İHALE DÜNYASI
İHALE DÜNYASI
Hydromorphone hydrochloride, a hydrogenated ketone of morphine, is an opioid analgesic. Hydromorphone Hydrochloride is a white to off-white powder. It is soluble in water and sparingly soluble in alcohol. The chemical name of hydromorphone hydrochloride is 4,5?-epoxy-3-hydroxy-17-methylmorphinan-6-one hydrochloride. The structural formula is: C 17 H 19 NO 3 *HCl M.W. 321.81 Each Hydromorphone Hydrochloride Tablet USP for oral administration, contains 4 mg or 8 mg hydromorphone hydrochloride USP. In addition, the tablets include lactose anhydrous and magnesium stearate. Each 5 mL (1 teaspoonful) of Hydromorphone Hydrochloride Oral Solution USP contains 5 mg of hydromorphone hydrochloride USP. In addition, other ingredients include FD&C Red No. 40, methyl paraben, propylene glycol, propylparaben, purified water, raspberry blend, saccharin sodium and sorbitol solution. structural formula
Hydromorphone hydrochloride tablets and hydromorphone hydrochloride oral solution are indicated for the management of pain in patients where an opioid analgesic is appropriate.
The usual starting dose for hydromorphone hydrochloride tablets is 2 mg to 4 mg, orally, every 4 to 6 hours. Appropriate use of the hydromorphone hydrochloride tablets must be decided by careful evaluation of each clinical situation. The usual adult dosage of hydromorphone hydrochloride oral solution is one-half (2.5 mL) to two teaspoonfuls (10 mL) (2.5 mg to 10 mg) every 3 to 6 hours as directed by the clinical situation. Oral dosages higher than the usual may be required in some patients. A gradual increase in dose may be required if analgesia is inadequate, as tolerance develops, or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect. Patients with hepatic and renal impairment should be started on a lower starting dose (see CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism ).
Hydromorphone hydrochloride tablets and hydromorphone hydrochloride oral solution are contraindicated in: patients with known hypersensitivity to hydromorphone, patients with respiratory depression in the absence of resuscitative equipment, and in patients with status asthmaticus. Hydromorphone hydrochloride tablets and hydromorphone hydrochloride oral solution are also contraindicated for use in obstetrical analgesia.
The major hazards of hydromorphone hydrochloride tablets and oral solution include respiratory depression and apnea. To a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest have occurred. The most frequently observed adverse effects are light-headedness, dizziness, sedation, nausea, vomiting, sweating, flushing, dysphoria, euphoria, dry mouth, and pruritus. These effects seem to be more prominent in ambulatory patients and in those not experiencing severe pain. Less Frequently Observed Adverse Reactions General and CNS Weakness, headache, agitation, tremor, uncoordinated muscle movements, alterations of mood (nervousness, apprehension, depression, floating feelings, dreams), muscle rigidity, paresthesia, muscle tremor, blurred vision, nystagmus, diplopia and miosis, transient hallucinations and disorientation, visual disturbances, insomnia, increased intracranial pressure Cardiovascular Flushing of the face, chills, tachycardia, bradycardia, palpitation, faintness, syncope, hypotension, hypertension Respiratory Bronchospasm and laryngospasm Gastrointestinal Constipation, biliary tract spasm, ileus, anorexia, diarrhea, cramps, taste alteration Genitourinary Urinary retention or hesitancy, antidiuretic effects Dermatologic Urticaria, other skin rashes, diaphoresis
Respiratory Depression Respiratory depression is the chief hazard of hydromorphone hydrochloride tablets and oral solution. 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 and oral solution 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 and oral solution 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 and oral solution can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing hydromorphone hydrochloride 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 WARNINGS and 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 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 and oral solution 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 and oral solution 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 and oral solution, 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 and oral solution should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure. --- BOXED WARNING: WARNING HYDROMORPHONE HYDROCHLORIDE TABLETS USP AND HYDROMORPHONE HYDROCHLORIDE ORAL SOLUTION USP 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.
Drug Interactions with Other CNS Depressants The concomitant use of other central nervous system depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers and alcohol may produce additive depressant effects. Respiratory depression, hypotension and profound sedation or coma may occur. When such combined therapy is contemplated, the dose of one or both agents should be reduced. Hydromorphone hydrochloride should not be taken with alcohol. Opioid analgesics, including hydromorphone hydrochloride tablets and oral solution may enhance the action of neuromuscular blocking agents and produce an excessive degree of respiratory depression. Interactions with Mixed Agonist/Antagonist Opioid Analgesics Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol, and buprenorphine) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic such as hydromorphone. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of hydromorphone and/or may precipitate withdrawal symptoms in these patients.