the active substance. Caution with an existing opioid dependence! In this case, the use of naloxone can cause an acute withdrawal syndrome.

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

1. Panchagnula R et al. (2005) Transdermal delivery of naloxone: skin permeation, pharmacokinetic, irritancy and stability studies. Int J Pharm 293:213-223.
2. Summerfield JA (1980) Naloxone modulates the perception of itch in man. Br J Clin Pharmacol 10:180-183.