DRUGS & SUPPLEMENTS
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Efudix is indicated for the treatment of patients with:
Efudix® (fluorouracil injection) is a nucleoside metabolic inhibitor indicated for the treatment of patients with
Efudix is recommended for administration either as an intravenous bolus or as an intravenous infusion. Do not inject the entire contents of the vial directly into patients. Individualize the dose and dosing schedule of Efudix based on tumor type, the specific regimen administered, disease state, response to treatment, and patient risk factors.
Withhold Efudix for any of the following:
Upon resolution or improvement to Grade 1 diarrhea, mucositis, myelosuppression, or palmar-plantar erythrodysesthesia, resume Efudix administration at a reduced dose.
There is no recommended dose for resumption of Efudix administration following development of any of the following adverse reactions:
Efudix is supplied in a pharmacy bulk package consisting of a vial. The pharmacy bulk package can be used to prepare doses for more than one patient. It is not supplied with a sterile transfer device, which is required for dispensing when multiple doses will be prepared from the single vial. The 50 mL vial is only intended for preparation in a Pharmacy Admixture Service under appropriate conditions for cytotoxic drugs . Store vial at room temperature.
Using aseptic conditions, penetrate the container closure once with a suitable sterile transfer device or dispensing set that allows measured distribution of the contents. Record the date and time the vial was opened on the vial label. Discard the pharmacy bulk package 4 hours after penetration of the container closure.
Withdraw the calculated dose for an individual patient into a sterile syringe. Inspect the solution in syringe for particulate matter and discoloration prior to administration or further dilution. Discard syringe if the solution is discolored or contains particulate matter.
Do not administer in the same intravenous line concomitantly with other medicinal products.
For bolus administration, store undiluted Efudix in the syringe for up to 4 hours at room temperature (25°C). Administer Efudix as an intravenous bolus through an established intravenous line.
Store diluted solutions of Efudix for up to 4 hours at room temperature (25°C) prior to administration to the patient. For intravenous infusion regimens, administer through a central venous line using an infusion pump.
Efudix (fluorouracil injection USP) is supplied as:
Based on postmarketing reports, patients with certain homozygous or certain compound heterozygous mutations in the DPD gene that result in complete or near complete absence of DPD activity are at increased risk for acute early-onset of toxicity and severe, life-threatening, or fatal adverse reactions caused by Efudix (e.g., mucositis, diarrhea, neutropenia, and neurotoxicity). Patients with partial DPD activity may also have increased risk of severe, life-threatening, or fatal adverse reactions caused by Efudix.
Withhold or permanently discontinue Efudix based on clinical assessment of the onset, duration and severity of the observed toxicities in patients with evidence of acute early-onset or unusually severe toxicity, which may indicate near complete or total absence of DPD activity. No Efudix dose has been proven safe for patients with complete absence of DPD activity. There is insufficient data to recommend a specific dose in patients with partial DPD activity as measured by any specific test.
Efudix can cause cardiotoxicity, including angina, myocardial infarction/ischemia, arrhythmia, and heart failure, based on postmarketing reports. Reported risk factors for cardiotoxicity are administration by continuous infusion rather than intravenous bolus and presence of coronary artery disease. Withhold Efudix for cardiotoxicity. The risks of resumption of Efudix in patients with cardiotoxicity that has resolved have not been established.
Efudix can cause hyperammonemic encephalopathy in the absence of liver disease or other identifiable cause, based on postmarketing reports. Signs or symptoms of hyperammonemic encephalopathy began within 72 hours after initiation of Efudix infusion; these included altered mental status, confusion, disorientation, coma, or ataxia, in the presence of concomitant elevated serum ammonia level. Withhold Efudix for hyperammonemic encephalopathy and initiate ammonia-lowering therapy. The risks of resumption of Efudix in patients with hyperammonemic encephalopathy that has resolved have not been established.
Efudix can cause neurologic toxicity, including acute cerebellar syndrome and other neurologic events, based on postmarketing reports. Neurologic symptoms included confusion, disorientation, ataxia, or visual disturbances. Withhold Efudix for neurologic toxicity. There are insufficient data on the risks of resumption of Efudix in patients with neurologic toxicity that has resolved.
Efudix can cause severe diarrhea. Withhold Efudix for Grade 3 or 4 diarrhea until resolved or decreased in intensity to Grade 1, then resume Efudix at a reduced dose. Administer fluids, electrolyte replacement, or antidiarrheal treatments as necessary.
