Meningitis: What It Is and How to Avoid It Watch Video

Zerit

Generic Name: Stavudine
Class: Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
VA Class: AM800
Chemical Name: 2′,3′-Didehydro-3′-deoxythymidine
CAS Number: 3056-17-5

Warning(s)

  • Lactic acidosis and severe hepatomegaly with steatosis (including some fatalities) reported in patients receiving nucleoside reverse transcriptase inhibitors (NRTIs) alone or in conjunction with other antiretrovirals.1 (See Lactic Acidosis and Severe Hepatomegaly with Steatosis under Cautions.)

  • Fatal lactic acidosis reported in pregnant women who received stavudine and didanosine with other antiretrovirals.1 Use stavudine in conjunction with didanosine with caution in pregnant women and only if potential benefits outweigh risks.1 (See Pregnancy under Cautions.)

  • Fatal and nonfatal pancreatitis reported when stavudine used in an antiretroviral regimen that included didanosine in both antiretroviral-naive and antiretroviral-experienced patients, regardless of degree of immunosuppression.1 (See Pancreatitis under Cautions.)

REMS:

FDA approved a REMS for stavudine to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antiretroviral; nucleoside reverse transcriptase inhibitor (NRTI).1 2 4 6 7 11 12 20 21 23 24 200

Uses for Zerit

Treatment of HIV Infection

Treatment of HIV-1 infection in conjunction with other antiretrovirals.1

Not included in preferred, alternative, or acceptable antiretroviral regimens recommended for initial treatment in HIV-infected adults and adolescents.200

Dual NRTI option of stavudine and lamivudine not recommended for initial antiretroviral regimens in adults or adolescents because of toxicity (e.g., lactic acidosis, peripheral neuropathy, pancreatitis).200 Use dual NRTI option of stavudine and either lamivudine or emtricitabine in initial antiretroviral regimens in pediatric patients only in special circumstances.201

Slideshow: Flashback: FDA Drug Approvals 2013

Dual NRTI option of stavudine and didanosine not recommended at any time because of high incidence of toxicity (e.g., lactic acidosis, peripheral neuropathy, pancreatitis).200 202 (See Pregnancy under Cautions.)

Dual NRTI option of stavudine and zidovudine not recommended at any time because of antagonistic antiretroviral effects.200 201 202

Postexposure Prophylaxis of HIV

Postexposure prophylaxis of HIV infection in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.199 Used in conjunction with other antiretrovirals.199

Postexposure prophylaxis of HIV infection in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.198 Used in conjunction with other antiretrovirals.198

Zerit Dosage and Administration

Administration

Oral Administration

Administer orally without regard to meals.1

Reconstitution

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

Agitate solution well prior to administration of each dose.1

Dosage

Pediatric Patients

Treatment of HIV Infection
Oral

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

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

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

≥60 kg: 40 mg every 12 hours.1

Adults

Treatment of HIV
Oral

<60 kg: 30 mg every 12 hours.1

≥60 kg: 40 mg every 12 hours.1

Postexposure Prophylaxis of HIV
Occupational Exposure
Oral

<60 kg: 30 mg twice daily.199

≥60 kg: 40 mg twice daily; if toxicity develops, use 20–30 mg twice daily.199

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.199

Nonoccupational Exposure
Oral

<60 kg: 30 mg twice daily.198

≥60 kg: 40 mg twice daily.198

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.198

Special Populations

Renal Impairment

Treatment of HIV Infection

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

Dosage adjustments recommended in adults with renal impairment, including those undergoing hemodialysis.1

Table 1. Stavudine Dosage in Adults with Renal Impairment1

Clcr (mL/minute)

Weight <60 kg

Weight ≥60 kg

26–50

15 mg every 12 hours

20 mg every 12 hours

10–25

15 mg every 24 hours

20 mg every 24 hours

Hemodialysis patients

15 mg every 24 hours given after completion of dialysis on dialysis days and at same time of day on nondialysis days

20 mg every 24 hours given after completion of dialysis on dialysis days and at same time of day on nondialysis days

Cautions for Zerit

Contraindications

  • Known hypersensitivity to stavudine or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving NRTIs (including stavudine) alone or in conjunction with other antiretrovirals.1 Reported most frequently in women; obesity and long-term NRTI therapy also may be risk factors.1 Has been reported in patients with no known risk factors.1

Fatalities reported in pregnant women receiving stavudine in conjunction with didanosine.1 (See Pregnancy under Cautions.)

Use particular caution in patients with known risk factors for liver disease.1

Interrupt stavudine therapy if there are clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of markedly increased serum aminotransferase concentrations).1

Consider permanently discontinuing stavudine in patients with confirmed lactic acidosis.1

Hepatotoxicity

Increased risk of liver function abnormalities, including severe and potentially fatal hepatic adverse events, in patients with preexisting liver dysfunction (e.g., chronic active hepatitis).1 Monitor such patients.1

Fatal hepatotoxicity and hepatic failure reported during postmarketing experience in HIV-infected individuals receiving stavudine, didanosine, and hydroxyurea concomitantly.1 (See Specific Drugs under Interactions.)

Pancreatitis

Fatal and nonfatal pancreatitis reported in patients receiving stavudine in conjunction with didanosine in both treatment-naive and previously-treated patients, regardless of degree of immunosuppression.1

If pancreatitis is suspected, interrupt therapy with stavudine, didanosine, and any other agent toxic to the pancreas.1 Reinitiate stavudine following a confirmed diagnosis of pancreatitis only if using particular caution and close patient monitoring;1 avoid concomitant use of didanosine.1

REMS

In 2010, the FDA required and approved a REMS for stavudine; that required that a medication guide be provided to the patient each time the drug was dispensed and required the manufacturer to periodically submit REMS assessments to FDA.81 In May 2011, FDA rescinded the REMS requirement for stavudine; however, the medication guide remains part of stavudine approved product labeling.82

Other Warnings and Precautions

Peripheral Neuropathy

Peripheral neuropathy, manifested by numbness, tingling, or pain in the hands or feet, reported.1 May be severe and dose related; occurs more frequently in patients with advanced HIV, history of peripheral neuropathy, or in those receiving other drugs associated with neuropathy (e.g., didanosine).1

Monitor for development of peripheral neuropathy.1 Consider permanently discontinuing stavudine if peripheral neuropathy occurs.1 Symptoms may resolve if the drug discontinued promptly, but may worsen temporarily in some patients following discontinuance.1

Other Nervous System Effects

Motor weakness, which may be rapidly ascending and has been fatal in some cases, reported rarely in patients receiving stavudine in conjunction with other antiretrovirals.1 75 Most reported cases of motor weakness occurred in the setting of lactic acidosis.1 75

Evolution of motor weakness may mimic clinical presentation of Guillain-Barré syndrome (including respiratory failure).1

Discontinue stavudine if motor weakness develops.1 Symptoms may continue or worsen following discontinuance.1

Considerations in Patients Coinfected with HIV and HCV

Hepatic decompensation, sometimes fatal, reported in HIV-infected patients coinfected with HCV receiving antiretroviral therapy concomitantly with interferon alfa (or peginterferon alfa) and ribavirin.1 80

If antiretroviral therapy used concomitantly with interferon alfa (or peginterferon alfa) with or without ribavirin, closely monitor for toxicities, especially hepatic decompensation.1 80 (See Specific Drugs under Interactions.)

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.1

Lipoatrophy or lipodystrophy reported more frequently with stavudine than with other NRTIs (e.g., abacavir, tenofovir, zidovudine).1 Incidence and severity of these effects reported with stavudine-containing regimens are cumulative over time;1 switching to other NRTIs (abacavir, tenofovir) has resulted in increases in limb fat, but modest or no improvement in clinical lipoatrophy.1

Monitor for symptoms or signs of lipoatrophy or lipodystrophy; question patients about body changes related to such effects.1

Because of potential risks associated with stavudine (including lipoatrophy or lipodystrophy), consider benefits versus risks of the drug for each patient and consider alternative antiretrovirals.1

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.1

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.1

Specific Populations

Pregnancy

Category C.1

Antiretroviral Pregnancy Registry at 800-258-4263 or .1 202

Experts state use in pregnant women only in special circumstances when preferred and alternative NRTIs cannot be used.202

Although the manufacturers state use dual NRTI option of stavudine and didanosine with caution and only if potential benefits clearly outweigh potential risks,1 217 experts state do not use dual NRTI option of stavudine and didanosine at any time, including during pregnancy.200 202

Fatal lactic acidosis reported in pregnant women receiving stavudine and didanosine with other antiretrovirals.1 49 202 Unclear whether pregnancy potentiates risk of lactic acidosis and severe hepatotoxicity with steatosis that occurs in NRTI-treated individuals.1

Clinicians caring for pregnant patients receiving stavudine should be alert for early diagnosis of lactic acidosis and hepatitis steatosis syndrome.1

Do not use dual NRTI option of stavudine and zidovudine in pregnant women because of potential antagonistic antiretroviral effects.202

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1 202

Pediatric Use

Use in pediatric patients from birth through adolescence supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients.1

Adverse effects in pediatric patients generally similar to those reported in adults.1

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults, but increased sensitivity cannot be ruled out.1

Peripheral neuropathy or peripheral neuropathic symptoms reported in geriatric individuals; closely monitor for signs and symptoms of peripheral neuropathy.1

Substantially eliminated by the kidneys; geriatric patients more likely to have decreased renal function; monitor renal function and adjust dosage accordingly.1 18

Hepatic Impairment

Safety and efficacy not established in patients with clinically important hepatic disease.1

Increased incidence of liver function abnormalities, including potentially fatal hepatic adverse effects, reported in patients with preexisting hepatic impairment (e.g., chronic active hepatitis).1

Monitor patients with liver function abnormalities.1 Interrupt or discontinue stavudine if liver disease worsens.1

Renal Impairment

Dosage adjustments recommended based on degree of renal impairment.1 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Headache, diarrhea, peripheral neurologic symptoms/neuropathy, rash, nausea and vomiting.1

Interactions for Zerit

Does not inhibit CYP1A2, 2C9, 2C19, 2D6, or 3A4.1 Interactions with drugs metabolized by CYP isoenzymes unlikely.1

Not expected to affect pharmacokinetics of protein-bound drugs.1

Specific Drugs

Drug

Interaction

Comments

Abacavir

In vitro evidence of additive antiretroviral effects1

Atazanavir

No in vitro evidence of antagonistic antiretroviral effects203

Clarithromycin

Pharmacokinetic interactions unlikely38

Darunavir

Pharmacokinetic interactions unlikely204

No in vitro evidence of antagonistic antiretroviral effects204

Didanosine

No clinically important pharmacokinetic interactions1

Concomitant use of didanosine and stavudine (with or without hydroxyurea): Increased risk of toxicities (pancreatitis, peripheral neuropathy, hyperlactatemia)1 200

In vitro evidence of additive or synergistic antiretroviral effects;28 29 antagonism also reported29

Experts state concomitant use of didanosine and stavudine not recommended at any time, including in pregnant women200 202

Manufacturers state use concomitantly with caution; avoid concomitant use during pregnancy unless potential benefits outweigh risks1 217

Avoid concomitant use of didanosine, stavudine, and hydroxyurea1

Doxorubicin

Inhibits stavudine phosphorylation in vitro1

Clinical importance unknown; use concomitantly with caution1

Emtricitabine

No clinically important pharmacokinetic interactions218

In vitro evidence of additive or synergistic antiretroviral effects218

Etravirine

No in vitro evidence of antagonistic antiretroviral effects214

Fluconazole

Pharmacokinetic interactions unlikely38

Fosamprenavir

In vitro evidence of synergistic antiretroviral effects205

Ganciclovir

Pharmacokinetic interactions unlikely54

Hydroxyurea

Concomitant use of stavudine and didanosine (with or without hydroxyurea): Possible increased risk of toxicities (pancreatitis, peripheral neuropathy, hepatotoxicity)1

Avoid concomitant use of hydroxyurea and stavudine1

Indinavir

No clinically important change in indinavir concentrations or AUC; decreased peak concentrations and increased AUC of stavudine206

Interferon (interferon alfa, peginterferon alfa)

Possible increased risk of potentially fatal hepatic decompensation in HIV-infected patients coinfected with HCV receiving antiretroviral agents and interferon alfa (or peginterferon alfa) with or without ribavirin1 80

If stavudine used in patients receiving interferon alfa (or peginterferon alfa) with or without ribavirin, closely monitor for toxicities, especially hepatic decompensation; consider discontinuing stavudine as medically appropriate; consider discontinuing or reducing dosage of interferon alfa (or peginterferon alfa) and/or ribavirin if worsening toxicities, including hepatic decompensation (Child-Pugh >6), occur1 80

Lamivudine

No clinically important pharmacokinetic interactions1

In vitro evidence of additive or synergistic antiretroviral effects28 29

Lopinavir/ritonavir

No clinically important pharmacokinetic interactions207

Maraviroc

No in vitro evidence of antagonistic antiretroviral effects224

Methadone

Decreased stavudine peak concentrations and AUC;31 200 no change in methadone concentrations31

Dosage adjustments not necessary200

Nelfinavir

No effect on concentrations or AUC of either drug1

In vitro evidence of additive or synergistic antiretroviral effects28 32 208

Nevirapine

No clinically important effect on stavudine peak concentrations or AUC215

In vitro evidence of additive or synergistic antiretroviral effects215

Raltegravir

In vitro evidence of additive to synergistic antiretroviral effects225

Ribavirin

In vitro evidence that ribavirin can reduce phosphorylation of stavudine; no evidence of pharmacokinetic or pharmacodynamic interactions (e.g., loss of virologic suppression of HIV or HCV) in HIV infected patients coinfected with HCV receiving stavudine and ribavirin1 80

Possible increased risk of potentially fatal hepatic decompensation in HIV-infected patients coinfected with HCV receiving antiretroviral agents and interferon alfa (or peginterferon alfa) with or without ribavirin1 80

Possible increase in adverse effects (lactic acidosis, pancreatitis)65 66 68

Clinical importance unknown; use concomitantly with caution1

If stavudine used in patients receiving interferon alfa (or peginterferon alfa) with or without ribavirin, closely monitor for toxicities, especially hepatic decompensation; consider discontinuing stavudine as medically appropriate; consider discontinuing or reducing dosage of interferon alfa (or peginterferon alfa) and/or ribavirin if worsening toxicities, including hepatic decompensation (Child-Pugh >6), occur1 80

Rifabutin

Decreased stavudine peak concentrations and AUC38

Rilpivirine

Pharmacokinetic interactions unlikely226

No in vitro evidence of antagonistic antiretroviral effects226

Saquinavir

In vitro evidence of additive or synergistic antiretroviral effects28 32 210

Tenofovir

In vitro evidence of additive or synergistic antiretroviral effects221

Tipranavir

Ritonavir-boosted tipranavir: No clinically important effect on stavudine pharmacokinetics211

In vitro evidence of additive antiretroviral effects211

Zidovudine

In vitro and in vivo evidence of antagonistic antiretroviral effects1 26

Do not use concomitantly at any time1 200 201 202

Zerit Pharmacokinetics

Absorption

Bioavailability

Well absorbed; peak plasma concentrations attained within 1 hour.1 Bioavailability is 86%.1

Stavudine capsules and oral solution are bioequivalent.1

Food

Food delays time to peak concentrations; no effect on AUC.69

Special Populations

Peak plasma concentration and time to peak concentration not altered in patients with renal impairment.1

Distribution

Extent

Not well characterized.1 Distributed into semen.74

Distributed into CSF in adults and pediatric patients.1 70 71

Not known whether crosses the placenta or is distributed into human milk.1

Plasma Protein Binding

Negligible.1

Elimination

Metabolism

Metabolism has only limited role in stavudine clearance.1 Unchanged stavudine is the major drug component circulating in plasma.1 Minor metabolites include oxidized stavudine, glucuronide conjugates of the drug and its oxidized metabolite, and an N-acetylcysteine conjugate of the ribose after glycosidic cleavage (suggests thymine is also a metabolite).1

Intracellularly, stavudine is phosphorylated and converted by cellular enzymes to the active 5′-triphosphate metabolite.1 2 4 8 17 22

Elimination Route

In healthy individuals, approximately 95% of a dose eliminated in urine (73.7% as unchanged drug) and 3% eliminated in feces (62% as unchanged drug).1

In HIV-infected adults, 40% of dose eliminated in urine as unchanged drug by glomerular filtration and active tubular secretion over 12–24 hours.1

Removed by hemodialysis.1 18 Not known whether removed by peritoneal dialysis.1

Half-life

1.6 hours following single oral dose in HIV-infected adults.1 Mean terminal elimination half-life is 2.3 hours following single oral dose in healthy individuals.1

Half-life is 0.96 hours in pediatric patients 5 weeks to 15 years of age; 1.59 hours in those 14–28 days of age; 5.27 hours in those 1 day of age.1

Special Populations

Pharmacokinetics not altered in patients with hepatic impairment (Child-Pugh class B or C).1

Apparent oral clearance of stavudine decreases and terminal elimination half-life increases as Clcr decreases.1

Stability

Storage

Oral

Capsules

25°C in tightly closed container; may be exposed to 15–30°C.1

Powder for Solution

25°C in tightly closed container; may be exposed to 15–30°C.1 Protect from excessive moisture.1

Following reconstitution with water, store in refrigerator at 2–8°C.1 Discard unused portions after 30 days.1

Actions and Spectrum

  • Analog of thymidine, a naturally occurring pyrimidine.1 2 3 4 6 8 9 16

  • Pharmacologically related to, but structurally different from, other NRTIs (e.g., abacavir, didanosine, emtricitabine, lamivudine, zidovudine); also differs pharmacologically and structurally from other currently available antiretrovirals.1

  • Active in vitro against HIV-11 2 3 4 9 10 11 12 16 17 20 21 23 24 27 28 and HIV-2.27

  • Inhibits replication of HIV by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).1 2 3 4 9 12 16 17 21 23

  • HIV-1 with reduced susceptibility to stavudine have been produced in vitro and have emerged during therapy with the drug.1 27

  • Stavudine-resistant HIV may be cross-resistant to some other NRTIs (e.g., abacavir, zidovudine).1 27

Advice to Patients

  • Stavudine medication guide must be provided to the patient each time the drug is dispensed; importance of patient reading the medication guide prior to initiating stavudine therapy and each time prescription is refilled.1

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician during therapy.1 Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.1

  • Importance of using in conjunction with other antiretrovirals–not for monotherapy.1

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.1

  • Advise patients that sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to AIDS and death.226

  • Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.200 Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.1 200

  • If a dose is missed, it should be taken as soon as possible.1 If a dose is skipped, do not take a double dose to make up for the missed dose.1

  • Possibility of lactic acidosis; importance of early recognition of symptoms of hyperlactatemia or lactic acidosis (unexplained weight loss, abdominal discomfort, nausea, vomiting, fatigue, dyspnea, motor weakness) and immediately seeking medical attention if such symptoms occur.1 Discontinuance of stavudine may be required.1

  • Increased risk of potentially fatal hepatotoxicity, which may occur in patients receiving stavudine in conjunction with didanosine and hydroxyurea; importance of avoiding this regimen.1

  • Possibility of peripheral neuropathy; importance of patient and/or caregivers recognizing manifestations of peripheral neuropathy (numbness, tingling, or pain in hands or feet) and reporting these symptoms to a clinician.1 Advise patients that peripheral neuropathy occurs most frequently in patients with advanced HIV-1 disease or history of peripheral neuropathy and that discontinuance of stavudine may be needed if this adverse effect occurs.1

  • Increased risk of potentially fatal pancreatitis, which may occur in patients receiving stavudine in conjunction with didanosine; importance of avoiding this regimen.1 Importance of avoiding alcohol while receiving stavudine (increases risk of pancreatitis or liver damage) and closely monitoring for symptoms of pancreatitis.1

  • Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.1

  • Advise diabetic patients that stavudine oral solution contains 50 mg of sucrose/mL.1

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise HIV-infected women not to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Stavudine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

15 mg*

Stavudine Capsules

Zerit

Bristol-Myers Squibb

20 mg*

Stavudine Capsules

Zerit

Bristol-Myers Squibb

30 mg*

Stavudine Capsules

Zerit

Bristol-Myers Squibb

40 mg*

Stavudine Capsules

Zerit

Bristol-Myers Squibb

For solution

1 mg/mL*

Stavudine for Oral Solution

Zerit

Bristol-Myers Squibb

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Stavudine 40MG Capsules (CAMBER PHARMACEUTICALS): 60/$129.99 or 180/$369.97

Zerit 1MG/ML Solution (B-M SQUIBB ONCOLOGY/IMMUNOLOGY): 200/$87.99 or 600/$255.97

Zerit 15MG Capsules (B-M SQUIBB ONCOLOGY/IMMUNOLOGY): 60/$363.99 or 180/$1,050.34

Zerit 20MG Capsules (B-M SQUIBB ONCOLOGY/IMMUNOLOGY): 60/$388.98 or 180/$1,126.01

Zerit 30MG Capsules (B-M SQUIBB ONCOLOGY/IMMUNOLOGY): 60/$416.98 or 180/$1,197.99

Zerit 40MG Capsules (B-M SQUIBB ONCOLOGY/IMMUNOLOGY): 60/$426.97 or 180/$1,225.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 7, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Bristol-Myers Squibb. Zerit (stavudine) capsules and powder for oral solution prescribing information. Princeton, NJ; 2012 Jan.

2. Ho HT. Cellular pharmacology of 2′,3′-dideoxy-2′, 3′-didehydrothymidine, a nucleoside analog active against human immunodeficiency virus. Antimicrob Agents Chemother. 1989; 33:844-9. [PubMed 2764535]

3. Yarchoan R, Mitsuya H. Clinical and basic advances in the antiretroviral therapy of human immunodeficiency virus infection. Am J Med. 1989; 87:191-200. [IDIS 261900] [PubMed 2474251]

4. Hitchcock MJM. 2′3′-Didehydro-2′,3′-dideoxythymidine (D4T), an anti-HIV agent. Antiviral Chem. 1991; 2:125-32.

5. August EM, Birks EM. 3′-Deoxythymidin-2′-ene permeation of human lymphocyte H9 cells by nonfacilitated diffusion. Mol Pharmacol. 1991; 39:246-9. [PubMed 1847498]

6. Martin JC, Hitchcock MJM, Fridland A et al. Comparative studies of 2′3′-didehydro-2′,3′-dideoxythymidine (D4T) with other pyrimidine nucleoside analogues. Ann NY Acad Sci. 1990; 616:22-8. [PubMed 1964029]

7. Zhu Z, Hitchcock MJM. Metabolism and DNA interaction of 2′3′-didehydro-2′,3′-dideoxythymidine in human bone marrow cells. Mol Pharmacol. 1991; 40:838-45. [PubMed 1658614]

8. August EM, Marongiu ME, Lin T-S et al. Initial studies on the cellular pharmacology of 3′-deoxythymidin-2′-ene (d4T): a potent and selective inhibitor of human immunodeficiency virus. Biochem Pharmacol. 1988; 37:4419-22. [PubMed 2849444]

9. Yarchoan R, Mitsuya H, Myers CE et al. Clinical pharmacology of 3′-azido-2′,3′-dideoxythymidine (zidovudine) and related dideoxynucleosides. N Engl J Med. 1989; 321:726-38. [IDIS 258616] [PubMed 2671731]

10. 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. [IDIS 306938] [PubMed 8093363]

11. De Clercq E. HIV inhibitors targeted at reverse transcriptase. AIDS Res Hum Retroviruses. 1992; 8:119-34. [PubMed 1371690]

12. Yarchoan R. Anti-retroviral therapy of AIDS and related disorders: general principles and specific development of dideoxynucleosides. Pharmacol Ther. 1989; 40:329-48. [PubMed 2646649]

13. Funk MB, Linde R, Wintergerst U et al. Preliminary experiences with triple therapy including nelfinavir and two reverse transcriptase inhibitors in previously untreated HIV-infected children. AIDS. 1999; 13:1653-8. [PubMed 10509566]

14. Krogstad P, Lee S, Johnson G et al. Nucleoside-analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir for pretreated children infected with human immunodeficiency virus type 1. Clin Infect Dis. 2002; 34:991-1001. [IDIS 480417] [PubMed 11880966]

15. Yogev R, Lee S, Wiznia A et al. Stavudine, nevirapine and ritonavir in stable antiretroviral therapy-experienced children with human immunodeficiency virus infection. Pediatr Infect Dis J. 2002; 21:119-25. [IDIS 477734] [PubMed 11840078]

16. Mansuri MM, Hitchcock MJM, Buroker RA et al. Comparison of in vitro biological properties and mouse toxicities of three thymidine analogs active against human immunodeficiency virus. Antimicrob Agents Chemother. 1990; 34:637-41. [PubMed 1693057]

17. Balzarini J, Herdewijn P. Differential patterns of intracellular metabolism of 2′,3′-didehydro-2′,3′-dideoxythymidine and 3′-azido-2′,3′-dideoxythymidine, two potent anti-human immunodeficiency virus compounds. J Biol Chem. 1989; 264:6127-33. [PubMed 2539371]

18. Eron JJ, Murphy RL, Peterson D et al. A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: selection of thymidine analog regimen therapy (START II). AIDS. 2000; 14:1601-10. [PubMed 10983647]

20. Hamamoto Y, Nakashima H, Matsui T et al. Inhibitory effect of 2′,3′-didehydro-2′,3′-dideoxynucleosides on infectivity, cytopathic effects, and replication of human immunodeficiency virus. Antimicrob Agents Chemother. 1987; 31:907-10. [PubMed 3039911]

21. Mansuri MM, Starrett Jr JE, Ghazzouli I et al. 1-(2,3-Dideoxy-beta-D-glycero-pent-2-enofuranosyl)thymine. A highly potent and selective anti-HIV agent. J Med Chem. 1989; 32:461-6. [PubMed 2536441]

22. Marongiu ME, August EM. Effect of 3′-deoxythymidin-2′-ene (d4T) on nucleoside metabolism in H9 cells. Biochem Pharmacol. 1990; 39:1523-8. [PubMed 2159760]

23. Lin TS, Schinazi RF. Potent and selective in vitro activity of 3′-deoxythymidin-2′-ene (3′-deoxy-2′,3′-didehydrothymidine) against human immunodeficiency virus. Biochem Pharmacol. 1987; 36:2713-8. [PubMed 2443141]

24. Baba M, Pauwels R, Herdewijn P et al. Both 2′,3′-dideoxythymidine and its 2′,3′-unsaturated derivative (2′,3′-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro. Biochem Biophys Res Commun. 1987; 142:128-34. [PubMed 3028398]

26. Havlir DV, Tierney C, Friedland GH et al. In vivo antagonism with zidovudine plus stavudine combination therapy. J Infect Dis. 2000; 182:321-5. [IDIS 450347] [PubMed 10882616]

27. Lea AP. Stavudine: a review of its pharmacodynamic and pharmacokinetic properties and clinical potential in HIV infection. Drugs. 1996; 51:846-64. [PubMed 8861550]

28. Merrill DP, Moonis M, Chou TC et al. Lamivudine or stavudine in two- and three-drug combinations against human immunodeficiency virus type 1 replication in vitro. J Infect Dis. 1996; 173:355-64. [IDIS 362747] [PubMed 8568296]

29. Deminie CA, Bechtold CM, Stock D et al. Evaluation of reverse transcriptase and protease inhibitors in two-drug combinations against human immunodeficiency virus replication. Antimicrob Agents Chemother. 1996; 40:1346-51. [PubMed 8725999]

30. Zhu QY, Scarborough A, Polsky B et al. Drug combinations and effect parameters of zidovudine, stavudine, and nevirapine in standardized drug-sensitive and resistant HIV type 1 strains. AIDS Res Hum Retroviruses. 1996; 12:507-17. [PubMed 8679306]

31. Rainey PM, Friedland G, McCance-Katz EF et al. Interaction of methadone with didanosine and stavudine. J Acquir Immune Defic Syndr. 2000; 24:241-8. [IDIS 452905] [PubMed 10969348]

32. Patick AK, Boritzki TJ, Bloom LA. Activities of the human immunodeficiency virus type 1 (HIV-1) protease inhibitor nelfinavir mesylate in combination with reverse transcriptase and protease inhibitors against acute HIV-1 infection in vitro. Antimicrob Agents Chemother. 1997; 41:2159-64. [PubMed 9333041]

