VIVITROL - naltrexone
Alkermes, Inc.
1 INDICATIONS AND USAGE
Treatment with VIVITROL should be part of a comprehensive management program that includes psychosocial support.
1.1 Alcohol Dependence
VIVITROL is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment with VIVITROL. Patients should not be actively drinking at the time of initial VIVITROL administration.
1.2 Opioid Dependence
VIVITROL is indicated for the prevention of relapse to opioid dependence, following opioid detoxification.
2 DOSAGE AND ADMINISTRATION
VIVITROL must be prepared and administered by a healthcare provider.
Prior to initiating VIVITROL, an opioid-free duration of a minimum of 7�10 days is recommended for patients, to avoid precipitation of opioid withdrawal that may be severe enough to require hospitalization [see Warnings and Precautions (5.3)].
The recommended dose of VIVITROL is 380 mg delivered intramuscularly every 4 weeks or once a month. The injection should be administered by a healthcare provider as an intramuscular (IM) gluteal injection, alternating buttocks for each subsequent injection, using the carton components provided [see How Supplied/Storage and Handling (16)]. The needles provided in the carton are customized needles. VIVITROL must not be injected using any other needle. The needle lengths (either 1 1/2 or 2 inches) may not be adequate in every patient because of body habitus. Body habitus should be assessed prior to each injection for each patient to assure that needle length is adequate for intramuscular administration. For patients with a larger amount of subcutaneous tissue overlying the gluteal muscle, the administering healthcare provider may utilize the supplied 2-inch needle with needle protection device to help ensure that the injectate reaches the intramuscular mass. For very lean patients, the 1 1/2-inch needle may be appropriate to prevent the needle contacting the periosteum. Either needle may be used for patients with average body habitus. Healthcare providers should ensure that the VIVITROL injection is given correctly, and should consider alternate treatment for those patients whose body habitus precludes an intramuscular gluteal injection with one of the provided needles.
VIVITROL must not be administered intravenously or subcutaneously.
If a patient misses a dose, he/she should be instructed to receive the next dose as soon as possible.
Pretreatment with oral naltrexone is not required before using VIVITROL.
2.1 Reinitiation of Treatment in Patients Previously Discontinued
There are no data to specifically address reinitiation of treatment. Patients reinitiating treatment with VIVITROL should be opioid-free at the time of dose administration [see Indications and Usage (1), Contraindications (4), and Warnings and Precautions (5.3)].
2.2 Switching From Oral Naltrexone
There are no systematically collected data that specifically address the switch from oral naltrexone to VIVITROL.
2.3 Switching from Buprenorphine, Buprenorphine/Naloxone, or Methadone
There are no systematically collected data that specifically address the switch from buprenorphine or methadone to VIVITROL; however, review of postmarketing case reports have indicated that some patients may experience severe manifestations of precipitated withdrawal when being switched from opioid agonist therapy to opioid antagonist therapy [see Warnings and Precautions (5.3)]. Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks. Healthcare providers should be prepared to manage withdrawal symptomatically with non-opioid medications
3 DOSAGE FORMS AND STRENGTHS
VIVITROL is an injectable suspension for single use. VIVITROL contains 380 mg of naltrexone in a microsphere formulation per vial (337 mg of naltrexone per gram of microspheres) and 4 mL diluent.
4. CONTRAINDICATIONS
VIVITROL is contraindicated in:
Patients receiving opioid analgesics [see Warnings and Precautions (5.3)].
Patients with current physiologic opioid dependence [see Warnings and Precautions (5.3)].
Patients in acute opioid withdrawal [see Warnings and Precautions (5.3)].
Any individual who has failed the naloxone challenge test or has a positive urine screen for opioids [see Warnings and Precautions (5.3)].
Patients who have previously exhibited hypersensitivity to naltrexone, PLG, carboxymethylcellulose, or any other components of the diluent
DRUG INTERACTIONS
Patients taking VIVITROL may not benefit from opioid-containing medicines. Naltrexone antagonizes the effects of opioid-containing medicines, such as cough and cold remedies, antidiarrheal preparations and opioid analgesics.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
There are no adequate and well-controlled studies of either naltrexone or VIVITROL in pregnant women. VIVITROL should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category C: Reproduction and developmental studies have not been conducted for VIVITROL. Studies with naltrexone administered via the oral route have been conducted in pregnant rats and rabbits.
Teratogenic Effects: Naltrexone has been shown to increase the incidence of early fetal loss when given to rats at doses ≥30 mg/kg/day (11 times the human exposure based on an AUC(0-28d) comparison) and to rabbits at oral doses ≥60 mg/kg/day (2 times the human exposure based on an AUC(0-28d) comparison).
There was no evidence of teratogenicity when naltrexone was administered orally to rats and rabbits during the period of major organogenesis at doses up to 200 mg/kg/day (175- and 14-times the human exposure based on an AUC(0-28d) comparison, respectively).
OVERDOSAGE
There is limited experience with overdose of VIVITROL. Single doses up to 784 mg were administered to 5 healthy subjects. There were no serious or severe adverse events. The most common effects were injection site reactions, nausea, abdominal pain, somnolence, and dizziness. There were no significant increases in hepatic enzymes.
In the event of an overdose, appropriate supportive treatment should be initiated.
11 DESCRIPTION
VIVITROL� (naltrexone for extended-release injectable suspension) is supplied as a microsphere formulation of naltrexone for suspension, to be administered by intramuscular injection. Naltrexone is an opioid antagonist with little, if any, opioid agonist activity.
Naltrexone is designated chemically as morphinan-6-one, 17 (cyclopropylmethyl) 4,5-epoxy-3,14-dihydroxy-(5α) (CAS Registry # 16590-41-3). The molecular formula is C20 H23 NO4 and its molecular weight is 341.41 in the anhydrous form (ie, < 1% maximum water content).
Naltrexone base anhydrous is an off-white to a light tan powder with a melting point of 168-170�C (334-338�F). It is insoluble in water and is soluble in ethanol.
VIVITROL is provided as a carton containing a vial each of VIVITROL microspheres and diluent, one 5-mL syringe, one 1-inch 20-gauge preparation needle, two 1 1/2-inch 20-gauge and two 2-inch 20-gauge administration needles with needle protection device.
VIVITROL microspheres consist of a sterile, off-white to light tan powder that is available in a dosage strength of 380 mg of naltrexone per vial. Naltrexone is incorporated in 75:25 polylactide-co-glycolide (PLG) at a concentration of 337 mg of naltrexone per gram of microspheres.
The diluent is a clear, colorless solution. The composition of the diluent includes carboxymethylcellulose sodium salt, polysorbate 20, sodium chloride, and water for injection. The microspheres must be suspended in the diluent prior to injection.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of action
Naltrexone is an opioid antagonist with highest affinity for the mu opioid receptor. Naltrexone has little or no opioid agonist activity.
Naltrexone has few, if any, intrinsic actions besides its opioid blocking properties. However, it does produce some pupillary constriction, by an unknown mechanism.
