Ingredient matches for Estradiol Cypionate
Estradiol
Estradiol 17ß-cypionate (a derivative of Estradiol) is reported as an ingredient of Estradiol Cypionate in the following countries:
- United States
International Drug Name Search
Thursday, September 29, 2016
Nimesulide Germed Pliva
Nimesulide Germed Pliva may be available in the countries listed below.
Ingredient matches for Nimesulide Germed Pliva
Nimesulide
Nimesulide is reported as an ingredient of Nimesulide Germed Pliva in the following countries:
- Italy
International Drug Name Search
Wednesday, September 28, 2016
Oxycodone and Acetaminophen Capsules
Dosage Form: capsule
Oxycodone and Acetaminophen Capsules USP CII
Rev. B 5/2011
0658
Rx only
WARNING
Hepatotoxicity
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product.
Oxycodone and Acetaminophen Capsules Description
Oxycodone, USP 14-hydroxydihydrocodeinone, is a semisynthetic opioid analgesic which occurs as a white, odorless, crystalline powder having a saline, bitter taste. It is derived from the opium alkaloid thebaine and may be represented by the following structural formula:
Acetaminophen, USP 4'-hydroxyacetanilide, is a non-opiate, non-salicylate analgesic and antipyretic which occurs as a white, odorless, crystalline powder, possessing a slightly bitter taste. It may be represented by the following structural formula:
Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 1, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, FD&C Red No. 40, gelatin, iron oxide black, lactose monohydrate, magnesium stearate, pregelatinized starch, propylene glycol, shellac glaze and titanium dioxide.
Oxycodone and Acetaminophen Capsules - Clinical Pharmacology
Central Nervous System
Oxycodone is a semisynthetic pure opioid agonist whose principal therapeutic action is analgesia. Other pharmacological effects of oxycodone include anxiolysis, euphoria and feelings of relaxation. These effects are mediated by receptors (notably μ and κ) in the central nervous system for endogenous opioid-like compounds such as endorphins and enkephalins. Oxycodone produces respiratory depression through direct activity at respiratory centers in the brain stem and depresses the cough reflex by direct effect on the center of the medulla.
Acetaminophen is a non-opiate, non-salicylate analgesic and antipyretic. The site and mechanism for the analgesic effect of acetaminophen has not been determined. The antipyretic effect of acetaminophen is accomplished through the inhibition of endogenous pyrogen action on the hypothalamic heat-regulating centers.
Gastrointestinal Tract and Other Smooth Muscle
Oxycodone reduces motility by increasing smooth muscle tone in the stomach and duodenum. In the small intestine, digestion of food is delayed by decreases in propulsive contractions. Other opioid effects include contraction of biliary tract smooth muscle, spasm of the Sphincter of Oddi, increased ureteral and bladder sphincter tone, and a reduction in uterine tone.
Cardiovascular System
Oxycodone may produce a release of histamine and may be associated with orthostatic hypotension, and other symptoms, such as pruritus, flushing, red eyes, and sweating.
Pharmacokinetics
Absorption and Distribution
The mean absolute oral bioavailability of oxycodone in cancer patients was reported to be about 87%. Oxycodone has been shown to be 45% bound to human plasma proteins in vitro. The volume of distribution after intravenous administration is 211.9 ± 186.6 L.
Absorption of acetaminophen is rapid and almost complete from the GI tract after oral administration. With overdosage, absorption is complete in 4 hours. Acetaminophen is relatively uniformly distributed throughout most body fluids. Binding of the drug to plasma proteins is variable; only 20% to 50% may be bound at the concentrations encountered during acute intoxication.
Metabolism and Elimination
A high portion of oxycodone is N-dealkylated to noroxycodone during first-pass metabolism. Oxymorphone is formed by the O-demethylation of oxycodone. The metabolism of oxycodone to oxymorphone is catalyzed by CYP2D6. Free and conjugated noroxycodone, free and conjugated oxycodone, and oxymorphone are excreted in human urine following a single oral dose of oxycodone. Approximately 8% to 14% of the dose is excreted as free oxycodone over 24 hours after administration. Following a single, oral dose of oxycodone, the mean ± SD elimination half-life is 3.51 ± 1.43 hours.
Acetaminophen is metabolized in the liver via cytochrome P450 microsomal enzyme. About 80 to 85% of the acetaminophen in the body is conjugated principally with glucuronic acid and to a lesser extent with sulfuric acid and cysteine. After hepatic conjugation, 90 to 100% of the drug is recovered in the urine within the first day.
About 4% of acetaminophen is metabolized via cytochrome P450 oxidase to a toxic metabolite which is further detoxified by conjugation with glutathione, present in a fixed amount. It is believed that the toxic metabolite NAPQI (N acetyl-p-benzoquinoneimine, N-acetylimidoquinone) is responsible for liver necrosis. High doses of acetaminophen may deplete the glutathione stores so that inactivation of the toxic metabolite is decreased. At high doses, the capacity of metabolic pathways for conjugation with glucuronic acid and sulfuric acid may be exceeded, resulting in increased metabolism of acetaminophen by alternate pathways.
Indications and Usage for Oxycodone and Acetaminophen Capsules
Oxycodone and Acetaminophen Capsules USP are indicated for the relief of moderate to moderately severe pain.
Contraindications
Oxycodone and Acetaminophen Capsules should not be administered to patients with known hypersensitivity to oxycodone, acetaminophen, or any other component of this product.
Oxycodone is contraindicated in any situation where opioids are contraindicated including patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment) and patients with acute or severe bronchial asthma or hypercarbia. Oxycodone is contraindicated in the setting of suspected or known paralytic ileus.
Warnings
Misuse, Abuse and Diversion of Opioids
Oxycodone 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.
Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing Oxycodone and Acetaminophen Capsules in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Concerns about misuse, 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.
