Xtampza Er

Limitations of Use

• Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations, [see Warnings and Precautions (5.1)], reserve XTAMPZA 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.
• XTAMPZA ER is not indicated as an as-needed (prn) analgesic.

 Important Dosage and Administration Instructions

• XTAMPZA ER should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks.
• XTAMPZA ER single doses greater than 36 mg (equivalent to 40 mg oxycodone hydrochloride [HCl]) or a total daily dose greater than 72 mg (equivalent to 80 mg oxycodone HCl) are to be administered only to 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 HCl 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 of time consistent with individual patient treatment goals [see Warnings and Precautions (5)]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of XTAMPZA ER for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.
• Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)].
• Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with XTAMPZA ER. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions (5.2)].
• XTAMPZA ER is administered, twice daily, every 12 hours, and must be taken with food. Instruct patients to take XTAMPZA ER capsules with approximately the same amount of food for every dose in order to ensure consistent plasma levels are achieved [see Clinical Pharmacology (12.3)].
• Patients who are unable to swallow XTAMPZA ER should be instructed to sprinkle the capsule contents on soft foods or into a cup and then administer directly into the mouth and immediately swallow. XTAMPZA ER may also be administered through a gastrostomy or nasogastric feeding tube [see Dosage and Administration (2.7)].
• The maximum daily dose of XTAMPZA ER is 288 mg per day (eight 36 mg capsules, equivalent to 320 mg oxycodone HCl per day) as the safety of the excipients in XTAMPZA ER for doses over 288 mg/day has not been established.
• XTAMPZA ER is formulated with oxycodone base. The following table describes the equivalent amount of oxycodone HCl present in other oxycodone products.

 Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose

Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with XTAMPZA ER [see Warnings and Precautions (5.2)].

Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program).

Consider prescribing naloxone, based on the patient's risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient [see Warnings and Precautions (5.1, 5.2, 5.3)].

Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose.

 Initial Dosing

 Dosage Modifications in Patients with Hepatic Impairment

For patients with hepatic impairment, start dosing patients at 1/3 to 1/2 the usual starting dose followed by careful dose titration. Regularly evaluate for adverse events such as respiratory depression. Use of alternate analgesics is recommended for patients who require an XTAMPZA ER dose of less than 9 mg [see Use in Specific Populations (8.5), Clinical Pharmacology (12.3)].

 Titration and Maintenance of Therapy

Individually titrate XTAMPZA ER to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving XTAMPZA ER to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as to reassess for the development of addiction, abuse, and misuse. 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 use of opioid therapy for an extended period of time, periodically reassess the continued need for the use of opioid analgesics.

Patients who experience breakthrough pain may require a dose increase of XTAMPZA 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 XTAMPZA ER dose. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after a dosage increase), consider reducing the dosage [see Warnings and Precautions (5)]. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Because steady-state plasma concentrations are approximated in 1 to 2 days, XTAMPZA ER dosage may be adjusted every 1 to 2 days. If unacceptable opioid-related adverse reactions are observed, the subsequent dose may be reduced. Adjust the dose 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. As a guideline, the total daily oxycodone dose usually can be increased by 25% to 50% of the current dose, each time an increase is clinically indicated.

 Safe Reduction or Discontinuation of XTAMPZA ER

Do not abruptly discontinue XTAMPZA ER in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.

When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking XTAMPZA ER, there are a variety of factors that should be considered, including the total daily dose of opioid (including XTAMPZA ER) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist.

There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on XTAMPZA ER who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.

It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.

When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time, and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and Precautions (5.14), Drug Abuse and Dependence (9.3)].

 Administration of XTAMPZA ER

Instruct patients to always take XTAMPZA ER capsules with food and with approximately the same amount of food in order to ensure consistent plasma levels are achieved [see Dosage and Administration (2.1), Clinical Pharmacology (12.3)].

For patients who have difficulty swallowing, XTAMPZA ER can also be taken by sprinkling the capsule contents on soft foods or sprinkling the contents into a cup and then administering directly into the mouth or through a gastrostomy or nasogastric feeding tube. Patients who are unable to swallow a capsule should be instructed to:

1. Open the capsule.
2. Sprinkle the capsule contents (microspheres) onto a small amount of soft food (e.g., applesauce, pudding, yogurt, ice cream, or jam) or into a cup and then administer directly into the mouth and swallow immediately.
3. Rinse the mouth to ensure all capsule contents (microspheres) have been swallowed.
4. Discard the XTAMPZA ER capsule shells after the contents have been sprinkled on soft food or into a cup and then administered directly into the mouth.

The contents of the XTAMPZA ER capsules (microspheres) may be administered through a nasogastric tube or gastrostomy tube. When administering XTAMPZA ER through a nasogastric or gastrostomy tube:

1. Flush the tube with water.
2. Open an XTAMPZA ER capsule and carefully pour the microspheres directly into the tube. Do not pre-mix the capsule contents with the liquid that you will be using to flush them through the tube.
3. Draw up 15 mL of water into a syringe, insert the syringe into the tube, and flush the microspheres through the tube.
4. Repeat the flushing two more times, each with 10 mL of water, to ensure no microspheres remain in the tube.

Alternatively, milk or liquid nutritional supplement may be used as vehicles for flush and administration through feeding tubes.

Pregnancy

Lactation

Females and Males of Reproductive Potential

Pediatric Use

Safety and effectiveness of XTAMPZA ER in pediatric patients below the age of 18 years have not been established.

Geriatric Use

In controlled pharmacokinetic studies in elderly subjects (greater than 65 years) the clearance of oxycodone was slightly reduced. Compared to young adults, the plasma concentrations of oxycodone were increased approximately 15% [see Clinical Pharmacology (12.3)]. Of the total number of subjects entered into the titration phase of the Phase 3 study for XTAMPZA ER (740), 88 (12%) were age 65 and older. In this clinical trial with appropriate initiation of therapy and dose titration, no untoward or unexpected adverse reactions were seen in the elderly patients who received XTAMPZA ER. Thus, the usual doses and dosing intervals may be appropriate for elderly patients. 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 in 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 XTAMPZA ER slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.8)].

Hepatic Impairment

A study in patients with hepatic impairment demonstrated greater plasma oxycodone concentrations than those seen at equivalent doses in persons with normal hepatic function. A similar effect on plasma oxycodone concentrations can be expected for patients with hepatic impairment taking XTAMPZA ER. Therefore, in the setting of hepatic impairment, start dosing patients at 1/3 to 1/2 the usual starting dose followed by careful dose titration. Use of alternative analgesics is recommended for patients who require a dose of XTAMPZA ER less than 9 mg [see Dosage and Administration (2.4), Clinical Pharmacology (12.3)].

Renal Impairment

In patients with renal impairment, as evidenced by decreased creatinine clearance (<60 mL/min), the concentrations of oxycodone in the plasma are approximately 50% higher than in subjects with normal renal function. Follow a conservative approach to dose initiation and adjust according to the clinical situation. Use of alternative analgesics is recommended for patients who require a dose of XTAMPZA ER less than 9 mg [see Clinical Pharmacology (12.3)].

Sex Differences

In pharmacokinetic studies with XTAMPZA ER, healthy female subjects demonstrate up to 20% higher oxycodone plasma exposures than males, even after considering differences in body weight or BMI. The clinical relevance of a difference of this magnitude is low for a drug intended for chronic usage at individualized dosages. In the Phase 3 clinical trial there was a greater frequency of typical opioid adverse events for females than males; there was no male/female difference detected for efficacy.