The medical letter on drugs and therapeutics january 20 2014

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On Drugs and Therapeutics
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IN THIS ISSUE (starts on next page)

Sofosbuvir (Sovaldi) for Chronic Hepatitis C .....................................................p 5
Antiviral Drugs for Influenza 2013-2014 ........................................................... p 6
In Brief: Ponatinib (Iclusig) Returns ................................................................. p 8

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The Medical Letter

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On Drugs and Therapeutics
Published by The Medical Letter, Inc. • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication
Volume 56 (Issue 1434)
January 20, 2014

ALSO IN THIS ISSUE

Antiviral Drugs for Influenza 2013-2014 .......p 6
In Brief: Ponatinib (Iclusig) Returns .............p 8

Sofosbuvir (Sovaldi) for Chronic
Hepatitis C
The FDA has approved the nucleotide polymerase
inhibitor sofosbuvir (Sovaldi – Gilead) for use in
combination with other antiviral drugs for treatment of
chronic hepatitis C virus (HCV) infection.

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with peginterferon and ribavirin for 24 weeks and
those with genotype 4 infection are treated with peginteferon and ribavirin for 48 weeks. Interferon must
be injected and is associated with a high incidence
of adverse effects, including flu-like symptoms, fatigue, psychiatric disorders, hematologic abnormalities, and autoimmune disorders.2
CLINICAL STUDIES — Sustained virologic response
(SVR) rates 12 weeks after stopping treatment with

sofosbuvir are shown in table 2.3-5
Table 2. Some Clinical Trials with Sofosbuvir
Clinical Trial

SVR12 Rates

Patients with HCV genotype 1 (or 4, 5, or 6)

Table 1. Pharmacology
Class
Route
Formulation
Tmax
Metabolism

Elimination
Half-life
(terminal)

Nucleotide polymerase inhibitor
Oral
400-mg tablets
~0.5-2 hrs (sofosbuvir)
2-4 hrs (inactive metabolite)
Activated in liver by hydrolysis and phosphoramidate
cleavage followed by phosphorylation; dephosphorylation results in formation of inactive metabolite
Urine (~80%), feces (14%), expired air (2.5%)
0.4 hrs (sofosbuvir)
27 hrs (inactive metabolite)

ACTIVITY — Sofosbuvir is a uridine nucleotide
analog prodrug that is converted to an active
metabolite in the liver. It inhibits the HCV NS5B RNAdependent RNA polymerase, which is essential for
viral replication. In vitro, sofosbuvir has potent activity
against all HCV genotypes (1-6), including strains
resistant to protease inhibitors. The prevalence of
HCV genotypes in the US is 79% genotype 1, 13%
genotype 2, 6% genotype 3, and 2% genotypes 4, 5,
and 6 combined.
STANDARD THERAPY — The current standard of
care for patients with HCV genotype 1 infection is
peginterferon and ribavirin plus a protease inhibitor
such as telaprevir (Incivek), boceprevir (Victrelis), or
simeprevir (Olysio)1 for a total of 24-48 weeks. Patients with HCV genotype 2 or 3 infection are treated

NEUTRINO (open-label; 327 treatment-naive patients)1
Sofosbuvir + P + R x 12 wks
90%
Historical control rate2
60%
Patients with HCV genotype 2 or 3

GT2

GT3

FISSION (open-label; 496 treatment-naive patients)1
Sofosbuvir + R x 12 wks
97%
P + R x 24 wks

78%

56%
63%

POSITRON (double-blind; 278 patients intolerant, ineligible, or
unwilling to take interferon)3
Sofosbuvir + R x 12 wks
93%
61%
Placebo x 12 wks
0%
0%
FUSION (double-blind; 195 treatment-experienced patients)3
Sofosbuvir + R x 12 wks
86%
30%
Sofosbuvir + R x 16 wks
94%
62%
Historical control rate4
overall 25%
VALENCE (open-label; 323 treatment-naive and treatmentexperienced patients)5
Sofosbuvir + R x 12 wks
93%
—
Sofosbuvir + R x 24 wks
—
84%
GT = genotype; P = peginterferon; R = ribavirin; SVR12 = HCV RNA <25 IU/mL

12 wks after stopping treatment.
1. E Lawitz et al. N Engl J Med 2013; 368:1878.
2. Based on treatment with telaprevir (8 or 12 weeks) or boceprevir (24 or 44
weeks) and peginterferon/ribavirin (24-48 weeks).
3. IM Jacobson et al. N Engl J Med 2013; 368:1867.
4. Based on treatment with peginterferon and ribavirin for 48 weeks.
5. S Zeuzem et al. Hepatology 2013; 58(4) suppl 1:733A. Abs. 1085.

