XTAMPZA ER (Page 10 of 11)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long term studies in animals to evaluate the carcinogenic potential of oxycodone have not been conducted.

Mutagenesis

Oxycodone was genotoxic in the in vitro mouse lymphoma assay. Oxycodone was negative when tested at appropriate concentrations in the in vitro chromosomal aberration assay, the in vitro bacterial reverse mutation assay (Ames test), and the in vivo bone marrow micronucleus assay in mice.

Impairment of Fertility

In a study of reproductive performance, rats were administered a once daily gavage dose of the vehicle or oxycodone hydrochloride (0.5, 2, and 8 mg/kg). Male rats were dosed for 28 days before cohabitation with females, during the cohabitation and until necropsy (2-3 weeks post-cohabitation). Females were dosed for 14 days before cohabitation with males, during cohabitation and up to Gestation Day 6. Oxycodone HCl did not affect reproductive function in male or female rats at any dose tested (≤ 8 mg/kg/day), up to 1.3 times a human dose of 60 mg/day.

13.2 Animal Toxicology

The safety of beeswax, carnauba wax, and myristic acid in XTAMPZA ER in doses exceeding a total daily dose of 288 mg oxycodone per day (equivalent to 320 mg oxycodone HCl per day) has not been studied.

14 CLINICAL STUDIES

An enriched-enrollment, randomized-withdrawal, double-blind, placebo-controlled, parallel group, study was conducted in 740 patients with persistent, moderate-to-severe chronic lower back pain, with inadequate pain control from their prior therapy. During screening, patients stopped their prior opioid analgesics and/or non-opioid analgesics prior to starting XTAMPZA ER treatment. Patients were titrated to a stable and tolerated dose between 18 mg (equivalent to 20 mg oxycodone HCl) twice daily and 72 mg (equivalent to 80 mg oxycodone HCl) twice daily of XTAMPZA ER in an open-label fashion during the first six weeks of the trial. Optional use of rescue medication (acetaminophen 500 mg tablets) up to 2 tablets every 4-6 hours was permitted during the dose titration phase, up to 2000 mg per day. XTAMPZA ER was titrated once every three to seven days until a stable and tolerable dose was identified (maximum dose of 72 mg [equivalent to 80 mg oxycodone HCl] twice daily).

Following the titration phase, 389 subjects (53%) met the study randomization criteria of adequate analgesia (pain reduction of at least 2 points from screening baseline to a score of 4 or less on a 0-10 numerical rating scale) and acceptable tolerability of XTAMPZA ER and entered the randomized, double-blind maintenance phase. Subjects discontinued from the dose-titration phase for the following reasons: failure to meet entrance criteria (18%), adverse events (13%), subject request (7%) and lack of efficacy (5%). Patients were randomized at a ratio of 1:1 into a 12-week double-blind maintenance phase with their fixed stable dose of XTAMPZA ER (or matching placebo). Patients randomized to placebo were given a blinded taper of XTAMPZA ER according to a prespecified tapering schedule; XTAMPZA ER was decreased by 25% to 35% every 5 days for the higher doses of XTAMPZA ER and up to 50% every 5 days for the mid-to-lower doses of XTAMPZA ER over the first 20 days of the double-blind maintenance phase. Patients were allowed to use rescue medication (acetaminophen 500 mg tablets) up to a maximum dose of 2000 mg per day. During the double-blind maintenance phase, 122 patients (63%) completed the 12-week treatment with XTAMPZA ER and 100 (51%) completed with placebo. Overall, 11% of patients discontinued due to lack of efficacy (4% of XTAMPZA ER patients and 17% of placebo patients), and 7% discontinued due to adverse events (7% of XTAMPZA ER patients and 7% of placebo patients).

In this study, there was a significant difference in pain reduction, favoring XTAMPZA ER, between XTAMPZA ER (doses of 36-144 mg per day, equivalent to 40-160 mg of oxycodone HCl) and placebo, based on the primary endpoint of change in average pain intensity from randomization baseline to Week 12 of the double-blind maintenance phase.

