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Stavudine

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

Medically reviewed by Drugs.com. Last updated on Feb 1, 2021.

Warning

  • 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. (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. Use stavudine in conjunction with didanosine with caution in pregnant women and only if potential benefits outweigh risks. (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. (See Pancreatitis under Cautions.)

Introduction

Antiretroviral; HIV nucleoside reverse transcriptase inhibitor (NRTI).

Uses for Stavudine

Treatment of HIV Infection

Treatment of HIV-1 infection in adults, adolescents, and pediatric patients; used in conjunction with other antiretrovirals.

Experts state stavudine not recommended for initial treatment regimens in antiretroviral-naive adults and adolescents.

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

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

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

Postexposure Prophylaxis following Occupational Exposure to HIV

Postexposure prophylaxis of HIV infection following occupational exposure (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.

USPHS recommends 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir disoproxil fumarate (tenofovir DF) as the preferred regimen for PEP. Stavudine is one of several alternative agents that may be used in conjunction with other antiretrovirals for PEP, but use only with expert consultation. Because of risk of toxicity (e.g., peripheral neuropathy, pancreatitis, lactic acidosis), dual NRTI option of stavudine and didanosine should not be used in PEP regimens.

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible. Do not delay initiation of PEP while waiting for expert consultation.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV

Postexposure prophylaxis of HIV infection following nonoccupational exposure (nPEP) in individuals exposed 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. Used in conjunction with other antiretrovirals.

Stavudine Dosage and Administration

Administration

Oral Administration

Administer orally every 12 hours without regard to meals.

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. Shake vigorously until completely dissolved; solution may appear slightly hazy.

Agitate solution well prior to administration of each dose.

Dosage

Pediatric Patients

Treatment of HIV Infection
Oral

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

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

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

≥60 kg: 40 mg every 12 hours.

Adults

Treatment of HIV Infection
Oral

<60 kg: 30 mg every 12 hours.

≥60 kg: 40 mg every 12 hours.

Postexposure Prophylaxis of HIV†
Occupational Exposure†
Oral

<60 kg: 30 mg twice daily.

>60 kg: 40 mg twice daily.

Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).

Initiate PEP as soon as possible following exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Nonoccupational Exposure†
Oral

<60 kg: 30 mg twice daily.

>60 kg: 40 mg twice daily.

Use in conjunction with other antiretrovirals.

Initiate nPEP as soon as possible following exposure to HIV (preferably ≤72 hours after exposure); continue for 28 days.

Special Populations

Renal Impairment

Treatment of HIV Infection

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

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

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 Stavudine

Contraindications

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

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. Reported most frequently in women; obesity and long-term NRTI therapy also may be risk factors. Has been reported in patients with no known risk factors.

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

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

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).

Consider permanently discontinuing stavudine in patients with confirmed lactic acidosis.

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). Monitor such patients.

Fatal hepatotoxicity and hepatic failure reported during postmarketing experience in HIV-infected individuals receiving stavudine, didanosine, and hydroxyurea concomitantly. (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.

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

Other Warnings and Precautions

Peripheral Neuropathy

Peripheral neuropathy, manifested by numbness, tingling, or pain in the hands or feet, reported. 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).

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

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. Most reported cases of motor weakness occurred in the setting of lactic acidosis.

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

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

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.

If antiretroviral therapy used concomitantly with interferon alfa (or peginterferon alfa) with or without ribavirin, closely monitor for toxicities, especially hepatic decompensation. (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.

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

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

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.

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 jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.

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.

Specific Populations

Pregnancy

Category C.

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

Experts state stavudine is not recommended for initial treatment regimens in antiretroviral-naive pregnant women.

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

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

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

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

Lactation

Distributed into human milk (see Distribution under Pharmacokinetics).

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

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.

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

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.

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

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

Hepatic Impairment

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

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

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

Renal Impairment

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

Common Adverse Effects

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

Interactions for Stavudine

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

Not expected to affect pharmacokinetics of protein-bound drugs.

