Professional Information
Cough/Cold Combinations (Systemic)
Note: Products containing phenylpropanolamine were removed from the U.S. and Canadian Markets in November 2000.{61}
1) Brompheniramine, Phenylephrine and Codeine
2) Brompheniramine, Phenylephrine, Codeine and Guaifenesin *
3) Brompheniramine, Phenylephrine, Hydrocodone and Guaifenesin *
4) Brompheniramine, Pseudoephedrine, and Dextromethorphan †
5) Carbinoxamine, Pseudoephedrine, and Dextromethorphan †
6) Chlorpheniramine and Codeine *
7) Chlorpheniramine and Dextromethorphan †
8) Chlorpheniramine and Hydrocodone †
9) Chlorpheniramine, Ephedrine, and Guaifenesin †
10) Chlorpheniramine, Ephedrine, Phenylephrine, and Carbetapentane †
11) Chlorpheniramine, Ephedrine, Phenylephrine, Dextromethorphan, Ammonium Chloride, and Ipecac †
12) Chlorpheniramine, Pheniramine, Pyrilamine, Phenylephrine, Hydrocodone, Salicylamide, Caffeine, and Ascorbic Acid †
13) Chlorpheniramine, Phenylephrine, Codeine, and Ammonium Chloride †
14) Chlorpheniramine, Phenylephrine, Codeine, and Potassium Iodide †
15) Chlorpheniramine, Phenylephrine, and Dextromethorphan †
16) Chlorpheniramine, Phenylephrine, Dextromethorphan, and Guaifenesin †
17) Chlorpheniramine, Phenylephrine, Dextromethorphan, Guaifenesin, and Ammonium Chloride †
18) Chlorpheniramine, Phenylephrine, and Hydrocodone †
19) Chlorpheniramine, Phenylephrine, Hydrocodone, Acetaminophen, and Caffeine †
20) Chlorpheniramine, Pseudoephedrine, and Codeine
21) Chlorpheniramine, Pseudoephedrine, Codeine and Acetaminophen *
22) Chlorpheniramine, Pseudoephedrine, and Dextromethorphan
23) Chlorpheniramine, Pseudoephedrine, Dextromethorphan, and Acetaminophen
24) Chlorpheniramine, Pseudoephedrine, Dextromethorphan, and Guaifenesin *
25) Chlorpheniramine, Pseudoephedrine, and Hydrocodone †
26) Chlorpheniramine, Pyrilamine, Phenylephrine, Pseudoephedrine and Hydrocodone †
27) Codeine, Ammonium Chloride, and Guaifenesin *
28) Codeine and Guaifenesin †
29) Dextromethorphan and Acetaminophen
30) Dextromethorphan and Guaifenesin
31) Dextromethorphan and Iodinated Glycerol †
32) Diphenhydramine, Codeine, and Ammonium Chloride *
33) Diphenhydramine, Dextromethorphan, and Ammonium Chloride *
34) Doxylamine, Codeine, and Acetaminophen *
35) Doxylamine, Etafedrine, and Hydrocodone *
36) Doxylamine, Pseudoephedrine, Dextromethorphan, and Acetaminophen
37) Ephedrine and Guaifenesin †
38) Hydrocodone and Guaifenesin †
39) Hydrocodone and Homatropine †
40) Hydrocodone and Potassium Guaiacolsulfonate †
41) Hydrocodone *
42) Pheniramine, Codeine, and Guaifenesin *
43) Pheniramine, Phenylephrine, Codeine, Sodium Citrate, Sodium Salicylate, and Caffeine †
44) Pheniramine, Phenylephrine, and Dextromethorphan *
45) Pheniramine, Pyrilamine, Hydrocodone, Potassium Citrate, and Ascorbic Acid †
46) Pheniramine, Pyrilamine and Phenyltoloxamine †
47) Phenylephrine, Codeine and Guaifenesin †
48) Phenylephrine and Guaifenesin †
49) Phenylephrine and Hydrocodone
50) Phenylephrine, Hydrocodone, and Guaifenesin
51) Phenyltoloxamine and Hydrocodone *
52) Promethazine and Codeine †
53) Promethazine, Codeine, and Potassium Guaiacolsulfonate *
54) Promethazine and Dextromethorphan †
55) Promethazine and Potassium Guaiacolsulfonate *
56) Promethazine and Phenylephrine †
