Lotemax Eye Ointment

loteprednol etabonate

Dosage Form: ophthalmic ointment
FULL PRESCRIBING INFORMATION

Indications and Usage for Lotemax Eye Ointment

LOTEMAX® ointment is a corticosteroid indicated for the treatment of post-operative inflammation and pain following ocular surgery.

Lotemax Eye Ointment Dosage and Administration

Apply a small amount (approximately ½ inch ribbon) into the conjunctival sac(s) four times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the post-operative period.

Dosage Forms and Strengths

LOTEMAX is supplied sterile in a 3.5 gram tube filled with loteprednol etabonate ophthalmic ointment, 0.5%.

Contraindications

LOTEMAX ointment, as with other ophthalmic corticosteroids, is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures.

Warnings and Precautions

Intraocular pressure (IOP) increase

Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. If this product is used for 10 days or longer, IOP should be monitored even though it may be difficult in children and uncooperative patients.

Cataracts

Use of corticosteroids may result in posterior subcapsular cataract formation.

Delayed healing

The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids.

The initial prescription and renewal of the medication order beyond 14 days should be made by a physician only after examination of the patient with the aid of magnification such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.

Bacterial infections

Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions, steroids may mask infection or enhance existing infection. If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated.

Viral infections

Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex).

Fungal infections

Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. Fungal culture should be taken when appropriate.

Contact Lens Wear

Patients should not wear contact lenses during their course of therapy with LOTEMAX ointment.

Amblyopia

LOTEMAX (loteprednol etabonate ophthalmic ointment), 0.5% should not be used in children following ocular surgery.  Its use may interfere with amblyopia treatment by hindering the child’s ability to see out of the operated eye (see Pediatric Use, 8.4).

Topical ophthalmic use only

Lotemax is not indicated for intraocular administration.

Adverse Reactions

Adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera.

The most common ocular adverse event reported at approximately 25% in subjects in clinical studies with Lotemax ointment was anterior chamber inflammation. Other common adverse events, with an incidence of 4-5%, were conjunctival hyperemia, corneal edema, and eye pain. Many of these events may have been the consequence of the surgical procedure. The only non-ocular adverse event occurring at ≥ 1% was headache (1.5%).

USE IN SPECIFIC POPULATIONS

Pregnancy

Teratogenic effects: Pregnancy Category C. Loteprednol etabonate has been shown to be embryotoxic (delayed ossification) and teratogenic (increased incidence of meningocele, abnormal left common carotid artery, and limb flexures) when administered orally to rabbits during organogenesis at a dose of 3 mg/kg/day (150 times the maximum daily clinical dose), a dose which caused no maternal toxicity. The no-observed-effect-level (NOEL) for these effects was 0.5 mg/kg/day (25 times the maximum daily clinical dose). Oral treatment of rats during organogenesis resulted in teratogenicity (absent innominate artery at ≥ 5 mg/kg/day doses, and cleft palate and umbilical hernia at ≥ 50 mg/kg/day) and embryotoxicity (increased post-implantation losses at 100 mg/kg/day and decreased fetal body weight and skeletal ossification with ≥ 50 mg/kg/day). Treatment of rats with 0.5 mg/kg/day (25 times the maximum daily clinical dose) during organogenesis did not result in any reproductive toxicity. Loteprednol etabonate was maternally toxic (significantly reduced body weight gain during treatment) when administered to pregnant rats during organogenesis at doses of ≥ 5 mg/kg/day.

Oral exposure of female rats to 50 mg/kg/day of loteprednol etabonate from the start of the fetal period through the end of lactation, a maternally toxic treatment regimen (significantly decreased body weight gain), gave rise to decreased growth and survival, and retarded development in the offspring during lactation; the NOEL for these effects was 5 mg/kg/day. Loteprednol etabonate had no effect on the duration of gestation or parturition when administered orally to pregnant rats at doses up to 50 mg/kg/day during the fetal period.

LOTEMAX should be used during pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus.

Nursing Mothers

It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Systemically administered steroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Caution should be exercised when LOTEMAX ointment is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

LOTEMAX (loteprednol etabonate ophthalmic ointment) 0.5% should not be used in children following ocular surgery.  Its use may interfere with amblyopia treatment by hindering the child’s ability to see out of the operated eye.

Geriatric Use

No overall differences in safety and effectiveness have been observed between elderly and younger patients.

Lotemax Eye Ointment Description

LOTEMAX (loteprednol etabonate ophthalmic ointment) 0.5% is a sterile, topical corticosteroid for ophthalmic use. Loteprednol etabonate is a white to off-white powder.

Loteprednol etabonate is represented by the following structural formula:

Chemical Name:

chloromethyl 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-1,4-diene-17β-carboxylate

Each gram contains:

ACTIVE: Loteprednol Etabonate 5 mg (0.5%);

INACTIVES: Mineral Oil and White Petrolatum.

Lotemax Eye Ointment - Clinical Pharmacology

Mechanism Of Action

Corticosteroids inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation. While glucocorticoids are known to bind to and activate the glucocorticoid receptor, the molecular mechanisms involved in glucocorticoid/glucocorticoid receptor-dependent modulation of inflammation are not clearly established. However, corticosteroids are thought to inhibit prostaglandin production through several independent mechanisms.

Pharmacokinetics

The systemic exposure to loteprednol etabonate following ocular administration of LOTEMAX ointment has not been studied in humans. However, results from a bioavailability study with LOTEMAX suspension in normal volunteers established that plasma concentrations of loteprednol etabonate and Δ¹ cortienic acid etabonate (PJ 91), its primary, inactive metabolite, were below the limit of quantitation (1 ng/mL) at all sampling times. The results were obtained following the ocular administration of one drop in each eye of 0.5% loteprednol etabonate suspension, 8 times daily for 2 days or 4 times daily for 42 days. The maximum systemic exposure to loteprednol following administration of the ointment product dosed four times daily is not expected to exceed exposures attained with LOTEMAX suspension dosed up to two drops four times daily.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term animal studies have not been conducted to evaluate the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse lymphoma tk assay, or in a chromosome aberration test in human lymphocytes, or in vivo in the single dose mouse micronucleus assay. Treatment of male and female rats with up to 50 mg/kg/day and 25 mg/kg/day of loteprednol etabonate, respectively, (2500 and 1250 times the maximum daily clinical dose, respectively) prior to and during mating did not impair fertility in either gender.

Clinical Studies

In two independent, randomized, multicenter, double-masked, parallel-group, vehicle-controlled studies in 805 subjects meeting a protocol-specified threshold amount of anterior chamber inflammation, LOTEMAX ointment was more effective compared to its vehicle for complete resolution of post-operative anterior chamber cell, flare, and pain following cataract surgery. Primary endpoint was complete resolution of anterior chamber cells and flare (cell count of 0 and no flare) and no pain at post-operative day 8. The individual clinical trial results are provided below.

In the 2 studies, Lotemax had statistically significant higher incidence of complete clearing of anterior chamber cells and flare at post-operative day 8 (24-32% vs. 11-14%) and also had a statistically significant higher incidence of subjects that were pain free at post-operative day 8 (73-78% vs. 41-45%).

How Supplied/Storage and Handling

LOTEMAX (loteprednol etabonate ophthalmic ointment), 0.5% is a sterile ointment supplied in a tin tube with a pink polypropylene cap in the following size:

3.5 gram (NDC 24208-443-35)

Do not use if tamper evident skirt is visible on bottom of cap.

Storage: Store between 15°–25°C (59°–77°F).

Rx only.

Patient Counseling Information

Risk of Contamination

Patients should be advised not to touch the eyelid or surrounding areas with the tip of the tube. The cap should remain on the tube when not in use.

Patients should be advised to wash hands prior to using LOTEMAX ointment.

Do not use if tamper evident skirt is visible on bottom of cap.

Contact Lens Wear

Patients should also be advised not to wear contact lenses during their course of therapy.

Risk of Secondary Infection

If pain, redness, itching or inflammation becomes aggravated, the patient should be advised to consult a physician.

MANUFACTURER INFORMATION

Bausch & Lomb Incorporated

Tampa, Florida 33637 USA

©Bausch & Lomb Incorporated

U.S. Patent No. 4,996,335

Lotemax is a registered trademark of Bausch & Lomb Incorporated

Principal Display Panel - Tube label

NDC 24208-443-35

Lotemax

loteprednol etabonate

ophthalmic ointment 0.5%

Sterile

Rx only

Net. wt.

1/8oz. (3.5g)

USUAL DOSAGE:

See Package Insert.

See crimp of tube or carton for Lot Number and Expiration Date.

DO NOT USE IF TAMPER EVIDENT SKIRT ON BOTTOM OF CAP IS VISIBLE.

Principal display panel - carton label

NDC 24208-443-35

Bausch & Lomb

Lotemax

loteprednol etabonate

ophthalmic ointment 0.5%

Sterile

Rx only

Net. wt. 1/8oz. (3.5g)

LOTEMAX  loteprednol etabonate  ointment

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 24208-443 Route of Administration OPHTHALMIC DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LOTEPREDNOL ETABONATE (LOTEPREDNOL) LOTEPREDNOL ETABONATE 5 mg  in 1 g

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 24208-443-35 1 TUBE In 1 CARTON contains a TUBE 1 3.5 g In 1 TUBE This package is contained within the CARTON (24208-443-35)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA200738	04/15/2011

Labeler - Bausch & Lomb Incorporated (196603781)

Revised: 04/2011Bausch & Lomb Incorporated

More Lotemax Eye Ointment resources

• Lotemax Eye Ointment Side Effects (in more detail)
• Lotemax Eye Ointment Dosage
• Lotemax Eye Ointment Use in Pregnancy & Breastfeeding
• Lotemax Eye Ointment Drug Interactions
• Lotemax Eye Ointment Support Group
• 0 Reviews for Lotemax Eye - Add your own review/rating

Compare Lotemax Eye Ointment with other medications

• Conjunctivitis
• Cyclitis
• Iritis
• Keratitis
• Postoperative Ocular Inflammation
• Rosacea
• Seasonal Allergic Conjunctivitis

loteprednol ophthalmic

Generic Name: loteprednol ophthalmic (lo te PRED nol off THAL mik)

Brand Names: Alrex, Lotemax

What is loteprednol ophthalmic?

Loteprednol is in a group of drugs called corticosteroids. It prevents the release of substances in the body that cause inflammation.

Loteprednol ophthalmic (for the eye) is used to treat eye swelling caused by surgery, infection, allergies, and other conditions.

Loteprednol ophthalmic may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about loteprednol ophthalmic?

Do not use this medication while you are wearing contact lenses. This medication may contain a preservative that can be absorbed by soft contact lenses. Wait at least 15 minutes after using loteprednol before putting your contact lenses in. Do not allow the dropper to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye. Stop using loteprednol and call your doctor at once if you have signs of a new eye infection such as swelling, redness, irritation, or drainage, or if you have problems with your vision, or severe pain, burning, or stinging when you use the eye drops. Call your doctor if your symptoms do not improve after 2 days of treatment.

What should I discuss with my healthcare provider before using loteprednol ophthalmic?

You should not use this medication if you are allergic to loteprednol, or if you have any type of fungal, viral, or bacterial infection of your eye.

If you have any of these other conditions, you may need a dose adjustment or special tests to safely use this medication:

• 
  

  glaucoma;

  
  


• 
  

  cataracts (or if you have recently had cataract surgery); or

  
  


• 
  

  herpes infection of your eye.

  
  

FDA pregnancy category C. It is not known whether loteprednol is harmful to an unborn baby. Before taking this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether loteprednol ophthalmic passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use loteprednol ophthalmic?

Use this medication exactly as it was prescribed for you. Do not use the medication in larger amounts, or use it for longer than recommended by your doctor. Follow the instructions on your prescription label.

Do not use this medication for longer than 2 weeks unless your doctor tells you to.

Wash your hands before using the eye drops.

Shake the eye drops well just before each use.

To apply the eye drops:

• 
  

  Tilt your head back slightly and pull down on the lower eyelid. Hold the dropper above the eye with the dropper tip down. Look up and away from the dropper. Squeeze out a drop and close your eye.

  
  


• 
  

  Gently press your finger to the inside corner of the eye (near the nose) for about 1 minute to keep the liquid from draining into your tear duct.

  
  

Do not allow the dropper to touch any surface, including the eyes or hands. If the dropper becomes contaminated it could cause an infection in your eye, which can lead to vision loss or serious damage to the eye.

Do not use this medication while you are wearing contact lenses. This medication may contain a preservative that can be absorbed by soft contact lenses. Wait at least 15 minutes after using loteprednol before putting your contact lenses in.

Call your doctor if your symptoms do not improve after 2 days of treatment.

To be sure loteprednol is not causing harmful effects, your vision may need to be checked after using the medication for 10 days or longer. Do not miss any scheduled visits to your doctor.

Store loteprednol ophthalmic with the cap on at room temperature, away from moisture and heat. Do not use the eye drops if the liquid changes colors or has particles in it. Call your doctor for a new prescription.

What happens if I miss a dose?

Use the medication as soon as you remember the missed dose. If it is almost time for your next dose, skip the missed dose and use the medicine at your next regularly scheduled time. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

An overdose of loteprednol ophthalmic is not likely to cause life-threatening symptoms.

What should I avoid while using loteprednol ophthalmic?

Avoid using other medications in your eyes during treatment with loteprednol ophthalmic unless your doctor has told you to.

Loteprednol ophthalmic side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using loteprednol and call your doctor at once if you have any of these serious side effects:

• 
  

  signs of a new eye infection such as swelling, redness, irritation, or drainage;

  
  


• 
  

  problems with your vision; or

  
  


• 
  

  severe pain, burning or stinging when using the eye drops.

  
  

Less serious side effects may include:

• 
  

  minor burning when using the eye drops;

  
  


• 
  

  dry, red, itchy, or watery eyes;

  
  


• 
  

  feeling that something is in your eye;

  
  


• 
  

  being more sensitive to light;

  
  


• 
  

  headache; or

  
  


• 
  

  runny nose, sore throat.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Loteprednol ophthalmic Dosing Information

Usual Adult Dose for Seasonal Allergic Conjunctivitis:

Instill 1 drop (0.2% suspension) into the affected eye(s) 4 times daily.

Usual Adult Dose for Acne Rosacea:

Instill 1-2 drops (0.5% suspension) into the affected eye(s) 4 times daily. The dose may be increased up to 1 drop hourly, if necessary, during the first week.

Usual Adult Dose for Iritis:

Instill 1-2 drops (0.5% suspension) into the affected eye(s) 4 times daily. The dose may be increased up to 1 drop hourly, if necessary, during the first week.

Usual Adult Dose for Keratitis:

Instill 1-2 drops (0.5% suspension) into the affected eye(s) 4 times daily. The dose may be increased up to 1 drop hourly, if necessary, during the first week.

Usual Adult Dose for Conjunctivitis:

Instill 1-2 drops (0.5% suspension) into the affected eye(s) 4 times daily. The dose may be increased up to 1 drop hourly, if necessary, during the first week.

Usual Adult Dose for Cyclitis:

Instill 1-2 drops (0.5% suspension) into the affected eye(s) 4 times daily. The dose may be increased up to 1 drop hourly, if necessary, during the first week.

Usual Adult Dose for Postoperative Ocular Inflammation:

0.5% suspension:
Instill 1 to 2 drops into the operated eye(s) beginning 24 hours after surgery and continuing for 2 weeks.

0.5% ointment:
Apply a small amount (approximately ½ inch ribbon) into the conjunctival sac(s) four times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period.

What other drugs will affect loteprednol ophthalmic?

It is not likely that other drugs you take orally or inject will have an effect on loteprednol used in the eyes. But many drugs can interact with each other. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More loteprednol ophthalmic resources

• Loteprednol ophthalmic Side Effects (in more detail)
• Loteprednol ophthalmic Dosage
• Loteprednol ophthalmic Use in Pregnancy & Breastfeeding
• Loteprednol ophthalmic Drug Interactions
• Loteprednol ophthalmic Support Group
• 0 Reviews for Loteprednol - Add your own review/rating

• Alrex Prescribing Information (FDA)


• Alrex Drops MedFacts Consumer Leaflet (Wolters Kluwer)


• Alrex Advanced Consumer (Micromedex) - Includes Dosage Information


• Lotemax Prescribing Information (FDA)


• Lotemax Drops MedFacts Consumer Leaflet (Wolters Kluwer)

Compare loteprednol ophthalmic with other medications

• Conjunctivitis
• Cyclitis
• Iritis
• Keratitis
• Postoperative Ocular Inflammation
• Rosacea
• Seasonal Allergic Conjunctivitis

Where can I get more information?

• Your pharmacist can provide more information about loteprednol ophthalmic.

See also: loteprednol side effects (in more detail)

Lamivudine/Zidovudine

Pronunciation: la-MIV-ue-deen/zye-DOE-vue-deen
Generic Name: Lamivudine/Zidovudine
Brand Name: Combivir

One of the 2 active ingredients in Lamivudine/Zidovudine, zidovudine, has been associated with certain blood disorders (eg, low white blood cell levels, severe anemia), especially in patients with advanced HIV disease, and muscle pain and inflammation, when it is used for long periods of time. High levels of lactic acid in the blood and severe liver problems, which may be life-threatening, have been reported with the use of Lamivudine/Zidovudine.

Some patients with both HIV and hepatitis B infection who were taking lamivudine have developed severe worsening of their hepatitis B after they stopped taking lamivudine. Patients who have both HIV and hepatitis B infection and who stop using Lamivudine/Zidovudine should have their liver function closely checked for at least several months after their last dose.

Lamivudine/Zidovudine is used for:

Treating HIV infection in combination with other medicines.

Lamivudine/Zidovudine is an antiviral combination. Lamivudine and zidovudine are both nucleoside analogues that work together to slow the growth of HIV by blocking an enzyme needed by the virus to reproduce.

Do NOT use Lamivudine/Zidovudine if:

• you are allergic to any ingredient in Lamivudine/Zidovudine


• you are also taking stavudine, zalcitabine, or other medicines containing lamivudine or zidovudine


• you have severe kidney problems, decreased liver function, abnormal liver function tests, or high levels of lactic acid in the blood (lactic acidosis)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Lamivudine/Zidovudine:

Some medical conditions may interact with Lamivudine/Zidovudine. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you weigh less than 66 lbs (30 kg)


• if you have a history of liver problems (eg, abnormal liver function tests, hepatitis B infection) or lactic acidosis


• if you have a history of kidney problems, a bone marrow disorder, pancreas problems, abnormal blood cell counts, or nerve or muscle problems


• if you are significantly overweight

Some MEDICINES MAY INTERACT with Lamivudine/Zidovudine. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Interferon alfa or ribavirin because serious liver problems may occur


• Stavudine because its effectiveness may be decreased by Lamivudine/Zidovudine


• Clarithromycin, doxorubicin, rifampin, or zalcitabine because they may decrease Lamivudine/Zidovudine's effectiveness


• Acetaminophen, ganciclovir, ibuprofen, methadone, probenecid, trimethoprim/sulfamethoxazole, valproic acid, vancomycin, or zalcitabine because they may increase the risk of Lamivudine/Zidovudine's side effects or toxic effects

This may not be a complete list of all interactions that may occur. Ask your health care provider if Lamivudine/Zidovudine may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Lamivudine/Zidovudine:

Use Lamivudine/Zidovudine as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Lamivudine/Zidovudine by mouth with or without food.


• Continue to use Lamivudine/Zidovudine even if you feel well. Do not miss any doses.


• Taking Lamivudine/Zidovudine at the same time each day will help you remember to take it.


• If you miss a dose of Lamivudine/Zidovudine, take it as soon as possible. If it is within 2 hours of your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Lamivudine/Zidovudine.

Important safety information:

• Lamivudine/Zidovudine may cause drowsiness or dizziness. These effects may be worse if you take it with alcohol or certain medicines. Use Lamivudine/Zidovudine with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• The risk of side effects may be greater and additional benefits may not be obtained if you take Lamivudine/Zidovudine in high doses. Do NOT take more than the recommended dose without checking with your doctor.


• Lamivudine/Zidovudine is not a cure for HIV infection. Patients may still get illnesses and infections associated with HIV. Remain under the care of your doctor.


• Lamivudine/Zidovudine does not stop the spread of HIV to others through blood or sexual contact. Use barrier methods of birth control (eg, condoms) if you have HIV infection. Do not share needles, injection supplies, or items like toothbrushes or razors.


• When your medicine supply is low, get more from your doctor or pharmacist as soon as you can. Do not stop taking Lamivudine/Zidovudine, even for a short period of time. If you do, the virus may grow resistant to the medicine and become harder to treat.


• Do not stop taking Lamivudine/Zidovudine without first checking with your doctor. Some conditions, including hepatitis B, may become worse if Lamivudine/Zidovudine is suddenly stopped.


• Changes in body fat (eg, an increased amount of fat in the upper back, neck, breast, and trunk, and loss of fat from the legs, arms, and face) may occur in some patients taking Lamivudine/Zidovudine. The cause and long-term effects of these changes are unknown. Discuss any concerns with your doctor.


• Lab tests, including blood cell counts and liver and kidney function tests, may be performed while you use Lamivudine/Zidovudine. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Lamivudine/Zidovudine should not be used in CHILDREN weighing less than 66 lbs (30 kg); safety and effectiveness in these children have not been confirmed. Caution is advised when using Lamivudine/Zidovudine in CHILDREN with a history of pancreatitis, or children who have taken other medicines for HIV infection.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Lamivudine/Zidovudine while you are pregnant. Lamivudine/Zidovudine is found in breast milk. Do not breast-feed while taking Lamivudine/Zidovudine. Mothers infected with HIV should not breast-feed. There is a risk of passing the HIV infection or Lamivudine/Zidovudine to the baby.

Possible side effects of Lamivudine/Zidovudine:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Appetite loss; changes in body fat; cough; diarrhea; dizziness; fatigue; headache; indigestion; nasal problems; sleeplessness or other sleep problems; tiredness; weakness.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); dark urine; depression; fast or irregular heartbeat; infection (fever, chills, sore throat); inflammation of the pancreas (severe stomach pain, nausea, vomiting); joint pain; mental or mood changes; muscle pain; nausea; numbness, tingling, or weakness in arms or legs; seizures; shortness of breath; stomach tenderness or pain; swelling or soreness of the mouth or tongue; unusual bleeding or bruising; unusual tiredness; unusual weakness or exhaustion; vomiting; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Lamivudine/Zidovudine side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include confusion; dizziness; drowsiness; headache; nausea; seizures; tiredness; vomiting.

Proper storage of Lamivudine/Zidovudine:

Store Lamivudine/Zidovudine at room temperature or in the refrigerator, between 36 and 86 degrees F (2 and 30 degrees C). Store in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Lamivudine/Zidovudine out of the reach of children and away from pets.

General information:

• If you have any questions about Lamivudine/Zidovudine, please talk with your doctor, pharmacist, or other health care provider.


• Lamivudine/Zidovudine is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Lamivudine/Zidovudine. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Lamivudine/Zidovudine resources

• Lamivudine/Zidovudine Side Effects (in more detail)
• Lamivudine/Zidovudine Use in Pregnancy & Breastfeeding
• Drug Images
• Lamivudine/Zidovudine Drug Interactions
• Lamivudine/Zidovudine Support Group
• 1 Review for Lamivudine/Zidovudine - Add your own review/rating

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• HIV Infection
• Nonoccupational Exposure
• Occupational Exposure

Lymphazurin 1%

Generic Name: isosulfan blue (Subcutaneous route)

eye-soe-SUL-fan BLOO

Commonly used brand name(s)

In the U.S.

• Lymphazurin

In Canada

• Lymphazurin 1%

Available Dosage Forms:

• Solution

Therapeutic Class: Diagnostic Agent, Lymphatic Visualization

Uses For Lymphazurin 1%

Isosulfan blue injection is used as an aid in a procedure called lymphography (medical imaging procedure) to test how well your lymphatic system is working in certain parts of your body. It is a blue dye that works by staining the lymph nodes and lymph vessels. This creates a contrast between the lymph nodes and vessels and helps your doctor check for serious medical problems such as lymphedema, chyluria (lymph in the urine), chylous ascites (lymph in the stomach), chylothorax (lymph in the chest), cancer of the lymph nodes, or other problems of the lymphatic system.

This medicine is available only with your doctor's prescription.

Before Using Lymphazurin 1%

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 isosulfan blue injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

No information is available on the relationship of age to the effects of isosulfan blue injection in geriatric patients.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

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. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

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:

• Asthma, history of—Use with caution. May be more likely to experience side effects.

Proper Use of isosulfan blue

This section provides information on the proper use of a number of products that contain isosulfan blue. It may not be specific to Lymphazurin 1%. Please read with care.

A doctor will give you this medicine in a hospital. This medicine is given as a shot under your skin.

Precautions While Using Lymphazurin 1%

It is very important that your doctor check your progress closely while you are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to receive it.

This medicine may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Tell your doctor or nurse right away if you have cold clammy skin; confusion; dizziness; lightheadedness; a skin rash; itching; shortness of breath; sweating; swelling of the face, tongue, and throat; or trouble with breathing after you get the injection.

Make sure your doctor knows if you have had an allergic reaction to any dye or medicine given during a test or procedure.

Make sure any doctor or dentist who treats you knows that you are using this medicine. This medicine may affect the results of certain medical tests.

This medicine may cause your urine to turn blue for up to 24 hours after you receive this medicine. Talk to your doctor if you have any questions.

Lymphazurin 1% Side Effects

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:

Less common

• Cold, clammy skin


• confusion


• cough


• difficulty with swallowing


• dizziness


• fast heartbeat


• fast, weak pulse


• hives or welts


• itching


• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs


• lightheadedness


• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue


• redness of the skin


• shortness of breath


• skin rash


• sweating


• tightness in the chest


• troubled breathing


• unusual tiredness or weakness


• wheezing

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:

Incidence not known

• Blue discoloration of the skin

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.

See also: Lymphazurin% side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Lymphazurin 1% resources

• Lymphazurin 1% Side Effects (in more detail)
• Lymphazurin 1% Use in Pregnancy & Breastfeeding
• Lymphazurin 1% Support Group
• 0 Reviews for Lymphazurin% - Add your own review/rating

Compare Lymphazurin 1% with other medications

• Diagnosis and Investigation

Levatol

Dosage Form: tablet
Levatol® tablets

(penbutolol sulfate)

20mg

Rx Only

Levatol Description

Levatol® (penbutolol sulfate) is a synthetic ß-receptor antagonist for oral administration. The chemical name of penbutolol sulfate is (S)-1-tert-butylamino-3-(o-cyclopentylphenoxy)-2-propanol sulfate. It is provided as the levorotatory isomer. The empirical formula for penbutolol sulfate is C36H60N2O8S. Its molecular weight is 680.94. A dose of 20 mg is equivalent to 29.4 µmol. The structural formula is as follows:

Penbutolol is a white, odorless, crystalline powder. Levatol® is available as tablets for oral administration. Each tablet contains 20 mg of penbutolol sulfate. It also contains corn starch, D&C Yellow No. 10, lactose, magnesium stearate, povidone, silicon dioxide, talc, titanium dioxide, synthetic black iron oxide, hypromellose, simethicone and other inactive ingredients.

Levatol - Clinical Pharmacology

Penbutolol is a ß-1, ß-2 (nonselective) adrenergic receptor antagonist. Experimental studies showed a dose-dependent increase in heart rate in reserpinized (norepinephrine-depleted) rats given penbutolol intravenously at doses of 0.25 to 1.0 mg/kg, suggesting that penbutolol has some intrinsic sympathomimetic activity. In human studies, however, heart rate decreases have been similar to those seen with propranolol.

Penbutolol antagonizes the heart rate effects of exercise and infused isoproterenol. The ß-blocking potency of penbutolol is approximately 4 times that of propranolol. An oral dose of less than 10 mg will reduce exercise-induced tachycardia to one-half its usual level; maximum antagonism follows doses of 10 to 20 mg. The peak effect is between 1.5 and 3 hours after oral administration. The duration of effect exceeds 20 hours during a once-daily dosing regimen. During chronic administration of penbutolol, the duration of antihypertensive effects permits a once-daily dosage schedule.

Acute hemodynamic effects of penbutolol have been studied following single intravenous doses between 0.1 and 4 mg. The cardiovascular responses included significant reductions in heart rate, left ventricular maximum dP/dt, cardiac output, stroke volume index, stroke work, and stroke work index. Systolic pressure and mean arterial pressure were reduced, and total peripheral resistance was increased.

Chronic administration of penbutolol to hypertensive patients results in the hemodynamic pattern typical of ß-adrenergic blocking drugs: a reduction in cardiac index, heart rate, systolic and diastolic blood pressures, and the product of heart rate and mean arterial pressure both at rest and with all levels of exercise, without significant change in total peripheral resistance. Penbutolol causes a reduction in left ventricular contractility. Penbutolol decreases glomerular filtration rate, but not significantly.

Clinical trial doses of 10 to 80 mg per day in single daily doses have reduced supine and standing systolic and diastolic blood pressures. In most studies, effects were small, generally a change in blood pressure 5 to 8/3 to 5 mm Hg greater than seen with a placebo measured 24 hours after dosing. It is not clear whether this relatively small effect reflects a characteristic of penbutolol or the particular population studied (the population had relatively mild hypertension but did not appear unusual in other respects). In a direct comparison of penbutolol with adequate doses of twice daily propranolol, no difference in blood pressure effect was seen. In a comparison of placebo and 10-, 20-, and 40-mg single daily doses of penbutolol, no significant dose-related difference was seen in response to active drug at 6 weeks, but, compared to the 10-mg dose, the two larger doses showed greater effects at 2 and 4 weeks and reached their maximum effect at 2 weeks. In several studies, dose increases from 40 to 80 mg were without additional effect on blood pressure. Response rates to penbutolol are unaffected by sex or age but are greater in caucasians than blacks.

Penbutolol decreases plasma renin activity in normal subjects and in patients with essential and renovascular hypertension. The mechanisms of the antihypertensive actions of ß-receptor antagonists have not been established. However, factors that may be involved are: (1) competitive antagonism of catecholamines at peripheral adrenergic receptor sites (especially cardiac) that leads to decreased cardiac output; (2) a central nervous system (CNS) action that results in a decrease in tonic sympathetic neural outflow to the periphery; and (3) a reduction of renin secretion through blockade of ß-receptors involved in release of renin from the kidneys.

Penbutolol dose dependently increases the RR and QT intervals. There is no influence on the PR, QRS, or QT c (corrected) intervals.

Pharmacokinetics:

Following oral administration, penbutolol is rapidly and completely absorbed. Peak plasma concentrations of penbutolol occur between 2 and 3 hours after oral administration and are proportional to single and multiple doses between 10 and 40 mg once a day. The average plasma elimination half-life of penbutolol is approximately 5 hours in normal subjects. There is no significant difference in the plasma half-life of penbutolol in healthy elderly persons or patients on renal dialysis. Twelve to 24 hours after oral administration of doses up to 120 mg, plasma concentrations of parent drug are 0% to 10% of the peak level. No accumulation of penbutolol is observed in hypertensive patients after 8 days of therapy at doses of 40 mg daily or 20 mg twice a day. Penbutolol is approximately 80% to 98% bound to plasma proteins.

The metabolism of penbutolol in humans involves conjugation and oxidation. The metabolites are excreted principally in the urine. When radiolabeled penbutolol was administered to humans, approximately 90% of the radioactivity was excreted in the urine. Approximately 1/6 of the dose of penbutolol was recovered as penbutolol conjugate while the remaining fraction was not identified. Conjugated penbutolol has a plasma elimination half-life of approximately 20 hours in healthy persons, 25 hours in healthy elderly persons, and 100 hours in patients on renal dialysis. Thus, accumulation of penbutolol conjugate may be expected upon multiple-dosing in renal insufficiency. An oxidative metabolite of penbutolol, 4-hydroxy penbutolol, has been identified in small quantities in plasma and urine. It is 1/8 to 1/15 times as active as the parent compound in blocking isoproterenol-induced ß-adrenergic receptor responses in isolated guinea-pig trachea and is 1/8 to 1 times as potent in anesthetized dogs.

Indications and Usage for Levatol

Levatol® is indicated in the treatment of mild to moderate arterial hypertension. It may be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Contraindications

Levatol® is contraindicated in patients with cardiogenic shock, sinus bradycardia, second and third degree atrioventricular conduction block, bronchial asthma, and those with known hypersensitivity to this product (see WARNINGS).

Warnings

Cardiac Failure: Sympathetic stimulation may be essential for supporting circulatory function in patients with heart failure, and its inhibition by ß-adrenergic receptor blockade may precipitate more severe failure. Although ß-blockers should be avoided in overt congestive heart failure, Levatol® can, if necessary, be used with caution in patients with a history of cardiac failure who are well compensated, on treatment with vasodilators, digitalis and/or diuretics. Both digitalis and penbutolol slow AV conduction. Beta-adrenergic receptor antagonists do not inhibit the inotropic action of digitalis on heart muscle. If cardiac failure persists, treatment with Levatol® should be discontinued.

Patients Without History of Cardiac Failure: Continued depression of the myocardium with ß-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first evidence of heart failure, patients receiving Levatol® should be given appropriate treatment, and the response should be closely observed. If cardiac failure continues despite adequate intervention with appropriate drugs, Levatol® should be withdrawn (gradually, if possible).

Exacerbation of Ischemic Heart Disease Following Abrupt Withdrawal: Hypersensitivity to catecholamines has been observed in patients who were withdrawn from therapy with ß-blocking agents; exacerbation of angina and, in some cases, myocardial infarction have occurred after abrupt discontinuation of such therapy. When discontinuing Levatol®, particularly in patients with ischemic heart disease, the dosage should be reduced gradually over a period of 1 to 2 weeks and the patient should be monitored carefully. If angina becomes more pronounced or acute coronary insufficiency develops, administration of Levatol® should be reinstated promptly, at least on a temporary basis, and appropriate measures should be taken for the management of unstable angina. Patients should be warned against interruption or discontinuation of therapy without the physician’s advice. Because coronary artery disease is common and may not be recognized, it may not be prudent to discontinue Levatol® abruptly, even in patients who are being treated only for hypertension.

Nonallergic Bronchospasm (eg, chronic bronchitis,emphysema): Levatol® is contraindicated in bronchial asthma. In general, patients with bronchospastic diseases should not receive ß-blockers. Levatol® should be administered with caution because it may block bronchodilation produced by endogenous catecholamine stimulation of ß-2 receptors.

Major Surgery: Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Diabetes Mellitus and Hypoglycemia: Beta-adrenergic receptor blockade may prevent the appearance of signs and symptoms of acute hypoglycemia, such as tachycardia and blood pressure changes. This is especially important in patients with labile diabetes. Beta-blockade also reduces the release of insulin in response to hyperglycemia; therefore, it may be necessary to adjust the dose of hypoglycemic drugs. Beta-adrenergic blockade may also impair the homeostatic response to hypoglycemia; in that event, the spontaneous recovery from hypoglycemia may be delayed during treatment with ß-adrenergic receptor antagonists.

Thyrotoxicosis: Beta-adrenergic blockade may mask certain clinical signs (eg, tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of ß-adrenergic receptor blockers that might precipitate a thyroid storm.

Precautions

Information for Patients:

Patients, especially those with evidence of coronary artery insufficiency, should be warned against interruption or discontinuation of Levatol® without the physician’s advice. Although cardiac failure rarely occurs in properly selected patients, those being treated with ß-adrenergic receptor antagonists should be advised of the symptoms of heart failure and to report such symptoms immediately, should they develop.

Drug Interactions:

Levatol® has been used in combination with hydrochlorothiazide in at least 100 patients without unexpected adverse reactions.

In one study, the combination of penbutolol and alcohol increased the number of errors in the eye-hand psychomotor function test.

Penbutolol increases the volume of distribution of lidocaine in normal subjects. This could result in a requirement for higher loading doses of lidocaine.

Cimetidine has no effect on the clearance of penbutolol. The major metabolite of penbutolol is a glucuronide, and it has been shown that cimetidine does not inhibit glucuronidation.

Synergistic hypotensive effects, bradycardia, and arrhythmias have been reported in some patients receiving ß-adrenergic blocking agents when an oral calcium antagonist was added to the treatment regimen.

Generally, Levatol® should not be used in patients receiving catecholamine-depleting drugs.

Digoxin:

Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Anesthesia:

Care should be taken when using anesthetic agents that depress the myocardium, such as ether, cyclopropane, and trichloroethylene, and it is prudent to use the lowest possible dose of Levatol®. Levatol®, like other ß-blockers, is a competitive inhibitor of ß-receptor agonists, and its effect on the heart can be reversed by cautious administration of such agents (eg, dobutamine or isoproterenol — see OVERDOSAGE). Manifestations of excessive vagal tone (eg, profound bradycardia, hypotension) may be corrected with atropine 1 to 3 mg IV in divided doses.

Risk of Anaphylactic Reaction:

While taking ß-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Carcinogenesis, Mutagenesis, and Impairment of Fertility:

There was no evidence of carcinogenicity observed in a 21-month study in mice or a 2-year study in rats. Mice were given penbutolol in the diet for 18 months at doses up to 395 mg/kg/day (about 500 times the Maximum Recommended Human Dose (MRHD) of 40 mg in a 50 kg person). Rats were given 141 mg/kg/day for the same length of time. Mice were observed for 3 months and rats for 5.5 to 7 months after termination of treatment before necropsy was performed.

No evidence of mutagenic activity of penbutolol was seen in the Salmonella mutagenicity test (Ames test), the point mutation induction test (Saccharomyces), and the micronucleus test.

Penbutolol had no adverse effects on fertility or general reproductive performance in mice and rats at oral doses up to 172 mg/kg/day.

Pregnancy

Teratogenic Effects: Pregnancy Category C:

Teratology studies in rats and rabbits revealed no teratogenic effects related to treatment with penbutolol at oral doses up to 200 mg/kg/day (250 times the MRHD). In rabbits, a slight increase in the intrauterine fetal mortality and a reduced 24-hour offspring survival rate were observed in the groups treated with 125 mg/kg/day (156 times the MRHD) but not in the groups treated with 0.2 and 5 mg (0.25 to 6 times the MRHD).

There are no adequate and well-controlled studies in pregnant women. Levatol® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects:

In a perinatal and postnatal study in rats, the pup body weight and pup survival rate were reduced at the highest dose level of 160 mg/kg/day (200 times the MRHD).

Nursing Mothers:

It is not known whether Levatol® is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Levatol® is administered to a nursing woman.

Pediatric Use:

Safety and effectiveness of Levatol® in pediatric patients have not been established.

Geriatric Use:

Clinical studies of Levatol® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic 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.

Adverse Reactions

Levatol® is usually well tolerated in properly selected patients. Most adverse effects observed during clinical trials have been mild and reversible.

Table 1 lists the adverse reactions reported from 4 controlled studies conducted in the United States involving once-a-day administration of Levatol® (at doses ranging from 10 to 120 mg) as monotherapy or in combination with hydrochlorothiazide. Levatol® doses above 40 mg/day are not, however, recommended. The table includes only those events where the prevalence rate in the Levatol® group was at least 1.5%, or where the reaction is of particular interest.

Over a dose range from 10 to 40 mg, once a day, fatigue, nausea, and sexual impotence occurred at a greater frequency as the dose was increased.

Table 1 ADVERSE REACTIONS DURING CONTROLLED US STUDIES

Body System Experience	Penbutolol (N=628)	Placebo (N=212)	Propranolol (N=266)
Body as a Whole	%	%	%
Asthenia	1.6	0.9	4.9
Pain, chest	2.4	2.8	2.3
Pain, limb	2.4	1.4	1.5
Digestive System
Diarrhea	3.3	1.9	2.6
Nausea	4.3	0.9	2.3
Dyspepsia	2.7	1.4	5.3
Nervous System
Dizziness	4.9	2.4	4.2
Fatigue	4.4	1.9	2.6
Headache	7.8	6.1	7.5
Insomnia	1.9	0.9	2.6
Respiratory System
Cough	2.1	0.5	1.1
Dyspnea	2.1	1.4	3.4
Upper respiratory infection	2.5	3.3	4.9
Skin and Appendages
Sweating, excessive	1.6	0.5	2.3
Urogenital System
Impotence, sexual	0.5	0.0	0.8

In a double-blind clinical trial comparing Levatol® (40 mg and greater once a day) and propranolol (40 mg or more twice a day), heart rates of less than 60 beats/min. were recorded at least once in 25% of the patients in the group receiving Levatol® and in 37% of the patients in the propranolol group. Corresponding figures for heart rates of less than 50 beats/min. were 1.2% and 6% respectively. No symptoms associated with bradycardia were reported.

Discontinuations of Levatol® because of adverse reactions have ranged between 2.4% and 6.9% of patients in double-blind, parallel, controlled clinical trials, as compared to 1.8% to 4.1% in the corresponding control groups that were given placebo. The frequency and severity of adverse reactions have not increased during long-term administration of Levatol®. The prevalence of adverse reactions reported from 4 controlled clinical trials (referred to in Table 1) as reasons for discontinuation of therapy by >0.5% of the Levatol® group is listed in Table 2.

Table 2 DISCONTINUATIONS DURING CONTROLLED US STUDIES

Body System Experience	Penbutolol (N=628)	Placebo (N=212)	Propranolol (N=266)
Body as a Whole	%	%	%
Asthenia	0.6	0.0	0.4
Pain, chest	0.6	1.4	0.4
Digestive System
Nausea	0.8	0.0	0.8
Nervous System
Depression	0.6	0.5	0.8
Dizziness	0.6	0.0	0.4
Fatigue	0.5	0.5	0.0
Headache	0.6	0.5	0.4

Potential Adverse Effects: In addition, certain adverse effects not listed above have been reported with other ß-blocking agents and should also be considered as potential adverse effects of Levatol®.

Central Nervous System: Reversible mental depression progressing to catatonia (an acute syndrome characterized by disorientation for time and place), short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance (neuropsychometrics).

Cardiovascular: Intensification of AV block (see CONTRAINDICATIONS).

Allergic: Erythematous rash, fever combined with aching and sore throat, laryngospasm, and respiratory distress.

Hematologic: Agranulocytosis, nonthrombocytopenic and thrombocytopenic purpura.

Gastrointestinal: Mesenteric arterial thrombosis and ischemic colitis.

Miscellaneous: Reversible alopecia and Peyronie’s disease. The oculomucocutaneous syndrome associated with the ß-blocker practolol has not been reported with Levatol® during investigational use and extensive foreign clinical experience.

Overdosage

There is no actual experience with Levatol® overdose. The signs and symptoms that would be expected with overdosage of ß-adrenergic receptor antagonists are symptomatic bradycardia, hypotension, bronchospasm, and acute cardiac failure. In addition to discontinuation of Levatol®, gastric emptying, and close observation of the patient, the following measures might be considered as appropriate:

Excessive Bradycardia: Administer atropine sulfate to induce vagal blockade. If bradycardia persists, intravenous isoproterenol hydrochloride may be administered cautiously; larger than usual doses may be needed. In refractory cases, the use of a transvenous cardiac pacemaker may be necessary.

Hypotension: Sympathomimetic drug therapy, such as dopamine, dobutamine, or levarterenol, may be considered if hypotension persists despite correction of bradycardia. In refractory cases, administration of glucagon hydrochloride has been reported to be useful.

Bronchospasm: A ß-2-agonist or isoproterenol hydrochloride may be administered. Additional therapy with aminophylline may be considered.

Acute Cardiac Failure: Institute conventional therapy immediately. Intravenous administration of dobutamine and glucagon hydrochloride has been reported to be useful.

Heart Block (Second or Third Degree): Isoproterenol hydrochloride or a transvenous cardiac pacemaker may be used.

Levatol Dosage and Administration

The usual starting and maintenance dose of Levatol®, used alone or in combination with other antihypertensive agents, such as thiazide-type diuretics, is 20 mg given once daily.

Doses of 40 mg and 80 mg have been well-tolerated but have not been shown to give a greater antihypertensive effect. The full effect of a 20- or 40-mg dose is seen by the end of 2 weeks. A dose of 10 mg also lowers blood pressure, but the full effect is not seen for 4 to 6 weeks.

How is Levatol Supplied

Levatol® (penbutolol sulfate) 20 mg tablets are capsule-shaped, film-coated, yellow tablets scored on both sides and imprinted in black with “SP 22” on one side. They are supplied as follows:

         Bottles of 100            NDC 52244-450-10

Store at 20°-25°C (68°-77°F); excursions permitted between 15°-30°C (59°-86°F) [See USP Controlled Room Temperature]. Keep tightly closed and protect from light.

ANIMAL TOXICOLOGY

Studies in rats indicated that the combination of penbutolol, triamterene, and hydrochlorothiazide (up to 40, 50 and 25 mg/kg respectively) increased the incidence and severity of renal tubular dilation and regeneration when compared to that in rats treated only with triamterene and hydrochlorothiazide. Dogs administered the same doses of triamterene and hydrochlorothiazide alone and in combination with penbutolol had an increase in serum alkaline phosphatase and serum alanine transferase, but there were no gross or microscopic abnormalities observed. No significant toxicologic findings were observed in rats and dogs treated with a combination of penbutolol and hydrochlorothiazide.

Actient Pharmaceuticals, LLC

Lake Forest, IL 60045

Levatol® is a registered trademark of Actient Pharmaceuticals, LLC.

Rev. 1 05/2011

PRINCIPAL DISPLAY PANEL

NDC 52244-450-10

Levatol® tablets

(penbutolol sulfate)

20 mg

Rx only

100 tablets

Levatol  penbutolol sulfate  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 52244-450 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PENBUTOLOL SULFATE (PENBUTOLOL) PENBUTOLOL SULFATE 20 mg

Inactive Ingredients Ingredient Name Strength STARCH, CORN   D&C YELLOW NO. 10   LACTOSE   MAGNESIUM STEARATE   POVIDONE   SILICON DIOXIDE   TALC   TITANIUM DIOXIDE   FERROSOFERRIC OXIDE   HYPROMELLOSES   SILICON DIOXIDE

Product Characteristics Color YELLOW Score 2 pieces Shape OVAL (capsule-shaped) Size 14mm Flavor Imprint Code SP;22 Contains

Packaging # NDC Package Description Multilevel Packaging 1 52244-450-10 100 TABLET In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA018976	01/25/2012

Labeler - Actient Pharmaceuticals, LLC (962685223)

Revised: 01/2012Actient Pharmaceuticals, LLC

lurasidone

loo-RAS-i-done

Oral route(Tablet)

Elderly patients with dementia-related psychosis treated with atypical antipsychotic drugs are at an increased risk of death compared to placebo. Although the causes of death in clinical trials were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that antipsychotic drugs may increase mortality. It is unclear from these studies to what extent the mortality findings may be attributed to the antipsychotic drug as opposed to patient characteristics. Lurasidone hydrochloride is not approved for the treatment of patients with dementia-related psychosis .

Commonly used brand name(s)

In the U.S.

• Latuda

Available Dosage Forms:

• Tablet

Therapeutic Class: Antipsychotic

Uses For lurasidone

Lurasidone is used to treat symptoms of psychotic (mental) disorders, such as schizophrenia. lurasidone should not be used to treat behavioral problems in elderly patients who have dementia.

lurasidone is available only with your doctor's prescription.

Before Using lurasidone

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 lurasidone, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to lurasidone 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 lurasidone 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 lurasidone in the elderly. However, lurasidone should not be used for behavioral problems in older adults with dementia.

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

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 taking lurasidone, 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 lurasidone 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.

• Ketoconazole


• Metoclopramide


• Rifampin

Using lurasidone 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.

• Diltiazem

Using lurasidone 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.

• Digoxin


• Lithium


• Midazolam

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 lurasidone. Make sure you tell your doctor if you have any other medical problems, especially:

• Alzheimer's disease or dementia or


• Dehydration or


• Heart attack, history of or


• Heart failure or


• Heart or blood vessel disease or


• Heart rhythm problems or


• Hypotension (low blood pressure) or


• Hypovolemia (low amount of blood) or


• Stroke, history of or—May cause side effects to become worse.