The proportion of patients (responders) in each group who demonstrated improvement in their weekly average pain scores from screening baseline to Week 12, is shown in Figure 2. The figure is cumulative, so that patients whose change from screening is, for example, 30%, are also included at every level of improvement below 30%. Patients who did not complete the study were classified as non-responders. Treatment with XTAMPZA ER resulted in a higher proportion of responders, defined as patients with at least a 30% and 50% improvement as compared to placebo.

Figure 2: Responder Analysis for Pain Intensity: Percent Reduction/Improvement (Intent-to-Treat Population)

Figure 2
(click image for full-size original)

16 HOW SUPPLIED/STORAGE AND HANDLING

XTAMPZA ER capsules are supplied in 100-count bottles with a child-resistant closure and as a hospital unit dose package with 10 individually blistered capsules per card; two cards per carton as follows:

Table 8: Summary of XTAMPZA ER Capsule Strengths and Packaging Configurations
Strength Capsule Description NDC Number(100-count Bottles with a child-resistant closure) NDC Number(20-count Hospital Unit Dose Blister Cartons)
9 mg(equivalent to 10 mg oxycodone HCl) Size 3, ivory cap printed with “XTAMPZA ER” and white body printed with “9 mg” NDC 24510-110-10 NDC 24510-110-20
13.5 mg(equivalent to 15 mg oxycodone HCl) Size 2, Swedish orange cap printed with “XTAMPZA ER” and white body printed with “13.5 mg” NDC 24510-115-10 NDC 24510-115-20
18 mg(equivalent to 20 mg oxycodone HCl) Size 1, rich yellow cap printed with “XTAMPZA ER” and white body printed with “18 mg” NDC 24510-120-10 NDC 24510-120-20
27 mg(equivalent to 30 mg oxycodone HCl) Size 0, light gray cap printed with “XTAMPZA ER” and white body printed with “27 mg” NDC 24510-130-10 NDC 24510-130-20
36 mg(equivalent to 40 mg oxycodone HCl) Size 00, flesh color cap printed with “XTAMPZA ER” and white body printed with “36 mg” NDC 24510-140-10 NDC 24510-140-20

Store at 25°C (77°F); excursions permitted between 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].

Dispense in tight, light-resistant container, with child-resistant closure.

Store XTAMPZA ER securely and dispose of properly [see Patient Counseling Information (17)].

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Storage and Disposal:

Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store XTAMPZA ER securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home [see Warnings and Precautions (5.1, 5.3), Drug Abuse and Dependence (9.2)]. Inform patients that leaving XTAMPZA ER unsecured can pose a deadly risk to others in the home.

Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused XTAMPZA ER should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines.

Addiction, Abuse, and Misuse

Inform patients that the use of XTAMPZA ER, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.1)]. Instruct patients not to share XTAMPZA ER with others and to take steps to protect XTAMPZA ER from theft or misuse.

Life-Threatening Respiratory Depression

Inform patients of the risk of life-threatening respiratory depression including information that the risk is greatest when starting XTAMPZA ER or when the dosage is increased, and that it can occur even at recommended dosages [see Warnings and Precautions (5.3)]. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.

Accidental Ingestion

Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions (5.3)].

Interactions with Benzodiazepines and other CNS Depressants

Inform patients and caregivers that potentially fatal additive effects may occur if XTAMPZA ER is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions (5.6), Drug Interactions (7)].

Serotonin Syndrome

Inform patients that XTAMPZA ER could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications. [see Drug Interactions (7)].

MAOI Interaction

Inform patients to avoid taking XTAMPZA ER while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking XTAMPZA ER [see Drug Interactions (7)].

Adrenal Insufficiency

Inform patients that XTAMPZA ER could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [see Warnings and Precautions (5.8)].

Food Effect

Because food has an effect on absorption of oxycodone from XTAMPZA ER, each dose of XTAMPZA ER should be taken with food in order to ensure that appropriate plasma levels are consistently achieved. Instruct patients to take XTAMPZA ER with approximately the same amount of food regardless of whether they swallow the capsule whole or sprinkle on soft food or into a cup and then administer directly into the mouth.

