![[U.S. Food and Drug Administration]](https://webarchive.library.unt.edu/eot2008/20090118023212im_/http://www.fda.gov/icon/header.gif){kind=icon}
(Posted: 4/30/99, Climara added: 6/10/99)
Note: The following summaries include only those safety-related sections that have been modified, and therefore do not contain all the information needed for safe and effective prescribing. Contact the manufacturer for the complete labeling/package insert.
NB: Comparison made to 1999 Physicians' Desk Reference (PDR), if drug's labeling included in the PDR.
|
(zafirlukast) |
(doxorubicin) |
(spironolactone) |
(mepivacaine HCl) |
|
(estradiol transdermal) |
(lamivudine/zidovudine) |
(betaine anhydrous) |
(lidocaine) |
|
(venlafaxine HCl) |
(lidocaine/prilocaine) |
(edetate disodium) |
(lamivudine) |
|
(amifostine) |
(alendronate Na) |
(dalteparin Na) |
|
|
(fluvastatin Na) |
(metoprolol tartrate) |
(bupivacaine) |
|
|
(famotidine) |
(metoclopramide) |
(pyridostigmine bromide) |
(naltrexone HCl) |
|
|
(aprotinin) |
(cidofovir) |
(latanoprost) |
|
|
(ondansetron HCl) |
(bupropion HCl) |
|
"Cases of symptomatic hepatitis and hyperbilirubinemia without other attributable cause, have occurred in patients who have received the recommended dose of Accolate (40 mg/day). In rare cases, patients have progressed to hepatic failure. In most, but not all patients, the clinical symptoms abated and the liver enzymes returned to normal or near normal after stopping Accolate."
"Rare cases of symptomatic hepatitis and hyperbilirubinemia, without other attributable cause, have occurred in patients who had received the recommended doses of Accolate (40 mg/day). In these patients, the liver enzymes returned to normal or near normal after stopping Accolate."
Replaced with the following text -
"Cases of symptomatic hepatitis and hyperbilirubinemia, without other attributable cause, have occurred in patients who have received the recommended daily dose of Accolate (40 mg/day). In rare cases, patients have progressed to hepatic failure. In most, but not all patients, the clinical symptoms abated and the liver enzymes returned to normal or near normal after stopping Accolate."
Seventh paragraph revised (new text in italics) -
"Hypersensitivity reactions, including urticaria, angioedema and rashes, with or without blistering, have been reported in association with Accolate therapy. Additionally, there have been reports of patients experiencing agranulocytosis, bleeding, bruising, or edema in association with Accolate therapy."
"Pediatric patients are at increased risk for developing delayed cardiotoxicity."
"Cells treated with doxorubicin have been shown to manifest the characteristic morphologic changes associated with apoptosis or programmed cell death. Doxorubicin-induced apoptosis may be an integral component of the cellular mechanism of action relating to therapeutic effects, toxicities, or both."
Text added as new paragraph prior to last sentence in section
"Following administration of 10 to 75-mg/m2 doses of doxorubicin to 60 children and adolescents ranging from 2 months to 20 years of age, doxorubicin clearance averaged 1443 +/- 114 mL/min/m2. Further analysis demonstrated that clearance in 52 children greater than 2 years of age (1540 mL/min/m2) was increased compared with adults. However, clearance in infants younger than 2 years of age (813 mL/min/m2) was decreased compared with older children and approached the range of clearance values determined in adults."
First paragraph, second sentence revised (new text in italics) -
"Irreversible myocardial toxicity, manifested in its most severe form by life-threatening ["and potentially" deleted] or fatal congestive heart failure may occur either during therapy or months to years after termination of therapy."
Second paragraph, first sentence revised (new text in italics) -
"Cardiotoxicity may occur at lower doses in patients with prior mediastinal irradiation, concurrent cyclophosphamide therapy, exposure at an early age, and advanced age."
Monitoring Cardiac Function: Fifth paragraph, text added as last sentence -
"Pediatric patients receiving concomitant doxorubicin and actinomycin-D have manifested acute 'recall' pneumonitis at variable times after local radiation therapy."
"Pediatric patients treated with doxorubicin or other topoisomerase II inhibitors are at a risk for developing acute myelogenous leukemia and other neoplasms. The extent of increased risk associated with doxorubicin has not been precisely quantified."
Pediatric Use (new subsection):
"Pediatric patients are at increased risk for developing delayed cardiotoxicity. Follow-up cardiac evaluations are recommended periodically to monitor for this delayed cardiotoxicity (see WARNINGS).
"Doxorubicin, as a component of intensive chemotherapy regimens administered to pediatric patients, may contribute to prepubertal growth failure. It may also contribute to gonadal impairment, which is usually temporary."
