Verrucare

Fluorouracil:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• References
• How supplied/storage and handling
• Patient counseling information
• Verrucare (Fluorouracil) reviews

1 INDICATIONS AND USAGE

Verrucare (fluorouracil injection) is indicated for the treatment of patients with:

Verrucare (Fluorouracil)^® (fluorouracil injection) is a nucleoside metabolic inhibitor indicated for the treatment of patients with

• Adenocarcinoma of the Colon and Rectum (1.1)
• Adenocarcinoma of the Breast (1.2)
• Gastric Adenocarcinoma (1.3)
• Pancreatic Adenocarcinoma (1.4)

1.1 Adenocarcinoma of the Colon and Rectum

1.2 Adenocarcinoma of the Breast

1.3 Gastric Adenocarcinoma

1.4 Pancreatic Adenocarcinoma

2 DOSAGE AND ADMINISTRATION

• Verrucare is recommended for administration either as an intravenous bolus or as an intravenous infusion. (2.1)
• See Full Prescribing Information for dose individualization (2.1) and dose modifications due to adverse reactions (2.6)
• See Full Prescribing Information for recommended doses of Verrucare (Fluorouracil) for adenocarcinoma of the colon and rectum (2.2) and for recommended doses of Verrucare (Fluorouracil) as a component of a chemotherapy regimen for adenocarcinoma of the breast (2.3), gastric adenocarcinoma (2.4), pancreatic adenocarcinoma (2.5)
• Pharmacy Bulk Package: Prepare doses for more than one patient in a Pharmacy Admixture Service under appropriate conditions for cytotoxic drugs. Do not inject entire contents of vial directly into patients. Use within 4 hours of puncture (2.7, 2.8)

2.1 General Dosage Information

Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) based on tumor type, the specific regimen administered, disease state, response to treatment, and patient risk factors.

2.2 Recommended Dosage for Adenocarcinoma of the Colon and Rectum

• The recommended dose of Verrucare, administered in an infusional regimen in combination with leucovorin alone, or in combination with leucovorin and oxaliplatin or irinotecan, is 400 mg/m² by intravenous bolus on Day 1, followed by 2400 mg/m² to 3000 mg/m² intravenously as a continuous infusion over 46 hours every two weeks.
• The recommended dose of Verrucare (Fluorouracil), if administered in a bolus dosing regimen in combination with leucovorin, is 500 mg/m² by intravenous bolus on Days 1, 8, 15, 22, 29, and 36 in 8-week cycles.

2.3 Recommended Dosage for Adenocarcinoma of the Breast

• The recommended dose of Verrucare (Fluorouracil), administered as a component of a cyclophosphamide-based multidrug regimen, is 500 mg/m² or 600 mg/m² intravenously on Days 1 and 8 every 28 days for 6 cycles.

2.4 Recommended Dosage for Gastric Adenocarcinoma

• The recommended dose of Verrucare, administered as a component of a platinum-containing multidrug chemotherapy regimen, is 200 mg/m² to 1000 mg/m² intravenously as a continuous infusion over 24 hours. The frequency of dosing in each cycle and the length of each cycle will depend on the dose of Verrucare (Fluorouracil) and the specific regimen administered.

2.5 Recommended Dosage for Pancreatic Adenocarcinoma

• The recommended dose of Verrucare (Fluorouracil), administered as an infusional regimen in combination with leucovorin or as a component of a multidrug chemotherapy regimen that includes leucovorin, is 400 mg/m² intravenous bolus on Day 1, followed by 2400 mg/m² intravenously as a continuous infusion over 46 hours every two weeks.

2.6 Dose Modifications

Withhold Verrucare for any of the following:

• Development of angina, myocardial infarction/ischemia, arrhythmia, or heart failure in patients with no history of coronary artery disease or myocardial dysfunction
• Hyperammonemic encephalopathy
• Acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances
• Grade 3 or 4 diarrhea
• Grade 2 or 3 palmar-plantar erythrodysesthesia (hand-foot syndrome)
• Grade 3 or 4 mucositis
• Grade 4 myelosuppression

Upon resolution or improvement to Grade 1 diarrhea, mucositis, myelosuppression, or palmar-plantar erythrodysesthesia, resume Verrucare (Fluorouracil) administration at a reduced dose.

There is no recommended dose for resumption of Verrucare (Fluorouracil) administration following development of any of the following adverse reactions:

• Cardiac toxicity
• Hyperammonemic encephalopathy
• Acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances

2.7 Preparation for Administration

Verrucare (Fluorouracil) 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.

2.8 Administration

Do not administer in the same intravenous line concomitantly with other medicinal products.

