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Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces (1996)

Chapter:4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS

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Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×

4

Strategy for Identifying and Dealing with Interactions

Although the committee clearly sees the value of investigations of the entire dose-response surface, that is, of all the responses to all the combinations of all the agents to which military personnel might be exposed (see discussion in Chapter 1), the virtually infinite number of interactions of the many drugs, biologics, and chemicals makes it practically impossible to study and define all of them at once. Because of this it is not feasible to predict and eliminate all potentially adverse interactions. Therefore, the committee urges that studies be focused on those interactions that are likely to occur, that may compromise military unit or individual effectiveness, or, although rare, that may cause severe consequences. Although numerous schemes to categorize such interactions can be devised, the committee chose to categorize interactions in three ways: (1) those which are known from properly conducted and documented human investigations; (2) those which may be potential because of the individual characteristics of the agents, such as their known target organ toxicities, pharmacokinetics, or mechanisms of action in animals or other nonhuman systems; and (3) those which, given the present state of understanding, are unknown.

The committee proposes using these three categories to facilitate study, discussion, and action. To place various combinations of agents into one of the categories, the committee proposes constructing and then using a matrix (described later in this chapter). Finally, the committee proposes planning a research agenda in tiers, by category, using surveillance, toxicology, and epidemiology tools and approaches. Table 4-1 illustrates the varied research

Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×

approaches based on the three categories. Chapter 5 gives details of the tiered approach.

KNOWN INTERACTIONS

Only a relatively small number of the total number of possible interactions of various agents have been studied. Examples include protein binding displacement interactions (Udall, 1974); the interaction of acetaminophen and ethanol (McClain et al., 1980); and the role of the hepatic cytochrome P450 enzyme system in metabolizing compounds, thereby modulating their pharmacokinetics or organ toxicities (Levy and Bajpai, 1995). An example of military medicine drawing on current knowledge of interactions in its decisions is its procedures concerning vaccines. Live vaccine is not given soon after the administration of another live vaccine because of known interference with effectiveness; multiple live vaccines are given either concurrently or separated by more than 30 days.

Various strategies have been devised to alert decisionmakers to known interactions and to reduce the risk of such interactions. However, it is reasonable to assume that military operational requirements may necessitate the use of those substances that are known to result in increased toxicity on the basis of a significant positive risk-benefit ratio. For example, troops in the Balkans during the spring-summer season wore permethrin-impregnated uniforms and topically applied DEET to exposed skin when tick-borne encephalitis posed a significant hazard. In such instances, surveillance to detect, minimize, or prevent progressive toxicity should be established.

TABLE 4-1 Categorical Approach

Interaction Type

Recommended Approaches

Known

  • Avoid unless benefit outweighs risk

  • Use surveillance to monitor outcomes and implement appropriate intervention

  • Study in depth

Potential

  • Use matrix approach to predict or identify the interaction

  • Conduct studies (in vitro, animal, or human volunteer)

  • Use surveillance

Unknown

  • Put in place surveillance systems to detect sentinel events and do follow-up studies

  • Do prospective screening studies of important combinations

Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×

POTENTIAL INTERACTIONS

Some potential interactions, although not yet defined, can be suspected on the basis of similar target organ toxicities, toxicokinetic patterns, pharmacokinetics, or pharmacodynamics. Building on its understanding of the literature on interactions, in which agents X and Y have been shown to manifest common toxicities, toxicokinetics, or mechanisms of action, the committee recommends the development and use of a matrix system to identify potential but untested interactions. Examples of such matrices are provided in Table 4-2 and Table 4-3. The outline of the matrix is formed by listing the drugs, biologics, and chemicals to which troops may be exposed on one axis and listing known target organ toxicities, mechanisms of action, and toxicokinetic properties on the other. Then, for each row and column, the particular properties of the agent are entered. For example, fluoroquinolones and acetylcholinesterase inhibitors both express neurotoxic effects.

Once the matrix has been generated, one may look down the columns and identify commonalities between agents that may predispose them to interact. For example, the common neurotoxicities of permethrin and DEET suggest that they may interact (Table 4-2).

Table 4-3 demonstrates how a matrix could operate in assessing various classes of agents (e. g., antiparasitic or antidiarrheal agents) for overlapping sites of action or toxicities. When fully developed, these cross-comparison matrices should permit a more focused approach to the consideration of the potential interactions of multiple agents. For example, agents that express neurotoxic effects, such as fluoroquinolones and the acetylcholinesterase inhibitors (i.e., pyridostigmine) or Japanese encephalitis virus vaccination (Piesner et al., 1996), might be suspected of demonstrating interactive neurotoxicities. Moreover, new knowledge about the liver cytochrome P450 isozymes, enzymes involved in the metabolism of chemicals, may enable prediction of such interactions.

The matrix approach described in this chapter would serve as a screening step. Determining that toxic interactions between combinations of agents actually occur requires appropriate in vitro, animal toxicity, human volunteer, or epidemiologic studies for validation. Identification of potential interactions using available methodologies, including the matrix, could prompt the initiation of assessment programs (see Chapter 5). Once alerted to potential interactions, decisionmakers can prioritize studies of the potential interactions that could cause severe health consequences or impair troop effectiveness, or studies of the agents to which large numbers of individuals will be exposed. Continued improvement and updating of such a matrix is expected to further enhance its utility and validity.

The committee emphasizes that this approach is just one practical method that can be used to grapple with a difficult subject; there are no completely fail-

Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×

safe methods. Even if it were possible to study all combinations of agents in epidemiologic or animal model systems, it is unlikely that such a strategy would work. Many confounding factors would be encountered in epidemiologic studies; for example, host susceptibility factors such as age, race, sex, and comorbid conditions could affect the results. In the case of experimental studies, although randomization minimizes the effects of confounding variables, there remain the problems of multiple comparisons and sample size considerations.

Finally, although epidemiologic studies are more likely to involve exposures of humans to mixtures of chemicals or other toxic agents and could thus provide a more reliable basis for risk assessment than toxicologic studies with animals, epidemiologic data are rarely available for the specific mixtures of agents and exposure situations of interest. Thus, the committee proposes an additional series of prospective animal toxicity studies (Chapter 5).

UNKNOWN INTERACTIONS

Despite a thorough literature review and the development and use of a matrix such as the one proposed by the committee, unpredictable interactive toxicities are certain to occur. The unpredictable and severe toxicities of thalidomide, benoxaprofen, temafloxacin, and FIAU/FIAC (Fialuridine) used as single agents provide such examples (Strom, 1994). Even less predictable toxicities should be expected when complex mixtures of agents are used together. Early identification of such unusual or unpredictable events will require the use of a variety of toxicologic and epidemiologic tools. The surveillance tools that are required to investigate hitherto unknown interactions and that are currently available to the military were described in Chapter 3. Chapter 5 expands the discussion to specific toxicology and epidemiology approaches.

Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×

TABLE 4-2 Organ Toxicities, Pharmacodynamic, and Pharmacokinetic Properties of Drugs, Biologics, Chemicals, Recreational Substances, and Environmental Factors to Which Deployed U.S. Military Personnel May Be Exposed

Class of Agent

Specific Agent

Site of Action or Toxicity

Pharmacodynamic or Pharmacokinetic Characteristics

Smokes, obscurants

Diesel fuel

Fog Oil

Red phosphorous

Hexachlorethane

Zinc chloride

Titanium dioxide

Airways

Airways

Airways

Airways

Airways

Airways

 

Riot control agents*

CN (mace)

CS (O-chlorobenzylidene malonitrile)

Mucous membranes (eyes, nose, mouth, lung), skin

Mucous membranes (eyes, nose, mouth, lung), skin

 

Chemical warfare weapons*

Nerve agents: GA (tabun), GB (sarin), GD (soman), GF, VX

CNS, lung

Cholinesterase inhibitor (butyrylcholinesterase, acetylcholinesterase)