"Pediatric patients are also at risk of developing secondary acute myeloid leukemia."
"Caregivers of pediatric patients receiving doxorubicin should be counseled to take precautions (such as wearing latex gloves) to prevent contact with the patient's urine and other body fluids for at least 5 days after each treatment."
"A clinical study using 15 ml of 2% epidural mepivacaine at the T 9-10 interspace in 62 patients, 20-79 years of age, demonstrated a 40% decrease in the amount of mepivacaine required to block a given number of dermatomes in the elderly (60-79 years, N=13) as compared to young adults 20-39 years).
"Another study using 10 ml of 2% lumbar epidural mepivacaine in 161 patients, 19-75 years of age, demonstrated a strong inverse relationship between patient age and the number of dermatomes blocked per cc of mepivacaine injected."
"Mepivacaine and mepivacaine metabolites are known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal functions."
"Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of ["antiretroviral" deleted] nucleoside analogues alone or in combination, including lamivudine, zidovudine, and other antiretrovirals (see WARNINGS)."
"Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of ["antiretroviral" deleted] nucleoside analogues alone or in combination, including lamivudine, zidovudine, and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering Combivir to any patient [", and particularly to those" deleted] with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with Combivir should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations)."
"In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of Epivir and/or Retrovir. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Epivir and/or Retrovir. ["or a combination of these factors." deleted]
"Endocrine and Metabolic: Hyperglycemia.
General: Sensitization reactions (including anaphylaxis), vasculitis.
Hepatobiliary Tract and Pancreas: Lactic acidosis and hepatic steatosis
(see WARNINGS), pancreatitis.
Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis.
Nervous: Seizures.
Skin: Alopecia, erythema multiforme, Stevens-Johnson syndrome, urticaria."
"Do not use if powder does not completely dissolve or gives a colored solution."
"["Gently dry the area of application with cotton gauze. Remove the clear protective liner and apply the patch." deleted] Isolate the procedure area with cotton rolls and use suction as appropriate. Dry the tissue with air or gauze. Remove the DentiPatch system from its packaging and peel off the clear protective liner. Immediately apply the DentiPatch system using firm pressure. Allow the patch to remain in place until the desired anesthetic effect is produced but not for longer than 15 minutes. ["The lowest dosage that results in effective anesthesia should be used." deleted] Experience in children is inadequate to recommend a pediatric dose at this time."
"Clinical studies of Endrate did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
"This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function."
In addition, the following March 8th changes are noted -
"Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of ["antiretroviral" deleted] nucleoside analogues alone or in combination, including lamivudine, other antiretrovirals (see WARNINGS)."
"Lamivudine is a synthetic nucleoside analogue. ["In vitro studies have shown that," deleted] Intracellularly, lamivudine is phosphorylated to its active 5'-triphosphate metabolite, lamivudine triphosphate (L-TP)["which has an intracellular half-life of 10.5 to 15.5 hours" deleted]. The principal mode of action of L-TP is inhibition of ["HIV" deleted] reverse ["transcription" deleted] transcriptase (RT) via viral DNA chain termination after incorporation of the nucleoside analogue. ["L-TP also inhibits the RNA- and DNA- dependent DNA polymerase activities of reverse transcriptase (RT)." deleted] L-TP is a weak inhibitor of mammalian DNA polymerases alpha and beta, and mitochondrial DNA polymerase ["alpha, beta, and gamma DNA polymerases" deleted]."
"Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of ["antiretroviral" deleted] nucleoside analogues alone or in combination, including lamivudine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering Epivir to any patient [", and particularly to those" deleted] with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with Epivir should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
"The complete prescribing information for Retrovir should be consulted before combination therapy with Epivir and Retrovir is initiated."
"A study in which lactating rats were administered 45 mg/kg of lamivudine showed that lamivudine concentrations in milk were slightly greater than those in plasma. Although it is not known if lamivudine is excreted in human milk, there is the potential for adverse effects from lamivudine in nursing infants. ["Mothers should be instructed to discontinue nursing if they are receiving lamivudine." deleted] Mothers should be instructed not to breastfeed if they are receiving Epivir."
"In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of Epivir ["in clinical practice" deleted]. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to ["either" deleted] a combination of their seriousness, frequency of reporting, or potential causal connection to Epivir ["or a combination of these factors" deleted].
"Endocrine and Metabolic: Hyperglycemia.
General: Anaphylaxis, weakness.
Hepatobiliary Tract and Pancreas: Lactic acidosis and hepatic steatosis
(see WARNINGS).
Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis.
Nervous: Peripheral neuropathy.
Skin: Alopecia, rash, pruritus, urticaria."
