Stavudine

224.21

224.21

1308068-626-2

BO9LE4QFZF

759897

DTXSID1023819

C1428

White to off white crystalline solid|Colorless granular solid from ethanol/benzene

J05AF04|J - Antiinfectives for systemic use

2938901000

78.9

-0.8

2',3'-didehydro-3'-deoxythymidine appears as white crystalline solid or powder. Odorless. (NTP, 1992)

1.5±0.1 g/cm3

165-166 °C

220.3±31.5 °C

-46 ° (C=0.69, H2O)

H2O: 5-10 g/100 mL at 21 ºC

−20°C

9.5X10-12 mm Hg at 25 deg C /Estimated/

LD50 oral in rat: 4gm/kg

D25 -39.4° (c = 0.701 in water); D20 -46.1° (c = 0.7 in water)

Henry's Law constant = 2.3X10-15 atm-cu m/mole at 25 °C /Estimated/

Hydroxyl radical reaction rate constant = 1.21X10-10 cu cm/molec-sec at 25 °C /Estimated/|Ozone reaction rate constant = 2.1X10-16 cu cm/molec-sec at 25 °C /Estimated/

Water soluble.

Alcohols and Polyols

2',3'-DIDEHYDRO-3'-DEOXYTHYMIDINE is sensitive to heat. Incompatible with strong oxidizing agents (NTP, 1992).

NONH for all modes of transport

2

36/37/38

26-36

XP2075000

Xi

Stable. Combustible. Incompatible with strong oxidizing agents.

P201, P202, P260, P261, P263, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P314, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

H302

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl stavudine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Zapor MJ et al; Antiretrovirals, Part II: Focus on Non-protease Inhibitor Antiretrovirals (NRTIs, NNRTIs, and Fusion Inhibitors); Psychosomatics 45 (6): 524-35 (2004)

Literature sources indicate that this chemical is combustible. (NTP, 1992)

|Danger|H302 (66.67%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P261, P263, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P314, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 3 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this chemical under refrigerated temperatures, and keep it away from oxidizing materials. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

Side effects include peripheral neuropathy tingling, burning, numbness, or pain in the hands or feet), fatal lactic acidosis has been reported in patients treated with stavudine (ZERIT) in combination with other antiretroviral agents, severe liver enlargement, inflammation (pain and swelling) of the liver, and liver failure.

Stavudine is a well known cause of liver injury and is regularly listed in case series of drug induced liver injury and acute liver failure. Mild and transient elevations in liver enzymes occur in up to half of patients on stavudine, but elevations above 5 times normal occur in only 5% to 13% of treated patients. Clinically apparent hepatotoxicity due to stavudine is well described and is usually marked by lactic acidosis, marked hepatic steatosis (microvesicular fat), and progressive hepatic synthetic dysfunction (LASH). This form of liver injury typically arises only after 2 to 6 months of therapy and is preceded by nonspecific prodromal symptoms of anorexia, nausea, vomiting, diarrhea, and weakness which is followed by dyspnea, jaundice and confusion. Lactic acidosis often accompanies the hepatic injury and may be the predominant clinical feature. Jaundice arises late and serum enzymes are unusually only mildly or moderated elevated, the pattern being mixed or actually cholestatic. Pancreatitis, myopathy and neuropathy may also occur. Lipodystrophy is frequently present. Liver histology during the early course of injury demonstrates marked microvesicular fat with little hepatocyte injury. Subsequently, cholestasis arises and the fatty change may evolve to a macrovesicular pattern. Late changes include ballooning cell degeneration, Mallory bodies and fibrosis. The hepatotoxicity associated with stavudine can be rapidly fatal, but is potentially reversable with intensive support and early withdrawal of therapy (Case 1). Monitoring of patients on stavudine demonstrates that asymptomatic elevations of serum lactate (hyperlactatemia) usually precedes the appearance of clinical symptoms and acidosis. Once lactic acidosis is present, however, the mortality rate is high (33% to 50%) (Case 2). Preexisting liver injury, female sex, older age, obesity, alcohol use and concurrent therapy with didanosine, ribavirin and tenofovir appear to increase the risk of this syndrome in patients taking stavudine.