Sofosbuvir plus ribavirin for 12 or 24 weeks was also
effective for treatment of HCV/HIV co-infection in
patients infected with HCV genotype 1, 2, or 3 (SVR12
rates: 76% [24 weeks], 88% [12 weeks], and 92% [24
weeks], respectively).6

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5


In HCV-infected patients with hepatocellular
carcinoma awaiting liver transplantation, treatment
with sofosbuvir plus ribavirin for up to 48 weeks
prevented HCV recurrence at post-transplant week 12
in 64% of patients who had undetectable HCV RNA
levels at transplant.7
Use of sofosbuvir plus simeprevir with or without
ribavirin in treatment-naive and prior null responder patients with HCV genotype 1 infection is under investigation. An interim analysis of one study found high rates
of viral clearance in all treatment groups; addition of
ribavirin did not improve efficacy.8
ADVERSE EFFECTS — Sofosbuvir was generally

well tolerated in clinical trials. The most common adverse effects with use of sofosbuvir in combination
with ribavirin or peginterferon plus ribavirin included
fatigue, headache, nausea, insomnia, and anemia;
all of these are associated with use of peginterferon
and ribavirin alone.
Sofosbuvir is not teratogenic in animals, but it has
not been studied in pregnant women. Use of ribavirin
(which is teratogenic and embryotoxic) or peginterferon/ribavirin is contraindicated during pregnancy
(category X).
DRUG INTERACTIONS — Sofosbuvir is a substrate of
P-glycoprotein (P-gp) and should not be administered
with potent P-gp inducers such as rifampin.9 Unlike protease inhibitors, sofosbuvir and its metabolites are not
inhibitors, inducers, or substrates of CYP450 enzymes.
DOSAGE, ADMINISTRATION, AND COST — The recommended dosage of sofosbuvir is 400 mg orally once
daily with or without food. For patients with HCV genotype 1 or 4 infection, sofosbuvir should be given with
peginterferon and ribavirin for 12 weeks. In patients with
HCV genotype 1 infection who cannot take interferon,
use of sofosbuvir plus ribavirin for 24 weeks may be considered as an alternative.10 Sofosbuvir should be given
with ribavirin for 12 weeks in patients infected with HCV
genotype 2 and for 24 weeks in those with HCV genotype 3 infection. The cost of a 28-tablet bottle of Sovaldi
is $28,000.11 A 12-week supply of tablets would cost
$84,000. A 24-week supply would cost $168,000.
CONCLUSION — Sofosbuvir (Sovaldi) appears to
be the most effective drug available to date for treatment of chronic hepatitis C. In combination with other drugs, it has produced higher sustained virologic
response rates with shorter treatment durations than
the current standard of care. For some patients, at
least, it offers the possibility of oral treatment without the debilitating side effects of interferon. □

6

1. Simeprevir (Olysio) for chronic hepatitis C. Med Lett Drugs Ther
2014; 56:1.
2. Antiviral drugs. Treat Guidel Med Lett 2013; 11:19.
3. E Lawitz et al. Sofosbuvir for previously untreated chronic hepatitis
C infection. N Engl J Med 2013; 368:1878.
4. IM Jacobson et al. Sofosbuvir for hepatitis C genotype 2 or 3 in
patients without treatment options. N Engl J Med 2013; 368:1867.
5. S Zeuzem et al. Sofosbuvir + ribavirin for 12 or 24 weeks for patients with HCV genotype 2 or 3: the VALENCE trial. Hepatology
2013; 58(4) suppl 1:733A. Abs. 1085.
6. M Sulkowski et al. All-oral therapy with sofosbuvir plus ribavirin
for the treatment of HCV genotype 1, 2, and 3 infection in patients
co-infected with HIV (PHOTON-1). Hepatology 2013; 58(4) suppl
1:313a. Abs. 212.
7. MP Curry et al. Pretransplant sofosbuvir and ribavirin to prevent
recurrence of HCV infection after liver transplantation. Hepatology
2013; 58(4) suppl 1:314A. Abs. 213.
8. IM Jacobson et al. SVR results of a once-daily regimen of simeprevir (SMV, TMC435) plus sofosbuvir (SOF, GS-7977) with or without
ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatmentnaive and prior null responder patients. The COSMOS study. Presented at 64th annual meeting of the American Association for the
Study of Liver Diseases, Washington, DC November 1-5, 2013.
Abs. LB-3.
9. Inducers and inhibitors of CYP enzymes and P-glycoprotein. Med
Lett Drugs Ther 2013; 55:e44.
10. A Osinusi et al. Sofosbuvir and ribavirin for hepatitis C genotype
1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA 2013; 310:804.
11. Approximate wholesale acquisition cost (WAC). Source:
Analy$ource® Monthly (Selected from FDB MedKnowledge™)
January 5, 2014. Reprinted with permission by FDB, Inc. All rights
reserved. ©2014. www.fdbhealth.com/policies/drug-pricing-policy.
Actual retail price may be higher.

Antiviral Drugs for Influenza 2013-2014
Antiviral drugs can be used for treatment of influenza and
as an adjunct to influenza vaccination1 for prophylaxis. Frequently updated information on antiviral resistance is available at www.cdc.gov/flu/professionals/antivirals.
NEURAMINIDASE INHIBITORS — Oseltamivir (Tamiflu),
which is taken orally, and zanamivir (Relenza), which is
inhaled, can be used for either chemoprophylaxis or treatment. When used for chemoprophylaxis after exposure to
susceptible strains of seasonal influenza A or B viruses,
they have generally been about 70-90% effective.2
In mild illness, treatment with a neuraminidase inhibitor
started within 48 hours after the onset of illness in patients infected with a susceptible strain of influenza virus
can decrease the duration of fever and symptoms.3 It may
also reduce the risk of complications such as pneumonia.
In hospitalized and critically ill patients, these drugs may
decrease the risk of death and shorten the duration of
hospitalization, even when they are started as late as 5
days after the onset of symptoms.4-6 The typical duration
of treatment is 5 days, but a prolonged treatment course
(e.g., 10 days) may be beneficial for critically ill or immunocompromised patients, in whom viral replication may be
protracted.

The Medical Letter • Volume 56 • Issue 1434 • January 20, 2014


Table 1. Antiviral Drugs for Seasonal Influenza: 2013-2014
Adult Dosage
Treatment2
Prophylaxis1

Drug

Formulations

Oseltamivir –
Tamiflu
(Genentech)

30, 45, 75 mg capsules; 75 mg PO
6 mg/mL oral
once/d4
suspension

Zanamivir –
Relenza7
(GSK)

5 mg/blister
for inhalation8

2 inhalations
(10 mg) once/d

Pediatric Dosage
Prophylaxis1
Treatment2

Cost3

75 mg PO
bid x 5d4,5

30-75 mg
PO once/d6

30-75 mg
PO bid6 x 5d

$110.60

2 inhalations
(10 mg) bid
x 5d

>5 yrs:
2 inhalations
(10 mg) once/d

>7 yrs:
2 inhalations
(10 mg) bid x 5d

59.00

1. For post-exposure prophylaxis in households, a 10-day course is recommended. For prophylaxis of exposures in institutions, the drug should be taken for at
least 2 weeks and continued for 1 week after the end of the outbreak. For prophylaxis during community outbreaks, oseltamivir has been shown to be effective
and safe when taken for up to 42 days, and zanamivir for up to 28 days. Some experts would use twice-daily therapeutic doses for post-exposure prophylaxis in
highly immunocompromised persons.
2. Hospitalized, critically ill, or immunocompromised patients may require longer treatment.
3. Approximate wholesale acquisition cost (WAC) for 5 days’ treatment at adult dosages. Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™)
January 5, 2014. Reprinted with permission by FDB, Inc. All rights reserved. ©2014. www.fdbhealth.com/policies/drug-pricing-policy. Actual retail prices may be
higher.

4. In patients with CrCl 10-30 mL/min, the dose should be 75 mg every other day or 30 mg once/d for prophylaxis and 75 mg once/d for treatment.
5. In adults with pneumonia or severe lower respiratory tract disease, some experts recommend 150 mg bid x 10 days for treatment (off-label).
6. Dose for children >1 yr old: <15 kg: 30 mg; 16-23 kg: 45 mg; 24-40 kg: 60 mg; >40 kg: 75 mg (once daily for prophylaxis and twice daily for treatment). Although
not FDA-approved for prophylaxis for children <1 year, the ACIP and CDC recommend that children 3 months to <1 year old receive 3 mg/kg once/day. The
FDA-approved dose for treatment of infants >2 weeks to <1 year old is 3 mg/kg bid. The American Academy of Pediatrics recommends 3.5 mg/kg once daily for
prophylaxis and twice daily for treatment for infants 9-11 months old.
7. Not recommended for use in patients with underlying respiratory disease such as asthma or COPD.
8. Available in a carton containing 5 rotadisks (each rotadisk contains four 5-mg blisters of the active drug in a lactose carrier) and a Diskhaler inhalation device.
Zanamivir should not be used in a nebulizer.

Resistance can occur to oseltamivir,7 especially in
immunocompromised patients with prolonged viral
shedding, but recently almost all of the circulating
influenza A and B viruses tested by the CDC have
been susceptible to both oseltamivir and zanamivir.
The rare oseltamivir-resistant isolates have remained
susceptible to zanamivir.
Adverse Effects – Nausea, vomiting, and headache
are the most common adverse effects of oseltamivir;
taking the drug with food may reduce the incidence of
nausea and vomiting. Neuropsychiatric events including self-injury and delirium have occurred in some
patients, particularly children treated with oseltamivir,
but it is not clear that the drug was the cause of these
events.8 Bronchospasm can occur with inhaled zanamivir; the drug should not be used in patients with underlying airway disease. Neuraminidase inhibitors administered within 48 hours before or <2 weeks after administration of the live-attenuated intranasal influenza
vaccine (FluMist Quadrivalent) may interfere with the
vaccine’s efficacy.
Formulations – Oral oseltamivir can be administered
safely and effectively by nasogastric tube in critically ill
patients.9 Zanamivir, which is available in an IV formulation on a compassionate use basis from the manufacturer (GSK: 1-877-626-8019), has been used successfully to treat some severely ill patients with proven or
suspected oseltamivir resistance.10

INDICATIONS FOR TREATMENT — Even healthy persons with uncomplicated influenza can benefit from treatment with antiviral drugs. Treatment is recommended as

soon as possible for patients with influenza signs and
symptoms who are at high risk for complications, including children <2 years old, persons <19 years old receiving
long-term aspirin therapy, adults >65 years old, morbidly
obese patients (BMI >40), women who are pregnant or
<2 weeks postpartum, persons of American Indian/Alaska Native heritage, residents of nursing homes and other
chronic care facilities, and persons of any age who have
certain chronic medical conditions11 or are immunosuppressed. Treatment is also recommended for patients with
suspected or confirmed influenza who show signs of clinical deterioration, develop symptoms of lower respiratory
tract infection, or require hospitalization.
INDICATIONS FOR CHEMOPROPHYLAXIS — Chemoprophylaxis with antiviral drugs is not recommended
for healthy persons exposed to influenza. It can be considered for unvaccinated persons (or those unlikely to
respond to vaccination) at high risk for complications of
the disease, for unvaccinated healthcare workers who
come into close contact with a person with confirmed
or suspected influenza during the infectious period (24
hours before onset of fever to 24 hours after its resolution), and to help control outbreaks in nursing homes.
When indicated, chemoprophylaxis should be started
within 48 hours after exposure to the virus.
PREGNANCY — Pregnant women with influenza are at
high risk for complications, including death. Even though
oseltamivir and zanamivir are both classified as category C (risk cannot be ruled out) for use during pregnancy,
prompt treatment with one of these antiviral medications
is recommended. Chemoprophylaxis can be considered

The Medical Letter • Volume 56 • Issue 1434 • January 20, 2014

7

for pregnant (or <2 weeks postpartum) women who
have had close contact with someone likely to have
been infected with influenza. Clinical experience during
pregnancy has been most extensive with oseltamivir.
CONCLUSION — Chemoprophylaxis with antiviral drugs
is not recommended for healthy persons exposed to influenza. A neuraminidase inhibitor, either oseltamivir (Tamiflu) or zanamivir (Relenza), remains the drug of choice
for treatment of patients with influenza. Oseltamivir is preferred for treatment of pregnant women. □
1. Influenza vaccine for 2013-2014. Med Lett Drugs Ther 2013;
55:73.
2. AE Fiore et al. Antiviral agents for the treatment and chemoprophylaxis of influenza – recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR Recomm Rep 2011;
60:1.
3. SA Harper et al. Seasonal influenza in adults and children – diagnosis, treatment, chemoprophylaxis, and institutional outbreak
management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 2009; 48:1003.
4. JK Louie et al. Neuraminidase inhibitors for critically ill children
with influenza. Pediatrics 2013; 132:e1539.
5. N Lee et al. Outcomes of adults hospitalized with severe influenza. Thorax 2010; 65:510.
6. JK Louie et al. Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1) pdm09. Clin Infect Dis
2012; 55:1198.
7. QM Le et al. A community cluster of oseltamivir-resistant cases of
2009 H1N1 influenza. N Engl J Med 2010; 362:86.
8. S Toovey et al. Post-marketing assessment of neuropsychiatric
adverse events in influenza patients treated with oseltamivir: an
updated review. Adv Ther 2012; 29:826.
9. RE Ariano et al. Enteric absorption and pharmacokinetics of oseltamivir in critically ill patients with pandemic (H1N1) influenza.
CMAJ 2010; 182:357.
10. AH Gaur et al. Intravenous zanamivir for oseltamivir-resistant
2009 H1N1 influenza. N Engl J Med 2010; 362:88.
11. CDC. Influenza antiviral medications: summary for clinicians.

Available at www.cdc.gov/flu/professionals/antivirals/summaryclinicians.htm. Accessed January 6, 2014.

IN BRIEF

Coming Soon in The Medical Letter:
Perampanel (Fycompa) for Epilepsy
Two Drugs for Psoriatic Arthritis
In Brief: Rosiglitazone (Avandia) Unbound
Coming Soon in Treatment Guidelines:
Drugs for HIV Infection
Drugs for Diabetes

The Medical Letter

®

On Drugs and Therapeutics
EDITOR IN CHIEF: Mark Abramowicz, M.D.
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EDITOR: Jean-Marie Pflomm, Pharm.D.
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Jules Hirsch, M.D., Rockefeller University
David N. Juurlink, BPhm, M.D., Ph.D., Sunnybrook Health Sciences Centre

Richard B. Kim, M.D., University of Western Ontario
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Sandip K. Mukherjee, M.D., F.A.C.C., Yale School of Medicine
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1. In brief: ponatinib (Iclusig) marketing and sales suspended. Med
Lett Drugs Ther 2013; 55:93.
2. FDA. FDA drug safety communication: FDA requires multiple
new safety measures for leukemia drug Iclusig; company expected to resume marketing. Available at www.fda.gov/drugs/
drugsafety/ucm379554.htm. Accessed January 10, 2014.

8

The Medical Letter • Volume 56 • Issue 1434 • January 20, 2014


The Medical Letter

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Online Continuing Medical Education
To take CME exams and earn credit, go to:
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Issue 1434 Questions
(Correspond to questions #7-12 in
Comprehensive Exam #70, available July 2014)

Sofosbuvir (Sovaldi) for Chronic Hepatitis C
1.

Sofosbuvir has potent activity against hepatitis C genotypes:
a. 1 and 2 only
b. 1, 2, 3, and 4
c. 1 and 3 only
d. 1-6

2.

In patients with HCV genotype 1 infection, treatment with
sofosbuvir rather than a protease inhibitor has been associated with:
a. a shorter duration of treatment with interferon
b. a higher sustained virologic response rate
c. a shorter duration of treatment with ribavirin
d. all of the above

3.

The approximate wholesale acquisition cost of a single tablet
of sofosbuvir is:
a. $18
b. $92
c. $250
d. $1000

Antiviral Drugs for Influenza 2013-2014
4.

In mild influenza illness, treatment with a neuraminidase inhibitor
started within 48 hours after the onset of illness can:
a. decrease the duration of symptoms
b. decrease the duration of fever
c. reduce the risk of pneumonia
d. all of the above

5.

Among circulating influenza A and B strains tested recently by the CDC:
a. oseltamivir-resistant strains have been common
b. oseltamivir-resistant strains have also been resistant
to zanamivir
c. rare oseltamivir-resistant isolates have remained
susceptible to zanamivir
d. none of the above

6.

A gravida 3, para 2, 32-year-old woman beginning the 14th
week of pregnancy was exposed to a family member with
confirmed influenza and now has had fever for 24 hours. She says
she does not want any treatment because she does not want
to risk harming her baby. You could tell her that:
a. the drugs approved for treatment of influenza have
been proven to be safe for use in pregnancy
b. influenza is not especially dangerous for pregnant women
c. pregnant women with influenza are at high risk of
complications, including death

d. clinical experience of safety during pregnancy has
been most extensive with zanamivir

ACPE UPN: Per Issue Exam: 0379-0000-14-434-H01-P; Release: January 20, 2014, Expire: January 20, 2015
Comprehensive Exam 70: 0379-0000-14-070-H01-P; Release: July 2014, Expire: July 2015

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credit (1.3 CEU).
The American Academy of Nurse Practitioners (AANP) and the American Academy of Physician Assistants
(AAPA) accept AMA Category 1 credit for the Physician’s Recognition Award from organizations accredited by the
ACCME.
This activity, being ACCME (AMA) approved, is acceptable for Category 2-B credit by the American Osteopathic
Association (AOA).
Physician Assistants: The National Commission on Certification of Physician Assistants (NCCPA) accepts AMA
PRA Category 1 Credit(s)™ from organizations accredited by ACCME. NCCPA also accepts AAFP Prescribed credits
for recertification. The Medical Letter is accredited by both ACCME and AAFP.
Physicians in Canada: Members of The College of Family Physicians of Canada are eligible to receive Mainpro-M1
credits (equivalent to AAFP Prescribed credits) as per our reciprocal agreement with the American Academy of Family
Physicians.
Physicians, nurse practitioners, pharmacists, and physician assistants may earn 1 credit with this exam.
MISSION:
The mission of The Medical Letter’s Continuing Medical Education Program is to support the professional development
of healthcare professionals including physicians, nurse practitioners, pharmacists, and physician assistants by providing
independent, unbiased drug information and prescribing recommendations that are free of industry influence. The program
content includes current information and unbiased reviews of FDA-approved and off-label uses of drugs, their mechanisms
of action, clinical trials, dosage and administration, adverse effects, and drug interactions. The Medical Letter delivers
educational content in the form of self-study material.
The expected outcome of the CME Program is to increase the participant’s ability to know, or apply knowledge into

practice after assimilating, information presented in materials contained in The Medical Letter.
The Medical Letter will strive to continually improve the CME program through periodic assessment of the program and
activities. The Medical Letter aims to be a leader in supporting the professional development of healthcare professionals
through Core Competencies by providing continuing medical education that is unbiased and free of industry influence.
The Medical Letter is supported solely by subscription fees and accepts no advertising, grants, or donations.
GOAL:
Through this program, The Medical Letter expects to provide the healthcare community with unbiased, reliable, and
timely educational content that they will use to make independent and informed therapeutic choices in their practice.
LEARNING OBJECTIVES:
Activity participants will read and assimilate unbiased reviews of FDA-approved and off-label uses of drugs and
other treatment modalities. Activity participants will be able to select and prescribe, or confirm the appropriateness
of the prescribed usage of, the drugs and other therapeutic modalities discussed in The Medical Letter with specific
attention to clinical trials, pathophysiology, dosage and administration, drug metabolism and interactions, and patient
management. Activity participants will make independent and informed therapeutic choices in their practice.
Upon completion of this program, the participant will be able to:
1. Review the efficacy and safety of sofosbuvir (Sovaldi) for treatment of chronic hepatitis C.
2. Discuss the recommendations for antiviral chemoprophylaxis and treatment of seasonal influenza.
Privacy and Confidentiality: The Medical Letter guarantees our firm commitment to your privacy. We do not sell any
of your information. Secure server software (SSL) is used for commerce transactions through VeriSign, Inc. No credit
card information is stored.
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Microsoft IE 6.0+, Mozilla Firefox 2.0+ or any other compatible Web browser. Dial-up/high-speed connection.
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