![[U.S. Food and Drug Administration]](https://webarchive.library.unt.edu/eot2008/20081028113846im_/http://www.fda.gov/icon/header.gif){kind=icon}
(Posted: 7/19/99)
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.
|
(cefpodoxime proxetil) |
(ibutilide fumarate) |
(pemoline) |
(cyclophosphamide) |
|
(norethindrone acetate/ ethinyl estradiol) |
(fludarabine phosphate) |
(isoflurane) |
(etodolac) |
|
(isoproterenol HCl) |
(lomefloxacin HCl) |
(cisatracurium besylate) |
(ritonavir) |
|
(paroxetine HCl) |
& PLATINOL-AQ (cisplatin) |
(fluoxetine HCl) |
(carbidopa/ levodopa) |
|
(butorphanol tartrate) |
(diethylpropion HCl) |
(nelfinavir mesylate) |
(streptozocin) |
"Gently tap the bottle to loosen powder. Add 25 mL distilled water and shake vigorously for 15 seconds to wet powder. Add 32 mL distilled water and shake vigorously for 3 minutes or until all particles are suspended."
deleted and replaced with -
"Shake bottle to loosen powder. Add approximately 1/2 the total amount of distilled water required for constitution (total water=57 mL). Shake vigorously to wet powder. Add remaining water and shake vigorously."
"In a double-blind, parallel group study, 302 patients with atrial fibrillation (n=201) or atrial flutter (n=101) that occurred 1 to 7 days after coronary artery bypass graft or valvular surgery and lasted 1 hour to 3 days were randomized to receive two 10-minute infusions of placebo, or 0.25, 0.5 or 1 mg of ibutilide fumarate. Among patients with atrial flutter, conversion rates at 1.5 hours were: placebo, 4%; 0.25 mg ibutilide fumarate, 56%; 0.5 mg ibutilide, 61%; and 1 mg ibutilide fumarate, 78%. Among patients with atrial fibrillation, conversion rates at 1.5 hours were: placebo, 20%; 0.25 mg ibutilide fumarate, 28%; 0.5 mg ibutilide fumarate, 42%, and 1 mg ibutilide fumarate, 44%. The majority of patients (53% and 72% in the 0.5-mg and 1-mg dose groups, respectively) converted to sinus rhythm remained in sinus rhythm for 24 hours. Patients were not given other antiarrhythmic drugs within 24 hours of ibutilide fumarate infusion in this study."
"In the post-cardiac surgery study (see CLINICAL STUDIES), similar types of medical events were reported. In the 1 mg ibutilide fumarate treatment group (N=70), 2 patients (2.9%) developed sustained polymorphic ventricular tachycardia and 2 other patients (2.9%) developed nonsustained polymorphic ventricular tachycardia. Polymorphic ventricular tachycardia was not reported in the 73 patients in the 0.5 mg dose group or in the 75 patients in the 0.25 mg dose group."
"In the post-cardiac surgery study (see CLINICAL STUDIES), one or two intravenous infusions of 0.5 mg (0.005 mg/kg per dose for patients less than 60 kg) was effective in terminating atrial fibrillation or atrial flutter."
"Cylert should not be used by patients until there has been a complete discussion of the risks and benefits of Cylert therapy and written informed consent has been obtained (see PATIENT INFORMATION/CONSENT FORM). A supply of Patient Information/Consent Forms as printed at the end of this insert is available, free of charge, by calling (847) 937-7302. Permission to use the Patient Information/Consent Form by photocopy reproduction is hereby granted by Abbott Laboratories."
Boxed Warning previously located in WARNING section moved here and revised (new text in italics) -
"Because of its association with life threatening hepatic failure, Cylert should not ordinarily be considered as first line drug therapy for ADHD (see INDICATIONS AND USAGE). Because Cylert provides an observable symptomatic benefit, patients who fail to show substantial clinical benefit within 3 weeks of completing dose titration, should be withdrawn from Cylert therapy.
"Since Cylert's marketing in 1975, ["13" deleted] 15 cases of acute hepatic failure have been reported to the FDA. While the absolute number of reported cases is not large, the rate of reporting ranges from 4 to 17 times the rate expected in the general population. This estimate may be conservative because of under reporting and because the long latency between initiation of Cylert treatment and the occurrence of hepatic failure may limit recognition of the association. If only a portion of actual cases were recognized and reported, the risk could be substantially higher.
