Typhoid Vaccine (Monograph)

Brand names: Typhim Vi, Vivotif
Drug class: Vaccines
ATC class: J07AP01
VA class: IM100

Medically reviewed by Drugs.com on Jul 14, 2023. Written by ASHP.

Introduction

Commercially available in US as an oral live, attenuated vaccine (typhoid vaccine live oral Ty21a; Vivotif) and as a parenteral inactivated Vi polysaccharide vaccine (typhoid Vi polysaccharide vaccine; Typhim Vi). Other typhoid vaccines (e.g., inactivated whole-cell vaccines, inactivated protein-conjugated Vi polysaccharide vaccines) may be available in other countries.

Uses for Typhoid Vaccine

Prevention of Typhoid Fever

Prevention of typhoid fever in US travelers planning to visit areas with a recognized risk of exposure to Salmonella enterica serovar Typhi.

Prevention of typhoid fever in individuals with intimate exposure (e.g., household contact) to a known typhoid carrier.

Prevention of typhoid fever in laboratory personnel with frequent contact with Salmonella Typhi bacilli.

Typhoid fever is a potentially severe and occasionally life-threatening, febrile, enteric illness caused by Salmonella Typhi. Usually acquired by ingestion of food and/or water contaminated with feces from individuals who have typhoid fever or are chronic typhoid carriers. Overall case-fatality rate in patients who receive early and appropriate antibacterial treatment is typically <1%; if left untreated, case-fatality rate may be ≥10–20%. Approximately 2–4% of individuals with acute typhoid fever develop a chronic carrier state.

Typhoid fever is uncommon in the US, but endemic in many less well-developed areas of the world that have poor sanitation and primitive water systems. About 22 million cases of typhoid fever and about 200,000 typhoid-related deaths occur annually worldwide. In the US, about 300–400 confirmed cases of typhoid fever are reported annually, almost all in recent travelers to other countries (most commonly southern Asia).

USPHS Advisory Committee on Immunization Practices (ACIP) and CDC state that routine vaccination against typhoid fever not recommended for individuals residing in the US, but preexposure vaccination is recommended for those at high risk of exposure to Salmonella Typhi.

When vaccination against typhoid fever indicated, either typhoid vaccine live oral Ty21a or typhoid Vi polysaccharide vaccine can be used unless contraindicated. Consider that the vaccines have different contraindications (see Contraindications under Cautions) and different minimum age limits for use in children (see Pediatric Use under Cautions). Other factors to consider when selecting a typhoid vaccine include immunization schedule, response time, patient compliance, storage facilities, and immunocompetence of the vaccinee (see Warnings/Precautions under Cautions). Because typhoid vaccine live oral Ty21a is self-administered over a 1-week period and compliance errors (i.e., dosing errors, improper storage) may occur, typhoid Vi polysaccharide vaccine may be preferred if compliance is likely to be a problem.

Efficacy of typhoid vaccine live oral Ty21a and typhoid Vi polysaccharide vaccine appear to be comparable when administered as recommended; neither vaccine is expected to provide protection against typhoid fever in all vaccine recipients.

Typhoid vaccines will not provide protection against S. enterica serovar Paratyphi or any Salmonella other than Salmonella Typhi and will not provide protection against other bacteria known to cause enteric disease.

Typhoid vaccines are not used for treatment of typhoid fever and should not be used in individuals with acute Salmonella Typhi infection or in chronic typhoid carriers.

There is no evidence to support use of typhoid vaccine to control common source outbreaks or disease following natural disasters or in individuals attending rural summer camps.

Preexposure Vaccination Against Typhoid Fever in High-risk Groups

Travelers to areas with a recognized risk of exposure to Salmonella Typhi should be vaccinated against typhoid fever. The disease is endemic in many less well-developed areas of the world that have poor sanitation and primitive water systems.

CDC recommends typhoid vaccination for travelers to many Asian, African, and Latin American countries, but no longer recommends typhoid vaccination for travelers to certain Eastern European and certain Asian countries. In recent years, most US cases of typhoid fever reported in individuals who had traveled to southern Asia (especially the Indian subcontinent including India, Bangladesh, or Pakistan) or Africa.

Although risk is greatest for travelers who have prolonged exposure to possibly contaminated food and beverages in areas with persistent typhoid epidemics or in smaller cities and villages or rural areas outside usual tourist itinerary, even short-term travel (<1 week) to high-incidence areas is associated with risk for typhoid fever.

In addition to vaccination, individuals traveling to areas with risk of typhoid fever should use caution in selecting food and water in these areas since the vaccines are not 100% effective and vaccine-induced immunity can be overwhelmed by a large inoculum of Salmonella Typhi. (See Limitations of Vaccine Effectiveness under Cautions.)

Vaccination against typhoid fever and other precautions (safe food and water precautions, frequent handwashing) are especially important for travelers to high-risk areas because fluoroquinolone-resistant and multidrug-resistant Salmonella Typhi have become common or are reported with increasing frequency in many regions of the world (e.g., Indian subcontinent, Africa).

The most recent information regarding geographic areas with a recognized risk of typhoid fever and additional information on vaccination and other precautions for prevention of typhoid fever are available from CDC at [Web] and [Web].

Close contacts of chronic typhoid carriers with intimate exposure (e.g., household contact) to a documented Salmonella Typhi chronic carrier (defined as excretion of Salmonella Typhi in urine or stool for >1 year) should be vaccinated against typhoid fever.

Laboratory personnel routinely exposed to cultures of Salmonella Typhi or specimens containing the bacilli or who work in laboratory environments where these cultures or specimens are routinely handled should be vaccinated against typhoid fever.

Related/similar drugs

Vivotif, Typhim Vi

Typhoid Vaccine Dosage and Administration

Administration

Typhoid vaccine live oral Ty21a: Administer orally.

Typhoid Vi polysaccharide vaccine: Administer by IM injection.

Oral Administration

Typhoid Vaccine Live Oral Ty21a

Administer orally as enteric-coated capsules.

Take with cool or lukewarm (≤37°C [body temperature]) liquid (water) approximately 1 hour before a meal.

Swallow whole immediately after placement in mouth; do not chew.

Do not administer to individuals with acute GI illness or persistent diarrhea or vomiting. (See Acute Illness under Cautions.)

Capsules must be refrigerated (2–8°C) until just prior to administration. It is essential that remaining capsules be placed back in the refrigerator after each dose until the 4-dose vaccination series is completed. (See Storage under Stability.)

IM Administration

Typhoid Vi Polysaccharide Vaccine

Administer IM undiluted. Do not mix with any other vaccine.

Should appear clear and colorless; discard if turbid or contains particulates.

IM injections preferably should be made into the deltoid area in adults and into the deltoid or anterolateral thigh in children.

Do not inject into gluteal area or any area where there may be a nerve trunk.

To ensure delivery into muscle, make IM injections at a 90° angle to the skin using a needle length appropriate for individual's age and body mass.

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination; such reactions occur most frequently in adolescents and young adults. Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination. If syncope occurs, observe patient until symptoms resolve.

If multiple vaccines are administered during a single health-care visit, give each parenteral vaccine using different syringe and different injection site. Separate injection sites by ≥1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.

Dosage

Dosing schedules (i.e., number of doses, timing prior to potential exposure) differ between typhoid vaccine live oral Ty21a and typhoid Vi polysaccharide vaccine. Follow dosage recommendations for the specific preparation used.

Pediatric Patients

Preexposure Vaccination Against Typhoid Fever in High-risk Groups

Children and Adolescents ≥6 Years of Age (Typhoid Vaccine Live Oral Ty21a; Vivotif)

Oral

Primary immunization consists of 4 doses. Each dose consists of one enteric-coated capsule.

Give first dose on a selected date; give second, third, and fourth doses every other day after first dose over a 1-week period (e.g., Sunday, Tuesday, Thursday, and Saturday or day 0, 2, 4, and 6).

Complete the 4-dose regimen ≥1 week prior to potential exposure to Salmonella Typhi.

Duration of response and optimum booster schedule not established. Revaccination with same 4-dose regimen recommended every 5 years in those with continuing or repeated exposure to Salmonella Typhi. (See Duration of Immunity under Cautions.)

Data not available regarding use as a booster in individuals previously vaccinated with typhoid Vi polysaccharide vaccine or any other typhoid vaccine.

Children and Adolescents ≥2 Years of Age (Typhoid Vi Polysaccharide Vaccine; Typhim Vi)

IM

Primary immunization consists of a single 25-mcg dose. The dose consists of 0.5 mL from the commercially available prefilled single-dose syringe or multidose vial.

Administer the vaccine dose ≥2 weeks prior to potential exposure to Salmonella Typhi.

Duration of response and optimum booster schedule not established. Revaccination with a single 0.5-mL dose recommended every 2 years in those with continuing or repeated exposure to Salmonella Typhi. (See Duration of Immunity under Cautions.)

Data not available regarding use as a booster in individuals previously vaccinated with typhoid vaccine live oral Ty21a or any other typhoid vaccine.

Adults

Preexposure Vaccination Against Typhoid Fever in High-risk Groups

Adults ≥18 Years of Age (Typhoid Vaccine Live Oral Ty21a; Vivotif)

Oral

Primary immunization consists of 4 doses. Each dose consists of one enteric-coated capsule.

Give first dose on a selected date; give second, third, and fourth doses every other day after first dose over a 1-week period (e.g., Sunday, Tuesday, Thursday, and Saturday or day 0, 2, 4, and 6).

Complete the 4-dose regimen ≥1 week prior to potential exposure to Salmonella Typhi.

Duration of response and optimum booster schedule not established. Revaccination with same 4-dose regimen recommended every 5 years in those with continuing or repeated exposure to Salmonella Typhi. (See Duration of Immunity under Cautions.)

Data not available regarding use as a booster in individuals previously vaccinated with typhoid Vi polysaccharide vaccine or any other typhoid vaccine.

Adults ≥18 Years of Age (Typhoid Vi Polysaccharide Vaccine; Typhim Vi)

IM

Primary immunization consists of a single 25-mcg dose. The dose consists of 0.5 mL from the commercially available prefilled single-dose syringe or multidose vial.

Administer the vaccine dose ≥2 weeks prior to potential exposure to Salmonella Typhi.

Duration of response and optimum booster schedule not established. Revaccination with a single 0.5-mL dose recommended every 2 years in those with continuing or repeated exposure to Salmonella Typhi. (See Duration of Immunity under Cautions.)

Data not available regarding use as a booster in individuals previously vaccinated with typhoid vaccine live oral Ty21a or any other typhoid vaccine.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Typhoid Vaccine

Contraindications

• Typhoid vaccine live oral Ty21a: Hypersensitivity to any component of the vaccine or enteric-coated capsule.

• Typhoid Vi polysaccharide vaccine: Hypersensitivity to any ingredient in the formulation.

Warnings/Precautions

Warnings

Individuals with Altered Immunocompetence

Typhoid vaccine live oral Ty21a: Contains live, attenuated bacteria and should not be used in individuals with congenital or acquired immunodeficiencies, including HIV-infected individuals and those receiving immunosuppressive therapy. Manufacturer states safety not established in individuals deficient in ability to mount a humoral or cell-mediated immune response; do not use in such individuals, regardless of any possible benefits. May be used in healthy immunocompetent individuals who reside in a household with immunocompromised patients.

Typhoid Vi polysaccharide vaccine: May be used in individuals with altered immunocompetence, including HIV-infected patients; those who are severely immunocompromised because of congenital immunodeficiency, leukemia, lymphoma, aplastic anemia, generalized malignancy, or therapy with alkylating agents, antimetabolites, radiation, or corticosteroids; patients with solid organ transplants or chronic immunosuppressive therapy; or patients with asplenia, renal failure, diabetes mellitus, alcoholism, or alcoholic cirrhosis.

ACIP states that recommendations concerning use of typhoid Vi polysaccharide vaccine in individuals with altered immunocompetence are the same as those for individuals who are not immunocompromised. However, immunization may be less effective in individuals with altered immunocompetence since antibody responses to vaccine antigens may be reduced in such individuals.

Sensitivity Reactions

Hypersensitivity Reactions

Allergic reactions (e.g., anaphylactic shock, pruritus, rash, urticaria, difficulty breathing, hypotension, serum sickness) have been reported rarely with typhoid vaccines.

Prior to administration, take all known precautions to prevent adverse reactions, including a review of patient’s history with respect to health status and possible sensitivity to the vaccine, similar vaccines, or vaccine components.

Epinephrine and other appropriate agents should be readily available in case anaphylaxis or other serious allergic reaction occurs.

General Precautions

Transmission of Vaccine Bacteria

Typhoid vaccine live oral Ty21a: Contains live, attenuated bacteria and the vaccine strain may be shed transiently in the stool of vaccinees. Secondary transmission of the vaccine bacteria not documented.

Acute Illness

Decision whether to administer or delay vaccination in an individual with a current or recent febrile illness depends largely on the severity of symptoms and etiology of the illness.

Typhoid vaccine live oral Ty21a: Manufacturer states do not administer to individuals with acute febrile illness or acute GI illness (e.g., diarrhea or vomiting). The oral vaccine requires replication in the gut; may not be effective if given during GI illness or at time of ongoing diarrhea.

Typhoid Vi polysaccharide vaccine: Manufacturer states may be deferred in individuals with acute infection or febrile illness, unless withholding the vaccine poses greater risk.

ACIP states that minor acute illness, such as mild upper respiratory tract infection (with or without fever) generally does not preclude vaccination, but defer vaccination in individuals with moderate or severe acute illness (with or without fever) until they have recovered from the acute phase of the illness.

Limitations of Vaccine Effectiveness

Typhoid vaccines may not protect all vaccine recipients against typhoid fever. Vaccine-induced immunity can be overwhelmed by large inoculum of Salmonella Typhi.

Regardless of vaccination status, take precautions against exposure to Salmonella Typhi (e.g., safe food and water precautions, frequent handwashing).

Typhoid vaccine live oral Ty21a: It is essential that all 4 doses be administered as recommended. Complete the 4-dose regimen ≥1 week before potential exposure to Salmonella Typhi. (See Dosage under Dosage and Administration.)

Typhoid Vi polysaccharide vaccine: Administer dose ≥2 weeks before potential exposure to Salmonella Typhi. (See Dosage under Dosage and Administration.)

Will not provide protection against Salmonella Paratyphi or any Salmonella other than Salmonella Typhi and will not provide protection against other bacteria that cause enteric disease.

Not used for treatment of typhoid fever. Do not use in individuals with acute Salmonella Typhi infection or in chronic typhoid carriers.

No evidence to support use of typhoid vaccine to control common source outbreaks or disease following natural disasters or in individuals attending rural summer camps.

Duration of Immunity

Duration of protection after primary immunization with typhoid vaccines and need for revaccination or subsequent doses not fully determined.

Typhoid vaccine live oral Ty21a: Some evidence suggests that protection against typhoid fever persists for at least 5 years (possibly 7 years) after completion of 4-dose vaccination series. Revaccination recommended every 5 years in those with continuing or repeated exposure to Salmonella Typhi.

Typhoid Vi polysaccharide vaccine: Limited data indicate that antibody titers remain elevated for at least 12 months after a single dose in children 5–15 years of age residing in typhoid-endemic areas and for at least 36 months in healthy US adults. Revaccination recommended every 2 years in individuals with continuing or repeated exposure to Salmonella Typhi.

Improper Storage and Handling

Improper storage or handling of vaccines may reduce vaccine potency resulting in reduced or inadequate immune response in vaccinees.

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.

Typhoid vaccine live oral Ty21a: Unstable when exposed to ambient temperatures and must be shipped and stored at 2–8°C. Do not administer if it has been mishandled or has not been stored at recommended temperatures. (See Storage under Stability.)

Typhoid Vi polysaccharide vaccine: Not adversely affected by elevated temperatures (e.g., those that occur in tropical areas). (See Storage under Stability.) May be preferred in situations in which continuous refrigeration cannot be ensured.

If there are concerns about mishandling, contact the manufacturer or state or local immunization or health departments for guidance on whether the vaccine is usable.

Specific Populations

Pregnancy

Data not available regarding use of typhoid vaccines in pregnant women.

Typhoid vaccine live oral Ty21a: Use during pregnancy only if clearly needed. ACIP states that live vaccines generally are contraindicated during pregnancy.

Typhoid Vi polysaccharide vaccine: Use during pregnancy only when clearly needed. Manufacturer suggests that delaying vaccination until second or third trimester is a reasonable precaution to minimize possibility of teratogenicity.

Lactation

Data not available regarding use of typhoid vaccines in nursing women.

Typhoid vaccine live oral Ty21a: Not known whether distributed into milk. ACIP states that, although live vaccines do multiply in the woman’s body, most have not been shown to distribute into breast milk.

Typhoid Vi polysaccharide vaccine: Not known whether distributed into milk. Manufacturer states use with caution. Although specific data not available, ACIP states breast-feeding generally not a contraindication for inactivated vaccines since inactivated organisms in the vaccines do not multiply within the body and such vaccines appear to pose no special problems for the woman or her nursing infant.

Pediatric Use

Typhoid vaccine live oral Ty21a: Safety and efficacy not established in children <6 years of age; not indicated in this age group.

Typhoid Vi polysaccharide vaccine: Safety and efficacy not established in children <2 years of age. As with other polysaccharide vaccines, antibody response may be inadequate in children <2 years of age. Manufacturer states a decision whether to use the vaccine in children <2 years of age^{† [off-label]} depends on risk incurred by the child on the basis of the epidemiological context.

Common Adverse Effects

Typhoid vaccine live oral Ty21a: Abdominal pain, nausea, headache, fever, diarrhea, vomiting, rash.

Typhoid Vi polysaccharide vaccine: Injection site reactions (pain, tenderness, erythema, induration), malaise/generalized aches, headache, myalgia/muscle aches, nausea, diarrhea, feverishness, decreased activity/lethargy, vomiting.

Drug Interactions

Other Vaccines

Typhoid vaccine live oral Ty21a: May be administered concurrently with or at any interval before or after inactivated vaccines, recombinant vaccines, polysaccharide vaccines, toxoids, or parenteral live vaccines. If use of the live, attenuated typhoid vaccine is warranted, do not delay because of administration of other live virus vaccines (injectable or intranasal).

Typhoid Vi polysaccharide vaccine: Specific interaction studies not available. Because it is an inactivated vaccine, it generally can be administered concurrently with (using different syringes and different injection sites) or at any interval before or after inactivated vaccines, recombinant vaccines, polysaccharide vaccines, toxoids, or live vaccines.

Specific Drugs

Stability

Storage

Oral

Capsules

Typhoid vaccine live oral Ty21a: 2–8°C in a dry place protected from light.

Must be shipped and stored only at 2–8°C. Potency adversely affected by exposure to temperatures exceeding 2–8°C.

Any remaining capsules must be placed back in a refrigerator after each dose until 4-dose vaccination series completed.

Does not contain thimerosal or any other preservatives.

Parenteral

Injection, for IM Use

Typhoid Vi polysaccharide vaccine: 2–8°C. Do not freeze.

Does not contain thimerosal, but contains phenol 0.25% as a preservative.

Actions

• Typhoid vaccine live oral Ty21a: Contains live Salmonella Typhi of the attenuated Ty21a strain and is commercially available for oral administration as enteric-coated capsules.

• Typhoid Vi polysaccharide vaccine: Sterile solution of purified cell surface Vi (“virulence”) polysaccharide extracted from Salmonella Typhi of the Ty2 strain in isotonic phosphate-buffered 0.9% sodium chloride for IM injection.

• Principal mode of transmission of typhoid infection is enteric (i.e., through fecal contamination and oral ingestion); most commonly acquired through food and/or water contaminated with feces from an infected person or a chronic typhoid carrier. Onset of illness usually gradual with signs and symptoms such as high fever, headache, malaise, anorexia, lethargy, abdominal pain and tenderness, splenomegaly, hepatomegaly, and rose spots. Invasive infection and mortality from typhoid infection typically higher in infants, elderly individuals, and those with immunosuppressive conditions, hemoglobinopathies, malignancies, and HIV infection.

• Efficacy of typhoid vaccine live oral Ty21a and typhoid Vi polysaccharide vaccine for prevention of typhoid fever appear to be comparable when the vaccines are administered as recommended; neither vaccine is expected to provide protection against typhoid fever in all vaccine recipients.

• Data obtained principally from studies involving populations where typhoid is endemic indicate that both vaccine types provide protection against typhoid fever in approximately 50–80% of vaccinees. Experience in individuals from areas without endemic disease (e.g., US residents) who travel to endemic regions is limited; however, seroconversion rates following primary immunization with typhoid vaccine live oral Ty21a or typhoid Vi polysaccharide vaccine in such individuals appear to be comparable to or higher than those attained in residents of endemic areas.

• Typhoid vaccine live oral Ty21a: Stimulates active immunity to typhoid fever by inducing production of both intestinal and serum antibodies and cell-mediated immune responses. Following primary immunization, serum titers of antibodies to the O antigen of Salmonella Typhi appear to correlate with protection against typhoid fever. Following oral administration, the vaccine strain replicates in the gut and may elicit a local immune response in the intestinal tract. Ability of Salmonella Typhi to elicit a protective immune response depends on possession by the bacilli of a complete lipopolysaccharide. The vaccine strain (Ty21a) in the oral vaccine is limited in its ability to produce a complete lipopolysaccharide; however, sufficient complete lipopolysaccharide apparently is produced to elicit an adequate immune response.

• Typhoid Vi polysaccharide vaccine: Stimulates active immunity to Salmonella Typhi by inducing production of antibodies to the Vi antigen. The Vi antigen is considered to be a virulence factor of Salmonella Typhi, apparently protecting the organism from the actions of complement; antibodies to the Vi antigen confer protection against typhoid fever.

• Reduced immune responses to typhoid vaccine and lower antibody titers may occur in immunocompromised individuals (e.g., HIV-infected individuals, those with leukemia, lymphoma, or generalized malignancy, those receiving immunosuppressive therapy).

• Minimum titer of anti-typhoid antibodies conferring protection against typhoid following vaccination with typhoid vaccine not established.

Advice to Patients

• Prior to administration of typhoid vaccine, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient's legal representative (VISs are available at [Web]).

• Advise patient and/or patient's parent or guardian of the risks and benefits of vaccination with typhoid vaccine.

• Advise patient and/or patient's parent or guardian that routine typhoid vaccination not recommended in the US, but may be used to prevent typhoid in individuals at high risk of exposure to typhoid (e.g., certain travelers, household contacts of a typhoid carrier, certain laboratory personnel).

• Advise patient and/or patient's parent or guardian that oral or parenteral typhoid vaccine may not provide protection in all vaccinees. In addition to vaccination, importance of taking other precautions against exposure to typhoid fever (e.g., safe food and water precautions, frequent handwashing).

• When using typhoid vaccine live oral Ty21a, importance of completing 4-dose vaccination series as directed (i.e., dose every other day for 4 doses). Advise vaccinees to swallow capsules whole with cool or lukewarm liquid on an empty stomach 1 hour before a meal and store remaining capsules in the refrigerator until entire 4-dose regimen is completed. Importance of completing the vaccination series ≥1 week prior to possible exposure to typhoid fever and importance of revaccination with the 4-dose series every 5 years if at continued or repeated risk of exposure.

• When using typhoid Vi polysaccharide vaccine, importance of receiving the dose ≥2 weeks prior to possible exposure to typhoid fever and importance of revaccination every 2 years if at continued or repeated risk of exposure.

• Importance of notifying clinicians if patient is immunocompromised since oral typhoid vaccine should not be used in individuals with a weakened immune system (e.g., leukemia, lymphoma, HIV/AIDS) or in those receiving treatment that may weaken the immune system (e.g., high-dose corticosteroids). (See Individuals with Altered Immunocompetence under Cautions.)

• Importance of informing clinicians of a history of allergic reactions to typhoid vaccine or any ingredient in the formulation.

• Importance of informing clinicians if any adverse reactions (including allergic reactions) occur with typhoid vaccine. Clinicians or individuals can report any adverse reactions that occur following vaccination to the Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or [Web]. Also can be reported to the manufacturer at 800-533-5899 (PaxVax) or 800-822-2463 (Sanofi Pasteur).

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses. Importance of notifying clinicians if receiving therapy with anti-infective or antimalarial agents. (See Specific Drugs under Interactions.)

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing 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.

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