Specific Drugs

Drug

Interaction

Comments

Abacavir

In vitro evidence of additive antiretroviral effects

Atazanavir

No in vitro evidence of antagonistic antiretroviral effects

Clarithromycin

Pharmacokinetic interactions unlikely

Darunavir

Pharmacokinetic interactions unlikely

No in vitro evidence of antagonistic antiretroviral effects

Didanosine

No clinically important pharmacokinetic interactions

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

In vitro evidence of additive or synergistic antiretroviral effects; antagonism also reported

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

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

Avoid concomitant use of didanosine, stavudine, and hydroxyurea

Dolutegravir

No in vitro evidence of antagonistic antiretroviral effects

Doxorubicin

Inhibits stavudine phosphorylation in vitro

Clinical importance unknown; use concomitantly with caution

Emtricitabine

No clinically important pharmacokinetic interactions

In vitro evidence of additive or synergistic antiretroviral effects

Etravirine

No in vitro evidence of antagonistic antiretroviral effects

Fluconazole

Pharmacokinetic interactions unlikely

Fosamprenavir

In vitro evidence of synergistic antiretroviral effects

Ganciclovir

Pharmacokinetic interactions unlikely

Hydroxyurea

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

Avoid concomitant use of hydroxyurea and stavudine

Indinavir

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

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 ribavirin

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), occur

Lamivudine

No clinically important pharmacokinetic interactions

In vitro evidence of additive or synergistic antiretroviral effects

Lopinavir/ritonavir

No clinically important pharmacokinetic interactions

Maraviroc

No in vitro evidence of antagonistic antiretroviral effects

Methadone

Decreased stavudine peak concentrations and AUC; no change in methadone concentrations

Dosage adjustments not necessary

Nelfinavir

No effect on concentrations or AUC of either drug

In vitro evidence of additive or synergistic antiretroviral effects

Nevirapine

No clinically important effect on stavudine peak concentrations or AUC

In vitro evidence of additive or synergistic antiretroviral effects

Raltegravir

In vitro evidence of additive to synergistic antiretroviral effects

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 ribavirin

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 ribavirin

Possible increase in adverse effects (lactic acidosis, pancreatitis)

Clinical importance unknown; use concomitantly with caution

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), occur

Rifabutin

Decreased stavudine peak concentrations and AUC

Rilpivirine

Pharmacokinetic interactions unlikely

No in vitro evidence of antagonistic antiretroviral effects

Saquinavir

In vitro evidence of additive or synergistic antiretroviral effects

Simeprevir

Clinically important interactions not expected

Tenofovir

In vitro evidence of additive or synergistic antiretroviral effects

Tipranavir

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

In vitro evidence of additive antiretroviral effects

Zidovudine

In vitro and in vivo evidence of antagonistic antiretroviral effects

Do not use concomitantly at any time

Stavudine Pharmacokinetics

Absorption

Bioavailability

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

Stavudine capsules and oral solution are bioequivalent.

Food

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

Special Populations

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

Distribution

Extent

Not well characterized. Distributed into semen.

Distributed into CSF in adults and pediatric patients.

Ex vivo studies indicate stavudine crosses human placenta.

Distributed into human milk; breast milk to maternal plasma concentration ratios of 1–1.76 reported.

Plasma Protein Binding

Negligible.

Elimination

Metabolism

Metabolism has only limited role in stavudine clearance. Unchanged stavudine is the major drug component circulating in plasma. 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).

Intracellularly, stavudine is phosphorylated and converted by cellular enzymes to the active 5′-triphosphate metabolite.

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).

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

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

Half-life

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

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.

Special Populations

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

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

Stability

Storage

Oral

Capsules

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

Powder for Solution

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

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

Actions and Spectrum

  • Analog of thymidine, a naturally occurring pyrimidine.

  • 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.

  • Active in vitro against HIV-1 and HIV-2.

  • Inhibits replication of HIV by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).

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

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

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.

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

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

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

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

  • 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. 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.

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

  • 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. Discontinuance of stavudine may be required.

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

  • 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. 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.

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

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

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

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

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

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

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* 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

AHFS DI Essentials™. © Copyright 2021, Selected Revisions February 9, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

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