What are the side effects of Vivitrol?
As with any medication, Vivitrol treatment does carry a risk of side effects. They include the following. The list below includes side effects or adverse events discovered during clinical trails or afterward, in the post-marketing surveillance period (at least two years after its release on the market):
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- Risk of Opioid Overdose Following Treatment
Vivitrol treatment reduces your opioid tolerance. This means that, after treatment, if opioids are used, there is a greater risk of accidental overdose. For example, patients may try to use the same amount of opioids they did before treatment, and their lowered tolerance can lead to overdose.
Using opioids after a missed dose can also lead to overdose.
Attempting to overcome Vivitrol with opioids can also lead to fatal overdose. Overcoming the Vivitrol barrier with large amounts of opioids can bring on a sudden, life-endangering opioid intoxication.
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- Reaction at Injection Site
Self-administration of Vivitrol is not recommended. Instead, Vivitrol must be prepared and administered by your treatment provider.
One reason why is so is the possibility of an injection site reaction, which may be severe in some cases, even requiring surgery.
Let your healthcare provider know immediately if any of the following occurs at the injection site:
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- Hardening of the area
- Severe pain
- Swelling
- Blistering
- Lumps
- Formation of an open wound or a dark scab
Your provider should also know about any other reaction you experience at the injection site, especially if it worsens or doesn’t improve within two weeks.
Hypersensitivity reactions have been reported with Vivitrol treatment.
These reactions can include anaphylaxis, a severe allergic reaction that involves the entire body. With anaphylaxis, there is a danger of anaphylactic shock, a condition in which blood pressure suddenly drops and airways narrow.
Anaphylaxis can occur within minutes and up to half an hour or longer after exposure (or, in this case, injection). Signs include:
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- Low blood pressure
- Hives, itching, flushing, going pale or other skin reaction
- Tightening of your airways
- Swollen throat or tongue
- Wheezing or trouble breathing
- Rapid, weak pulse
- Fainting/dizziness
If anaphylaxis occurs, an epinephrine injection can be administered by your healthcare provider. A follow-up trip to the emergency room is recommended after the epinephrine shot is administered. If you are on your own and do not have access to epinephrine shot, go to directly to the emergency room.
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- Precipitated Opioid Withdrawal
The minimum time from last opioid use to starting Vivitrol is seven to 10 days.
There is a danger of precipitated (sudden, intense) opioid withdrawal that may require hospitalization if Vivitrol treatment is started before opioids are out of your system.
The minimum time from last opioid use to starting Vivitrol is seven to 10 days.
There is a danger of precipitated (sudden, intense) opioid withdrawal that may require hospitalization if Vivitrol treatment is started before opioids are out of your system.
A negative urine test for opioids is not sufficient for ensuring a patient is free of opioids. In this case, a naloxone challenge test can be administered if your healthcare provider feels there is a risk of precipitated withdrawal.
Both hepatitis and “clinically significant” liver dysfunction have occurred during Vivitrol treatment. It is recommended that treatment with Vivitrol be suspended with any signs of acute hepatitis. Let your healthcare provider know if you experience any of the following symptoms of hepatitis while on Vivitrol:
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- Sudden nausea or vomiting
- Fatigue
- Joint Pain
- Muscle Pain
- Loss of appetite
- Abdominal pain/discomfort (beneath your ribs on your upper right side, especially)
- Fever (low-grade)
- Intense itching
- Dark-colored urine
- Bowel movements that are clay-colored (pale or light)
- Yellowing of the whites of your eyes or skin
Vivitrol treatment is not indicated for use in patients with liver failure or acute hepatitis. Those with acute liver disease should notify their healthcare provider, who should carefully weigh the hepatotoxic effects of Vivitrol with any perceived benefit.
It has been noted that excessive doses of Naltrexone (the active ingredient in Vivitrol) can cause injury to liver cells.