57) Promethazine, Phenylephrine, and Codeine †
58) Promethazine, Phenylephrine, and Potassium Guaiacolsulfonate *
59) Pseudoephedrine, Codeine, and Guaifenesin
60) Pseudoephedrine and Dextromethorphan
61) Pseudoephedrine, Dextromethorphan, and Acetaminophen
62) Pseudoephedrine, Dextromethorphan, and Guaifenesin
63) Pseudoephedrine, Dextromethorphan, Guaifenesin, and Acetaminophen
64) Pseudoephedrine and Guaifenesin
65) Pseudoephedrine, Hydrocodone, and Guaifenesin †
66) Pseudoephedrine, Hydrocodone, and Potassium Guaiacolsulfonate †
67) Pyrilamine and Codeine †
68) Pyrilamine, Phenylephrine, Hydrocodone, and Ammonium Chloride *
69) Pyrilamine, Pseudoephedrine, Dextromethorphan, and Acetaminophen †
70) Triprolidine, Pseudoephedrine, and Codeine
71) Triprolidine, Pseudoephedrine, Codeine, and Guaifenesin *
{62}
VA CLASSIFICATION
Brompheniramine, Phenylephrine and Codeine (Systemic)
Primary: RE502
Brompheniramine, Phenylephrine, Codeine, and Guaifenesin (Systemic)
Primary: RE504
Brompheniramine, Phenylephrine, Hydrocodone and Guaifenesin (Systemic)
Primary: RE504
Brompheniramine, Pseudoephedrine, and Dextromethorphan (Systemic)
Primary: RE502
Carbinoxamine, Pseudoephedrine, and Dextromethorphan (Systemic)
Primary: RE502
Chlorpheniramine and Codeine (Systemic)
Primary: RE507
Chlorpheniramine and Dextromethorphan (Systemic)
Primary: RE507
Chlorpheniramine, Ephedrine, and Guaifenesin (Systemic)
Primary: RE503
Chlorpheniramine, Ephedrine, Phenylephrine, and Carbetapentane (Systemic)
Primary: RE502
Chlorpheniramine, Ephedrine, Phenylephrine, Dextromethorphan, Ammonium Chloride, and Ipecac (Systemic)
Primary: RE504
Chlorpheniramine and Hydrocodone (Systemic)
Primary: RE301
Chlorpheniramine, Pheniramine, Pyrilamine, Phenylephrine, Hydrocodone, Salicylamide, Caffeine, and Ascorbic Acid (Systemic)
Primary: RE301
Chlorpheniramine, Phenylephrine, Codeine, and Ammonium Chloride (Systemic)
Primary: RE301
Chlorpheniramine, Phenylephrine, Codeine, and Potassium Iodide (Systemic)
Primary: RE301
Chlorpheniramine, Phenylephrine, and Dextromethorphan (Systemic)
Primary: RE502
Chlorpheniramine, Phenylephrine, Dextromethorphan, and Guaifenesin (Systemic)
Primary: RE504
Chlorpheniramine, Phenylephrine, Dextromethorphan, Guaifenesin, and Ammonium Chloride (Systemic)
Primary: RE504
Chlorpheniramine, Phenylephrine, and Hydrocodone (Systemic)
Primary: RE301
Chlorpheniramine, Phenylephrine, Hydrocodone, Acetaminophen, and Caffeine (Systemic)
Primary: RE301
Chlorpheniramine, Pseudoephedrine, and Codeine (Systemic)
Primary: RE301
Chlorpheniramine, Pseudoephedrine, Codeine, and Acetaminophen (Systemic)
Primary: RE506
Chlorpheniramine, Pseudoephedrine, Dextromethorphan, and Acetaminophen (Systemic)
Primary: RE506
Chlorpheniramine, Pseudoephedrine, and Dextromethorphan (Systemic)
Primary: RE502
Chlorpheniramine, Pseudoephedrine, Dextromethorphan, and Guaifenesin (Systemic)
Primary: RE504
Chlorpheniramine, Pseudoephedrine, and Hydrocodone (Systemic)
Primary: RE301
Chlorpheniramine, Pyrilamine, Phenylephrine, Pseudoephedrine and Hydrocodone (Systemic)
Primary: RE502
Codeine, Ammonium Chloride, and Guaifenesin (Systemic)
Primary: RE301
Codeine and Guaifenesin (Systemic)
Primary: RE301
Dextromethorphan and Acetaminophen (Systemic)
Primary: RE302
Dextromethorphan and Guaifenesin (Systemic)
Primary: RE302
