Relistor Tablets

Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain

​Relistor Tablets and RELISTOR injection are indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain.

Opioid-Induced Constipation in Adult Patients with Advanced Illness

RELISTOR injection is indicated for the treatment of OIC in adult patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient.

Limitations of Use

Use of RELISTOR injection beyond four months has not been studied in the advanced illness population.

Relistor Tablets is used to treat constipation caused by opioids (narcotic pain medicines), in adults with long-lasting pain that is not caused by cancer. Relistor Tablets is used when other medicines for constipation (laxatives) have not worked well.

Relistor Tablets is available only with your doctor's prescription.

Important Administration Information

Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain

Opioid-Induced Constipation in Adult Patients with Advanced Illness

The pre-filled syringe is only for patients who require a RELISTOR injection dose of 8 mg or 12 mg. Use the vial for patients who require other doses of RELISTOR injection.

Table 1 below shows the recommended weight-based dose of RELISTOR injection and the corresponding injection volume. The recommended dosage regimen is one dose administered subcutaneously every other day, as needed. Do not administer more frequently than one dose per 24-hour period.

Dosage in Patients with Renal Impairment

The recommended dosage of RELISTOR in patients with moderate and severe renal impairment (i.e., creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault), is shown below by

Indication:

OIC in Adult Patients with Chronic Non‑Cancer Pain

OIC in Adult Patients with Advanced Illness

RELISTOR injection: The recommended dosage regimen is one dose every other day, as needed is shown in Table 2.

Dosage in Patients with Hepatic Impairment

OIC in Adult Patients with Chronic Non-Cancer Pain

Preparation and Administration of RELISTOR Injection

See also:
What is the most important information I should know about Relistor Tablets?

RELISTOR is contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.

Use Relistor Tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Relistor Tablets. Talk to your pharmacist if you have questions about this information.
• Relistor Tablets is given as an injection under the skin. A health care provider will teach you how to use it. Be sure you understand how to use Relistor Tablets. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Relistor Tablets is colorless to pale yellow in color. Do not use Relistor Tablets if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• If you are using the single-use vials, inject Relistor Tablets right after you draw it into the syringe. If you are not able to inject the medicine right away, it may be stored in the syringe at room temperature for up to 24 hours. You do not need to protect the syringe from light during this time.
• If you are using the prefilled syringes, do not remove the syringe from the tray until you are ready to inject Relistor Tablets.
• Relistor Tablets may be injected into the upper arm, abdomen, or thigh. Do NOT inject Relistor Tablets into the upper arm if you are injecting yourself.
• Rotate injection sites as directed by your health care provider. Do not inject into scars, stretch marks, or areas where the skin is bruised, tender, red, or hard.
• Do not use a vial of Relistor Tablets more than 1 time, even if there is medicine left in the vial.
• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• Use Relistor Tablets as your doctor has told you. If you miss a dose of Relistor Tablets and you take it on a regular basis, use it as soon as you remember. Continue to use it as directed by your doctor.

Ask your health care provider any questions you may have about how to use Relistor Tablets.

Use: Labeled Indications

Opioid-induced constipation with advanced illness (injection only): Treatment of opioid-induced constipation in adults with advanced illness or pain caused by active cancer who require opioid dosage escalation for palliative care.

Opioid-induced constipation with chronic non-cancer pain (tablets and injection): Treatment of opioid-induced constipation in adults with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (eg, weekly) opioid dosage escalation.

See also:
What other drugs will affect Relistor Tablets?

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

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

See also:
What are the possible side effects of Relistor Tablets?

Serious and important adverse reactions described elsewhere in the labeling include:

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 to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Opioid-Induced Constipation in Adult Patients with Chronic Non-Cancer Pain

The safety of Relistor Tablets was evaluated in a double-blind, placebo-controlled trial in adult patients with OIC and chronic non-cancer pain receiving opioid analgesia. This study (Study 1) included a 12-week, double-blind, placebo-controlled period in which adult patients were randomized to receive Relistor Tablets 450 mg orally (200 patients) or placebo (201 patients). After 4 weeks of double-blind treatment administered once daily, patients continued 8 weeks of double-blind treatment on an as needed basis (but not more than once daily).

