Stavudine Capsules

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

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

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

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

Stavudine Capsules are contraindicated in patients with clinically significant hypersensitivity to stavudine or to any of the components contained in the formulation.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Reproduction studies have been performed in rats and rabbits with exposures (based on Cmax) up to 399 and 183 times, respectively, of that seen at a clinical dosage of 1 mg/kg/day and have revealed no evidence of teratogenicity. The incidence in fetuses of a common skeletal variation, unossified or incomplete ossification of sternebra, was increased in rats at 399 times human exposure, while no effect was observed at 216 times human exposure. A slight post-implantation loss was noted at 216 times the human exposure with no effect noted at approximately 135 times the human exposure. An increase in early rat neonatal mortality (birth to 4 days of age) occurred at 399 times the human exposure, while survival of neonates was unaffected at approximately 135 times the human exposure. A study in rats showed that stavudine is transferred to the fetus through the placenta. The concentration in fetal tissue was approximately one-half the concentration in maternal plasma. Animal reproduction studies are not always predictive of human response.

There are no adequate and well-controlled studies of stavudine in pregnant women. Stavudine should be used during pregnancy only if the potential benefit justifies the potential risk.

Fatal lactic acidosis has been reported in pregnant women who received the combination of stavudine and didanosine with other antiretroviral agents. It is unclear if pregnancy augments the risk of lactic acidosis/hepatic steatosis syndrome reported in nonpregnant individuals receiving nucleoside analogues [see Boxed Warning and Warnings and Precautions (5.1)]. The combination of stavudine and didanosine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk. Healthcare providers caring for HIV-infected pregnant women receiving stavudine should be alert for early diagnosis of lactic acidosis/hepatic steatosis syndrome.

Antiretroviral Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant women exposed to stavudine and other antiretroviral agents, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.

Nursing Mothers

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. Studies in lactating rats demonstrated that stavudine is excreted in milk. Although it is not known whether stavudine is excreted in human milk, there exists the potential for adverse effects from stavudine in nursing infants. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving stavudine.

Pediatric Use

Use of stavudine in pediatric patients from birth through adolescence is supported by evidence from adequate and well-controlled studies of stavudine in adults with additional pharmacokinetic and safety data in pediatric patients [see Dosage and Administration (2.2) and Adverse Reactions (6.2)].

Adverse reactions and laboratory abnormalities reported to occur in pediatric patients in clinical studies were generally consistent with the safety profile of stavudine in adults. These studies include ACTG 240, where 105 pediatric patients ages 3 months to 6 years received stavudine 2 mg/kg/day for a median of 6.4 months; a controlled clinical trial where 185 newborns received stavudine 2 mg/kg/day either alone or in combination with didanosine from birth through 6 weeks of age; and a clinical trial where 8 newborns received stavudine 2 mg/kg/day in combination with didanosine and nelfinavir from birth through 4 weeks of age.

Stavudine pharmacokinetics have been evaluated in 25 HIV-1-infected pediatric patients ranging in age from 5 weeks to 15 years and in weight from 2 to 43 kg after IV or oral administration of single doses and twice-daily regimens and in 30 HIV-1-exposed or -infected newborns ranging in age from birth to 4 weeks after oral administration of twice-daily regimens [see Clinical Pharmacology (12.3,Table 9)].

Geriatric Use

Clinical studies of stavudine did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently than younger patients. Greater sensitivity of some older individuals to the effects of stavudine cannot be ruled out.

In a monotherapy Expanded Access Program for patients with advanced HIV-1 infection, peripheral neuropathy or peripheral neuropathic symptoms were observed in 15 of 40 (38%) elderly patients receiving 40 mg twice daily and 8 of 51 (16%) elderly patients receiving 20 mg twice daily. Of the approximately 12,000 patients enrolled in the Expanded Access Program, peripheral neuropathy or peripheral neuropathic symptoms developed in 30% of patients receiving 40 mg twice daily and 25% of patients receiving 20 mg twice daily. Elderly patients should be closely monitored for signs and symptoms of peripheral neuropathy.

Stavudine 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, it may be useful to monitor renal function. Dose adjustment is recommended for patients with renal impairment [see Dosage and Administration (2.3)].

Renal Impairment

Data from two studies in adults indicated that the apparent oral clearance of stavudine decreased and the terminal elimination half-life increased as creatinine clearance decreased. Based on these observations, it is recommended that the stavudine dosage be modified in patients with reduced creatinine clearance and in patients receiving maintenance hemodialysis [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)].

Experience with adults treated with 12 to 24 times the recommended daily dosage revealed no acute toxicity. Complications of chronic overdosage include peripheral neuropathy and hepatic toxicity. Stavudine can be removed by hemodialysis; the mean ± SD hemodialysis clearance of stavudine is 120 ± 18 mL/min. Whether stavudine is eliminated by peritoneal dialysis has not been studied.

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 mcg/mL, without metabolic activation) and increased the frequency of transformed foci in mouse fibroblast cells (concentrations of 25 to 2500 mcg/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.

Capsules

Stavudine  Capsules  USP,  15  mg  are  dark  red  opaque/light  yellow  opaque  size  '4'  hard  gelatin  capsule  filled  with  white  to  off  white granular powder and imprinted with 'E' on dark red opaque cap and '76' on light yellow opaque body with black ink.