Dextromethorphan and Iodinated Glycerol (Systemic)
Primary: RE302
Diphenhydramine, Codeine, and Ammonium Chloride (Systemic)
Primary: RE301
Diphenhydramine, Dextromethorphan, and Ammonium Chloride (Systemic)
Primary: RE502
Doxylamine, Codeine, and Acetaminophen (Systemic)
Primary: RE509
Doxylamine, Etafedrine, and Hydrocodone (Systemic)
Primary: RE502
Doxylamine, Pseudoephedrine, Dextromethorphan, and Acetaminophen (Systemic)
Primary: RE506
Ephedrine and Guaifenesin (Systemic)
Primary: RE516
Hydrocodone and Guaifenesin (Systemic)
Primary: RE301
Hydrocodone and Homatropine (Systemic)
Primary: RE301
Hydrocodone and Potassium Guaiacolsulfonate (Systemic)
Primary: RE301
Pheniramine, Codeine, and Guaifenesin (Systemic)
Primary: RE301
Pheniramine, Phenylephrine, Codeine, Sodium Citrate, Sodium Salicylate, and Caffeine (Systemic)
Primary: RE301
Pheniramine, Phenylephrine, and Dextromethorphan (Systemic)
Primary: RE502
Pheniramine, Pyrilamine, Hydrocodone, Potassium Citrate, and Ascorbic Acid (Systemic)
Primary: RE301
Pheniramine, Pyrilamine, and Phenyltoloxamine (Systemic)
Primary: RE501
Phenylephrine, Codeine and Guaifenesin (Systemic)
Primary: RE513
Phenylephrine and Guaifenesin (Systemic)
Primary: RE516
Phenylephrine and Hydrocodone (Systemic)
Primary: RE512
Phenylephrine, Hydrocodone, and Guaifenesin (Systemic)
Primary: RE301
Phenyltoloxamine and Hydrocodone (Systemic)
Primary: RE301
Promethazine and Codeine (Systemic)
Primary: RE301
Promethazine, Codeine, and Potassium Guaiacolsulfonate (Systemic)
Primary: RE301
Promethazine and Dextromethorphan (Systemic)
Primary: RE507
Promethazine and Potassium Guaiacolsulfonate (Systemic)
Primary: RE599
Promethazine and Phenylephrine (Systemic)
Primary: RE501
Promethazine, Phenylephrine, and Codeine (Systemic)
Primary: RE301
Promethazine, Phenylephrine, and Potassium Guaiacolsulfonate (Systemic)
Primary: RE503
Pseudoephedrine, Codeine, and Guaifenesin (Systemic)
Primary: RE301
Pseudoephedrine and Dextromethorphan (Systemic)
Primary: RE512
Pseudoephedrine, Dextromethorphan, and Acetaminophen (Systemic)
Primary: RE515
Pseudoephedrine, Dextromethorphan, and Guaifenesin (Systemic)
Primary: RE513
Pseudoephedrine, Dextromethorphan, Guaifenesin, and Acetaminophen (Systemic)
Primary: RE514
Pseudoephedrine and Guaifenesin (Systemic)
Primary: RE516
Pseudoephedrine, Hydrocodone, and Guaifenesin (Systemic)
Primary: RE301
Pseudoephedrine, Hydrocodone, and Potassium Guaiacolsulfonate
Primary: RE301
Pyrilamine and Codeine (Systemic)
Primary: RE301
Pyrilamine, Phenylephrine, Hydrocodone, and Ammonium Chloride (Systemic)
Primary: RE301
Pyrilamine, Pseudoephedrine, Dextromethorphan, and Acetaminophen (Systemic)
Primary: RE506
Triprolidine, Pseudoephedrine, and Codeine (Systemic)
Primary: RE301
Triprolidine, Pseudoephedrine, Codeine, and Guaifenesin (Systemic)
Primary: RE301
Note: Due to the large number of cough/cold products available and the different ingredients they contain, the listing that normally appears in this section has been omitted to save space. To aid the reader in readily finding the combination(s) and/or product(s) of interest, these have been grouped in the Category section and in the Advice for the Patient monograph according to the following major categories:
• Antihistaminic (H 1-receptor)-decongestant-antitussive
• Antihistaminic (H 1-receptor)-decongestant-expectorant
• Antihistaminic (H 1-receptor)-decongestant-antitussive-expectorant
• Antihistaminic (H 1-receptor)-decongestant-antitussive-expectorant-analgesic
• Antihistaminic (H 1-receptor)-decongestant-antitussive-analgesic
• Antihistaminic (H 1-receptor)-decongestant-expectorant-analgesic
• Antihistaminic (H 1-receptor)-antitussive
• Antihistaminic (H 1-receptor)-antitussive-expectorant
• Antihistaminic (H 1-receptor)-antitussive-analgesic
• Antihistaminic (H 1-receptor)-expectorant
• Antitussive-expectorant
• Antitussive-analgesic
• Antitussive-anticholinergic
• Decongestant-antitussive
• Decongestant-antitussive-expectorant
• Decongestant-antitussive-expectorant-analgesic
• Decongestant-antitussive-analgesic
• Decongestant-expectorant
• Decongestant-expectorant-analgesic
Other combination products that are used in the symptomatic treatment of colds, but which do not contain either an antitussive or an expectorant, can be found in Antihistamines and Decongestants (Systemic) ; Antihistamines, Decongestants, and Analgesics (Systemic) ; Antihistamines, Decongestants, and Anticholinergics (Systemic) ; and Decongestants and Analgesics (Systemic) .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
*Not commercially available in the U.S.
†Not commercially available in Canada.
Category:
Antihistaminic (H 1-receptor)-decongestant—Pheniramine, Pyrilamine, and Phenyltoloxamine; Promethazine and Phenylephrine;
Antihistaminic (H 1-receptor)-decongestant-antitussive— Brompheniramine, Phenylephrine and Codeine; Brompheniramine, Pseudoephedrine, and Dextromethorphan; Carbinoxamine, Pseudoephedrine, and Dextromethorphan; Chlorpheniramine, Pyrilamine, Phenylephrine, Pseudoephedrine and Hydrocodone; Chlorpheniramine, Ephedrine, Phenylephrine, and Carbetapentane; Chlorpheniramine, Phenylephrine, and Dextromethorphan; Chlorpheniramine, Phenylephrine, and Hydrocodone; Chlorpheniramine, Pseudoephedrine, and Codeine; Chlorpheniramine, Pseudoephedrine, and Dextromethorphan; Chlorpheniramine, Pseudoephedrine, and Hydrocodone; Doxylamine, Etafedrine, and Hydrocodone; Pheniramine, Phenylephrine, and Dextromethorphan; Promethazine, Phenylephrine, and Codeine; Triprolidine, Pseudoephedrine, and Codeine;
Antihistaminic (H 1-receptor)-decongestant-expectorant— Chlorpheniramine, Ephedrine, and Guaifenesin; Promethazine, Phenylephrine, and Potassium Guaiacolsulfonate;
Antihistaminic (H 1-receptor)-decongestant-antitussive-expectorant—Brompheniramine, Phenylephrine, Codeine, and Guaifenesin ; Brompheniramine, Phenylephrine, Hydrocodone, and Guaifenesin; Chlorpheniramine, Ephedrine, Phenylephrine, Dextromethorphan, Ammonium Chloride, and Ipecac; Chlorpheniramine, Phenylephrine, Codeine, and Ammonium Chloride ; Chlorpheniramine, Phenylephrine, Codeine, and Potassium Iodide; Chlorpheniramine, Phenylephrine, Dextromethorphan, and Guaifenesin; Chlorpheniramine, Phenylephrine, Dextromethorphan, Guaifenesin, and Ammonium Chloride; Chlorpheniramine, Pseudoephedrine, Dextromethorphan, and Guaifenesin; Pyrilamine, Phenylephrine, Hydrocodone, and Ammonium Chloride; Triprolidine, Pseudoephedrine, Codeine, and Guaifenesin;
Antihistaminic (H 1-receptor)-decongestant-antitussive-expectorant-analgesic—Pheniramine, Phenylephrine, Codeine, Sodium Citrate, Sodium Salicylate, and Caffeine;