XTAMPZA ER may be taken as intact capsules or, alternately, may be administered as a sprinkle on soft foods or sprinkled into a cup and administered directly into the mouth, or through a nasogastric or gastric feeding tube [see Dosage and Administration (2.1, 2.6)].

Important Administration Instructions [see Dosage and Administration (2.1, 2.5, 2.6), Warnings and Precautions (5.3)]

Instruct patients how to properly take XTAMPZA ER, including the following:

  • Taking XTAMPZA ER with food
  • Swallowing XTAMPZA ER capsules whole or sprinkling the capsule contents on soft food or into a cup and administering directly into the mouth
  • Using XTAMPZA ER exactly as prescribed to reduce the risk of life-threatening adverse reactions (e.g., respiratory depression)

Important Discontinuation Instructions

In order to avoid developing withdrawal symptoms, instruct patients not to discontinue XTAMPZA ER without first discussing a tapering plan with the prescriber [see Dosage and Administration (2.5)]

Hypotension

Inform patients that XTAMPZA ER may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [see Warnings and Precautions (5.9)].

Anaphylaxis

Inform patients that anaphylaxis has been reported with ingredients contained in XTAMPZA ER. Advise patients how to recognize such a reaction and when to seek medical attention [see Contraindications (4), Adverse Reactions (6)].

Pregnancy

Neonatal Opioid Withdrawal Syndrome

Inform female patients of reproductive potential that prolonged use of XTAMPZA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)].

Embryofetal Toxicity

Advise females of reproductive potential that XTAMPZA ER can cause fetal harm and to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)].

Lactation

Advise patients that breastfeeding is not recommended during treatment with XTAMPZA ER [see Use in Specific Populations (8.2)].

Infertility

Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6.2)].

Driving or Operating Heavy Machinery

Inform patients that XTAMPZA ER may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication [see Warnings and Precautions (5.14)].

Constipation

Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention.

Healthcare professionals can telephone Collegium Pharmaceutical’s Medical Affairs Department (1-855-331-5615) for information on this product.

Manufactured by: Patheon Pharmaceuticals, Cincinnati, OH 45237

U.S. Patent Nos. 7,399,488; 7,771,707; 8,449,909; 8,557,291; 8,758,813; 8,840,928; 9,044,398; 9,248,195; 9,592,200; 9,682,075; 9,737,530; 9,763,883; 9,968,598; 10,004,729; and 10,188,644.

Medication GuideXTAMPZA® ER (ex tamp’ zah ee ar)(oxycodone) extended-release capsules, CII
This Medication Guide has been approved by the U.S. Food and Drug Administration. Issued: October 2019

XTAMPZA ER is:

  • A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage pain severe enough to require daily, around-the-clock, long-term treatment with an opioid, when other pain treatments such as non-opioid pain medicines or immediate-release opioid medicines do not treat your pain well enough or you cannot tolerate them.
  • A long-acting (extended-release) opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed by your healthcare provider, you are at risk for opioid addiction, abuse, and misuse that can lead to death.
  • Not for use to treat pain that is not around-the-clock.

Important information about XTAMPZA ER:

  • Get emergency help right away if you take too much XTAMPZA ER (overdose). When you first start taking XTAMPZA ER, when your dose is changed, or if you take too much (overdose), serious life-threatening breathing problems that can lead to death may occur.
  • Taking XTAMPZA ER with other opioid medicines, benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death.
  • Never give anyone else your XTAMPZA ER. They could die from taking it. Selling or giving away XTAMPZA ER is against the law.
  • Store XTAMPZA ER securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home.

Do not take XTAMPZA ER if you have:

  • severe asthma, trouble breathing, or other lung problems.
  • a bowel blockage or have narrowing of the stomach or intestines.

Before taking XTAMPZA ER, tell your healthcare provider if you have a history of:

  • head injury, seizures
  • problems urinating
  • liver, kidney, thyroid problems
  • pancreas or gallbladder problems
  • abuse of street or prescription drugs, alcohol addiction, or mental health problems.

Tell your healthcare provider if you are:

  • pregnant or planning to become pregnant. Prolonged use of XTAMPZA ER during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated.
  • breastfeeding. Not recommended during treatment with XTAMPZA ER. It may harm your baby.
  • taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking XTAMPZA ER with certain other medicines can cause serious side effects that could lead to death.

When taking XTAMPZA ER:

  • Do not change your dose. Take XTAMPZA ER exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.
  • Take your prescribed dose every 12 hours, at the same time every day. Do not take more than your prescribed dose. If you miss a dose, take your next dose at your usual time.
  • If you cannot swallow XTAMPZA ER capsules, see the detailed Instructions for Use.
  • Always take XTAMPZA ER capsules with approximately the same amount of food to ensure enough medicine is absorbed.
  • Swallow XTAMPZA ER whole. Do not snort, or inject XTAMPZA ER because this may cause you to overdose and die.
  • The contents of the XTAMPZA ER capsules may be sprinkled on soft food, sprinkled into a cup and then put directly into the mouth, or given through a nasogastric or gastrostomy tube.
  • Call your healthcare provider if the dose you are taking does not control your pain.
  • Do not stop taking XTAMPZA ER without talking to your healthcare provider.
  • Dispose of expired, unwanted, or unused XTAMPZA ER by promptly flushing down the toilet, if a drug take-back option is not readily available. Visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines.

While taking XTAMPZA ER DO NOT:

  • Drive or operate heavy machinery, until you know how XTAMPZA ER affects you. XTAMPZA ER can make you sleepy, dizzy, or lightheaded.
  • Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with XTAMPZA ER may cause you to overdose and die.

The possible side effects of XTAMPZA ER are:

  • constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe.

Get emergency medical help if you have:

  • trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.

These are not all the possible side effects of XTAMPZA ER. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. For more information, go to dailymed.nlm.nih.gov

Manufactured by: Patheon Pharmaceuticals, 2110 Galbraith Road, Cincinnati, OH 45237, www.collegiumpharma.com or call 855-331-5615

Instructions for Use
XTAMPZA® ER (ex tamp’ zah ee ar)(oxycodone) extended-release capsules, CII

Always take XTAMPZA ER with approximately the same amount of food. If you cannot swallow XTAMPZA ER capsules, tell your healthcare provider. If your healthcare provider tells you that you can take XTAMPZA ER by sprinkling the capsule contents, follow these steps:

XTAMPZA ER can be opened and the contents inside the capsule can be sprinkled onto soft foods (such as, applesauce, pudding, yogurt, ice cream, or jam) as follows:

figure 1

  • Open the XTAMPZA ER capsule and sprinkle the contents over about one tablespoon of the soft food listed above (See Figure 1).

figure 2

  • Swallow all of the soft food and sprinkled capsule contents right away. Do not save any of the soft food and capsule contents for another dose (See Figure 2).

figure 3

  • Rinse your mouth to make sure you have swallowed all of the capsule contents. (See Figure 3).

figure 4

  • Flush the empty capsule down the toilet right away (See Figure 4).

XTAMPZA ER capsule contents can also be sprinkled into a cup and then put directly into the mouth.

Giving XTAMPZA ER through a nasogastric or gastrostomy tube:

Use water, milk, or a liquid nutritional supplement to flush the tube when giving XTAMPZA ER.

Step 1: Flush the nasogastric or gastrostomy tube with liquid.
Step 2: Open an XTAMPZA ER capsule and carefully pour the contents of the capsule directly into the tube. Do not pre-mix the capsule contents with the liquid used to flush the capsule contents through the tube.
Step 3: Draw up 15 mL of liquid into a syringe, insert the syringe into the tube, and flush the contents of the capsule through the tube to give the dose.
Step 4:Flush the tube two more times, each time with 10 mL of liquid, to ensure that none of the contents of the capsule are left in the tube.

This Instruction for Use has been approved by the U.S. Food and Drug Administration. Issued: December 2016

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.