The most common adverse reactions in adult patients with OIC and chronic non-cancer pain receiving Relistor Tablets are shown in Table 4. Adverse reactions of abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal.

The safety of RELISTOR injection was evaluated in a double-blind, placebo-controlled trial in adult patients with OIC and chronic non-cancer pain receiving opioid analgesia. This study (Study 2) included a 4-week, double-blind, placebo-controlled period in which adult patients were randomized to receive RELISTOR injection 12 mg subcutaneously once daily (150 patients) or placebo (162 patients). After 4 weeks of double-blind treatment, patients began an 8‑week open-label treatment period during which RELISTOR injection 12 mg subcutaneously was administered less frequently than the recommended dosage regimen of 12 mg once daily.

The most common adverse reactions in adult patients with OIC and chronic non-cancer pain receiving RELISTOR injection are shown in Table 5. The adverse reactions in the table below may reflect symptoms of opioid withdrawal.

During the 4-week double-blind period, in patients with OIC and chronic non-cancer pain that received RELISTOR every other day, there was a higher incidence of adverse reactions, including nausea (12%), diarrhea (12%), vomiting (7%), tremor (3%), feeling of body temperature change (3%), piloerection (3%), and chills (2%) as compared to daily RELISTOR dosing. Use of RELISTOR injection 12 mg subcutaneously every other day is not recommended in patients with OIC and chronic non-cancer pain. The rates of discontinuation due to adverse reactions during the double-blind period (Study 2) were higher in the RELISTOR once daily (7%) than the placebo group (3%). Abdominal pain was the most common adverse reaction resulting in discontinuation from the double-blind period in the RELISTOR once daily group (2%).

The safety of RELISTOR injection was also evaluated in a 48-week, open-label, uncontrolled trial in 1034 adult patients with OIC and chronic non-cancer pain (Study 3). Patients were allowed to administer RELISTOR injection 12 mg subcutaneously less frequently than the recommended dosage regimen of 12 mg once daily, and took a median of 6 doses per week. A total of 624 patients (60%) completed at least 24 weeks of treatment and 477 (46%) completed the 48‑week study. The adverse reactions seen in this study were similar to those observed during the 4-week double-blind period of Study 2. Additionally, in Study 3, investigators reported 4 myocardial infarctions (1 fatal), 1 stroke (fatal), 1 fatal cardiac arrest and 1 sudden death. It is not possible to establish a relationship between these events and RELISTOR.

Opioid-Induced Constipation in Adult Patients with Advanced Illness

The safety of RELISTOR injection was evaluated in two, double-blind, placebo-controlled trials in adult patients with OIC and advanced illness receiving palliative care: Study 4 included a single‑dose, double‑blind, placebo-controlled period, whereas Study 5 included a 14-day multiple dose, double-blind, placebo-controlled period.

The most common adverse reactions in adult patients with OIC and advanced illness receiving RELISTOR injection are shown in Table 6 below.

The rates of discontinuation due to adverse reactions during the double-blind, placebo-controlled clinical trials (Study 4 and Study 5) were comparable between RELISTOR (1%) and placebo (2%).

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of RELISTOR injection. Because reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Gastrointestinal

Perforation, cramping, vomiting

General Disorders and Administration Site Disorders

Diaphoresis, flushing, malaise, pain. Cases of opioid withdrawal have been reported.

Relistor Tablets is a pheriphally-acting μ-opioid antagonists that acts on the gastrointestinal tract to decrease opioid-induced constipation without producing analgesic effects or withdrawal symptoms. It is also a weak CYP2D6 inhibitor. FDA approved in 2008.