Eraxis

The most serious adverse reactions reported with ERAXIS are:

• Hepatic effects [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of ERAXIS for Injection was assessed in 929 individuals, including 257 healthy subjects and 672 patients in clinical trials of candidemia, other forms of Candida infections, and esophageal candidiasis. A total of 633 patients received ERAXIS at daily doses of either 50 mg or 100 mg. A total of 481 patients received ERAXIS for ≥14 days.

Candidemia/Other Candida Infections

Three studies (one comparative vs. fluconazole, two non-comparative) assessed the efficacy and safety of ERAXIS (100 mg) in patients with candidemia and other Candida infections.

The data described below reflect exposure to ERAXIS and fluconazole in 127 and 118 patients, respectively, with candidemia and other forms of invasive candidiasis, in the randomized, comparative trial of the efficacy and safety of ERAXIS to that of fluconazole. In ERAXIS-treated patients, the age range was 16-89 years, the gender distribution was 51% male and 49% female, and the race distribution was 72% White, 18% Black/African American, 9% other races. Patients were randomized to receive once daily IV ERAXIS (200 mg loading dose followed by 100 mg maintenance dose) or IV fluconazole (800 mg loading dose followed by 400 mg maintenance dose). Treatment was administered for at least 14 and not more than 42 days.

The number of patients with adverse reactions leading to discontinuation of study medication was 11.5% in the ERAXIS arm and 21.6% in the fluconazole arm. The most common adverse reactions leading to study drug discontinuation were multi-organ failure and systemic Candida infection in the ERAXIS arm.

Table 2 presents adverse reactions that were reported in ≥5% of subjects receiving ERAXIS or fluconazole therapy in this trial.

Table 2: Adverse Reactions Reported in ≥5% of Subjects Receiving ERAXIS or Fluconazole Therapy for Candidemia/other Candida Infections*, **

Esophageal Candidiasis

The data described below reflect exposure to ERAXIS and fluconazole in 300 and 301 patients, respectively, with esophageal candidiasis in a randomized trial comparing the efficacy and safety of ERAXIS to that of oral fluconazole. In ERAXIS-treated patients, the age range was 18-68 years, the gender distribution was 42% male and 58% female and the race distribution was 15% White, 49% Black/African American, 15% Asian, 0.3 % Hispanic, 21% other races. Patients were randomized to receive IV ERAXIS (100 mg on day 1, followed by 50 mg per day) or oral fluconazole (200 mg on day 1, followed by 100 mg per day) for 7 days beyond resolution of symptoms (range, 14-21 days).

Twenty eight (9%) patients in the ERAXIS arm and 36 (12%) patients in the fluconazole arm had adverse reactions leading to discontinuation of study medication. The most common adverse reactions leading to study drug discontinuation were maculopapular rash for the ERAXIS arm. The most common adverse reactions leading to discontinuation were rash and increased AST for the fluconazole arm.

Table 3 presents adverse reactions that were reported in ≥5% of subjects receiving ERAXIS therapy.

Table 3 Adverse Reactions Reported in ≥5% of Subjects Receiving ERAXIS or Fluconazole Therapy for Esophageal Candidiasis*, **

Less Common Adverse Reactions

The following selected adverse reactions occurred in <2% of patients:

Blood and Lymphatic: coagulopathy, thrombocytopenia

Cardiac: atrial fibrillation, bundle branch block (right), sinus arrhythmia, ventricular extrasystoles

Eye: eye pain, vision blurred, visual disturbance

General and Administration Site: infusion related reaction, peripheral edema, rigors

Hepatobiliary: abnormal liver function tests, cholestasis, hepatic necrosis

Infections: clostridial infection

Investigations: amylase increased, bilirubin increased, CPK increased, electrocardiogram QT prolonged, gammaglutamyl transferase increased, lipase increased, potassium decreased, prothrombin time prolonged, urea increased

Nervous System: convulsion, dizziness

Respiratory, Thoracic and Mediastinal: cough

Skin and Subcutaneous Tissue: angioneurotic edema, erythema, pruritus, sweating increased, urticaria

Vascular: flushing, hot flushes, thrombophlebitis superficial

Post-marketing Experience

The following adverse reactions have been identified during post approval use of anidulafungin. 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.