Antihistaminic (H 1-receptor)-decongestant-antitussive-analgesic—Chlorpheniramine, Pheniramine, Pyrilamine, Phenylephrine, Hydrocodone, Salicylamide, Caffeine, and Ascorbic Acid; Chlorpheniramine, Phenylephrine, Hydrocodone, Acetaminophen, and Caffeine; Chlorpheniramine, Pseudoephedrine, Codeine, and Acetaminophen; Chlorpheniramine, Pseudoephedrine, Dextromethorphan, and Acetaminophen; Doxylamine, Pseudoephedrine, Dextromethorphan, and Acetaminophen; Pyrilamine, Pseudoephedrine, Dextromethorphan, and Acetaminophen ;
Antihistaminic (H 1-receptor)-antitussive—Chlorpheniramine and Codeine; Chlorpheniramine and Dextromethorphan ; Chlorpheniramine and Hydrocodone; Phenyltoloxamine and Hydrocodone; Promethazine and Codeine; Promethazine and Dextromethorphan; Pyrilamine and Codeine ;
Antihistaminic (H 1-receptor)-antitussive-expectorant— Diphenhydramine, Codeine, and Ammonium Chloride; Diphenhydramine, Dextromethorphan, and Ammonium Chloride; Pheniramine, Codeine, and Guaifenesin; Pheniramine, Pyrilamine, Hydrocodone, Potassium Citrate, and Ascorbic Acid; Promethazine, Codeine, and Potassium Guaiacolsulfonate;
Antihistaminic (H 1-receptor)-antitussive-analgesic— Doxylamine, Codeine, and Acetaminophen;
Antitussive-expectorant—Codeine, Ammonium Chloride, and Guaifenesin; Codeine and Guaifenesin; Dextromethorphan and Guaifenesin; Dextromethorphan and Iodinated Glycerol; Hydrocodone and Guaifenesin;
Antitussive-analgesic—Dextromethorphan and Acetaminophen;
Antitussive-anticholinergic—Hydrocodone and Homatropine;
Decongestant-antitussive—Phenylephrine and Hydrocodone; Pseudoephedrine and Dextromethorphan;
Decongestant-antitussive-expectorant —Phenylephrine, Codeine and Guaifenesin ; Phenylephrine, Hydrocodone, and Guaifenesin ; Pseudoephedrine, Codeine, and Guaifenesin ; Pseudoephedrine, Dextromethorphan, and Guaifenesin; Pseudoephedrine, Hydrocodone, and Guaifenesin; Pseudoephedrine, Hydrocodone, and Potassium Guaiacolsulfonate;
Decongestant-antitussive-expectorant-analgesic —Pseudoephedrine, Dextromethorphan, Guaifenesin, and Acetaminophen;
Decongestant-antitussive-analgesic —Pseudoephedrine, Dextromethorphan, and Acetaminophen;
Decongestant-expectorant—Ephedrine and Guaifenesin; Phenylephrine and Guaifenesin; Pseudoephedrine and Guaifenesin; {62}
Indications
Accepted
Note: Products containing phenylpropanolamine were removed from the U.S. and Canadian Markets in November 2000.{61}
Cough (treatment)—Combination products containing antitussives and/or expectorants may be indicated for the symptomatic relief of cough due to colds and minor upper respiratory infections. {01}
Cough and nasal congestion (treatment)—Combination products containing antitussives and/or expectorants, and nasal decongestants may be indicated for the symptomatic relief of cough and nasal congestion due to the common cold and other respiratory infections. Also, products containing antihistamines may provide relief of the cough, nasal congestion, rhinorrhea, and sneezing associated with allergy and the common cold. However, controlled clinical studies have not demonstrated that antihistamines are significantly more effective than placebo in relieving cold symptoms. {02}
Cold symptoms (treatment)—Combination products containing antihistamines, antitussives or expectorants, nasal decongestants, and analgesics may be indicated for the temporary relief of coughs, nasal congestion, and associated aches, pains, and general discomfort due to colds, flu, or allergy. The antihistamine in these cold combinations may provide relief of nasal congestion, rhinorrhea, and sneezing. It may also serve as an adjunct because of its anticholinergic drying effects. However, in many cough/cold combinations, the dosage level of the antihistamine is below that required to obtain a significant effect. Also, controlled clinical studies have not demonstrated that antihistamines are significantly more effective than placebo in relieving cold symptoms. {02}
Unaccepted
Cough/cold combination products that contain both an antitussive and an expectorant usually do not offer any advantage over products that contain only one of these agents. In some cases, their combination may be detrimental in the treatment of coughs, since antitussives should be used only in the treatment of dry coughs and not for productive coughs.
Some products containing an anticholinergic have been used to help dry excessive nasal secretions associated with the common cold and allergic rhinitis; however, the efficacy of anticholinergics for this use in these combination products has not been established. In most products, the anticholinergic is included in doses below the therapeutic level in an attempt to prevent abuse by deliberate overdosage (e.g., in combinations containing a narcotic antitussive) {23}.
Combination products that contain an analgesic are generally not recommended for regular use for the treatment of cold symptoms during the common cold or acute allergic rhinitis since they may mask fever, which may indicate a secondary bacterial infection.
Ammonium chloride, calcium iodide, citric acid, guaiacol carbonate, iodinated glycerol, ipecac, potassium citrate, potassium guaiacolsulfonate, potassium iodide, and sodium citrate are included as expectorants in these combinations; however, the Food and Drug Administration (FDA) has not found them to be useful for this indication. Therefore, FDA has requested manufacturers to reformulate their products to replace these ingredients with guaifenesin. {08}
Pharmacology/Pharmacokinetics
Antihistamine-containing—See Antihistamines (Systemic) .
Decongestant-containing—See:
• Ephedrine in Bronchodilators, Adrenergic (Systemic) .
• Pseudoephedrine (Systemic).
Dextromethorphan-containing—See Dextromethorphan (Systemic) .
Opioid (narcotic) antitussive–containing—See Opioid (Narcotic) Analgesics (Systemic) .
Expectorant-containing—See:
• Guaifenesin (Systemic).
Analgesic-containing—See:
• Acetaminophen (Systemic).
• Acetaminophen and Salicylates (Systemic).
• Salicylates (Systemic).
Homatropine-containing—See Anticholinergics/Antispasmodics (Systemic) .
Precautions to Consider
Antihistamine-containing—See Antihistamines (Systemic) .
Antihistamine- and decongestant-containing—See Antihistamines and Decongestants (Systemic) .
Decongestant-containing—See:
• Ephedrine in Bronchodilators, Adrenergic (Systemic) .
Note: Products containing phenylpropanolamine were removed from the U.S. and Canadian Markets in November 2000.{61}
• Pseudoephedrine (Systemic).
