Vibativ

VIBATIV®
(vy-'ba-tiv)
(telavancin) for Injection

Read this Medication Guide before you receive VIBATIV. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

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

VIBATIV can cause serious side effects, including:

• Increased risk of death. VIBATIV was associated with an increased risk of death compared to vancomycin in people who already had kidney problems and were treated for bacterial pneumonia that you can get when you are in the hospital.
• New or worsening kidney problems. Your healthcare provider should do a blood test to check your kidneys before you start, while you receive, and after you stop receiving VIBATIV.
• VIBATIV may harm your unborn baby. Women who can become pregnant should have a blood pregnancy test before receiving VIBATIV.
  • Talk to your healthcare provider if you are pregnant or plan to become pregnant. Your healthcare provider will decide if VIBATIV is the right medicine for you.
  • Women who can become pregnant should use effective birth control (contraception) while receiving VIBATIV.
  • If you become pregnant while receiving VIBATIV, tell your healthcare provider right away. Talk to your healthcare provider about taking part in the VIBATIV Pregnancy Registry. This is a study to learn how VIBATIV affects pregnancy and babies. You can enroll in this registry by calling 1-855-633-8479.

What is VIBATIV?

VIBATIV is a prescription antibacterial medicine used alone, or with other medicines, to treat adults with certain types of germs (bacteria) that cause:

• Serious skin infections
• Hospital-Acquired Bacterial Pneumonia (HABP)
• Ventilator-Associated Bacterial Pneumonia (VABP)

It is not known if VIBATIV is safe or effective in children under 18 years of age.

Who should not take VIBATIV?

Do not take VIBATIV if you:

• are allergic to telavancin or any of the ingredients in VIBATIV. See the end of this Medication Guide for a complete list of ingredients in VIBATIV.

What should I tell my healthcare provider before receiving VIBATIV?

Before you receive VIBATIV, tell your healthcare provider if you:

• have had a serious allergic reaction to VIBATIV or vancomycin
• have kidney problems
• have diabetes
• have or have had heart problems, including QTc prolongation or a family history of it
• have high blood pressure
• have any other medical conditions
• are breastfeeding or plan to breastfeed. It is not known if VIBATIV passes into breast milk. You and your healthcare provider should decide if you will breastfeed while receiving VIBATIV.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. VIBATIV and other medicines can affect each other causing side effects.

Especially tell your healthcare provider if you take:

• a Non-Steroidal Anti-Inflammatory Drug (NSAID)
• certain blood pressure medicines called ACE Inhibitors or ARBs
• water pills (diuretics)
• a blood thinner
• medicine to control your heart rate or rhythm (antiarrhythmics)

Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.

How will I receive VIBATIV?

• VIBATIV is given by your healthcare provider through a needle placed into your vein (IV infusion) slowly over 1 hour, 1 time each day, for 7 to 21 days.
• Do not stop receiving VIBATIV unless your healthcare provider tells you to, even if you feel better.
• Your healthcare provider will do blood tests before you start and while you receive VIBATIV.

What are the possible side effects of VIBATIV?

VIBATIV may cause serious side effects, including:

See “What is the most important information I should know about VIBATIV?”

• Serious allergic reactions. Allergic reactions can happen in people who take VIBATIV, even after only one dose. Stop taking VIBATIV and get emergency medical help right away if you get any of the following symptoms of a severe allergic reaction:
  • hives
  • trouble breathing or swallowing
  • swelling of the lips, tongue, face
  • throat tightness, hoarseness
  • rapid heartbeat
  • faint
• Infusion-related reactions. People who receive VIBATIV too quickly can have a certain type of skin reaction called “Red-man Syndrome”. Signs and symptoms of Red-man Syndrome can include:
  • red color (flushing)
  • rash
  • itching
• Problems with the electrical system of your heart (QTc prolongation). Tell your healthcare provider right away if you have a change in your heartbeat such as a fast or irregular heartbeat or if you had a fainting episode.

Call your healthcare provider right away if you have any of the serious side effects listed above.

The most common side effects of VIBATIV include:

• change in your sense of taste
• nausea
• vomiting
• foamy urine
• diarrhea

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

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

How should I store VIBATIV?

• Store VIBATIV in the original package
• Keep VIBATIV refrigerated between 35°F to 46°F (2°C to 8°C)
• Keep out of heat

Keep VIBATIV and all medicines out of the reach of children.

General Information about the safe and effective use of VIBATIV.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use VIBATIV for a condition for which it is not prescribed.

This Medication Guide summarizes the most important information about VIBATIV. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about VIBATIV that is written for health professionals.

For more information, go to www.vibativ.com or call 1-855-633-8479.

What are the ingredients in VIBATIV?