"Of the ["13" deleted] 15 cases reported as of ["May 1996" deleted] December 1999, ["11" deleted] 12 resulted in death or liver transplantation, usually within four weeks of the onset of signs and symptoms of liver failure. The earliest onset of hepatic abnormalities occurred six months after initiation of Cylert. Although some reports described dark urine and nonspecific prodromal symptoms (e.g., anorexia, malaise, and gastrointestinal symptoms), in other reports it was not clear if any prodromal symptoms preceded the onset of jaundice.
"Treatment with Cylert should be initiated only in individuals without liver disease and with normal baseline liver function tests. It is ["also" deleted] not clear if ["the recommended" deleted] baseline and periodic liver function testing are predictive of these instances of acute liver failure; however, it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery. Accordingly, the following liver monitoring program is recommended: Serum ALT (SGPT) levels should be determined at baseline, and every two weeks thereafter. If Cylert therapy is discontinued and then restarted, liver function test monitoring should be done at baseline and reinitiated at the frequency above.
"Cylert should be discontinued if ["clinically significant hepatic dysfunction is observed during its use" deleted] serum ALT (SGPT) is increased to a clinically significant level, or any increase greater than or equal to 2 times the upper limit of normal, or if clinical signs and symptoms suggest liver failure (see PRECAUTIONS).
"The physician who elects to use Cylert should obtain written informed consent from the patient prior to initiation of Cylert therapy (see PATIENT INFORMATION/CONSENT FORM)."
"Patients should be informed that Cylert therapy has been associated with liver abnormalities ranging from reversible liver function test increases that do not cause any symptoms to liver failure, which may result in death. Patients should be informed that the risk of liver failure in the general population is relatively rare; however patients taking Cylert are at a greater risk of developing liver failure than that expected in the general population. At present, there is no way to predict who is likely to develop liver failure; however only patients without liver disease and with normal baseline liver function tests should initiate Cylert therapy. Patients should be advised to follow their doctors directives for liver function tests prior to and during Cylert therapy. Patients should be advised to be alert for signs of liver dysfunction (jaundice, anorexia, gastrointestinal complaints, malaise, etc.) and to report them to their doctor immediately if they should occur.
"The physician who elects to use Cylert should obtain written informed consent from patients prior to initiation of Cylert therapy (see PATIENT INFORMATION/CONSENT FORM)."
Laboratory Test: Subsection revised (new text in italics) -
"Since Cylert's market introduction, there have been reports of elevated liver enzymes associated with its use. Many of these patients had this increase detected several months after starting Cylert. Most patients were asymptomatic, with the increase in liver enzymes returning to normal after Cylert was discontinued. ["Liver function tests should be performed prior to and periodically during therapy with Cylert. Treatment with Cylert should be initiated only in individuals without liver disease and with normal baseline liver function tests." deleted]
"["The relationship, if any, between reversible elevations in liver function tests and the occurrence of life threatening hepatic failure in patients on long-term therapy with Cylert is not known. Liver function testing may not predict the onset of acute liver failure. Nonetheless, Cylert should be discontinued if clinically significant liver function test abnormalities are revealed at any time during therapy with this drug (see WARNINGS)." deleted]
"Treatment with Cylert should be initiated only in individuals without liver disease and with normal baseline liver function tests. It is not clear if baseline and periodic liver function testing are predictive of these instances of acute liver failure; however it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery. Accordingly, the following liver monitoring program is recommended.
"Serum ALT (SGPT) levels should be determined at baseline, and every two weeks thereafter. If Cylert therapy is discontinued and then restarted, liver function test monitoring should be done at baseline and reinitiated at the frequency above. Cylert should be discontinued if serum ALT (SGPT) is increased to a clinically significant level, or any increase greater than or equal to 2 times the upper limit of normal, or if clinical signs and symptoms suggest liver failure (see WARNINGS)."
"There have been reports of hepatic dysfunction, ranging from asymptomatic reversible increase in liver enzymes to hepatitis, jaundice and ["life-threatening" deleted] fatal hepatic failure, in patients taking Cylert (see BOXED WARNING and PRECAUTIONS ["and WARNINGS" deleted])."
