Zerit

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

ZERIT®
(Zair-it)
(stavudine) Oral Solution

ZERIT® Capsules and ZERIT® for Oral Solution

Read this Medication Guide before you start taking ZERIT and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment. You and your healthcare provider should talk about your treatment with ZERIT before you start taking it and at regular checkups. You should stay under your healthcare provider's care when taking ZERIT.

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

ZERIT can cause serious side effects, including:

1. Build up of acid in your blood (lactic acidosis). Lactic acidosis can cause death and must be treated in the hospital. The risk of lactic acidosis may be higher if you:

• have liver problems
• are pregnant. There have been deaths reported in pregnant women who get lactic acidosis after taking ZERIT and VIDEX, or ZERIT and VIDEX EC (didanosine).
• are female
• are overweight
• have been treated for a long time with other medicines used to treat HIV

It is important to call your healthcare provider right away if you:

• feel weak or tired
• have unusual (not normal) muscle pain
• have trouble breathing
• have stomach pain with nausea and vomiting
• feel cold, especially in your arms and legs
• feel dizzy or light-headed
• have a fast or irregular heartbeat

2. Liver problems. Some people (including pregnant women) who have taken ZERIT have had serious liver problems. These problems include liver enlargement (hepatomegaly), fat in the liver (steatosis), liver failure, and death due to liver problems. Your healthcare provider should check your liver function while you are taking ZERIT. You should be especially careful if you have a history of heavy alcohol use or liver problems. Use of ZERIT with VIDEX EC or VIDEX (didanosine) may increase your risk for liver damage.

It is important to call your healthcare provider right away if you have:

• yellowing of your skin or the white of your eyes (jaundice)
• dark urine
• pain on the right side of your stomach
• swelling of your stomach
• easy bruising or bleeding
• loss of appetite
• nausea or vomiting

3. Swelling of the pancreas (pancreatitis) that may cause death has occurred when ZERIT was used with VIDEX EC or VIDEX (didanosine). Pancreatitis can happen at any time during your treatment with ZERIT.

It is important to call your healthcare provider right away if you have:

• stomach pain
• swelling of your stomach
• nausea and vomiting
• fever

What is ZERIT?

ZERIT is a prescription medicine used with other HIV medicines to treat human immunodeficiency virus (HIV) infection in children and adults. ZERIT belongs to a class of drugs called nucleoside analogues.

ZERIT will not cure your HIV infection. At present there is no cure for HIV infection. Even while taking ZERIT, you may continue to have HIVrelated illnesses, including infections with other disease-producing organisms. Continue to see your healthcare provider regularly and report any medical problems that occur.

Who should not take ZERIT?

Do not take ZERIT if you:

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

What should I tell my healthcare provider before taking ZERIT?

Before you take ZERIT, tell your healthcare provider if you:

• have or had liver problems (such as hepatitis)
• have or had problems with your pancreas (pancreatitis)
• have or had kidney problems
• have or had persistent numbness, tingling, or pain in the hands or feet (neuropathy)
• have gallstones
• drink alcoholic beverages
• have any other medical conditions
• are pregnant or plan to become pregnant. It is not known if ZERIT will harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking ZERIT. You and your healthcare provider will decide if you should take ZERIT while you are pregnant.
  Pregnancy Registry: There is a pregnancy registry for women who take antiviral medicines during pregnancy. The purpose of the registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry.
• are breastfeeding or plan to breastfeed. Do not breastfeed. It is not known if ZERIT can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV-1 should not breastfeed because HIV-1 can be passed to the baby in the breast milk.

Tell your healthcare provider about all the medicines that you take, including prescription and non-prescription medicines, vitamins, or herbal supplements. ZERIT may affect the way other medicines work, and other medicines may affect how ZERIT works.

Especially tell your healthcare provider if you take:

• COMBIVIR®, RETROVIR®, TRIZIVIR® (zidovudine or AZT)
• VIDEX® or VIDEX EC® (didanosine)
• ADRIAMYCIN®, RUBEX® (doxorubicin)
• COPEGUS®, REBETOL®, RIBASPHERE®, RIBAVIRIN®, VIRAZOLE® (ribavirin)
• ROFERON-A®, INTRON-A®, and others (interferon)
• HYDREA®, DROXIA® (hydroxyurea)

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

Ask your healthcare provider if you are not sure if you take one of the medicines listed above.

