Dsuvia

Important Administration Instructions

DSUVIA is only to be administered by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks.

DSUVIA is only to be used in a certified medically supervised healthcare setting, such as hospitals, surgical centers, and emergency departments.

DSUVIA treatment must be discontinued prior to the patient leaving the certified medically supervised setting.

Dosage Information

The recommended dosage of DSUVIA is 30 mcg sublingually as needed with a minimum of 1 hour between doses. Do not exceed 12 tablets in 24 hours.

Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions ]. Because the risk of overdose increases as opioid doses increase, reserve the use of additional doses of DSUVIA for patients in whom a single dose is insufficiently effective and in whom the expected benefits of using additional doses of an opioid clearly outweigh the substantial risks.

The maximum cumulative daily dose of sufentanil is 360 mcg or 12 tablets (12 tablets x 30 mcg/dose).

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 addition, abuse, and misuse [see Warnings and Precautions ].

Respiratory depression can occur at any time during opioid therapy, especially when initiating and following additional doses of DSUVIA. Consider this risk when initiating dosing and when making dose adjustments [see Warnings and Precautions ].

Administration of DSUVIA

• Single-use product / Do not reuse.
• Do not use if pouch seal is broken.
• Do not use if the Single-Dose Applicator (SDA) is damaged.
• Wear gloves when administering DSUVIA.
• Instruct the patient to not chew or swallow the tablet.
• Instruct the patient to not eat or drink and minimize talking for 10 minutes after receiving the tablet. If a patient experiences excessive dry mouth, ice chips should be provided prior to administration of DSUVIA.

Administration Instructions

Pregnancy

Risk Summary

Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions ]. There are no available data with sufentanil in pregnant women to inform a drug-associated risk for major birth defects and miscarriage.

In animal reproduction studies, embryolethality and maternal toxicity were noted in rabbits when sufentanil was administered intravenously at 4.4 times the maximum human daily dose of 360 mcg/60 kg/day, based on a body surface area comparison during organogenesis. Decreased live fetuses and pup survival were noted in rats treated with sufentanil late in gestation and throughout lactation at doses below the human daily dose of 360 mcg. No malformations were observed in either rats or rabbits at doses below the human daily dose of 360 mcg [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 non-medical 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, must be available for reversal of opioid-induced respiratory depression in the neonate. DSUVIA is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including DSUVIA, can prolong labor through actions which 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 dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Data

Animal Data

Pregnant rats were treated with intravenous sufentanil doses of 0.005, 0.02, or 0.08 mg/kg/day (0.14, 0.6, or 2.2 times the maximum human daily dose of 360 mcg/60 kg, based on body surface area, respectively). No malformations or embryotoxic effects were noted despite maternal toxicity (increased mortality in the mid- and high-dose group).

Pregnant rabbits were treated with intravenous sufentanil doses of 0.005, 0.02, or 0.08 mg/kg/day (0.2, 1.0, or 4.4 times the maximum human daily dose of 360 mcg/60 kg, based on body surface area, respectively). Decreased live fetuses per litter and decreased litter size in the high dose group were noted in the presence of maternal toxicity (decreased body weight gain and mortality in the high-dose group).

No evidence of malformations or adverse effects on the fetus was reported in a published study in which pregnant rats were administered 10, 50, or 100 mcg/kg/day sufentanil (0.2, 1.4, or 2.8 times the maximum human daily dose of 360 mcg/60 kg, based on body surface area) continuously from Gestation Day 5 through Gestation Day 20 via subcutaneously implanted osmotic minipumps.

Pregnant rats were treated intravenously with sufentanil 0.005, 0.02, or 0.08 mg/kg/day (0.14, 0.6, or 2.2 times the maximum human daily dose of 360 mcg/60 kg, based on body surface area, respectively) from Gestation Day 16 through Lactation Day 21. Sufentanil reduced birth weights in the mid- and high-dose groups, decreased live fetuses in the high-dose group, and decreased pup survival in all groups in the presence of maternal toxicity (decreased weight gain and increased mortality in all groups).

Lactation

Risk Summary

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

Clinical Considerations

Monitor infants exposed to DSUVIA 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 breast-feeding is stopped.

Females and Males of Reproductive Potential

Infertility

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. DSUVIA is not intended for chronic use [see Adverse Reactions , Clinical Pharmacology , Nonclinical Toxicology ].

Pediatric Use

The safety and efficacy of the use of DSUVIA in pediatric patients has not been established.

The ability of pediatric patients to comply with the sublingual dosing instructions for DSUVIA has not been evaluated.  Use of DSUVIA in younger children is not recommended as younger children may not be able to comply with the sublingual dosing instructions for DSUVIA and could swallow the tablet or spit it out, which could impact the efficacy and safety of DSUVIA.

Geriatric Use

No special population studies were performed using DSUVIA in elderly patients.

Of the 646 patients exposed to 30 mcg sufentanil or higher in the first hour of treatment, approximately 11% (72) of patients were ≥ 75 years of age and approximately 20% (126) patients were 65 to 75 years of age. The overall rate of adverse events and most common adverse events, such as nausea, tended to increase with age in patients who received sublingual sufentanil, although vomiting was less common in patients aged ≥ 75 years than in younger patients.

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. As the dose of DSUVIA cannot be titrated, monitor geriatric patients closely for signs of central nervous system and respiratory depression or consider an alternate medication that can be titrated [see Warnings and Precautions ].

Hepatic Impairment

Because sufentanil is extensively metabolized in the liver, its clearance may decrease in patients with hepatic impairment. Monitor closely for adverse events such as respiratory depression, sedation, and hypotension [see Clinical Pharmacology ].

Renal Impairment

Sufentanil and its metabolites are known to be excreted by the kidney. No significant changes have been observed in subjects with mild or moderate renal impairment.  Monitor closely for adverse events such as respiratory depression, sedation, and hypotension in patients with severe renal impairment [seeClinical Pharmacology ].