Olinvyk Side Effects Center

SIDE EFFECTS

The following adverse reactions are described, or described in greater detail, in other sections:

• Addiction, Abuse, and Misuse [see WARNINGS AND PRECAUTIONS]
• Life-threatening Respiratory Depression [see WARNINGS AND PRECAUTIONS]
• Neonatal Opioid Withdrawal Syndrome [see WARNINGS AND PRECAUTIONS]
• Interactions with Benzodiazepines or Other CNS Depressants [see WARNINGS AND PRECAUTIONS]
• Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS]
• Severe Hypotension [see WARNINGS AND PRECAUTIONS]
• Gastrointestinal Adverse Reactions [see WARNINGS AND PRECAUTIONS]
• Seizures [see WARNINGS AND PRECAUTIONS]
• Withdrawal [see WARNINGS AND PRECAUTIONS]

Clinical Studies 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.

A total of 1535 patients were treated with OLINVYK in controlled and open-label trials in patients with moderate to severe acute pain. Of these, 1181 patients received a total daily dose ≤27 mg and 354 patients received a total daily dose >27 mg during the first 24-hour treatment period. Among patients who received a daily dose of >27 mg, 198 patients received a daily dose between 27 mg and 40 mg, and 142 patients received a daily dose >40 mg.

The most common adverse drug reactions (≥10%) in controlled efficacy trials (Study 1 and Study 2) were nausea, vomiting, dizziness, headache, constipation, pruritus and hypoxia. Adverse reactions leading to discontinuation of OLINVYK were hypotension, hypoxia, nausea, hypoventilation, oxygen saturation decreased, alanine aminotransferase increased, aspartate aminotransferase increased, electrocardiogram QT prolongation, and urticaria. In two randomized, double-blind, placebo-and morphine-controlled studies, when stratified by 27 mg daily dosing limit, discontinuation of OLINVYK due to adverse reactions occurred in 4% of patients who received a daily dose ≤ 27 mg, and less than 1% of patients who received a daily dose >27 mg. In these same studies, discontinuation due to adverse reactions occurred in 5% of morphine-treated patients, and no placebo-treated patients. In an open-label safety study, discontinuation of OLINVYK due to adverse drug reactions occurred in 3% of patients who received a daily dose ≤ 27 mg, and 1% of patients who received a daily dose >27 mg.

In two randomized, double-blind, placebo-and morphine-controlled studies in patients with moderate to severe acute pain following either orthopedic surgery-bunionectomy (Study 1), or plastic surgery-abdominoplasty (Study 2), patients received one of three OLINVYK dosing regimens, a morphine-control regimen, or a volume-matched placebo-control regimen. All dosing regimens were administered via patient-controlled analgesia (PCA), allowing patients to individually titrate the dose available to an acceptable level of analgesia. Patients were treated for up to 48 hours in the bunionectomy study (Study 1), and for up to 24 hours in the abdominoplasty study (Study 2) [see Clinical Studies]. The loading dose for all OLINVYK treatment regimens was 1.5 mg; demand doses were 0.1, 0.35, or 0.5 mg, according to assigned treatment group; supplemental doses of 0.75 mg were permitted, beginning 1 hour after the loading dose, and hourly thereafter, as needed. The loading dose for the morphine treatment regimen was 4 mg; the demand dose was 1 mg; and supplemental doses of 2 mg were permitted, beginning 1 hour after the loading dose, and hourly thereafter, as needed. A lockout interval of 6 minutes was used for all PCA regimens.

In Study 1, a total of 136 patients received OLINVYK ≤27 mg/day, and 98 patients received OLINVYK >27 mg/day during the first 24 hours. In Study 2, a total of 180 patients received OLINVYK ≤27 mg/day, and 56 patients received OLINVYK >27 mg/day during the first 24 hours.

Table 1 and Table 2 list adverse drug reactions that were reported in ≥5% of OLINVYK-treated patients in each study, and that occurred at a frequency greater than placebo in at least one of the studies.

Table 3 lists adverse drug reactions that were reported in ≥5% of OLINVYK-treated patients for pooled Studies 1 and 2 stratified by total daily dose (≤27 mg/day or >27 mg/day).

These data are not an adequate basis for comparison of rates between the OLINVYK treatment group and the morphine treatment group. The OLINVYK and morphine dosing regimens studied are not considered equipotent.

Table 1: Adverse Drug Reactions Reported in ≥5% of OLINVYK-Treated Patients Following Orthopedic Surgery-Bunionectomy (Study 1)

Table 2: Adverse Drug Reactions Reported in ≥5% of OLINVYK-Treated Patients Following Plastic Surgery-Abdominoplasty (Study 2)

In an open-label safety study of patients with moderate to severe acute pain following a surgical procedure or due to a medical condition (Study 3), a total of 768 patients received at least one dose of OLINVYK. OLINVYK was administered via clinician-administered bolus dosing, PCA, or a combination of the two. Bolus dosing was initiated at 1 to 2 mg, with supplemental doses of 1 to 3 mg every 1 to 3 hours, as needed, based on individual patient need and previous response to OLINVYK. If OLINVYK was administered via PCA, the loading dose was 1.5 mg, the demand dose was 0.5 mg, and the lockout interval was 6 minutes. Supplemental doses of 1 mg were given as needed, taking into account the patient's utilization of PCA demand doses, individual patient need, and previous response to OLINVYK.

In Study 3, for the patients within the highest cumulative dose group (exposure >36 mg), the mean cumulative exposure was 67 mg (range: 37 mg to 224 mg) and the mean cumulative duration of exposure was 54 hours (range: 6 hours to 143 hours). The mean cumulative dose of OLINVYK administered to patients in the Study 3 was 30 mg over a mean cumulative duration of 29 hours. The most frequent condition treated in Study 3 was post-surgical acute pain, and included (in order of decreasing frequency): orthopedic, gynecologic, colorectal, general, plastic, urologic, neurologic (including spinal), bariatric, and cardiothoracic surgical procedures.

In Study 3, of the 768 patients treated with OLINVYK, 32% were age 65 years or older and 78% had a Body Mass Index ≥25 kg/m². OLINVYK was administered as needed; 55% of patients received OLINVYK via clinician bolus administration only, and 45% of patients received OLINVYK via PCA self-administration or a combination of clinician bolus-and PCA self-administration.

In Study 3 (open-label), a total of 592 patients received OLINVYK ≤27 mg/day and 176 received OLINVYK >27 mg during the first 24 hours. Adverse drug reactions reported in ≥5% of patients receiving OLINVYK in Study 3, stratified by total daily dose (≤27 mg/day or >27 mg/day), are presented in Table 4.

Table 3: Adverse Drug Reactions Reported in ≥5% OLINVYK-Treated Patients in Study 3 (Open-Label)

Adverse Drug Reactions Reported in >1% to <5% of Patients in the controlled and open-label studies (Study 1, Study 2, and Study 3) are listed in descending order of frequency within System Organ Class in Table 5.

Table 4: Adverse Drug Reactions Reported in >1% to <5% of Patients in Studies 1-3

DRUG INTERACTIONS

Table 6 includes clinically significant drug interactions with OLINVYK.

Table 6: Clinically Significant Drug Interactions with OLINVYK

Drug Abuse And Dependence

Controlled Substance

OLINVYK contains oliceridine, a Schedule II controlled substance.

Abuse

OLINVYK contains oliceridine, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. OLINVYK can be abused and is subject to misuse, abuse, addiction, and criminal diversion [see WARNINGS AND PRECAUTIONS].

The abuse potential of oliceridine was evaluated in healthy, nondependent, recreational opioid users at doses of 1, 2, and 4 mg. Intravenous morphine was used as a positive control at doses of 10 and 20 mg. Statistically significant differences were observed between all doses of oliceridine and placebo on most subjective effects (e.g., Drug Liking VAS) and pupillometry endpoints (e.g., miosis). Intravenous administration of oliceridine demonstrated comparable subjective effects when compared to dose-matched levels of intravenously administered morphine.

All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Prescription abuse is the intentional, non-therapeutic use of a drug, even once, for its rewarding psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.

“Drug seeking” behavior is very common in persons with substance use disorders. Drug seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering of prescriptions, and reluctance to provide prior medical records or contact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers or healthcare prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of true addiction.

OLINVYK injection, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity and frequency, and renewal requests, as required by law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

There were no reports of diversion of OLINVYK during the clinical development program.

Risk Specific to Abuse of OLINVYK Injection

Abuse of OLINVYK injection poses a risk of overdose and death. The risk is increased with concurrent use of OLINVYK with alcohol and other central nervous system depressants.

Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy.

Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).

Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

OLINVYK should not be abruptly discontinued in a physically-dependent patient [see DOSAGE AND ADMINISTRATION]. If OLINVYK is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: 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 [see Nonclinical Toxicology].

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use In Specific Populations].

Read the entire FDA prescribing information for Olinvyk (Oliceridine Injection)