Olinvyk

Important Dosage and Administration Instructions

For intravenous administration only.

OLINVYK should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks.

Individual single doses greater than 3 mg have not been evaluated.

The cumulative daily dose should not exceed 27 mg.

OLINVYK 30 mg/30 mL (1mg/mL) vial is intended for patient-controlled analgesia (PCA) use only.  Draw OLINVYK directly from the vial into the PCA syringe or IV bag without diluting.

Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions ]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of OLINVYK 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.

Use of OLINVYK beyond 48 hours has not been studied in controlled clinical trials.  

There is variability in opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. 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 ( 5.1)].

Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with OLINVYK. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions ( 5)].

Inspect OLINVYK for particulate matter and discoloration prior to administration.  The solution is a clear, colorless, preservative free solution for intravenous use. If visibly opaque particles, discoloration, or other foreign particles are observed, do not use.

Initial Dosage

OLINVYK can be administered by a healthcare provider with an initial dose of 1.5 mg.  For PCA, the initial dose can be followed by access to patient demand doses with a 6-minute lock-out.  The recommended demand dose is 0.35 mg.  A demand dose of 0.5 mg may be considered for some patients if the potential benefit outweighs the risks. Supplemental doses of 0.75 mg OLINVYK can be administered by healthcare providers, beginning 1 hour after the initial dose, and hourly thereafter as needed.

Onset of analgesic effect is expected within 2 to 5 minutes after the initial dose [see Clinical Pharmacology ( 12.2)].

Do not administer single doses greater than 3 mg [see Adverse Reactions ].

The cumulative total daily dose should not exceed 27 mg. If patients reach a 27 mg cumulative daily dose and analgesia is still required, an alternative analgesic regimen should be administered until OLINVYK can be resumed the next day.  Alternative analgesia may include multi-modal therapies. The safety of OLINVYK beyond 48 hours of use was not evaluated in controlled clinical trials [see Warnings and Precautions ].

Conversion Between Morphine Intravenous Injection and OLINVYK Intravenous Injection

Based on data collected in clinical studies, an initial 1 mg dose of OLINVYK is approximately equipotent to morphine 5 mg [see Clinical Pharmacology ].  As individual patients differ in their response to opioid drugs, this comparison should be used only as a guide.

Titration and Maintenance of Therapy

Titrate the dose based upon the individual patient’s response to their initial dose of OLINVYK. Individually titrate OLINVYK to a dose that provides adequate analgesia and minimizes adverse reactions.  Continually reevaluate patients receiving OLINVYK to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as to reassess for the development of addiction, abuse, or misuse [see Warnings and Precautions ].  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.

If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the OLINVYK dosage.  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 ].  Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Safe Reduction or Discontinuation of OLINVYK

When a patient who has been taking opioids regularly and may be physically dependent no longer requires therapy with OLINVYK, taper the dose gradually while regularly evaluating 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 OLINVYK in a physically-dependent patient [see Warnings and Precautions ( 5.1), Drug Abuse and Dependence ( 9.3); Nonclinical Toxicology ].

Pregnancy

Risk Summary

Use of opioid analgesics for an extended period of time during pregnancy may result in neonatal opioid withdrawal syndrome [see Warnings and Precautions ].  There are no available data on OLINVYK use in pregnant women to evaluate for a drug-associated risk of major birth defects and miscarriage or adverse maternal outcomes.  There are adverse outcomes reported within detal exposure to opioid analgesics (see Clinical Considerations).

In animal reproductive studies, oliceridine reduced live litter size at birth and increased postnatal pup mortality between birth and Postnatal Day 4 when administered intravenously to rats from organogenesis through weaning at doses producing clinically relevant plasma exposure.  Oliceridine had no effect on embryo-fetal development in rats and rabbits when administered intravenously during organogenesis at doses producing plasma exposures 7 and 8 times the estimated plasma exposure at the maximum recommended human dose (MRHD) on an AUC basis, respectively (see Data).

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Use of opioid analgesics for an extended period of time 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 ].

Labor or Delivery

Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates.  An opioid antagonist, such as naloxone, should be available for reversal of opioid induced respiratory depression in the neonate.  OLINVYK is not recommended for use in pregnant women during and immediately prior to labor, when other analgesic techniques are more appropriate.  Opioid analgesics 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 OLINVYK during labor for signs of excess sedation and respiratory depression.

Data

Animal Data

Oliceridine administered via continuous intravenous infusion during the period of embryofetal organogenesis at doses of 6, 12, or 24 mg/kg/day to pregnant rats from Gestation Day (GD) 6 to 20 and 1.5, 3, or 6 mg/kg/day to pregnant rabbits from GD 7 to 29 had no effect on embryonic development at exposures 7 (rats) to 8 times (rabbits) the estimated plasma exposure at the MRHD of 27 mg/day on an AUC basis. Maternal toxicity (reduced body weight gain) was observed at ≥12 mg/kg/day in rats and at 6 mg/kg/day in rabbits.

In a pre−and post−natal development study in rats, oliceridine administered via continuous intravenous infusion at doses of 0.6, 2.4, and 6.0 mg/kg/day from Gestation Day 6 through Lactation Day 21 resulted in reduced live litter size at birth at 1.5 times the estimated plasma exposure at the MRHD on an AUC basis and lower pup survival between birth and Postnatal Day 4 at 0.6 times the estimated plasma exposure at the MRHD on an AUC basis.

Lactation

Risk Summary

It is not known whether oliceridine is present in human milk.  The effects of oliceridine on a breastfeeding infant and on milk production have not been evaluated. 

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for OLINVYK and any potential adverse effects on the breastfed infant from OLINVYK or from the underlying maternal condition.

Clinical Considerations

Monitor infants exposed to OLINVYK 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.

Females and Males of Reproductive Potential

Infertility

Human Data

Use of opioids for an extended period of time 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 , Clinical Pharmacology ].

Animal Data

Oliceridine administered intravenously for 14 days prior to cohabitation and administered through GD15 caused prolonged estrous cycle lengths and decreased the number of implantations and viable embryos in female rats at doses producing plasma exposures ≥ 3 times the MRHD on an AUC basis [see Nonclinical Toxicology ].

Pediatric Use

The safety and effectiveness of OLINVYK in pediatric patients has not been established.

Geriatric Use

Controlled clinical studies of OLINVYK did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Elderly patients (aged 65 years or older) may have increased sensitivity to OLINVYK.  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 and of concomitant disease or 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 OLINVYK slowly in geriatric patients and monitor for signs of central nervous system and respiratory depression [see Warnings and Precautions ( 5.8)].

Renal Impairment

In patients with end-stage renal disease, there was no clinically significant change in oliceridine clearance.  Therefore, dosage adjustment of OLINVYK in patients with renal impairment is not required [see Clinical Pharmacology ( 12.3)].

Hepatic Impairment

In patients with mild or moderate hepatic impairment, no adjustment of the initial dose is needed; however, these patients may require less frequent dosing.  When using OLINVYK in patients with severe hepatic impairment, consider reducing the initial dose, and administer subsequent doses only after a careful review of the patient’s severity of pain and overall clinical status [see Clinical Pharmacology ( 12.3)].

 Poor Metabolizers of CYP2D6 Substrates

In patients who are known or suspected to be poor CYP2D6 metabolizers, based on genotype or previous history/experience with other CYP2D6 substrates, less frequent dosing of OLINVYK may be required.  These patients should be closely monitored, and subsequent doses should be based on the patient’s severity of pain and response to treatment.  [See Warnings and Precautions ; Clinical Pharmacology ].