How should I take ZERIT?

• Take ZERIT exactly as your healthcare provider tells you to take it.
• Your healthcare provider will tell you how much ZERIT to take and when to take it.
• If your child will be taking ZERIT, your child's healthcare provider should give you instructions on how to give this medicine. If your child is taking ZERIT oral solution, shake the bottle well before measuring each dose.
• Your healthcare provider may change your dose. Do not change your dose of ZERIT without talking to your healthcare provider.
• ZERIT may be taken with or without food.
• Try not to miss a dose, but if you do, take it as soon as possible. If it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule.
• Some medicines may require your healthcare provider to monitor your therapy or change your therapy. Check with your healthcare provider.
• If your kidneys are not working well, your healthcare provider will need to do regular blood and urine tests to check how they are working while you take ZERIT. Your healthcare provider may also lower your dosage of ZERIT if your kidneys are not working well.
• If you take too much ZERIT, contact a poison control center or emergency room right away.

What should I avoid while taking ZERIT?

• Alcohol. You should avoid drinking alcohol while taking ZERIT. Alcohol may increase your risk of getting pain and swelling of your pancreas (pancreatitis) or may damage your liver.

What are the possible side effects of ZERIT?

ZERIT can cause serious side effects including:

• ZERIT can cause lactic acidosis, liver problems, and pancreatitis. See “What is the most important information I should know about ZERIT?”
• Neurologic symptoms. Symptoms include: weakness of your legs, feet, arms, or hands (motor weakness) and numbness or tingling in your hands or feet (neuropathy). These problems can happen more often in people who have advanced HIV disease, have a history of peripheral neuropathy, or in people who take other medicines that also are associated with neuropathy including didanosine. In some cases, neuropathy may temporarily worsen after you stop taking ZERIT. Neuropathy can be difficult to notice in children who take ZERIT. Ask your child's healthcare provider for the signs and symptoms of peripheral neuropathy in children.

It is important to call your healthcare provider right away if you have:

• numbness in your hands or feet
• tingling in your hands or feet
• weakness in your legs, feet, arms, or hands
• Changes in body fat (fat redistribution).
  Changes in body fat (lipoatrophy or lipodystrophy) have been seen in some people taking HIV medicines including ZERIT. Loss of body fat (lipoatrophy) happens more often in people who take ZERIT than in people who take other similar HIV medicines.
  These changes may include:

• more fat in or around your
  • trunk
  • upper back and neck (buffalo hump)
  • breast or chest
• loss of fat in your
  • legs
  • arms
  • face

Your healthcare provider will monitor you for changes in your body fat. It is important to tell your healthcare provider if you notice any of these changes.

• Changes in your immune system (immune reconstitution syndrome). Your immune system may begin to fight infections that have been in your body for a long time. Tell your healthcare provider if you start having new or worse symptoms of infection after you start taking HIV medicine.

The most common side effects of ZERIT include:

• headache
• diarrhea
• rash
• nausea
• vomiting

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of ZERIT. For more information, ask your healthcare provider or pharmacist.

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

How should I store ZERIT?

• Capsules:
  • Store ZERIT capsules in a tightly closed container at room temperature at 59°F to 86°F (15°C to 30°C).
• Oral solution:
  • Store ZERIT oral solution in the refrigerator at 36°F to 46°F (2°C to 8°C).
  • Store ZERIT oral solution in a tightly closed container.

Throw away any unused medicine after 30 days.

Keep ZERIT and all medicines out of the reach of children and pets.

General Information about the safe and effective use of ZERIT

If you have diabetes mellitus: ZERIT for Oral Solution contains 50 mg of sucrose (sugar) per mL.

Avoid doing things that can spread HIV-1 infection to others.

• Do not share needles or other injection equipment.
• Do not share personal items that can have blood or body fluids on them, like toothbrushes and razor blades.
• Do not have any kind of sex without protection. Always practice safe sex by using a latex or polyurethane condom to lower the chance of sexual contact with semen, vaginal secretions, or blood.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use ZERIT for a condition for which it was not prescribed. Do not give ZERIT to other people, even if they have the same symptoms as you have. It may harm them. Do not keep medicine that is out of date or that you no longer need. Dispose of unused medicines through community take-back disposal programs when available or place ZERIT in an unrecognizable closed container in the household trash.