Bottle of 60 Capsules             NDC 64980-354-06

Stavudine  Capsules  USP,  20  mg  are  light  brown  opaque/light  brown  opaque  size  '3'  hard  gelatin  capsule  filled  with  white  to  off  white granular powder and imprinted with 'E' on light brown opaque cap and '77' on light brown opaque body with black ink.

Bottle of 60 Capsules             NDC 64980-355-06

Stavudine  Capsules  USP,  30  mg  are  dark  orange  opaque/light  orange  opaque  size  '2'  hard  gelatin  capsule  filled  with  white  to  off  white granular powder and imprinted with 'C' on dark orange opaque cap and '36' on light orange opaque body with black ink.

Bottle of 60 Capsules             NDC 64980-356-06

Stavudine  Capsules  USP,  40  mg  are  dark  orange  opaque/dark  orange  opaque  size  '1'  hard  gelatin  capsule  filled  with  white  to  off  white granular powder and imprinted with 'C' on dark orange opaque cap and '37' on dark orange opaque body with black ink.

Bottle of 60 Capsules             NDC 64980-357-06

Storage

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Stavudine Capsules, USP

Read this Medication Guide before you start taking Stavudine Capsules 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 Stavudine Capsules before you start taking them and at regular check-ups. You should stay under your healthcare provider’s care when taking Stavudine Capsules.

What is the most important information I should know about Stavudine Capsules?

Stavudine Capsules 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 Stavudine Capsules and VIDEX, or Stavudine Capsules 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 Stavudine Capsules 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 Stavudine Capsules. You should be especially careful if you have a history of heavy alcohol use or liver problems. Use of Stavudine Capsules with VIDEX EC or VIDEX (didnosine) 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 Stavudine Capsules were used with VIDEX EC or VIDEX (didanosine). Pancreatitis can happen at any time during your treatment with Stavudine Capsules.

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

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

What are Stavudine Capsules?

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

Stavudine Capsules will not cure your HIV infection. At present there is no cure for HIV infection. Even while taking Stavudine Capsules, you may continue to have HIV-related 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 Stavudine Capsules?

Do not take Stavudine Capsules if you: 

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

What should I tell my healthcare provider before taking Stavudine Capsules?


Before you take Stavudine Capsules, 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 Stavudine Capsules will harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking Stavudine Capsules. You and your healthcare provider will decide if you should take Stavudine Capsules 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 stavudine 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. Stavudine Capsules may affect the way other medicines work, and other medicines may affect how Stavudine Capsules work. 

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 Stavudine Capsules? 

• Take Stavudine Capsules exactly as your healthcare provider tells you to take them.
• Your healthcare provider will tell you how much stavudine to take and when to take it.
• If your child will be taking Stavudine Capsules, your child’s healthcare provider should give you instructions on how to give this medicine.
• Your healthcare provider may change your dose. Do not change your dose of Stavudine Capsules without talking to your healthcare provider.
• Stavudine Capsules 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 Stavudine Capsules. Your healthcare provider may also lower your dosage of Stavudine Capsules if your kidneys are not working well.
• If you take too much stavudine, contact a poison control center or emergency room right away.

What should I avoid while taking Stavudine Capsules? 

• Alcohol. You should avoid drinking alcohol while taking Stavudine Capsules. 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 Stavudine Capsules? 

Stavudine Capsules can cause serious side effects including:

• Stavudine Capsules can cause lactic acidosis, liver problems, and pancreatitis. See “What is the most important information I should know about Stavudine Capsules?”
• 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 Stavudine Capsules. Neuropathy can be difficult to notice in children who take Stavudine Capsules. 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 Stavudine Capsules. Loss of body fat (lipoatrophy) happens more often in people who take Stavudine Capsules 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 Stavudine Capsules 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 Stavudine Capsules. 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 Stavudine Capsules? 

Store Stavudine Capsules in a tightly closed container at room temperature at 15° to 30°C (59° to 86°F).

Keep Stavudine Capsules and all medicines out of the reach of children and pets.

General information about the safe and effective use of Stavudine Capsules

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 or other barrier method 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 Stavudine Capsules for a condition for which they were not prescribed. Do not give Stavudine Capsules to other people, even if they have the same symptoms as you have. They 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 Stavudine Capsules in an unrecognizable closed container in the household trash.

This Medication Guide summarizes the most important information about Stavudine Capsules. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Stavudine Capsules that is written for health professionals. For more information, call (1-866-562-4597).

What are the ingredients in Stavudine Capsules?

Active Ingredient: stavudine

Inactive Ingredients: microcrystalline cellulose, sodium starch glycolate, anhydrous lactose, and magnesium stearate. The hard gelatin shell consists of gelatin, sodium lauryl sulfate, titanium dioxide, yellow iron oxide, and red iron oxide. The capsules are printed with black ink containing black iron oxide.

All brands listed are the trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited.

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

Distributed by:

Rising Pharmaceuticals, Inc.

Allendale, NJ 07401

Made in India

Code No.: TS/DRUGS/19/1993

Issued: 03/2017

Rising® NDC 64980-357-06
Stavudine Capsules, USP
40 mg
PHARMACIST: Detach and dispense the
enclosed Medication Guide to each patient.
60 Capsules                          Rx only