These medications /didanosine or hydroxyurea/ in combination with stavudine may increase the risk of potentially fatal hepatotoxicity or pancreatitis.|Medications that cause neuropathy (e.g., ethambutol, isoniazid, phenytoin, vincristine) should be used cautiously in patients receiving stavudine. Regimens containing stavudine, didanosine, and/or hydroxyurea are associated with an increased risk for neuropathy. Zidovudine and stavudine should not be used concomitantly because zidovudine antagonizes the effect of stavudine.|In vitro studies detected an antagonistic antiviral effect between stavudine and zidovudine at a molar ratio of 20 to 1, respectively; concurrent use is not recommended until in vivo studies demonstrate that these medications are not antagonistic in their anti-HIV activity; zidovudine may competitively inhibit the intracellular phosphorylation of stavudine and so these two medications in combination are not recommended.|... If stavudine is used in conjunction with didanosine (with or without hydroxyurea), there is an increased risk of pancreatitis, peripheral neuropathy, and liver function abnormalities. In addition, fatal pancreatitis and hepatotoxicity may occur more frequently in patients treated with stavudine used in conjunction with didanosine and hydroxyurea. If stavudine is used concomitantly with didanosine, patients should be closely monitored.

Type B lactic acidosis is a rare and often fatal complication seen in patients receiving the nucleotide analogues zidovudine, stavudine, didanosine, and lamivudine. We describe a case of a 51-year-old human immunodeficiency virus (HIV)-positive woman receiving three nucleotide analogues. She presented with nausea, vomiting, abdominal pain, and hepatic steatosis. Signs of mitochondrial toxicity were demonstrated by diffuse myopathy and pancreatitis. Serum riboflavin levels documented a deficiency that was treated with 50 mg of riboflavin daily. Immediately after treatment, serum blood urea nitrogen level, lactic acid levels, and arterial blood pH all returned to normal values. Her signs of mitochondrial toxicity also improved after treatment with riboflavin. Successful reversal of the patient's type B lactic acidosis after riboflavin therapy suggested that riboflavin deficiency plays a direct role in the development of nucleotide analogue-induced lactic acidosis. It is impossible to predict which patients are predisposed to the development of this syndrome. For this reason, it may be important to screen and treat riboflavin deficiency in patients on nucleoside analogues.|Lactic acidosis and severe hepatomegaly with steatosis, including some fatalities, have been reported rarely in patients receiving stavudine and also have been reported in patients receiving other NRTIs. Female gender, obesity, and long-term therapy with NRTIs may be risk factors. Fatal lactic acidosis has been reported in pregnant women who received antiretroviral regimens that included both didanosine and stavudine. Stavudine should be used with caution in patients with known risk factors for liver disease; however, lactic acidosis and severe hepatomegaly with steatosis have been reported in patients with no known risk factors.|Stavudine may exacerbate hepatic dysfunction in patients with pre-existing liver disease or a history of alcohol abuse.|Patients with renal function impairment may be at increased risk of toxicity due to decreased clearance of stavudine; patients with a creatinine clearance of < 50 mL/min (0.83 mL/sec) may require a reduction in dose).

Negligible

Stavudine's production and use as an antiviral(1) and in the treatment of AIDS(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a log Kow of -0.72(2) and a regression-derived equation(3), indicates that stavudine is expected to have very high mobility in soil(SRC). Volatilization of stavudine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.3X10-15 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Stavudine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.5X10-12 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a log Kow of -0.72(2) and a regression-derived equation(3), indicates that stavudine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.3X10-15 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 0.17(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), stavudine, which has an estimated vapor pressure of 9.5X10-12 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase. Particulate-phase stavudine may be removed from the air by wet and dry deposition(SRC). Stavudine does not absorb light with wavelengths >290 nm(3) and is not expected to be susceptible to direct photolysis by sunlight(SRC).