For bolus administration, store undiluted Verrucare (Fluorouracil) in the syringe for up to 4 hours at room temperature (25°C). Administer Verrucare (Fluorouracil) as an intravenous bolus through an established intravenous line.

Store diluted solutions of Verrucare (Fluorouracil) 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.

3 DOSAGE FORMS AND STRENGTHS

Verrucare (Fluorouracil) (fluorouracil injection USP) is supplied as:

• a pharmacy bulk package as a vial containing 2.5 g/50 mL (50 mg/mL) Verrucare (Fluorouracil)
• a pharmacy bulk package as a vial containing 5 g/100 mL (50 mg/mL) Verrucare (Fluorouracil)

Injection:

• 2.5 g in a 50 mL vial in a pharmacy bulk package
• 5 g in a 100 mL vial in a pharmacy bulk package (3)

4 CONTRAINDICATIONS

None.

None (4)

5 WARNINGS AND PRECAUTIONS

• Increased Risk of Serious or Fatal Adverse Reactions in Patients with Low or Absent Dipyrimidine Dehydrogenase Activity: Withhold or permanently discontinue Verrucare in patients with evidence of acute early-onset or unusually severe toxicity, which may indicate near complete or total absence of dipyrimidine dehydrogenase (DPD) activity. No Verrucare (Fluorouracil) dose has been proven safe in patients with absent DPD activity. (5.1)
• Cardiotoxicity: Verrucare (Fluorouracil) can cause cardiotoxicity, including angina, myocardial infarction/ischemia, arrhythmia, and heart failure. Withhold Verrucare (Fluorouracil) for cardiac toxicity. (5.2)
• Hyperammonemic Encephalopathy: Altered mental status, confusion, disorientation, coma, or ataxia with elevated serum ammonia level can occur within 72 hours of initiation of Verrucare (Fluorouracil). Withhold Verrucare (Fluorouracil) and initiate ammonia-lowering therapy. (5.3)
• Neurologic Toxicity: Verrucare (Fluorouracil) can cause acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances. Withhold Verrucare (Fluorouracil) for neurologic toxicity. (5.4)
• Diarrhea: Verrucare (Fluorouracil) can cause severe diarrhea. Withhold Verrucare (Fluorouracil) for severe diarrhea until resolved. (5.5)
• Palmar-Plantar Erythrodysesthesia (Hand-Foot Syndrome): Verrucare (Fluorouracil) can cause hand-foot syndrome. If severe, discontinue Verrucare (Fluorouracil) until resolved or decreased to Grade 1, then resume at a reduced dose. (5.6)
• Myelosuppression: Verrucare (Fluorouracil) can cause severe and fatal myelosuppression. Withhold Verrucare (Fluorouracil) until severe myelosuppression resolves, then resume at a reduced dose. (5.7)
• Mucositis: Verrucare (Fluorouracil) can cause severe mucositis. Discontinue Verrucare (Fluorouracil) until resolved or decreased to Grade 1, then resume at a reduced dose. (5.8)
• Increased Risk of Elevated INR with Warfarin: Concurrent administration with warfarin can result in clinically significant increases in coagulation parameters: Closely monitor INR and prothrombin time. (5.9)
• Embryofetal Toxicity: Verrucare (Fluorouracil) can cause fetal harm. Advise females and males of reproductive potential of the potential risk to a fetus. (5.10, 8.1, 8.6)

5.1 Increased Risk of Serious or Fatal Adverse Reactions in Patients with Low or Absent Dipyrimidine Dehydrogenase (DPD) Activity

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 Verrucare (Fluorouracil) (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 Verrucare (Fluorouracil).

Withhold or permanently discontinue Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) 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.

5.2 Cardiotoxicity

Verrucare 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 Verrucare (Fluorouracil) for cardiotoxicity. The risks of resumption of Verrucare (Fluorouracil) in patients with cardiotoxicity that has resolved have not been established.

5.3 Hyperammonemic Encephalopathy

Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) infusion; these included altered mental status, confusion, disorientation, coma, or ataxia, in the presence of concomitant elevated serum ammonia level. Withhold Verrucare (Fluorouracil) for hyperammonemic encephalopathy and initiate ammonia-lowering therapy. The risks of resumption of Verrucare (Fluorouracil) in patients with hyperammonemic encephalopathy that has resolved have not been established.

5.4 Neurologic Toxicity

Verrucare 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 Verrucare (Fluorouracil) for neurologic toxicity. There are insufficient data on the risks of resumption of Verrucare (Fluorouracil) in patients with neurologic toxicity that has resolved.

5.5 Diarrhea

Verrucare (Fluorouracil) can cause severe diarrhea. Withhold Verrucare (Fluorouracil) for Grade 3 or 4 diarrhea until resolved or decreased in intensity to Grade 1, then resume Verrucare (Fluorouracil) at a reduced dose. Administer fluids, electrolyte replacement, or antidiarrheal treatments as necessary.

5.6 Palmar-Plantar Erythrodysesthesia

Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) is administered as a continuous infusion than when Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) administration but may occur earlier. Institute supportive measures for symptomatic relief of HFS. Withhold Verrucare (Fluorouracil) administration for Grade 2 or 3 HFS; resume Verrucare (Fluorouracil) at a reduced dose when HFS is completely resolved or decreased in severity to Grade 1.

5.7 Myelosuppression

Verrucare 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 Verrucare (Fluorouracil) administration. Obtain complete blood counts prior to each treatment cycle, weekly if administered on a weekly or similar schedule, and as needed. Withhold Verrucare (Fluorouracil) until Grade 4 myelosuppression resolves; resume Verrucare (Fluorouracil) at a reduced dose when myelosuppression has resolved or improved to Grade 1 in severity.

5.8 Mucositis

Mucositis, stomatitis or esophagopharyngitis, which may lead to mucosal sloughing or ulceration, can occur with Verrucare (Fluorouracil). The incidence is reported to be higher with administration of Verrucare (Fluorouracil) by intravenous bolus compared with administration by continuous infusion. Withhold Verrucare (Fluorouracil) administration for Grade 3 or 4 mucositis; resume Verrucare (Fluorouracil) at a reduced dose once mucositis has resolved or decreased in severity to Grade 1.

5.9 Increased Risk of Elevated International Normalized Ratio with Warfarin

Clinically significant elevations in coagulation parameters have been reported during concomitant use of warfarin and Verrucare (Fluorouracil). Closely monitor patients receiving concomitant coumarin-derivative anticoagulants such as warfarin for INR or prothrombin time in order to adjust the anticoagulant dose accordingly .

5.10 Embryofetal Toxicity

Based on its mechanism of action, Verrucare (Fluorouracil) can cause fetal harm when administered to a pregnant woman. In animal studies, administration of Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) .

6 ADVERSE REACTIONS

The following adverse reactions are discussed in more detail in other sections of the labeling:

• Increased risk of serious or fatal adverse reactions in patients with low or absent dipyrimidine dehydrogenase activity
• Cardiotoxicity
• Hyperammonemic encephalopathy
• Neurologic toxicity
• Diarrhea
• Palmar-plantar erythrodysesthesia (hand-foot syndrome)
• Myelosuppression
• Mucositis
• Increased risk of elevated INR when administrated with warfarin

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.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Verrucare (Fluorouracil). 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.

Hematologic: pancytopenia

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

Psychiatric: euphoria

Miscellaneous: thrombophlebitis, epistaxis, nail changes (including loss of nails)

7 DRUG INTERACTIONS

7.1 Anticoagulants and CYP 2C9 Substrates

Elevated coagulation times have been reported in patients taking Verrucare (Fluorouracil) concomitantly with warfarin. While pharmacokinetic data are not available to assess the effect of Verrucare (Fluorouracil) administration on warfarin pharmacokinetics, the elevation of coagulation times that occurs with the Verrucare (Fluorouracil) prodrug capecitabine is accompanied by an increase in warfarin concentrations. Thus, the interaction may be due to inhibition of cytochrome P450 2C9 by Verrucare (Fluorouracil) or its metabolites.

8 USE IN SPECIFIC POPULATIONS

• Nursing Mothers: Discontinue drug or discontinue nursing.
• Females and Males of Reproductive Potential: Provide pregnancy planning and prevention counseling. (5.10, 8.1, 8.6)

8.1 Pregnancy

Teratogenic Effects

Pregnancy Category D

Risk Summary

There are no adequate and well-controlled studies with Verrucare (Fluorouracil) in pregnant women. Based on its mechanism of action, Verrucare (Fluorouracil) can cause fetal harm when administered to a pregnant woman. Administration of Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) 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 .

Animal Data

Malformations including cleft palate, skeletal defects and deformed appendages (paws and tails) were observed when Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) intramuscularly at doses lower than those administered in commonly used clinical treatment regimens. In rats, administration of Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) 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.

8.3 Nursing Mothers

It is not known whether Verrucare 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 Verrucare (Fluorouracil), 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.

8.4 Pediatric Use

The safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Reported clinical experience has not identified differences in safety or effectiveness between the elderly and younger patients.

8.6 Females and Males of Reproductive Potential

Contraception

Females

Based on its mechanism of action, Verrucare (Fluorouracil) can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with Verrucare (Fluorouracil) and for up to 3 months following cessation of therapy .

