Vivitrol, 380 mg, powder for the preparation of a suspension for intramuscular administration of prolonged action, 1 pc.

Vivitrol is a drug that is intended for drug treatment for drug and alcohol addiction, while it is equally effective for treating both types of addictions.

The use of Vivitrol is based on an active ingredient such as Naltrexone. Naltrexone blocks opioid receptors in the brain.

Let's take a closer look at how this drug works and why Vivitrol has such good reviews. There are special receptors in the brain, they are called “opioid”. They are divided into 4 types, but we will not go into these details. What interests us is that these receptors are responsible for getting that “high”. It is with opioid receptors that narcotic substances, products of the breakdown of ethanol, bind, as a result of which a person receives the desired intoxicating effect.

Release form and composition

Vivitrol is produced in the form of a powder for the preparation of a long-acting suspension for intramuscular (im) administration: a powdery mass from white (almost white) to light yellow-brown in color, does not contain visible foreign inclusions. The supplied solvent is a colorless, transparent liquid in which the powder is easily suspended, without agglomerates, into a white or slightly yellowish-brown suspension passing through the needle (included) with little or no resistance; At the same time, no solvent should come out of the needle without a suspension (430 mg each in glass bottles with a capacity of 5 ml, complete with a solvent - 4 ml, a syringe with a volume of 5 ml, one short needle for preparing a suspension and two needles for injection; in a cardboard pack 1 kit).

1 bottle of powder contains (including an excess of 12.9%) the active ingredient: naltrexone [encapsulated in polymer: 75:25 DL JN1 (copolymer of glycolic and lactic acids)] – 430 mg.

One bottle is designed to prepare 1 dose (4 ml) of the finished suspension, containing naltrexone - 380 mg.

1 bottle of solvent contains sodium chloride, polysorbate 20, sodium carmellose (sodium carboxymethylcellulose), water for injection.

Where to buy Vivitrol?

Today this is not a problem. Vivitrol is a drug that can be bought at any pharmacy chain or online pharmacy. Lately, I prefer to order medications online, as prices are more affordable.

You already understand that it is impossible to clearly call Vivitrol a panacea or a placebo. The drug showed itself very well in cases where the patients themselves had a strong motivation to quit drinking.

The support of doctors, and especially relatives, friends and family members, also plays a large role in the positive effects of Vivitrol.

Of course, the drug works, although it is not yet possible to call it an ideal remedy for combating alcoholism. However, it is also impossible to talk about it as a “dummy”, a means of mental influence - the drug helps, it works, just a lot depends on the human factor.

The drug Vivitrol will definitely help if the patient is surrounded by the attention of people who love him and is isolated from the pathological environment.
Good luck! And never lose hope! This article is worth sharing with friends. Press!

Pharmacological properties

Pharmacodynamics

The active component of Vivitrol, naltrexone, is an opioid receptor antagonist with the greatest affinity for OR-μ (opioid mu receptors). Naltrexone exhibits no pharmacological activity other than blockade of opioid receptors, but for unknown reasons can cause pupillary constriction. Does not contribute to the development of tolerance or mental/physiological dependence. Administration of Vivitrol to patients with physical opioid dependence causes withdrawal symptoms.

In patients with alcohol dependence, when taking naltrexone, the neurobiological mechanisms responsible for reducing alcohol consumption are activated; their effect has not been fully studied, but it is assumed that it is associated with the function of the endogenous opioid system.

Naltrexone, by competitively binding to OR-μ, blocks the effect of opiates. The blockade of the action of naltrexone can be reversed by the administration of high doses of opioids, which may result in an increase in histamine release, accompanied by a characteristic clinical picture. Communication with opioid receptors can block the action of endogenous opioid peptides.

Since naltrexone is not an aversive therapy, Vivitrol does not cause a disulfiram-like reaction when consuming opiates or alcohol.

Pharmacokinetics

• absorption: intramuscular administration of naltrexone is characterized by two peaks in the concentration of its level in the blood plasma - the initial one, reaching its maximum value after administration after about 2 hours, and the second - after 2-3 days. The concentration of the substance in the plasma begins to decrease after approximately 2 weeks, the process occurs gradually, and its indicators remain measurable for more than 1 month. For naltrexone and its main metabolite (6-beta-naltrexol), the maximum concentration (Cmax) and the total concentration during the entire observation period (AUC) in the blood plasma are proportional to the dose of Vivitrol administered intramuscularly. With a single dose of 380 mg of Vivitrol, the total exposure to naltrexone is 3-4 times higher than when taken orally at 50 mg/day for 4 weeks. The equilibrium concentration (Css) after the first administration is reached by the end of the interdose interval, the accumulation of naltrexone and its main metabolite after repeated administration is minimal (<15%);
• distribution: based on the results of in vitro studies, it was determined that naltrexone binds weakly to plasma proteins (up to 21%);
• metabolism: naltrexone is actively metabolized, its main metabolite, 6-beta-naltrexol, is formed with the participation of the cytosolic enzyme dihydrodiol dehydrogenase. Isoenzymes of the cytochrome P450 system do not participate in the metabolism of the drug. Naltrexone, its main metabolite and other metabolites (2-hydroxy-3-methoxy-6-beta-naltrexol, 2-hydroxy-3-methoxy-naltrexone) are conjugated with glucuronic acid. Due to reduced presystemic elimination, intramuscular administration of Vivitrol significantly reduces the formation of 6-beta-naltrexol compared to oral administration;
• excretion: naltrexone and its metabolites are excreted primarily by the kidneys, the amount of the drug excreted unchanged is minimal. The half-life (T1/2) of naltrexone and its main metabolite ranges from 5 to 10 days. For naltrexone, it depends on the degree of degradation of the polymer.

Pharmacokinetic parameters of naltrexone in special clinical cases:

• liver dysfunction: mild or moderate (class A and B on the Child-Pugh scale) - pharmacokinetics do not change, no dose adjustment is required for patients; severe liver dysfunction - pharmacokinetics have not been studied;
• renal dysfunction: mild degree with creatinine clearance (CC) from 50 to 80 ml/min - practically does not affect the effectiveness, dose adjustment is not required for patients; moderate and severe renal impairment - pharmacokinetics have not been studied;
• gender: according to the results of studies conducted with healthy patients of both sexes (18 women and men each), it was found that the pharmacokinetics of naltrexone is not affected by the gender of the patients;
• elderly patients, children and representatives of different races: pharmacokinetics have not been studied.