Miscellaneous: Second to last sentence deleted-
"Mild adverse reactions appearing early during the course of treatment with Cylert often remit with continuing therapy."
"Clinical improvement with Cylert is gradual. Using the recommended schedule of dosage titration, significant benefit may not be evident until the third or fourth week of drug administration. Because Cylert provides an observable symptomatic benefit, patients who fail to show substantial clinical benefit within 3 weeks of completing dose titration, should be withdrawn from Cylert therapy."
Revised and replaced with -
"Anaphylactic reactions have been reported; death has also been reported in association with this event. Possible cross-sensitivity with other alkylating agents has been reported.
"Interstitial pneumonitis has been reported as part of the postmarketing experience."
Other: Subsection revised (new text in italics) -
"["Rare instances of anaphylactic reaction including one death have been reported." deleted] Anaphylactic reactions have been reported; death has also been reported in association with this event. ["One instance of (p)ossible" deleted] Possible cross-sensitivity with other alkylating agents has been reported. SIADH (syndrome of inappropriate ADH secretion) has been reported with the use of cyclophosphamide. Malaise and asthenia have been reported as part of the postmarketing experience.
"Transfusion-associated graft-versus-host disease has been observed rarely after transfusion of non-irradiated blood in Fludara for Injection treated patients. Consideration should, therefore, be given to the use of irradiated blood products in those patients requiring transfusions while undergoing treatment with Fludara for Injection."
"Fludarabine phosphate has been shown to be non-mutagenic to several strains of Salmonella typhimurium, including TA-98, TA-100, TA-1535 and TA-1537. In addition, fludarabine phosphate was non-mutagenic to Chinese hamster ovary (CHO) cells at the hypoxanthine-guaninephosphoribosyltransferase (HGPRT) locus under both activated and non-activated metabolic conditions. Chromosomal aberrations were observed in an in vitro assay using CHO cells under metabolically activated conditions. Fludarabine phosphate was determined to cause increased sister chromatid exchanges using an in vitro sister chromatid exchange (SCE) assay under both metabolically activated and non-activated conditions. In addition, fludarabine phosphate has also been shown to be mutagenic as indicated by an increase in the number of micronucleated erythrocytes in the in vivo mouse micronucleus test at doses up to 1000 mg/kg."
"See PRECAUTIONS for information regarding malignant hyperthermia and elevated carboxyhemoglobin levels."
"Safety and efficacy of isoproterenol in pediatric patients has not been established.
"Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05-2.7 ug/kg/min have caused clinical deterioration, myocardial necrosis, congestive heart failure and death. The risks of cardiac toxicity appear to be increased by some factors [acidosis, hypoxemia, coadministration of corticosteroids, coadministration of methylxanthines (theophylline, theobromine) or aminophylline] that are especially likely to be present in these patients. If I.V. isoproterenol is used in children with refractory asthma, patient monitoring must include continuous assessment of vital signs, frequent electrocardiography, and daily measurements of cardiac enzymes, including CPK-MB. "
"Risk of phototoxicity may be reduced by taking lomefloxacin in the evening (See Dosage and Administration)"
Fourth paragraph, first two sentences revised (new text in italics) -
"The safety and efficacy of lomefloxacin in pediatric patinets and adolesscents (under the age of 18 years), pregnant women, and lactating women have not been established. (See PRECAUTIONS: Pediatric Use, Pregnancy and Nursing Mothers subsections.)
Former seventh paragraph moved up to become the fifth paragraph and revised (new text in italics) -
"Convulsions have been reported in patients receiving lomefloxacin. Whether the convulsions were directly related to lomefloxacin administration has not yet been established. However, convulsions, increased intracranial pressure, and toxic psychoses have been reported in patients receiving other quinolones. Nevertheless, lomefloxacin has been associated with a possible increased risk of seizures compared to other quinolones. Some of these may occur with a relative absence of predisposing factors. Quinolones may also cause central nervous system (CNS) stimulation, which may lead to tremors, restlessness, lightheadedness, confusion, and hallucinations. If any of these reactions occurs in patients receiving lomefloxacin, the drug should be discontinued and appropriate measures instituted. ["No evidence of an effect of lomefloxacin on the electrical activity of the brain has been demonstrated. Lomefloxacin does not alter cerebral blood flow or cerebral glucose uptake in the CNS based on positron emission tomography." deleted] However, until more information becomes available, lomefloxacin, like all other quinolones, should be used with caution in patients with known or suspected CNS disorders, such as severe cerebral arteriosclerosis, epilepsy, or other factors that predispose to seizures. (See Adverse Reactions.) Psychiatric disturbances, agitation, anxiety, and sleep disorders may be more common with lomefloxacin than other products in the quinolone class.
* "that sucralfate ["or" deleted] and antacids containing magnesium or aluminum , or Videx, (didanosine), chewable/buffered tablets or the pediatric powder for oral solution should not be taken within 4 hours before or 2 hours after taking lomefloxacin. (See PRECAUTIONS - Drug Interactions.)"
New last bullet added -
* "that convulsions have been reported in patients taking quinolones, including lomefloxacin, and to notify their physician before taking this drug if there is a history of this condition."
Drug Interactions: Antacids and sucralfate: First two sentences revised (new text in italics) -
"Sucralfate and antacids containing magnesium or aluminum, as well as formulations containing divalent and trivalent cations such as Videx, (didanosine), chewable/buffered tablets or the pediatric powder for oral solution, can form chelation complexes with lomefloxacin and interfere with its bioavailability. Sucralfate administered two hours before lomefloxacin resulted in a slower ["rate of" deleted] absortpion (mean Cmax decreased by 30% and mean Tmax increased by 1 hour) and a lesser extent of absorption (mean AUC decreased by approximately 25%)."
Geriatric use: Subsection revised (new text in italics) -
"Of the total number of ["patients in clinical trials" deleted] subjects in clinical studies of lomefloxacin, 25% were greater than or equal to 65 years ["of age" deleted] and 9% were greater than or equal to 75 years. No overall differences in safety or effectiveness were observed between these ["patients and younger patients" deleted] subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
"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. (See Clinical Pharmacology - Pharmacokinetics in the geriatric population.)"
"Maxaquin (lomefloxacin HCl) may be taken without regard to meals. Sucralfate and antacids containing magnesium or aluminum, or Videx, (didanosine), chewable/buffered tablets or the pediatric powder for oral solution should not be taken within 4 hours before or 2 hours after taking lomefloxacin. Risk of reaction to solar UVA light may be reduced by taking Maxaquin at least 12 hours before exposure to the sun (eg, in the evening).(See Clinical Pharmacology.)"
{Note: The following change appears in the 1999 PDR.]
"In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of cisatracurium besylate in conjunction with one or more anesthetic agents in clinical practice. 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 cisatracurium besylate.
General: Hypersensitivity reactions including anaphylactic or anaphylactoid responses which, in rare instances, were severe.
Musculoskeletal: Prolonged neuromuscular block, inadequate neuromuscular block."
"Alopecia ["has also been reported" deleted] ,malaise, and asthenia have been reported as part of postmarketing surveillance."
"If Patinol AQ [Patinol powder or Patinol soluion] contacts the skin or mucosae, immediately wash the skin or mucosae thoroughly with soap and water"
deleted and replaced with the following text -
"If Platinol AQ (Platinol powder or Platinol solution) contacts the skin or mucosa, immediately and thoroughly wash the skin with soap and water and flush the mucosa with water."
"erythema nodosum" added to alphabetical list. [Note: this change appears in the 1999 PDR.]
"Treatment should consist of those general measures employed in the management of any antidepressant.
"Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients.
"Activated charcoal should be administered. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely of benefit. No specific antidotes for fluoxetine are known.
"A specific caution involves patinets who are taking or have recently taken fluoxetine and might ingest excessive quantities of a tricyclic antidepressant. In such a case, accumulation of the parent tricyclic and/or an active metabolite may increase the possibility of clinically significant sequelae and extend teh time needed for close medical oservation (see Other Antidepressants under Precautions). "Based on experience in animals, which may not be relevant to humans, fluoxetine-induced seizures that fail to remit spontaneously may respond to diazepam.
"In managing overdose, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the Physicians' Desk Reference (PDR)."
[Note: new dosage form approved - 10 mg tablet.]