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- Depression & Feeling Suicidal
While taking Vivitrol, you should let your healthcare provider know about any signs of depression or suicidal thoughts you may have.
Signs of clinical depression include:
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- Trouble with concentration, decision-making, or recalling details
- Loss of interest in things you used to enjoy
- Persistent feelings of sadness, feeling empty or anxious
- Feelings of guilt, hopelessness, helplessness, worthlessness and pessimism
- Insomnia, sleeping too much, or early morning wakefulness
- Restlessness
- Fatigue
- Irritability
- Loss of appetite or overeating
- Aches and pain that do not go away
- Problems with digestion that do not improve with treatment
- Thoughts of suicide or suicidal attempts
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- Rapid accumulation of white blood cells in the lungs (Eosinophilic pneumonia)
In clinical trials for Vivitrol, a diagnosed and a suspected case of eosinophilic pneumonia occurred, both of which required hospitalization. Both cases resolved after antibiotic and corticosteroid treatment.
Seek immediate medical attention if you develop shortness of breath or other pneumonia symptoms while taking Vivitrol. Symptoms of pneumonia include:
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- Shortness of breath
- Coughing, may produce phlegm
- Pain in the chest when breathing or coughing
- Fever
- Sweating
- Shaking Chills
- Fatigue
- Nausea, diarrhea or vomiting
Adults 65 or over may experience:
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- Lower than normal temperature (may also occur in those with weakened immune systems)
- Confusion/changes in mental awareness
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- Blood and Lymphatic System Disorders
Increases in white blood cell count have been reported with Vivitrol treatment. High white blood cell counts are typically seen when the body is working to fight an infection. High white blood cell counts could also be a sign of stress, whether physical or emotional.
Swollen lymph nodes (lymphadenopathy) and inflammation of a gland in the neck (cervical adenitis) have also been reported with Vivitrol use.
The following cardiac conditions have been reported with Vivitrol treatment:
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- Angina Pectoris (chest pain or discomfort caused by coronary heart disease)
- Angina Unstable (chest pain or discomfort caused by inadequate blood flow through the heart)
- Atrial Fibrillation (irregular or “quivering” heartbeat)
- Cardiac Failure Congestive (heart muscle not pumping blood as well as it should)
- Coronary Artery Atherosclerosis (plaque buildup in the arteries that supply the heart with blood)
- Myocardial Infarction (heart attack)
- Palpitations (heart beating too hard, too fast, fluttering, or feeling like it has skipped a beat)
Blurry vision and conjunctivitis (commonly called pink eye) have been reported with Vivitrol use.
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- Gastrointestinal Disorders
A range of GI problems have been reported in those receiving Vivitrol treatment:
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- Abdominal discomfort
- Colitis (inflammation of the tissues that line the large intestine)
- Constipation
- Flatulence (buildup of gas in the digestive system)
- Gastroesophageal reflux disease (acidic fluids or food back up into the esophagus from the stomach)
- Gastrointestinal hemorrhage (digestive tract bleeding, which may show in stool or vomit)
- Hemorrhoids
- Acute pancreatitis (sudden inflammation of the pancreas)
- Paralytic Ileus (blockage of the intestines without a physical obstruction)
- Perirectal abscess (pus collection near the anus)
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- General Disorders and Administration Site Conditions
The following have been reported in Vivitrol patients:
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- Chest pain
- Chest tightness
- Chills
- Facial swelling (Face Edema)
- Irritability
- Lethargy
- Fever (Pyrexia)
- Rigors (shivering associated with fever)
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- Gallbladder, Bile Ducts or Bile Disorders (Hepatobiliary Disorders)
The following conditions have been observed and/or reported with Vivitrol use:
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- Acute cholecystitis (inflammation of the gallbladder)
- Cholelithiasis (gallstone formation)
Seasonal allergy and hypersensitivity reactions have been reported with the use of Vivitrol.