38. Piscitelli SC, Kelly G, Walker RE et al. A multiple drug interaction study of stavudine with agents for opportunistic infections in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 1999; 43:647-50. [IDIS 424139] [PubMed 10049281]

39. Kline MW, Fletcher CV, Federici ME et al. Combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus infection: pharmacokinetic properties, safety, and immunologic and virologic effects. Pediatrics. 1996; 97:886-90. [IDIS 368236] [PubMed 8657531]

41. Shafer RW, Iversen AKN, Winters MA et al. Drug resistance and heterogeneous long-term virologic responses of human immunodeficiency virus type 1-infected subjects to zidovudine and didanosine combination therapy. J Infect Dis. 1995; 172:70-8. [IDIS 350663] [PubMed 7541064]

47. Spruance SL, Pavia AT, Mellors JW et al. Clinical efficacy of monotherapy with stavudine compared with zidovudine in HIV-infected, zidovudine-experienced patients. A randomized, double-blind, controlled trial. Ann Intern Med. 1997; 126:355-63. [IDIS 380434] [PubMed 9054279]

48. Kline MW, Fletcher CV. A pilot study of combination therapy with indinavir, stavudine (d4T), and didanosine (ddI) in children infected with human immunodeficiency virus. J Pediatr. 1998; 132:543-6. [IDIS 404504] [PubMed 9544920]

49. Smyth AC. Bristol-Myers Squibb. Dear healthcare provider letter regarding fatal lactic acidosis in pregnant women treated throughout gestation with the combination of stavudine and didanosine 2001 Jan 5. From FDA web site.

50. Chene G, Angelini E, Cotte L et al. Role of long-term nucleoside-analogue therapy in lipodystrophy and metabolic disorders in human immunodeficiency virus-infected patients. Clin Infect Dis. 2002; 34:649-57. [IDIS 476867] [PubMed 11810598]

51. Hurst M, Noble S. Stavudine: an update of its use in the treatment of HIV infection. Drugs. 1999; 58:919-49. [PubMed 10595868]

54. Jung D, AbdelHameed MH, Teitelbaum P et al. The pharmacokinetics and safety profile of oral ganciclovir combined with zalcitabine or stavudine in asymptomatic HIV- and CMV-seropositive patients J Clin Pharmacol. 1999; 39:505-12.

55. Wintergerst U, Hoffmann F, Solder B et al. Comparison of two antiretroviral triple combinations including the protease inhibitor indinavir in children infected with human immunodeficiency virus. Pediatr Infect Dis J. 1998; 17:495-9. [IDIS 408835] [PubMed 9655541]

62. Kline MW, Van Dyke RB, Lindsey JC et al. Combination therapy with stavudine (d4T) plus didanosine (ddI) in children with human immunodeficiency virus infection. Pediatrics. 1999; 103:e62. [IDIS 435503] [PubMed 10224206]

64. Schering Corporation. Rebetron combination therapy containing Rebetol (ribavirin) capsules and Intron (interferon alfa-2b, recombinant) injection prescribing information. Kenilworth, NJ; 2001 Aug.

65. Lafeuillade A, Hittinger G, Chadapaud S. Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection. Lancet. 2001; 357:280-1. [IDIS 461915] [PubMed 11214134]

66. Kakuda TN, Brinkman K. Mitochondrial toxic effects and ribavirin. Lancet. 2001; 357:1802-3. [IDIS 469956] [PubMed 11407388]

67. Brinkman K, Kakuda TN. Mitochondrial toxicity of nucleoside analogue reverse transcriptase inhibitors: a looming obstacle for long-term antiretroviral therapy? Curr Opinion Infect Dis. 2000; 13:5-11.

68. Salmon-Ceron D, Chauvelot-Moachon L, Abad S et al. Mitochondrial toxic effects and ribavirin. Lancet. 2001; 357:1803-4. [IDIS 469957] [PubMed 11407389]

69. Kaul S, Christofalo B, Raymond RH et al. Effect of food on the bioavailability of stavudine in subjects with human immunodeficiency virus infection. Antimicrob Agents Chemother. 1998; 42:2295-8. [IDIS 412428] [PubMed 9736552]

70. Haworth SJ, Christofalo B, Anderson RD et al. A single-dose study to assess the penetration of stavudine into human cerebrospinal fluid in adults. J Acquir Immune Defic Syndr Hum Retrovirol. 1998; 17:235-8. [PubMed 9495223]

71. van Praag RME, van Weert ECM, van Heeswijk RPG et al. Stable concentrations of zidovudine, stavudine, lamivudine, abacavir, and nevirapine in serum and cerebrospinal fluid during 2 years of therapy. Antimicrob Agents Chemother. 2002; 46:896-9. [IDIS 477654] [PubMed 11850283]

72. Schaad HJ, Petty BG, Grasela DM et al. Pharmacokinetics and safety of a single dose of stavudine (d4T) in patients with severe hepatic impairment. Antimicrob Agents Chemother. 1997; 41:2793-6. [IDIS 397016] [PubMed 9420063]

73. Grasela DM, Stoltz RR, Barry M et al. Pharmacokinetics of single-dose oral stavudine in subjects with renal impairment and in subjects requiring hemodialysis. Antimicrob Agents Chemother. 2000; 44:2149-53. [IDIS 450051] [PubMed 10898689]

74. Taylor S, van Heeswijk RP, Hoetelmans RM et al. Concentrations of nevirapine, lamivudine and stavudine in semen of HIV-1-infected men. AIDS. 2000; 14:1979-84. [PubMed 10997403]

75. Stevens MR. Bristol-Myers Squibb. Dear healthcare provider letter regarding rare occurrences of rapidly ascending neuromuscular weakness, mimicking the clinical presentation of Guillain-Barre syndrome, in patients receiving stavudine in combination with other antiretrovirals. Princeton, NJ; 2002 Feb. From FDA web site.

80. Genentech USA. Pegasys (peginterferon alfa-2a) injection for subcutaneous use prescribing information. South San Francisco, CA; 2011 Sep.

81. Zerit (stavudine) capsules and powder for oral solution risk evaluation and mitigation strategy (REMS). From FDA website.

82. Marcus KA. Supplemental approval release REMS requirement. Silver Spring, MD: US Food and Drug Administration; 2011 May 11. From FDA website.

198. Center for Disease Control and Prevention. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: Recommendations from the U.S. Department of Health and Human Services. MMWR Recomm Rep. 2005; 54(No. RR-2):1-19.

199. Center for Disease Control and Prevention. Updated U.S. public health service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rep. 2005; 54(No. RR-9):1-17.

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (April 18, 2012). Updates may be available at HHS AIDS Information (AIDSinfo) website.

201. Panel on Antiretroviral Therapy and Medical Management of HIV-infected Children, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection (August 11, 2011). Updates may be available at HHS AIDS Information (AIDSinfo) website.

202. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States (July 31, 2012). Updates may be available at HHS AIDS Information (AIDSinfo) website.

203. Bristol-Myers Squibb. Reyataz (atazanavir sulfate) capsules prescribing information. Princeton, NJ; 2012 Mar.

204. Janssen. Prezista (darunavir) oral suspension and tablets prescribing information. Titusville, NJ; 2012 Jun.

205. ViiV Healthcare. Lexiva (fosamprenavir calcium) tablets and oral suspension prescribing information. Research Triangle Park, NC; 2012 Feb.

206. Merck Sharp & Dohme. Crixivan (indinavir sulfate) capsules prescribing information. Whitehouse Station, NJ; 2012 Apr.

207. Abbott Laboratories. Kaletra (lopinavir/ritonavir) tablets and oral solution prescribing information. North Chicago, IL; 2012 Feb.

208. ViiV Healthcare. Viracept (nelfinavir mesylate) tablets and oral powder prescribing information. Research Triangle Park, NC; 2012 Apr.

210. Genentech USA. Invirase (saquinavir mesylate) capsules and tablets prescribing information. South San Francisco, CA; 2012 Feb.

211. Boehringer Ingelheim. Aptivus (tipranavir) capsules and oral solution prescribing information. Ridgefield, CT; 2012 Apr.

213. Bristol-Myers Squibb. Sustiva (efavirenz) capsules and tablets prescribing information. Princeton, NJ; 2012 Jun.

214. Janssen. Intelence (etravirine) tablets prescribing information. Raritan, NJ; 2012 Mar.

215. Boehringer Ingelheim. Viramune (nevirapine) tablets and oral suspension prescribing information. Ridgefield, CT; 2011 Nov.

217. Bristol-Myers Squibb. Videx EC (didanosine) delayed-release capsules enteric-coated beadlets prescribing information. Princeton, NJ; 2011 Nov.

218. Gilead Sciences. Emtriva (emtricitabine) capsules and oral solution prescribing information. Foster City, CA; 2012 Jul.

219. ViiV Healthcare. Epivir (lamivudine) tablet, film coated and solution prescribing information. Research Triangle Park, NC; 2011 Nov.

221. Gilead Sciences. Viread (tenofovir disoproxil fumarate) tablets prescribing information. Foster City, CA; 2012 Jan.

224. ViiV Healthcare. Selzentry (maraviroc) tablets prescribing information. Research Triangle Park, NC; 2011 Nov.

225. Merck Sharp & Dohme . Isentress (raltegravir) tablets prescribing information. Whitehouse Station, NJ; 2011 Feb.

226. Tibotec Therapeutics. Edurant (rilpivirine) tablets prescribing information. Raritan, NJ; 2011 May.

Hide
(web2)