Efudix can cause palmar-plantar erythrodysesthesia, also known as hand-foot syndrome (HFS). Symptoms of HFS include a tingling sensation, pain, swelling, and erythema with tenderness, and desquamation. HFS occurs more commonly when Efudix is administered as a continuous infusion than when Efudix is administered as a bolus injection, and has been reported to occur more frequently in patients with previous exposure to chemotherapy. HFS is generally observed after 8 to 9 weeks of Efudix administration but may occur earlier. Institute supportive measures for symptomatic relief of HFS. Withhold Efudix administration for Grade 2 or 3 HFS; resume Efudix at a reduced dose when HFS is completely resolved or decreased in severity to Grade 1.
Efudix can cause severe and fatal myelosuppression which may include neutropenia, thrombocytopenia, and anemia. The nadir in neutrophil counts commonly occurs between 9 and 14 days after Efudix administration. Obtain complete blood counts prior to each treatment cycle, weekly if administered on a weekly or similar schedule, and as needed. Withhold Efudix until Grade 4 myelosuppression resolves; resume Efudix at a reduced dose when myelosuppression has resolved or improved to Grade 1 in severity.
Mucositis, stomatitis or esophagopharyngitis, which may lead to mucosal sloughing or ulceration, can occur with Efudix. The incidence is reported to be higher with administration of Efudix by intravenous bolus compared with administration by continuous infusion. Withhold Efudix administration for Grade 3 or 4 mucositis; resume Efudix at a reduced dose once mucositis has resolved or decreased in severity to Grade 1.
Clinically significant elevations in coagulation parameters have been reported during concomitant use of warfarin and Efudix. Closely monitor patients receiving concomitant coumarin-derivative anticoagulants such as warfarin for INR or prothrombin time in order to adjust the anticoagulant dose accordingly .
Based on its mechanism of action, Efudix can cause fetal harm when administered to a pregnant woman. In animal studies, administration of Efudix at doses lower than a human dose of 12 mg/kg caused teratogenicity. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during and for 3 months following cessation of therapy with Efudix .
The following adverse reactions are discussed in more detail in other sections of the labeling:
To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals USA, Inc. at 1-866-832-8537 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
The following adverse reactions have been identified during postapproval use of Efudix. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Gastrointestinal: gastrointestinal ulceration, nausea, vomiting
Allergic Reactions: anaphylaxis and generalized allergic reactions
Neurologic: nystagmus, headache
Dermatologic: dry skin; fissuring; photosensitivity, as manifested by erythema or increased pigmentation of the skin; vein pigmentation
Ophthalmic: lacrimal duct stenosis, visual changes, lacrimation, photophobia
Miscellaneous: thrombophlebitis, epistaxis, nail changes (including loss of nails)
Elevated coagulation times have been reported in patients taking Efudix concomitantly with warfarin. While pharmacokinetic data are not available to assess the effect of Efudix administration on warfarin pharmacokinetics, the elevation of coagulation times that occurs with the Efudix prodrug capecitabine is accompanied by an increase in warfarin concentrations. Thus, the interaction may be due to inhibition of cytochrome P450 2C9 by Efudix or its metabolites.
Pregnancy Category D
There are no adequate and well-controlled studies with Efudix in pregnant women. Based on its mechanism of action, Efudix can cause fetal harm when administered to a pregnant woman. Administration of Efudix to rats and mice during selected periods of organogenesis, at doses lower than a human dose of 12 mg/kg, caused embryolethality and teratogenicity. Malformations included cleft palate and skeletal defects. In monkeys, maternal doses of Efudix higher than an approximate human dose of 12 mg/kg resulted in abortion. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus .
Malformations including cleft palate, skeletal defects and deformed appendages (paws and tails) were observed when Efudix was administered by intraperitoneal injection to mice at doses at or above 10 mg/kg (approximately 0.06 times a human dose of 12 mg/kg on a mg/m2 basis) for 4 days during the period of organogenesis. Similar results were observed in hamsters administered Efudix intramuscularly at doses lower than those administered in commonly used clinical treatment regimens. In rats, administration of Efudix by intraperitoneal injection at doses greater than 15 mg/kg (approximately 0.2 times a human dose of 12 mg/kg on a mg/m2 basis) for a single day during organogenesis resulted in delays in growth and malformations including micro-anophthalmos. In monkeys, administration of Efudix during organogenesis at doses approximately equal to a human dose of 12 mg/kg on a mg/m2 basis resulted in abortion; at a 50% lower dose, resorptions and decreased fetal body weights were reported.
It is not known whether Efudix or its metabolites are present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from Efudix, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
The safety and effectiveness in pediatric patients have not been established.
Reported clinical experience has not identified differences in safety or effectiveness between the elderly and younger patients.
Based on its mechanism of action, Efudix can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with Efudix and for up to 3 months following cessation of therapy .
Efudix may damage spermatozoa. Advise males with female partners of reproductive potential to use effective contraception during and for 3 months following cessation of therapy with Efudix .
Advise females of reproductive potential that, based on animal data, fertility may be impaired while receiving Efudix .
Advise males of reproductive potential that, based on animal data, fertility may be impaired while receiving Efudix .
Administer uridine triacetate within 96 hours following the end of Efudix infusion for management of Efudix overdose.
Efudix® (fluorouracil injection USP), a nucleoside metabolic inhibitor, is a colorless to faint yellow aqueous, sterile, nonpyrogenic injectable solution available in a 50 mL and 100 mL Pharmacy Bulk Package for intravenous administration. Each mL contains 50 mg Efudix, USP in water for injection, USP, pH is adjusted to 8.6 to 9.4 with sodium hydroxide.
Chemically, Efudix, USP, a fluorinated pyrimidine, is 5-fluoro-2,4 (1H,3H)-pyrimidinedione. It is a white to practically white crystalline powder which is sparingly soluble in water. The structural formula is:
C4H3FN2O2 M.W. 130.08
Efudix is a nucleoside metabolic inhibitor that interferes with the synthesis of deoxyribonucleic acid and to a lesser extent inhibits the formation of ribonucleic acid (RNA); these affect rapidly growing cells and may lead to cell death. Efudix is converted to three main active metabolites: 5-fluoro-2′-deoxyuridine-5′-monophosphate (FdUMP), 5-fluorouridine-5′-triphosphate (FUTP) and 5-fluoro-2′-deoxyuridine-5′-triphosphate (FdUTP). These metabolites have several effects including the inhibition of thymidylate synthase by FdUMP, incorporation of FUTP into RNA and incorporation of FdUTP into DNA.
Following bolus intravenous injection, Efudix distributes throughout the body including the intestinal mucosa, bone marrow, liver, cerebrospinal fluid and brain tissue.
Following bolus intravenous injection, 5 to 20 % of the parent drug is excreted unchanged in the urine in six hours. The remaining percentage of the administered dose is metabolized, primarily in the liver. The metabolites of Efudix (e.g., urea and α-fluoro-ß-alanine) are excreted in the urine over 3 to 4 hours.
Following bolus intravenous injection of Efudix, as a single agent, the elimination half-life increased with dose from 8 to 20 minutes.
Carcinogenicity studies have not been performed with Efudix. Efudix was mutagenic in vitro in the bacterial reverse mutation (Ames) assay and induced chromosomal aberrations in hamster fibroblasts in vitro and in mouse bone marrow in the in vivo mouse micronucleus assay.
Administration of Efudix intraperitoneally to male rats at dose levels equal to or greater than 1.7-fold the human dose of 12 mg/kg induced chromosomal aberrations in spermatogonia and inhibition of spermatogonia differentiation resulting in transient infertility. In female rats, intraperitoneal administration of Efudix during the pre-ovulatory phases of oogenesis at dose levels equal to or greater than 0.33 times a human dose of 12 mg/kg resulted in decreased incidence of fertile matings, increased pre-implantation loss, and fetotoxicity.
"OSHA Hazardous Drugs." OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html
Efudix® is available in two pharmacy bulk vials as follows:
PHARMACY BULK PACKAGES
2.5 g/50 mL vial
5 g/100 mL vial
The 50 mL and 100 mL pharmacy bulk packages are packaged 5 vials per shelf pack.
Store at 20° to 25°C (68° to 77°F). Do not freeze. Protect from light. Retain in carton until time of use.
Efudix is a cytotoxic drug. Follow applicable special handling and disposable procedures .
Teva Pharmaceuticals USA, Inc.
North Wales, PA 19454
Rev. D 1/2017
(fluorouracil injection USP)
2.5 grams/50 mL
For Intravenous Use Only
PHARMACY BULK PACKAGE
NOT FOR DIRECT INFUSION
CAUTION: Cytotoxic Agent
5 x 50 mL Vials
(fluorouracil injection USP)
5 grams/100 mL
For Intravenous Use Only
PHARMACY BULK PACKAGE
NOT FOR DIRECT INFUSION
CAUTION: Cytotoxic Agent
5 x 100 mL Vials
Depending on the reaction of the Efudix after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Efudix not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Efudix addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology