Data from FDA - Curated by EPG Health - Last updated 22 December 2016

Indication(s)

1 INDICATIONS AND USAGE TROXYCA ER is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. TROXYCA ER is a combination opioid agonist/opioid antagonist product indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. (1) Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve TROXYCA ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. (1) TROXYCA ER is not indicated as an as-needed (prn) analgesic. (1) Limitations of Use: Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations [see Warnings and Precautions (5.1)], reserve TROXYCA ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. TROXYCA ER is not indicated as an as-needed (prn) analgesic.

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

Acute and Advanced Heart Failure

Acute and Advanced Heart Failure

What are the most effective treatments for acute heart failure? Can you define advanced heart failure? Discover here...

+ 3 more

Allergic Rhinitis

Allergic Rhinitis

Allergic rhinitis causes great strain on the workforce. Help to reduce sick days and improve productivity with appropriate treatment options.

+ 4 more

Anticoagulation Therapy for Stroke Prevention

Anticoagulation Therapy for Stroke Prevention

Anticoagulation therapy for Stroke Prevention Learning Zone offers a deep-dive into atrial fibrillation causes, consequences, diagnosis and management to help you deliver optimal care and prevent strokes in patients living with this common arrhythmia.

Load more

Related Content

Advisory information

contraindications
4 CONTRAINDICATIONS TROXYCA ER is contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions (5.2)] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.6)] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.10)] Hypersensitivity (e.g., anaphylaxis) to oxycodone or naltrexone or any other components of the TROXYCA ER formulation [see Adverse Reactions (6.1)] Significant respiratory depression (4) Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (4) Known or suspected gastrointestinal obstruction, including paralytic ileus (4) Hypersensitivity to oxycodone or naltrexone (4)
Adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2)] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.3)] Interactions with CNS Depressants [see Warnings and Precautions (5.5)] Adrenal Insufficiency [see Warnings and Precautions (5.7)] Severe Hypotension [see Warnings and Precautions (5.8)] Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.10)] Seizures [see Warnings and Precautions (5.11)] Withdrawal [see Warnings and Precautions (5.12)] Most common adverse reactions: nausea, constipation, vomiting, headache, and somnolence. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. In controlled and uncontrolled studies, the most common adverse reactions were nausea, constipation, vomiting, headache, and somnolence. The most common adverse reactions leading to discontinuation (≥1% in any of the treatment phases) were nausea, constipation, vomiting, somnolence, headache, fatigue, and dizziness. In a randomized, placebo-controlled, double-blind study in subjects with moderate-to-severe chronic low back pain, 410 subjects received TROXYCA ER. This study utilized an enriched enrollment with a randomized withdrawal design in which subjects were titrated to effect on open-label TROXYCA ER for up to 42 days. Once their pain was controlled, 280 subjects were randomized to and received active treatment with TROXYCA ER (146 subjects) or were tapered off TROXYCA ER using a double-dummy design and treated with placebo (134 subjects) for 12 weeks. Adverse reactions reported in ≥2% of subjects receiving TROXYCA ER in either the titration phase or maintenance phase of the placebo-controlled study are presented in Table 2. Table 2. Adverse Drug Reactions Reported in ≥2% of Subjects Receiving TROXYCA ER in the Placebo-Controlled Study System Organ Class Open-Label Titration Phase TROXYCA ER (N=410) Double-Blind Maintenance Phase TROXYCA ER (N=146) Double-Blind Maintenance Phase Placebo (N=134) Adverse Drug Reaction (ADR) n (%) n (%) n (%) Gastrointestinal disorders Abdominal painAbdominal pain also includes Abdominal discomfort, Abdominal pain lower, Abdominal pain upper, Abdominal tenderness, Epigastric discomfort, and Gastrointestinal pain. 12 ( 2.9) 2 ( 1.4) 8 ( 6.0) Constipation 61 (14.9) 5 ( 3.4) 3 ( 2.2) Diarrhea 9 ( 2.2) 8 ( 5.5) 6 ( 4.5) Dry mouth 13 ( 3.2) 0 0 Nausea 84 (20.5) 21 (14.4) 5 ( 3.7) Vomiting 37 ( 9.0) 9 ( 6.2) 4 ( 3.0) General disorders and administration site conditions Drug withdrawal syndromeDrug withdrawal syndrome ADR includes Drug withdrawal syndrome and Withdrawal syndrome MedDRA Preferred Terms or a score of greater than or equal to 13 on the Clinical Opiate Withdrawal Scale. 