Dextromethorphan-containing—See Dextromethorphan (Systemic) .
Opioid (narcotic) antitussive–containing—See Opioid (Narcotic) Analgesics (Systemic) .
Expectorant-containing—See:
• Guaifenesin (Systemic).
Analgesic-containing—See:
• Acetaminophen (Systemic).
• Acetaminophen and Salicylates (Systemic).
• Salicylates (Systemic).
Homatropine-containing—See Anticholinergics/Antispasmodics (Systemic) .
Laboratory value alterations
Table 1. Laboratory value alterations
| The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance): | Legend: I=Antihistamine-containing II=Decongestant-containing III=Antitussive-containing IV=Expectorant-containing V=Analgesic-containing |
||||
|---|---|---|---|---|---|
| I |
II |
III |
IV |
V |
|
| With diagnostic test results |
|||||
| Copper sulfate urine sugar tests (false-positive test results may occur with chronic use of salicylates in doses equivalent in salicylate content to 2.4 grams or more of aspirin a day) |
 |
||||
| Gastric emptying studies (opioids delay gastric emptying, thereby invalidating test results) |
|
||||
| Gerhardt test for urine aceto-acetic acid (aspirin or sodium salicylate may cause interference because reaction with ferric chloride produces a reddish color that persists after boiling) |
|
||||
| Glucose, blood (acetaminophen may cause falsely decreased blood glucose values when measured by the glucose oxidase/peroxidase method but probably not when measured by the hexokinase/glucose-6-phosphate dehydrogenase [G6PD] method) |
|||||
| (values may be falsely increased when certain instruments are used in glucose analysis if high acetaminophen concentrations are present; consult manufacturer's instruction manual) |
|
||||
| Glucose enzymatic urine sugar tests (false-negative test results may occur with chronic use of salicylates in doses equivalent in salicylate content to 2.4 grams or more of aspirin a day) |
|
||||
| Hepatobiliary imaging using technetium Tc 99m disofenin, technetium Tc 99m lidofenin, technetium Tc 99m mebrofenin (delivery of these technetium Tc 99m–labeled radiopharmaceuticals to the small bowel may be prevented because opioids may cause constriction of the sphincter of Oddi and increased biliary tract pressure; these actions result in delayed visualization and thus resemble obstruction of the common bile duct) |
|
||||
| 5-hydroxyindoleacetic acid (5-HIAA), urine (urinary determinations may be falsely increased when nitrosonaphthol reagent is used because of color interference by guaifenesin metabolites) {15} {16} (acetaminophen may cause false-positive results in qualitative screening tests using nitrosonaphthol reagent; the quantitative test is unaffected) |
|||||
| (aspirin may alter results when fluorescent method is used) |
|
||||
| Pancreatic function determinations using bentiromide (administration of acetaminophen prior to the bentiromide test will invalidate test results because acetaminophen is also metabolized to an arylamine and will thus increase the apparent quantity of para-aminobenzoic acid [PABA] recovered; it is recommended that acetaminophen be discontinued at least 3 days prior to administration of bentiromide) |
|
||||
| Skin tests using allergen extracts (antihistamines contained in these combinations may inhibit the cutaneous histamine response thus producing false-negative results; it is recommended that antihistamine-containing medication be discontinued at least 72 hours before testing begins) |
|
||||
| Thyroid function tests (iodides may alter the results of these tests, and a high intake of inorganic iodides has also been shown to interfere with determination of protein bound iodine [PBI]; these effects have not been reported with iodinated glycerol in usual recommended doses, but they should be kept in mind for patients receiving prolonged therapy) |
|
||||
| Uric acid, serum (acetaminophen may cause falsely increased values when the phosphotungstate uric acid test method is used) |
|
||||
| Vanillylmandelic acid (VMA), urine (guaifenesin or its metabolites may cause color interference with urinary determinations) {15} (values may be falsely increased or decreased by salicylates, depending on the method used) |
