"Nov. 1, 2012 -- Two more drugs made by the New England Compounding Center (NECC) are crawling with various kinds of bacteria, FDA tests reveal.
The NECC is the Massachusetts compounding pharmacy whose drugs are the likely source of th"...
Due to the risk of severe adverse events when the epidural route of administration is employed, patients must be observed in a fully equipped and staffed environment for at least 48 hours after administration. The facility must be equipped to resuscitate patients with severe opiate overdosage, and the personnel must be familiar with the use and limitations of specific narcotic antagonists (naloxone, naltrexone) in such cases.
No clinical studies have evaluated the safety of administration of DepoDur (morphine sulfate xr liposome injection) into the intrathecal space. DepoDur (morphine sulfate xr liposome injection) is intended for administration by the epidural route only. However, cases of intrathecal administration of DepoDur (morphine sulfate xr liposome injection) have been reported during post-marketing experience. In all cases, signs of prolonged respiratory depression were observed requiring narcotic antagonist (naloxone) administration or ventilatory support.
Prolonged and serious respiratory depression or apnea has occurred when administration of epidural DepoDur (morphine sulfate xr liposome injection) was associated with subarachnoid puncture. In these cases, respiratory depression has occurred within 12 hours of DepoDur (morphine sulfate xr liposome injection) administration following apparent recovery from anesthesia. Respiratory depression resulting from DepoDur (morphine sulfate xr liposome injection) can be treated successfully with a naloxone bolus or, more commonly, a naloxone infusion; intubation and mechanical ventilation may be necessary in some cases.
Because intrathecal leakage from the epidural space may occur through a breached dural membrane, especially when the epidural drug is administered in a bolus, DepoDur (morphine sulfate xr liposome injection) should not be administered to a patient following a recent dural puncture without vigilant monitoring of respiratory function for a prolonged period (48 hours) with provision for emergency mechanical ventilation to minimize the risk of serious respiratory depression.
DepoDur (morphine sulfate xr liposome injection) should be administered by or under the direction of a physician experienced in the techniques associated with epidural drug administration and familiar with patient management following epidural opiate administration, including the management of respiratory depression.
Prior to drug administration, the physician should be familiar with patient conditions (such as infection at the injection site, bleeding diathesis, current and anticipated anticoagulant therapy, etc.) that call for special evaluation of the benefit versus risk potential.
Respiratory depression is the chief hazard of all opiate preparations. Respiratory depression occurs more frequently in elderly or debilitated patients and in those suffering from conditions accompanied by hypoxia or hypercapnia in whom even moderate therapeutic doses may significantly decrease pulmonary ventilation.
Administration of opiates with or without coadministration of other sedative or hypnotic drugs can worsen airway obstruction in patients with obstructive sleep-apnea syndrome. Patients who are obese are at particular risk for this syndrome, which may be undiagnosed prior to administration.
Respiratory depression can occur with DepoDur (morphine sulfate xr liposome injection) . Four percent of the patients who received DepoDur (morphine sulfate xr liposome injection) required treatment with narcotic antagonists for respiratory depression. Ninety percent of events of respiratory depression started within the first 24 hours after dosing with DepoDur (morphine sulfate xr liposome injection) . However, the incidence of respiratory depression starting after 48 hours, potentially related to DepoDur (morphine sulfate xr liposome injection) , was 0.6% (5 of 900 patients). Patients at increased risk of respiratory depression such as those with impaired respiratory drive, sleep apnea, concomitant sedation or the elderly, may require monitoring for periods longer than 48 hours.
Because of the risk of respiratory depression, the facility must be equipped to resuscitate patients. Patients must be closely monitored in a fully equipped and staffed environment for a minimum of 48 hours.
If the surgical procedure is cancelled after the administration of DepoDur (morphine sulfate xr liposome injection) , the risk of respiratory depression may be increased, and patients should be monitored with a high level of vigilance.
Epidural local anesthetics should not be used before or after DepoDur (morphine sulfate xr liposome injection) except:
- in the form of a 3 mL test dose with lidocaine 1.5% and epinephrine 1:200,000 or
- a therapeutic dose of bupivacaine 0.25% - 20 mL. (See PRECAUTIONS: DRUG INTERACTIONS) Do not mix or co-administer DepoDur (morphine sulfate xr liposome injection) with any other medications including local anesthetics. Once DepoDur (morphine sulfate xr liposome injection) has been administered, no other medication should be administered into the epidural space for at least 48 hours.
Misuse, Abuse and Diversion of Opiates
The active ingredient of DepoDur (morphine sulfate xr liposome injection) is morphine, a n-opiate agonist. DepoDur (morphine sulfate xr liposome injection) is a Schedule II controlled substance. Such drugs are sought by drug abusers and people with addiction disorders. Diversion of Schedule II products is an act subject to criminal penalty. DepoDur (morphine sulfate xr liposome injection) can be abused in a manner similar to other opiate agonists, legal or illicit.
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.
DepoDur (morphine sulfate xr liposome injection) , like all other opiates, may cause severe hypotension in an individual whose ability to maintain blood pressure has already been compromised by a depleted blood volume or concurrent administration of drugs such as phenothiazines or general anesthetics (see also PRECAUTIONS: DRUG INTERACTIONS). DepoDur (morphine sulfate xr liposome injection) may produce orthostatic hypotension and syncope in ambulatory patients. In a patient who progresses to circulatory shock, DepoDur (morphine sulfate xr liposome injection) may make resuscitation more difficult due to vasodilatation.
DepoDur (morphine sulfate xr liposome injection) should not be administered to patients with gastrointestinal obstruction, especially paralytic ileus, because DepoDur (morphine sulfate xr liposome injection) diminishes propulsive peristaltic waves in the gastrointestinal tract and may prolong the obstruction.
Use with Other Central Nervous System Depressants
The central nervous depressant effects of morphine are potentiated by the presence of other CNS depressants such as alcohol, other opiates, sedatives, antihistaminics or psychotropic drugs. Use of neuroleptics or general anesthetics in conjunction with epidural morphine may increase the risk of respiratory depression.
Labor and Delivery
DepoDur (morphine sulfate xr liposome injection) should not be administered to women for vaginal labor and delivery. DepoDur (morphine sulfate xr liposome injection) has only been administered to women undergoing cesarean section following clamping of the umbilical cord.
Epidural delivery of opiates is accompanied by risk to the patients and requires a high level of skill to be successfully accomplished. The task of treating these patients must be undertaken by experienced clinical teams, well-versed in patient selection and emerging standards of care. It is critical to adjust the dose of DepoDur (morphine sulfate xr liposome injection) for each individual patient, taking into account the patient's age, body mass, physical status, prior experience with opiate analgesics, risk factors for respiratory depression, and medications to be co administered before or during surgery (see DOSAGE AND ADMINISTRATION).
Seizures may result from high doses of morphine. Patients with known seizure disorders should be carefully observed for evidence of morphine-induced seizure activity.
Use in Hepatic or Renal Disease
After morphine sulfate has been released from DepoDur (morphine sulfate xr liposome injection) and is absorbed systemically, its distribution, metabolism and excretion are expected to be the same as other morphine formulations.
DepoDur (morphine sulfate xr liposome injection) is intended for single-dose administration; therefore accumulation of morphine or its metabolites is not expected even in patients with impaired hepatic or renal function.
Use in Biliary Surgery or Disorders of the Biliary Tract
Morphine is released into the systemic circulation after epidural administration. Therefore, smooth muscle hypertonicity may result in biliary colic.
DepoDur (morphine sulfate xr liposome injection) should be used with caution in patients with biliary tract disease, including acute pancreatitis, as morphine may cause spasm of the sphincter of Oddi and diminish biliary and pancreatic secretions.
Use with Disorders of the Urinary System
The use of epidural opiate analgesia has been associated with disturbances of micturition, especially in males with prostatic hypertrophy. Early recognition of urinary retention and prompt intervention is indicated.
Patients with reduced circulating blood volume, impaired myocardial function or those receiving sympatholytic drugs should be monitored for the possible occurrence of orthostatic hypotension, a frequent complication in single-dose epidurally administered morphine analgesia.
Intravenous or Intramuscular Administration
Administration of DepoDur (morphine sulfate xr liposome injection) via the intravenous or intramuscular routes has not been studied in humans and DepoDur (morphine sulfate xr liposome injection) should not be administered by these routes.
Carcinogenicity/Mutagenicity/Impairment of Fertility
Studies in animals to evaluate the carcinogenic potential of morphine sulfate have not been conducted. No formal studies to assess the mutagenic potential of morphine have been conducted. In the published literature, the results of in-vitro studies showed that morphine is non-mutagenic in the Drosophila melanogaster lethal mutation assay and produced no evidence of chromosomal aberrations when incubated with murine splenocytes. Contrary to these results, morphine was found to increase DNA fragmentation when incubated in vitro with a human lymphoma cell line. In vivo, morphine has been reported to produce an increase in the frequency of micronuclei in bone marrow cells and immature red blood cells in the mouse micronucleus test and to induce chromosomal aberrations in murine lymphocytes and spermatids. Some of the in–vivo clastogenic effects reported with morphine in mice may be directly related to increases in glucocorticoid levels produced by morphine in this species.
Teratogenic Effects (Pregnancy Category C)
No formal studies to assess the teratogenic effects of morphine in animals have been performed. Several literature reports indicate that morphine administered subcutaneously during the early gestational period in mice and hamsters produced neurological, soft tissue and skeletal abnormalities. With one exception, the effects that have been reported were following doses that were maternally toxic and the abnormalities noted were characteristic of those observed when maternal toxicity is present. In one study, following subcutaneous infusion of doses greater than or equal to 0.15 mg/kg in mice, exencephaly, hydronephrosis, intestinal hemorrhage, split supraoccipital, malformed sternebrae, and malformed xiphoid were noted in the absence of maternal toxicity. In the hamster, morphine sulfate given subcutaneously on gestation day eight produced exencephaly and cranioschisis. Morphine was not a significant teratogen in the rat at exposure levels significantly beyond that normally encountered in clinical practice. In one study, however, decreased litter size and viability were observed in the offspring of male rats administered morphine at doses approximately 3-fold the maximum recommended human daily dose (MRHDD) for 10 days prior to mating. In two studies performed in the rabbit, no evidence of teratogenicity was reported at subcutaneous doses up to 100 mg/kg.
In humans, the frequency of congenital anomalies has been reported to be no greater than expected among the children of 70 women who were treated with morphine during the first four months of pregnancy or in 448 women treated with this drug anytime during pregnancy. Furthermore, no malformations were observed in the infant of a woman who attempted suicide by taking an overdose of morphine and other medication during the first trimester of pregnancy.
Published literature indicates that exposure to morphine during pregnancy is associated with reduction in growth and a host of behavioral abnormalities in the offspring of animals. Morphine treatment during gestational periods of organogenesis in rats, hamsters, guinea pigs and rabbits resulted in the following treatment-related embryotoxicity and neonatal toxicity in one or more studies: decreased litter size, embryo-fetal viability, fetal and neonatal body weights, absolute brain and cerebellar weights, lengths or widths at birth and during the neonatal period, delayed motor and sexual maturation, and increased neonatal mortality, cyanosis and hypothermia. Decreased fertility in female offspring, and decreased plasma and testicular levels of luteinizing hormone and testosterone, decreased testes weights, seminiferous tubule shrinkage, germinal cell aplasia, and decreased spermatogenesis in male offspring were also observed. Behavioral abnormalities resulting from chronic morphine exposure of fetal animals included altered reflex and motor skill development, mild withdrawal, and altered responsiveness to morphine persisting into adulthood.
Morphine sulfate should be used by a pregnant woman only if the need for opiate analgesia clearly outweighs the potential risks to the fetus.
Labor and Delivery
In studies of epidural administration of morphine sulfate injection, small amounts of morphine were detected in breast milk. The degree to which morphine sulfate is excreted in human milk following administration of DepoDur (morphine sulfate xr liposome injection) has not been studied. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from morphine, a decision should be made whether or not to allow nursing during the first 48 hours following DepoDur (morphine sulfate xr liposome injection) administration.
The safety and effectiveness of DepoDur (morphine sulfate xr liposome injection) in pediatric patients below the age of 18 years have not been established and use in this population is not recommended.
Use in the Elderly
DepoDur (morphine sulfate xr liposome injection) was studied in clinical trials of 876 subjects; 222 were 65 years of age and older, and 43 of these patients were 75 years of age and over. The efficacy and opiate adverse event profiles in these elderly patients, at the same or lower dose of DepoDur, were similar to those in younger adults (see DOSAGE AND ADMINISTRATION). However, elderly patients (65 years of age or older) may have increased sensitivity to morphine. Comorbid conditions may predispose the elderly population to serious adverse events such as respiratory depression, ileus, hypotension and myocardial infarction.
In general, caution should be exercised in the selection of the dose of DepoDur (morphine sulfate xr liposome injection) for an elderly patient. Dosing normally should be at the low end of the range.
DepoDur (morphine sulfate xr liposome injection) should be administered to elderly patients ( > 65 years) after careful evaluation of their underlying medical condition and consideration of the risks associated with DepoDur (morphine sulfate xr liposome injection) . Provision for vigilant perioperative monitoring should be arranged for elderly patients receiving DepoDur (morphine sulfate xr liposome injection) .
Last reviewed on RxList: 10/13/2009
This monograph has been modified to include the generic and brand name in many instances.
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