Stavudine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Stavudine does not absorb light with wavelengths >290 nm(2) and is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 0.17 was calculated for stavudine(SRC), using a log Kow of -0.72(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low.

The Koc of stavudine is estimated as 10 (SRC), using a log Kow of -0.72(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that stavudine is expected to have very high mobility in soil.

The Henry's Law constant for stavudine is estimated as 2.3X10-15 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that stavudine is expected to be essentially nonvolatile from water surfaces(2). Stavudine's Henry's Law constant indicates that volatilization from moist soil surfaces will not occur(SRC). Stavudine is not expected to volatilize from dry soil surfaces(SRC) based upon a an estimated vapor pressure of 9.5X10-12 mm Hg(SRC), determined from a fragment constant method(3).

Although it is not known whether stavudine is distributed into human milk, the drug is distributed into milk in rats.

Occupational exposure to stavudine may occur through inhalation of dust and dermal contact with this compound at workplaces where stavudine is produced or used. Exposure to the stavudine among the general population may be limited to those administered the drug (an antiviral). (SRC)

Although it is not known whether stavudine is distributed into human milk, the drug is distributed into milk in rats.

For the treatment of human immunovirus (HIV) infections.|FDA Label|Hard capsulesZerit is indicated in combination with other antiretroviral medicinal products for the treatment of HIV-infected adult patients and paediatric patients (over the age of three months) only when other antiretrovirals can not be used. The duration of therapy with Zerit should be limited to the shortest time possible.Powder for oral solutionZerit is indicated in combination with other antiretroviral medicinal products for the treatment of HIV-infected adult patients and paediatric patients (from birth) only when other antiretrovirals can not be used. The duration of therapy with Zerit should be limited to the shortest time possible.

Stavudine is a first generation nucleoside analogue and reverse transcriptase inhibitor used in combination with other agents in the therapy of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Stavudine is an uncommon, but well established cause of clinically apparent acute and chronic liver injury.

Antiviral Agents

Stavudine in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection. Additionally, stavudine is indicated for the treatment of patients with HIV infection who have received prolonged previous treatment with zidovudine. /Included in US product labeling/

Lactic acidosis and severe hepatomegaly with steatosis, including some fatalities, have been reported rarely in patients receiving stavudine and also have been reported in patients receiving other NRTIs. Female gender, obesity, and long-term therapy with NRTIs may be risk factors. Fatal lactic acidosis has been reported in pregnant women who received antiretroviral regimens that included both didanosine and stavudine. Stavudine should be used with caution in patients with known risk factors for liver disease; however, lactic acidosis and severe hepatomegaly with steatosis have been reported in patients with no known risk factors. Generalized fatigue, digestive symptoms (nausea, vomiting, abdominal pain, sudden unexplained weight loss), respiratory symptoms (tachypnea, dyspnea), or neurologic symptoms (including motor weakness) might be indicative of lactic acidosis development, and patients should be advised to contact their clinician immediately if these symptoms occur. Stavudine therapy should be discontinued in any patient with clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations). Permanent discontinuance of stavudine therapy should be considered in patients with confirmed lactic acidosis. Because an increased risk of potentially fatal hepatotoxicity may occur in patients receiving stavudine in conjunction with didanosine and hydroxyurea, patients receiving such regimens should be closely monitored for signs of hepatotoxicity.|Lactic acidosis is a serious complication of antiretroviral therapy. Symptomatic hyperlactatemia is a milder form of this syndrome, but its incidence is unclear. In this prospective ongoing observational study of a large cohort of HIV-infected adults, hyperlactataemia was diagnosed in 64 patients. Incidences were 18.3/1000 person-years with antiretroviral therapy, and 35.8/1000 person-years for stavudine (d4T) regimens. Ten of the 64 patients developed lactic acidosis during the first 13 months of treatment (incidence 2.9/1000 treated person-years). In four of ten patients, symptoms were absent or mild. More patients on d4T first-line therapy developed lactic acidosis than patients previously treated with other drugs (p = 0.008). Despite the occurrence of one death, the subsequent outcome for the remaining patients was favourable after antiretroviral therapy was stopped and supportive treatment with vitamins and antioxidants initiated. The early diagnosis of cases was the result of great vigilance and, combined with routine measurements of the anion gap, might be the most crucial factor explaining the low mortality rate observed here.|Potentially severe peripheral neuropathy, manifested by numbness, tingling, or pain in the hands or feet, has been reported in about 52% of patients receiving stavudine alone and in 8-21% of patients receiving stavudine in conjunction with other antiretroviral agents (indinavir and either lamivudine or didanosine). Stavudine-associated peripheral neuropathy appears to be dose-related, and has been reported most frequently in patients with advanced HIV, patients with a history of peripheral neuropathy, or patients receiving other neurotoxic drugs, including didanosine. Symptoms of peripheral neuropathy generally resolve if stavudine therapy is promptly discontinued; however, symptoms may worsen temporarily in some patients following discontinuance of the drug. If such symptoms resolve completely, patients may tolerate resumption of stavudine therapy using a reduced dosage. If neuropathy recurs after stavudine therapy is reinitiated, consideration should be given to permanently discontinuing the drug.|Pancreatitis, which has been fatal in some cases, has occurred in patients receiving stavudine in conjunction with didanosine (with or without hydroxyurea) and has been reported in both treatment-naive and previously treated patients, regardless of degree of immunosuppression. In an early clinical study evaluating stavudine, pancreatitis was observed in less than 1% of adult patients receiving stavudine monotherapy. Patients receiving didanosine in conjunction with stavudine (with or without hydroxyurea) may be at increased risk of pancreatitis; there have been at least 2 fatalities related to pancreatitis in patients receiving didanosine concomitantly with stavudine, indinavir, and hydroxyurea. There also has been at least one death related to pancreatitis in a patient receiving didanosine in conjunction with stavudine and nelfinavir. Stavudine, didanosine, hydroxyurea, and any other agent toxic to the pancreas should be discontinued in any patient who develops suspected pancreatitis.|For more Drug Warnings (Complete) data for STAVUDINE (20 total), please visit the HSDB record page.

Phenotypic analysis of HIV isolates from stavudine-treated patients revealed, in 3 of 20 paired isolates, a 4- to 12-fold decrease in susceptibility to stavudine in vitro.|Five of 11 stavudine post-treatment isolates developed moderate resistance to zidovudine (9- to 176-fold) and 3 of those 11 isolates developed moderate resistance to didanosine (7- to 29-fold).

Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Stavudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.

Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. (See all compounds classified as Anti-HIV Agents.)|Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033) (See all compounds classified as Antimetabolites.)|Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. (See all compounds classified as Reverse Transcriptase Inhibitors.)

Following oral administration, stavudine is rapidly absorbed (bioavailability is 68-104%).|46 ± 21 L|Renal cl=272 mL/min [Healthy subjects receiving 80 mg PO]|Stavudine is rapidly absorbed following oral administration, and peak plasma concentrations of the drug are attained within 1 hour after the dose. Oral bioavailability of stavudine is reported to be about 86% in adults and 77% in pediatric patients 5 weeks to 15 years of age.|Data from single- and multiple-dose studies indicate that peak plasma concentrations and AUC of stavudine increase in proportion to dose over the dosage range 0.03 -4 mg/kg; there is no evidence that accumulation occurs following multiple doses.|Binding of stavudine to serum proteins is negligible over the concentration range of 0.01-11.4 ug/mL.|Distribution of stavudine into body tissues and fluids has not been fully characterized. The apparent volume of distribution of stavudine following a single oral dose averages 66 L in HIV-infected adults. Following a single IV dose in HIV-infected individuals, the volume of distribution is 58 L in adults and 0.73 L/kg in pediatric patients 5 weeks to 15 years of age.|For more Absorption, Distribution and Excretion (Complete) data for STAVUDINE (12 total), please visit the HSDB record page.

