Naltrexone Side Effects

In Summary

Commonly reported side effects of naltrexone include: streptococcal pharyngitis, syncope, anxiety, arthralgia, arthritis, dizziness, drowsiness, fatigue, frequent headaches, headache, joint stiffness, nasopharyngitis, nausea, nervousness, obsessive compulsive disorder, panic attack, pharyngitis, posttraumatic stress disorder, sedation, sinus headache, vomiting, induration at injection site, malaise, pain at injection site, and tenderness at injection site. Other side effects include: muscle cramps, muscle rigidity, muscle spasm, stiffness, depression, and twitching. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to naltrexone: oral tablet

Along with its needed effects, naltrexone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking naltrexone:

• Skin rash

• Abdominal or stomach pain (severe)
• blurred vision, aching, burning, or swollen eyes
• chest pain
• confusion
• discomfort while urinating or frequent urination
• fever
• hallucinations or seeing, hearing, or feeling things that are not there
• itching
• mental depression or other mood or mental changes
• ringing or buzzing in the ears
• shortness of breath
• swelling of the face, feet, or lower legs
• weight gain

Some side effects of naltrexone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach cramping or pain (mild or moderate)
• anxiety, nervousness, restlessness or trouble sleeping
• headache
• joint or muscle pain
• nausea or vomiting
• unusual tiredness

• Chills
• constipation
• cough, hoarseness, runny or stuffy nose, sinus problems, sneezing, or sore throat
• diarrhea
• dizziness
• fast or pounding heartbeat
• increased thirst
• irritability
• loss of appetite
• sexual problems in males

For Healthcare Professionals

Applies to naltrexone: compounding powder, intramuscular powder for injection extended release, oral tablet

General

General side effects have rarely included an opioid withdrawal-like symptom complex. This has been known to occur in a small number of patients receiving naltrexone. Symptoms include tearfulness, mild nausea, abdominal cramps, restlessness, bone or joint pain, myalgia, and nasal symptoms.^[Ref]

In one study, few symptoms were reported following the first week. However, stomach cramps, inability to sleep, and frightening thoughts were reported by 30% or more of subjects through the third week of therapy.

The effects of an opiate may be attenuated during self-administration of small doses of an opioid drug. Patients taking naltrexone may not benefit from opioid-containing medications, such as cough and cold preparations, antidiarrheal preparations, and opioid analgesics. However, patients treated with naltrexone may respond to lower doses of opioids than previously used. Patients who self-administer large doses of an opioid drug could sustain serious injury (including coma) or die if high opiate plasma concentrations remain beyond the therapeutic effectiveness of naltrexone.

The opioid withdrawal-like symptom complex may be attributable to naltrexone or may represent occult opioid usage.^[Ref]

Nervous system

Nervous system side effects reported during treatment for alcohol dependence have included headache (7%), dizziness (4%), nervousness (4%), fatigue (4%), insomnia (3%), anxiety (2%), and somnolence (2%).

Nervous system side effects reported in greater than 10% of patients during treatment for opioid dependence have included headaches, nervousness, anxiety, difficulty sleeping, and low energy. Loss of appetite, increased energy, irritability, and dizziness have been reported in less than 10% of patients. Asthenia, agitation, hyperkinesia, nervousness, fatigue, restlessness, confusion, disorientation, and somnolence have been reported rarely.

Nervous system side effects associated with extended-release injectable solution have frequently included headache, dizziness, syncope, somnolence, insomnia, and sedation. Dysgeusia, attention disturbance, mental impairment, and convulsions have been reported rarely.^[Ref]

Psychiatric

Psychiatric side effects reported during treatment of alcohol dependence have included depression (up to 15%), suicidal ideation (up to 1%), and suicide attempts.

Psychiatric side effects reported during treatment of opioid dependence have included feeling down (less than 10%). Depression, paranoia, hallucinations, bad dreams, and nightmares have been reported rarely. Anxiety and abnormal thinking have also been reported.

Psychiatric side effects associated with extended-release injectable suspension have frequently included anxiety, sleep disorder, and depression. Irritability, decreased libido, abnormal dreams, alcohol withdrawal syndrome, euphoric mood, and delirium have been reported rarely.^[Ref]

Depression and suicidal ideation or attempts have occurred in all study groups receiving naltrexone for treatment of alcohol dependence. These conditions also have been reported in data collected from postmarketing experience during treatment of opioid dependence.^[Ref]

Gastrointestinal

Gastrointestinal side effects reported during treatment for alcohol dependence have included nausea (10%) and vomiting (3%).

Gastrointestinal side effects reported in greater than 10% of patients during treatment for opioid dependence have included abdominal pain, abdominal cramps, nausea, and vomiting. Loss of appetite, diarrhea, constipation, and increased thirst have been reported in less than 10% of patients. Hemorrhoids, ulcer, diarrhea, excessive gas, increased appetite, and dry mouth have been reported rarely.

Gastrointestinal side effects associated with extended-release injectable solution have frequently included nausea, vomiting, diarrhea, abdominal pain, and dry mouth. Constipation, toothache, tooth abscess, flatulence, gastroesophageal reflux, hemorrhoids, colitis, gastrointestinal hemorrhage, paralytic ileus, gastroenteritis, and perirectal abscess have been reported rarely.^[Ref]

Hepatic

Hepatic side effects have included hepatocellular injury, hepatitis, and elevated liver transaminases and bilirubin.

Hepatic side effects associated with extended-release injectable suspension have rarely included cholelithiasis, increased aspartate aminotransferase (AST) level, increased alanine aminotransferase (ALT) level, and acute cholecystitis.^[Ref]

In clinical studies, doses greater than 50 mg a day consistently resulted in more frequent and more significant elevations of serum transaminase levels when compared to placebo.