4. Hypocalcemia: ["Reports of clinically relevant hypocalcemia are rare, but" deleted] Serum calcium levels should be monitored in patients at risk of hypocalcemia, such as those with nephrotic syndrome or patients receiving multiple doses of Ethyol. If necessary, calcium supplements can be administered."
"The safety and effectiveness in pediatric patients have not been established."
"In clinical trials, the maximum single dose of Ethyol was 1300 mg/m2. No information is available on single doses higher than this in adults. In the setting of a clinical trial, children have received single Ethyol doses up to 2700 mg/m2 ["with no unexpected effects. Multiple infusions (up to three) of 740-910 mg/m2 doses of Ethyol have been administered within a 24-hour period under study conditions without unexpected effects." deleted] At the higher doses, anxiety and reversible urinary retention occurred. Administration of Ethyol at 2 and 4 hours after the initial dose has not led to ["increased or cumulative side effects, such as" deleted] increased nausea and vomiting or hypotension. The most likely symptom of overdosage is hypotension, which should be managed by infusion of normal saline and other supportive measures, as clinically indicated."
"Esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophageal erosions, occasionally with bleeding and rarely followed by esophageal stricture, have been reported in patients receiving treatment with Fosamax."
"esophagitis, esophageal erosions, esophageal ulcers, rarely esophageal stricture, and oropharyngeal ulceration. Rarely, gastric or duodenal ulcers, some severe and with complications have been reported (see WARNINGS, PRECAUTIONS, General and Information for Patients and DOSAGE AND ADMINISTRATION)."
Skin (new subsection): "rash (occasionally with photosensitivity)."
"This may occur especially if patients do not drink a full glass of water with Fosamax and/or if they lie down in less than 30 minutes ["and" deleted] or before their first food of the day.
Third paragraph, second sentence revised (new text in italics) -
"Rarely, a rash (occasionally made worse by sunlight) has occurred."
"Extremely rare allergic reactions including anaphylaxis and anaphylactic shock have been reported."
"The following patient complaints have been reported and are listed in decreasing order of frequency with the exception of hypersensitivity reactions which is listed first since it may be the most serious.
deleted and replaced with -
"The following adverse events have been reported: hypersensitivity reactions such as skin rash and urticaria, and extremely rare cases of anaphylactic shock and bullous eruption including Toxic Epidermal Necrolysis. In the majority of these cases, the patients were on other medications which may have caused or contributed to the events.
"The following patient complaints have also been reported: abdominal pain, distension or discomfort, nausea, vomiting, constipation, tiredness, drowsiness or dizziness and dry mouth."
Last paragraph revised -
"["In postmarketing experiences," deleted] There have been rare reports of paralytic ileus associated with abdominal distension. Most of these reports occurred in the setting of acute dysentery, overdose, and with very young children of less than two years of age."
In addition, the following changes are noted:
"In a pooled analysis of all Lescol (fluvastatin sodium) placebo-controlled studies persistent transaminase elevations (greater than 3 times the upper limit of normal [ULN] on two consecutive weekly measurements) occurred in 0.2%, 1.5%, and 2.7% of patients treated with 20, 40, and 80 mg (40 mg b.i.d.) Lescol (fluvastatin sodium), respectively. Ninety-one percent of the cases of persistent liver function test abnormalities (20 of 22 patients) occurred within 12 weeks of therapy and in all patients with persistent liver function test abnormalities there was an abnormal liver function test present at baseline or by week 8."
Third paragraph revised (new text in italics) -
"It is recommended that liver function tests be performed before ["the initiation of treatment, at 6 and 12 weeks after initiation of therapy or elevation in dose, and periodically thereafter (e.g., semiannually)." deleted] initiation of therapy and at 12 weeks following initiation of treatment or elevation in dose. ["Liver enzyme changes generally occur in the first 3 months of treatment with Lescol (fluvastatin sodium). Patients who develop increased transaminase levels should be monitored with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality(ies) return to normal." deleted] Patients who develop transaminase elevations or signs and symptoms of liver disease should be monitored to confirm the finding and should be followed thereafter with frequent liver function tests until the levels return to normal. Should an increase in AST or ALT of three times the upper limit of normal or greater persist (found on two consecutive occasions), withdrawal of fluvastatin sodium therapy is recommended."
"Clinical laboratory findings may include elevated levels of serum transaminase, alkaline phosphatase, and lactate dehydrogenase."
"Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, and heartburn have been reported in about 1 of 100 patients. Post-marketing experience reveals very rare reports of hepatitis, jaundice and non-specific hepatic dysfunction. Isolated cases of transaminase, alkaline phosphatase, and lactic acid dehydrogenase elevations have also been reported."
