5 WARNINGS AND PRECAUTIONS
5.1 Lactic Acidosis/Severe Hepatomegaly with Steatosis
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including stavudine and other antiretrovirals. Although relative rates of lactic acidosis have not been assessed in prospective well-controlled trials, longitudinal cohort and retrospective studies suggest that this infrequent event may be more often associated with antiretroviral combinations containing stavudine. Female gender, obesity, and prolonged nucleoside exposure may be risk factors. Fatal lactic acidosis has been reported in pregnant women who received the combination of stavudine and didanosine with other antiretroviral agents. 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 [see Use in Specific Populations (8.1)].
Particular caution should be exercised when administering ZERIT to any patient with known risk factors for liver disease; however, cases of lactic acidosis have also been reported in patients with no known risk factors. Generalized fatigue, digestive symptoms (nausea, vomiting, abdominal pain, and unexplained weight loss); respiratory symptoms (tachypnea and dyspnea); or neurologic symptoms, including motor weakness [see Warnings and Precautions (5.3)] might be indicative of the development of symptomatic hyperlactatemia or lactic acidosis syndrome.
Treatment with ZERIT (stavudine) should be suspended in any patient who develops clinical or laboratory findings suggestive of symptomatic hyperlactatemia, lactic acidosis, or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations). Permanent discontinuation of ZERIT should be considered for patients with confirmed lactic acidosis.
5.2 Hepatic Toxicity
The safety and efficacy of ZERIT have not been established in HIV-infected patients with significant underlying liver disease. During combination antiretroviral therapy, patients with preexisting liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities, including severe and potentially fatal hepatic adverse events, and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Hepatotoxicity and hepatic failure resulting in death were reported during postmarketing surveillance in HIV-infected patients treated with hydroxyurea and other antiretroviral agents. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. This combination should be avoided. [See Adverse Reactions (6).]
Use with Interferon and Ribavirin-Based Regimens
In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as stavudine. Although no evidence of a pharmacokinetic or pharmacodynamic (eg, loss of HIV-1/HCV virologic suppression) interaction was seen when ribavirin was coadministered with stavudine in HIV-1/HCV co-infected patients [see Drug Interactions (7)], hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon and ribavirin. Patients receiving interferon with or without ribavirin and stavudine should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. Discontinuation of stavudine should be considered as medically appropriate. Dose reduction or discontinuation of interferon, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (eg, Child-Pugh >6) (see the full prescribing information for interferon and ribavirin).
5.3 Neurologic Symptoms
Motor weakness has been reported rarely in patients receiving combination antiretroviral therapy including ZERIT. Most of these cases occurred in the setting of lactic acidosis. The evolution of motor weakness may mimic the clinical presentation of Guillain-Barré syndrome (including respiratory failure). If motor weakness develops, ZERIT should be discontinued. Symptoms may continue or worsen following discontinuation of therapy.
Peripheral sensory neuropathy, manifested by numbness, tingling, or pain in the hands or feet, has been reported in patients receiving ZERIT therapy. Peripheral neuropathy, which can be severe, is dose related and occurs more frequently in patients with advanced HIV-1 disease, a history of peripheral neuropathy, or in patients receiving other drugs that have been associated with neuropathy, including didanosine [see Adverse Reactions (6)].
Patients should be monitored for the development of peripheral neuropathy. Stavudine-related peripheral neuropathy may resolve if therapy is withdrawn promptly. If peripheral neuropathy develops permanent discontinuation of ZERIT should be considered. In some cases, symptoms may worsen temporarily following discontinuation of therapy.
5.4 Pancreatitis
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. The combination of ZERIT and didanosine and any other agents that are toxic to the pancreas should be suspended in patients with suspected pancreatitis. Reinstitution of ZERIT after a confirmed diagnosis of pancreatitis should be undertaken with particular caution and close patient monitoring; avoid use in combination with didanosine.
5.5 Fat Redistribution
Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy.
In randomized controlled trials of treatment-naive patients, clinical lipoatrophy or lipodystrophy developed in a higher proportion of patients treated with stavudine compared to other nucleosides (tenofovir or abacavir). Dual energy x-ray absorptiometry (DEXA) scans demonstrated overall limb fat loss in stavudine-treated patients compared to limb fat gain or no gain in patients treated with other nucleosides (abacavir, tenofovir, or zidovudine). The incidence and severity of lipoatrophy or lipodystrophy are cumulative over time with stavudine-containing regimens. In clinical trials, switching from stavudine to other nucleosides (tenofovir or abacavir) resulted in increases in limb fat with modest to no improvements in clinical lipoatrophy. Patients receiving ZERIT should be monitored for symptoms or signs of lipoatrophy or lipodystrophy and questioned about body changes related to lipoatrophy or lipodystrophy. Given the potential risks of using ZERIT including lipoatrophy or lipodystrophy, a benefit-risk assessment for each patient should be made and an alternative antiretroviral should be considered.
5.6 Immune Reconstitution Syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including ZERIT. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia (PCP), or tuberculosis), which may necessitate further evaluation and treatment.
Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.
6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
When ZERIT is used in combination with other agents with similar toxicities, the incidence of adverse reactions may be higher than when stavudine is used alone.
6.1 Clinical Trial Experience in Adults
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Selected adverse reactions that occurred in adult patients receiving ZERIT in a controlled monotherapy study (Study AI455-019) are provided in Table 2.
Table 2: Selected Adverse Reactions in Study AI455-019a (Monotherapy)
|
Percent (%) |
Adverse Reaction |
ZERITb (40 mg twice daily) (n=412) |
zidovudine (200 mg 3 times daily) (n=402) |
a The incidences reported included all severity grades and all reactions regardless of causality. |
b Median duration of stavudine therapy = 79 weeks; median duration of zidovudine therapy = 53 weeks. |
Headache |
54 |
49 |
Diarrhea |
50 |
44 |
Peripheral Neurologic
Symptoms/Neuropathy |
52 |
39 |
Rash |
40 |
35 |
Nausea and Vomiting |
39 |
44 |
Pancreatitis was observed in 3 of the 412 adult patients who received ZERIT in study AI455-019.
Selected adverse reactions that occurred in antiretroviral-naive adult patients receiving ZERIT from two controlled combination studies are provided in Table 3.
Table 3: Selected Adverse Reactionsa in START 1 and START 2b Studies (Combination Therapy)
|
Percent (%) |
|
START 1 |
START 2b |
Adverse Reaction |
ZERIT + lamivudine + indinavir (n=100c) |
zidovudine + lamivudine + indinavir (n=102) |
ZERIT + didanosine + indinavir (n=102c) |
zidovudine + lamivudine + indinavir (n=103) |
a The incidences reported included all severity grades and all reactions regardless of causality. |
b START 2 compared two triple-combination regimens in 205 treatment-naive patients. Patients received either ZERIT (40 mg twice daily) plus didanosine plus indinavir or zidovudine plus lamivudine plus indinavir. |
c Duration of stavudine therapy = 48 weeks. |
Nausea |
43 |
63 |
53 |
67 |
Diarrhea |
34 |
16 |
45 |
39 |
Headache |
25 |
26 |
46 |
37 |
Rash |
18 |
13 |
30 |
18 |
Vomiting |
18 |
33 |
30 |
35 |
Peripheral Neurologic Symptoms/Neuropathy |
8 |
7 |
21 |
10 |
Selected laboratory abnormalities reported in a controlled monotherapy study (Study AI455-019) are provided in Table 4.
Table 4: Selected Laboratory Abnormalities in Study AI455-019a,b
|
Percent (%) |
Parameter |
ZERIT (40 mg twice daily) (n=412) |
zidovudine (200 mg 3 times daily) (n=402) |
a Data presented for patients for whom laboratory evaluations were performed. |
b Median duration of stavudine therapy = 79 weeks; median duration of zidovudine therapy = 53 weeks. |
ULN = upper limit of normal. |
AST (SGOT) (>5.0 x ULN) |
11 |
10 |
ALT (SGPT) (>5.0 x ULN) |
13 |
11 |
Amylase (≥1.4 x ULN) |
14 |
13 |
Selected laboratory abnormalities reported in two controlled combination studies are provided in Tables 5 and 6.