Patients who develop liver disease from other cause or who take naltrexone in excess may be more prone to hepatocellular injury.^[Ref]

Musculoskeletal

Musculoskeletal side effects reported in greater than 10% of patients during treatment for opioid dependence have included joint and muscle pain. Tremors, twitching, and painful shoulders, legs or knees have been reported rarely.

Musculoskeletal side effects associated with extended-release injectable suspension have frequently included arthralgia, arthritis, joint stiffness, and muscle cramps. Limb pain, muscle spasms, and joint stiffness have been reported rarely.^[Ref]

Respiratory

Respiratory side effects, during treatment of opioid dependence, have rarely included: nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucous, sinus trouble, heavy breathing, hoarseness, cough, and shortness of breath.

Respiratory side effects associated with extended-release injectable solution have frequently included upper respiratory infection and pharyngitis. Pharyngolaryngeal pain, dyspnea, sinus congestion, bronchitis, pneumonia, and chronic obstructive airways disease have been reported rarely.^[Ref]

Cardiovascular

Cardiovascular side effects reported during treatment of opioid dependence have rarely included nose bleeds, phlebitis, edema, increased blood pressure, EKG changes, palpitations and tachycardia.

Cardiovascular side effects associated with extended release injectable suspension have rarely included palpitations, atrial fibrillation, myocardial infarction, angina pectoris, unstable angina, congestive cardiac failure, ischemic stroke, cerebral arterial aneurysm, hypertension, deep venous thrombosis, pulmonary embolism, hot flushes, and coronary artery atherosclerosis.^[Ref]

Genitourinary

Genitourinary side effects reported in greater than 10% of patients during treatment of opioid dependence have included delayed ejaculation and decreased potency. Increased frequency of or discomfort during urination and increased or decreased sexual interest has been reported rarely.

Genitourinary side effects associated with extended-release injectable solution have rarely included urinary tract infection.^[Ref]

Dermatologic

Dermatologic side effects reported during treatment of opioid dependence have rarely included oily skin, pruritus, acne, athletes foot, cold sores, alopecia, and rash.

Dermatologic side effects associated with the extended-release injectable suspension have included pain, tenderness, induration, swelling, erythema, bruising, pruritus, abscess, sterile abscess, and necrosis. Some cases required surgical intervention, including debridement of necrotic tissue. Some cases resulted in significant scarring. The reported cases occurred primarily in female patients.^[Ref]

Ocular

Ocular side effects reported during treatment of opioid dependence have rarely included blurred vision, burning, and increased sensitivity to light.

Ocular side effects associated with extended-release injectable suspension have rarely included conjunctivitis.^[Ref]

Other

Other side effects associated with treatment of opioid dependence have rarely included feeling of "clogged" ears, aching, and tinnitus.

Other side effects reported during treatment of opioid dependence have rarely included chills, weight loss, weight gain, yawning, fever, head "pounding", inguinal pain, swollen glands, "side" pains, cold feet, and "hot spells".

Other side effects associated with extended-release injectable suspension have frequently included asthenia and back pain/stiffness. Pyrexia, lethargy, rigors, chest pain/tightness, influenza, seasonal allergy, missed abortion, and decreased weight have been reported rarely.^[Ref]

Endocrine

Endocrine side effects associated with opioid antagonists have included a change in the baseline levels of hypothalamic, pituitary gland, and gonadal hormones. The clinical significance of these changes is unknown.^[Ref]

Other

Other side effects reported during ultra-rapid opioid detoxification programs with naltrexone have included withdrawal signs and symptoms and fatalities. The cause of death is unknown.^[Ref]

Hematologic

Hematologic side effects have included a single case report of idiopathic thrombocytopenic purpura. This patient may have been previously sensitized to naltrexone.

Hematologic side effects associated with extended-release injectable suspension have rarely included increased white blood cell count.^[Ref]

Local

Local side effects associated with extended-release injectable suspension have frequently included tenderness, pruritus, ecchymosis, nodules, swelling, and pain at injection site.

The FDA has received 196 reports of injection site reactions including cellulitis, induration, hematoma, abscess, sterile abscess, and necrosis. Sixteen patients required surgical intervention ranging from incision and drainage in the cases of abscesses to extensive surgical debridement in the cases that resulted in tissue necrosis.^[Ref]

Naltrexone is administered as an intramuscular gluteal injection and should not be administered intravenously, subcutaneously, or inadvertently into fatty tissue. Physicians should instruct patients to monitor the injection site and contact them if they develop pain, swelling, tenderness, induration, bruising, pruritus, or redness at the injection site that does not improve or worsens within two weeks. Physicians should promptly refer patients with worsening injection site reactions to a surgeon.

Healthcare providers should ensure that the naltrexone injection is given correctly with the prepackaged 1½-inch needle that is specifically designed for this drug.

Data shows that there is a variable depth of subcutaneous tissue dependent on the gender and weight of the patient. Women may be physiologically at higher risk for injection site reactions due to typically higher gluteal fat thickness.^[Ref]

Metabolic

Metabolic side effects associated with extended-release injectable suspension have frequently included anorexia, decreased appetite, and other appetite disorders. Increased appetite, heat exhaustion, dehydration, and hypercholesterolemia have been reported rarely.^[Ref]

Hypersensitivity

Hypersensitivity side effects associated with extended-release injectable solution have rarely included reactions such as angioneurotic edema and urticaria.^[Ref]

Some side effects of naltrexone may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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