Administration of Oxycodone and Acetaminophen Capsules should be closely monitored for the following potentially serious adverse reactions and complications:
Respiratory Depression
Respiratory depression is a hazard with the use of oxycodone, one of the active ingredients in Oxycodone and Acetaminophen Capsules, as with all opioid agonists. Elderly and debilitated patients are at particular risk for respiratory depression as are non-tolerant patients given large initial doses of oxycodone or when oxycodone is given in conjunction with other agents that depress respiration. Oxycodone should be used with extreme caution in patients with acute asthma, chronic obstructive pulmonary disorder (COPD), cor pulmonale, or preexisting respiratory impairment. In such patients, even usual therapeutic doses of oxycodone may decrease respiratory drive to the point of apnea. In these patients alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose.
In case of respiratory depression, a reversal agent such as naloxone hydrochloride may be utilized (see OVERDOSAGE).
Head Injury and Increased Intracranial Pressure
The respiratory depressant effects of opioids include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, and may be markedly exaggerated in the presence of head injury, other intracranial lesions or a preexisting increase in intracranial pressure. Oxycodone produces effects on pupillary response and consciousness which may obscure neurologic signs of worsening in patients with head injuries.
Hypotensive Effect
Oxycodone may cause severe hypotension particularly in individuals whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs which compromise vasomotor tone such as phenothiazines. Oxycodone, like all opioid analgesics of the morphine-type, should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure. Oxycodone may produce orthostatic hypotension in ambulatory patients.
Hepatotoxicity
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products.
The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen.
Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if they feel well.
Hypersensitivity/anaphylaxis
There have been postmarketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue Oxycodone and Acetaminophen Capsules USP immediately and seek medical care if they experience these symptoms. Do not prescribe Oxycodone and Acetaminophen Capsules USP for patients with acetaminophen allergy.
Precautions
General
Opioid analgesics should be used with caution when combined with CNS depressant drugs, and should be reserved for cases where the benefits of opioid analgesia outweigh the known risks of respiratory depression, altered mental state, and postural hypotension.
Acute Abdominal Conditions
The administration of Oxycodone and Acetaminophen Capsules or other opioids may obscure the diagnosis or clinical course in patients with acute abdominal conditions.
Oxycodone and Acetaminophen Capsules should be given with caution to patients with CNS depression, elderly or debilitated patients, patients with severe impairment of hepatic, pulmonary, or renal function, hypothyroidism, Addison's disease, prostatic hypertrophy, urethral stricture, acute alcoholism, delirium tremens, kyphoscoliosis with respiratory depression, myxedema, and toxic psychosis.
Oxycodone and Acetaminophen Capsules may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Oxycodone may aggravate convulsions in patients with convulsive disorders, and all opioids may induce or aggravate seizures in some clinical settings.
Following administration of Oxycodone and Acetaminophen Capsules, anaphylactic reactions have been reported in patients with a known hypersensitivity to codeine, a compound with a structure similar to morphine and oxycodone. The frequency of this possible cross-sensitivity is unknown.
Interactions with Other CNS Depressants
Patients receiving other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, centrally-acting anti-emetics, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with Oxycodone and Acetaminophen Capsules may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced.
Interactions with Mixed Agonist/Antagonist Opioid Analgesics
Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) 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 oxycodone. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of oxycodone and/or may precipitate withdrawal symptoms in these patients.
Ambulatory Surgery and Postoperative Use
Oxycodone and other morphine-like opioids have been shown to decrease bowel motility. Ileus is a common postoperative complication, especially after intra-abdominal surgery with use of opioid analgesia. Caution should be taken to monitor for decreased bowel motility in postoperative patients receiving opioids. Standard supportive therapy should be implemented.
Use in Pancreatic/Biliary Tract Disease
Oxycodone may cause spasm of the Sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids like oxycodone may cause increases in the serum amylase level.
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, and 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 should not be abruptly discontinued (see DOSAGE AND ADMINISTRATION, Cessation of Therapy).
Information for Patients/Caregivers
The following information should be provided to patients receiving Oxycodone and Acetaminophen Capsules USP by their physician, nurse, pharmacist, or caregiver:
- Patients should be aware that Oxycodone and Acetaminophen Capsules USP contain oxycodone, which is a morphine-like substance.
- Patients should be instructed to keep Oxycodone and Acetaminophen Capsules USP in a secure place out of the reach of children. In the case of accidental ingestion, emergency medical care should be sought immediately.
- When Oxycodone and Acetaminophen Capsules USP are no longer needed, the unused capsules should be destroyed by flushing down the toilet.
- Patients should be advised not to adjust the medication dose themselves. Instead, they must consult with their prescribing physician.
- Patients should be advised that Oxycodone and Acetaminophen Capsules USP may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating heavy machinery).
- Patients should not combine Oxycodone and Acetaminophen Capsules USP with alcohol, opioid analgesics, tranquilizers, sedatives, or other CNS depressants unless under the recommendation and guidance of a physician. When coadministered with another CNS depressant, Oxycodone and Acetaminophen Capsules can cause dangerous additive central nervous system or respiratory depression, which can result in serious injury or death.
- The safe use of Oxycodone and Acetaminophen Capsules USP during pregnancy has not been established; thus, women who are planning to become pregnant or are pregnant should consult with their physician before taking Oxycodone and Acetaminophen Capsules USP.
- Nursing mothers should consult with their physicians about whether to discontinue nursing or discontinue Oxycodone and Acetaminophen Capsules USP because of the potential for serious adverse reactions to nursing infants.
- Patients who are treated with Oxycodone and Acetaminophen Capsules USP for more than a few weeks should be advised not to abruptly discontinue the medication. Patients should consult with their physician for a gradual discontinuation dose schedule to taper off the medication.