Vivitrol - analogues

Naltrexone is an analogue of Vivitrol, available in tablet form.

Comparing them, I consider the high cost of treatment to be the main disadvantage of Vivitrol.

But compared to Naltrexone, Vivitrol

• much better tolerated by the body;
• has a less toxic effect on the liver;
• side effects are more rare.

Other analogues of Vivitrol:

• Naltima;
• Naltrex;
• Naxon;
• Antakson.

Indications for use

According to the instructions, Vivitrol is recommended for the treatment of alcohol dependence only in patients who are able to abstain from drinking alcohol before starting the course (they also need to restrain themselves from actively drinking alcohol at the beginning of treatment).

The drug is prescribed to prevent relapse into opioid addiction after opioid detoxification. Opiate-dependent patients (including those receiving treatment for alcoholism) should not take opioids at the beginning of treatment.

Taking Vivitrol should be part of a comprehensive program to eliminate addiction, one of the components of which should be psychosocial support.

Reviews of Vivitrol

The problem of alcohol addiction in society is one of the most acute. Therefore, there are a lot of reviews about Vivitrol on forums and websites dedicated to this topic. Typically, messages are left by relatives of patients who suffer from alcohol addiction.

Quite often there are stories that after the injection, patients feel unwell - severe headache , joint and stomach pain . In addition, an apathetic or depressive state, weakness, nervousness, and so on persist for quite a long time.

However, many users report the effectiveness of this treatment. Of course, this requires a long time, regular monitoring of the patient’s condition and psychological support, but relatives of alcoholics are ready to do almost anything for their recovery.

However, there are cases where it was not possible to cure alcohol addiction with Vivitrol. The reason for this lies in the fact that the patients could not abstain from consuming alcoholic beverages at the beginning of therapy, even for several days. Therefore, the treatment did not bring the expected effect.

Contraindications

• simultaneous use of narcotic analgesics;
• concomitant use of opioids;
• opioid withdrawal syndrome (sudden withdrawal of opioids);
• no results of a naloxone challenge test, a positive test result for the presence of opioids in the urine;
• severe liver failure (including hepatitis);
• pregnancy period;
• lactation (breastfeeding);
• children and adolescents under 18 years of age;
• individual hypersensitivity to any components included in the drug and solvent.

Instructions for use of Vivitrol: method and dosage

The injection should only be administered by qualified healthcare professionals. To prepare the solution and carry out the procedure, you must use only the components contained in the package; replacing them is not allowed.

Vivitrol is a long-acting drug; it is recommended to be administered intramuscularly once every 28 days or once a month at a dose of 380 mg. The drug is injected into the muscle of the right and left buttocks alternately.

The solution prepared from the suspension cannot be administered intravenously or subcutaneously.

If you miss a regular injection, the next dose should be administered as quickly as possible.

Before starting IM administration of naltrexone, oral administration is not required.

There is no data on resuming therapy after a break.

There are no systematic data on the results of switching patients from oral naltrexone to Vivitrol.

To prepare the suspension, use only the solvent supplied in the kit. The drug must be administered using the needle included in the kit. For injection, all packaging components are required - vials with powder and solvent, a needle for preparing the suspension and an injection needle with a protective cap. The kit also includes a spare injection needle with a protective cap. Replacement of components included in the kit is strictly prohibited.

To ensure accurate dosing, you must strictly follow the directions for preparation and administration of the drug.

During the preparation and administration of the suspension, aseptic rules should be strictly observed.

Recommendations for the procedure:

1. 45 minutes before the injection, remove the package with the drug from the refrigerator and allow it to warm to room temperature.
2. To loosen the powder before diluting, to facilitate mixing, tap the bottom of the bottle on a hard surface.
3. The aluminum safety caps must be removed from both bottles (the drug cannot be used if the bottle caps are missing or damaged).
4. The necks of the bottles should be wiped with an alcohol wipe.
5. To prepare the suspension, a short needle must be placed on a syringe, and 3.4 ml of solvent must be drawn from the bottle with the solvent, while a certain amount of the solvent will remain in the bottle. Add 3.4 ml of solvent into the bottle with the powder and shake the bottle vigorously for about 1 minute to mix the solvent and powder. Make sure that the suspension is homogeneous; it should be milky white, free of lumps, and flow freely down the walls of the bottle.
6. After visually assessing the prepared suspension, using the same short needle, draw 4.2 ml into the syringe.
7. Replace the needle on the syringe for preparing the suspension with a needle for injection. Before injection, tap the syringe to release air bubbles, then gently press the plunger, leaving 4 ml of suspension in it. Everything is ready for immediate injection.
8. Insert the needle of the syringe deep into the gluteal muscle, using a suction movement of the piston, check whether the needle has entered the vessel; there should be no blood in the syringe. A spare needle in the kit is necessary if blood appears and you need to repeat the procedure, having first replaced the first needle with it. The suspension should be injected with a smooth movement deep into the gluteal muscle. Injections are performed alternately into different buttocks.
9. After the procedure, the needle should be covered with a protective cap, holding it away from you and pressing it against a hard surface with one hand. The safety cap prevents splashing of liquid, the remains of which may be on and in the needle after injection. Used/unused packaging components should be thrown away.

Similar drugs:

• Naltrexone Oral tablets
• Naloxone Injection Solution
• Naloxone hydrochloride Substance-powder
• Antaxone Rectal solution
• Naltrexone hydrochloride Substance-powder
• Prodetoxon Tablets
• Naltrexone FV Capsule
• Antaxone Capsule
• Naloxone tridecanoate Substance-powder

** The Drug Directory is intended for informational purposes only. For more complete information, please refer to the manufacturer's instructions. Do not self-medicate; Before starting to use Vivitrol, you should consult a doctor. EUROLAB is not responsible for the consequences caused by the use of information posted on the portal. Any information on the site does not replace medical advice and cannot serve as a guarantee of the positive effect of the drug.

Are you interested in Vivitrol? Do you want to know more detailed information or do you need a doctor's examination? Or do you need an inspection? You can make an appointment with a doctor - the Euro lab is always at your service! The best doctors will examine you, advise you, provide the necessary assistance and make a diagnosis. You can also call a doctor at home . Euro lab clinic is open for you around the clock.