Phosphorylated intracellularly to stavudine triphosphate, the active substrate for HIV-reverse transcriptase.|The metabolic fate of stavudine has not been elucidated in humans. Intracellularly, in both virus-infected and uninfected cells, stavudine is converted to stavudine monophosphate by cellular thymidine kinase. The monophosphate is subsequently converted to stavudine diphosphate and then to stavudine triphosphate, presumably by the same cellular kinases involved in the metabolism of zidovudine. Intracellular (host cell) conversion of stavudine to the triphosphate derivative is necessary for the antiviral activity of the drug.

0.8-1.5 hours (in adults)|Intracellular half life of stavudine triphosphate: Approximately 3.5 hours. /Stavudine triphosphate/|Normal renal function: Adults: 0.8 to 1.5 hours (intravenous); 1.14 to 1.74 hours (oral). Children (5 weeks to 15 years): 0.83 to 1/39 hours (intravenous); 0.7 to 1.22 hours (oral). Neonates (14 to 28 days) 1.3 to 1.88 (oral). Neonates (day of birth): 3.26 to 7.28 (oral). Renal function impairment (creatinine clearance 26 to 50 mL/min): Approximately 1 to 6 hours. Renal function impairment (creatinine clearance 9 to 25 mL/min): Approximately 3.7 to 5.5 hours. Renal function impairment (creatinine clearance > 50 mL/min): Approximately 1.3 to 2.1 hours. Renal function impairment (hemodialysis patients): Approximately 4.0 to 6.8 hours.|Twenty-two patients were studied after the first oral dose of 0.67, 1.33, 2.67, or 4 mg/kg of body weight; 17 of them underwent an additional steady-state pharmacokinetic evaluation after thrice-daily dosing of the above doses. ... The mean values for plasma elimination half-life ranged from 1 to 1.6 hr.

Stavudine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.|Enzymatic conversion of stavudine to d4T-triphosphate appears to be complex, involving several steps and enzymes. Stavudine is first converted to dideoxydidehydrothymidine-5'-monophosphate (d4T-monophosphate) by thymidine kinase. Subsequently, d4T-monophosphate is converted to dideoxydidehydrothymidine-5'-diphosphate (d4T-diphosphate), and then to d4T-triphosphate, presumably by the same cellular kinases involved in the metabolism of zidovudine. ... d4T-Triphosphate is a structural analog of thymidine triphosphate, the natural substrate for viral RNA-directed DNA polymerase. ... d4T-triphosphate appears to compete with thymidine triphosphate for viral RNA-directed DNA polymerase and incorporation into viral DNA. Following incorporation of d4T-triphosphate into the viral DNA chain instead of thymidine triphosphate, synthesis is terminated prematurely because the absence of the 3'-hydroxy group on the drug prevents further 5' to 3' phosphodiester linkages.|Stavudine is phosphorylated by cellular kinases to the active metabolite stavudine triphosphate. Stavudine triphosphate inhibits the activity of HIV reverse transcriptase both by competing with the natural substrate deoxythymidine triphosphate (Ki =0.0083 to 0.032 uM), and by its incorporation into viral DNA causing a termination of DNA chain elongation because stavudine lacks the essential 3'-OH group. Stavudine triphosphate inhibits cellular DNA polymerase beta and gamma, and markedly reduces the synthesis of mitochondrial DNA.|d4T-Triphosphate can bind to and inhibit some mammalian cellular DNA polymerases, particularly beta- and gamma-polymerases, in vitro, and markedly reduce the synthesis of mitochondrial DNA. ...gamma-polymerase, an enzyme involved in mitochondrial DNA synthesis, is the polymerase most susceptible to inhibition. However, d4T-triphosphate and other dideoxynucleoside triphosphates appear to have much greater affinity for viral RNA-directed DNA polymerase than for mammalian DNA polymerases. ... Inhibition of beta- and gamma-polymerases by these drugs may account, to some extent, for the toxic effects associated with stavudine and other nucleosides in humans.