- Patients should be advised that Oxycodone and Acetaminophen Capsules USP are a potential drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
- Do not take Oxycodone and Acetaminophen Capsules USP if you are allergic to any of its ingredients.
- If you develop signs of allergy such as a rash or difficulty breathing stop taking Oxycodone and Acetaminophen Capsules USP and contact your healthcare provider immediately.
- Do not take more than 4000 milligrams of acetaminophen per day. Call your doctor if you took more than the recommended dose.
Laboratory Tests
Although oxycodone may cross-react with some drug urine tests, no available studies were found which determined the duration of detectability of oxycodone in urine drug screens. However, based on pharmacokinetic data, the approximate duration of detectability for a single dose of oxycodone is roughly estimated to be one to two days following drug exposure.
Urine testing for opiates may be performed to determine illicit drug use and for medical reasons such as evaluation of patients with altered states of consciousness or monitoring efficacy of drug rehabilitation efforts. The preliminary identification of opiates in urine involves the use of an immunoassay screening and thin-layer chromatography (TLC). Gas chromatography/mass spectrometry (GC/MS) may be utilized as a third-stage identification step in the medical investigational sequence for opiate testing after immunoassay and TLC. The identities of 6-keto opiates (e.g., oxycodone) can further be differentiated by the analysis of their methoximetrimethylsilyl (MO-TMS) derivative.
Drug/Drug Interactions with Oxycodone
Opioid analgesics may enhance the neuromuscular-blocking action of skeletal muscle relaxants and produce an increase in the degree of respiratory depression.
Patients receiving CNS depressants such as other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, centrally-acting anti-emetics, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with Oxycodone and Acetaminophen Capsules may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced. The concurrent use of anticholinergics with opioids may produce paralytic ileus.
Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, naltrexone, and butorphanol) should be administered with caution to a patient who has received or is receiving a pure opioid agonist such as oxycodone. These agonist/antagonist analgesics may reduce the analgesic effect of oxycodone or may precipitate withdrawal symptoms.
Drug/Drug Interactions with Acetaminophen
Alcohol, ethyl: Hepatotoxicity has occurred in chronic alcoholics following various dose levels (moderate to excessive) of acetaminophen.
Anticholinergics: The onset of acetaminophen effect may be delayed or decreased slightly, but the ultimate pharmacological effect is not significantly affected by anticholinergics.
Oral Contraceptives: Increase in glucuronidation resulting in increased plasma clearance and a decreased half-life of acetaminophen.
Charcoal (activated): Reduces acetaminophen absorption when administered as soon as possible after overdose.
Beta Blockers (Propranolol): Propranolol appears to inhibit the enzyme systems responsible for the glucuronidation and oxidation of acetaminophen. Therefore, the pharmacologic effects of acetaminophen may be increased.
Loop diuretics: The effects of the loop diuretic may be decreased because acetaminophen may decrease renal prostaglandin excretion and decrease plasma renin activity.
Lamotrigine: Serum lamotrigine concentrations may be reduced, producing a decrease in therapeutic effects.
Probenecid: Probenecid may increase the therapeutic effectiveness of acetaminophen slightly.
Zidovudine: The pharmacologic effects of zidovudine may be decreased because of enhanced nonhepatic or renal clearance of zidovudine.
Drug/Laboratory Test Interactions
Depending on the sensitivity/specificity and the test methodology, the individual components of Oxycodone and Acetaminophen Capsules may cross-react with assays used in the preliminary detection of cocaine (primary urinary metabolite, benzoylecgonine) or marijuana (cannabinoids) in human urine. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. The preferred confirmatory method is gas chromatography/mass spectrometry (GC/MS). Moreover, clinical considerations and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
Acetaminophen may interfere with home blood glucose measurement systems; decreases of > 20% in mean glucose values may be noted. This effect appears to be drug, concentration and system dependent.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Animal studies to evaluate the carcinogenic potential of oxycodone and acetaminophen have not been performed.
Mutagenesis
The combination of oxycodone and acetaminophen has not been evaluated for mutagenicity. Oxycodone alone was negative in a bacterial reverse mutation assay (Ames), an in vitro chromosome aberration assay with human lymphocytes without metabolic activation and an in vivo mouse micronucleus assay. Oxycodone was clastogenic in the human lymphocyte chromosomal assay in the presence of metabolic activation and in the mouse lymphoma assay with or without metabolic activation.
Fertility
Animal studies to evaluate the effects of oxycodone on fertility have not been performed.
Pregnancy
Teratogenic Effects
Pregnancy Category C
Animal reproductive studies have not been conducted with Oxycodone and Acetaminophen Capsules. It is also not known whether Oxycodone and Acetaminophen Capsules can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Oxycodone and Acetaminophen Capsules should not be given to a pregnant woman unless in the judgment of the physician, the potential benefits outweigh the possible hazards.
Nonteratogenic Effects
Opioids can cross the placental barrier and have the potential to cause neonatal respiratory depression. Opioid use during pregnancy may result in a physically drug-dependent fetus. After birth, the neonate may suffer severe withdrawal symptoms.
Labor and Delivery
Oxycodone and Acetaminophen Capsules are not recommended for use in women during and immediately prior to labor and delivery due to its potential effects on respiratory function in the newborn.
Nursing Mothers
Ordinarily, nursing should not be undertaken while a patient is receiving Oxycodone and Acetaminophen Capsules because of the possibility of sedation and/or respiratory depression in the infant. Oxycodone is excreted in breast milk in low concentrations, and there have been rare reports of somnolence and lethargy in babies of nursing mothers taking an oxycodone/acetaminophen product. Acetaminophen is also excreted in breast milk in low concentrations.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Special precaution should be given when determining the dosing amount and frequency of Oxycodone and Acetaminophen Capsules for geriatric patients, since clearance of oxycodone may be slightly reduced in this patient population when compared to younger patients.
Hepatic Impairment
In a pharmacokinetic study of oxycodone in patients with end-stage liver disease, oxycodone plasma clearance decreased and the elimination half-life increased. Care should be exercised when oxycodone is used in patients with hepatic impairment.
Renal Impairment
In a study of patients with end stage renal impairment, mean elimination half-life was prolonged in uremic patients due to increased volume of distribution and reduced clearance. Oxycodone should be used with caution in patients with renal impairment.
Adverse Reactions
Serious adverse reactions that may be associated with oxycodone and acetaminophen capsule use include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, and shock (see OVERDOSAGE).
The most frequently observed non-serious adverse reactions include lightheadedness, dizziness, drowsiness or sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include euphoria, dysphoria, constipation, and pruritus.
Hypersensitivity reactions may include: Skin eruptions, urticarial, erythematous skin reactions.
Hematologic reactions may include: Thrombocytopenia, neutropenia, pancytopenia, hemolytic anemia. Rare cases of agranulocytosis has likewise been associated with acetaminophen use. In high doses, the most serious adverse effect is a dose-dependent, potentially fatal hepatic necrosis. Renal tubular necrosis and hypoglycemic coma also may occur.
Other adverse reactions obtained from postmarketing experiences with Oxycodone and Acetaminophen Capsules are listed by organ system and in decreasing order of severity and/or frequency as follows:
Body as a Whole: Anaphylactoid reaction, allergic reaction, malaise, asthenia, fatigue, chest pain, fever, hypothermia, thirst, headache, increased sweating, accidental overdose, non-accidental overdose
Cardiovascular: Hypotension, hypertension, tachycardia, orthostatic hypotension, bradycardia, palpitations, dysrhythmias
Central and Peripheral Nervous System: Stupor, tremor, paraesthesia, hypoaesthesia, lethargy, seizures, anxiety, mental impairment, agitation, cerebral edema, confusion, dizziness
Fluid and Electrolyte: Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis
Gastrointestinal: Dyspepsia, taste disturbances, abdominal pain, abdominal distention, sweating increased, diarrhea, dry mouth, flatulence, gastro-intestinal disorder, nausea, vomiting, pancreatitis, intestinal obstruction, ileus
Hepatic: Transient elevations of hepatic enzymes, increase in bilirubin, hepatitis, hepatic failure, jaundice, hepatotoxicity, hepatic disorder
Hearing and Vestibular: Hearing loss, tinnitus
Hematologic: Thrombocytopenia
Hypersensitivity: Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria, anaphylactoid reaction
Metabolic and Nutritional: Hypoglycemia, hyperglycemia, acidosis, alkalosis
Musculoskeletal: Myalgia, rhabdomyolysis
Ocular: Miosis, visual disturbances, red eye
Psychiatric: Drug dependence, drug abuse, insomnia, confusion, anxiety, agitation, depressed level of consciousness, nervousness, hallucination, somnolence, depression, suicide
Respiratory System: Bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, aspiration, hypoventilation, laryngeal edema
Skin and Appendages: Erythema, urticaria, rash, flushing
Urogenital: Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, urinary retention
Drug Abuse and Dependence
Oxycodone and Acetaminophen Capsules are a Schedule II controlled substance. Oxycodone is a mu-agonist opioid with an abuse liability similar to morphine. Oxycodone, like morphine and other opioids used in analgesia, can be abused and is subject to criminal diversion.
Drug addiction is defined as an abnormal, compulsive use, use for non-medical purposes of a substance despite physical, psychological, occupational or interpersonal difficulties resulting from such use, and continued use despite harm or risk of harm. Drug addiction is a treatable disease, utilizing a multi-disciplinary approach, but relapse is common. Opioid addiction is relatively rare in patients with chronic pain but may be more common in individuals who have a past history of alcohol or substance abuse or dependence. Pseudoaddiction refers to pain relief seeking behavior of patients whose pain is poorly managed. It is considered an iatrogenic effect of ineffective pain management. The health care provider must assess continuously the psychological and clinical condition of a pain patient in order to distinguish addiction from pseudoaddiction and thus, be able to treat the pain adequately.
Physical dependence on a prescribed medication does not signify addiction. Physical dependence involves the occurrence of a withdrawal syndrome when there is sudden reduction or cessation in drug use or if an opiate antagonist is administered. Physical dependence can be detected after a few days of opioid therapy. However, clinically significant physical dependence is only seen after several weeks of relatively high dosage therapy. In this case, abrupt discontinuation of the opioid may result in a withdrawal syndrome. If the discontinuation of opioids is therapeutically indicated, gradual tapering of the drug over a 2 week period will prevent withdrawal symptoms. The severity of the withdrawal syndrome depends primarily on the daily dosage of the opioid, the duration of therapy and medical status of the individual.
The withdrawal syndrome of oxycodone is similar to that of morphine. This syndrome is characterized by yawning, anxiety, increased heart rate and blood pressure, restlessness, nervousness, muscle aches, tremor, irritability, chills alternating with hot flashes, salivation, anorexia, severe sneezing, lacrimation, rhinorrhea, dilated pupils, diaphoresis, piloerection, nausea, vomiting, abdominal cramps, diarrhea and insomnia, and pronounced weakness and depression.
“Drug-seeking” behavior is very common in addicts and drug abusers. 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 physician(s). “Doctor Shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated infection.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Oxycodone, like other opioids, has been diverted for non-medical use. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.
Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Like other opioid medications, Oxycodone and Acetaminophen Capsules are subject to the Federal Controlled Substances Act. After chronic use, Oxycodone and Acetaminophen Capsules should not be discontinued abruptly when it is thought that the patient has become physically dependent on oxycodone.
Interactions with Alcohol and Drugs of Abuse
Oxycodone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.
Overdosage
Following an acute overdosage, toxicity may result from the oxycodone or the acetaminophen.