Table 5: Selected Laboratory Abnormalities in START 1 and START 2 Studies (Grades 3–4)
|
Percent (%) |
|
START 1 |
START 2 |
Parameter |
ZERIT + lamivudine + indinavir (n=100) |
zidovudine + lamivudine + indinavir (n=102) |
ZERIT + didanosine + indinavir (n=102) |
zidovudine + lamivudine + indinavir (n=103) |
ULN = upper limit of normal. |
Bilirubin (>2.6 x ULN) |
7 |
6 |
16 |
8 |
AST (SGOT) (>5 x ULN) |
5 |
2 |
7 |
7 |
ALT (SGPT) (>5 x ULN) |
6 |
2 |
8 |
5 |
GGT (>5 x ULN) |
2 |
2 |
5 |
2 |
Lipase (>2 x ULN) |
6 |
3 |
5 |
5 |
Amylase (>2 x ULN) |
4 |
<1 |
8 |
2 |
Table 6: Selected Laboratory Abnormalities in START 1 and START 2 Studies (All Grades)
|
Percent (%) |
|
START 1 |
START 2 |
Parameter |
ZERIT + lamivudine + indinavir (n=100) |
zidovudine + lamivudine + indinavir (n=102) |
ZERIT + didanosine + indinavir (n=102) |
zidovudine + lamivudine + indinavir (n=103) |
Total Bilirubin |
65 |
60 |
68 |
55 |
AST (SGOT) |
42 |
20 |
53 |
20 |
ALT (SGPT) |
40 |
20 |
50 |
18 |
GGT |
15 |
8 |
28 |
12 |
Lipase |
27 |
12 |
26 |
19 |
Amylase |
21 |
19 |
31 |
17 |
6.2 Clinical Trial Experience in Pediatric Patients
Adverse reactions and serious laboratory abnormalities reported in pediatric patients from birth through adolescence during clinical trials were similar in type and frequency to those seen in adult patients. [See Use in Specific Populations (8.4).]
6.3 Postmarketing Experience
The following adverse reactions have been identified during postmarketing use of ZERIT. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to ZERIT, or a combination of these factors.
Body as a Whole: abdominal pain, allergic reaction, chills/fever, and redistribution/accumulation of body fat [see Warnings and Precautions (5.5)].
Digestive Disorders: anorexia.
Exocrine Gland Disorders: pancreatitis, including fatal cases [see Warnings and Precautions (5.4)].
Hematologic Disorders: anemia, leukopenia, thrombocytopenia, neutropenia, and macrocytosis.
Liver: symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis [see Warnings and Precautions (5.1)], hepatitis and liver failure.
Metabolic Disorders: lipoatrophy, lipodystrophy [see Warnings and Precautions (5.5)], diabetes mellitus and hyperglycemia.
Musculoskeletal: myalgia.
Nervous System: insomnia, severe motor weakness (most often reported in the setting of lactic acidosis) [see Warnings and Precautions (5.1, 5.3)].
Use with Didanosine- and Hydroxyurea-Based Regimens
When stavudine is used in combination with other agents with similar toxicities, the incidence of these toxicities may be higher than when stavudine is used alone. Thus, patients treated with ZERIT in combination with didanosine, with or without hydroxyurea, may be at increased risk for pancreatitis and hepatotoxicity, which may be fatal, and severe peripheral neuropathy [see Warnings and Precautions (5)]. The combination of ZERIT and hydroxyurea, with or without didanosine, should be avoided.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
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.
8.3 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 ZERIT.
8.4 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 ZERIT 2 mg/kg/day for a median of 6.4 months; a controlled clinical trial where 185 newborns received ZERIT 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 ZERIT 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)].
8.5 Geriatric Use
Clinical studies of ZERIT (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 ZERIT 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.
ZERIT 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)].
8.6 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 ZERIT 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)].
11 DESCRIPTION
ZERIT® is the brand name for stavudine (d4T), a synthetic thymidine nucleoside analogue, active against the human immunodeficiency virus type 1 (HIV-1). The chemical name for stavudine is 2′,3′-didehydro-3′-deoxythymidine. Stavudine has the following structural formula:
Stavudine is a white to off-white crystalline solid with the molecular formula C10H12N2O4 and a molecular weight of 224.2. The solubility of stavudine at 23°C is approximately 83 mg/mL in water and 30 mg/mL in propylene glycol. The n-octanol/water partition coefficient of stavudine at 23°C is 0.144.