Active ingredient: telavancin hydrochloride

Inactive ingredients: hydroxypropylbetadex, Ph. Eur (hydroxypropyl-beta-cyclodextrin), mannitol, sodium hydroxide and hydrochloric acid

This Medication Guide has been approved by the U.S. Food and Drug Administration

Vibativ is part of the drug class:

• Glycopeptide antibacterials

FETAL RISK

• Women of childbearing potential should have a serum pregnancy test prior to administration of Vibativ.
• Avoid use of Vibativ  during pregnancy unless potential benefit to the patient outweighs potential risk to the fetus.
• Adverse developmental outcomes observed in 3 animal species at clinically relevant doses raise concerns about potential adverse developmental outcomes in humans.

KIDNEY INJURY

• Vibativ can cause new or worsening kidney problems in patients.

Absorption

Plasma Concentrations

In healthy young adults, pharmacokinetics are linear following single IV doses of 5–12.5 mg/kg or multiple IV doses of 7.5–15 mg/kg given once daily for up to 7 days.1

Steady-state concentrations achieved by day 3 of once-daily dosage.1

Special Populations

AUC increased in patients with renal impairment;1 mean AUC is increased approximately 29% in those with Clcr 30–50 mL/minute and 118% in those with Clcr <30 mL/minute.1

Distribution

Extent

Concentration in skin blister fluid is 40% of plasma concentrations after administration of 7.5 mg/kg once daily for 3 days.1

Concentrations in pulmonary epithelial lining fluid and alveolar macrophages exceed MIC90 of S. aureus for at least 24 hours after a dose in healthy individuals receiving telavancin 10 mg/kg once daily for 3 days.1

Not known whether telavancin is distributed into milk in humans.1

Plasma Protein Binding

90%, primarily albumin.1 Protein binding not affected by renal or hepatic impairment.1

Elimination

Metabolism

Metabolic pathway not elucidated to date.1 Three hydroxylated metabolites identified; the major metabolite is THRX-651540.1

Not metabolized by CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 3A4, 3A5, or 4A11.1

Elimination Route

Approximately 76% of a dose recovered in urine; <1% of dose recovered in feces.1

In adults with end-stage renal disease, approximately 5.9% of a dose is removed by 4 hours of hemodialysis.1 In vitro date indicate telavancin may be removed by continuous venovenous hemofiltration (CVVH).1

Half-life

Approximately 8 hours in adults.1

Special Populations

Pharmacokinetics not altered in geriatric individuals based solely on age.1

Pharmacokinetics altered by decreased renal function.1

No clinically important change in pharmacokinetics in adults with moderate hepatic impairment (Child-Pugh class B).1 8 Not evaluated in adults with severe hepatic impairment (Child-Pugh class C).1

In the U.S.

• Vibativ

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Antibiotic

Chemical Class: Glycopeptide

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 have not been performed on the relationship of age to the effects of telavancin injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of telavancin injection 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 telavancin injection.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while 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 receiving 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 not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Bepridil
• Cisapride
• Dronedarone
• Heparin
• Levomethadyl
• Mesoridazine
• Pimozide
• Piperaquine
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

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.

• Alfuzosin
• Amiodarone
• Amitriptyline
• Amoxapine
• Anagrelide
• Apomorphine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Buserelin
• Chlorpromazine
• Cholera Vaccine, Live
• Ciprofloxacin
• Clarithromycin
• Clomipramine
• Clozapine
• Crizotinib
• Dabrafenib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Deutetrabenazine
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Droperidol
• Efavirenz
• Erythromycin
• Escitalopram
• Fingolimod
• Flecainide
• Fluconazole
• Fluoxetine
• Foscarnet
• Gatifloxacin
• Gemifloxacin
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Ivabradine
• Ketoconazole
• Lapatinib
• Leuprolide
• Levofloxacin
• Lopinavir
• Lumefantrine
• Mefloquine
• Methadone
• Metronidazole
• Mifepristone
• Moxifloxacin
• Nafarelin
• Nilotinib
• Norfloxacin
• Nortriptyline
• Octreotide
• Ondansetron
• Paliperidone
• Panobinostat
• Pasireotide
• Pazopanib
• Pimavanserin
• Pitolisant
• Posaconazole
• Procainamide
• Prochlorperazine
• Promethazine
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Ribociclib
• Salmeterol
• Sevoflurane
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• Sulpiride
• Sunitinib
• Tacrolimus
• Telithromycin
• Tetrabenazine
• Toremifene
• Trifluoperazine
• Trimipramine
• Triptorelin
• Vandetanib
• Vemurafenib
• Vinflunine
• Voriconazole
• Zuclopenthixol

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:

• Congestive heart failure or
• Diabetes or
• Hypertension (high blood pressure)—Use of this medicine may lead to kidney problems.

• Heart rhythm problems (eg, QT prolongation), or a family history of—Use with caution. May make these conditions worse.

• Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• If you have an allergy to telavancin or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have heart failure (weak heart).
• If you or a family member have a long QT on ECG.
• If you are getting a heparin infusion through a vein.

This is not a list of all drugs or health problems that interact with Vibativ.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

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:

• Foamy urine.
• Change in taste.
• Upset stomach or throwing up.
• Headache.
• 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.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this medicine is refilled. If you have any questions about Vibativ, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Vibativ. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Vibativ.

Review Date: October 4, 2017

Complicated Skin and Skin Structure Infections

Vibativ is indicated for the treatment of adult patients with complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), or Enterococcus faecalis (vancomycin-susceptible isolates only).

HABP/VABP

Vibativ is indicated for the treatment of adult patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP), caused by susceptible isolates of Staphylococcus aureus (both methicillin-susceptible and -resistant isolates). Vibativ should be reserved for use when alternative treatments are not suitable.

USAGE

Combination therapy may be clinically indicated if the documented or presumed pathogens include Gram-negative organisms.

Appropriate specimens for bacteriological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to telavancin. Vibativ may be initiated as empiric therapy before results of these tests are known.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Vibativ and other antibacterial drugs, Vibativ should be used only to treat 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.

Intravenous Unfractionated Heparin Sodium

Use of intravenous unfractionated heparin sodium is contraindicated with Vibativ administration because the activated partial thromboplastin time (aPTT) test results are expected to be artificially prolonged for 0 to 18 hours after Vibativ administration [see Warnings and Precautions (5.5) and Drug Interactions (7.1)].

Known Hypersensitivity to Vibativ

Vibativ is contraindicated in patients with known hypersensitivity to telavancin.

Drug-Laboratory Test Interactions

Effects of Telavancin on Coagulation Test Parameters

Telavancin binds to the artificial phospholipid surfaces added to common anticoagulation tests, thereby interfering with the ability of the coagulation complexes to assemble on the surface of the phospholipids and promote clotting in vitro. These effects appear to depend on the type of reagents used in commercially available assays. Thus, when measured shortly after completion of an infusion of Vibativ, increases in the PT, INR, aPTT, and ACT have been observed. These effects dissipate over time, as plasma concentrations of telavancin decrease.

Urine Protein Tests

Telavancin interferes with urine qualitative dipstick protein assays, as well as quantitative dye methods (e.g., pyrogallol red-molybdate). However, microalbumin assays are not affected and can be used to monitor urinary protein excretion during Vibativ treatment.

Vibativ contains telavancin hydrochloride (Figure 1), a lipoglycopeptide antibacterial that is a synthetic derivative of vancomycin.

The chemical name of telavancin hydrochloride is vancomycin,N3''-[2-(decylamino)ethyl]-29-[[(phosphono-methyl)-amino]-methyl]- hydrochloride. Telavancin hydrochloride has the following chemical structure:

Figure 1: Telavancin Hydrochloride

Telavancin hydrochloride is an off-white to slightly colored amorphous powder with the empirical formula C80H106Cl2N11O27P•xHCl (where x = 1 to 3) and a free-base molecular weight of 1755.6. It is highly lipophilic and slightly soluble in water.

Vibativ is a sterile, preservative-free, white to slightly colored lyophilized powder containing telavancin hydrochloride (equivalent to either 250 mg or 750 mg of telavancin as the free base) for intravenous use. The inactive ingredients are Hydroxypropylbetadex, Ph. Eur (hydroxypropyl-beta-cyclodextrin) (2500 mg per 250 mg telavancin, 7500 mg per 750 mg telavancin), mannitol (312.5 mg per 250 mg telavancin, 937.5 mg per 750 mg telavancin), and sodium hydroxide and hydrochloric acid used in minimal quantities for pH adjustment. When reconstituted, it forms a clear to slightly colored solution with a pH of 4.5 (4.0 to 5.0).

• Cartons of 10 individually packaged 250 mg single-dose vials (NDC 62847-002-01)
• Cartons of 10 individually packaged 750 mg single-dose vials (NDC 62847-001-01)

Store original packages at refrigerated temperatures of 2 to 8°C (35 to 46 °F). Excursions to ambient temperatures (up to 25 °C (77 °F)) are acceptable. Avoid excessive heat.

You should not use Vibativ if you are allergic to telavancin, or if you are also using a certain type of heparin.

To make sure Vibativ is safe for you, tell your doctor if you have:

• a history of kidney problems;

• diabetes;

• heart disease, high blood pressure;

• heart rhythm disorder, or history of Long QT syndrome; or

• if you are allergic to vancomycin.

If you are able to become pregnant, you may need a pregnancy test before you start using Vibativ. You are considered able to become pregnant unless you have ovarian failure, have had a tubal ligation or hysterectomy, or have been in menopause or not had a menstrual period in 2 years.

FDA pregnancy category C. You may not be able to use Vibativ if you are pregnant. It is not known whether telavancin will harm an unborn baby. In animal studies, telavancin caused birth defects. Use effective birth control to prevent pregnancy during your treatment with Vibativ, and tell your doctor if you become pregnant.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of Vibativ on the baby.

It is not known whether telavancin passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.