HYDROMORPHONE HYDROCHLORIDE injection, solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

HYDROMORPHONE HYDROCHLORIDE (UNII: L960UP2KRW) (HYDROMORPHONE - UNII:Q812464R06)

Available from:

Hospira, Inc.

Administration route:

INTRAMUSCULAR

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Hydromorphone Hydrochloride Injection is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see Warnings and Precautions (5.1)] , reserve Hydromorphone Hydrochloride Injection for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products): Hydromorphone Hydrochloride Injection should not be used for an extended ‎period of time unless the pain ‎remains severe enough to require an opioid ‎analgesic and for which alternative treatment options continue to ‎be inadequate. Hydromorphone Hydrochloride Injection is contraindicated in patients with: Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.4)] . There are no available data with Hydromorphone Hydrochloride Injection in pregnant women to inform a drug-associated risk for major birth defects and miscarriage or adverse maternal outcomes‎.‎ There are adverse outcomes reported with fetal exposure to opioid analgesics (see Error! Hyperlink reference not valid. ) . In published animal reproduction studies, neural tube defects were noted following subcutaneous injection of hydromorphone to pregnant hamsters at doses 6.4 times the HDD and soft tissue and skeletal abnormalities were noted following subcutaneous continuous infusion of 3 times the HDD to pregnant mice. No malformations were noted at 4 or 40.5 times the HDD in pregnant rats or rabbits, respectively [see Error! Hyperlink reference not valid. ] . Based on animal data, advise pregnant women of the potential risk to a fetus. 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 (5.4)] . 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. Hydromorphone Hydrochloride Injection is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including Hydromorphone Hydrochloride Injection, 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 No effects on teratogenicity or embryotoxicity were observed in pregnant rats given oral doses up to 7 mg/kg/day which is 3-fold higher than the human dose of 24 mg Hydromorphone Hydrochloride Injection (4 mg every 4 hours), on a body surface area basis. In a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of hydromorphone hydrochloride (19 to 258 mg/kg) on Gestation Day 8 to pregnant hamsters (6.4 to 87.2 times the HDD of 24 mg/day based on body surface area). The findings cannot be clearly attributed to maternal toxicity. No neural tube defects were noted at 14 mg/kg (4.7 times the human daily dose of 24 mg/day). In a published study, CF-1 mice were treated subcutaneously with continuous infusion of 7.5, 15, or 30 mg/kg/day hydromorphone hydrochloride (1.5, 3, or 6.1 times the human daily dose of 24 mg based on body surface area) via implanted osmotic pumps during organogenesis (Gestation Days 7 to 10). Soft tissue malformations (cryptorchidism, cleft palate, malformed ventricles and retina), and skeletal variations (split supraoccipital, checkerboard and split sternebrae, delayed ossification of the paws and ectopic ossification sites) were observed at doses 3 times the human dose of 24 mg/day based on body surface area. The findings cannot be clearly attributed to maternal toxicity. Risk Summary Low levels of opioid analgesics have been detected in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Hydromorphone Hydrochloride Injection and any potential adverse effects on the breastfed infant from Hydromorphone Hydrochloride Injection or from the underlying maternal condition. Clinical Considerations Monitor infants exposed to hydromorphone hydrochloride through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of hydromorphone is stopped, or when breast-feeding is stopped. 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 [see Adverse Reactions (6), Clinical Pharmacology (12.2)]. The safety and effectiveness of Hydromorphone Hydrochloride Injection in pediatric patients has not been established. Elderly patients (aged 65 years or older) may have increased sensitivity to hydromorphone. 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 Hydromorphone Hydrochloride Injection slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.6)] . Hydromorphone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. The pharmacokinetics of hydromorphone are affected by hepatic impairment. Due to increased exposure of hydromorphone, patients with moderate hepatic impairment should be started at one fourth to one half the recommended starting dose depending on the degree of hepatic dysfunction and closely monitored during dose titration. The pharmacokinetics of hydromorphone in patients with severe hepatic impairment has not been studied. A further increase in Cmax and AUC of hydromorphone in this group is expected and should be taken into consideration when selecting a starting dose [see Clinical Pharmacology (12.3)] . The pharmacokinetics of hydromorphone are affected by renal impairment. In addition, in patients with severe renal impairment, hydromorphone appeared to be more slowly eliminated with a longer terminal elimination half-life. Start patients with renal impairment on one-fourth to one-half the usual starting dose depending on the degree of impairment. Patients with renal impairment should be closely monitored during dose titration. [see Clinical Pharmacology (12.3)] Hydromorphone Hydrochloride Injection contains hydromorphone, a Schedule II controlled substance. Hydromorphone Hydrochloride Injection contains hydromorphone, a substance with high potential for misuse and abuse, which can lead to the development of ‎substance use disorder, including addiction [see Warnings and Precautions (5.1)]. Misuse is the intentional use, for therapeutic purposes, of a drug by an ‎individual in a way other than ‎‎prescribed by a healthcare provider or for ‎whom it was not prescribed.‎ Abuse is the intentional non-therapeutic use of a drug, even once, for its desirable 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 to other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of Hydromorphone Hydrochloride Injection increases ‎risk of overdose, which may lead to ‎central nervous system and ‎respiratory depression, hypotension, seizures, and death. The risk is ‎increased with ‎concurrent abuse of Hydromorphone Hydrochloride ‎Injection with alcohol and/or other CNS ‎depressants.‎ Abuse of and addiction to opioids 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 ‎‎addiction.‎ All patients treated with opioids require careful and frequent reevaluation ‎for signs of misuse, abuse, and ‎addiction, because use of opioid analgesic ‎products carries the risk of addiction even under appropriate ‎medical use. ‎Patients at high risk of Hydromorphone Hydrochloride Injection abuse ‎include those with a ‎history of prolonged use of any opioid, including products containing ‎hydromorphone, those with a history of drug or alcohol abuse, ‎or those ‎who use Hydromorphone Hydrochloride Injection in combination with ‎other abused drugs.‎ "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 with prescriptions and reluctance to provide prior medical records or contact information for other treating health care provider(s). "Doctor shopping" (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. Hydromorphone Hydrochloride Injection, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal 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. Risks Specific to Abuse of Hydromorphone Hydrochloride Injection Abuse of Hydromorphone Hydrochloride Injection poses a risk of overdose and death. The risk is increased with concurrent use of Hydromorphone Hydrochloride Injection with alcohol and/or other CNS depressants. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV. Both tolerance and physical dependence can develop during use of 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 a 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 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 use. Hydromorphone Hydrochloride Injection should not be abruptly discontinued in a physically-dependent patient [see Dosage and Administration (2.6)]. If Hydromorphone Hydrochloride Injection is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur, typically ‎characterized by restlessness, lacrimation, rhinorrhea, 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. 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 (8.1)] . Parenteral drug products should be inspected visually for particulate matter and discoloration prior to ‎‎‎administration, whenever solution and container permit. Do not use if color is darker than pale yellow, if it ‎‎is ‎discolored in any other way, or if it contains a precipitate.‎ NexJect™ Single-dose Prefilled Syringe Instructions for use – NexJect Prefilled Syringe NOTE : To prevent needlestick injuries, do not be recap, purposely bend, or break by hand used ‎needles. Do not recap, purposely bend, or break by ‎hand blunt Cannulas. Distributed by Hospira, Inc., Lake Forest, IL 60045 USA LAB-1382-3.0 Revised: 12/2023

Product summary:

Safety and Handling Instructions Access to drugs with a potential for abuse such as Hydromorphone Hydrochloride Injection presents an occupational hazard for addiction in the health care industry. Routine procedures for handling controlled substances developed to protect the public may not be adequate to protect health care workers. Implementation of more effective accounting procedures and measures to restrict access to drugs of this class (appropriate to the practice setting) may minimize the risk of self-administration by health care providers. How Supplied Hydromorphone Hydrochloride Injection is supplied as a sterile solution in single‑dose NexJectTM prefilled syringes for intravenous, intramuscular, and subcutaneous administration, and available as follows: NDC 0409-1805-01 Clamshell of 10 0.5 mL fill in 1.5 mL NexJect™ Single-dose Prefilled Syringe with Luer Lock 0.25 mg/0.5 mL NDC 0409-4264-01 Clamshell of 10 0.5 mL fill in 1.5 mL NexJect™ Single-dose Prefilled Syringe with Luer Lock 0.5 mg/0.5 mL NDC 0409-1283-37 Clamshell of 10 1 mL fill in 1.5 mL NexJect™ Single-dose Prefilled Syringe with Luer Lock 1 mg/mL NDC 0409-1312-36 Clamshell of 10 1 mL fill in 1.5 mL NexJect™ Single-dose Prefilled Syringe with Luer Lock 2 mg/mL NDC 0409-1380-01 Clamshell of 10 1 mL fill in 1.5 mL NexJect™ Single-dose Prefilled Syringe with Luer Lock 4 mg/mL Note that a needle is not included. PROTECT FROM LIGHT Keep covered in carton until time of use. Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].

Authorization status:

New Drug Application

Summary of Product characteristics

HYDROMORPHONE HYDROCHLORIDE- HYDROMORPHONE HYDROCHLORIDE INJECTION,
SOLUTION
HOSPIRA, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
HYDROMORPHONE
HYDROCHLORIDE INJECTION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
HYDROMORPHONE HYDROCHLORIDE INJECTION.
HYDROMORPHONE HYDROCHLORIDE INJECTION, FOR INTRAVENOUS, INTRAMUSCULAR,
OR
SUBCUTANEOUS USE, CII
INITIAL U.S. APPROVAL: 1984
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE ​OF
HYDROMORPHONE
HYDROCHLORIDE ​INJECTION
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_.
•
•
•
•
RECENT MAJOR CHANGES
Boxed Warning
12/2023
Indications and Usage (1)​
12/2023
Dosage and Administration (2.1, 2.2, 2.5)​
12/2023
Warnings and Precautions (5.5)
12/2023
INDICATIONS AND USAGE
Hydromorphone Hydrochloride Injection is an opioid agonist indicated
for the management of pain severe
enough to require an opioid analgesic and for which alternative
treatments are inadequate. (1)
Limitations of Use (1)
Because of the risks of addiction, abuse, and misuse with opioids,
which can occur at any dosage or
duration (5.1), reserve Hydromorphone Hydrochloride Injection for use
in patients for whom alternative
treatment options (e.g., non-opioid analgesics or opioid combination
products):
•
•
Hydromorphone Hydrochloride Injection should not be used for an
extended ​​period of time unless the pain
remains severe enough to require an opioid ​​analgesic and for
which alternative treatment options
continue to be inadequate.
HYDROMORPHONE HYDROCHLORIDE INJECTION EXPOSES USERS TO RISKS OF
ADDICTION, ABUSE,
AND MISUSE, WHICH CAN LEAD TO OVERDOSE AND DEATH. ASSESS PATIENT'S
RISK BEFORE
PRESCRIBING AND REASSESS REGULARLY FOR THESE BEHAVIORS AND CONDITIONS.
(5.1).
SERIOUS, LIFE-THREATENING, OR FATAL RESPIRATORY DEPRESSION MAY OCCUR
WITH USE OF
HYDROMORPHONE HYDROCHLORIDE INJECTION, ESPECIALLY DURING INITIATION OR
FOLLOWING A
DOSAGE INCREASE. TO REDUCE THE RISK OF RESPIRATORY D