Hypersensitivity reactions include angioneurotic edema (swelling beneath the skin) and urticaria (rash consisting of round, red welts that itch and can be accompanied by swelling).
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- Infections and Infestations
The following have also been reported in patients treated with Vivitrol:
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- Bronchitis
- Gastroenteritis
- Laryngitis
- Pneumonia
- Sinusitis
- Tooth abscess
- Upper respiratory tract infection
- Urinary tract infection
- Advanced HIV disease (in HIV-infected patients)
Both weight gain and weight loss have been reported in Vivitrol patients.
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- Metabolism and Nutrition Disorders
Some Vivitrol patients have experienced the following:
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- Increased appetite
- Dehydration
- Heat exhaustion
- Hypercholesterolemia (High cholesterol)
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- Musculoskeletal and Connective Tissue Disorders
The following side effects affecting the muscles, bones, ligaments, tendons and connective tissues have also been reported in Vivitrol patients:
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- Joint stiffness
- Muscle spasms
- Myalgia (aches and pains in muscles, ligaments, soft connective tissue of the muscles, organs, bones, tendons and facia)
- Limb pain
The following nervous system disorder symptoms have been observed and/or reported in Vivitrol patients:
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- Cerebral arterial aneurysm (brain aneurysm)
- Convulsions
- Disturbance in attention
- Dysgeusia (distorted sense of taste)
- Mental impairment
- Migraine
- Ischemic stroke
- Paresthesia (burning or prickling sensations, usually in the hands, feet, arms or legs)
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- Pregnancy, Puerperium, and Perinatal Conditions
A type of miscarriage in which the fetus dies or doesn’t form, yet the embryonic tissues and placenta remain in the uterus, has been reported with Vivitrol use.
The following psychiatric disorders have been observed and/or reported in Vivitrol patients:
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- Abnormal dreams
- Agitation
- Alcohol withdrawal syndrome
- Euphoric mood
- Delirium
- Decreased libido (sex drive)
Rxlist also includes “impotence” and “difficulty having an orgasm” as two side effects of Vivitrol.
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- Respiratory, Thoracic (Chest), and Mediastinal (Membrane separating the lungs) Disorders
The following chest, lung and breathing symptoms were observed and/or reported with Vivitrol treatment:
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- Chronic obstructive pulmonary disease (COPD)
- Dyspnea (Trouble breathing)
- Pharyngolaryngeal pain (pharynx and larynx pain)
- Sinus congestion
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- Skin and Subcutaneous Tissue Disorders
The following adverse effects affecting the skin and tissues below the skin were reported with Vivitrol patients.
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- Night sweats
- Pruritus (itchy skin)
- Increased sweating
The adverse vascular system effects below have been noted/observed in patients taking Vivitrol:
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- Deep venous thrombosis (blood clot in a vein deep inside the body)
- Hot flushes
- Pulmonary embolism (sudden blockage of a lung artery)
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- Increase in Eosinophil (a type of white blood cell) Count
Increases in eosinophil counts were noted during clinical trials for those taking Vivitrol versus placebo. Over several months, with continued Vivitrol use, eosinophil counts returned to a normal level.
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- Decreased Platelet (Blood Cells that Aid in Clotting) Count
Decreased platelet count was noted with 380-milligram doses of Vivitrol.
In alcohol dependent patients, Vivitrol patients experienced a mean decrease of 17.8 × 103 /µL versus 2.6 × 103 /µL for those on placebos during clinical trials.
In opioid-dependent patients, Vivitrol patients experienced a mean decrease of 62.8 × 103 /µL versus 39.9 × 103 /µL for those taking a placebo during clinical trials after 24 weeks of Vivitrol treatment.
Vivitrol was not found to be associated with an increase in “bleeding-related adverse events” in controlled, randomized trials.
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- Elevations in Certain Liver Enzyme Levels
Elevated ALT, AST, and GGT levels have been associated with Vivitrol treatment, especially in populations who have Hepatitis C and/or HIV.