This Medication Guide summarizes the most important information about ZERIT. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about ZERIT that is written for health professionals. For more information, go to http://www.bms.com/products/Pages/ prescribing.aspx or call 1-800-321-1335.

What are the ingredients in ZERIT?

Active Ingredient: stavudine

Inactive Ingredients:

ZERIT Capsules: microcrystalline cellulose, sodium starch glycolate, lactose, and magnesium stearate.

The gelatin shell contains: gelatin, titanium oxide, and iron oxide.

ZERIT for Oral Solution: methylparaben, propylparaben, sodium carboxymethylcellulose, sucrose, and antifoaming and flavoring agents.

Avoid drinking alcohol. It may increase your risk of pancreas or liver damage while you are taking stavudine.

Taking this medication will not prevent you from passing HIV to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Zerit is a prescription medicine used with other HIV medicines to treat human immunodeficiency virus (HIV) infection in children and adults. 

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your healthcare provider about all the medicines that you take, including prescription and non-prescription medicines, vitamins, or herbal supplements. Zerit may affect the way other medicines work, and other medicines may affect how Zerit works.

Especially tell your healthcare provider if you take:

• Combivir, Retrovir, Trizivir (zidovudine or AZT)
• Videx or Videx EC (didanosine)
• Adriamycin, Rubex (doxorubicin)
• Copegus, Rebetol, Ribasphere, Ribavirin, Virazole (ribavirin)
• Roferon-A, Intron-A, and others (interferon)
• Hydrea, Droxia (hydroxyurea)

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

Ask your healthcare provider if you are not sure if you take one of the medicines listed above.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Zerit, there are no specific foods that you must exclude from your diet when receiving this medication.

WARNING: LACTIC ACIDOSIS and HEPATOMEGALY with STEATOSIS; PANCREATITIS

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including Zerit and other antiretrovirals. Fatal lactic acidosis has been reported in pregnant women who received the combination of Zerit and didanosine with other antiretroviral agents. The combination of Zerit and didanosine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk.

Fatal and nonfatal pancreatitis have occurred during therapy when Zerit was part of a combination regimen that included didanosine in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression.

Administration

Oral Administration

Administer orally every 12 hours without regard to meals.1

Reconstitute powder for oral solution at time of dispensing by adding the amount of purified water specified to provide a solution containing 1 mg/mL.1 Shake vigorously until completely dissolved; solution may appear slightly hazy.1

Agitate solution well prior to administration of each dose.1

Dosage

Pediatric Patients

Birth to 13 days of age: 0.5 mg/kg every 12 hours.1

≥14 days of age weighing <30 kg: 1 mg/kg every 12 hours.1

≥30 kg to <60 kg: 30 mg every 12 hours.1

≥60 kg: 40 mg every 12 hours.1

Adults

<60 kg: 30 mg every 12 hours.1

≥60 kg: 40 mg every 12 hours.1

<60 kg: 30 mg twice daily.199

>60 kg: 40 mg twice daily.199

Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).199

Initiate PEP as soon as possible following exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.199

<60 kg: 30 mg twice daily.198

>60 kg: 40 mg twice daily.198

Use in conjunction with other antiretrovirals.198

Initiate nPEP as soon as possible following exposure to HIV (preferably ≤72 hours after exposure); continue for 28 days.198

Special Populations

Renal Impairment

Stavudine clearance may be altered in pediatric patients with renal impairment;1 data insufficient to recommend specific dosage adjustments in such children.1

Dosage adjustments recommended in adults with renal impairment, including those undergoing hemodialysis.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 performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of stavudine in children.

Geriatric

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

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

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

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

• Didanosine
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Hydroxyurea
• Orlistat
• Ribavirin
• Zidovudine

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

• Methadone

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:

• Alcohol abuse, active or history of, or
• Gallstones, active or history of, or
• Liver disease (includes hepatitis) or
• Obesity (being overweight) or
• Pancreatitis (inflammation of the pancreas), history of or
• Peripheral neuropathy (nerve disorder), history of or
• Use of other HIV medicines for a long period of time—Use with caution. May cause side effects to become worse.

• Diabetes—The oral liquid contains sucrose (sugar), which can make this condition worse.

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

Zerit is unlikely to interact with drugs metabolized by cytochrome P450 isoenzymes.