"In clinical studies, elderly patients exhibited a greater spread and higher maximal level of analgesia than younger patients. Elderly patients also reached the maximal level of analgesia more rapidly than younger patients, and exhibited a faster onset of motor blockade. The total plasma clearance was decreased and the terminal half-life was lengthened in these patients."
(For Marcaine HCl) Text added as new tenth paragraph -
"In clinical studies, elderly patients reached the maximal spread of analgesia and maximal motor blockade more rapidly than younger patients. Elderly patients also exhibited higher peak plasma concentrations following administration of this product. The total plasma clearance was decreased in these patients."
"Patients over 65 years, particularly those with hypertension, may be at increased risk for experiencing the hypotensive effects of Marcaine Spinal."
Geriatric Use (new subsection):
[Note: bracketed italicized words appear in Marcaine Spinal labeling only. Bracketed unitalicized words appear in Marcaine HCl labeling only]
"Patients over 65 years, particularly those with hypertension, may be at increased risk for developing hypotension while undergoing [spinal] anesthesia with Marcaine [Spinal]. (See [PRECAUTIONS, General and] ADVERSE REACTIONS [, Cardiovascular System].)
"Elderly patients may require lower doses of Marcaine [Spinal]. (See PRECAUTIONS, [Epidural Anesthesia] [General] and DOSAGE AND ADMINISTRATION.)
In clinical studies, differences in various pharmacokinetic parameters have been observed between elderly and younger patients. (See CLINICAL PHARMACOLOGY, [Pharmacokinetics].)
"This product is known to be substantially excreted by the kidney/s, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. (See CLINICAL PHARMACOLOGY [,Pharmacokinetics].)"
"Patients over 65 years, particularly those with hypertension, may be at increased risk for experiencing the hypotensive effects of Marcaine."
Cardiovascular System: (Marcaine Spinal only) Second sentence revised (new text in italics) -
"Hypotension due to loss of sympathetic tone is a commonly encountered extension of the clinical pharmacology of spinal anesthesia. This is more commonly observed in elderly patients, particularly those with hypertension, and patients with shrunken blood volume, shrunken interstitial fluid volume, cephalad spread of the local anesthetic, and/or mechanical obstruction of venous return."
"Dosages of Marcaine should be reduced for elderly and/or debilitated patients and patients with cardiac and/or liver disease."
In addition the following changes are noted -
"Concomitant therapy with the tetralol-class calcium channel blocker mibefradil (see WARNINGS, Skeletal Muscle and PRECAUTIONS, Drug Interactions)."
Subsection has been relocated ahead of the subsection Liver Dysfunction and has been extensively revised. Two subsections added: Myopathy caused by drug interactions and Reducing the risk of myopathy. Contact the company for a copy of the new labeling/package insert.
"Patients should be advised to report promptly unexplained muscle pain, tenderness or weakness [,"particularly if accompanied by malaise and fever" deleted] (see WARNINGS, Skeletal Muscle)."
Drug Interactions: Subsection revised ["Mibefradil (see Contraindications)" deleted.]
"[Immunosuppressive Drugs] deleted and replaced with 'Cyclosporine' "
Antipyrine: Text added at end of subsection -
"(see Warnings, Skeletal Muscle)"
"creatine phosphokinase" replaced by "creatine kinase" and "(CPK)" by "(CK)".
Concomitant Therapy: First paragraph, last sentence revised (new text in italics) -
"In uncontrolled clinical studies, most of the patients who have developed myopathy were receiving concomitant therapy with ["immunosuppressive drugs" deleted] cyclosporine, gemfibrozil or niacin (nicotinic acid)(see WARNINGS, Skeletal Muscle)."
"In patients taking ["immunosuppressive drugs" deleted] cyclosporine concomitantly with lovastatin (see WARNINGS, Skeletal Muscle), therapy should begin with 10 mg of Mevacor and should not exceed 20 mg/day."
Concomitant Therapy - Subsection deleted and replaced with -
"Concomitant Lipid-Lowering Therapy: Mevacor is effective alone or when used concomitantly with bile-acid sequestrants. Use of Mevacor with fibrates or niacin should generally be avoided. However, if Mevacor is used in combination with fibrates or niacin, the dose of Mevacor should not exceed 20 mg (see WARNINGS, Skeletal Muscle)."
"Hypersensitivity to any component of these products. Cross sensitivity in this class of compounds has been observed. Therefore, Pepcid should not be administered to patients with a history of hypersensitivity to other H2-receptor antagonists."