** Attention! The information presented in this medication guide is intended for medical professionals and should not be used as a basis for self-medication. The description of the drug Vivitrol is provided for informational purposes only and is not intended for prescribing treatment without the participation of a doctor. Patients need to consult a specialist!

If you are interested in any other drugs and medications, their descriptions and instructions for use, information about the composition and form of release, indications for use and side effects, methods of use, prices and reviews of drugs, or you have any other questions and suggestions - write to us, we will definitely try to help you.

Side effects

The results of clinical studies lasting up to six months in patients taking Vivitrol therapy:

• alcohol dependence: 9% of patients stopped treatment due to side effects. In the placebo group, under the same conditions, 7% of subjects stopped treatment. The most common reason for refusal of the drug was: reactions at the injection site – 3%; nausea – 2%; pregnancy – 1%; headache – 1%; suicidal behavior – 0.3%. Moreover, in the placebo group, treatment was stopped due to reactions at the injection site in only 1% of cases;
• Opioid dependence: 2% of both opioid dependent patients and placebo subjects discontinued due to side effects.

Frequent adverse reactions from systems and organs (more than 5% of cases) in patients with alcoholism, encountered during clinical studies, with mild to moderate severity:

• digestive system: nausea/vomiting, diarrhea, dry mouth, gastrointestinal upset, frequent urge to defecate, abdominal pain, frequent loose stools, stomach discomfort, decreased/impaired appetite, anorexia;
• respiratory system: infection of the upper respiratory tract (sinusitis, laryngitis, nasopharyngitis, pharyngitis, including streptococcal);
• musculoskeletal system: joint pain, arthritis, joint stiffness, limb pain, back pain, muscle spasm/twitching, muscle stiffness;
• skin and subcutaneous tissues: rash, papules, prickly heat;
• nervous system: headache, dizziness, migraine, fainting, anxiety, drowsiness, sedation;
• general reactions: asthenia, lethargy, hemorrhages, lethargy;
• local reactions: compaction, pain, soreness, swelling, itching.

In patients with opioid dependence, side effects were generally the same as those observed in the treatment of alcohol dependence.

Frequent adverse reactions from systems and organs (more than 2% of cases) in patients with opioid dependence, encountered during clinical studies, with mild to moderate severity:

• respiratory system: flu, nasopharyngitis;
• nervous system: insomnia, headache;
• cardiovascular system: increased blood pressure (BP);
• general disorders, reactions at the injection site: pain;
• digestive system: toothache;
• laboratory parameters: increased activity of liver transaminases alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the enzyme gamma-glutamyl transpeptidase (GGT).

Side effects identified during pre-registration clinical trials of the drug:

• digestive system: dysgeusia, increased appetite, constipation, flatulence, gastrointestinal bleeding, colitis, tooth abscess, hemorrhoids, paralytic ileus, pararectal abscess, gastroenteritis, abdominal discomfort, cholelithiasis, acute pancreatitis, increased AST and ALT activity, acute cholecystitis, reflux esophagitis;
• mental disorders: sleep disturbance, irritability, alcohol withdrawal syndrome, euphoria, agitation, delirium;
• nervous system: migraine, impaired attention, decreased mental performance, convulsions, aneurysms of cerebral arteries, ischemic stroke, paresthesia;
• sensory organs: conjunctivitis, blurred vision;
• musculoskeletal system: muscle spasm, pain in the limbs, joint stiffness, myalgia;
• skin and subcutaneous tissues: hyperhidrosis, including at night, itching;
• respiratory system: shortness of breath, sore throat, nasal congestion, bronchitis, obstructive bronchitis, pneumonia, sinusitis, laryngitis, upper respiratory tract infections;
• metabolism: dehydration, heat stroke, hypercholesterolemia;
• cardiovascular system: pulmonary thrombosis, deep vein thrombosis, hot flashes, atrial fibrillation, rapid heartbeat, myocardial infarction, angina pectoris (including unstable), atherosclerosis of the coronary arteries, chronic heart failure;
• hematopoietic system: lymphadenopathy (including inflammation of the cervical lymph nodes), increased levels of leukocytes in the blood;
• allergic reactions: seasonal allergies, angioedema, urticaria;
• immune system: in HIV-infected patients, progression of HIV infection;
• urinary system: decreased libido, spontaneous abortion, urinary tract infections;
• general reactions: trembling, chills, chest pain/tightness, fever, increase/decrease in body weight, facial swelling, lethargy.

pharmachologic effect

A drug for the treatment of alcohol dependence, an opioid receptor antagonist with the highest affinity for opioid μ-receptors. Apart from opioid receptor antagonism, the drug has no or very little intrinsic activity.

Naltrexone blocks the effects of opioids by competitively binding to opioid receptors in the brain. The neurobiological mechanisms responsible for the reduction in alcohol consumption observed in alcohol-dependent patients treated with naltrexone are not fully understood, but the mechanism of action is thought to involve the endogenous opioid system.

The blockade can be overcome by increasing the dose of opioids, which is manifested by symptoms such as increased histamine secretion.

When using the drug for unknown reasons, a narrowing of the pupil is observed.

The use of Vivitrol is not accompanied by the development of tolerance or mental and physiological dependence. In patients with physical opioid dependence, administration of the drug causes withdrawal symptoms.

Vivitrol is not an aversive therapy and does not cause a disulfiram-like reaction when taking opiates or alcohol.

Overdose

Data on naltrexone overdose are very limited. When a single dose of 784 mg was administered to 5 healthy subjects, no serious side effects were observed.

Symptoms of a naltrexone overdose may include the most common side effects: reactions at the injection site, abdominal pain, nausea, drowsiness, dizziness. No significant increase in liver enzyme activity was noted.

If such reactions occur, maintenance treatment is recommended.

How to use Vivitrol

Vivitrol is used only intramuscularly, in the buttocks, exclusively using a syringe with a needle included in the kit with the drug.

The product is injected in one motion into the outer upper quadrant of the buttock, which alternate with each subsequent use of the product.

A painful lump may occur at the injection site, so the condition of this area should be carefully monitored and, at the slightest sign of discomfort, seek medical help. In advanced cases, surgical intervention is possible.