Males

Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) .

Infertility

Females

Advise females of reproductive potential that, based on animal data, fertility may be impaired while receiving Verrucare (Fluorouracil) .

Males

Advise males of reproductive potential that, based on animal data, fertility may be impaired while receiving Verrucare (Fluorouracil) .

10 OVERDOSAGE

Administer uridine triacetate within 96 hours following the end of Verrucare (Fluorouracil) infusion for management of Verrucare (Fluorouracil) overdose.

11 DESCRIPTION

Verrucare (Fluorouracil)^® (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 Verrucare (Fluorouracil), USP in water for injection, USP, pH is adjusted to 8.6 to 9.4 with sodium hydroxide.

Chemically, Verrucare (Fluorouracil), 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

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Verrucare is a nucleoside metabolic inhibitor that interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits the formation of ribonucleic acid (RNA); these affect rapidly growing cells and may lead to cell death. Verrucare (Fluorouracil) 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.

12.3 Pharmacokinetics

Distribution

Following bolus intravenous injection, Verrucare (Fluorouracil) distributes throughout the body including the intestinal mucosa, bone marrow, liver, cerebrospinal fluid and brain tissue.

Elimination

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 Verrucare (Fluorouracil) (e.g., urea and α-fluoro-ß-alanine) are excreted in the urine over 3 to 4 hours.

Following bolus intravenous injection of Verrucare (Fluorouracil), as a single agent, the elimination half-life increased with dose from 8 to 20 minutes.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been performed with Verrucare (Fluorouracil). Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) 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 Verrucare (Fluorouracil) 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.

15 REFERENCES

"OSHA Hazardous Drugs." OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Verrucare ^® (fluorouracil injection USP) is available in two pharmacy bulk vials as follows:

PHARMACY BULK PACKAGES

The 50 mL and 100 mL pharmacy bulk packages are packaged 5 vials per shelf pack.

16.2 Storage and Handling

Store at 20° to 25°C (68° to 77°F). Do not freeze. Protect from light. Retain in carton until time of use.

Verrucare (Fluorouracil) is a cytotoxic drug. Follow applicable special handling and disposable procedures .

17 PATIENT COUNSELING INFORMATION

Advise:

• Patients to notify their healthcare provider if they have a known DPD deficiency. Advise patients if they have complete or near complete absence of DPD activity, they are at an increased risk of severe and life-threatening mucositis, diarrhea, neutropenia and neurotoxicity .
• Patients of the risk of cardiotoxicity. Advise patients to immediately contact their healthcare provider or to go to an emergency room for new onset of chest pain, shortness of breath, dizziness, or lightheadedness .
• Patients to immediately contact their healthcare provider or go to an emergency room for new onset of confusion, disorientation, or otherwise altered mental status; difficulty with balance or coordination; or visual disturbances .
• Patients to contact their healthcare provider for severe diarrhea or for painful mouth sores with decreased oral intake of food or fluids .
• Patients to contact their healthcare provider for tingling or burning, redness, flaking, swelling, blisters, or sores on the palms of their hands or soles of their feet .
• Patients of the importance of keeping appointments for blood tests. Instruct patients to monitor their temperature on a daily basis and to immediately contact their healthcare provider for fever or other signs of infection .
• Patients to notify their healthcare provider of all drugs they are taking, including warfarin or other coumarin-derivative anticoagulants. Advise patients of the importance of keeping appointments for blood tests .
• Females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Verrucare (Fluorouracil) and for up to 3 months after the last dose of Verrucare (Fluorouracil). Instruct female patients to contact their healthcare provider if they become pregnant, if pregnancy occurs during Verrucare (Fluorouracil) treatment or during the 3 months following the last dose .
• Females and males of reproductive potential may have impaired fertility while receiving Verrucare (Fluorouracil), based on animal data .
• Nursing mothers to discontinue nursing .

Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

Rev. D 1/2017

• NDC 0703-3018-12 Rx only

Adrucil®

(fluorouracil injection USP)

2.5 grams/50 mL

(50 mg/mL)

For Intravenous Use Only

PHARMACY BULK PACKAGE

NOT FOR DIRECT INFUSION

CAUTION: Cytotoxic Agent

5 x 50 mL Vials

TEVA

• NDC 0703-3019-12 Rx only

Adrucil®

(fluorouracil injection USP)

5 grams/100 mL

(50 mg/mL)

For Intravenous Use Only

PHARMACY BULK PACKAGE

NOT FOR DIRECT INFUSION

CAUTION: Cytotoxic Agent

5 x 100 mL Vials

TEVA

Lactic Acid:

• Verrucare (Lactic Acid) reviews

FOR INDUSTRIAL USE ONLY

KEEP OUT OF REACH OF CHILDREN

NOT FOR HUMAN USE

Attention

For External Use Only

Wash hands thoroughly after handling.

Do not mix with bleach or other chlorinated products – will cause chlorine gas.

Get medical advice/ attention if you feel unwell.

DIRECTIONS:

IMPORTANT: Do not further dilute with water or mix with any other teat dips. If product in dip cup becomes visibly dirty, discard contents and replenish with fresh product. Do not reuse or return any unused product to the original container.

Udder Prep: When using an udder wash step before milking, make sure to wash teats with appropriate udder wash solution using proper cleaning procedures. Teats should then be dried with single-service towels.

Directions for Teat Dipping

Pre-Milk Dipping: Before each cow is milked, and using fresh Verrucare (Lactic Acid), dip each teat full-length into the teat dip cup. Wipe teats after dipping using single-service towels to avoid contamination of milk.

Post-Milk Dipping: Using fresh Verrucare (Lactic Acid), dip each teat full-length into the teat dip cup. Do not wipe. Allow to air dry. Do not turn cows out in freezing weather until the product is completely dry.

Directions for Teat Spraying

Pre-Milk Spraying: Before each cow is milked, and using fresh Verrucare (Lactic Acid), spray entire teat. Wipe teats after dipping using single-service towels to avoid contamination of milk.

Post-Milk Spraying: Using fresh Verrucare (Lactic Acid), spray entire teat immediately after each milking. Do not wipe. Allow to air dry. Do not turn cows out in freezing weather until the product is completely dry.

Expanded Usage: When freshening cows, begin dipping teats twice daily for about 10 days before calving. PRECAUTION: Verrucare (Lactic Acid) is not intended to cure or help the healing of chapped or irritated teats. As with any germicide, irritation or sensitization may occur in sensitive animals. In case of teat irritation or chapping, have the condition examined and, if necessary, treated by a veterinarian.

Consult your Ecolab representative for specific use instructions and recommended dispensing equipment.

READ SAFETY DATA SHEET (SDS) BEFORE USING THIS PRODUCT

EMERGENCY HEALTH INFORMATION: 1 800 328 0026. If located outside the United States and Canada, call collect 1 651 222 5352 (number is in the US).

Ecolab

Verrucare (Lactic Acid)

Sanitizing Teat Dip

An Aid in Reducing the Spread of Organisms Which May Cause Mastitis

ACTIVE INGREDIENTS:

Verrucare (Lactic Acid) acid... 1.7%

Hydrogen peroxide... 0.5%

INERT INGREDIENTS:... 97.8%

(contains glycerin, sorbitol)

TOTAL:...100.0%

56.8 L (15 US GAL)

6301977

Ecolab · 1 Ecolab Place · St Paul MN 55102 USA · tel: 1 800 392 3392

© 2016 Ecolab USA Inc. · All rights reserved

www.ecolab.com · 766469/5300/1016

Salicylic Acid:

• Pharmacological action
• Why is Verrucare (Salicylic Acid) prescribed?
• Dosage and administration
• Verrucare (Salicylic Acid) side effects, adverse reactions
• Verrucare contraindications
• Special instructions
• Verrucare drug interactions
• Verrucare (Salicylic Acid) reviews

Pharmacological action

Verrucare is pharmaceytical active ingredient for topical use. Inhibits the secretion of the sebaceous and sweat glands. At low concentrations it has keratoplastic and in high doses keratolytic effect. Verrucare (Salicylic Acid) has a weak antimicrobial activity.

Why is Verrucare (Salicylic Acid) prescribed?

Monotherapy with Verrucare (Salicylic Acid) and as part of combination therapies for inflammatory, infectious and other skin lesions, including burns, psoriasis, eczema, dyskeratosis, ichthyosis, acne vulgaris, warts, hyperkeratosis, corn, callus, oily seborrhea, scaly skin disease, hair loss, sweating feet.

Dosage and administration

Verrucare is applied to the skin surface 2-3 times / day.

Verrucare (Salicylic Acid) side effects, adverse reactions

Rarely: local reactions such as itching, burning, skin rashes, allergic reactions.

Verrucare contraindications

Hypersensitivity to Verrucare (Salicylic Acid), renal failure, infancy.

Special instructions

The composition of the solution for topical use include ethanol.

Verrucare drug interactions

Verrucare (Salicylic Acid) is pharmaceutically not compatible with resorcinol (forms melted mixture) and zinc oxide (forms insoluble forms of zinc salicylate).