SYMPTOMS: This compound may cause irritation. ACUTE/CHRONIC HAZARDS: When heated to decomposition this compound emits toxic fumes of carbon monoxide, carbon dioxide and nitrogen oxides. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Stavudine can be removed by hemodialysis; the mean +/- SD hemodialysis clearance of stavudine is 120 +/- 18 mL/min. ... the mean +/- SD percentage of the stavudine dose recovered in the dialysate, timed to occur between 2-6 hours post-dose, was 31 +/- 5%. ...Whether stavudine is eliminated by peritoneal dialysis has not been studied.|Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/SIGNS AND SYMPTOMS/ ... Complications of chronic overdosage include peripheral neuropathy and hepatic toxicity.|/SIGNS AND SYMPTOMS/ Lactic acidosis and severe hepatomegaly with steatosis, including some fatalities, have been reported in patients receiving stavudine and also have been reported in patients receiving other nucleoside reverse transcriptase inhibitors (NRTIs). Although relative rates of lactic acidosis have not been assessed in prospective well-controlled studies, longitudinal cohort and retrospective studies suggest that this adverse effect may occur more often with antiretroviral regimens that include stavudine. Female gender, obesity, and long-term therapy with NRTIs also may be risk factors. Fatal lactic acidosis has been reported in pregnant women who received antiretroviral regimens that included both stavudine and didanosine. In addition, deaths attributed to hepatotoxicity have occurred in patients who received antiretroviral regimens that included stavudine, didanosine, and hydroxyurea.|/SIGNS AND SYMPTOMS/ Rapidly ascending neuromuscular weakness, which has been fatal in some cases, has been reported rarely in patients receiving stavudine in conjunction with other antiretroviral agents. Most reported cases of motor weakness occurred in the setting of lactic acidosis or symptomatic elevations of serum lactate concentrations. The evolution of motor weakness may mimic the clinical presentation of Guillain-Barre syndrome (including respiratory failure), and symptoms may continue or worsen following discontinuance of antiretroviral therapy.|/CASE REPORTS/ Pancreatitis, which has been fatal in some cases, has occurred in patients receiving stavudine in conjunction with didanosine (with or without hydroxyurea) and has been reported in both treatment-naive and previously treated patients, regardless of degree of immunosuppression. In an early clinical study evaluating stavudine, pancreatitis was observed in less than 1% of adult patients receiving stavudine monotherapy. Patients receiving didanosine in conjunction with stavudine (with or without hydroxyurea) may be at increased risk of pancreatitis; there have been at least 2 fatalities related to pancreatitis in patients receiving didanosine concomitantly with stavudine, indinavir, and hydroxyurea. There also has been at least one death related to pancreatitis in a patient receiving didanosine in conjunction with stavudine and nelfinavir.|For more Human Toxicity Excerpts (Complete) data for STAVUDINE (8 total), please visit the HSDB record page.

2',3' Didehydro 3' deoxythymidine

Zerit|Oral: Capsules: 15 mg Zerit (with parabens), (Bristol-Myers Squibb), 20 mg Zerit (with parabens), (Bristol-Myers Squibb) 30 mg Zerit (with parabens), (Bristol-Myers Squibb) 40 mg Zerit (with parabens), (Bristol-Myers Squibb); For solution: 1 mg/mL Zerit (with parabens), (Bristol-Myers Squibb).

While data specific to stavudine were not available(SRC, 2005), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils into aquifers(1).

Human drugs -> Zerit -> EMA Drug Category|Antivirals for systemic use -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients