Obiltoxaximab Intravenous Infusion

Included as part of the PRECAUTIONS section.

ANTHIM®
(an(t)-thim) obiltoxaximab Injection, for Intravenous use

What is the most important information I should know about ANTHIM?

ANTHIM can cause serious side effects, including:

• Serious allergic reactions. Tell your healthcare provider right away if you have itching, hives, rash, throat irritation, cough, dizziness, shortness of breath or chest discomfort while receiving ANTHIM.

What is ANTHIM?

• ANTHIM is a prescription medicine used along with antibiotic medicines to treat people with inhalational anthrax. ANTHIM can also be used to prevent anthrax disease when there are no other treatment options.
• The effectiveness of ANTHIM has been studied only in animals with inhalational anthrax. There have been no studies in people who have inhalational anthrax.
• The safety of ANTHIM was studied in healthy adults. There have been no studies of ANTHIM in children younger than 18 years.
• ANTHIM is not used in prevention or treatment of anthrax meningitis.

Before you receive ANTHIM, tell your healthcare provider about all of your medical conditions, including if you are:

• allergic to obiltoxaximab or any of the ingredients in ANTHIM. See the end of this leaflet for a list of ingredients in ANTHIM.
• allergic to diphenhydramine (Benadryl®)
• pregnant or planning to become pregnant. It is not known if ANTHIM will harm your unborn baby.
• breastfeeding or plan to breastfeed. It is not known if ANTHIM passes into your breast milk. You and your healthcare provider should decide if you will receive ANTHIM or breastfeed.

Tell your healthcare provider about all the medicines you take, including prescription and over-thecounter medicines, vitamins, and herbal supplements.

How will I receive ANTHIM?

• You will be given 1 dose of ANTHIM by a healthcare provider through a vein (IV or intravenous infusion). It takes about 1 hour and 30 minutes to give you the full dose of medicine.
• Your healthcare provider should give you a medicine called diphenhydramine (Benadryl®) before you receive ANTHIM to help reduce your chances of developing a skin reaction from ANTHIM.  Benadryl may be given to you to take by mouth or through a vein.
• Benadryl may make you sleepy, and you should use caution if you will be driving or operating equipment.

What are the possible side effects of ANTHIM?

The most common side effects of ANTHIM include headache, itching, upper respiratory tract infections, cough, IV site bruising, swelling and/or pain, stuffy nose (nasal congestion), hives, and pain in the hands or feet.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of ANTHIM. For more information, ask your healthcare provider.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov.

General information about the safe and effective use of ANTHIM.

• This patient information leaflet summarizes the most important information about ANTHIM. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about ANTHIM that is written for health professionals.

What are the ingredients in ANTHIM?

Active ingredient: Obiltoxaximab

Inactive ingredients: L-histidine, sorbitol and polysorbate 80

The following clinically important adverse reactions are described elsewhere in the labeling:

• Hypersensitivity and Anaphylaxis [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 ANTHIM has been studied only in healthy volunteers. It has not been studied in patients with inhalational anthrax.

The safety of ANTHIM was evaluated in 320 healthy subjects treated with one or more 16 mg/kg IV doses in three clinical studies. Study 1 was a placebo-controlled study evaluating a single dose of ANTHIM vs. placebo (210 subjects received ANTHIM, 70 received placebo). Study 2 was a repeat-dose study in which 70 subjects received the first dose, but 34 and 31 subjects received a second dose of ANTHIM in sequences A (2 weeks apart) and B ( ≥ 4 months apart), respectively. Study 3 was a drug interaction study of a single dose of ANTHIM with ciprofloxacin in 40 subjects (20 subjects received ANTHIM alone and 20 subjects received ANTHIM plus ciprofloxacin for 9 days).

Subjects were 18 to 79 years of age, 54% were male, 70% Caucasian, 26% Black/African American, 2% American Indian/Alaska Native, 1% Asian and 10% Hispanic.

ANTHIM infusion was discontinued in 8/320 healthy subjects (2.5%) in clinical trials due to hypersensitivity reactions or anaphylaxis [see WARNINGS AND PRECAUTIONS].

The most frequently reported adverse reactions were headache, pruritus, infections of the upper respiratory tract, cough, vessel puncture site bruise, infusion site swelling, urticaria, nasal congestion, infusion site pain, and pain in extremity.

Table 3 shows the adverse reactions that occurred in ≥ 1.5% of healthy subjects receiving a single dose of ANTHIM (16 mg/kg IV) and more frequently than those receiving placebo.

Table 3: Adverse Reactions Reported in ≥ 1.5% of Healthy Adult Subjects Exposed to a Single Dose of ANTHIM 16 mg/kg IV

Overall in the single-dose population, subjects who received pre-medication with diphenhydramine were less likely to experience adverse reactions with administration of ANTHIM compared to those who did not (42% vs. 58% respectively). Specifically, the incidence of the following adverse reactions was lower in the subjects who received diphenhydramine prior to ANTHIM infusion compared to those who did not: headache (5% vs. 16%), cough (1% vs. 8%), rash (2% vs. 7%), pruritus (3% vs. 4%) throat irritation (0 vs. 3%), rhinorrhea (0 vs. 3%), and infusion site erythema (0% vs. 4%). Somnolence was only reported in subjects who were pretreated with diphenhydramine.

Clinically important adverse reactions that were reported in < 1.5% of subjects exposed to ANTHIM and at rates higher than in placebo subjects are listed below:

• General disorders and administration site conditions: chest discomfort/pain, fatigue, pyrexia, intravenous site discoloration
• Musculoskeletal and connective tissue disorders: myalgia, musculoskeletal pain
• Respiratory, thoracic and mediastinal disorders: oropharyngeal pain, sinus congestion, rhinorrhea, dysphonia, dyspnea
• Investigations: lymphocyte count decreased, neutrophil count decreased, white blood count decreased, increased creatine phosphokinase
• Cardiac disorders: palpitations, cyanosis
• Neurologic disorders: dizziness
• Gastrointestinal disorders: vomiting, dry mouth

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The development of anti-ANTHIM antibodies was evaluated in all subjects receiving single and double doses of ANTHIM in studies 1, 2 and 3. Eight subjects (2.5%) who received at least one dose of IV ANTHIM were positive for a treatment-emergent anti-therapeutic antibody (ATA) response. Quantitative titers were low ranging from 1:20 - 1:320. There was no evidence of altered PK or toxicity profile in subjects with ATA development.

The incidence of antibody formation is highly dependent on the sensitivity and specificity of the immunogenicity assay. Additionally, the observed incidence of any antibody positivity in an assay is highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to obiltoxaximab with the incidence of antibodies to other products may be misleading.

Read the entire FDA prescribing information for Anthim (Obiltoxaximab Intravenous Infusion)

• Cellcept
• Cortisporin Otic Solution
• Cortisporin Otic Suspension
• Idhifa
• Penicillin G Potassium
• Penicillin VK

• Rituxan
• Vyxeos
• Zevalin
• Zovirax
• Zovirax Injection

© Anthim Patient Information is supplied by Cerner Multum, Inc. and Anthim Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.