HYDROMORPHONE HYDROCHLORIDE tablet HYDROMORPHONE HYDROCHLORIDE solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

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

Available from:

Rhodes Pharmaceuticals L.P.

INN (International Name):

HYDROMORPHONE HYDROCHLORIDE

Composition:

HYDROMORPHONE HYDROCHLORIDE 2 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets are 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 (5.2)] , reserve hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: - Have not been tolerated or are not expected to be tolerated, - Have not provided adequate analgesia or are not expected to provide adequate analgesia. Hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets 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 oral solution and hydromorphone hydrochloride tablets are contraindicated in patients with: - Significant respiratory depression [see Warnings and Precautions (5.3)] - Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.8)] - Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.12)] - Hypersensitivity to hydromorphone, hydromorphone salts, any other components of the product, or sulfite-containing medications (e.g., anaphylaxis) [see Warnings and Precautions (5.16), Adverse Reactions (6.1)] Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.5)]. There are no available data with hydromorphone hydrochloride in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, reduced postnatal survival of pups, and decreased were noted following oral treatment of pregnant rats with hydromorphone during gestation and through lactation at doses 0.8 times the human daily dose of 24 mg/day (HDD), respectively. In published 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 Data]. 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 (5.5)] . 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 oral solution or hydromorphone hydrochloride tablets 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 oral solution or hydromorphone hydrochloride tablets, 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 hydromorphone hydrochloride from Gestation Day 6 to 17 via oral gavage doses of 1, 5, or 10 mg/kg/day (0.4, 2, or 4 times the HDD of 24 mg based on body surface area, respectively). Maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in the two highest dose groups). There was no evidence of malformations or embryotoxicity reported. Pregnant rabbits were treated with hydromorphone hydrochloride from Gestation Day 7 to 19 via oral gavage doses of 10, 25, or 50 mg/kg/day (8.1, 20.3, or 40.5 times the HDD of 24 mg based on body surface area, respectively). Maternal toxicity was noted in the two highest dose groups (reduced food consumption and body weights). There was no evidence of malformations or embryotoxicity reported. 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. Increased pup mortality and decreased pup body weights were noted at 0.8 and 2 times the human daily dose of 24 mg in a study in which pregnant rats were treated with hydromorphone hydrochloride from Gestation Day 7 to Lactation Day 20 via oral gavage doses of 0, 0.5, 2, or 5 mg/kg/day (0.2, 0.8, or 2 times the HDD of 24 mg based on body surface area, respectively). Maternal toxicity (decreased food consumption and body weight gain) was also noted at the two highest doses tested. 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 oral solution or hydromorphone hydrochloride tablets and any potential adverse effects on the breastfed infant from hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets 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 (6.2), Clinical Pharmacology (12.2), Nonclinical Toxicology (13.1)]. The safety and effectiveness of hydromorphone hydrochloride in pediatric patients have 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 slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.8)] . 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 regularly evaluate renal function. The pharmacokinetics of hydromorphone is affected by hepatic impairment. Due to increased exposure of hydromorphone, patients with hepatic impairment should be started at one-fourth to one-half the recommended starting dose depending on the degree of hepatic dysfunction and regularly evaluated 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 is 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 regularly evaluated during dose titration [see Clinical Pharmacology (12.3)]. Hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets contain hydromorphone, a Schedule II controlled substance. Hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets contain 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 (5.2)]. 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 other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of hydromorphone hydrochloride 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 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 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 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 healthcare 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, 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 Abuse of hydromorphone hydrochloride oral solution or hydromorphone hydrochloride tablets poses a risk of overdose and death. The risk is increased with concurrent use of hydromorphone hydrochloride with alcohol and/or other CNS depressants. Hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets are approved for oral use only. 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 use. Do not abruptly discontinue hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets in a patient physically dependent on opioids. Rapid tapering of hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. When discontinuing hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see Dosage and Administration (2.7), Warnings and Precautions (5.14)]. 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)].

Product summary:

Hydromorphone hydrochloride is available as follows: Oral Solution 5 mg/5 mL : a clear, colorless to pale yellow, slightly viscous liquid. NDC 42858-304-16:   Bottles of 1 pint (473 mL) 2 mg Tablets: light orange, round, flat-faced tablets, with beveled edges, debossed with a "P" on one side and the number "2" on the opposite side. NDC 42858-301-01:   Bottles of 100 4 mg Tablets : light yellow, round, flat-faced tablets, with beveled edges, debossed with a "P" on one side and the number "4" on the opposite side. NDC 42858-302-01:   Bottles of 100 NDC 42858-302-50:   Bottles of 500 8 mg Tablets : white, triangular shaped tablets debossed with a "P" and an inverted "P" separated with a bisect on one side of the tablet and debossed with the number "8" on the other side of the tablet. NDC 42858-303-01:   Bottles of 100 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light. Store hydromorphone hydrochloride oral solution and hydromorphone hydrochloride tablets securely and dispose of properly.

Authorization status:

New Drug Application Authorized Generic

Patient Information leaflet

HYDROMORPHONE HYDROCHLORIDE- HYDROMORPHONE HYDROCHLORIDE SOLUTION
Rhodes Pharmaceuticals L.P.
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MEDICATION GUIDE
HYDROMORPHONE HYDROCHLORIDE (HYE" DROE MOR' FONE HYE" DROE KLOR' IDE)
TABLETS AND ORAL SOLUTION, CII
This Medication Guide has been approved by the U.S. Food
and Drug Administration.
Issued: 12/2023
Hydromorphone hydrochloride tablets and hydromorphone hydrochloride
oral solution are:
•
Strong prescription pain medicines that contains an opioid (narcotic)
that is used to manage pain
severe enough to require an opioid analgesic, when other pain
treatments such as non-opioid pain
medicines do not treat your pain well enough or you cannot tolerate
them.
•
Opioid pain medicines that can put you at risk for overdose and death.
Even if you take your dose
correctly as prescribed you are at risk for opioid addiction, abuse,
and misuse that can lead to
death.
Important information about hydromorphone hydrochloride:
•
Get emergency help or call 911 right away if you take too much
hydromorphone hydrochloride
tablets or hydromorphone hydrochloride oral solution (overdose). When
you first start taking
hydromorphone hydrochloride tablets or hydromorphone hydrochloride
oral solution, when your
dose is changed, or if you take too much (overdose), serious or
life-threatening breathing
problems that can lead to death may occur. Talk to your healthcare
provider about naloxone, a
medicine for the emergency treatment of an opioid overdose.
•
Taking hydromorphone hydrochloride tablets or hydromorphone
hydrochloride oral solution with
other opioid medicines, benzodiazepines, alcohol, or other central
nervous system depressants
(including street drugs) can cause severe drowsiness, decreased
awareness, breathing problems,
coma, and death.
•
Never give anyone else your hydromorphone hydrochloride tablets or
hydromorphone
hydrochloride oral solution. They could die from taking it. Selling or
giving away
hydromorphone hydrochloride tablets or hydromorphone hydrochloride
oral solution is against
the law.
•
Sto

Summary of Product characteristics

HYDROMORPHONE HYDROCHLORIDE- HYDROMORPHONE HYDROCHLORIDE TABLET
HYDROMORPHONE HYDROCHLORIDE- HYDROMORPHONE HYDROCHLORIDE SOLUTION
RHODES PHARMACEUTICALS L.P.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
HYDROMORPHONE
HYDROCHLORIDE ORAL SOLUTION AND HYDROMORPHONE HYDROCHLORIDE TABLETS
SAFELY
AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR HYDROMORPHONE
HYDROCHLORIDE
ORAL SOLUTION AND HYDROMORPHONE HYDROCHLORIDE TABLETS.
HYDROMORPHONE HYDROCHLORIDE ORAL SOLUTION
HYDROMORPHONE HYDROCHLORIDE TABLETS, FOR ORAL USE, CII
INITIAL U.S. APPROVAL: JANUARY 1984
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROMORPHONE
HYDROCHLORIDE
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_.
ENSURE ACCURACY WHEN PRESCRIBING, DISPENSING, AND ADMINISTERING
HYDROMORPHONE
HYDROCHLORIDE ORAL SOLUTION. DOSING ERRORS DUE TO CONFUSION BETWEEN MG
AND ML CAN
RESULT IN ACCIDENTAL OVERDOSE AND DEATH. (2.1, 5.1)
HYDROMORPHONE HYDROCHLORIDE ORAL SOLUTION OR HYDROMORPHONE
HYDROCHLORIDE TABLETS
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. (5.2)
SERIOUS, LIFE-THREATENING, OR FATAL RESPIRATORY DEPRESSION MAY OCCUR,
ESPECIALLY UPON
INITIATION OR FOLLOWING A DOSAGE INCREASE. TO REDUCE THE RISK OF
RESPIRATORY
DEPRESSION, PROPER DOSING AND TITRATION OF HYDROMORPHONE HYDROCHLORIDE
ORAL
SOLUTION OR HYDROMORPHONE HYDROCHLORIDE TABLETS ARE ESSENTIAL. (5.3)
ACCIDENTAL INGESTION OF HYDROMORPHONE HYDROCHLORIDE ORAL SOLUTION OR
HYDROMORPHONE HYDROCHLORIDE TABLETS, ESPECIALLY BY CHILDREN, CAN
RESULT IN A FATAL
OVERDOSE OF HYDROMORPHONE. (5.3)
CONCOMITANT USE OF OPIOIDS WITH BENZODIAZEPINES OR OTHER CENTRAL
NERVOUS SYSTEM
(CNS) DEPRESSANTS, INCLUDING ALCOHOL, MAY RESULT IN PROFOUND SEDATION,
RESPIRATORY
DEPRESSION, COMA, AND DEATH. RESERVE CONCOMITANT PRESCRIBING FOR USE
IN PATIENTS
FOR WHOM ALTERNATIVE TREATMENT OPTIONS