Injections are performed monthly, the treatment period is determined individually by the doctor, based on the specific results of each patient.

special instructions

At least 7-10 days before starting therapy with Vivitrol, patients with opioid dependence must stop taking opioids to avoid the development of acute withdrawal syndrome and/or to prevent exacerbation of an existing withdrawal syndrome.

The absence of opioids in the urine is often an insufficient indicator to confirm their absence in the body; if there is a risk of developing withdrawal syndrome, a provocative test with naloxone must be done before starting a course of Vivitrol therapy.

If hypersensitivity reactions develop, such as urticaria, anaphylaxis, angioedema, you should immediately stop further use of the drug and consult a doctor.

Therapy with Vivitrol not only does not eliminate, but does not even reduce the symptoms associated with stopping alcohol intake.

It is unknown what effect the drug has on the birth process.

Depression and suicidal behavior

Family members and caregivers of patients treated with Vivitrol should be warned to closely monitor for signs of depression or suicidal behavior and report them promptly to their healthcare provider.

Data from controlled clinical studies of suicidal behavior when taking Vivitrol (suicidal intentions, suicide attempts, completed suicides):

• patients with alcohol dependence: suicidal behavior was observed infrequently, but was more common in patients receiving Vivitrol than in the placebo group (1% vs. 0). In some episodes, such behavior was recorded after the completion of the study, but was a consequence of depression that appeared during drug therapy. Two suicides were recorded in which patients were treated with Vivitrol. Depression-related discontinuation occurred more frequently in the Vivitrol group (1%) than in the placebo group (0). A 24-week placebo-controlled study showed that depression-related adverse events occurred in: 10% of the Vivitrol 380 mg group; in the placebo group – in 5%;
• patients with opioid dependence: suicidal side effects were observed in 5% of patients receiving Vivitrol injections and in 10% of patients receiving oral naltrexone. A placebo-controlled study lasting 24 weeks showed a complete absence of depression-related adverse events in both the Vivitrol 380 mg group and the placebo group.

Injection site reactions

Vivitrol injections may be accompanied by swelling, tenderness, pain, induration, itching, and erythema. But in some cases, very strong reactions are possible at the injection site of the suspension. In a clinical study, a case of lump formation that continued to grow four weeks after injection was reported, leading to necrosis that required surgical removal.

During post-registration monitoring, reactions at the injection site such as compactions, inflammation of the subcutaneous tissue, hematomas, abscesses, sterile abscesses, and necrosis were also noted. Some of them needed to be removed promptly; in some cases, mainly in women, scars formed at the injection site.

Vivitrol should only be injected into the gluteal muscle; accidental subcutaneous injection increases the likelihood of serious adverse reactions at the injection site. The injection needle included in the kit is specially designed for administering the Vivitrol suspension, and it should absolutely not be replaced with any other. When the needle length is insufficient due to body type, other treatment should be prescribed. Before giving an injection, the doctor must make sure that the needle is suitable for the patient.

Patients should be warned of the obligation to inform the attending physician of the occurrence of any reactions at the site of administration of the suspension. At the first sign of an abscess, significant swelling, inflammation of the subcutaneous tissue or necrosis, the doctor should decide whether surgical intervention is necessary.

Retinal artery occlusion

During clinical and post-registration observations, there were no cases of retinal artery obstruction. After injection of other drugs containing a copolymer of lactic and glycolic acid, occlusion of the retinal artery in post-registration studies was observed extremely rarely and only with the concomitant presence of an abnormal arteriovenous anastomosis. To avoid the drug entering a blood vessel, the suspension should be injected strictly into the gluteal muscle.

Hepatotoxicity

Exceeding the recommended dosage of naltrexone may cause hepatocellular disorders.

In patients with acute hepatitis and acute liver failure, the use of Vivitrol is contraindicated. In acute liver diseases, the prescription of naltrexone should be carefully weighed and justified taking into account the risk of severe liver dysfunction. The ratio of the safe dose of naltrexone to the dose causing liver damage is less than 5.

Vivitrol, when used in recommended doses, is not hepatotoxic.

It is necessary to inform patients at the beginning of therapy about the likelihood of liver disorders and recommend that they seek medical help if symptoms of hepatitis occur. Drug therapy in this situation should be interrupted.

Eosinophilic pneumonia

During clinical studies, one case of eosinophilic pneumonia and one case of suspected eosinophilic pneumonia were diagnosed. Both times, patients required hospitalization and treatment with antibiotics and glucocorticosteroids (GCS).

The possibility of eosinophilic pneumonia occurring during Vivitrol therapy cannot be excluded, and therefore patients are advised to immediately consult a doctor if symptoms such as hypoxia and progressive shortness of breath occur.

The specialist should take into account that the development of eosinophilic pneumonia is possible in patients with antibiotic resistance.

Elimination of opioid receptor blockade with Vivitrol

For patients receiving Vivitrol treatment, in emergency situations, regional anesthesia or the use of non-narcotic analgesics is the preferred method of pain control.

If it is necessary to use narcotic analgesics for the purpose of anesthesia or analgesia, patients must be provided with long-term medical supervision.

Therapy with narcotic analgesics should be carried out by specially trained personnel (to avoid breathing problems), capable of performing artificial ventilation (ALV) in case of complications.

Regardless of the medications used to eliminate the effects of naltrexone, the patient must be kept in a specially equipped intensive care unit under the constant supervision of qualified medical professionals.

Opioid overdose while trying to overcome opioid receptor blockade

After opioid detoxification, patients typically have reduced tolerance to opioids. Vivitrol blocks the effects of exogenous opioids for 28 days, but patients have been known to receive lethal doses of opioids when they take them before a new dose of Vivitrol or when they miss their next dose of the drug.

After treatment with Vivitrol, there may be an increase in sensitivity to opioids, which can cause potentially life-threatening opioid intoxication (including respiratory failure or respiratory arrest and collapse). Patients should be warned that they may become more sensitive to even low doses of opioids after completing Vivitrol treatment. We must not forget about the decrease in tolerance to opiates at the end of the dosing interval (one month after the previous injection and when the next injection is missed). Patients and their families should be informed about opioid hypersensitivity during these periods and the risk of overdose.

