Naltrexone and bupropion

Take naltrexone and bupropion only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

naltrexone and bupropion comes with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Follow your doctor's instructions carefully on a reduced-calorie diet plan and regular exercise. Talk with your doctor before starting any exercise program.

Swallow the tablet whole. Do not crush, break, or chew it.

Take naltrexone and bupropion with food. However, do not take it with high-fat meals. This may increase your risk of seizures.

Dosing

The dose of naltrexone and bupropion will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of naltrexone and bupropion. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release tablets):
  • For weight loss:
    • Adults—At first, one tablet in the morning taken on week 1. Your doctor will increase your dose to one tablet in the morning and one tablet in the evening on week 2. Then, two tablets in the morning and one tablet in the evening on week 3. On week 4, two tablets in the morning and two tablets in the evening.
    • Children—Use is not recommended.

Missed Dose

If you miss a dose of naltrexone and bupropion, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

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.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• 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.

This information should not be used to decide whether or not to take naltrexone and bupropion or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to naltrexone and bupropion. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Hypersensitivity to bupropion, naltrexone, or any other component of the formulation; concomitant use of other bupropion-containing products (eg, including [but not limited to] Wellbutrin, Wellbutrin SR, Wellbutrin XL, Aplenzin, Zyban); chronic opioid, opiate agonist (eg, methadone) or partial agonist (eg, buprenorphine) use; acute opioid withdrawal; uncontrolled hypertension; seizure disorder or a history of seizures; bulimia or anorexia nervosa; abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs; concomitant use of MAO inhibitors (concurrently or within 14 days of discontinuing the MAO inhibitor or naltrexone/bupropion); initiation of naltrexone/bupropion in a patient receiving linezolid or intravenous (IV) methylene blue; pregnancy

Administer twice daily doses in the morning and in the evening; do not administer with high-fat meals. Do not cut, chew, or crush tablets.

Ajmaline: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Ajmaline. Monitor therapy

Alcohol (Ethyl): BuPROPion may enhance the adverse/toxic effect of Alcohol (Ethyl). Specifically, alcohol tolerance may decrease during treatment. Alcohol (Ethyl) may enhance the adverse/toxic effect of BuPROPion. Specifically, seizure threshold may be lowered. Management: Patients receiving bupropion should be advised to minimize or avoid alcohol consumption due to possible lower alcohol tolerance, and lower seizure threshold associated with heavy alcohol consumption/abrupt discontinuation of heavy consumption. Consider therapy modification

Amifampridine: May enhance the adverse/toxic effect of BuPROPion. Specifically, both drugs have the potential to decrease the seizure threshold, possibly increasing the risk for seizures. Monitor therapy

Analgesics (Opioid): Naltrexone may diminish the therapeutic effect of Analgesics (Opioid). Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification

Antihepaciviral Combination Products: May decrease the serum concentration of BuPROPion. Monitor therapy

Anti-Parkinson Agents (Dopamine Agonist): May enhance the adverse/toxic effect of BuPROPion. Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose. Monitor therapy

Citalopram: BuPROPion may enhance the adverse/toxic effect of Citalopram. BuPROPion may increase the serum concentration of Citalopram. Management: Initiate citalopram at the lower end of the normal dose range in patients receiving bupropion, and consider limiting the maximum citalopram adult dose to 20 mg/day during concomitant bupropion treatment. Consider therapy modification

CloZAPine: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine. Monitor therapy

CYP2B6 Inducers (Moderate): May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy

CYP2B6 Inhibitors (Weak): May increase the serum concentration of BuPROPion. Exceptions: Prasugrel. Monitor therapy

CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy

Digoxin: BuPROPion may decrease the serum concentration of Digoxin. Monitor therapy

Dipyrone: May decrease the serum concentration of BuPROPion. Monitor therapy

DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Efavirenz: May decrease the serum concentration of BuPROPion. Management: Monitor for decreased response to bupropion in patients treated with efavirenz. Increased bupropion doses may be required. Avoid the use of naltrexone/bupropion for weight management in patients receiving efavirenz. Monitor therapy

Eliglustat: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor. Consider therapy modification

Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Monitor therapy

FLUoxetine: BuPROPion may enhance the adverse/toxic effect of FLUoxetine. BuPROPion may increase the serum concentration of FLUoxetine. Monitor therapy

FluvoxaMINE: BuPROPion may enhance the adverse/toxic effect of FluvoxaMINE. BuPROPion may increase the serum concentration of FluvoxaMINE. Monitor therapy

Indoramin: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin. Monitor therapy

Ioflupane I 123: BuPROPion may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Isavuconazonium Sulfate: May decrease the serum concentration of BuPROPion. Monitor therapy

Lopinavir: May decrease the serum concentration of BuPROPion. Concentrations of the active metabolite, hydroxybupropion, may also be decreased. Management: Monitor bupropion response closely. Significant bupropion dose adjustments may be necessary to maintain adequate response. Avoid the use of naltrexone/bupropion for weight management in patients receiving lopinavir. Monitor therapy

Lorcaserin: BuPROPion may enhance the serotonergic effect of Lorcaserin. This could result in serotonin syndrome. Management: Seek alternatives to this combination when possible. Consider therapy modification

Lumacaftor: May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy

MAO Inhibitors: May enhance the hypertensive effect of BuPROPion. Avoid combination

Methylnaltrexone: May enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Avoid combination

Metoprolol: CYP2D6 Inhibitors may increase the serum concentration of Metoprolol. Management: Consider an alternative for one of the interacting drugs in order to avoid metoprolol toxicity. If the combination must be used, monitor response to metoprolol closely. Metoprolol dose reductions may be necessary. Consider therapy modification

MiFEPRIStone: May increase the serum concentration of CYP2B6 Substrates. Monitor therapy

Naldemedine: Opioid Antagonists may enhance the adverse/toxic effect of Naldemedine. Specifically, the risk for opioid withdrawal may be increased. Avoid combination

Naloxegol: Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Avoid combination

Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Monitor therapy

Nilotinib: May decrease the serum concentration of CYP2B6 Substrates. Monitor therapy

OCT2 Substrates: BuPROPion may increase the serum concentration of OCT2 Substrates. Monitor therapy

PARoxetine: BuPROPion may enhance the adverse/toxic effect of PARoxetine. BuPROPion may increase the serum concentration of PARoxetine. Monitor therapy

Perhexiline: CYP2D6 Inhibitors may increase the serum concentration of Perhexiline. Management: Consider alternatives to this combination if possible. If combined, monitor for increased perhexiline serum concentrations and toxicities (eg, hypoglycemia, neuropathy, liver dysfunction). Perhexiline dose reductions will likely be required. Consider therapy modification

Propafenone: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Monitor therapy

Ritonavir: May decrease the serum concentration of BuPROPion. Mixed effects on concentrations of the active hydroxybupropion metabolite have been reported. Management: Monitor for decreased bupropion effects. Significant bupropion dose adjustments may be necessary to maintain adequate response. Avoid the use of naltrexone/bupropion for weight management in patients receiving ritonavir. Monitor therapy

Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Consider therapy modification

Thioridazine: CYP2D6 Inhibitors may increase the serum concentration of Thioridazine. Avoid combination

Thiotepa: May increase the serum concentration of CYP2B6 Substrates. Monitor therapy

Tricyclic Antidepressants: BuPROPion may decrease the metabolism of Tricyclic Antidepressants. Management: Seek alternatives when possible. Monitor patients receiving these combinations closely for increased serum concentrations (when testing is available) and toxic effects of the tricyclic antidepressant. Exceptions: Amoxapine; Protriptyline. Consider therapy modification

Vortioxetine: BuPROPion may enhance the adverse/toxic effect of Vortioxetine. BuPROPion may increase the serum concentration of Vortioxetine. Management: The vortioxetine dose should be reduced by 50% when used together with bupropion. Following cessation of bupropion, the vortioxetine dose should be returned to the normal level. Consider therapy modification

>10%:

Central nervous system: Headache (18%), sleep disorder (14%)

Gastrointestinal: Nausea (33%), constipation (19%), vomiting (11%)

1% to 10%:

Cardiovascular: Hypertension (≤6%), increased blood pressure (≤6%), palpitations (2%), myocardial infarction (<2%), presyncope (<2%), tachycardia (<2%)

Central nervous system: Dizziness (10%), insomnia (9%; ≥65 years of age: 11%), depression (6%; ≥ 65 years of age: 7%), anxiety (4% to 6%), fatigue (4%), irritability (3%), disturbance in attention (<2% to 3%), abnormal dreams (<2%), agitation (<2%), altered mental status (<2%), amnesia (<2%), derealization (<2%), emotional lability (<2%), equilibrium disturbance (<2%), feeling abnormal (<2%), feeling hot (<2%), intention tremor (<2%), jitteriness (<2%), lethargy (<2%), memory impairment (<2%), nervousness (<2%), tension (<2%), vertigo (<2%)

Dermatologic: Hyperhidrosis (3%), alopecia (<2%)

Endocrine: Hot flash (4%), dehydration (<2%), increased thirst (<2%)

Gastrointestinal: Xerostomia (8%), diarrhea (7%), upper abdominal pain (4%), viral gastroenteritis (4%), abdominal pain (3%), dysgeusia (2%), cholecystitis (<2%), eructation (<2%), hematochezia (<2%), hernia (<2%), lower abdominal pain (<2%), motion sickness (<2%), swelling of lips (<2%)

Genitourinary: Urinary tract infection (3%), erectile dysfunction (<2%), irregular menses (<2%), urinary urgency (<2%), vaginal dryness (<2%), vaginal hemorrhage (<2%)

Hematologic & oncologic: Decreased hematocrit (<2%)

Hepatic: Increased liver enzymes (<2%)

Infection: Kidney infection (<2%), staphylococcal infection (<2%)

Neuromuscular & skeletal: Tremor (4%), strain (2%), herniated disk (<2%), jaw pain (<2%), weakness (<2%)

Otic: Tinnitus (3%)

Renal: Increased serum creatinine (<2%)

Respiratory: Pneumonia (<2%)

<1% (Limited to important or life-threatening): Increased heart rate (resting), loss of consciousness, malaise, syncope

Contrave is not approved for use in the treatment of major depressive disorder or other psychiatric disorders. Contrave contains bupropion, the same active ingredient as some other antidepressant medications (including, but not limited to, Wellbutrin, Wellbutrin SR, Wellbutrin XL, and Aplenzin). Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in subjects over age 24; there was a reduction in risk with antidepressant use in subjects aged 65 and older. In patients of all ages who are started on Contrave, monitor closely for worsening, and for the emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. Contrave is not approved for use in pediatric patients.