Depade

Dosage Forms & Strengths

tablet

• 50mg

microspheres for IM injection

• 380mg

Opioid Dependence

Prevention of relapse after opioid detoxification; to be used only after patient has been opioid-free for 7-10 days and after negative naloxone challenge (no symptom withdrawal after naloxone administration)

PO: 25 mg initially, then observation for 1 hr, then 50 mg once daily starting on day 2; flexible dosing regimens can be employed to accommodate patient convenience or ensure compliance

IM: 380 mg in gluteal muscle every 4 weeks for maintenance of abstinence

Alcohol Dependence

Treatment in patients who have been able to abstain from alcohol in outpatient settings before treatment initiation

PO: 50 mg once daily for ≤12 weeks

IM: 380 mg in gluteal muscle every 4 weeks for maintenance of abstinence

Hepatitis (Orphan)

Orphan designation for treatment of autoimmune hepatitis

Sponsor

• TaiwanJ Pharmaceuticals Co., Ltd, Room 204 A, Bldg 53; 195 Chung Hsing Rd., Sec 4; Chutung, Hsinchu, Taiwan

Postherpetic Neuralgia (Orphan)

Orphan designation for treatment of postherpetic neuralgia

Sponsor

• Allodynic Therapeutics, LLC; 1785 NE 123rd Street; North Miami, FL 33181-2537

Safety and efficacy not established

Crohn Disease (Orphan)

Treatment in pediatric patients

Orphan indication sponsor

• Jill P Smith, MD, Pennsylvania State University, 500 University Drive, Hershey, PA 17033

• It is used to help keep you alcohol-free.
• It is used to keep a drug-free state.
• It may be given to you for other reasons. Talk with the doctor.

• If you have an allergy to naltrexone or any other part of Depade (naltrexone tablets).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are taking an opioid drug on a regular basis, are addicted to an opioid drug, or are having withdrawal signs.
• If you have taken a pain drug within the past 7 to 10 days.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Depade with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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 (the active ingredient contained in Depade) 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 (the active ingredient contained in Depade) 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 (the active ingredient contained in Depade)

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

Oral Tablets:
50 mg orally once a day

Extended-release injectable suspension:
380 mg every 4 weeks (or once a month) via intramuscular gluteal injection, alternating buttocks

Naltrexone undergoes extensive hepatic metabolism and has the potential to cause further hepatic injury in patients with liver dysfunction. Therefore, the use of naltrexone is not recommended in patients with acute hepatitis or liver failure and should be used with caution in patients with active liver disease.

No dosage adjustment is required in patients with mild or moderate liver dysfunction who are receiving the extended-release suspension.

Summary of Use during Lactation

Limited data indicate that naltrexone is minimally excreted into breastmilk. If naltrexone is required by the mother, it is not a reason to discontinue breastfeeding.

Drug Levels

Naltrexone is used as maintenance treatment of opiate dependence in opiate-detoxified patients. Peak plasma levels of 40 to 50 mcg/L at 1 hour after the dose and average plasma levels of 3 to 5 mcg/L have been reported in adults taking daily maintenance doses. Oral bioavailability is 5 to 40% in adults. Naltrexone is metabolized to active beta-naltrexol and to other inactive metabolites.

Maternal Levels. One lactating woman who was 1.5 months postpartum and taking 50 mg of oral naltrexone daily during pregnancy and lactation had her milk sampled several times between 3.7 and 23 hours after her dose. Naltrexone milk levels were undetectable (<2 mcg/L) by 8 hours after the dose while beta-naltrexol milk levels remained detectable throughout the study period and averaged 46 mcg/L. The half-life of elimination from milk was 2.5 and 7.7 hours for naltrexone and beta-naltrexol, respectively. The authors reported that an exclusively breastfed infant would receive about 7 mcg/kg daily of naltrexone including the active metabolite, equivalent to 0.86% of the maternal weight-adjusted dosage.[1]

Infant Levels. A 1.5 month-old breastfed male infant of a mother who was taking 50 mg of oral naltrexone daily during pregnancy and lactation had undetectable (<2 mcg/L) plasma levels of both naltrexone and beta-naltrexol 9.5 hours after the maternal dose, 30 minutes after starting a feeding.[1]

Effects in Breastfed Infants

A 1.5-month-old breastfed infant of a mother who was taking 50 mg of oral naltrexone daily during pregnancy and lactation was reportedly healthy with no naltrexone-related adverse effects.[1]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Buprenorphine, Methadone

References

1. Chan CF, Page-Sharp M, Kristensen JH et al. Transfer of naltrexone and its metabolite 6,beta-naltrexol into human milk. J Hum Lact. 2004;20:322-6. PMID: 15296587

LactMed Record Number

372

Last Revision Date

20170411

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.