Naltrexone (Tablets, Capsules) Instructions for Use

ATC Code

N07BB04 (Naltrexone)

Active Substance

Naltrexone (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Competitive opioid receptor antagonist

Pharmacotherapeutic Group

Opioid receptor antagonist

Pharmacological Action

Competitive antagonist of opioid receptors. It eliminates the central and peripheral effects of opioids, including endogenous endorphins. It acts more intensively and for a longer duration than naloxone.

In alcoholism, it binds to opioid receptors and blocks the effects of endorphins. It reduces the craving for alcohol and prevents relapses.

Long-term use of naltrexone does not cause tolerance or dependence.

Pharmacokinetics

After oral administration, Naltrexone is almost completely absorbed from the gastrointestinal tract. The C_max of naltrexone and its active metabolite 6-β-naltrexol in blood plasma is reached within 1 hour.

With long-term use, Naltrexone does not accumulate in the body, while the concentration of 6-β-naltrexol in plasma reaches 40%. This is explained by the fact that the T_1/2 of the metabolite is longer than that of naltrexone.

95% of the naltrexone dose is biotransformed in the liver into pharmacologically active metabolites, the main one being 6-β-naltrexol, which is also an opioid antagonist. The second metabolite is 2-hydroxy-3-methoxy-6-β-naltrexol. Naltrexone and its metabolites undergo enterohepatic recirculation.

Naltrexone and its metabolites are excreted mainly by the kidneys. The amount of free naltrexone excreted in the urine is less than 1%, and the amount of free and conjugated 6-β-naltrexol is approximately 38%. The average T_1/2 of naltrexone is 4 hours, and that of 6-β-naltrexol is 13 hours.

Indications

Treatment of alcohol dependence (as part of combination therapy) and blockade of the effects of exogenously administered opioids; complex therapy of opioid dependence to maintain a state in the patient where opioids cannot exert their characteristic effect; to prevent relapse of opioid dependence after opioid detoxification.

ICD codes

Dosage Regimen

Administer orally as tablets or capsules. The dose, regimen, and duration of treatment are established individually by the physician based on the clinical situation.

For alcohol dependence, the usual maintenance dose is 50 mg once daily. Initiate treatment after confirming the patient is opioid-free for 7-10 days.

For opioid dependence, use to maintain a drug-free state. Initiate only after a naloxone challenge test confirms the patient is opioid-free and has completed detoxification.

Begin treatment with a test dose of 25 mg. Observe the patient for signs of precipitated withdrawal. If no withdrawal signs occur, proceed with the standard regimen.

For some patients, a alternate-day dosing regimen of 100 mg every other day or 150 mg every third day may be utilized. Adhere strictly to the prescribed schedule.

Take with food or antacids if gastrointestinal upset occurs. Swallow the tablet or capsule whole; do not crush or chew.

Discontinue naltrexone at least 48 hours before any planned surgical procedure requiring opioid analgesia. Inform all treating physicians of naltrexone use.

Regularly monitor liver function via blood tests during therapy. Report any symptoms of hepatitis, such as abdominal pain, jaundice, or dark urine, immediately.

Adverse Reactions

From the nervous system agitation, prostration, irritability, dizziness; rarely – depression, paranoia, feeling of fatigue, confusion, disorientation in time and space, hallucinations, nightmares, drowsiness, decreased visual acuity, pain and burning sensation in the eyes, photophobia, pain and feeling of fullness in the ears, tinnitus.

From the digestive system decreased appetite, diarrhea, constipation; rarely – dry mouth, flatulence, exacerbation of hemorrhoid symptoms, erosive and ulcerative lesions of the gastrointestinal tract, increased activity of liver transaminases.

From the urinary system rarely – frequent or difficult urination.

From the reproductive system delayed ejaculation, decreased sexual potency; rarely – increased or decreased libido.

Dermatological reactions rash; rarely – increased sebaceous gland secretion, tinea pedis, skin changes corresponding to the 1st stage of frostbite.

From the respiratory system rarely – hyperemia of nasal vessels, nosebleed, rhinorrhea, sneezing, dry throat, increased mucus secretion, sinusitis, difficulty breathing, tracheophony, cough, shortness of breath.

From the cardiovascular system rarely – phlebitis, edema, increased blood pressure, nonspecific ECG changes, tachycardia, feeling of heat in the extremities, sensation of sudden flushing of the face.

Other possible feeling of chills; rarely – increased or loss of appetite, weight gain, pathological yawning, fever, pain in the groin area, enlarged lymph nodes, lymphocytosis; one case of idiopathic thrombocytopenic purpura has been described in a patient who was apparently sensitized to naltrexone during previous treatment.

Contraindications

Hypersensitivity to naltrexone; patients taking opioid analgesics, including patients with current physical opioid dependence; patients in a state of acute opioid withdrawal (opioid withdrawal syndrome); patients who have not passed a naloxone challenge test or have a positive test for the presence of opioids in the urine; severe liver dysfunction (including acute hepatitis and liver failure); pregnancy, lactation (breastfeeding); children and adolescents under 18 years of age.

With caution impaired liver and/or kidney function.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in acute hepatitis, liver failure. Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with impaired kidney function.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Should be used with caution in elderly patients.

Special Precautions

Naltrexone can only be used in cases where the patient has not taken opioid analgesics for at least 7-10 days.

Use with caution in patients with impaired liver and/or kidney function.

Naltrexone should be discontinued at least 48 hours before surgery that will require the use of opioid analgesics.

Taking excessive doses of naltrexone can lead to hepatocellular disorders. Prescribing naltrexone to patients with acute liver diseases should be carefully considered and justified, taking into account the risk of liver function impairment. When used in recommended doses, Naltrexone is not hepatotoxic. Patients should be warned about the risk of liver disorders and advised to seek medical help if symptoms of hepatitis occur. If such symptoms occur, naltrexone treatment should be discontinued. Regular monitoring of liver function is recommended during treatment.

It should be borne in mind that when using naltrexone, the likelihood of complete recovery from opioid dependence is variable.

Effect on the ability to drive vehicles and machinery

During the use of naltrexone, patients should exercise caution when driving vehicles and machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with naltrexone, the effectiveness of opioid receptor agonists (antitussives, analgesics) is reduced.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.