"Revia Tablets also contain: ["alginic acid, FD&C Yellow 6" deleted] lactose, microcrystalline cellulose, ["stearic acid and sugar" deleted], crospovidone, colloidal silicon dioxide, magnesium stearate, hydroxypropyl methylcellulose, titanium dioxide, polyethylene glycol, polysorbate 80, yellow iron oxide and red iron oxide."
"Naltrexone appears to have extra-hepatic sites of drug metabolism and its major metabolite undergoes active tubular secretion (see Metabolism above). Adequate studies of naltrexone in patients with severe hepatic or renal impairment have not been conducted (see PRECAUTIONS: Special Risk Patients)."
Note: "Opioid" substituted for "Narcotic" throughout.
" Any individual with a history of sensitivity to Revia ["(naltrexone hydrochloride)" deleted] or any other components of this product. It is not known if there is any cross-sensitivity with naloxone or the phenanthrene containing opioids."
"While Revia is a potent antagonist with a prolonged pharmacologic effect (24 to 72 hours), the blockade produced by Revia is surmountable. This is useful in patients who may require analgesia, but poses a potential risk to individuals who attempt, on their own, to overcome the blockade by administering large amounts of exogenous opioids. Indeed, any attempt by a patient to overcome the antagonism by taking opioids is very dangerous and may lead to a fatal overdose. Injury may arise because the plasma concentration of exogenous opioids attained immediately following their acute administration may be sufficient to overcome the competitive receptor blockade. As a consequence, the patient may be in immediate danger of suffering life endangering opioid intoxication (e.g., respiratory arrest, circulatory collapse). ["Also, lesser amounts of exogenous opioids may prove dangerous if they are taken in a manner (i.e., relatively long after the last dose of naltrexone) and in an amount so that they persist in the body longer than effective concentrations of naltrexone and its metabolites." deleted] Patients should be told of the serious consequences of trying to overcome the opiate blockade (see Information for Patients ["section" deleted]).
"There is also the possibility that a patient who had been treated with naltrexone will respond to lower doses of opioids than previously used, particularly if taken in such a manner that high plasma concentrations remain in the body beyond the time that naltrexone exerts its therapeutic effects. This could result in potentially life-threatening opioid intoxication (respiratory compromise or arrest, circulatory collapse, etc.). Patients should be aware that they may be more sensitive to lower doses of opioids after naltrexone treatment is discontinued"
Ultra Rapid Opioid Withdrawal (new subsection):
"Safe use of Revia in rapid opiate detoxification programs has not been established (see ADVERSE REACTIONS)."
"Severe opioid withdrawal syndromes precipitated by the accidental ingestion of Revia have been reported in opioid-dependent individuals. Symptoms of withdrawal have usually appeared within five minutes of ingestion of Revia and have lasted for up to 48 hours. Mental status changes including confusion, somnolence and visual hallucinations have occurred. Significant fluid losses from vomiting and diarrhea have required intravenous fluid administration. In all cases patients were closely monitored and therapy with non-opioid medications was tailored to meet individual requirements.
"Use of Revia does not eliminate or diminish withdrawal symptoms. If Revia is initiated early in the abstinence process, it will not preclude the patient's experience of the full range of signs and symptoms that would be experienced if Revia had not been started. Numerous adverse events are known to be associated with withdrawal."
Special Risk Patients: Renal Impairment (new subsection): "Revia and its primary metabolite are excreted primarily in the urine, and caution is recommended in administering the drug to patients with renal impairment."
Hepatic Impairment (new subsection): "Cautions should be exercised when naltrexone hydrochloride is administered to patients with liver disease. An increase in naltrexone AUC of approximately 5- and 10-fold in patients with compensated and decompensated liver cirrhosis, respectively, compared with subjects with normal liver function has been reported. These data also suggest that alterations in naltrexone bioavailability are related to liver disease severity."
Information for Patients: Second to last paragraph revised (new text in italics) -
"You should take Revia as directed by your physician. If you attempt to self-administer heroin or any other opiate drug, in small doses while on Revia, you will not perceive any effect. Most important, however, if you attempt to self-administer large doses of heroin or any other opioid while on Revia, you may die or sustain serious injury, including coma. Carcinogenesis, Mutagenesis and Impairment of Fertility: Existing text deleted and replaced with new text -
See new labeling/package insert.
Pregnancy: Category C: Existing text deleted and replaced with new text -
See new labeling/package insert.
Pediatric Use: Subsection revised (new text in italics) -
"The safe use of Revia in ["subjects" deleted] pediatric patients younger than 18 years old has not been established."
"In an open label safety study with approximately 570 individuals with alcoholism receiving REVIA, the following new-onset adverse reactions occurred in 2% or more of the patients: nausea (10%), headache (7%), dizziness (4%), nervousness (4%), fatigue (4%), insomnia (3%), vomiting (3%), anxiety (2%) and somnolence (2%).