Capsules: ZERIT is available as capsules for oral administration containing either 15, 20, 30, or 40 mg of stavudine. Each capsule also contains inactive ingredients microcrystalline cellulose, sodium starch glycolate, lactose, and magnesium stearate. The hard gelatin shell consists of gelatin, titanium dioxide, and iron oxides. The capsules are printed with edible inks.
Powder for Oral Solution: ZERIT is available as a dye-free, fruit-flavored powder in bottles with child-resistant closures providing 200 mL of a 1 mg/mL stavudine oral solution upon constitution with water per label instructions. The powder for oral solution contains the following inactive ingredients: methylparaben, propylparaben, sodium carboxymethylcellulose, sucrose, and antifoaming and flavoring agents.
17 PATIENT COUNSELING INFORMATION
See MEDICATION GUIDE.
17.1 General
Patients should be advised that ZERIT is not a cure for HIV-1 infection, and that they may continue to experience illnesses associated with HIV-1 infection, including opportunistic infections. Patients should be advised to remain under the care of a physician when using ZERIT and the importance of adherence to any antiretroviral regimen including those that contain ZERIT.
Patients should be advised to 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.
- 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 breast milk.
Patients should be informed that when ZERIT is used in combination with other agents with similar toxicities, the incidence of adverse reactions may be higher than when ZERIT is used alone.
Patients should be instructed that if they miss a dose, to take it as soon as possible. If it is almost time for the next dose, skip the missed dose and continue the regular dosing schedule.
Patients should be instructed if they take too much ZERIT, they should contact a poison control center or emergency room right away.
Patients should be informed that the Centers for Disease Control and Prevention (CDC) recommend that HIV-infected mothers not nurse newborn infants to reduce the risk of postnatal transmission of HIV infection.
Patients with diabetes should be aware that ZERIT for Oral Solution contains 50 mg of sucrose (sugar) per mL.
17.2 Lactic Acidosis
Patients should be informed of the importance of early recognition of symptoms of symptomatic hyperlactatemia or lactic acidosis syndrome, which include unexplained weight loss, abdominal discomfort, nausea, vomiting, fatigue, dyspnea, and motor weakness. Patients in whom these symptoms develop should seek medical attention immediately. Discontinuation of ZERIT therapy may be required.
17.3 Hepatic Toxicity
Patients should be informed that an increased risk of hepatotoxicity, which may be fatal, may occur in patients treated with ZERIT in combination with didanosine and hydroxyurea. This combination should be avoided.
17.4 Peripheral Neuropathy
Patients should be informed that an important toxicity of ZERIT (stavudine) is peripheral neuropathy. Patients should be aware that peripheral neuropathy is manifested by numbness, tingling, or pain in hands or feet, and that these symptoms should be reported to their physicians. Patients should be counseled that peripheral neuropathy occurs with greatest frequency in patients who have advanced HIV-1 disease or a history of peripheral neuropathy, and discontinuation of ZERIT may be required if toxicity develops.
Caregivers of young children receiving ZERIT therapy should be instructed regarding detection and reporting of peripheral neuropathy.
17.5 Pancreatitis
Patients should be informed that an increased risk of pancreatitis, which may be fatal, may occur in patients treated with the combination of ZERIT and didanosine. This combination should be avoided. Patients should be closely monitored for symptoms of pancreatitis.
The patient should be instructed to avoid alcohol while taking ZERIT. Alcohol may increase the patient’s risk of pancreatitis or liver damage.
17.6 Fat Redistribution
Patients should be informed that redistribution or accumulation of body fat may occur in individuals receiving antiretroviral therapy including ZERIT. Patients receiving ZERIT should be monitored for clinical signs and symptoms of lipoatrophy/lipodystrophy. Patients should be routinely questioned about body changes related to lipoatrophy/lipodystrophy.
Medication Guide
ZERIT® (Zair-it)
(stavudine)
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 check-ups. 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 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 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
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.
ZERIT®, VIDEX®, VIDEX EC®, HYDREA®, and DROXIA® are registered trademarks of Bristol-Myers Squibb Company. All other trademarks are the property of their respective owners.
Distributed by:
Bristol-Myers Squibb Company
Princeton, NJ 08543 USA
This Medication Guide has been approved by the U.S. Food and Drug Administration.
1286696A5
MF#0152-07
Rev December 2012