"Tenuate and Tenuate Dospan are indicated in the management of
exogenous obesity as a short-term adjunct ( a few weeks) in a regimen of weight
reduction based on caloric restriction in patients with an initial body mass index
(BMI) of 30 kg/m2 or higher and who have not responded to appropriate weight
reducing regimen (diet and/or exercise) alone. Below is a chart of BMI based on
various heights and weights. BMI is calculated by taking the patient's weight, in
kilograms (kg), divided by the patient's height, in meters (m), squared. Metric conversions are as follows: pounds divided by 2.2 = kg; inches x 0.0254 = meters."
Body Mass Index (BMI), kg/m2 Weight (pounds) Height (feet, inches) 5'0" 5'3" 5'6" 5'9" 6'0" 6'3" 140 27 25 23 21 19 18 150 29 27 24 22 20 19 160 31 28 26 24 22 20 170 33 30 28 25 23 21 180 35 32 29 27 25 23 190 37 34 31 28 26 24 200 39 36 32 30 27 25 210 41 37 34 31 29 26 220 43 39 36 33 30 28 230 45 41 37 34 31 29 240 47 43 39 36 33 30 250 49 44 40 37 34 31
"The usefulness of agents of this class (see CLINICAL PHARMACOLOGY) should be measured against possible risk factors inherent in their use as those described below. Tenuate and Tenuate Dospan are indicated for use as monotherapy only.
"Pulmonary hypertension, advanced arteriosclerosis, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines, glaucoma, severe hypertension. (See Precautions.)
"Agitated states.
"Patients with a history of drug abuse.
"Use in combination with other anorectic agents is contraindicated.
"During or within 14 days following the administration of monoamine oxidase inhibitors, hypertensive crises may result."
" Tenuate and Tenuate Dospan should not be used in combination with other anorectic agents, including prescribed drugs, over-the-counter preparations, and herbal products.
"In a case-control epidemiological study, the use of anorectic agents, including diethylpropion, was associated with an increased risk of developing pulmonary hypertension, a rare, but often fatal disorder. The use of anorectic agents for longer than 3 months was associated with a 23-fold increase in the risk of developing pulmonary hypertension. Increased risk of pulmonary hypertension with repeated courses of therapy cannot be excluded.
"The onset or aggravation of exertional dyspnea, or unexplained symptoms of angina pectoris, syncope, or lower extremity edema suggest the possibility of occurrence of pulmonary hypertension. Under these circumstances, Tenuate or Tenuate Dospan should be immediately discontinued, and the patient should be evaluated for the possible presence of pulmonary hypertension.
"Valvular heart disease associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine has been reported. Possible contributing factors include use for extended periods of time, higher than recommended dose, and/or use in combination with other anorectic drugs. Valvulopathy has been very rarely reported with Tenuate and Tenuate Dospan monotherapy, but the causal relationship remains uncertain. The potential risk of possible serious adverse effects such as valvular heart disease and pulmonary hypertension should be assessed carefully against the potential benefit of weight loss. Baseline cardiac evaluation should be considered to detect preexisting valvular heart diseases or pulmonary hypertension prior to initiation of Tenuate or Tenuate Dospan treatment. Tenuate and Tenuate Dospan are not recommended in patients with known heart murmur or valvular heart disease. Echocardiogram during and after treatment could be useful for detecting any valvular disorders which may occur.
"To limit unwarranted exposure and risks, treatment with Tenuate or Tenuate Dospan should be continued only if the patient has satisfactory weight loss within the first 4 weeks of treatment (e.g., weight loss of at least 4 pounds, or as determined by the physician and patient).
"Tenuate and Tenuate Dospan are not recommended for patients who used any anorectic agents within the prior year.
"If tolerance develops, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued. Tenuate or Tenuate Dospan may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving a motor vehicle; the patient should therefore be cautioned accordingly.
"Prolonged use of diethylpropion hydrochloride may induce dependence with withdrawal syndrome on cessation of therapy. Hallucinations have occurred rarely following high doses of the drug. Several cases of toxic psychosis have been reported following excessive use of the drug and some have been reported in which the recommended dose appears not to have been exceeded. Psychosis abated after the drug was discontinued.
"When central nervous system active agents are used, consideration must always be given to the possibility of adverse interactions with alcohol."
"Because Tenuate and Tenuate Dospan are monoamines, hypertension may result when either agent is used with monoamine oxidase (MAO) inhibitors (See CONTRAINDICATIONS).
"Efficacy of diethylpropion with other anorectic agents has not been studied and the combined use may have the potential for serious cardiac problems; therefore, the concomitant use with other anorectic agents is contraindicated."
Pregnancy: Teratogenic Effects: Pregnancy Category B: Subsection revised (new text in italics) -
"Reproduction studies have been performed in rats at doses up to ["9 times the human dose" deleted] 1.6 times the human dose (based on mg/m2) and have revealed no evidence of impaired fertility or harm to the fetus due to diethylpropion hydrochloride. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
"Spontaneous reports of congenital malformations have been recorded in humans, but no causal relationship to diethylpropion has been established."
Pediatric Use: Subsection revised (new text in italics) -
"Since safety and effectiveness in ["children" deleted] pediatric patients below the age of ["12" deleted] 16 have not been established, Tenuate or Tenuate Dospan is not recommended for use in pediatric patients ["under 12" deleted] 16 years of age and under."
"Precordial pain, arrhythmia (including ventricular), ECG changes, tachycardia, elevation of blood pressure, palpitation and rare reports of pulmonary hypertension. Valvular heart disease associated with the use of some anorectic agents such as fenfluramine and dexfenfluramine, both independently and especially when used in combination, have been reported. Valvulopathy has been very rarely reported with Tenuate or Tenuate Dospan monotherapy, but the causal relationship remains uncertain."
Central Nervous System: "and cerebovascular accidnet" added to end of subsection.
Information on Efavirenz as a coadministered drug added. See new labeling/package insert.
Table 2: "Effect of Coadministered Drug on Nelfinavir Plasma AUC and Cmax"
Information on Efavirenz as a coadministered drug added. See new labeling/package insert.
Footnote to Table 2 revised (new text in italics) -
"* Using ["an experimental (soft gelatin capsule)" deleted] the soft gelatin capsule formulation of saquinavir 1200mg
"Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving protease inhibitors. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established."
Information For Patients: Text added as new sixth paragraph -
"Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving protease inhibitors and that the cause and long term health effects of these conditions are not known at this time."
Drug Interactions: Anti-HIV Protease Inhibitors: Saquinavir:
First sentence revised (new text in italics) -
"Coadministration of saquinavir (using ["an experimental" deleted] the soft gelatin capsule formulation of saquinavir 1200 mg) with Viracept resulted in an 18% increase in nelfinavir plasma AUC and a 4-fold increase in saquinavir plasma AUC."
Anti-HIV reverse transcriptase inhibitors: Efavirenz (new subsection):
"Coadministration of efavirenz with Viracept increased nelfinavir AUC by 20% with no change in efavirenz AUC. A dose adjustment is not needed when efavirenz is administered with Viracept."
Pregnancy, Fertility and Reproduction - Pregnancy Category B: Text added at end of subsection -
"Antiretroviral Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant women exposed to Viracept and other antiretroviral agents, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling (800) 258-4263."
"The following additional adverse experiences have been reported from postmarketing surveillance as at least possibly related or of unknown relationship to Viracept:
Body as a Whole: redistribution/accumulation of body fat (see PRECAUIONS, Fat Redistribution)
Digestive System: jaundice
Metabolic/Nutritional System: bilirubinemia, edema, metabolic acidosis"
"Patients unable to swallow tablets may place whole tablets or crushed tablets in a small amount of water to disperse before ingestion or they may mix crushed tablets in a small amount of food. Once mixed with food or dispersed in water, the entire contents must by consumed I order to obtain the full dose. It is recommended that the entire contents by consumed immediately after mixing with food or dispersing in water. The drinking glass should be rinsed and the rinse swallowed to insure the entire dose is consumed. Acidic food or juice (e.g., orange juice, apple juice or apple sauce) are not recommended to be used in combination with Viracept, because the combination may result in a bitter taste. (See, DOSAGE AND ADMINISTRATION, Pediatric Patients)."
"Spontaneous reports have been received of local inflammation (i.e., edema, erythema, burning, tenderness) following extravasation of the product. In most cases, these events resolved the same day or within a few days."
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