Moxatag

Name: Moxatag

Description

MOXATAG (amoxicillin extended-release) tablets for oral administration are provided as blue film-coated, oval shaped tablets that contain 775 mg of amoxicillin as the trihydrate and are printed with “MB111” on one side in black edible ink.

Amoxicillin is a semi-synthetic antibiotic, an analog of ampicillin, with bactericidal activity against gram-positive and gram-negative microorganisms.

Chemically, amoxicillin is (2 S,5 R,6 R)-6-[(R)-(-)-2-amino-2-(phydroxyphenyl) acetamido]-3,3-dimethyl-7-oxo-4-thia-1azabicyclo[3.2.0]heptane-2-carboxylic acid trihydrate. Its chemical name

The amoxicillin molecular formula is C16H19N3O5S•3H2O, and the molecular weight is 419.45.

MOXATAG is an extended release tablet formulation consisting of three components, one immediate-release and two delayed-release, each containing amoxicillin. The three components are combined in a specific ratio to prolong the release of amoxicillin from MOXATAG compared to immediate-release amoxicillin.

Each tablet contains amoxicillin, crospovidone, FD&C Blue #2 lake, hypromellose, hypromellose acetate succinate, iron oxide, magnesium stearate, methacrylic acid copolymer, microcrystalline cellulose, polyethylene glycol 400, polyoxyl 35 castor oil, povidone, shellac, colloidal silicon dioxide, sodium lauryl sulfate, talc, titanium dioxide, and triethyl citrate.

Side effects

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.

Clinical Study Experience

Tonsillitis and/or Pharyngitis

In a controlled Phase 3 trial, 302 adult and pediatric patients ( ≥ 12 years) were treated with MOXATAG 775 mg once-daily for 10 days and 306 adult and pediatric patients ( ≥ 12 years) were treated with penicillin VK 250 mg QID for 10 days.

In this clinical trial, the majority of treatment-emergent adverse reactions were of a mild and transient nature with similar frequency reported in both treatment groups. Discontinuation due to drug-related treatment-emergent adverse reactions occurred in 1.3% of the MOXATAG-treated patients and 3.3% of the penicillin VK-treated patients.

The most frequently reported adverse reactions ( ≥ 1%) which were suspected or probably drug-related are shown in Table 1.

Table 1: Drug-Related Treatment-Emergent Adverse Reactions by System Organ Class Experienced by ≥ 1% of Patients in Either Treatment Group – ITT/Safety Population

System Organ Class/
Preferred Term*
Number (%) of patients
MOXATAG
(N =302)
Penicillin VK
(N = 306 )
Patients with at least one drug-related treatment-emergent adverse event 32 (10.6) 45 (14.7)
Infections and infestations
  Vulvovaginal mycotic infection 6 (2.0) 8 (2.6)
Gastrointestinal disorders
  Diarrhea 5 (1.7) 6 (2.0)
  Nausea 4(1.3) 2 (0.7)
  Vomiting 2 (0.7) 5 (1.6)
  Abdominal pain 1 (0.3) 3 (1.0)
Nervous system disorders
  Headache 3 (1.0) 3 (1.0)
*Presented in decreasing order of frequency in the MOXATAG column within each system organ class.

Adverse Reactions For Other Amoxicillin Products

The following adverse reactions have been reported for other products containing amoxicillin:

Infections and Infestations: Mucocutaneous candidiasis.

Gastrointestinal: Nausea, vomiting, diarrhea, and hemorrhagic/pseudomembranous colitis.

Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment.

Hypersensitivity Reactions: Anaphylaxis (See WARNINGS AND PRECAUTIONS).

Serum sickness like reactions, erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson Syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis and urticaria have been reported. (NOTE: These hypersensitivity reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, amoxicillin should be discontinued unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to amoxicillin therapy.)

Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted, but the significance of this finding is unknown. Hepatic dysfunction including cholestatic jaundice, hepatic cholestasis and acute cytolytic hepatitis have been reported.

Hemic and Lymphatic Systems: Anemia, including hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia, and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

Central Nervous System: Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioral changes, and/or dizziness have been reported rarely.

Renal: Crystalluria has also been reported.

Miscellaneous: Tooth discoloration (brown, yellow, or gray staining) has been rarely reported. Most reports occurred in pediatric patients. Discoloration was reduced or eliminated with brushing or dental cleaning in most cases.

Moxatag Overview

Amoxicillin is a prescription medication used to treat certain bacterial infections such as pneumonia, bronchitis, gonorrhea, and certain types of ulcers.  It can also treat bacterial infections of the ears, nose, throat, urinary tract, and skin.  This medication belongs to a group of drugs called penicillin antibiotics,  which work by blocking the growth of bacteria.

Amoxicillin comes as a capsule, tablet, and oral suspension forms. This medication is taken up to 3 times daily, with or without food.

Common side of amoxicillin effects include nausea, vomiting, diarrhea, and headache.

Manufacturer

  • Middlebrook Pharmaceuticals, Inc.

  • Shionogi Inc.

  • Victory Pharma, Inc.

Inform MD

Before taking amoxicillin, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • are allergic to penicillin or any other medications
  • develop watery and bloody stools (with or without stomach cramps and fever) 2 or more months after having taken the last dose of the antibiotic. This is not typical, and your doctor should be notified.
  • have a history of diarrhea caused by taking antibiotics
  • have phenylketonuria
  • have kidney disease
  • have asthma
  • have hay fever
  • are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

How should I take amoxicillin?

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take this medicine at the same time each day.

The Moxatag brand of amoxicillin should be taken with food, or within 1 hour after eating a meal.

Some forms of amoxicillin may be taken with or without food. Check your medicine label to see if you should take your amoxicillin with food or not.

You may need to shake amoxicillin liquid well just before you measure a dose. Follow the directions on your medicine label.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one. You may place the liquid directly on the tongue, or you may mix it with water, milk, baby formula, fruit juice, or ginger ale. Drink all of the mixture right away. Do not save any for later use.

The chewable tablet should be chewed before you swallow it.

Do not crush, chew, or break an extended-release tablet. Swallow it whole.

While using amoxicillin, you may need frequent blood tests. Your kidney and liver function may also need to be checked.

If you are taking amoxicillin with clarithromycin and/or lansoprazole to treat stomach ulcer, use all of your medications as directed. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

Use this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Amoxicillin will not treat a viral infection such as the flu or a common cold.

Do not share this medicine with another person, even if they have the same symptoms you have.

This medicine can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using amoxicillin.

Store at room temperature away from moisture, heat, and light.

You may store liquid amoxicillin in a refrigerator but do not allow it to freeze. Throw away any liquid amoxicillin that is not used within 14 days after it was mixed at the pharmacy.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include confusion, behavior changes, a severe skin rash, urinating less than usual, or seizure (black-out or convulsions).

Before Using Moxatag

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of amoxicillin in children. However, newborns and infants 3 months of age and younger have incompletely developed kidney functions, which may need a lower dose of this medicine.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of amoxicillin in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution and an adjustment in the dose for patients receiving amoxicillin.

Pregnancy

Pregnancy Category Explanation
All Trimesters B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Chlortetracycline
  • Cholera Vaccine, Live
  • Demeclocycline
  • Doxycycline
  • Lymecycline
  • Meclocycline
  • Methacycline
  • Methotrexate
  • Minocycline
  • Oxytetracycline
  • Rolitetracycline
  • Tetracycline
  • Venlafaxine
  • Warfarin

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Acenocoumarol
  • Khat
  • Probenecid

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Allergy to penicillins or cephalosporin antibiotics (e.g., cefaclor, cefadroxil, cephalexin, Ceftin®, or Keflex®) or
  • Mononucleosis (viral infection)—Should not be used in patients with these conditions.
  • Kidney disease, severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
  • Phenylketonuria (PKU)—The chewable tablet contains phenylalanine, which can make this condition worse.

What are some other side effects of Moxatag?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Upset stomach or throwing up.
  • Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Indications and usage

Tonsillitis and/or Pharyngitis

Moxatag is a penicillin-class antibacterial indicated for the treatment of tonsillitis and/or pharyngitis secondary to Streptococcus pyogenes (S. pyogenes) in adults and pediatric patients 12 years and older.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Moxatag and other antibacterial drugs, Moxatag should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Use in specific populations

Pregnancy

Teratogenic Effects. Pregnancy Category B. Reproduction studies have been performed in mice and rats at doses up to 2000 mg/kg (12.5 and 25 times the human dose in mg/m2) and have revealed no evidence of impaired fertility or harm to the fetus due to amoxicillin. 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.

Labor and Delivery

Oral ampicillin-class antibiotics are poorly absorbed during labor. Studies in guinea pigs showed that intravenous administration of ampicillin slightly decreased the uterine tone and frequency of contractions but moderately increased the height and duration of contractions. However, it is not known whether use of amoxicillin in humans during labor or delivery has immediate or delayed adverse effects on the fetus, prolongs the duration of labor, or increases the likelihood that forceps delivery or other obstetrical intervention or resuscitation of the newborn will be necessary.

Nursing Mothers

Penicillins have been shown to be excreted in human milk. Amoxicillin use by nursing mothers may lead to sensitization of infants. Caution should be exercised when amoxicillin is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Moxatag in pediatric patients 12 years of age and older have been established based on results of a clinical trial that included adults and pediatric patients (12 years and older). [see Clinical Studies (14)] Sixty-three (21%) of the study participants were pediatric patients 12 years of age and older. There were no significant differences in treatment response or adverse reactions from adults.

The safety and effectiveness of Moxatag in pediatric patients younger than 12 years has not been established.

Geriatric Use

Clinical studies with Moxatag did not include a sufficient number of patients aged 65 years and over to determine whether they respond differently from younger patients. Other reported clinical experiences with amoxicillin have not yet identified differences in responses between the elderly and younger patients, but a greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidneys, and the risk of adverse 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.

Renal Impairment

Moxatag has not been studied in patients with renal impairment; however, a reduction of amoxicillin dose is generally recommended for patients with severe renal impairment. Therefore, Moxatag is not recommended for use in patients with severe renal impairment (CrCl <30 mL/min) or patients on hemodialysis.

Clinical pharmacology

Mechanism of Action

Amoxicillin is an antibacterial drug. [see Clinical Pharmacology (12.4)]

Pharmacokinetics

Moxatag is an extended-release formulation of amoxicillin intended to provide once-daily dosing. Following the administration of Moxatag with a low-fat meal in healthy subjects, mean amoxicillin AUC0-∞, Cmax, and Tmax values were 29.8 μg•h/mL, 6.6 μg/mL and 3.1 hours, respectively. The mean plasma concentration-time curve is shown below in Figure 1.

Figure 1. Mean Amoxicillin Plasma Concentrations Following a Single Oral Dose of Moxatag With a Low-Fat Meal in Healthy Subjects (N=20)

Administration of Moxatag with food decreases the rate, but not the extent of amoxicillin absorption. Compared to immediate-release amoxicillin suspension, the rate of amoxicillin absorption following administration of Moxatag was slower, resulting in a lower Cmax and longer Tmax. Total amoxicillin exposure (AUC) achieved with Moxatag is similar to that observed after oral administration of a comparable dose of immediate-release amoxicillin suspension.

Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. Amoxicillin is approximately 20% protein bound in human serum.

Amoxicillin is primarily cleared by renal excretion. Approximately 60% of an oral dose of immediate-release amoxicillin is eliminated unchanged in urine. The half-life of amoxicillin after oral administration of Moxatag is approximately 1.5 hours, similar to that of immediate-release amoxicillin. No accumulation of amoxicillin was observed after once-daily dosing of 775 mg of Moxatag for 7 days.

Drug Interactions

In a study of healthy adult subjects, amoxicillin AUC was similar whereas Cmax increased approximately 35% following the administration of lansoprazole with Moxatag given with food.

Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of Moxatag and probenecid may result in increased and prolonged blood levels of amoxicillin. The clinical relevance of this finding has not been evaluated.

Microbiology

Mechanism of Action

Amoxicillin is similar to penicillin in its bacterial action against susceptible organisms during the stage of active multiplication. It acts through the inhibition of cell wall biosynthesis that leads to the death of the bacteria.

Mechanism of Resistance

To date there are no known mechanisms of resistance to penicillin or amoxicillin in Streptococcus pyogenes.

Moxatag has been shown to be active in vitro against isolates of the microorganism S. pyogenes and in clinical infections as described in the INDICATIONS AND USAGE section.

Gram-Positive Bacteria:

Streptococcus pyogenes

The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptibility breakpoint of amoxicillin (as determined by susceptibility tests using the class representative agents penicillin or ampicillin).

Gram-Positive Bacteria:

Streptococcus spp. (Group B, C, and G; Beta-hemolytic)

Susceptibility Test Methods:

When available, the clinical microbiology laboratory should provide cumulative in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.

Dilution Techniques

Quantitative methods are used to determine antimicrobial MICs. These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized method (broth or agar)1,2.

Susceptibility of beta-hemolytic streptococcal isolates to amoxicillin may be inferred by testing penicillin. An organism that is susceptible to penicillin can be considered susceptible to amoxicillin when used for approved indications2. If testing is performed, any beta hemolytic streptococcal isolate found to be nonsusceptible should be reidentified, retested, and if confirmed, submitted to a public health laboratory.

Quality Control

Standardized susceptibility test procedures1,2 require the use of laboratory controls to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test. Standard amoxicillin powder should provide the following range of MIC values provided in Table 2. For the disk diffusion technique, the criteria in Table 2 should be achieved.

Table 2. Acceptable Quality Control Ranges for Amoxicillina
aQC limits for testing E. coli 35218 when tested on Haemophilus Test Medium (HTM) are greater than 256 mcg/mL for amoxicillin; testing amoxicillin may help to determine if the isolate has maintained its ability to produce beta-lactamase2.
bATCC = American Type Culture Collection

Quality Control Organism

Minimum Inhibitory Concentrations (mcg/mL)

Disk Diffusion Zone
Diameters
(mm)

Streptococcus pneumoniae ATCCb 49619

0.03–0.12

---

Klebsiella pneumoniae
ATCC 700603

>128

---

Principal display panel - professional sample

Professional Sample

NDC 69442-030-11
1 blister
containing 1 tablet

Moxatag®
(amoxicillin extended release tablets)
1 Day of Therapy

775 mg

Professional Sample - NOT TO BE SOLD
Rx only

Vernalis
THERAPEUTICS

Moxatag® 775 mg
(amoxicillin extended release tablets)

Dosage: Please take as directed.
Do no chew or crush the tablet.
Each extended-release tablet contains 775 mg of
amoxicillin as the trihydrate.
Store at 25°C (77°F): (see insert).

See package insert for complete prescribing
information.

Manufactured in Ireland for:
Vernalis (R&D) Ltd

Distributed by: Vernalis Therapeutics, Inc.
Berwyn, PA 19312

Rev. 1115.

Vernalis
THERAPEUTICS

Moxatag 
amoxicillin tablet, film coated, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:69442-030
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
amoxicillin (amoxicillin anhydrous) amoxicillin anhydrous 775 mg
Inactive Ingredients
Ingredient Name Strength
crospovidone  
FD&C blue no. 2  
hypromelloses  
hypromellose acetate succinate 16070722 (3 mm2/s)  
ferric oxide red  
magnesium stearate  
methacrylic acid - methyl methacrylate copolymer (1:1)  
cellulose, microcrystalline  
polyethylene glycol 400  
polyoxyl 35 castor oil  
POVIDONES  
shellac  
SILICON DIOXIDE  
sodium lauryl sulfate  
talc  
titanium dioxide  
triethyl citrate  
Product Characteristics
Color blue (blue) Score no score
Shape OVAL (OVAL) Size 22mm
Flavor Imprint Code MB;111;
Contains     
Packaging
# Item Code Package Description
1 NDC:69442-030-01 30 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE
2 NDC:69442-030-10 10 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE
3 NDC:69442-030-11 10 TABLET, FILM COATED, EXTENDED RELEASE in 1 BLISTER PACK
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA050813 01/15/2016
Labeler - Vernalis Therapeutics, Inc. (079561686)
Revised: 06/2016   Vernalis Therapeutics, Inc.

What is Moxatag?

Moxatag (amoxicillin) is a penicillin antibiotic that fights bacteria.

Moxatag is used to treat tonsillitis and/or pharyngitis secondary to Streptococcus pyogenes (S. pyogenes) in adults and children 12 yrs and older. Moxatag is an extended release tablet consisting of three parts, an immediate-release and two delayed-release components, each containing amoxicillin.

Amoxicillin may also be used for purposes not listed in this medication guide.

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