P&T News: March 2001

Tetanus Toxoid Shortage

Joan M. Murhammer, R.Ph., Clinical Pharmacist, Drug Information Center, Department of Pharmaceutical Care
Peer Review Status: Internally Peer Reviewed by Stanley Perlman, M.D., Professor, Department of Pediatrics

The available products which contain tetanus toxoids and their indications for use include:^3-5

Diphtheria and Tetanus Toxoids, Adsorbed for Adult Use (Td) Adults and children (> 7 years of age) The preferred product for active immunization and for wound management. Tetanus Toxoid, Adsorbed (TT) Adults and children (> 7 years of age) For active immunization and for wound management in patients for whom the diphtheria component is contraindicated. Tetanus Toxoid, Fluid Adults and children (> 7 years of age) Patients with a rare reaction to the aluminum in the adsorbed product. Sometimes used for cell-mediated immunity testing. As an alternative to TT for active immunization and for wound management in patients when diphtheria is contraindicated. Diphtheria and Tetanus Toxoids, Adsorbed for Pediatric Use (DT) Children 6 weeks of age up to 7 years of age For routine childhood immunization when the pertussis component is contraindicated. Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine (DTaP) Children 6 weeks of age up to 7 years of age Preferred product for routine childhood immunizations.

The following information is provided to clarify when each tetanus immunization product should be used.

Combination tetanus and diphtheria products are preferred to tetanus toxoid alone for active immunization and in managing wounds because these products also enhance diphtheria protection.^3-5 The recommended products for active immunization and wound management are:

• Patients <7 years: DTaP ( diphtheria and tetanus toxoids and acellular pertussis vaccine); if pertussis is contraindicated: DT (diphtheria and tetanus toxoids, adsorbed for pediatric use);
• Adults and children >7 years: Td (diphtheria and tetanus toxoids, adsorbed for adult use).

After the primary immunization series is completed, patients who suffer wounds that are severe/contaminated (tetanus-prone) should receive a Td booster dose if it has been more than 5 years since the previous tetanus dose. Severe or contaminated wounds that are considered tetanus-prone include: wounds contaminated with dirt, feces, and saliva; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns, and frostbite. For clean, minor wounds at low risk for tetanus, a Td booster is indicated if more than 10 years have passed since the last tetanus dose.

For patients with an incomplete tetanus immunization series, unknown immunization history, or who are HIV positive,³ tetanus immune globulin (TIG) and Td or DT should be initiated for patients with severe/contaminated (tetanus-prone) wounds. Patients with clean/minor wounds should start the tetanus immunization series with Td vaccine.^3-5

Single-component tetanus toxoids as either the fluid or adsorbed product are only routinely recommended for use if there is a contraindication to the diphtheria component of the combination vaccine. Even if the Td shortage persists, immunization with these single-component products should be limited to patients with tetanus-prone wounds. Of the single-component vaccines, TT is preferred over tetanus toxoid, fluid. TT is also used when tetanus immune globulin (TIG) needs to be administered for passive immunization in unimmunized or incompletely immunized patients with a tetanus-prone wound. Tetanus toxoid, fluid should not be administered concurrently with tetanus immune globulin.⁴ The rate of seroconversion is essentially the same for TT and tetanus toxoid, fluid; however, TT induces more persistent antitoxin titers than tetanus toxoid, fluid. The only reason to use tetanus toxoid, fluid would be if a patient had a rare reaction to the aluminum in the adsorbed product. Tetanus toxoid, fluid is also sometimes used for cell-mediated immunity testing. Both tetanus products have the same dosage, administration, and adverse reactions. The total number of doses required for immunization does differ between the products. Full immunization with TT requires 3 doses, while tetanus toxoid, fluid requires 4 doses.⁴

The CDC recommendations for use of Td during the shortage are ranked in order from highest priority (1) to lowest priority (6) as follows:¹

1. Persons traveling to a country where the risk for diphtheria is high.* *Travelers to certain countries may be at substantial risk for exposure to toxigenic strains of C. diphtheriae, especially with prolonged travel, extensive contact with children, or exposure to poor hygiene. Based on surveillance data and consultation with the World Health Organization, countries with highest risk are: Africa -- Algeria, Egypt, and sub-Saharan Africa; Americas -- Brazil, Dominican Republic, Ecuador, and Haiti; Asia/Oceania -- Afghanistan, Bangladesh, Cambodia, China, India, Indonesia, Iran, Iraq, Laos, Mongolia, Myanmar, Nepal, Pakistan, Philippines, Syria, Thailand, Turkey, Vietnam, and Yemen; Europe -- Albania and all countries of the former Soviet Union. 2. Persons requiring tetanus vaccination for prophylaxis in wound management. 3. Persons who have received <3 doses of vaccine containing tetanus and diphtheria toxoids. 4. Pregnant women and persons at occupational risk for tetanus-prone injuries who have not been vaccinated with Td within the last 10 years. 5. Adolescents who have not been vaccinated with a vaccine containing tetanus and diphtheria toxoids within the last 10 years. 6. Adults who have not been vaccinated with Td within the last 10 years.

Prescribers are asked to follow the CDC's recommendations for prioritizing the use of available supplies of Td vaccine. If Td is not available, TT can be used as an alternative for persons >7 years of age who require immediate boosting with tetanus toxoids (e.g., wound management), or who are unlikely to return to clinic if vaccination is delayed. If TT is administered, patients and providers must weigh risks and benefits of subsequent vaccination with Td. Arthus-type reactions may occur among persons who receive multiple doses of tetanus toxoid, especially within short intervals (<10 years). On the other hand, if vaccination with Td is delayed for >10 years following TT administration, persons may be inadequately protected against diphtheria.¹

If the single-component vaccine is required, patients also receiving TIG should receive tetanus toxoid, adsorbed and patients not requiring TIG should receive tetanus toxoid, fluid until Td is back in full supply.^3-5

It is important to keep up with pediatric vaccinations, especially when immunizing children <2 years of age, to ensure adequate protection against diphtheria, tetanus, and pertussis.²

The tetanus toxoid shortage may last for 12 to 18 months.² For the current availability of tetanus-containing products at UIHC, please call the Pharmacy that serves your area or the Drug Information Center at 6-2600.

References:

1. http://www.cdc.gov/nip/news/td-shortage.htm (accessed February 28,2001).

2. http://www.ashp.org/shortage/tetanus-update.html (accessed February 28, 2001).

3. American Academy of Pediatrics. Pickering LK, ed. 2000 Redbook: Report of the Committee on Infectious Disease. 25th ed. Elk Grove Village, IL: American Academy of Pediatrics;2000.

4. McEvoy, GK. American Hospital Formulary System: Drug Information. Bethesda, MD: American Society of Health-Systems Pharmacists;2000.

5. ACP Task Force on Adult Immunization and Infectious Diseases Society of America. Guide for Adult Immunization. 3rd ed. Philadelphia, PA: North American College of Physicians;1994.

DRUGS ADDED TO STOCK

CASPOFUNGIN
Injection: 50 mg and 70 mg
Caspofungin (Cancidas® - Merck) is an injectable antifungal agent indicated for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (i.e., amphotericin B, amphotericin B lipid complex, and/or itraconazole).
Note: Caspofungin has been designated as a protocol drug. Criteria for the use of caspofungin include:

1) Documented invasive aspergillosis infection by culture, by histology, or by appropriate imaging studies and refractory to conventional amphotericin B treatment of > 1 gm and/or treatment with amphotericin B lipid complex.

2) Documented invasive aspergillosis infection by culture, by histology, or by appropriate imaging studies and intolerant of conventional amphotericin B and/or amphotericin B lipid complex (i.e., experienced a rise in serum creatinine to > 3.0 mg/dl; increase from baseline serum creatinine of > 1.5 mg/dl; or an estimated creatinine clearance of <25 ml/min/1.73m2).

3) Infection Diseases consult.

DOXERCALCIFEROL
Capsule: 2.5 mcg
Injection: 4 mcg
Doxercalciferol (Hectorol® - Bone Care International) is an analog of vitamin D that is indicated for the reduction of intact parathyroid hormone levels for the management of secondary hyperparathyroidism in patients undergoing chronic renal dialysis.

IRON SUCROSE
Injection: 100 mg vial
Iron sucrose injection (Venofer® - American Regent) is indicated for the treatment of iron deficiency anemia in patients undergoing chronic hemodialysis who are receiving supplemental erythropoietin therapy. It causes fewer hypersensitivity reactions than other injectable iron preparations, particularly iron dextran injection.

LEVONORGESTREL
Intrauterine Device
Levonorgestrel intrauterine device (Mirena® - Berlex) is indicated as a contraceptive device for up to 5 years duration.

DIDANOSINE DELAYED-RELEASE CAPSULES
The 125 mg, 200 mg, and 250 mg strengths of Videx EC® have been added to stock.

KETAMINE INJECTION
A 10 mg per ml concentration has been added to stock.

LEVETIRACETAM (KEPPRA®) TABLETS
A 750 mg tablet has been added to stock.

MAGNESIUM SULFATE (EPSOM SALT) CRYSTALS
A 120 gm bottle has been added to stock.

OSELTAMIVIR ORAL SOLUTION
A 60 mg per 5 ml oral solution has been added to stock.

ALBUTEROL PRESERVATIVE FREE INHALATION SOLUTION 0.083%, 3 ml (VENTOLIN NEBS®)
Discontinued by the manufacturer. Albuterol inhalation solution 0.083% with preservatives, 3 ml is available.

BIGGY® AGAR SLANTS
Discontinued due to low use. Other diagnostic measures for Candida are available.

CALCITRIOL INJECTION 2 mcg/1 ml INJECTION (CALCIJEX®)
Discontinued by the manufacturer. Calcitriol 1 mcg per 1 ml injection is available.

CARBINOXAMINE/PSEUDOEPHEDRINE SYRUP 120 ml (RONDEC®)
Reformulated product now duplicates Dimetapp Elixir®.

CASTELLANI PAINT WITHOUT BASIC FUCHSIN
Discontinued due to low use. Castellani Paint with basic fuchsin is available.

CHOLERA VACCINE
Discontinued by the manufacturer.

DIHYDROTACHYSTEROL 0.125 mg TABLETS
Discontinued due to low use. Dihydrotachysterol 0.2 mg tablets and oral solution are available.

EPHEDRINE CAPSULES
Discontinued due to low use. Midodrine capsules and pseudoephedrine tablets are available.

ERGOTAMINE TARTRATE 1 mg AND CAFFEINE 100 mg TABLETS (CAFERGOT®, ERCAF®, WIGRAINE®)
Discontinued due to low use. Dihydroergotamine injection and nasal spray, sumatriptan, naratriptan, and Fiorinal® are available.

FERUMOXIDES INJECTION (FERIDEX®)
Discontinued due to low use. Other diagnostic agents are available.

IOPANOIC ACID 500 mg TABLETS (TELEPAQUE®)
Discontinued due to low use. Other diagnostic agents are available.

LEVAMISOLE TABLET 50 mg (ERGAMISOL®)
Discontinued by the manufacturer.

NONOXYNOL 9 CONTRACEPTIVE GEL (GYNOL II®)
Discontinued due to low use. Other contraceptive products are available.

OXYTETRACYCLINE AND POLYMYXIN B OPHTHALMIC OINTMENT
Discontinued due to low use. Polymyxin B and bacitracin ophthalmic ointment, gentamicin ophthalmic ointment, tobramycin ophthalmic ointment, and erythromycin ophthalmic ointment are available.

SODIUM FLUORIDE CAPSULES 25 mg
Discontinued due to low use. Sodium fluoride oral solution is available.

TIMOLOL MALEATE OPHTHALMIC SOLUTION 0.25%, 0.45 ml
Discontinued due to low use. Timolol maleate ophthalmic solution 0.25%, 5 ml is available.

TRIAMCINOLONE ACETONIDE INJECTION 100 mg/5 ml
Discontinued due to low use. Triamcinolone acetonide 200 mg/5 ml injection is available.

TRIFLUOPERAZINE 1 mg TABLETS
Discontinued due to low use. Trifluoperazine 2 mg, 5 mg, and 10 mg tablets are available.

TYPHOID VACCINE (H-P)
Discontinued by the manufacturer. Typhoid vaccine live oral capsules and typhoid vi polysaccharide injectable vaccine are available.

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