 

Vesicants: HD (distilled mustard), HL (mustard-lewisite mixture), HT (mustard-T mixture)

Skin, airways, eyes, CNS (poorly defined)

DNA alkylation and cross-linking in rapidly dividing cells

 

Cyanide: AC (hydrogen cyanide), CK (cyanogen chloride)

CNS, heart

Binds to Fe3+, inhibits cytochrome, prevents intracellular oxygen utilization

 

Pulmonary agents: CG (phosgene), PFIB (perfluoroisobutylene: pyrolysis of Teflon)

Lung

Acylation of cells at alveolar-capillary membranes with pulmonary edema

Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×

Biologics/vaccines

Live-attenuated vaccines, routine

 
 

Adenovirus types 4 and 7

Measles, mumps, rubella

None recognized

None recognized

 
 

Poliovirus, oral

Typhoid

CNS

None recognized

Paralysis, 1:2,000,000

 

Varicella-zoster virus

Skin (liver)

Varicella-zoster virus-like rash (5%); Reye syndrome occurs with varicella-zoster virus infection and aspirin; not reported with vaccine, but warning to avoid aspirin for 2 weeks after vaccination

 

(Vaccina virus)

Killed vaccines, routine Tetanus, diphtheria

Hepatitis A and B viruses

Influenza virus

Menigococcal (groups A, C, Y, and W-135)

Area of operation-specific vaccines, killed

Skin

None recognized

None recognized

None recognized

None recognized

 
 

Cholera

Japanese encephalitis

Plague

Rabies

Yellow fever

Tick-borne encephalitis

None recognized

Anaphylaxis (rare), CNS

None recognized

None recognized

CNS

None recognized

 
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×

Class of Agent

Specific Agent

Site of Action or Toxicity

Pharmacodynamic or Pharmacokinetic Characteristics

 

Biological weapon vaccines

 
 

Anthrax

Botulinum

Immunoglobulins

None recognized

None recognized

 
 

Serum immune globulin

Hepatitis B virus Ig

Rabies IG

CNS

None recognized

None recognized

Large intravenous doses, aseptic meningitis

Drugs, commonly used, prescription

NSAIDS

Antibiotics, oral

Analgesics

Decongestants

CNS, renal, gastrointestinal

Multiple organs, depends on specific agent

Dizziness, headache (>3%), aseptic meningitis (<1%)

 

Antihistamines

Airways

 
 

Contraceptives, oral

Vitamins

Liver, skin

None at usual dosage

Induce cytochrome P450 enzymes

 

Iron

Antifungal agents (oral)

None at usual dosage

Liver

Blocks absorption of some oral antibiotics

Induce cytochrome P450 enzymes

Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×

Drugs, area of operation, for prophylaxis (P) or therapy

Antimalarial agents

 
 

Chloroquine (P)

Primaquine (P)

Mefloquine (P)

Halofantrine

Doxycycline (P)

Quinine, quinidine

Artemisins

Antidiarrheal agents

CNS, hematologic

Hematologic, CNS, cardiac, central cholinergic system

CNS, cardiac

Cardiac, CNS

Skin, liver, CNS

Ototoxicity, CNS

Cardiac

 
 

Fluoroquinolones

(ciprofloxacin)

Trimethoprim-sulfamethoxazole

Loperamide

Atropine sulfate-diphenoxylate

(Lomotil)

Antifungal agents

CNS, musculoskeletal, liver

Skin, CNS

Skin

Liver

GABA inhibitors, liver failure

 

Topical

None recognized

 
 

Azoles (oral)

Antiviral agents

Liver

Induce cytochrome P450 enzymes

 

Acyclovir

Ribavirin (intravenous)

Antiparasitic agents

Renal

None recognized

 
 

Metronidazole

Trimethoprim-sulfamethoxazole

Mebendazole

CNS, skin

Skin, CNS

Liver, hematologic

 
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×

Class of Agent

Specific Agent

Site of Action or Toxicity

Pharmacodynamic or Pharmacokinetic Characteristics

 

Praziquantel

Ivermectin

CNS, liver

CNS

 
 

Permethrin cream

CNS

Concentrated in fat; acute CNS toxicity

 

Antibacterial agents

   
 

Penicillin V (oral)

Amoxicillin (oral)

Cephalexin (oral)

Skin

Skin

Skin

 
 

Erythromycin (oral)

Skin, liver

Induces cytochrome P450 enzymes

 

Trimethoprim-sulfamethoxazole (oral)

Clindamycin

Metronidazole (oral)

Skin, CNS

CNS, skin

CNS, skin

 
 

Ceftriaxone (intramuscular, intravenous)

Doxycycline (oral)

Skin, liver

Skin, liver

Pseudocholelithiasis

Drugs, anti-biological warfare

Fluoroquinolone (ciprofloxin)

CNS, musculoskeletal, liver

 

Drugs, chemical warfare prophylaxis and treatment

Pyridostigmine

Atropine

Pralidoxime chloride

Diazepam

Nervous system

Skin (decreased sweating)

CNS

A cholinesterase inhibitor

An anticholinergic agent

Breaks the nerve agent–enzyme bond

Anticonvulsant

Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×

Recreational drugs

Caffeine (coffee, soft drinks)

Nicotine (smokeless tobacco)

Alcohol

CNS

CNS

Liver

 

Occupational exposures

Noise

Carbon monoxide

Exercise

Heat

Cold

Ototoxicity

Ototoxicity

Musculoskeletal

Musculoskeletal, CNS, liver

Skin, musculoskeletal

 

Insect repellants

DEET

Permethrin

CNS

CNS

 

NOTE: CNS = central nervous system; Ig = immunoglobulin; NSAIDs = nonsteroidal anti-inflammatory drugs; and GABA = γ-aminobutyric acid.

*Identified using standard military terminology for chemical agents (see Chemical Casualty Care Office, 1995).

Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×

TABLE 4-3 Potential Interactions of Drugs, Biologics, Chemicals, Recreational Substances, and Environmental Factors

 

Chemical Agents

 

Site of Action, Toxicity

Smokes, Obscurants

Riot Control Agents

Nerve Agents

Vesicants

Cyanide

Phosgene, PFIB

Nervous system (central, peripheral)

 

+

?

+

 

Ototoxicity

 

Mucous membranes, conjunctiva

 

+

 

+

Airways, lungs

+

+

+

+

 

+

Cardiac

 

+

 

Cutaneous, skin

 

+

 

+

 

Hepatic

 

Renal

 

Musculoskeletal

 

Hematologic, lymphoid

 

Immunologic

 

Gastrointestinal

 

Reproductive, endocrine

 

NOTE: PFIB = perfluoroisobutylene (Teflon pyrolysis); NSAIDs = nonsteroidal anti-inflammatory drugs; beta-lactams are penicillin and cephalosporin; “+” denotes that the specified agent is active at the specified site. “?” denotes that the association of agent and site is ill-defined.

Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
 

Vaccines

Site of Action, Toxicity

Live Attenuated, Routine

Killed, Routine

Area-of-Operation Specific

Biological Weapons-Specific

Immunoglobulins

Nervous system (central, peripheral)

+   +   +

Ototoxicity

 

Mucous membranes, conjunctiva

 

Airways, lungs

 

Cardiac

 

Cutaneous, skin

+

 

Hepatic

+

 

Renal

 

Musculoskeletal

 

Hematologic, lymphoid

 

Immunologic

 

+

Gastrointestinal

 

Reproductive, endocrine

 
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
 

Commonly Used Prescription Drugs

Site of Action, Toxicity

NSAIDs

Antibiotics

Analgesics

Decongestants

Antihistamines

Contraceptives, Oral

Vitamins

Iron

Antifungal, Agents, Oral

Nervous system (central, peripheral)

+

+

 

Ototoxicity

 

+

 

Mucous membranes, conjunctiva

 

Airways, lungs

 

+

 

Cardiac

 

Cutaneous, skin

 

+

 

+

 

Hepatic

 

+

 

+

 

+

Renal

+

+

 

Musculoskeletal

 

+

 

Hematologic, lymphoid

 

+

 

Immunologic

 

Gastrointestinal

+

+

 

Reproductive, endocrine

 

+

 

+

Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
 

Antimalarial Agents

Site of Action, Toxicity

Chloroquine

Primaquine

Mefloquine

Halofantrin

Doxycycline

Quinine

Artemisins

Nervous system (central, peripheral)

+

+

+

+

+

+

Ototoxicity

 

+

 

Mucous membranes, conjunctiva

 

Airways, lungs

 

Cardiac

 

+

+

+

 

+

Cutaneous, skin

 

+

 

Hepatic

 

+

 

Renal

 

Musculoskeletal

 

Hematologic, lymphoid

+

+

 

Immunologic

 

Gastrointestinal

 

Reproductive, endocrine

 
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
 

Antidiarrheal Agents

 

Antiviral Agents

Site of Action, Toxicity

Fluoroquinolones

Trimethoprimsulfamethoxazone

Loperamide

Lomotil

Acyclovir

Ribavirin

Nervous system (central, peripheral)

+

+

 

Ototoxicity

 

Mucous membranes, conjunctiva

 

Airways, lungs

 

Cardiac

 

Cutaneous, skin

 

+

+

 

Hepatic

+

 

+

 

Renal

 

+

 

Musculoskeletal

+

 

Hematologic, lymphoid

 

Immunologic

 

Gastrointestinal

 

Reproductive, endocrine

 
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
 

Antiparasitic Agents

Insert Repellants

Site of Action, Toxicity

Metronidazole

Mebendazole

Praziquante

Permethrin

DEET

Nervous system (central, peripheral)

+

 

+

+

+

Ototoxicity

 

Mucous membranes, conjunctiva

 

Airways, lungs

 

Cardiac

 

cCutaneous, skin

+

 

Hepatic

 

+

+

 

Renal

 

Musculoskeletal

 

Hematologic, lymphoid

 

+

 

Immunologic

 

Gastrointestinal

 

Reproductive, endocrine

 
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
 

Antibacterial Agents

Nerve Agents

Site of Action, Toxicity

Beta-Lactams

Erythromycin

Clindamycin

Pyridostigmine

Atropine

Pralidoxime

Nervous system (central, peripheral)

 

+

+

 

Ototoxicity

 

Mucous membranes, conjunctiva

 

Airways, lungs

 

Cardiac

 

Cutaneous, skin

+

+

+

 

+

 

Hepatic

 

+

 

Renal

 

Musculoskeletal

 

Hematologic, lymphoid

 

Immunologic

+

+

 

Gastrointestinal

 

Reproductive, endocrine

 
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
 

Miscellaneous Agents

Site of Action, Toxicity

Caffeine

Nicotine

Alcohol

Noise

Carbon Monoxide

Nervous system (central, peripheral)

+

+

 

Ototoxicity

 

+

+

Mucous membranes, conjunctiva

 

Airways, lungs

 

Cardiac

 

Cutaneous, skin

 

+

Hepatic

 

+

 

Renal

 

Musculoskeletal

 

Hematologic, lymphoid

 

Immunologic

 

Gastrointestinal

 

Reproductive, endocrine

 
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page34
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page35
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page36
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page37
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page38
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page39
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page40
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page41
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page42
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page43
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page44
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page45
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page46
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page47
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page48
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page49
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
Page50
Suggested Citation:"4: STRATEGY FOR IDENTIFYING AND DEALING WITH INTERACTIONS." Institute of Medicine. 1996. Interactions of Drugs, Biologics, and Chemicals in U.S. Military Forces. Washington, DC: The National Academies Press. doi: 10.17226/5515.
×
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