Immune: Anaphylactic shock, anaphylactic reaction, bronchospasm [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Eraxis (Anidulafungin)

Other drugs may interact with anidulafungin, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

In the U.S.

• Eraxis

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Antifungal

Pharmacologic Class: Glucan Synthesis Inhibitor

Chemical Class: Echinocandin

Anidulafungin is an antifungal medicine. It is used to treat fungal infections in the blood, abdomen or stomach, and esophagus (part of your throat where food passes from the pharynx to the stomach).

This medicine is to be given only by or under the direct supervision of a doctor.

It is very important that your doctor check you closely while you are receiving this medicine. This is to make sure the medicine has worked properly. Blood tests may be needed to check for unwanted effects.

Tell your doctor right away if you have any symptoms of liver problems including dark-colored urine or pale stools, nausea, vomiting, loss of appetite, pain in your upper stomach, or yellow skin or eyes.

This medicine may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth after receiving this medicine.

It is important to tell your doctor if you are pregnant, planning to become pregnant.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Black, tarry stools
• chills
• cough
• decreased urine
• dry mouth
• fever
• increased thirst
• irregular heartbeat
• loss of appetite
• lower back or side pain
• mood or mental changes
• muscle pain or cramps
• nausea or vomiting
• numbness or tingling in the hands, feet or lips
• painful or difficult urination
• pale skin
• seizures
• shortness of breath
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness

• Abdominal or stomach pain
• back pain
• bleeding gums
• blood in the urine or stools
• bloody stools
• bluish color of skin
• blurred or loss of vision
• changes in skin color
• chest pain
• chest tightness
• clay-colored stools
• constipation
• dark urine
• depression
• diarrhea
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drowsiness
• extra heartbeats
• fainting
• fast heartbeat
• flushed, dry skin
• flushing
• fruit-like breath odor
• headache
• hives or welts
• incoherent speech
• increased hunger
• increased urination
• irregular fast heartbeat
• irritability
• itching
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• metallic taste
• muscle spasms (tetany) or twitching
• muscle weakness
• nervousness
• pain, redness, or swelling in the arm or leg
• pain, tenderness, and swelling of foot or leg
• pinpoint red spots on the skin
• pounding in the ears
• redness of the skin
• restlessness
• skin rash
• slow heartbeat
• sore mouth or tongue
• sweating
• swelling of the feet or lower legs
• swollen glands
• trembling
• trouble breathing
• unexplained weight loss
• unpleasant breath odor
• unusually warm skin
• vomiting of blood
• weakness
• weight loss
• white patches in the mouth or throat or on the tongue
• white patches with diaper rash
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• belching
• bloating or swelling of the face, arms, hands, lower legs, or feet
• disturbed color perception
• double vision
• eye pain
• feeling of warmth
• feeling unusually cold
• halos around light
• indigestion
• loss of bowel control
• night blindness
• over bright appearance of lights
• rapid weight gain
• redness of the face, neck, arms, and occasionally, upper chest
• shivering
• stomach discomfort or upset
• tingling of the hands or feet
• tunnel vision
• unusual weight gain or loss
• upper stomach pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Recommended Dosing

Candidemia and other Candida infections (intra-abdominal abscess, and peritonitis)

The recommended dose is a single 200 mg loading dose of Eraxis on Day 1, followed by 100 mg daily dose thereafter. Duration of treatment should be based on the patient's clinical response. In general, antifungal therapy should continue for at least 14 days after the last positive culture.

Esophageal Candidiasis

The recommended dose is a single 100 mg loading dose of Eraxis on Day 1, followed by 50 mg daily dose thereafter. Patients should be treated for a minimum of 14 days and for at least 7 days following resolution of symptoms. Duration of treatment should be based on the patient's clinical response. Because of the risk of relapse of esophageal candidiasis in patients with HIV infections, suppressive antifungal therapy may be considered after a course of treatment.

Preparation for Administration

Eraxis for Injection must be reconstituted with sterile Water for Injection and subsequently diluted only with 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline). The compatibility of reconstituted Eraxis with intravenous substances, additives, or medications other than 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline) has not been established.

Reconstitution 50 mg/vial

Aseptically reconstitute each 50 mg vial with 15 mL of sterile Water for Injection to provide a concentration of 3.33 mg/mL. The reconstituted solution can be stored for up to 24 hours at temperatures up to 25°C (77°F) prior to dilution into the infusion solution.

Reconstitution 100 mg/vial

Aseptically reconstitute each 100 mg vial with 30 mL of sterile Water for Injection to provide a concentration of 3.33 mg/mL. The reconstituted solution can be stored for up to 24 hours at temperatures up to 25°C (77°F) prior to dilution into the infusion solution.

Dilution and Infusion

Aseptically transfer the contents of the reconstituted vial(s) into the appropriately sized IV bag (or bottle) containing either 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP (normal saline). See Table 1 for the dilution and infusion instructions for each dose.

Caution: The rate of infusion should not exceed 1.1 mg/minute (equivalent to 1.4 mL/minute or 84 mL/hour when reconstituted and diluted per instructions) [see Warnings and Precautions (5.2)].

The infusion solution may be stored for up to 48 hours at temperatures up to 25°C (77°F), or stored frozen for at least 72 hours prior to administration.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If particulate matter or discoloration is identified, discard the solution.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal carcinogenicity studies of anidulafungin have not been conducted.

Anidulafungin was not genotoxic in the following in vitro studies: bacterial reverse mutation assays, a chromosome aberration assay with Chinese hamster ovary cells, and a forward gene mutation assay with mouse lymphoma cells. Anidulafungin was not genotoxic in mice using the in vivo micronucleus assay.

Anidulafungin produced no adverse effects on fertility in male or female rats at intravenous doses of 20 mg/kg/day (equivalent to 2 times the proposed therapeutic maintenance dose of 100 mg/day on the basis of relative body surface area).

Animal Toxicology and/or Pharmacology

In 3 month studies, liver toxicity, including single cell hepatocellular necrosis, hepatocellular hypertrophy and increased liver weights were observed in monkeys and rats at doses equivalent to 5–6 times human exposure. For both species, hepatocellular hypertrophy was still noted one month after the end of dosing.

Hepatic Effects

Inform patients about the risk of developing abnormal liver function tests and/or hepatic dysfunction. Advise the patient that liver function tests may be monitored during treatment.

Hypersensitivity

Inform the patient that anaphylactic reactions, including shock were reported with Eraxis. Inform the patient if these reactions occur, Eraxis may be discontinued and appropriate treatment administered.

Inform the patient that Eraxis is also known to cause infusion-related adverse reactions, possibly histamine-mediated. Inform the patient to report symptoms including rash, urticaria, flushing, pruritus, dyspnea, and hypotension to their healthcare provider.

Pregnant Women and Nursing Mothers

Inform patients that Eraxis has not been studied in pregnant women or nursing mothers so the effects of Eraxis on pregnant women or nursing infants are not known. Instruct patients to tell their healthcare provider if they are pregnant, become pregnant, or are thinking about becoming pregnant. Instruct patients to tell their healthcare provider if they plan to breast-feed their infant.

This product's label may have been updated. For current full prescribing information, please visit www.pfizer.com.

LAB-0336-9.0
November 2013

Use Eraxis exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Eraxis is injected into a vein through an IV. You may be shown how to use an IV at home. Do not self-inject this medicine if you do not understand how to give the injection and properly dispose of used needles, IV tubing, and other items used to inject the medicine.

Eraxis is a powder medicine that must be mixed with a liquid (diluent) before using it. You will then need to dilute this mixture into a solution with another liquid in an IV bag. If you are using the injections at home, be sure you understand how to properly mix and store the medicine.

Eraxis is sometimes given for up to 14 days after lab tests show that the infection has cleared. Use this medicine for the full prescribed length of time. This medicine will not treat a viral infection such as the flu or a common cold.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Store the dry powder medicine in a refrigerator. Do not freeze.

After you mix the powder and diluent, you may store the Eraxis mixture at room temperature for up to 24 hours before further diluting it. The final diluted solution may be stored at room temperature for up to 48 hours.

You may also store the diluted solution in a freezer for at least 72 hours before using it.

Do not use Eraxis diluted solution if it has changed colors or has particles in it. Call your pharmacist for new medication.

Other drugs may interact with Eraxis, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.