Signs and Symptoms
Toxicity from oxycodone poisoning includes the opioid triad of: pinpoint pupils, depression of respiration, and loss of consciousness. Serious overdosage with oxycodone is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest, and death may occur.
In acetaminophen overdosage: dose-dependent potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and coagulation defects may also occur.
Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.
Treatment
A single or multiple drug overdose with oxycodone and acetaminophen is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption. Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered.
Oxycodone
Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The narcotic antagonist naloxone hydrochloride is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to narcotics, including oxycodone. Since the duration of action of oxycodone may exceed that of the antagonist, the patient should be kept under continued surveillance, and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. A narcotic antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.
Acetaminophen
Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation. Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.
Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose dependent and occurs early in the course of intoxication.
Oxycodone and Acetaminophen Capsules Dosage and Administration
Dosage should be adjusted according to the severity of the pain and the response of the patient. It may occasionally be necessary to exceed the usual dosage recommended below in cases of more severe pain or in those patients who have become tolerant to the analgesic effect of opioids. If pain is constant, the opioid analgesic should be given at regular intervals on an around-the-clock schedule. Oxycodone and Acetaminophen Capsules USP are given orally.
The usual adult dosage is one capsule every 6 hours as needed for pain. The total daily dose of acetaminophen should not exceed 4 grams.
Cessation of Therapy
In patients treated with Oxycodone and Acetaminophen Capsules USP for more than a few weeks who no longer require therapy, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.
How is Oxycodone and Acetaminophen Capsules Supplied
Oxycodone and Acetaminophen Capsules USP are available as:
5 mg / 500 mg: Red opaque cap and white opaque body filled with white powder. Imprinted in black ink stylized barr 658. Available in bottles of 100 capsules.
Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature].
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
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TEVA PHARMACEUTICALS USA
Sellersville, PA 18960
Rev. B 5/2011
PRINCIPAL DISPLAY PANEL
Oxycodone and Acetaminophen Capsules USP 5 mg/500 mg 100s Label Text
NDC 0555-0658-02
OXYCODONE and
ACETAMINOPHEN
Capsules USP
5 mg/500 mg*
Rx only
100 Capsules
TEVA
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| ANDA | ANDA040289 | 08/17/2011 | |
| Labeler - Barr Laboratories Inc. (802716563) |
More Oxycodone and Acetaminophen Capsules resources
- Oxycodone and Acetaminophen Capsules Side Effects (in more detail)
Desoximetasone
Scheme
Rec.INN
ATC (Anatomical Therapeutic Chemical Classification)
D07AC03,D07XC02
CAS registry number (Chemical Abstracts Service)
0000382-67-2
Chemical Formula
C22-H29-F-O4
Molecular Weight
376
Therapeutic Categories
Dermatological agent
Adrenal cortex hormone, glucocorticoid
Chemical Name
Pregna-1,4-diene-3,20-dione, 9-fluoro-11,21-dihydroxy-16-methyl-, (11ß,16α)-
Foreign Names
- Desoximetasonum (Latin)
- Desoximetason (German)
- Désoximétasone (French)
- Desoximetasona (Spanish)
Generic Names
- Desossimetasone (OS: DCIT)
- Desoximetasone (OS: BAN, USAN)
- Désoximétasone (OS: DCF)
- Desoxymethasone (OS: BAN)
- Hoe 304 (IS)
- R 2113 (IS)
- Desoximetasone (PH: USP 32)
Brand Names
- Denomix (Desoximetasone and Neomycin)
Combiphar, Indonesia - Dercason
Global Multi Pharmalab, Indonesia - Desicort
Taro, Israel - Desoximetasone
Clay-Park, United States; Fougera, United States; Taro, United States - Dexigen
Ifars, Indonesia - Dexocort
Kimia Farma, Indonesia - Esperson
Jugoremedija, Serbia; Sanofi-Aventis, Brazil; Sanofi-Aventis, Indonesia; Sanofi-Aventis, Philippines; Sanofi-Aventis, Taiwan - Flubason
Sanofi-Aventis, Italy; Sanofi-Aventis S.A., Spain - Ibaril
Bipharma, Netherlands; Sanofi-Aventis, Denmark; Sanofi-Aventis, Finland; Sanofi-Aventis, Norway - Inerson
Interbat, Indonesia - Lerskin
Nufarindo, Indonesia - Topcort
Sanbe, Indonesia - Topicort
Medicis, United States; sanofi-aventis, Canada; Taro, United States - Topicorte
Roussel Laboratories, Ethiopia; Sanofi-Aventis, Netherlands; Sanofi-Aventis, Thailand - Topisolon
Sanofi-Aventis, Germany - Topisolone
Hoechst, Ethiopia
International Drug Name Search
Glossary
| BAN | British Approved Name |
| DCF | Dénomination Commune Française |
| DCIT | Denominazione Comune Italiana |
| IS | Inofficial Synonym |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
Click for further information on drug naming conventions and International Nonproprietary Names.
Mepact 4 mg powder for suspension for infusion
1. Name Of The Medicinal Product
MEPACT
2. Qualitative And Quantitative Composition
One vial contains 4 mg mifamurtide*.
After reconstitution, each ml of suspension in the vial contains 0.08 mg mifamurtide.
*fully synthetic analogue of a component of Mycobacterium sp. cell wall.
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Powder for suspension for infusion.
White to off-white homogeneous lyophilised powder.
4. Clinical Particulars
4.1 Therapeutic Indications
MEPACT is indicated in children, adolescents and young adults for the treatment of high
4.2 Posology And Method Of Administration
MEPACT treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of osteosarcoma.
Posology
The recommended dose of mifamurtide for all patients is 2 mg/m2 body surface area. It should be administered as adjuvant therapy following resection: twice weekly at least 3 days apart for 12 weeks, followed by once.
Paediatric patients
The safety and efficacy of MEPACT have been established in children from the age of 2 years. It is not recommended for use in children below the age of 2 due to a lack of data on efficacy and safety in this age group.
Elderly patients
None of the patients treated in the osteosarcoma studies were 65 or older and in the phase III randomised study, only patients up to age 30 years were included. Therefore, there are not sufficient data to recommend the use of MEPACT in patients>30 years of age.
Patients with impaired renal or hepatic function
The pharmacokinetics of mifamurtide in patients with renal or hepatic impairment have not been formally studied. Caution should be used in these patients because dose adjustment information is not available.
Continued monitoring of the kidney and liver function is recommended if MEPACT is used beyond completion of chemotherapy until all therapy is completed.
Method of administration
MEPACT must be reconstituted, filtered using the filter provided and further diluted prior to administration. The reconstituted, filtered and diluted suspension for infusion is a homogenous, white to off-white, opaque liposomal suspension, free of visible particles and free of foam and lipid lumps.
After reconstitution, filtering using the filter provided and further dilution, MEPACT is administered by intravenous infusion over a period of 1 hour.
MEPACT must not be administered as a bolus injection.
For further instructions on reconstitution, filtering using the filter provided and dilution prior to administration, see section 6.6.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Concurrent use with ciclosporin or other calcineurin inhibitors (see section 4.5).
Concurrent use with high
4.4 Special Warnings And Precautions For Use
Respiratory distress
In patients with a history of asthma or other chronic obstructive pulmonary disease, consideration should be given to administration of bronchodilators on a prophylactic basis. Two patients with pre
Neutropenia
Administration of MEPACT was commonly associated with transient neutropenia, usually when used in conjunction with chemotherapy. Episodes of neutropenic fever should be monitored and managed appropriately. MEPACT may be given during periods of neutropenia, but subsequent fever attributed to the treatment should be monitored closely. Fever or chills persisting for more than 8 hours after administration of MEPACT should be evaluated for possible sepsis.
Inflammatory response
Association of MEPACT with signs of pronounced inflammatory response, including pericarditis and pleuritis, was uncommon. It should be used with caution in patients with a history of autoimmune, inflammatory or other collagen diseases. During MEPACT administration, patients should be monitored for unusual signs or symptoms, such as arthritis or synovitis, suggestive of uncontrolled inflammatory reactions.
Cardiovascular disorders
Patients with a history of venous thrombosis, vasculitis or unstable cardiovascular disorders should be closely monitored during MEPACT administration. If symptoms are persistent and worsening, administration should be delayed or discontinued. Haemorrhage was observed in animals at very high doses. These are not expected at the recommended dose, however monitoring of clotting parameters after the first dose and once again after several doses is recommended.
Allergic reactions
Occasional allergic reactions have been associated with MEPACT treatment, including rash, shortness of breath and Grade 4 hypertension. It may be difficult to distinguish allergic reactions from exaggerated inflammatory responses, but patients should be monitored for signs of allergic reactions.
Gastrointestinal toxicity
Nausea, vomiting and loss of appetite are very common adverse reactions to MEPACT. Gastrointestinal toxicity may be exacerbated when MEPACT is used in combination with high dose, multi-agent chemotherapy and was associated with an increased use of parenteral nutrition.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Limited studies of the interaction of MEPACT with chemotherapy have been conducted. Although these studies are not conclusive, there is no evidence of interference of MEPACT with the anti
It is recommended to separate the administration times of MEPACT and doxorubicin or other lipophilic medicinal products if used in the same chemotherapy regimen.
The use of MEPACT concurrently with ciclosporin or other calcineurin inhibitors is contraindicated due to their hypothesised effect on splenic macrophages and mononuclear phagocytic function (see section 4.3).
Also, it has been demonstrated in vitro that high
Because mifamurtide acts through stimulation of the immune system, the chronic or routine use of corticosteroids should be avoided during treatment with MEPACT.
In vitro interaction studies showed that liposomal and non
In a large controlled randomised study, MEPACT used at the recommended dose and schedule with other medicinal products that have known renal (cisplatin, ifosfamide) or hepatic (high-dose methotrexate, ifosfamide) toxicities did not exacerbate those toxicities and there was no need to adjust mifamurtide dose.
4.6 Pregnancy And Lactation
Pregnancy
There are no data from the use of mifamurtide in pregnant patients. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). MEPACT should not be used during pregnancy and in women not using effective contraception.
Lactation
It is unknown whether mifamurtide is excreted in human milk. The excretion of mifamurtide in milk has not been studied in animals. A decision on whether to continue/discontinue breast
4.7 Effects On Ability To Drive And Use Machines
No studies of the effects on the ability to drive and use machines have been performed. Some very common or common undesirable effects of MEPACT treatment (such as dizziness, vertigo, fatigue and blurred vision) may have an effect on the ability to drive and use machines.
4.8 Undesirable Effects
Each of the 248 patients treated with MEPACT during the early phase single arm studies in patients with mostly advanced malignancies experienced at least one undesirable effect. Many of the most frequently reported undesirable effects as shown in the following summary table are thought to be related to the mechanism of action of mifamurtide. The majority of these events were reported as either mild or moderate. This profile is consistent whether summarising all early studies (n=248) or only those studies in osteosarcoma (n=51). It is likely that undesirable effects also occurred in the large randomised study, but they were not recorded because only serious and life
Adverse reactions are classified according to system organ class and frequency. Frequency groupings are defined according to the following convention: Very common (
Table 1. Adverse reactions associated with MEPACT in
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Blood and lymphatic system disorders
Anaemia has most commonly been reported when MEPACT is used in conjunction with chemotherapeutic agents. In a randomised controlled trial, the incidence of myeloid malignancy (acute myeloid leukaemia/myelodysplastic syndrome) was the same in patients receiving MEPACT plus chemotherapy as in patients receiving only chemotherapy (approximately 2.5%).
Metabolism and nutritional disorders
Anorexia (21%) was very commonly reported in trials of MEPACT in late stage cancer patients.
Nervous system disorders
Consistent with other generalised symptoms, the most common nervous system disorders were headache (50%) and dizziness (17%).
Ear and labyrinth disorders
Although hearing loss may be attributable to ototoxic chemotherapy, like cisplatin, it is unclear whether MEPACT in conjunction with multi-agent chemotherapy may increase hearing loss.
A higher percentage of objective and subjective hearing loss was observed overall in patients who received MEPACT and chemotherapy (12 % and 7%, respectively) in the phase III study (see Section 5.1 for a description of the trial) compared to those patients that received only chemotherapy (7% and 1%). All patients received a total dose of cisplatin of 480 mg/m2 as part of their induction (neoadjuvant) and/or maintenance (adjuvant) chemotherapy regimen.
Cardiac and vascular disorders
Mild-moderate tachycardia (50%), hypertension (26%) and hypotension (29%) were commonly reported in uncontrolled trials of MEPACT. One serious incident of subacute thrombosis was reported in early studies, but no serious cardiac events were associated with MEPACT in a large randomised controlled trial.
Respiratory disorders
Respiratory disorders, including dyspnoea (21%), cough (18%) and tachypnoea (13%) were very commonly reported, and two patients with pre-existing asthma developed mild to moderate respiratory distress associated with MEPACT treatment in a phase II study.
Gastrointestinal disorders
Gastrointestinal disorders were frequently associated with MEPACT administration, including nausea (57%) and vomiting (44%) in about half of patients, constipation (17%), diarrhoea (13%) and abdominal pain.
Skin and subcutaneous disorders
Hyperhidrosis (11%) was very common in patients receiving MEPACT in uncontrolled studies.
Musculoskeletal and connective tissue disorders
Low grade pain was common in patients receiving MEPACT, including myalgia (31%), back pain (15%), extremity pain (12%) and arthralgia (10%).
General disorders and administration site conditions
The majority of patients experience chills (89%), fever (85%) and fatigue (53%). These are typically mild to moderate, transient in nature and generally respond to palliative treatment (e.g., paracetamol for fever). Other generalised symptoms that were typically mild to moderate and very common included hypothermia (23%), malaise (13%), pain (15%), asthenia (13%) and chest pain (11%). Oedema, chest discomfort, local infusion or catheter site reactions and 'feeling cold' were less frequently reported in these patients, mostly with late stage malignant disease.
Investigations
Increase in blood urea and blood creatinine was associated with MEPACT use in one patient with osteosarcoma.
4.9 Overdose
No case of overdose has been reported. The maximum tolerated dose in phase I studies was 4-6 mg/m2 with a high variability of adverse reactions. Signs and symptoms that were associated with higher doses and/or were dose limiting were not life
In the event of an overdose, it is recommended that appropriate supportive treatment be initiated. Supportive measures should be based on institutional guidelines and the clinical symptoms observed. Examples include paracetamol for fever, chills and headache and anti-emetics (other than steroids) for nausea and vomiting.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Other cytokines and immunomodulators, ATC code: L03AX15
Mechanism of action
Mifamurtide (muramyl tripeptide phosphatidyl ethanolamine, MTP-PE) is a fully synthetic derivative of muramyl dipeptide (MDP), the smallest naturallyMycobacterium sp. It has similar immunostimulatory effects as natural MDP with the additional advantage of a longer halfin vivo targeting to macrophages by intravenous infusion.
MTP-PE is a specific ligand of NOD2, a receptor found primarily on monocytes, dendritic cells and macrophages. MTP-PE is a potent activator of monocytes and macrophages. Activation of human macrophages by MEPACT is associated with production of cytokines, including tumour necrosis factor (TNF-α), interleukin-1 (IL-1β), IL-6, IL-8, and IL-12 and adhesion molecules, including lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1). In vitro-treated human monocytes killed allogeneic and autologous tumor cells (including melanoma, ovarian, colon, and renal carcinoma), but had no toxicity towards normal cells.
In vivo administration of MEPACT resulted in the inhibition of tumour growth in mouse and rat models of lung metastasis, skin and liver cancer, and fibrosarcoma. Significant enhancement of disease-free survival was also demonstrated in the treatment of dog osteosarcoma and hemangiosarcoma with MEPACT as adjuvant therapy. The exact mechanism by which MEPACT activation of monocytes and macrophages leads to antitumour activity in animals and humans is not yet known.
Clinical safety and efficacy
The safety of liposomal mifamurtide has been assessed in more than 700 patients with various kinds and stages of cancer and in 21 healthy adult subjects (see section 4.8).
MEPACT significantly increased the overall survival of patients with newly
5.2 Pharmacokinetic Properties
After intravenous administration in 21 healthy adult subjects mifamurtide was cleared rapidly from plasma (minutes), resulting in a very low plasma concentration of total (liposomal and free) mifamurtide. The mean AUC was 17.0 +/- 4.71 h x nM and Cmax was 15.7 +/- 3.72 nM. In separate study in 14 patients, mean serum concentration
At 6 hours after injection of radiolabelled liposomes containing 6 mg mifamurtide, radioactivity was found in liver, spleen, nasopharynx, thyroid, and, to a lesser extent, in lung. The liposomes were phagocytosed by cells of the reticuloendothelial system. In 2 of 4 patients with lung metastases, radioactivity was associated with lung metastases. Mean half
5.3 Preclinical Safety Data
In sensitive species (rabbit and dog) the highest daily dose of liposomal mifamurtide that did not cause adverse effects was 0.1 mg/kg, corresponding to 1.2 and 2 mg/m2, respectively. The no2 recommend dose for humans.