"Depression ["(5-7%)" deleted], suicidal ideation ["(2%)" deleted], and ["attempted suicide (< 1%)" deleted] suicidal attempts have been reported in ["individuals on Revia, placebo and concurrent control groups" deleted] all groups when comparing naltrexone, placebo, or controls undergoing treatment for alcoholism.
"RATE RANGES OF NEW ONSET EVENTS
|
Naltrexone |
Placebo |
|
|
Depression |
0-15% |
0-17% |
|
Suicide Attempt/Ideation |
0-1% |
0-3% |
"Although no causal relationship with REVIA is suspected, physicians should be aware that treatment with Revia does not reduce the risk of suicide in these patients (see PRECAUTIONS)."
Opioid Addiction (Subsection formerly titled "Narcotic Addiction"): Post-marketing Experience (new subsection incorporating former "Other" subsection): New text in italics) -
"Data collected from post-marketing use of REVIA show that most events usually occur early in the course of drug therapy and are transient. It is not always possible to distinguish these occurrences from those signs and symptoms that may result from a withdrawal syndrome. Events that have been reported include anorexia, asthenia, chest pain, fatigue, headache, hot flushes, malaise, changes in blood pressure, agitation, dizziness, hyperkinesia, nausea, vomiting, tremor, abdominal pain, diarrhea, elevations in liver enzymes or bilirubin, hepatic function abnormalities or hepatitis, palpitations, myalgia, anxiety, confusion, euphoria, hallucinations, insomnia, nervousness, somnolence, abnormal thinking, dyspnea, rash, increased sweating, and vision abnormalities.
"Depression, suicide, attempted suicide and suicidal ideation have been reported in the post-marketing experience with Revia (naltrexone hydrochloride) used in the treatment of ["narcotic" deleted] opioid dependence. No causal relationship has been demonstrated. In the literature, endogenous opioids have been theorized to contribute to a variety of conditions. In some individuals the use of opioid antagonists has been associated with a change in baseline levels of some hypothalamic, pituitary, adrenal or gonadal hormones. The clinical significance of such changes is not fully understood.
"Adverse events, including withdrawal symptoms and death, have been reported with the use of Revia (naltrexone hydrochloride) in ultra rapid opiate detoxification programs. The cause of death in these cases is not known. (see WARNINGS)."
"In the mouse, rat and guinea pig, the oral LD50s were 1,100-1,550 ["+/-96" deleted] mg/kg; 1,450 ["+/- 265" deleted] mg/kg; and 1,490 ["+/-102" deleted] mg/kg, respectively. High doses of Revia (generally >/= 1,000 mg/kg) produced salivation, depression/reduced activity, trmors, and convulsions. ["In acute toxicity studies in the mouse, rat, and dog, cause of death was" deleted] Mortalities in animals due to high-dose Revia administration usually were due to clonic-tonic convulsions and/or respiratory failure."
"A dose of 50 mg once daily is recommended for most patients (see Individualization of Dosage). The placebo-controlled studies that demonstrated the efficacy of Revia as an adjunctive treatment of alcoholism used a dose regimen of Revia 50 mg once daily for up to 12 weeks. Other dose regimens or durations of therapy were not evaluated in these trials.
"A patient is a candidate for treatment with Revia if:
NARCAN Challenge Test: Intravenous: Existing text deleted and replaced with -
"Inject 0.2 mg Narcan.
Observe for 30 seconds for signs or symptoms of withdrawal.
If no evidence of withdrawal, inject 0.6 mg of Narcan.
Observe for an additional 20 minutes."
Subcutaneous: Existing text deleted and replaced with -
"Administer 0.8 mg Narcan.
Observe for 20 minutes for signs or symptoms of withdrawal.
"Note: Individual patients, especially those with opioid dependence, may respond to lower doses of Narcan. In some cases, 0.1 mg IV Narcan has produced a diagnostic response."
Withdrawal Signs: Subsection deleted.
Withdrawal Symptoms: Subsection deleted.
Interpretation of the Challenge: Existing text deleted and replaced with -
"Monitor vital signs and observe the patient for signs and symptoms of opioid withdrawal. These may include, but are not limited to: nausea, vomiting, dysphoria, yawning, sweating, tearing, rhinorhea, stuffy nose, craving for opioids, poor appetite, abdominal cramps, sense of fear, skin erythema, disrupted sleep patterns, fidgeting, uneasiness, poor ability to focus, mental lapses, muscle aches or cramps, pupillary dilation, piloerection, fever, changes in blood pressure, pulse or temperature, anxiety, depression, irritability, back ache, bone or joint pains, tremors, sensations of skin crawling or fasciculations. If signs or symptoms of withdrawal appear, the test is positive and no additional NARCAN should be administered.
