Professional Drug Information > d4T

Stavudine (Systemic)

VA CLASSIFICATION
Primary: AM890

Commonly used brand name(s): Zerit.

Another commonly used name is
d4T.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antiviral (systemic)—

Indications

Accepted

Human immunodeficiency virus (HIV) infection (treatment)—Stavudine in combination with other antiretroviral agents is indicated for the treatment of HIV–1 infection. ^{14} Additionally, stavudine is indicated for the treatment of patients with HIV infection who have received prolonged previous treatment with zidovudine. ^{{01} {13}{15}}
—The duration of clinical benefit from antiretroviral therapy may be limited. If disease progression occurs during stavudine treatment, an alternative antiretroviral therapy is recommended. ^{01}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    224.22 ^{11}

Mechanism of action/Effect:

Stavudine, a nucleoside analog of thymidine, is rapidly phosphorylated by cellular enzymes to its active moiety, stavudine triphosphate. Stavudine triphosphate inhibits human immunodeficiency virus (HIV) replication by competing with the natural substrate, deoxythymidine triphosphate, and by inhibiting viral DNA synthesis by acting as a terminator of chain elongation. In addition, stavudine triphosphate inhibits cellular DNA polymerases beta and gamma, and markedly reduces the synthesis of mitochondrial DNA. ^{01}

A concentration of stavudine ranging from 0.009 to 4 micromolesis required to inhibit HIV replication by 50% in vitro ^{04}{17}. The in vitro potency of stavudine against HIV is similar to that of zidovudine ^{05}.

Absorption:

Stavudine is rapidly absorbed with an oral bioavailability of 68.2 to 104.6% in adults, and 44.2 to 108.6% in children (ages 5 weeks to 15 years)^{{01} {05}{17}}.

Peak plasma concentrations (C _max) and area under the plasma concentration-time curve (AUC) increased in proportion to dose.^{17}

Stavudine may be taken with food or on an empty stomach. Administration with food results in a decrease in C _max of approximately 45%; however, the systemic availability, as measured by the AUC, remains unchanged. ^{01}

Distribution:

Crosses the blood-brain barrier and distributes into the cerebrospinal fluid (CSF) ^{{01} {02}}; the mean CSF to plasma concentration ratio was ^{01}59% (range, 24 to 94%) when measured in 8 children ^{17} Binding of stavudine to serum proteins was negligible over the concentration range of 0.01 to 11.4 micrograms/mL. Also, stavudine distributes equally between red blood cells and plasma ^{01}{17}.


Vol _D:

Adults: 0.8 to 1.1 L per kg (L/kg) ^{05}

Children: Approximately 0.73 L/kg (following 1 hour IV infusion) ^{{01} {17}}.


Protein binding:

Negligible ^{01}.

Biotransformation:

Phosphorylated intracellularly to stavudine triphosphate, the active substrate for HIV-reverse transcriptase ^{01}.

Half-life:


Normal renal function:

Adults: 0.8 to 1.5 hours (intravenous); 1.14 to 1.74 hours (oral)^{{01} {04} {05}{17}}.

Children (5 weeks to 15 years): 0.83 to 1.39 hours (intravenous); 0.7 to 1.22 hours (oral) ^{01}{17}.

Neonates (14 to 28 days): 1.3 to 1.88 hours (oral) ^{17}.

Neonates (day of birth): 3.26 to 7.28 hours (oral) ^{17}.



Renal function impairment (creatinine clearance >50 mL/min):

Approximately 1.3 to 2.1 hours ^{17}



Renal function impairment (creatinine clearance 26 to 50 mL/min):

Approximately 1 to 6 hours ^{17}



Renal function impairment (creatinine clearance 9 to 25 mL/min):

Approximately 3.7 to 5.5 hours ^{01}{17}.



Renal function impairment (hemodialysis patients):

Approximately 4.0 to 6.8 hours^{17}



Intracellular half-life of stavudine triphosphate:

Approximately 3.5 hours ^{01}.


Time to peak concentration:

0.5 to 1.5 hour ^{{01} {04}}.

Peak serum concentration:

Approximately 1.4 micrograms/mL (6.2 micromoles/L) after a single oral dose of 70 mg ^{01}.

Elimination:
Adults



• Renal—16 to 62% recovered in urine ^{17}


• Total body clearance—6.0 to 10.6 mL/min/kg (following 1 hour IV infusion) ^{17}


• Apparent oral clearance—5.4 to 10.6 mL/min/kg (following single oral dose) ^{17}
Children (ages 5 weeks to 15 years)



• Renal—18 to 50% recovered in urine ^{17}


• Total body clearance—5.99 to 13.51 mL/min/kg (following single oral dose) ^{17}


• Apparent oral clearance—9.46 to 18.04 mL/min/kg (following single oral dose) ^{17}
Neonates (ages 14 to 28 days)



• Apparent oral clearance—5.59 to 17.45 mL/min/kg (following single oral dose) ^{17}
Neonates (day of birth)



• Apparent oral clearance—2.28 to 7.88 mL/min/kg (following single oral dose)^{17}
Those with renal impairment



• Creatinine clearance >50 mL/min   • Apparent oral clearance—278 to 392 mL/min ^{17}
   • Renal clearance—102 to 232 mL/min ^{17}



• Creatinine clearance 26 to 50 mL/min   • Apparent oral clearance—152 to 230 mL/min ^{17}
   • Renal clearance—55 to 91 mL/min ^{17}



• Creatinine clearance 9 to 25 mL/min   • Apparent oral clearance—91 to 141 mL/min ^{17}
   • Renal clearance—14 to 20 mL/min ^{17}



• Creatinine clearance for hemodialysis patients (determined while patients were off dialysis)   • Apparent oral clearance—88 to 122 mL/min ^{17}

    Approximately 50% of an administered dose undergoes nonrenal elimination ^{03}. Although the exact metabolic fate is unknown, stavudine may be cleaved to thymine, and the subsequent degradation and/or utilization of thymine may account for the unrecovered stavudine ^{03}.
    In dialysis—   • Hemodialysis clearance of stavudine was 120 ± 18 mL per minute (mean ± standard deviation) in a study of 12 patients. ^{17}
   • Stavudine dose recovered in the dialysate, timed to occur between 2 to 6 hours post-dose, was 31 ± 5 % (mean ± standard deviation). ^{17}
   • It is not know whether stavudine is removed by peritoneal dialysis. ^{17}



Precautions to Consider

Carcinogenicity

From 2-year studies in mice and rats, stavudine was not carcinogenic at doses equivalent to 39 and 168 times the recommended human clinical exposures (AUC), respectively.^{14}

Mutagenicity

No evidence of mutagenicity was found in the Ames test, Escherichia coli reverse mutation assay, or the CHO/HGPRT mammalian cell forward gene mutation assay, with and without metabolic activation. Positive results were produced 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 produced an increased frequency of chromosome aberrations in human lymphocytes at concentrations of 25 to 250 micrograms per mL (mcg/mL), without metabolic activation, and increased the frequency of transformed foci in mouse fibroblast cells at 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 of mice following administration of oral doses of 600 to 2000 mg per kg of body weight (mg/kg) per day for 3 days. ^{01}

Pregnancy/Reproduction
Fertility—
No evidence of impaired fertility was seen in rats given stavudine at doses that resulted in peak serum concentrations that were up to 216 times those observed in humans who received a clinical dosage of 1 mg/kg per day. ^{01}

Pregnancy—
An Antiretroviral Pregnancy Registry has been established to monitor the outcomes of pregnant women exposed to stavudine. Physicians are encouraged by the manufacturer to register patients by calling (800) 258-4263.^{17}

Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. It is unclear if pregnancy augments the risk of lactic acidosis/hepatic steatosis syndrome reported in non-pregnant individuals receiving nucleoside analogues. The combination of didanosine and stavudine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk. ^{14}

Adequate and well-controlled studies have not been done in humans.^{01} It is not known whether stavudine crosses the placenta in humans.^{06} Also, it is not known whether stavudine reduces perinatal transmission of HIV infection, as does zidovudine.^{06} Stavudine should be used during pregnancy only if clearly needed.^{01}

Stavudine crosses the placenta in rats. Reproduction studies done in rats and rabbits exposed to levels of stavudine up to 399 and 183 times, respectively, those seen at a clinical dosage in humans of 1 mg/kg per day, based on peak serum concentrations, revealed no evidence of teratogenicity. The incidence of common skeletal variation, unossified or incomplete ossification of sternebra, in fetuses was increased in rats at 399 times the human exposure, but not at 216 times the human exposure. A slight postimplantation loss was seen at 216 times the human exposure, but no effect was seen at approximately 135 times the human exposure. An increase in rat neonatal mortality occurred at 399 times the human exposure, while survival was unaffected at approximately 135 times the human exposure. The concentration of stavudine in rat fetal tissue was approximately one-half the concentration of that in maternal plasma. ^{01}

FDA Pregnancy Category C.^{01}

Breast-feeding

It is not known whether stavudine is distributed into human breast milk. However, it has been found to pass readily into the milk of lactating rats. ^{01} Mothers should not breast-feed if they are taking stavudine.^{14}

There have been case reports of HIV being transmitted from an infected mother to her nursing infant through breast milk.^{{07} {08} {09}} Therefore, breast-feeding is not recommended in HIV-infected mothers, to avoid potential postnatal transmission of HIV to the nursing infant.^{01}

Pediatrics

Various pharmacokinetic studies have been done in children between birth and 15 years of age. The pharmacokinetic and side effect profiles of stavudine in children and neonates were similar to those in adults.^{01}{17}


Geriatrics


Although appropriate studies on the relationship of age to the effects of stavudine have not been performed in the geriatric population, geriatrics-specific problems are not expected to limit the usefulness of stavudine in the elderly. However, elderly patients are more likely to have age-related renal function impairment which may require the monitoring of renal function and a possible reduction in dose. ^{{01} {17}}

Elderly patients should be closely monitored for signs and symptoms of peripheral neuropathy due to higher than expected incidence of peripheral neuropathy or peripheral neuropathic symptoms in elderly patients in the monotherapy Expanded Access Program for patients with advanced HIV infection. ^{17}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Medications that may cause peripheral neuropathy, such as:
» Chloramphenicol or
» Cisplatin or
» Dapsone or
» Didanosine or
» Ethambutol or
» Ethionamide or
» Hydralazine or
» Isoniazid or
» Lithium or
» Metronidazole or
» Nitrofurantoin or
» Phenytoin or
» Vincristine or
» Zalcitabine    (since stavudine has been shown to cause peripheral neuropathy, other medications associated with the development of neuropathy should be avoided during stavudine therapy or, if concurrent use is necessary, used with caution ^{01})


» Didanosine or
» Hydroxyurea    (these medications in combination with stavudine may increase the risk of potentially fatal hepatotoxicity or pancreatitis ^{14})


» Zidovudine    (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 ^{{01} {12}}; zidovudine may competitively inhibit the intracellular phosphorylation of stavudine and so these two medications in combination are not recommended ^{14})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
» Alanine aminotransferase (ALT [SGPT]) and
Alkaline phosphatase and
» Aspartate aminotransferase (AST [SGOT])
Gamma-glutamyl transferase (GGT)    (serum values have increased to greater than 5 times the upper normal limit, but returned to baseline when therapy was discontinued ^{01}{14})


Amylase
Bilirubin
Mean corpuscular volume (MCV)    (may be increased ^{04}{14})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Alcoholism, active or a history of, or
Hepatic function impairment    (stavudine may exacerbate hepatic dysfunction in patients with pre-existing liver disease or a history of alcohol abuse ^{01})


» Peripheral neuropathy    (stavudine may cause peripheral neuropathy; if symptoms of peripheral neuropathy develop, stavudine therapy should be interrupted; if symptoms resolve completely, reinstatement of therapy at a lower dose may be considered ^{01})


» Renal function impairment    (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 ^{01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Alanine aminotransferase (ALT [SGPT]) and
Alkaline phosphatase and
» Aspartate aminotransferase (AST [SGOT])    (serum values may be increased to greater than 5 times the upper normal limit ^{01})


Amylase, serum and
Lipase, serum    (values may be increased ^{01})




Side/Adverse Effects

Note: 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 antiretroviral agents. Symptoms may include generalized fatigue, nausea, vomiting, abdominal pain, and sudden unexplained weight loss, tachypnea, dyspnea, or motor weakness. Patients should be informed of the importance of early recognition of symptoms of lactic acidosis.^{17}Fatal lactic acidosis has been reported in pregnant women who received the combination of didanosine and stavudine with other antiretroviral agents. The combination of didanosine and stavudine should be used with caution during pregnancy and is recommended only if the potential benefit clearly outweighs the potential risk. ^{14}{16}


Note: Fatal and nonfatal pancreatitis have occurred during therapy when stavudine was part of a combination regimen that included didanosine, with or without hydroxyurea, regardless of the degree of immunosuppression. ^{17}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent ^{{01} {04}}
    
Peripheral neuropathy ( tingling, burning, numbness, or pain in the hands or feet)

Note: Stavudine has been associated with peripheral sensory neuropathy which is dose related and can be severe. It occurs more frequently in patients being treated with neurotoxic drug therapy, including didanosine, in patients with advanced HIV infection, or in patients who have previously experienced peripheral neuropathy ^{17} Peripheral sensory neuropathy may also be seen with severe HIV disease. Therefore, differentiation between this side effect of stavudine and the complications of HIV disease may be difficult.^{10} Peripheral neuropathy occurred in 19 to 24% of adult patients with advanced HIV infection who were treated with stavudine, compared with 13% of adult patients with less advanced HIV infection who were treated with stavudine. It may resolve if stavudine therapy is stopped promptly. Symptoms may become worse temporarily after discontinuation of therapy. If symptoms resolve completely, resumption of treatment at a lower dose may be considered. ^{01}


Incidence less frequent ^{01}
    
Arthralgia (joint pain)
    
hypersensitivity or allergic reaction ^{17} ( cough; difficulty swallowing; dizziness; fast heartbeat; hives; itching; puffiness or swelling of the eyelids or around the eyes, face, lips or tongue; shortness of breath; skin rash; tightness in chest; unusual tiredness or weakness; wheezing )
    
myalgia (muscle pain)

Incidence rare ^{{01} {04}}
    
Anemia (unusual tiredness or weakness)^{04}
    
pancreatitis ( nausea, vomiting, severe abdominal pain)

Note: Pancreatitis was reported in 1% of patients enrolled in clinical trials. ^{01}


Incidence not determined
—Observed during clinical practice, estimates of frequency can not be determined ^{17}    
Hepatic steatosis (dark urine; light-colored stools; nausea and vomiting; upper right abdominal pain; yellow eyes and skin)
    
hepatitis (dark urine; general tiredness and weakness; light-colored stools; nausea and vomiting; upper right abdominal pain; yellow eyes and skin)
    
lactic acidosis (abdominal pain; dyspnea; generalized fatigue; motor weakness; nausea; sudden unexplained weight loss; tachypnea; vomiting ^{17})
    
leukopenia (black, tarry stools; chest pain; chills; cough; fever; painful or difficult urination; shortness of breath; sore throat; sores, ulcers, or white spots on lips or in mouth; swollen glands; unusual bleeding or bruising; unusual tiredness or weakness)
    
liver failure (headache; stomach pain; continuing vomiting; dark-colored urine; general feeling of tiredness or weakness; light-colored stools; yellow eyes or skin)
    
severe motor weakness (shakiness and unsteady walk; unsteadiness. trembling, or other problems with muscle control or coordination)
    
thrombocytopenia (black, tarry stools; bleeding gums; blood in urine or stools; pinpoint red spots on skin; unusual bleeding or bruising)
^{17}
Note: In rare cases, severe motor weakness has been reported in patients receiving combination antiretroviral therapy including stavudine. Although most cases occurred in the setting of lactic acidosis, it may mimic the clinical presentation of Guillain-Barre syndrome including respiratory failure and symptoms may continue or worsen following discontinuation of therapy. ^{17}




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent ^{01}
    
Anorexia ^{15}(loss of appetite; weight loss)
    
chills and fever
    
rash ^{15}

Incidence less frequent ^{01}
    
Asthenia (lack of strength or energy; weakness)
    
gastrointestinal disturbances (abdominal pain; diarrhea; loss of appetite; nausea or vomiting)
    
headache
    
insomnia (difficulty in sleeping )

Incidence not determined
—Observed during clinical practice, estimates of frequency can not be determined    
Fat redistribution (breast enlargement; buffalo hump; central obesity; facial wasting; peripheral wasting)^{17}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute
Adults treated with 12 to 24 times the recommended daily dose of stavudine showed no acute toxicity ^{01}.

Chronic
    
Hepatotoxicity ^{01}( dark or amber urine; loss of appetite ; pale stools; stomach pain; unusual tiredness or weakness ; yellow eyes or skin)
    
peripheral neuropathy ^{01}(tingling, burning, numbness, or pain in the hands or feet)


Treatment of overdose


To enhance elimination :
Stavudine can be removed by hemodialysis; the mean hemodialysis clearance of stavudine is 120 mL/min (±18 mL/min SD). Peritoneal dialysis has not been studied for stavudine. ^{14}



Supportive care:
Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Stavudine (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:

Pregnancy—Stavudine should be used during pregnancy only if the potential benefit clearly outweighs the potential risk. In addition, fatal lactic acidosis has been reported in pregnant women who received the combination of stavudine and didanosine with other antiretroviral agents.





Breast-feeding—Breast-feeding is not recommended, because of potential postnatal transmission of HIV to the nursing infant and because of the potential for serious adverse reactions in nursing infants.





Use in children—The pharmacokinetic and side effect profiles of stavudine in children and neonates were similar to those in adults.






Use in the elderly—Elderly patients should be closely monitored for signs and symptoms of peripheral neuropathy.
Other medications, especially didanosine, hydroxyurea, zidovudine or those associated with hepatotoxicity, pancreatitis, and peripheral neuropathy
Other medical problems, especially alcoholism, hepatic function impairment, pancreatitis (or history of pancreatitis), peripheral neuropathy, and renal function impairment

Proper use of this medication
» Importance of not taking more medication than prescribed; importance of not discontinuing medication without checking with physician

» Compliance with full course of therapy

» Importance of not missing doses and of taking at evenly spaced times

Not sharing medication with others

» Proper dosing
Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
» Regular visits to physician for blood tests

» Importance of not taking other medications concurrently without checking with physician

» Taking steps to avoid spreading HIV infection


Side/adverse effects
Signs of potential side effects, especially peripheral neuropathy, arthralgia, hypersensitivity or allergic reaction, myalgia, anemia, pancreatitis, hepatic steatosis, hepatitis, lactic acidosis, liver failure, severe motor weakness, and thrombocytopenia.


General Dosing Information
Patients with symptoms of peripheral neuropathy or clinically significant elevations in serum concentrations of hepatic transaminases should discontinue taking stavudine. If symptoms or serum enzyme elevations resolve completely, stavudine may be reintroduced at 50% of the regular dose. ^{01}However, if peripheral neuropathy recurs after resuming stavudine treatment, permanent discontinuation should be considered. ^{17}

Stavudine may be taken on a full or empty stomach. ^{01}

Since urinary excretion is a major route of elimination for stavudine in pediatric patients, the clearance of stavudine may be altered in children with renal impairment. Although insufficient data exists to recommend a dose adjustment for pediatric patients, a reduction in the dose and/or an increase in the interval between doses should be considered. ^{14}


Oral Dosage Forms

STAVUDINE CAPSULES

Usual adult and adolescent dose
Human immunodeficiency virus (HIV) infection
Adults and adolescents 60 kg of body weight or greater: Oral, 40 mg every twelve hours. ^{{01} {13}}

Adults and adolescents less than 60 kg of body weight: Oral, 30 mg every twelve hours. ^{{01} {13}}


Note: Patients with renal function impairment may require a reduction in dose as follows: ^{{01} {13}}

	Recommended dose based on patient's body weight
Creatinine clearance (mL/min)/(mL/sec)	³ 60 kg	< 60 kg
> 50/0.83	See Usual adult and adolescent dose	See Usual adult and adolescent dose
26-50/0.43-0.83	20 mg every 12 hours	15 mg every 12 hours
10-25/0.17-0.42	20 mg every 24 hours	15 mg every 24 hours

Data are insufficient to recommend a dose for patients with creatinine clearance < 10 mL per minute (0.17 mL per second). ^{01}
Recommended dose for hemodialysis patients is 20 mg every 24 hours (patients weighing 60 kg or more) or 15 mg every 24 hours (patients weighing less than 60 kg), administered after hemodialysis completion and at the same time of day on non-dialysis days. ^{14}


Usual pediatric dose
This dosage form is usually not used for children. See Stavudine for Oral Solution.

Strength(s) usually available
U.S.—


15 mg (Rx) [Zerit (lactose)]^{01}{14}


20 mg (Rx) [Zerit (lactose)]^{01}{14}


30 mg (Rx) [Zerit (lactose)]^{01}{14}


40 mg (Rx) [Zerit (lactose)]^{01}{14}

Canada—


15 mg (Rx) [Zerit (lactose)]^{13}


20 mg (Rx) [Zerit (lactose)]^{13}


30 mg (Rx) [Zerit (lactose)]^{13}


40 mg (Rx) [Zerit (lactose)]^{13}

Packaging and storage:
Store at controlled room temperature, preferably between 15 and 30 °C (59 and 86 °F), in a tight container. ^{01}

Auxiliary labeling:
   • Continue medicine for full time of treatment.


STAVUDINE FOR ORAL SOLUTION

Usual adult and adolescent dose
See Stavudine Capsules .

Usual pediatric dose
Human immunodeficiency virus (HIV) infection
Infants and children 30 kg of body weight or greater: Oral, 30 mg every twelve hours. ^{01}

Infants and children at least 14 days and less than 30 kg of body weight: Oral, 1 mg per kg of body weight every twelve hours. ^{01}{17}

Infants from birth to 13 days: Oral, 0.5 mg per kg of body weight every 12 hours. ^{17}


Strength(s) usually available
U.S.—


1 mg per mL (when reconstituted according to manufacturer's instructions) (available in 200-mL bottles) (Rx) [Zerit (antifoaming and flavoring agents) (methylparaben) ( propylparaben) (sucrose)]^{01}

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store at controlled room temperature, preferably between 15 and 30 °C (59 and 86 °F), in a tight container. Protect from excessive moisture. ^{01}

After reconstitution, store in a refrigerator (2 to 8 °C [36 to 46 °F]). ^{01}

Preparation of dosage form:
To prepare stavudine for oral solution, add 202 mL of purified water to each bottle and shake vigorously to dissolve. This will provide 200 mL of dispensable solution. The solution may appear slightly hazy. ^{01}

Stability:
Reconstituted solutions are stable for up to 30 days when refrigerated. ^{01}

Auxiliary labeling:
   • Shake prior to use.
   • Continue medicine for full time of treatment.

Additional information:
When dispensing, use original container with measuring cup provided.

Developed: 11/28/1994
Revised: 12/26/2002

References

1. Zerit package insert (Bristol-Myers Squibb—US), Rev 6/94, Rec 7/94; Rev 10/96, Rec 3/98.
   

2. Pizzo PA, Wilfert C. Antiretroviral therapy for infection due to human immunodeficiency virus in children. Clin Infect Dis 1994; 19: 177-96.
   

3. Cretton EM, Zhou Z, Kidd LB, et al. In vitro and in vivo disposition and metabolism of 3´-deoxy-2´,3´-didehydrothymidine. Antimicrob Agents Chemother 1993; 37(9): 1816-25.
   

4. Browne MJ, Mayer KH, Chafee SBD, et al. 2´,3´-didehydro-3´-deoxythymidine (d4T) in patients with AIDS or AIDS-related complex: a phase I trial. J Infect Dis 1993; 167: 21-9.
   

5. Dudley MN, Graham KK, Kaul S, et al. Pharmacokinetics of stavudine in patients with AIDS or AIDS-related complex. J Infect Dis 1992; 166: 480-5.
   

6. Cotton P. Trial halted after drug cuts maternal HIV transmission rate by two thirds. JAMA 1994; 271(11): 807.
   

7. Bradbeer CS. Mothers with HIV. Br Med J 1989; 299: 806-7.
   

8. Hira SK, Mangrola UG, Mwale C, et al. Apparent vertical transmission of human immunodeficiency virus type 1 by breast-feeding in Zambia. J Pediatr 1990; 117(3): 421-4.
   

9. Van de Perre P, Simonon A, Msellati P, et al. Postnatal transmission of human immunodeficiency virus type 1 from mother to infant. N Engl J Med 1991; 325(9): 593-8.
   

10. Yarchoan R, Thomas RV, Allain J-P, et al. Phase I studies of 2,3-dideoxycytidine in severe human immunodeficiency virus infection as a single agent and alternating with zidovudine. Lancet 1988; 1: 76-81.
    

11. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 685.
    

12. Panel comment, 8/94.
    

13. Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 32nd ed. Ottawa, Canada: Canadian Pharmaceutical Association; 1997. p. 1788-90.
    

14. Product Information: Zerit®, stavudine. Bristol-Myers Squibb Company, Princeton, NJ, (PI issued 12/2000) reviewed 01/2001.
    

15. Product Information: Zerit®, stavudine. Bristol-Myers Squibb Canada, Montreal, Canada, (PI issued 01/1998) reviewed 01/2001.
    

16. FDA Talk Paper: FDA/Bristol Myers Squibb Issues Caution for HIV Combination Therapy with Zerit and Videx in Pregnant Women. United States Food and Drug Administration, U.S. Department of Health and Human Services, Rockville, MD, 01/2001.
    

17. Product Information: Zerit®, stavudine. Bristol-Myers Squibb Company, Princeton, NJ, (PI issued 03/2002) reviewed 06/2002.
    

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