4 ( 1.0) 4 ( 2.7) 2 (1.5) Fatigue 13 ( 3.2) 5 ( 3.4) 1 ( 0.7) Edema peripheral 3 ( 0.7) 3 ( 2.1) 1 ( 0.7) Musculoskeletal and connective tissue disorders Arthralgia 3 ( 0.7) 3 ( 2.1) 1 ( 0.7) Back pain 5 ( 1.2) 3 ( 2.1) 8 ( 6.0) Muscle spasms 1 ( 0.2) 4 ( 2.7) 1 ( 0.7) Nervous system disorders Dizziness 24 ( 5.9) 6 ( 4.1) 1 ( 0.7) Headache 30 ( 7.3) 2 ( 1.4) 7 ( 5.2) Hypoesthesia 0 3 ( 2.1) 0 SomnolenceSomnolence also includes Sedation. 37 ( 9.0) 1 ( 0.7) 1 ( 0.7) Psychiatric disorders Insomnia 8 ( 2.0) 1 ( 0.7) 1 ( 0.7) Respiratory, thoracic and mediastinal disorders Oropharyngeal pain 1 ( 0.2) 4 ( 2.7) 1 ( 0.7) Skin and subcutaneous tissue disorders HyperhidrosisHyperhidrosis also includes Cold sweat. 10 ( 2.4) 4 ( 2.7) 1 ( 0.7) PruritusPruritus also includes Pruritus generalized. 27 ( 6.6) 3 ( 2.1) 0 Vascular disorders Hot flushHot flush also includes Flushing. 10 ( 2.4) 2 ( 1.4) 3 ( 2.2) An additional 395 subjects received at least one dose of TROXYCA ER in an open-label, 12-month safety study of subjects with moderate-to-severe chronic non-cancer pain. In this study, 193 subjects received TROXYCA ER for at least 6 months and 105 subjects received TROXYCA ER for approximately 12 months. Adverse reactions reported in ≥2% of subjects of the 12-month open-label safety study are presented in Table 3. Table 3. Adverse Drug Reactions Reported in ≥2% of Subjects in the 12-Month Open-Label Safety Study System Organ Class TROXYCA ER (N=395) Adverse Drug Reaction (ADR) n (%) Gastrointestinal disorders Abdominal painAbdominal pain also includes Abdominal discomfort, Abdominal pain lower, Abdominal pain upper, Abdominal tenderness, Epigastric discomfort, and Gastrointestinal pain. 33 ( 8.4) Constipation 84 (21.3) Diarrhea 36 ( 9.1) Dry mouth 9 ( 2.3) Nausea 100 (25.3) Vomiting 55 (13.9) General disorders and administration site conditions Fatigue 36 ( 9.1) Edema peripheral 15 ( 3.8) Musculoskeletal and connective tissue disorders Arthralgia 13 ( 3.3) Back pain 25 ( 6.3) Muscle spasms 9 ( 2.3) Nervous system disorders Dizziness 34 ( 8.6) Headache 46 (11.6) SomnolenceSomnolence also includes Sedation. 38 ( 9.6) Tremor 8 ( 2.0) Psychiatric disorders Depression 13 ( 3.3) Insomnia 20 ( 5.1) Restlessness 9 ( 2.3) Respiratory, thoracic and mediastinal disorders Cough 10 ( 2.5) Oropharyngeal pain 9 ( 2.3) Skin and subcutaneous tissue disorders HyperhidrosisHyperhidrosis also includes Cold sweat. 27 ( 6.8) PruritusPruritus also includes Pruritus generalized. 22 ( 5.6) Vascular disorders Hot flushHot flush also includes Flushing. 17 ( 4.3) Less Common Adverse Reactions The following adverse reactions occurred in patients taking TROXYCA ER in controlled and uncontrolled Phase 3 clinical trials with a frequency of <2%. Adverse reactions are listed in descending order of frequency within System Organ Class. Table 4. Adverse Drug Reactions Reported in <2% of Subjects in All Phases of the TROXYCA ER Phase 3 Studies System Organ Class Adverse Drug Reaction (ADR) Preferred Term Blood and lymphatic disorders Anemia, Lymphadenopathy Cardiac disorders Tachycardia, Palpitations, Bradycardia Ear and labyrinth disorders Vertigo, Tinnitus Eye disorders Lacrimation increased Gastrointestinal disorders Dyspepsia General disorders and administration site conditions Chills, Pain, Influenza like illness, Irritability, Chest painChest pain also includes Chest discomfort and Non-cardiac chest pain., Pyrexia, Edema, Malaise Immune system disorders Drug hypersensitivityDrug hypersensitivity also includes Hypersensitivity. Investigations Blood pressure increased, Blood testosterone decreased, Blood glucose increasedBlood glucose increased also includes Diabetes mellitus inadequate control., Liver function test abnormalLiver function test abnormal includes Alanine aminotransferase increased and Aspartate aminotransferase increased. Metabolism and nutrition disorders Decreased appetite, Gout Musculoskeletal and connective tissue disorders Myalgia, Muscle twitching, Musculoskeletal stiffness, Arthritis Nervous system disorders Paresthesia, Lethargy, Disturbance in attention, Migraine, Dysgeusia Psychiatric disorders Abnormal dreams, Confusional state, Disorientation, Libido decreased, Drug abuse Renal and urinary disorders Dysuria, Hematuria Respiratory, thoracic and mediastinal disorders Rhinorrhoea, Bronchitis chronic, Dyspnea, Dysphonia Skin and subcutaneous tissue disorders RashRash also includes Rash pruritic., Urticaria Surgical and medical procedures Intentional drug misuse 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of oxycodone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis and pharyngeal edema: Anaphylaxis and pharyngeal edema have been reported with ingredients contained in TROXYCA ER. Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology (12.2)]. Myocardial ischemia and ventricular fibrillation: Myocardial ischemia and ventricular fibrillation have been reported with oxycodone overdose.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION To be prescribed only by healthcare providers knowledgeable in use of potent opioids for management of chronic pain. (2.1) TROXYCA ER 60 mg/7.2 mg and 80 mg/9.6 mg capsules, single doses of TROXYCA ER greater than 40 mg/4.8 mg, or a total daily dose greater than 80 mg/9.6 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. (2.1) Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. (2.1) Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. (2.1) Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse. (2.1) Instruct patients to swallow TROXYCA ER capsules intact, or to sprinkle the capsule contents on applesauce and immediately swallow without chewing. (2.1, 2.5) Instruct patients not to crush, chew, or dissolve the pellets in the capsule to avoid the risk of release and absorption of a potentially fatal dose of oxycodone and to avoid release of sequestered naltrexone that could precipitate opioid withdrawal. (2.1, 2.5, 5.1) For opioid-naïve and opioid non-tolerant patients, initiate with the 10 mg/1.2 mg capsule every 12 hours. (2.1, 2.2) Do not abruptly discontinue TROXYCA ER. (2.4, 5.12) 2.1 Important Dosage and Administration Instructions TROXYCA ER should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. TROXYCA ER 60 mg/7.2 mg and 80 mg/9.6 mg capsules, single doses of TROXYCA ER greater than 40 mg/4.8 mg, or a total daily dose greater than 80 mg/9.6 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients who are opioid-tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5)]. Initiate the dosing regimen for each patient individually; taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24–72 hours of initiating therapy and following dosage increases with TROXYCA ER and adjust the dosage accordingly [see Warnings and Precautions (5.2)]. Instruct patients to swallow TROXYCA ER capsules whole [see Patient Counseling Information (17)]. Crushing, chewing, or dissolving the pellets in TROXYCA ER capsules will result in uncontrolled delivery of oxycodone and can lead to overdose or death [see Warnings and Precautions (5.1)]. Instruct patients who are unable to swallow TROXYCA ER capsules to sprinkle the capsule contents on applesauce and immediately swallow without chewing [see Dosage and Administration (2.5)]. Administer TROXYCA ER orally every 12 hours. 2.2 Initial Dosing Use of TROXYCA ER as the First Opioid Analgesic (opioid-naïve patients) Initiate treatment with TROXYCA ER with 10 mg/1.2 mg capsule orally every 12 hours. Use of TROXYCA ER in Patients who are not Opioid-Tolerant (opioid-non-tolerant patients) The starting dose for patients who are not opioid-tolerant is TROXYCA ER 10 mg/1.2 mg capsule orally, every 12 hours. Use of higher starting doses in patients who are not opioid-tolerant may cause fatal respiratory depression [see Warnings and Precautions (5.2)]. Conversion from Other Oral Oxycodone HCl Formulations to TROXYCA ER Patients receiving other oral oxycodone HCl formulations may be converted to TROXYCA ER by administering one half of the patient's total daily oral oxycodone HCl dose as TROXYCA ER every 12 hours. Conversion from Other Opioids to TROXYCA ER Discontinue all other around-the-clock opioid drugs when TROXYCA ER therapy is initiated. There is inter-patient variability in the relative potency of opioid drugs and formulations. Therefore, a conservative approach is advised when determining the total daily dosage of TROXYCA ER. It is safer to underestimate a patient's 24-hour TROXYCA ER dosage and provide rescue medication (e.g., immediate-release oxycodone) than to overestimate the 24-hour oxycodone dosage and manage an adverse reaction due to overdose. In a TROXYCA ER clinical trial with an open-label titration period, patients were converted from their prior opioid to TROXYCA ER using Table 1. Consider the following when using the information in Table 1: This is not a table of equianalgesic doses. The conversion factors in this table are only for the conversion from one of the listed oral opioid analgesics to TROXYCA ER. The table cannot be used to convert from TROXYCA ER to another opioid. Doing so will result in an overestimation of the dose of the new opioid and may result in fatal overdose. To calculate the estimated TROXYCA ER dose using Table 1: Calculate the approximate total daily oral oxycodone dose For patients on a single opioid, multiply the current total daily dose of the opioid by the appropriate conversion factor listed in Table 1. For patients on a regimen of more than one opioid, use Table 1 to calculate the total daily oral oxycodone dose for each opioid and sum the totals. For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products for calculating the approximate total daily oral oxycodone dose. Reduce the estimated total daily oxycodone dose by 50% to obtain the daily dose of TROXYCA ER. Divide the daily dose in half to obtain the every 12-hour dose of TROXYCA ER. After conversion, if the total daily opioid requirement is ≤20 mg per day of oral oxycodone, initiate therapy with TROXYCA ER 10 mg/1.2 mg every 12 hours (i.e., TROXYCA ER 20 mg per day). Always round the dose down, if necessary, to the appropriate TROXYCA ER strength(s) available. Provide rescue medication as needed (e.g., immediate-release oxycodone). Table 1. Conversion Factors to TROXYCA ERUse this formula to calculate total daily dose of TROXYCA ER: mg/day prior opioid × conversion factor = mg/day TROXYCA ER Prior Oral Opioid Approximate Oral Conversion Factor Codeine (including combination drugs) 0.1 Hydrocodone (including combination drugs) 0.67 Hydromorphone 2.67 Methadone See note on conversion below Morphine 0.67 Oxycodone (including combination drugs) 1 Tramadol See note on conversion below Transdermal fentanyl See note on conversion below Example conversion from a single opioid to TROXYCA ER: Step 1: Sum the total daily dose of the prior opioid. For example, extended-release hydrocodone 30 mg twice daily = 60 mg total daily dose of hydrocodone. Step 2: Calculate the equivalent dose of oral oxycodone based on the total daily dose of the current opioid using Table 1. In this example, 60 mg total daily dose of hydrocodone × 0.67 (conversion factor) = 40.2 mg of oral oxycodone daily. Step 3: Reduce the dose by 50% and divide in half to obtain the every 12-hour dose of TROXYCA ER. In this example, the total daily dose would be 20 mg, and the final dosing regimen would be TROXYCA ER 10 mg/1.2 mg every 12 hours. Close observation and frequent titration are warranted until pain management is stable on the new opioid. Monitor patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after converting patients to TROXYCA ER. Conversion from Transdermal Fentanyl to TROXYCA ER Treatment with TROXYCA ER can be initiated after the transdermal fentanyl patch has been removed for at least 18 hours. Although there has been no systematic assessment of such conversion, start with a conservative conversion: substitute 10 mg/1.2 mg of TROXYCA ER every 12 hours for each 25 mcg/hr fentanyl transdermal patch. Follow the patient closely during conversion from transdermal fentanyl to TROXYCA ER, as there is limited documented experience with this conversion. Conversion from Transdermal Buprenorphine to TROXYCA ER There has been no systematic assessment of this conversion. The recommended starting dose of TROXYCA ER in patients receiving transdermal buprenorphine is 10 mg/1.2 mg every 12 hours. Conversion from Tramadol to TROXYCA ER Tramadol has both serotonergic and opioid activity, and there has been no systematic assessment of this conversion. The recommended starting dose of TROXYCA ER in patients receiving tramadol is 10 mg/1.2 mg every 12 hours. Conversion from Methadone to TROXYCA ER Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma. 2.3 Titration and Maintenance of Therapy Individually titrate TROXYCA ER to a dosage that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving TROXYCA ER to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1)]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for opioid analgesics. Patients who experience breakthrough pain may require a dosage increase of TROXYCA ER, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the TROXYCA ER dosage. Because steady-state plasma concentrations are achieved within 48 hours, the total daily dose of TROXYCA ER may be adjusted by 20 mg/2.4 mg every 2 to 3 days as needed based on efficacy, safety, and tolerability. If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours. 2.4 Discontinuation of TROXYCA ER When a patient no longer requires therapy with TROXYCA ER, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue TROXYCA ER [see Warnings and Precautions (5.12), Drug Abuse and Dependence (9.3)]. 2.5 Administration of TROXYCA ER Instruct patients to swallow TROXYCA ER capsules intact. The capsules contain pellets that consist of oxycodone HCl and sequestered naltrexone HCl. The pellets in the capsules are not to be manipulated, i.e., crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of oxycodone [see Warnings and Precautions (5.1)]. Consuming TROXYCA ER capsules that have been altered by crushing, dissolving, or chewing the pellets can release sufficient naltrexone to precipitate withdrawal in opioid-dependent individuals [see Warnings and Precautions (5.12)]. Alternatively, the contents of the TROXYCA ER capsules (pellets) may be sprinkled over applesauce and then swallowed. This method is appropriate only for patients able to reliably swallow the applesauce without chewing. Other foods have not been tested and should not be substituted for applesauce. Instruct the patient to: Open the capsule. Sprinkle the pellets onto a small amount of applesauce and swallow immediately without chewing. Rinse the mouth to ensure all pellets have been swallowed. Discard the empty capsule shell after the contents have been sprinkled on applesauce. Do not administer TROXYCA ER pellets through a nasogastric or gastric tube.
Use in special populations
8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause fetal harm. (5.3, 8.1) Lactation: Not recommended. (8.2) Geriatric patients: Start at the low end of the dosing range and monitor closely for respiratory depression. (5.6, 8.5) Hepatic Impairment: Monitor patients closely for CNS or respiratory depression and for signs of withdrawal. (8.6, 12.3) Renal Impairment: Monitor patients closely for CNS or respiratory depression and for signs of withdrawal. (8.7, 12.3) 8.1 Pregnancy Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.3)]. There are no available data with TROXYCA ER in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. Because plasma naltrexone levels were detectable in some patients administered TROXYCA ER in the clinical trials [see Clinical Pharmacology (12.3)], the naltrexone component of TROXYCA ER may precipitate withdrawal in a fetus due to the immaturity of the fetal blood-brain barrier. Animal reproduction studies with oral administrations of oxycodone HCl in rats and rabbits during the period of organogenesis at doses equal to or 3-times, respectively, the human dose of 160 mg/day did not reveal evidence of teratogenicity or embryo-fetal toxicity. In several published studies, treatment of pregnant rats with oxycodone at clinically relevant doses and below, resulted in neurobehavioral effects in offspring [see Data]. Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy can occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.3)]. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. TROXYCA ER is not recommended for use in pregnant women during and immediately prior to labor, when use of shorter acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including TROXYCA ER, can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Data Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of oxycodone HCl administered during the period of organogenesis up to 16 mg/kg/day and up 25 mg/kg/day, respectively. These studies revealed no evidence of teratogenicity or embryo-fetal toxicity due to oxycodone. The highest doses tested in rats and rabbits were equivalent to approximately 1 and 3 times an adult human dose of 160 mg/day, respectively, on a mg/m2 basis. In published studies, offspring of pregnant rats administered oxycodone during gestation have been reported to exhibit neurobehavioral effects including altered stress responses, increased anxiety-like behavior (2 mg/kg/day IV from Gestation Day 8 to 21 and Postnatal Day 1, 3, and 5; 0.1-times an adult human dose of 160 mg/day, on a mg/m2 basis) and altered learning and memory (15 mg/kg/day orally from breeding through parturition; equivalent to an adult human dose of 160 mg/day, on a mg/m2 basis). 8.2 Lactation Risk Summary Oxycodone is present in breast milk. Published lactation studies report variable concentrations of oxycodone in breast milk with administration of immediate-release oxycodone to nursing mothers in the early postpartum period. The lactation studies did not assess breastfed infants for potential adverse reactions. Lactation studies have not been conducted with extended-release oxycodone, including TROXYCA ER, and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with TROXYCA ER. Clinical Considerations Monitor infants exposed to TROXYCA ER through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped or when breastfeeding is stopped. Because plasma naltrexone levels were detectable in some patients administered TROXYCA ER in the clinical trials [see Clinical Pharmacology (12.3)], the naltrexone component of TROXYCA ER may precipitate opioid withdrawal in a breastfed infant. 8.3 Females and Males of Reproductive Potential Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6.2), Clinical Pharmacology (12.2)]. 8.4 Pediatric Use The safety and efficacy of TROXYCA ER in patients less than 18 years of age have not been established. 8.5 Geriatric Use The pharmacokinetics of TROXYCA ER have not been investigated in elderly patients (≥65 years) although such patients were included in clinical studies. Clinical studies with TROXYCA ER did not include sufficient numbers of subjects aged 65 and older to determine if they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, concomitant disease, and use of other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of TROXYCA ER slowly in geriatric patients [see Warnings and Precautions (5.6)]. This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. 8.6 Hepatic Impairment Since oxycodone is extensively metabolized in the liver, its clearance may decrease in patients with hepatic impairment. Naltrexone is sequestered in the TROXYCA ER capsules and is not intended to be released when TROXYCA ER is used as directed. However, measurable naltrexone plasma concentrations have been observed in some patients in clinical trials with TROXYCA ER [see Clinical Pharmacology (12.3)]. An increase in naltrexone AUC in patients with compensated and decompensated liver cirrhosis, compared with subjects with normal liver function, has been reported [see Clinical Pharmacology (12.3)]. These data also suggest that alterations in naltrexone bioavailability are related to liver disease severity. Dose initiation of TROXYCA ER should follow a conservative approach in patients with hepatic impairment. In patients with hepatic impairment, there is a potential for differential increase in naltrexone exposure compared to oxycodone exposure. Hence, when administering TROXYCA ER to patients with hepatic impairment, monitor patients closely for signs of central nervous system or respiratory depression due to elevated levels of oxycodone and for signs of withdrawal due to elevated levels of naltrexone and adjust the dose based on the clinical response. 8.7 Renal Impairment Elimination of oxycodone is reported to be impaired in patients with renal impairment. Although naltrexone is sequestered in the TROXYCA ER formulations, measurable naltrexone plasma concentrations have been observed in some patients in clinical trials with TROXYCA ER [see Clinical Pharmacology (12.3)]. Since naltrexone and its primary metabolite are excreted primarily in urine, their plasma concentrations may be increased in patients with renal impairment. Dose initiation of TROXYCA ER should follow a conservative approach in patients with renal impairment. In patients with renal impairment, there is a potential for differential increase in naltrexone exposure compared to oxycodone exposure. Hence, when administering TROXYCA ER to patients with renal impairment, monitor patients closely for signs of central nervous system or respiratory depression due to elevated levels of oxycodone and for signs of withdrawal due to elevated levels of naltrexone and adjust the dose based on the clinical response. 8.8 Sex Differences There are no clinically significant differences in oxycodone pharmacokinetics following oral administration of TROXYCA ER to males or females; therefore, no specific dosage adjustment is recommended for the initiation or maintenance of TROXYCA ER doses based on the sex of the patient [see Clinical Pharmacology (12.3)].

Interactions

7 DRUG INTERACTIONS Table 5 includes clinically significant drug interactions with TROXYCA ER. Table 5: Clinically Significant Drug Interactions with TROXYCA ER Inhibitors of CYP3A4 and CYP2D6 Clinical Impact: The concomitant use of TROXYCA ER and CYP3A4 inhibitors can increase the plasma concentration of oxycodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of TROXYCA ER and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after stable dose of TROXYCA ER is achieved [see Warnings and Precautions (5.4)]. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oxycodone plasma concentration will decrease [see Clinical Pharmacology (12.3)], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to oxycodone. Intervention: If concomitant use is necessary, consider dosage reduction of TROXYCA ER until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the TROXYCA ER dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of TROXYCA ER and CYP3A4 inducers can decrease the plasma concentration of oxycodone [see Clinical Pharmacology (12.3)], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to oxycodone [see Warnings and Precautions (5.4)]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the oxycodone plasma concentration will increase [see Clinical Pharmacology (12.3)], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the TROXYCA ER dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider TROXYCA ER dosage reduction and monitor for signs of respiratory depression. Examples: Rifampin, carbamazepine, phenytoin Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effects, the concomitant use of CNS depressants can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Intervention: Consider dose reduction of one or both drugs. Monitor patients for signs of respiratory depression, sedation, and hypotension [see Warnings and Precautions (5.2)]. Examples Alcohol, benzodiazepines, and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids. Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue TROXYCA ER if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of TROXYCA ER and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use. Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact: Oxycodone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of TROXYCA ER and/or the muscle relaxant, as necessary. Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: The concomitant use of MAOIs can potentiate the effects of oxycodone and can increase the risk of anxiety, confusion, hypotension, respiratory depression, profound sedation, coma, and death. Intervention: Avoid concomitant use in patients receiving MAOIs or within 14 days of stopping treatment with an MAOI. Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when TROXYCA ER is used concomitantly with anticholinergic drugs. CNS Depressants: Concomitant use may cause hypotension, profound sedation, respiratory depression, coma, and death. If coadministration is required, consider dose reduction of one or both drugs because of additive pharmacological effects and monitor closely. (5.5, 7) Serotonergic Drugs: Concomitant use may result in serotonin syndrome. Discontinue TROXYCA ER if serotonin syndrome is suspected. (7) Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid use with TROXYCA ER because they may reduce analgesic effect of TROXYCA ER or precipitate withdrawal symptoms. (7) Monoamine Oxidase Inhibitors (MAOIs): Avoid TROXYCA ER in patients taking MAOIs or within 14 days of stopping such treatment. (7)

More information

Category Value
Authorisation number NDA207621
Orphan designation No
Product NDC 60793-537,60793-536,60793-535,60793-533,60793-532,60793-531
Date Last Revised 25-08-2016
Type HUMAN PRESCRIPTION DRUG
RXCUI 1806736
Storage and handling Bottle count for each of these strengths is 100. Store at 25°C (77°F); excursions permitted between 15° and 30°C (59° and 86°F). Dispense in tight (USP), light-resistant, child-resistant containers.
Marketing authorisation holder Pfizer Laboratories Div Pfizer Inc
Warnings WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and CYTOCHROME P450 3A4 INTERACTION. Addiction, Abuse, and Misuse TROXYCA ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing TROXYCA ER, and monitor all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions (5.1)]. WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and CYTOCHROME P450 3A4 INTERACTION See full prescribing information for complete boxed warning. TROXYCA ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient's risk before prescribing, and monitor regularly for these behaviors and conditions. (5.1) Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow TROXYCA ER capsules whole to avoid exposure to a potentially fatal dose of oxycodone. (5.2) Accidental ingestion of TROXYCA ER, especially by children, can result in fatal overdose of oxycodone. (5.2) Prolonged use of TROXYCA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. (5.3) Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in fatal overdose of oxycodone from TROXYCA ER. (5.4) Life-threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of TROXYCA ER. Monitor for respiratory depression, especially during initiation of TROXYCA ER or following a dose increase. Instruct patients to swallow TROXYCA ER capsules whole or to sprinkle the contents of the capsule on applesauce and swallow immediately without chewing. Crushing, chewing, or dissolving TROXYCA ER can cause rapid release and absorption of a potentially fatal dose of oxycodone [see Warnings and Precautions (5.2)]. Accidental Ingestion Accidental ingestion of even one dose of TROXYCA ER, especially by children, can result in a fatal overdose of oxycodone [see Warnings and Precautions (5.2)]. Neonatal Opioid Withdrawal Syndrome Prolonged use of TROXYCA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.3)]. Cytochrome P450 3A4 Interaction The concomitant use of TROXYCA ER with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentrations. Monitor patients receiving TROXYCA ER and any CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.4), Drug Interactions (7), Clinical Pharmacology (12.3)].