ALT (alanine aminotransferase) is an enzyme mostly found in the liver. Higher than normal ALT levels can indicate liver disease. Very high levels of more than 10 times the normal level can be found in acute hepatitis.
AST (aspartate aminotransferase) is an enzyme that is found in your muscles and, mostly, in the liver. If the liver suffers damage, it can release AST into the bloodstream. High levels may indicate liver disease (cirrhosis, hepatitis, mononucleosis, etc.), pancreatitis, or heart problems.
Gamma-glutamyl transferase (GGT) is also an enzyme. It can be found in many organs, but is most highly concentrated in the liver. Elevated GGT levels can indicate damage to or a disease affecting the liver or the bile ducts.
Alcohol-Dependent Patients
Elevated AST (aspartate aminotransferase) levels were found in 1.5% of Vivitrol patients with an alcohol addiction in short-term, controlled trials.
This percentage is similar to that of oral naltrexone patients and slightly higher than the incidence occurring with those on a placebo of 0.9%.
Opioid- Dependent Patients
In a controlled trail of opioid-dependent subjects, 89% of whom had Hepatitis C and 41% had HIV, elevated ALT, AST, and GGT levels were observed frequently and more common in those receiving the standard dose of Vivitrol (380 milligrams) versus those receiving a placebo.
(It should be noted that patients were excluded from the trail if they had ALT or AST levels three times the upper normal limit prior to Vivitrol treatment).
Twenty percent of Vivitrol patients in this study experienced an increase of more than three times the upper limit of normal for transaminases levels, versus 13% of placebo patients.
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- A mean maximal increase of ALT levels of 61 IU/L were reported in Vivitrol patients in the study, versus 48 IU/L in placebo patients.
- A mean maximal increase of AST levels of 40 IU/L were reported in Vivitrol patients in the study, versus 31 IU/L in placebo patients.
- An increase in AST to over three times the upper, normal limit was also more commonly seen in the Vivitrol arm (14%) versus the placebo arm (11%).
Symptoms of liver damage also include:
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- Nausea and vomiting
- Weight loss
- Feeling weak
- Fatigue
- Frequent itching
- Abdomen swelling and/or pain
- Leg or ankle swelling
- Yellowing of the skin and eyes (jaundice)
- Dark urine and/or light stool
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- Abnormal Creatinine Phosphokinase Levels
Creatine phosphokinase (CPK) is an enzyme that can found in your brain, muscles and heart. CPK can get into your bloodstream through damaged muscle. High levels point to heart or muscle injury and/or stress.
Eleven percent of Vivitrol patients experienced an increase in CPK to abnormal levels versus those receiving a placebo (8%) in short-term, controlled trials studying alcohol-dependent patients.
Sixteen percent of alcohol-dependent patients receiving Vivitrol treatment for over six months had an increase in CPK levels, in open-label trials. While the most frequent increases were in the one to two times the upper limit of normal, increases as high as 35 times the upper limit of normal were reported. The incidence of CPK increases to three times the upper limit of normal or higher were the same in the Vivitrol and placebo groups.
In opioid-dependent patients receiving Vivitrol treatment, nearly two in five (39%) experience increases in CPK to abnormal levels compared to placebo patients (32%). Increases as high as 41.8 times the upper limit or normal the placebo group and 22.1 times the upper limit of normal in the Vivitrol treated group.
Some side effects can be more prevalent in those addicted to opioids versus alcohol. Case in point, here are the results from clinical trials in alcohol dependent patients versus a Russian study on opioid dependent patients.
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- Retinal Artery Occlusion With Other Intramuscular Drug Products Containing Polylactide-co-glycolide (PLG) Microspheres
Retinal artery occlusion has been reported when another PLG microsphere-containing drug is injected during Vivitrol treatment. This event has occurred with abnormal arteriovenous anastomosis (abnormalities in a vessel shunting blood from an artery to a vein and bypassing a capillary).