The blockade caused by Vivitrol can be overcome, despite its strong antagonistic effect on opioid receptors and long-lasting pharmacological effect. Patients who attempt to overcome this blockade by administering high doses of exogenous opioids expose themselves to the risk of receiving a lethal dose. When the concentration of opioids in the plasma, immediately after their administration, is sufficient to overcome the competitive blockade of opioid receptors, life-threatening opioid intoxication can immediately develop, manifested by respiratory depression and collapse. Patients should be educated about the serious consequences that result from attempts to overcome opioid receptor blockade.

Effect of the drug on laboratory blood parameters

At the beginning of treatment with Vivitrol, an increase in the concentration of eosinophils in the blood was noted, but after several months of therapy this indicator returned to normal.

During therapy with high doses of the drug, an average decrease in platelet count of 17.8×103 μl was recorded. Patients with opioid dependence who received therapy for 24 weeks showed a decrease in platelet levels to an average of 62.8 x 103 μl. In the placebo group, this figure was 39.9 × 103 μl. But randomized controlled trials in all patients did not provide evidence of the effect of Vivitrol on increased bleeding.

The increase in AST activity with Vivitrol was the same as with oral naltrexone and was 1.5% compared to 0.9% in the placebo group.

Clinical studies of patients with opioid addiction lasting up to six months showed that in 89% of cases hepatitis C was diagnosed, in 41% of cases - HIV infection. Increases in liver enzymes and GGT were frequently observed in studies. Such side effects were more likely to be observed in the group of patients receiving Vivitrol therapy at a dose of 380 mg than in the placebo group. However, the study did not include patients whose ALT or AST activity exceeded the upper limit of normal (ULN) by more than 3 times. This increase in enzyme activity was observed in 20% of cases during treatment with Vivitrol and in 13% of cases in the placebo group.

When treating opioid addiction with Vivitrol, ALT/AST activity increased by an average of 61/40 IU/L; in the placebo group, by an average of 48/31 IU/L.

Increased CPK (creatine phosphokinase) activity: in clinical studies of patients receiving Vivitrol injections, the rate was typically 1–2 times the ULN. Similar results were observed with oral forms of naltrexone. But there are known cases of a 4-fold increase in ULN with oral naltrexone and even a 35-fold increase in CPK activity with Vivitrol injections.

When treating opioid addiction with Vivitrol, CPK activity above normal increased on average in 39% of patients, in the placebo group – in 32%.

There are known cases of increased CPK activity compared to ULN: in the placebo group – 41.8 times; in the group of patients treated with Vivitrol - 22.1 times.

In laboratory tests of urine using enzyme immunoassay, false-positive results for a number of drugs, especially opioids, are possible. Such studies must be carried out in accordance with the information provided in the instructions for conducting specific tests.

Impact on the ability to drive vehicles and complex mechanisms

Patients who experience dizziness during therapy should refrain from driving vehicles and machinery, as well as from other potentially hazardous activities that require concentration and speed of psychomotor reactions.

Powder for the preparation of suspension for intramuscular administration of Vivitrol (Vivitrol)

Instructions for medical use of the drug

Description of pharmacological action

Naltrexone is an opioid antagonist with the greatest affinity for mu opioid receptors. Apart from opioid receptor antagonism, the drug has little or no intrinsic activity. The use of the drug for unknown reasons may cause pupil constriction. The use of Vivitrol is not accompanied by the development of tolerance or mental and physiological dependence. In patients with physical opioid dependence, administration of the drug causes withdrawal symptoms. Naltrexone blocks the effects of opioids by competitively binding to opioid receptors in the brain. The neurobiological mechanisms responsible for the reduction in alcohol consumption observed in alcohol-dependent patients treated with naltrexone are not fully understood, but the mechanism of action is thought to involve the endogenous opioid system. The blockade can be overcome by increasing the dose of opioids, which is manifested by symptoms such as increased histamine secretion. Vivitrol is not an aversive therapy and does not cause a disulfiram-like reaction when taking opiates or alcohol.

Indications for use

Treatment of alcohol dependence in patients who are able to abstain from drinking alcohol before starting treatment. Patients should not actively consume alcohol when starting treatment with Vivitrol. Treatment with the drug should be part of an appropriate alcohol dependence treatment program that includes psychosocial support. To prevent the development of acute withdrawal syndrome in patients with opioid dependence and prevent exacerbation of existing ones, patients should stop taking opioids at least 7-10 days before starting treatment with Vivitrol. Since the absence of opioids in the urine is often not enough to confirm their absence in the body, if there is a risk of developing a withdrawal reaction, a naloxone challenge test should be performed before using Vivitrol. Children and elderly patients There are no data on the safety and effectiveness of the drug in children. Clinical trials of Vivitrol did not include enough patients over 65 years of age to compare treatment effects in older patients with those in younger patients.

Release form

powder for the preparation of a suspension for intramuscular administration of prolonged action 380 mg; bottle (bottle) with solvent in ampoules, syringe and needles, cardboard pack 1; powder for the preparation of a suspension for intramuscular administration of prolonged action 380 mg; bottle (bottle) with solvent in ampoules, syringe and needles, blister 1, cardboard pack 1;

Pharmacokinetics

Suction. Vivitrol is a long-acting drug intended for intramuscular injection every 4 weeks or once a month. After intramuscular administration, the change in plasma naltrexone concentration is characterized by an initial peak with a maximum approximately 2 hours after administration and a second peak 2–3 days later. Starting approximately 14 days after administration of the drug, its plasma concentration gradually decreases, but measurable concentrations remain for more than 1 month. Cmax and AUC of naltrexone and its main metabolite, 6-β-naltrexol, in blood plasma are proportional to the administered dose of Vivitrol. The total exposure to naltrexone after a single dose of 380 mg of Vivitrol is 3-4 times higher compared to its oral administration in the amount of 50 mg for 28 days. After the first injection, steady state concentration was reached at the end of the interdose interval. After repeated administration, minimal accumulation of naltrexone and 6-β-naltrexol in the blood is observed (Distribution. Naltrexone is weakly bound to plasma proteins in vitro (21%). Metabolism. Naltrexone is actively metabolized in the body. The main metabolite is 6-β-naltrexol, is formed by the cytosolic enzyme - dihydrodiol dehydrogenase. Enzymes of the cytochrome P450 system are not involved in the metabolism of the drug. Other metabolites are 2-hydroxy-3-methoxy-naltrexone and 2-hydroxy-3-methoxy-6-β-naltrexone. Naltrexone and its metabolites form conjugates with glucuronide. With intramuscular administration of the drug Vivitrol, compared to oral administration, significantly less 6-β-naltrexol is formed, which is caused by reduced first-pass metabolism in the liver. Excretion. Naltrexone and its metabolites are excreted mainly in the urine, and a minimal amount is excreted unchanged drug. T1/2 of naltrexone is 5–10 days and depends on the degradation of the polymer. T1/2 of 6-β-naltrexol is also 5–10 days. Pharmacokinetics in patients with renal and hepatic insufficiency. Liver failure. The pharmacokinetics of Vivitrol does not change in patients with mild or moderately severe liver dysfunction (Child-Pugh classes A and B); such patients do not require dose adjustment. The pharmacokinetics of Vivitrol have not been studied in patients with severe liver dysfunction. Kidney failure. The results of pharmacokinetic analyzes indicate that mild renal failure (Cl creatinine 50–80 ml/min) has almost no effect on the pharmacokinetics of Vivitrol and there is no need for dose adjustment. The pharmacokinetics of Vivitrol have not been studied in patients with moderate to severe renal failure. Influence of gender. A study conducted in healthy patients of both sexes (18 men and 18 women) showed that gender did not affect the pharmacokinetics of Vivitrol. The influence of age and race. The pharmacokinetics of Vivitrol have not been studied in elderly patients, children and representatives of different races.