Data from a six month dog study of daily intravenous injections of up to 0.5 mg/kg (10 mg/m2) MEPACT provide an 8- to 19-fold cumulative exposure safety margin for overt toxicity for the intended clinical dose in humans. Major toxic effects associated with these high daily and cumulative doses of MEPACT were mainly exaggerated pharmacological effects: pyrexia, signs of pronounced inflammatory response manifested as synovitis, bronchopneumonia, pericarditis and inflammatory necrosis of the liver and bone marrow. The following events were also observed: haemorrhage and prolongation of coagulation times, infarcts, morphological changes in the wall of small arteries, oedema and congestion of the central nervous system, minor cardiac effects, and slight hyponatraemia. MEPACT was not mutagenic and did not cause teratogenic effects in rats and rabbits. Embryotoxic effects were observed only at maternal toxic levels.
There were no results from general toxicity studies that suggested harmful effects on male or female reproductive organs. Specific studies addressing reproductive function, perinatal toxicity and carcinogenic potential have not been performed.
6. Pharmaceutical Particulars
6.1 List Of Excipients
1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
1,2-Dioleoyl-sn-glycero-3-phospho-L-serine monosodium salt (OOPS)
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
6.3 Shelf Life
Unopened vial of powder:
30 months
Reconstituted suspension:
Chemical and physical stability has been demonstrated for 6 hours up to 25ºC.
From a microbiological point of view, immediate use is recommended. If not used immediately, the reconstituted, filtered and diluted solution in
6.4 Special Precautions For Storage
Store in a refrigerator (2°C – 8°C). Do not freeze.
Keep the vial in the outer carton in order to protect from light.
For storage conditions of the reconstituted medicinal product, see section 6.3.
6.5 Nature And Contents Of Container
50 ml type I glass vial with a grey butyl rubber stopper, aluminium seal and plastic flip
Each carton contains one vial and one single
6.6 Special Precautions For Disposal And Other Handling
MEPACT must be reconstituted, filtered using the filter provided and further diluted using aseptic technique.
Each vial should be reconstituted with 50 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection. After reconstitution, each ml suspension in the vial contains 0.08 mg mifamurtide. The volume of reconstituted suspension corresponding to the calculated dose is extracted through the filter provided and further diluted with additional 50 ml sodium chloride 9 mg/ml (0.9 %) solution for injection according to the detailed instructions shown below.
Instructions for preparation of MEPACT for intravenous infusion
Materials provided in each package -
• MEPACT powder for suspension for infusion (vial)
• Filter for MEPACT
Materials required but not provided -
• Sodium chloride 9 mg/ml (0.9%) solution for injection, EP/USP 100 ml bag
• One single use 60 or 100 ml sterile syringe with luer lock
• Two medium (18) gauge sterile injection needles
It is recommended that the reconstitution of the liposomal suspension should be performed in a laminar flow cabinet utilising sterile gloves using aseptic technique.
The lyophilised powder should be allowed to reach a temperature between approximately 20°C – 25°C prior to reconstitution, filtering using the filter provided and dilution. This should take approximately 30 minutes.
1. The cap of the vial should be removed and the stopper cleaned using an alcohol pad.
2. The filter should be removed from the blister pack, and the cap removed from the filter spike. The spike should then be inserted into the vial septum firmly until seated. The filter luer connector cap should not be removed at this time.
3. The 100 ml sodium chloride 9 mg/ml (0.9%) solution for injection bag, needle and syringe should be unpacked (not provided in the pack).
4. The site of the sodium chloride 9 mg/ml (0.9%) solution for injection bag where the needle is going to be inserted should be swabbed with an alcohol pad.
5. Using the needle and syringe, 50 ml of sodium chloride 9 mg/ml (0.9%) solution for injection should be withdrawn from the bag.
6. After removing the needle from the syringe, the syringe should be attached to the filter by opening the filter luer connector cap (Figure 1).
Figure 1
7. The sodium chloride 9 mg/ml (0.9%) solution for injection is added to the vial by slow, firm depression of the syringe plunger. The filter and syringe must not be removed from the vial.
8. The vial should be allowed to stand undisturbed for one minute to ensure thorough hydration of the dry substance.
9. The vial should then be shaken vigorously for one minute while keeping the filter and syringe attached. During this time the liposomes are formed spontaneously (Figure 2).
Figure 2
10. The desired dose may be withdrawn from the vial by inverting the vial and slowly pulling back on the syringe plunger (Figure 3). Each ml reconstituted suspension contains 0.08 mg mifamurtide. The volume of suspension to be withdrawn for dose quantities is calculated as follows:
Volume to withdraw = [12.5 x calculated dose (mg)] ml
For convenience, the following table of concordance is provided:
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Figure 3
11. The syringe should then be removed from the filter and a new needle placed on the suspension
Figure 4
12. The bag should be gently swirled to mix the solution.
13. Patient identification, time and date should be added to the label on the bag containing the reconstituted, filtered and diluted liposomal suspension.
14. Chemical and physical in
15. From a microbiological point of view, the product should be used immediately. If not used immediately, in
16. The liposomal suspension is infused intravenously over about one hour.
Disposal
No special requirements.
7. Marketing Authorisation Holder
IDM PHARMA SAS
11-15 Quai De Dion Bouton
92816 Puteaux Cedex
France
8. Marketing Authorisation Number(S)
EU/1/08/502/001
9. Date Of First Authorisation/Renewal Of The Authorisation
06/03/2009
10. Date Of Revision Of The Text
05/01/2011
Tertensif Retard Paranova
Tertensif Retard Paranova may be available in the countries listed below.
Ingredient matches for Tertensif Retard Paranova
Indapamide
Indapamide hemihydrate (a derivative of Indapamide) is reported as an ingredient of Tertensif Retard Paranova in the following countries:
- Denmark
International Drug Name Search
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