Respiratory Depression – Respiratory depression is the chief hazard of hydromorphone hydrochloride tablets. Respiratory depression is more likely to occur in the elderly, in the debilitated, and in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation.
Hydromorphone hydrochloride tablets should be used with extreme caution in patients with chronic obstructive pulmonary disease or cor pulmonale, patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or in patients with preexisting respiratory depression. In such patients even usual therapeutic doses of opioid analgesics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.
Hydromorphone hydrochloride tablets contain hydromorphone, which is a potent Schedule II controlled opioid agonist. Schedule II opioid agonists, including morphine, oxymorphone, oxycodone, fentanyl, and methadone, have the highest potential for abuse and risk of producing respiratory depression. Alcohol, other opioids and central nervous system depressants (sedative-hypnotics) potentiate the respiratory depressant effects of hydromorphone, increasing the risk of respiratory depression that might result in death.
Misuse, Abuse, and Diversion of Opioids
Hydromorphone is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.
Hydromorphone hydrochloride tablets can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing hydromorphone hydrochloride tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Prescribers should monitor all patients receiving opioids for signs of abuse, misuse, and addiction. Furthermore, patients should be assessed for their potential for opioid abuse prior to being prescribed opioid therapy. Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse) or mental illness (e.g., depression). Opioids may still be appropriate for use in these patients, however, they will require intensive monitoring for signs of abuse.
Hydromorphone hydrochloride tablets have been reported as being abused by crushing, chewing, snorting, or injecting the dissolved product. These practices pose a significant risk to the abuser that could result in overdose or death (see
DRUG ABUSE AND DEPENDENCE).
Concerns about abuse, addiction, and diversion should not prevent the proper management of pain.
Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.
Interactions with Alcohol and Drugs of Abuse
Hydromorphone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.
Neonatal Withdrawal Syndrome – Infants born to mothers physically dependent on hydromorphone hydrochloride tablets will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms (see
DRUG ABUSE AND DEPENDENCE).
Head Injury and Increased Intracranial Pressure – The respiratory depressant effects of hydromorphone hydrochloride tablets with carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or preexisting increase in intracranial pressure. Opioid analgesics including hydromorphone hydrochloride tablets may produce effects on pupillary response and consciousness which can obscure the clinical course and neurologic signs of further increase in intracranial pressure in patients with head injuries.
Hypotensive Effect – Opioid analgesics, including hydromorphone hydrochloride tablets, may cause severe hypotension in an individual whose ability to maintain blood pressure has already been compromised by a depleted blood volume, or a concurrent administration of drugs such as phenothiazines or general anesthetics (see
PRECAUTIONS, Drug Interactions). Therefore, hydromorphone hydrochloride tablets should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure.
Special Risk Patients – Hydromorphone hydrochloride tablets should be given with caution and the initial dose should be reduced in the elderly or debilitated and those with severe impairment of hepatic, pulmonary or renal functions; myxedema or hypothyroidism; adrenocortical insufficiency (e.g., Addison's Disease); CNS depression or coma; toxic psychoses; prostatic hypertrophy or urethral stricture; gall bladder disease; acute alcoholism; delirium tremens; kyphoscoliosis or following gastrointestinal surgery.
The administration of opioid analgesics including hydromorphone hydrochloride tablets may obscure the diagnoses or clinical course in patients with acute abdominal conditions and may aggravate preexisting convulsions in patients with convulsive disorders.
Reports of mild to severe seizures and myoclonus have been reported in severely compromised patients, administered high doses of parenteral hydromorphone, for cancer and severe pain. Opioid administration at very high doses is associated with seizures and myoclonus in a variety of diseases where pain control is the primary focus.
Use in Drug and Alcohol Dependent Patients – Hydromorphone hydrochloride tablets should be used with caution in patients with alcoholism and other drug dependencies due to the increased frequency of opioid tolerance, dependence, and the risk of addiction observed in these patient populations. Abuse of hydromorphone hydrochloride tablets in combination with other CNS depressant drugs can result in serious risk to the patient.
Hydromorphone is an opioid with no approved use in the management of addictive disorders.
Use in Ambulatory Patients – Hydromorphone hydrochloride tablets may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating machinery). Patients should be cautioned accordingly. Hydromorphone hydrochloride may produce orthostatic hypotension in ambulatory patients.
Use in Biliary Tract Disease – Opioid analgesics including hydromorphone hydrochloride tablets should also be used with caution in patients about to undergo surgery of the biliary tract since it may cause spasm of the sphincter of Oddi.
Tolerance and Physical Dependence
Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist. Physical dependence and tolerance are not unusual during chronic opioid therapy.
The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis. Other 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.
In general, opioids used regularly should not be abruptly discontinued.