• Blood or bone marrow problems (e.g., agranulocytosis, leukopenia, neutropenia) or


• Diabetes or


• Dyslipidemia (high cholesterol or fats in the blood) or


• Hyperglycemia (high blood sugar) or


• Hyperprolactinemia (high prolactin in the blood) or


• Seizures, history of—Use with caution. May make these conditions worse.

• Kidney disease or


• Liver disease—You may need a dose adjustment. Talk with your doctor if you have concerns about this.

Proper Use of lurasidone

Take lurasidone only as directed by your doctor even if you feel well. Do not take more of lurasidone and do not take it more often than your doctor ordered. lurasidone works best if there is a constant amount in the blood. To keep blood levels constant, take lurasidone at the same time each day and do not miss any doses.

You must take lurasidone with food (containing at least 350 calories).

Dosing

The dose of lurasidone will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of lurasidone. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  
  • For schizophrenia:
    
    • Adults—At first, 40 milligrams (mg) once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 80 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of lurasidone, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using lurasidone

It is very important that your doctor check your progress at regular visits to make sure that lurasidone is working properly. Blood tests may be needed to check for unwanted effects.

lurasidone should not be used with certain other medications such as ketoconazole (Nizoral®) or rifampin (Rifadin®, Rimactane®). Make sure your doctor knows what medications you are taking or if you start a new medicine.

Stop taking lurasidone and check with your doctor right away if you have any of the following symptoms while using lurasidone: convulsions (seizures), difficulty with breathing, a fast heartbeat, a high fever, high or low blood pressure, increased sweating, loss of bladder control, severe muscle stiffness, unusually pale skin, or tiredness. These could be symptoms of a serious condition called neuroleptic malignant syndrome (NMS).

lurasidone may cause tardive dyskinesia (a movement disorder). Stop using lurasidone and check with your doctor right away if you have lip smacking or puckering, puffing of the cheeks, rapid or worm-like movements of the tongue, uncontrolled chewing movements, or uncontrolled movements of the arms and legs while you are using lurasidone.

lurasidone may increase the amount of sugar in your blood. Check with your doctor right away if you have increased thirst or increased urination. If you have diabetes, you may notice a change in the results of your urine or blood sugar tests. If you have any questions, check with your doctor.

lurasidone may increase your weight. Your doctor may need to check your weight on a regular basis while you are using lurasidone. Talk to your doctor about ways to prevent weight gain.

Lurasidone can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. If you can, avoid people with infections. Check with your doctor right away if you think you are getting an infection, or if you have a fever or chills, a cough or hoarseness, lower back or side pain, or painful or difficult urination.

Dizziness, lightheadedness, or fainting may occur, especially when you get up suddenly from a lying or sitting position. Getting up slowly may help. If the problem continues or gets worse, check with your doctor.

lurasidone may cause some people to become drowsy or dizzy, or to have trouble with thinking or controlling body movements. Make sure you know how you react to lurasidone before you drive, use machines, or do anything else that requires you to be alert, well-coordinated, or able to think well.

Avoid activities involving high temperature or humidity. lurasidone may reduce your body's ability to adjust to the heat.

Lurasidone may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies. If you or your caregiver notice any of these side effects, tell your doctor right away.

lurasidone will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for allergies or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicines including other narcotics; medicine for seizures (e.g., barbiturates); muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using lurasidone.

Before you have any medical tests, tell the medical doctor in charge that you are taking lurasidone. The results of some tests may be affected by lurasidone.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

lurasidone Side Effects

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 immediately if any of the following side effects occur:

More common

• Absence of or decrease in body movement


• difficulty with swallowing


• drooling


• inability to sit still


• incremental or ratchet-like movement of the muscle


• loss of balance control


• mask-like face


• muscle discomfort


• muscle trembling, jerking, or stiffness


• need to keep moving


• restlessness


• rigid or stiff muscles


• shakiness in the legs, arms, hands, or feet


• shuffling walk


• slow movements


• slow reflexes


• slurred speech


• stiffness of the arms and legs


• tic-like (jerky) movements of the head, face, mouth, and neck


• trembling or shaking of the hands or feet


• twisting movements of the body


• uncontrolled movements, especially of the face, neck, and back

Less common

• Arm, back, or jaw pain


• blurred vision


• burning while urinating


• changes in patterns and rhythms of speech


• chest pain or discomfort


• chills


• cold sweats


• confusion


• convulsions


• difficult or painful urination


• difficulty opening the mouth


• difficulty with breathing


• dizziness


• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position


• fast, pounding, or irregular heartbeat or pulse


• fixed position of the eye


• headache


• high fever


• inability to move the eyes


• inability to speak


• increased blinking or spasms of the eyelid


• increased sweating


• lockjaw


• loss of bladder control


• muscle spasm, especially of the neck and back


• nervousness


• pale skin


• pounding in the ears


• seizures


• severe muscle stiffness


• severe or sudden headache


• shortness of breath


• slow or fast heartbeat


• slurred speech


• sticking out of the tongue


• sweating


• temporary blindness


• tiredness


• trouble with breathing, speaking, or swallowing


• troubled breathing with exertion


• uncontrolled twisting movements of the neck, trunk, arms, or legs


• unusual bleeding or bruising


• unusual facial expressions


• unusual tiredness or weakness


• unusually pale skin


• weakness in the arm or leg on one side of the body, sudden and severe

Rare

• Black, tarry stools


• bloody urine


• breast pain or swelling


• cough


• dark-colored urine


• decreased frequency or amount of urine


• fever


• increased thirst


• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs


• loss of appetite


• lower back or side pain


• muscle cramps or spasms


• muscle pain or stiffness


• nausea


• sore throat


• sores, ulcers, or white spots on the lips or in the mouth


• swelling of the face, fingers, or lower legs


• swollen glands


• troubled breathing


• vomiting


• weight gain

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:

More common

• Acid or sour stomach


• anxiety


• belching


• drowsiness


• dry mouth


• heartburn


• hyperventilation


• indigestion


• irritability


• relaxed and calm


• sleepiness or unusual drowsiness


• sleeplessness


• stomach discomfort, upset, or pain


• trouble sleeping


• unable to sleep


• unusually deep sleep


• unusually long duration of sleep

Less common

• Abnormal dreams


• anxiety


• back pain


• blurred vision


• burning feeling in the chest or stomach


• decreased appetite


• diarrhea


• feeling of constant movement of self or surroundings


• indigestion


• itching


• sensation of spinning


• skin rash


• stomach upset


• sweating


• tenderness in the stomach area


• watering of mouth and drooling

Rare

• Decreased interest in sexual intercourse


• inability to have or keep an erection


• loss in sexual ability, desire, drive, or performance


• unexpected or excess milk flow from the breasts

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.

See also: lurasidone side effects (in more detail)

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More lurasidone resources

• Lurasidone Side Effects (in more detail)
• Lurasidone Dosage
• Lurasidone Use in Pregnancy & Breastfeeding
• Lurasidone Drug Interactions
• Lurasidone Support Group
• 33 Reviews for Lurasidone - Add your own review/rating

• Lurasidone MedFacts Consumer Leaflet (Wolters Kluwer)


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