RECENT MAJOR CHANGES

Warnings and Precautions, Central Nervous System Effects (5.3) 3/2010

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B. There are no adequate and well-controlled studies of valacyclovir or acyclovir in pregnant women. Based on prospective pregnancy registry data on 749 pregnancies, the overall rate of birth defects in infants exposed to acyclovir in utero appears similar to the rate for infants in the general population. Valacyclovir hydrochloride tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

A prospective epidemiologic registry of acyclovir use during pregnancy was established in 1984 and completed in April 1999. There were 749 pregnancies followed in women exposed to systemic acyclovir during the first trimester of pregnancy resulting in 756 outcomes. The occurrence rate of birth defects approximates that found in the general population. However, the small size of the registry is insufficient to evaluate the risk for less common defects or to permit reliable or definitive conclusions regarding the safety of acyclovir in pregnant women and their developing fetuses.

Animal reproduction studies performed at oral doses that provided up to 10 and 7 times the human plasma levels during the period of major organogenesis in rats and rabbits, respectively, revealed no evidence of teratogenicity.

8.3 Nursing Mothers

Following oral administration of a 500 mg dose of valacyclovir hydrochloride tablets to 5 nursing mothers, peak acyclovir concentrations (Cmax)in breast milk ranged from 0.5 to 2.3 times (median 1.4) the corresponding maternal acyclovir serum concentrations. The acyclovir breast milk AUC ranged from 1.4 to 2.6 times (median 2.2) maternal serum AUC. A 500 mg maternal dosage of valacyclovir hydrochloride tablets twice daily would provide a nursing infant with an oral acyclovir dosage of approximately 0.6 mg/kg/day. This would result in less than 2% of the exposure obtained after administration of a standard neonatal dose of 30 mg/kg/day of intravenous acyclovir to the nursing infant. Unchanged valacyclovir was not detected in maternal serum, breast milk, or infant urine. Caution should be exercised when valacyclovir hydrochloride tablets are administered to a nursing woman.

8.4 Pediatric Use

Valacyclovir hydrochloride tablets are indicated for treatment of cold sores in pediatric patients ≥12 years of age [see Indications and Usage (1.2) , Dosage and Administration (2.2) ].

The use of valacyclovir hydrochloride tablets for treatment of cold sores is based on 2 double-blind, placebo-controlled clinical trials in healthy adults and adolescents (≥12 years of age) with a history of recurrent cold sores [see Clinical Studies (14.1) ].

The efficacy and safety of valacyclovir have not been established in pediatric patients:

• <12 years of age with cold sores

• <18 years of age with genital herpes

• <18 years of age with herpes zoster

• for suppressive therapy following neonatal HSV infection.

In infants 1 month to <3 months of age, mean acyclovir exposures resulting from a 25 mg/kg dose were higher (Cmax: ↑30%, AUC: ↑60%) than acyclovir exposures following a 1 gram dose of valacyclovir in adults.

Labeling describing pediatric use information in pediatric patients with chickenpox (ages 2 to ≤ 18 years) and additional pharmacokinetic studies in pediatric patients (ages 3 months to < 12 years) treated with valacyclovir HCL is approved for GlaxoSmithKline’s Valtrex®* Caplets. However, due to GlaxoSmithKline’s marketing exclusivity rights, that additional pediatric information is not approved for this valacylcovir HCL tablet product.

8.5 Geriatric Use

Of the total number of subjects in clinical studies of valacyclovir hydrochloride tablets, 906 were 65 and over, and 352 were 75 and over. In a clinical study of herpes zoster, the duration of pain after healing (post- herpetic neuralgia) was longer in patients 65 and older compared with younger adults. Elderly patients are more likely to have reduced renal function and require dose reduction. Elderly patients are also more likely to have renal or CNS adverse events [see Dosage and Administration (2.4) , Warnings and Precautions ( 5.2 , 5.3 ), Clinical Pharmacology (12.3) ].

8.6** Renal Impairment**

Dosage reduction is recommended when administering valacyclovir hydrochloride tablets to patients with renal impairment [see Dosage and Administration (2.4) , Warnings and Precautions ( 5.2 , 5.3 )].

PHARMACIST-DETACH HERE AND GIVE INSTRUCTIONS TO PATIENT

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PATIENT INFORMATION

Valacyclovir Hydrochloride Tablets

Issued: March 2010

Rx only

Read the Patient Information that comes with valacyclovir hydrochloride tablets before you start using them and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. Ask your healthcare provider or pharmacist if you have questions.

What arevalacyclovir hydrochloride tablets?

Valacyclovir hydrochloride tablets are a prescription antiviral medicine. Valacyclovir hydrochloride tablets lower the ability of herpes viruses to multiply in your body.

Valacyclovir hydrochloride tablets are used in adults:

• to treat cold sores (also called fever blisters or herpes labialis)

• to treat shingles (also called herpes zoster)

• to treat or control genital herpes outbreaks in adults with normal immune systems

• to control genital herpes outbreaks in adults infected with the human immunodeficiency virus (HIV) with CD4+ cell count greater than 100 cells/mm3

• with safer sex practices to lower the chances of spreading genital herpes to others. Even with safer sex practices, it is still possible to spread genital herpes.

Valacyclovir hydrochloride tablets used daily with the following safer sex practices can lower the chances of passing genital herpes to your partner.

*Do not have sexual contact with your partner when you have any symptom or outbreakof genital herpes.

*Use a condommade of latex or polyurethane whenever you have sexual contact.

Valacyclovir hydrochloride tablets are used in children:

• to treat cold sores (for children ≥12 years of age)

Valacyclovir hydrochloride tablets** do not cure herpes infections**(cold sores, shingles, or genital herpes).

The efficacy of valacyclovir hydrochloride tablets has not been studied in children who have not reached puberty.

Labeling describing use of valacyclovir HCL in pediatric patients with chickenpox (ages of 2 to ≤ 18 years) is approved for GlaxoSmithKline’s Valtrex®* Caplets. However, due to GlaxoSmithKline’s marketing exclusivity rights, a description of that pediatric use is not approved for this valacyclovir HCL tablet product.

What are cold sores, shingles, and genital herpes?****

Cold soresare caused by a herpes virus that may be spread by kissing or other physical contact with the infected area of the skin. They are small, painful ulcers that you get in or around your mouth. It is not known if valacyclovir hydrochloride tablets can stop the spread of cold sores to others.

Shinglesis caused by the same herpes virus that causes chickenpox. It causes small, painful blisters that happen on your skin. Shingles occurs in people who have already had chickenpox. Shingles can be spread to people who have not had chickenpox or the chickenpox vaccine by contact with the infected areas of the skin. It is not known if valacyclovir hydrochloride tablets can stop the spread of shingles to others.

Genital herpesis a sexually transmitted disease. It causes small, painful blisters on your genital area. You can spread genital herpes to others, even when you have no symptoms. If you are sexually active, you can still pass herpes to your partner, even if you are taking valacyclovir hydrochloride tablets. Valacyclovir hydrochloride tablets, taken every day as prescribed and used with the following**safer sex practices,**can lower the chances of passing genital herpes to your partner.

• Do not have sexual contact with your partner when you have any symptom or outbreak of genital herpes.

• Use a condom made of latex or polyurethane whenever you have sexual contact.

Ask your healthcare provider for more information about safer sex practices.

Labeling describing use of valacyclovir HCL in pediatric patients with chickenpox (ages of 2 to ≤ 18 years) is approved for GlaxoSmithKline’s Valtrex®* Caplets. However, due to GlaxoSmithKline’s marketing exclusivity rights, a description of that pediatric use is not approved for this valacyclovir HCL tablet product.

Who should not takevalacyclovir hydrochloride tablets?

Do not take****valacyclovir hydrochloride tablets if you are allergic to any of its ingredients or to acyclovir. The active ingredient is valacyclovir. See the end of this leaflet for a complete list of ingredients in valacyclovir hydrochloride tablets.

Before takingvalacyclovir hydrochloride tablets, tell your healthcare provider:

**About all your medical conditions,**including:

*if you have had a bone marrow transplant or kidney transplant, or if you have**advanced HIV disease or “AIDS”.**Patients with these conditions may have a higher chance for getting a blood disorder called thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). TTP/HUS can result in death.

***if you have kidney problems.**Patients with kidney problems may have a higher chance for getting side effects or more kidney problems with valacyclovir hydrochloride tablets. Your healthcare provider may give you a lower dose of valacyclovir hydrochloride tablets.

***if you are 65 years of age or older.**Elderly patients have a higher chance of certain side effects. Also, elderly patients are more likely to have kidney problems. Your healthcare provider may give you a lower dose of valacyclovir hydrochloride tablets.

***if you are pregnant or planning to become pregnant.**Talk with your healthcare provider about the risks and benefits of taking prescription drugs (including valacyclovir hydrochloride tablets) during pregnancy.

***if you are breastfeeding.**Valacyclovir may pass into your milk and it may harm your baby. Talk with your healthcare provider about the best way to feed your baby if you are taking valacyclovir hydrochloride tablets.

***about all the medicines you take,**including prescription and non-prescription medicines, vitamins, and herbal supplements. Valacyclovir hydrochloride tablets may affect other medicines, and other medicines may affect valacyclovir hydrochloride tablets. It is a good idea to keep a complete list of all the medicines you take. Show this list to your healthcare provider and pharmacist any time you get a new medicine.

How should I takevalacyclovir hydrochloride tablets?

Take valacyclovir hydrochloride tablets exactly as prescribed by your healthcare provider. Your dose of valacyclovir hydrochloride tablets and length of treatment will depend on the type of herpes infection that you have and any other medical problems that you have.

• Do not stop valacyclovir hydrochloride tablets or change your treatment without talking to your healthcare provider.

• Valacyclovir hydrochloride tablets can be taken with or without food.

• If you are taking valacyclovir hydrochloride tablets to treat cold sores, shingles, or genital herpes, you should start treatment as soon as possible after your symptoms start. Valacyclovir hydrochloride tablets may not help you if you start treatment too late.

• If you miss a dose of valacyclovir hydrochloride tablets, take it as soon as you remember and then take your next dose at its regular time. However, if it is almost time for your next dose, do not take the missed dose. Wait and take the next dose at the regular time.

• Do not take more than the prescribed number of valacyclovir hydrochloride tablets each day. Call your healthcare provider right away if you take too many valacyclovir hydrochloride tablets.

Labeling describing use of valacyclovir HCL in pediatric patients with chickenpox (ages of 2 to ≤ 18 years) is approved for GlaxoSmithKline’s Valtrex®* Caplets. However, due to GlaxoSmithKline’s marketing exclusivity rights, a description of that pediatric use is not approved for this valacyclovir HCL tablet product.

What are the possible side effects ofvalacyclovir hydrochloride tablets?

Kidney failure and nervous system problems are not common, but can be serious in somepatients takingvalacyclovir hydrochloride tablets**.Nervous system problems include aggressive behavior, unsteady movement, shaky movements, confusion, speech problems, hallucinations (seeing or hearing things that are really not there), seizures, and coma. Kidney failure and nervous system problems have happened in patients who already have kidney disease and in elderly patients whose kidneys do not work well due to age.Always tell your healthcare provider if you have kidneyproblems before takingvalacyclovir hydrochloride tablets. Call your doctor right away if you get a nervous****system problem while you are taking valacyclovir hydrochloride tablets.**

Common side effects of valacyclovir hydrochloride tablets in adults include headache, nausea, stomach pain, vomiting, and dizziness. Side effects in HIV- infected adults include headache, tiredness, and rash. These side effects usually are mild and do not cause patients to stop taking valacyclovir hydrochloride tablets.

Other less common side effects in adults include painful periods in women, joint pain, depression, low blood cell counts, and changes in tests that measure how well the liver and kidneys work.

The most common side effect seen in children <18 years of age was headache.

Talk to your healthcare provider if you develop any side effects that concern you.

These are not all the side effects of valacyclovir hydrochloride tablets. 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 storevalacyclovir hydrochloride tablets?

• Store valacyclovir hydrochloride tablets at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

• Keep valacyclovir hydrochloride tablets in a tightly closed container.

• Do not keep medicine that is out of date or that you no longer need.

• Keep valacyclovir hydrochloride tablets and all medicines out of the reach of children.

Labeling describing storage of oral suspension of valacyclovir HCL is approved for GlaxoSmithKline’s Valtrex®* Caplets. However, due to GlaxoSmithKline’s marketing exclusivity rights, a description of that storage information is not approved for this valacyclovir HCL tablet product.

General information about****valacyclovir hydrochloride tablets

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use valacyclovir hydrochloride tablets for a condition for which they were not prescribed. Do not give valacyclovir hydrochloride tablets to other people, even if they have the same symptoms you have. They may harm them.

This leaflet summarizes the most important information about valacyclovir hydrochloride tablets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about valacyclovir hydrochloride tablets that is written for health professionals. More information is available at www.watson.com.

What are the ingredients invalacyclovir hydrochloride tablets?

**Active Ingredient:**valacyclovir hydrochloride

**Inactive Ingredients:**croscarmellose sodium, FD&C Blue #2, hydrogenated castor oil, hypromellose, polyethylene glycol, polysorbate 80, starch (corn), and titanium dioxide.

*Valtrex® is a registered trademark of GlaxoSmithKline, LLC

Manufactured for:

Watson Laboratories, Inc.

Corona, CA 92880 USA

Manufactured by:

Cipla Ltd.

Verna, Goa, INDIA

Issued: March 2010

Repackaging by:
****Rebel Distributors Corp
Thousand Oaks, CA 91320