Use during pregnancy

The drug is classified as category C in terms of toxicity. The effects of Vivitrol on pregnant women have not been studied. Vivitrol should be prescribed during pregnancy only if the potential benefit from its use outweighs the potential risk to the fetus. Following oral administration of naltrexone, excretion of naltrexone and 6-β-naltrexol into breast milk has been noted. Due to the potential for carcinogenicity and the potential for serious adverse effects in nursing infants, a decision should be made to discontinue Vivitrol therapy during breastfeeding or to discontinue lactation during treatment, depending on the importance of therapy to the mother.

Use for renal impairment

Patients with mild renal failure (creatinine clearance 50-80 ml/min) do not require dose adjustment. The pharmacokinetics of Vivitrol have not been studied in patients with moderate to severe renal failure. Due to the fact that naltrexone and its primary metabolite are excreted primarily in the urine, it is recommended that Vivitrol be administered with caution to patients with moderate or severe renal impairment.

Contraindications for use

- hypersensitivity to the active substance of the drug or to any of its fillers and solvent components; - patients taking narcotic analgesics; — patients with current physiological opioid dependence; - patients in a state of acute opioid withdrawal; - patients who have not passed the naloxone challenge test or who have a positive test result for the presence of opioids in the urine. With caution: - mild or moderately severe liver dysfunction - Child-Pugh classes A and B (no dose adjustment required); - severe liver dysfunction (the pharmacokinetics of Vivitrol have not been studied and should be prescribed with caution due to the risks associated with intramuscular injection, such as thrombocytopenia and coagulation disorders); - mild renal failure (creatinine Cl 50-80 ml/min - no dose adjustment required); - moderate and severe renal failure (the pharmacokinetics of the drug Vivitrol has not been studied) - due to the fact that naltrexone and its primary metabolite are excreted from the body mainly in the urine.

Side effects

In clinical studies lasting up to 6 months, 9% of patients treated with Vivitrol discontinued treatment due to side effects; In the placebo group, 7% of patients discontinued treatment due to side effects. The most common reasons for discontinuation of Vivitrol treatment were injection site reactions (3%), nausea (2%), pregnancy (1%), headache (1%) and suicidal adverse events (0.3%). In the group of patients receiving placebo injections, only 1% of patients discontinued treatment due to injection site reactions. The following are side effects that occurred in clinical trials in more than 5% of cases (common), the severity of these side effects was characterized as mild to moderate. From the gastrointestinal tract: nausea, vomiting, diarrhea, frequent bowel movements, gastrointestinal upset, loose stools, abdominal pain, stomach discomfort, dry mouth, anorexia, decreased appetite, impaired appetite. From the respiratory system: upper respiratory tract infections, laryngitis, sinusitis, pharyngitis (including streptococcal), nasopharyngitis. General disorders and reactions at the injection site: pain, soreness, induration, swelling, itching, hemorrhage, asthenia, anxiety, lethargy, lethargy. Musculoskeletal system: arthritis, joint pain, joint stiffness, back pain, limb pain, muscle spasm, muscle twitching, muscle stiffness. From the skin and subcutaneous tissues: rash, papular rashes, prickly heat. From the nervous system: headache, migraine, dizziness, fainting, drowsiness, sedation. Side effects identified during pre-registration studies of the drug: From the gastrointestinal tract: taste perversion, increased appetite, gastroesophageal reflux disease, constipation, flatulence, hemorrhoids, colitis, gastrointestinal bleeding, paralytic ileus, perirectal abscess, gastroenteritis, tooth abscess. General disorders and administration site reactions: fever, lethargy, trembling, chest pain, chest tightness, toothache, weight loss. Mental disorders: irritability, sleep disturbance, alcohol withdrawal syndrome, agitation, euphoria, delirium. From the nervous system: impaired attention, migraine, decreased mental activity, convulsions, ischemic stroke, cerebral artery aneurysms. From the musculoskeletal system: pain in the limbs, muscle spasms, stiffness in the joints. From the skin and subcutaneous tissues: increased sweating, incl. at night, itching, cellulite, conjunctivitis. From the respiratory system: sore throat, dyspnea, nasal congestion, COPD, flu, bronchitis, pneumonia. Metabolic: heat stroke, dehydration, hypercholesterolemia. From the cardiovascular system: increased blood pressure, hot flashes, deep vein thrombosis, pulmonary thrombosis, rapid heartbeat, atrial fibrillation, myocardial infarction, angina pectoris, unstable angina, congestive heart failure, atherosclerosis of the coronary arteries. From the blood and lymphatic system: lymphadenopathy, incl. cervical adenitis, increased levels of leukocytes in the blood. From the immune system: seasonal allergies, hypersensitivity reactions, incl. angioedema and urticaria. From the genitourinary system: miscarriage, decreased libido, urinary tract infections. From the hepatobiliary system: cholelithiasis, increased levels of ALT and AST, acute cholecystitis.

Directions for use and doses

IM, into the gluteal muscle, alternating buttocks. Vivitrol should only be administered by qualified healthcare professionals using the ingredients provided in the package. Packaging components must not be replaced. The recommended dose of Vivitrol is 380 mg IM once every 4 weeks or once a month. The drug Vivitrol cannot be administered intravenously! If the patient misses the next dose, the next injection should be given as quickly as possible. Oral naltrexone is not required before using Vivitrol. There are no data on resumption of treatment after a break. There is no systematic data on the transfer of patients from oral naltrexone to Vivitrol. Instructions for preparing the suspension To prepare the suspension, use only the solvent supplied. The drug should be administered only with the needle included in the kit. All packaging components - a bottle with powder, a bottle with solvent, a needle for preparing a suspension and an injection needle with a protective cap - are necessary for administering the drug. The kit also includes a spare injection needle with a protective cap. The components included in the kit should not be replaced (Fig. 1). To ensure accurate dosing, it is necessary to strictly follow the instructions for preparation and administration of the drug. It is necessary to follow the rules of asepsis. Instructions for medical use of the drug 1. Composition of the kit for preparing the suspension: 1 bottle with solvent; 1 bottle of powder; 1 disposable syringe; 2 injection needles with protective cap; 1 short needle for preparing the suspension. 2. The procedure for preparing the suspension: before use, remove the package with the drug from the refrigerator and allow it to warm to room temperature (approximately 45 minutes); - to facilitate mixing, tap the bottom of the bottle with powder on a hard surface to loosen the powder; - remove the aluminum caps from both bottles (do not use the drug if the bottle caps are damaged or missing); - wipe the necks of the bottles with an alcohol wipe; — put a short needle for preparing a suspension on the syringe and take 3.4 ml of solvent from the solvent bottle (a certain amount of solvent will remain in the bottle); — add 3.4 ml of solvent into a bottle with powder; - mix the solvent and powder by vigorously shaking the bottle for about 1 minute. Make sure the suspension is homogeneous before proceeding. A properly mixed suspension should have a milky white color, be free of lumps and should flow freely down the sides of the bottle. 3. The procedure for collecting the suspension is to immediately after preparation, withdraw 4.2 ml of the suspension into the syringe, using a needle to prepare the suspension; - remove this needle and put the injection needle on the syringe; - before injection, tap the syringe to release air bubbles, then gently press the plunger until 4 ml of suspension remains in the syringe. The suspension is ready for immediate administration. 4. Procedure for administering the suspension: before injection, a blood aspiration test should be performed. Gradually inject the drug with a smooth movement deep into the gluteal muscle. The suspension should be injected alternately into different buttocks; - If blood is aspirated or the needle is clogged, do not inject the drug. Replace the needle with a spare one, located in the package, and inject the drug into an adjacent place of the same gluteal muscle, again performing a blood aspiration test before injection. Vivitrol cannot be administered intravenously. 5. Disposal of used and unused packaging components - after administering the drug, cover the needle with a protective cap, pressing it with one hand against a hard surface and holding it away from you (using a protective cap prevents splashing of liquid that may remain on the needle after injection); — throw away used and unused packaging components.

Overdose

Data on overdose are very limited. Single doses of 784 mg were administered to 5 healthy volunteers. They reported no serious side effects. Symptoms: The most common side effects were injection site reactions, nausea, abdominal pain, drowsiness and dizziness. There were no significant increases in liver enzymes. Treatment: maintenance therapy.

Interactions with other drugs

The interaction of Vivitrol with other drugs has not been studied. Naltrexone is an antagonist of opioid-containing drugs (such as cough and cold medications, antidiarrheals and opioid analgesics). Since naltrexone is not a substrate of cytochrome enzymes, inducers or inhibitors of these enzymes are unlikely to affect the clearance of Vivitrol. No studies have been conducted to assess the clinical significance of the effect of other drugs on the metabolism of Vivitrol, so caution should be exercised and the possible risks and potential benefits should be assessed when prescribing Vivitrol together with other drugs. The safety indicators for using Vivitrol with and without antidepressants are the same.

Precautions for use

Elimination of blockade of the drug Vivitrol. In an emergency situation for patients treated with Vivitrol, regional analgesia, benzodiazepine sedation, and the use of non-narcotic analgesics or general anesthesia are the preferred method of pain control. In situations requiring the use of narcotic analgesia, the required dose of opioids may be higher than usual, resulting in more profound and prolonged respiratory depression. It is preferable to use a fast-acting narcotic analgesic that reduces the duration of respiratory depression. The amount of analgesic administered should be determined according to the needs of the patient. Non-receptor-mediated effects (eg, facial swelling, pruritus, generalized erythema, or bronchospasm) may occur, presumably due to histamine secretion. Regardless of the agent chosen to reverse Vivitrol blockade, the patient should be closely monitored by appropriately trained medical personnel in a designated intensive care unit. Depression and suicidal behavior. During controlled clinical trials of Vivitrol, adverse events of a suicidal nature (suicidal ideation, suicide attempts, completed suicides) were infrequent, but occurred more often in the group of patients treated with Vivitrol than in the group of patients receiving placebo (1% vs. 0). In some cases, suicidal thoughts and behavior appeared in the patient after completion of the study, but were a consequence of depression that developed during drug treatment. There were 2 suicides, in both cases the patients were treated with Vivitrol. Discontinuation due to depression occurred more frequently in the Vivitrol group (1%) than in the placebo group (0). In a 24-week placebo-controlled study, adverse events related to depressive mood were observed in 10% of patients treated with Vivitrol 380 mg and in 5% of patients receiving placebo injections. Patients with alcohol dependence should be closely monitored for signs of depression or suicidal ideation, incl. patients receiving treatment with Vivitrol. Family members and caregivers of patients should be advised to monitor closely for symptoms of depression or suicidal behavior and to immediately report such symptoms to their healthcare provider. Reactions at the injection site. Vivitrol injections may be accompanied by pain, tenderness, induration, swelling, erythema and itching. During clinical trials, one patient developed a lump that continued to enlarge 4 weeks after injection, followed by necrosis that required surgery to remove. Other cases of injection site reactions including abscess, sterile abscess, induration and necrosis have been observed during post-marketing surveillance, some of which required surgery to resolve. Patients should be warned to inform their physician if any reaction occurs at the injection site. Alcohol withdrawal. The use of the drug Vivitrol not only does not exclude, but also does not reduce the manifestation of symptoms associated with the withdrawal of alcohol intake. Retinal occlusion. Occlusion of the retinal artery after injection of another drug containing a copolymer of lactic and glycolic acid was very rare in post-registration studies and occurred in the presence of an abnormal arteriovenous anastomosis. During clinical and post-registration studies of Vivitrol, not a single case of retinal artery obstruction was observed. Vivitrol should be used as an IM injection into the gluteal muscle and accidental injection into a blood vessel should be avoided.

Special instructions for use

Hepatotoxicity. Taking excessive doses of naltrexone can lead to hepatocellular disorders. Naltrexone is contraindicated in acute hepatitis and acute liver failure. The prescription of Vivitrol to patients with acute liver disease should be carefully considered and justified, taking into account the risk of liver dysfunction. The ratio between a relatively safe oral dose of naltrexone and a dose that causes liver damage is ≤5. When used in recommended doses, Vivitrol is not hepatotoxic. Patients should be warned of the risk of liver problems and advised to seek medical attention if symptoms of hepatitis occur. If such symptoms occur, treatment with Vivitrol should be discontinued. Eosinophilic pneumonia. During clinical trials, one case of incident eosinophilic pneumonia and one case of suspected eosinophilic pneumonia were diagnosed. In both cases, patients required hospitalization and were treated with antibiotics and corticosteroids. The possibility of developing eosinophilic pneumonia in a patient receiving Vivitrol should be considered, and patients should be advised to immediately seek medical help if symptoms of pneumonia, such as progressive shortness of breath and hypoxia, appear. Clinicians should consider the possibility of eosinophilic pneumonia in patients who are resistant to antibiotics. Opioid overdose while trying to overcome opioid receptor blockade. Vivitrol is not intended for opioid blockade or treatment of opioid dependence. Although Vivitrol is a potent opioid receptor antagonist with long-lasting pharmacological effects, the blockade it causes can be overcome. Patients who attempt to overcome this blockade by administering large doses of exogenous opioids risk receiving a lethal dose of opioids and putting their lives in danger. The concentration of opioids in the plasma immediately after their administration may be sufficient to overcome the competitive blockade of opioid receptors, and, as a result, the patient may immediately develop life-threatening opioid intoxication, manifested by respiratory depression and vascular collapse. Patients should be aware of the serious consequences of attempting to overcome opioid receptor blockade. There is also the possibility that a patient treated with Vivitrol will become sensitive to lower doses of opioids than before treatment. This can cause potentially life-threatening opioid toxicity (respiratory failure or arrest, circulatory collapse, etc.). Patients should be warned that they may become sensitive to lower doses of opioids after stopping treatment with Vivitrol. The effect of the drug on the duration of labor and labor is unknown. The effect of the drug on laboratory blood parameters. In patients receiving treatment with Vivitrol, an increase in the level of eosinophils in the blood was noted, but after several months of treatment, the level of eosinophils returned to normal. In patients receiving high doses of the drug, a decrease in platelet levels was observed to an average of 17.8 × 103 μl. However, randomized controlled trials have not proven the effect of Vivitrol on increasing bleeding. The increase in blood AST levels during treatment with Vivitrol was the same as during treatment with oral naltrexone and was 1.5% compared to 0.9% in the placebo group. In clinical studies, patients receiving Vivitrol experienced increases in creatine phosphokinase levels, typically 1 to 2 times the upper limit of normal. A similar increase in creatine phosphokinase levels is also observed during treatment with oral naltrexone. However, there are known cases of a 4-fold and even 35-fold increase in the level of this enzyme in a group of patients receiving oral naltrexone and Vivitrol, respectively. Some ELISA urine tests may produce false-positive results for a number of drugs, especially opioids. See specific test instructions for more information. Vivitrol should be used immediately after preparing the suspension. Intended for single use only.

Storage conditions

At 2–8 °C (do not freeze).

Best before date

36 months

ATX classification:

N Nervous system

N07 Other drugs for the treatment of diseases of the nervous system

N07B Drugs used for psychological or physiological dependence on various substances

N07BB Drugs used for alcohol dependence

N07BB04 Naltrexone

Use during pregnancy and lactation

The effect of Vivitrol during pregnancy has not been studied. The drug is used only if the potential benefit to the mother significantly exceeds the possible risk to the fetus.

Following oral administration of Vivitrol, excretion of naltrexone and its primary metabolite 6-beta naltrexol into breast milk has been observed. Due to the fact that they are potentially carcinogenic and can cause serious side effects in infants, during lactation, depending on the degree of significance of the therapy for the mother, treatment with the drug should be discontinued or breastfeeding should be interrupted.

Vivitrol: patient reviews

In my practice, patients who could compare the effects of Naltrexone tablets and Vivitrol in the form of intramuscular injections clearly chose treatment with Vivitrol.

Here are their arguments:

1. Doesn't need to be taken every day. I did it and forgot for a month!
2. No traction. And I think this is the main thing.

The “disadvantages” of those undergoing Vivitrol treatment included the pain of the injection, unstable mood during the day, sleep disturbance and a feeling of lack of air at night.

Drug interactions

The interaction of Vivitrol with other substances/drugs has not been studied.

Naltrexone is an antagonist of drugs containing opiates (eg, opioid analgesics, cold, cough, diarrhea medications).

Inducers or inhibitors of enzymes of the cytochrome system should theoretically not affect the clearance of Vivitrol, since naltrexone is not a substrate of these enzymes.

Due to the fact that studies have not been conducted to assess the clinical significance of the effect of other drugs on the metabolism of Vivitrol, caution should be exercised when assessing the possible risks and potential benefits when prescribing Vivitrol concomitantly with other drugs.

Safety indicators when using Vivitrol with or without antidepressants are the same.

Vivitrol: course of treatment

Vivitrol is a long-acting drug, used once a month.

There is no need to take Naltrexone tablets before the Vivitrol injection.

The course of taking Vivitrol is at least six months. It is during this time that the patient finally develops motivation for sobriety.

At the same time, lengthening the course of treatment gives better results. It seems that a long-term state of sobriety causes in the sick person’s body the same addiction that previously existed to drink and illicit drugs.

According to the observations of my colleagues, after the first injection of Vivitrol, the craving for alcohol decreases by more than 4 times, and after the sixth injection - by 12 times.