"Warning: If the test is positive, do NOT initiate REVIA therapy. Repeat the challenge in 24 hours. If the test is negative, REVIA therapy may be started if no other contraindications are present. If there is any doubt about the result of the test, hold REVIA and repeat the challenge in 24 hours."
"Store at 25oC, with brief excursions permitted between 15oC and 30o (59oC - 86oF), controlled room temperature, see USP."
"Before reconstituting a vial, it should be inspected for cracks and/or a melted plug or any other indication that the integrity of the vacuum seal has been lost."
"Anaphylactic or anaphylactoid reactions are possible when Trasylol is administered. Hypersensitivity reactions are rare in patients with no prior exposure to aprotinin. The risk of anaphylaxis is increased in patients who are re-exposed to ["Trasylol" deleted] aprotinin-containing products. The benefit of Trasylol to patients undergoing primary CABG surgery should be weighed against the risk of anaphylaxis should a second exposure to aprotinin be required. (See WARNINGS and PRECAUTIONS)."
"Before initiating treatment with Trasylol in a patient with a history of prior exposure to aprotinin or products containing aprotinin, the recommendations below should be followed to manage a potential hypersensitivity or anaphylactic reaction: 1) Have standard emergency treatments for hypersensitivity or anaphylactic reactions readily available in the operating room (e.g., epinephrine, corticosteroids). 2) Administration of the test dose and loading dose should be done only when the conditions for rapid cannulation (if necessary) are present. 3) Delay the addition of Trasylol into the pump prime solution until after the loading dose has been safely administered. Additionally, administration of H1 and H2 blockers 15 minutes before the test dose may be considered."
"It should be noted that hypersensitivity/anaphylactic reactions can also occur in connection with application of the test-dose. (see WARNINGS)."
"Cases of acute renal failure resulting in dialysis and/or contributing to death have occurred with as few as one or two doses of Vistide."
Resistance: Text added as new third paragraph-
"The possibility of viral resistance should be considered for patients who show a poor clinical response or experience recurrent retinitis progression during therapy."
Existing text -
"Cidofovir pharmacokinetics have not been investigated in patients with renal insufficiency. No data are currently available on the pharmacokinetics of cidofovir in patients not requiring dialysis who have creatinine clearance values below 55 mL/min. The effect of dialysis on cidofovir pharmacokinetics is not known."
deleted and replaced with -
"Pharmacokinetic data collected from subjects with creatinine clearance values as low as 11 mL/min indicate that cidofovir clearance decreases proportionally with creatinine clearance.
"High flux hemodialysis has been shown to reduce the serum levels of cidofovir by approximately 75%.
"Initiation of therapy with Vistide is contraindicated in patients with serum creatinine > 1.5 mg/dL, a calculated creatinine clearance < or = to 55 mL/min, or urine protein > or = to 100 mg/dL (equivalent to > or = to 2+ proteinuria) (See CONTRAINDICATIONS)."
"Cases of acute renal failure resulting in dialysis and/or contributing to death have occurred with as few as one or two doses of Vistide."
Decreased Intraocular Pressure/Ocular Hypotony (new subsection):
"Decreased intraocular pressure may occur during Vistide therapy, and in some instances has been associated with decreased visual acuity. Intraocular pressure should be monitored during Vistide therapy."
Metabolic Acidosis: Existing text -
"Fanconi's syndrome and decreases in serum bicarbonate associated with evidence of renal tubular damage have been reported in patients receiving Vistide (see ADVERSE EVENTS). Serious metabolic acidosis, in association with liver failure, pancreatitis, mucormycosis, aspegillus, disseminated mycobacterial infection, and progression to death occurred in 1 patient (< 1%) receiving Vistide."
deleted and replaced with -
"Decreased serum bicarbonate associated with proximal tubule injury and renal wasting syndrome (including Fanconi's syndrome) has been reported in patients receiving Vistide (see ADVERSE REACTIONS). Cases of metabolic acidosis in association with liver dysfunction and pancreatitis resulting in death have been reported in patients receiving Vistide."
"Uveitis or iritis was reported in clinical trials and during postmarketing in patients receiving Vistide therapy. Treatment with topical corticosteroids with or without topical cycloplegic agents should be considered. Patients should be monitored for signs and symptoms of uveitis/iritis during Vistide therapy."
Drug Interactions: Probenecid: Text added at end of subsection-
"Zidovudine should either be temporarily discontinued or decreased by 50% when coadministered with probenecid on the day of Vistide infusion."
"The following events have been identified during post-marketing use of Xalatan in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The events, which have been chosen for inclusion due to their seriousness, frequency of reporting, possible causal connection to Xalatan, or a combination of these factors, include: eyelash changes (increased length, thickness, pigmentation, and number of lashes); eyelid skin darkening; intraocular inflammation (iritis/uveitis); macular edema, including cystoid macular edema, ["and" deleted] toxic epidermal necrolysis ,asthma, exacerbation of asthma, and dyspnea."
"There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration."
Text added as new last paragraph [5% with Glucose 7.5% Injection Only] -
"Transient pain, developing in the buttocks and radiating to the lateral thighs and calves, may be seen after spinal administration of Xylocaine 5% with Dextrose. Complete resolution of symptoms usually takes place within 3 days but may persist for up to 2 months."
Last two paragraphs revised (new text in italics) -
"The study populations in Table 6 consisted mainly of females undergoing laparoscopic procedures. ["The study populations in all trials thus far consisted mainly of women undergoing laparoscopic procedures. While some men were included in some trials with similar results, clearance of the drug is more rapid in men and sufficient numbers of men have not been clinically studied to be certain that efficacy and safety have been established. Few patients undergoing major abdominal surgery have been studied." deleted]
"In a placebo-controlled study conducted in 468 males undergoing outpatient procedures, a single 4 mg IV ondansetron dose prevented postoperative vomiting over a 24-hour study period in 79% of males receiving drug compared to 63% of males receiving placebo (P <0.001).
"Two other placebo-controlled studies were conducted in 2792 patients undergoing major abdominal or gynecological surgeries to evaluate a single 4 mg or 8 mg IV ondansetron dose for prevention of postoperative nausea and vomiting over a 24-hour study period. At the 4 mg dosage, 59% of patients receiving ondansetron versus 45% receiving placebo in the first study (P<0.001) and 41% of patients receiving ondansetron versus 30% receiving placebo in the second study (P <0.001) experienced no emetic episodes. No additional benefit was observed in patients who received IV ondansetron 8 mg compared to patients who received IV ondansetron 4 mg."
Pediatric Studies: Title of Table 7 revised (new text in italics) -
"Prevention of Postoperative Nausea and Vomiting in Pediatric Patients.
Prevention of Further Postoperative Nausea and Vomiting: Title of Table 8 revised (new text in italics) -
"Prevention of Further Postoperative Nausea and Vomiting in Adult Patients"
Last two paragraphs revised (revised text in italics) -
"The study populations in Table 8 ["all trials thus far" deleted] consisted ["of" deleted] mainly of women undergoing laparoscopic procedures. ["While some men were included in some trials with similar results, clearance of the drug is more rapid in men and sufficient numbers of men have not been clinically studied to be certain that efficacy and safety have been established. Few patients undergoing major abdominal surgery have been studied. deleted]"
Pediatric Studies: Title of Table 9 revised (new text in italics)
"Prevention of Further Postoperative Nausea and Vomiting in Pediatric Patients"
Repeat Dosing in Adults (new subsection):
"In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, IV dose of ondansetron 4 mg, administration of a second IV dose of ondansetron 4 mg postoperatively does not provide additional control of nausea and vomiting."
For patients who do not receive prophylactic Zofran injection and experience ["have" deleted] nausea and/or vomiting postoperatively, Zofran injection may be given to prevent futher episodes (see CLINICAL TRIALS).
"While recommended as a fixed dose for patients weighing more than 40 kg, few patients above 80 kg have been studied. In patients who do not acheive adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, IV dose of ondansetron 4 mg, administration of a second IV dose of 4 mg postoperatively does not provide additional control of nausea and vomiting."
"Health care providers are encouraged to register patients by calling ["(800)722-9292" deleted] (888)825-5249, ext. 39441."
"Also observed["was" deleted] were hyperglycemia, hypoglycemia, and syndrome of inappropriate antidiuretic hormone."
Hemic and Lymphatic: Subsection revised (new text in italics) -
"Infrequent was ecchymosis. Also observed were anemia, leukocytosis, leukopenia, lymphadenopathy, ["and" deleted] pancytopenia and thrombocytopenia."
Musculoskeletal: Subsection revised (new text in italics) -
"Infrequent were leg cramps and twitching. Also observed were arthritis and muscle rigidity/fever/rhabdomyolysis, and muscle weakness."
Skin: Subsection revised (new text in italics) -
"Frequent was sweating. Infrequent was acne and dry skin. Rare was maculopapular rash. Also observed were alopecia,angioedema, exfoliative dermatitis, and hirsutism."
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