Zidovudine: Zidovudine competitively inhibits the intracellular phosphorylation of stavudine. Therefore, use of zidovudine in combination with Zerit (stavudine) should be avoided.

Doxorubicin: In vitro data indicate that the phosphorylation of stavudine is inhibited at relevant concentrations by doxorubicin. The clinical significance of this interaction is unknown; therefore, concomitant use of stavudine with doxorubicin should be undertaken with caution.

Ribavirin: In vitro data indicate ribavirin reduces phosphorylation of lamivudine, stavudine, and zidovudine. The clinical significance of the interaction with stavudine is unknown; therefore, concomitant use of stavudine with ribavirin should be undertaken with caution. No pharmacokinetic (eg, plasma concentrations or intracellular triphosphorylated active metabolite concentrations) or pharmacodynamic (eg, loss of HIV-1/HCV virologic suppression) interaction was observed when ribavirin and lamivudine (n=18), stavudine (n=10), or zidovudine (n=6) were coadministered as part of a multi-drug regimen to HIV-1/HCV co-infected patients [see Warnings and Precautions (5.2)].

    Carcinogenesis, Mutagenesis, Impairment of Fertility

In 2-year carcinogenicity studies in mice and rats, stavudine was noncarcinogenic at doses which produced exposures (AUC) 39 and 168 times, respectively, human exposure at the recommended clinical dose. Benign and malignant liver tumors in mice and rats and malignant urinary bladder tumors in male rats occurred at levels of exposure 250 (mice) and 732 (rats) times human exposure at the recommended clinical dose.

Stavudine was not mutagenic in the Ames, E. coli reverse mutation, or the CHO/HGPRT mammalian cell forward gene mutation assays, with and without metabolic activation. Stavudine produced positive results in the in vitro human lymphocyte clastogenesis and mouse fibroblast assays, and in the in vivo mouse micronucleus test. In the in vitro assays, stavudine elevated the frequency of chromosome aberrations in human lymphocytes (concentrations of 25 to 250 µg/mL, without metabolic activation) and increased the frequency of transformed foci in mouse fibroblast cells (concentrations of 25 to 2500 µg/mL, with and without metabolic activation). In the in vivo micronucleus assay, stavudine was clastogenic in bone marrow cells following oral stavudine administration to mice at dosages of 600 to 2000 mg/kg/day for 3 days.

No evidence of impaired fertility was seen in rats with exposures (based on Cmax) up to 216 times that observed following a clinical dosage of 1 mg/kg/day.

Zerit (stavudine) is an antiviral medicine that prevents human immunodeficiency virus (HIV) from multiplying in your body.

Zerit is used to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS).

Zerit is not a cure for HIV or AIDS.

Do not use Zerit if you have ever had a severe allergic reaction to any medicine that contains zidovudine.

Zerit may cause a serious condition called lactic acidosis. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

Zerit can also cause serious or life-threatening effects on your liver or pancreas. Call your doctor at once if you have: stomach pain or swelling, fever, nausea, vomiting, easy bruising or bleeding, loss of appetite, dark urine, or jaundice (yellowing of the skin or eyes).

You should not take Zerit if you are allergic to stavudine.

Do not take this medicine with any other medicine that contains zidovudine or stavudine, including: Combivir, Trizivir, or Retrovir.

Some people taking Zerit develop a serious condition called lactic acidosis. This may be more likely in women, in people who are overweight or have liver disease, and in people who have taken HIV/AIDS medication for a long time. Talk with your doctor about your risk.

Zerit can also cause severe or life-threatening effects on your liver or pancreas. Tell your doctor if you have liver disease or a history of pancreatitis.

To make sure Zerit is safe for you, tell your doctor if you have ever had:

• kidney disease;

• liver disease;

• gallstones;

• numbness, tingling, or burning pain in your hands or feet;

• problems with your pancreas; or

• if you drink large amounts of alcohol.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection.

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

Women with HIV or AIDS should not breast feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

Taking this medicine will not prevent you from passing HIV to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Avoid drinking alcohol. It may increase your risk of pancreas or liver damage while you are taking Zerit.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• didanosine;

• zidovudine or AZT;

• doxorubicin;

• hydroxyurea;

• interferon-alfa; or

• ribavirin.

This list is not complete. Other drugs may interact with stavudine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.