During clinical trials and post-marketing surveillance, no retinal artery occlusions were reported.
Vivitrol should be injected into the gluteal muscle (intramuscular injection). Caution must be taken so that Vivitrol is not injected into a blood vessel.
Adverse Effects in Alcohol-Dependent Patients
For patients being treated for alcohol dependence, the following side effects occurred in 5% or more of patients and more frequently in Vivitrol versus placebo patients during clinical trials:
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- Nausea (29% versus 11% placebo)
- Any injection site reaction (65% versus 50%)
- Injection site induration (30% vs. 8%)
- Injection Site tenderness (45% vs. 39%)
- Injection site pruritus (8% versus 0%)
- Asthenic conditions (20% versus 12%)
- Injection site pain (13% versus 7%)
- Other injection site reaction (primarily nodules, swelling) (12% versus 4%)
- Dizziness, syncope (13 versus 4%)
- Insomnia (13% versus 2%)
- Arthralgia, arthritis, joint stiffness (9% versus 1%)
- Anorexia, appetite decreased NOS, appetite disorder NOS (11% versus 3%)
- Abdominal pain (11% versus 4%)
- Vomiting (12% versus 6%)
- Muscle cramps (5% versus 1%)
- Somnolence, sedation (5% versus 1%)
- Diarrhea (13% versus 10%)
- Rash (6% versus 3%)
- Headache (21% versus 18%)
- Anxiety (10% versus 8%)
- Pharyngitis (13% versus 11%)
- Depression (5% versus 4%)
- Back pain, stiffness (6% versus 5%)
- Dry mouth (5% versus 4%)
Please note that the incidence of the above side effects differed by Vivitrol dose. The numbers above reflect overall incidence.
It’s also important to know that most of the Vivitrol treated patients in this clinical trial experienced “mild” or “moderate” intensity of these side effects.
In those treated for Vivitrol for alcohol dependence for six months or less in clinical trials, nine percent had to discontinue treatment due to side effects.
Adverse Effects in Opioid Dependent Patients
In a long-term U.S. study, side effects were similar among both those addicted to opioids and those with an alcohol addiction.
Another study conducted in Russia showed the following side effects occurring in 2% of more of Vivitrol-treated, opioid-dependent patients at an incidence rate greater than that of the placebo-treated patients:
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- Aspartate Aminotransferase Increased (higher level of an enzyme mostly found in the liver and heart) (10% versus 2% placebo)
- Alanine Aminotranferase Increased (higher level of an enzyme mostly found in the liver and kidneys)(13% versus 6%)
- Nasopharyngitis (upper respiratory infection) (7% versus 2%)
- Insomnia (6% versus 1%)
- Gamma-glutamyltransferase increased (higher level of an enzyme found in the body highest concentration is in the liver) (7% versus 3%)
- Injection Site Pain (5% versus 1%)
- Hypertension (High Blood Pressure) (5% versus 3%)
- Toothache (4% versus 2%)
- Influenza (5% versus 4%)
- Headache (3% versus 2%)
The intensity of all side effects in this study were rated as “mild” or “moderate.”
In opioid-dependent subjects, two percent had to drop out due to side effects. However, this percentage was the same in those being treated with a placebo.
Overall, nine percent of Vivitrol patients versus seven percent of placebo patients stopped treatment because of side effects in controlled trials lasting six months or less. Reasons leading to Vivitrol patients dropping out were:
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- Injection site reaction (3%)
- Nausea (2%)
- Headache (1%)
- Pregnancy (1%)
- Suicide-related events (0.3%)
For more information, see Vivitrol’s full prescribing information.
One of the biggest barriers to overcoming addiction is the body’s continued cravings for drugs. Those cravings persist in early recovery, the time that is most vulnerable to relapse. A study published in the Journal of the American Medical Association found the first six months to be the most critical.