|
||||
| With physiology/laboratory test values |
|||||
| Amylase activity, plasma, and Lipase activity, plasma (may be increased because opioids can cause contractions of the sphincter of Oddi and increased biliary tract pressure; the diagnostic utility of determinations of these enzymes may be compromised for up to 24 hours after the medication has been given) |
|
||||
| Bilirubin, serum, and Lactate dehydrogenase (LDH), serum, and Prothrombin time and Transaminase, serum (prothrombin time and concentrations of bilirubin, LDH, and transaminase may be increased indicating acetaminophen-induced hepatotoxicity, especially in alcoholics, patients taking hepatic enzyme–inducing agents, or those with pre-existing hepatic disease, when single toxic doses [>8–10 grams] are taken or with prolonged use of lower doses [>3–5 grams a day]) |
|
||||
| Bleeding time (may be prolonged by aspirin for 4 to 7 days because of suppressed platelet aggregation; as little as 40 mg of aspirin affects platelet function for at least 96 hours following administration; however, clinical bleeding problems have not been reported with small doses [150 mg or less]) |
|
||||
| Platelet aggregation (may be transiently decreased by guaifenesin; however, effects on bleeding time are unlikely) |
|
||||
| Potassium, serum (concentrations may be decreased by aspirin or sodium salicylate because of increased potassium excretion caused by direct effect on renal tubules) |
|
||||
| Protirelin-induced thyroid-stimulating hormone (TSH) release (TSH response to protirelin may be decreased by aspirin in doses of 2 to 3.6 grams daily; peak TSH concentrations occur at the same time after administration but are reduced) |
|
||||
| Uric acid, serum (concentrations may be increased with doses of aspirin or sodium salicylate producing plasma salicylate concentrations below 100 to 150 mcg per mL or decreased with doses producing plasma salicylate concentrations above 100 to 150 mcg per mL) |
|
||||
Side/Adverse Effects
Antihistamine-containing—See Antihistamines (Systemic) .
Antihistamine- and decongestant-containing—See Antihistamines and Decongestants (Systemic) .
Decongestant-containing—See:
• Ephedrine in Bronchodilators, Adrenergic (Systemic) .
• Pseudoephedrine (Systemic).
Dextromethorphan-containing—See Dextromethorphan (Systemic) .
Opioid (narcotic) antitussive–containing—See Opioid (Narcotic) Analgesics (Systemic) .
Expectorant-containing—See:
• Guaifenesin (Systemic).
Analgesic-containing—See:
• Acetaminophen (Systemic).
• Acetaminophen and Salicylates (Systemic).
• Salicylates (Systemic).
Homatropine-containing—See Anticholinergics/Antispasmodics (Systemic) .
Patient Consultation
Note: Products containing phenylpropanolamine were removed from the U.S. and Canadian Markets in November 2000.
Table 2. Patient Consultation
| As an aid to patient consultation, refer to Advice for the Patient, Cough/Cold Combinations (Systemic) . In providing consultation, consider emphasizing the following selected information (» = major clinical significance): |
Legend I=Antihistamine-containing II=Decongestantcontaining |
III=Opioid (Narcotic) Antitussive–containing IV=Non-opioid Anti- tussive–containing V=Expectorant-containing |
VI=Analgesic- containing 1 VII=Anticholi- nergic containing |
||||
|---|---|---|---|---|---|---|---|
| I |
II |
III |
IV |
V |
VI |
VII |
|
| Before using this medication » Conditions affecting use, especially: |
|||||||
| Sensitivity to any of the medications in the combination being taken |
|
|
|
|
|
|
|
| Pregnancy— Concern for the fetus or newborn infant, especially with high-dose and/or long-term usage |
|
|
|
|
|
|
|
| Physical dependence in the neonate possible with regular use |
|
||||||
| Iodinated glycerol not recommended, because may induce fetal goiter |
|
||||||
| Breast-feeding— Antihistamines may cause excitement or irritability in nursing infant |
|
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| High risk for infants from sympathomimetic amines |
|
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| Concern with high doses and chronic use because of high salicylate intake by infant |
2 |
||||||
| Iodinated glycerol not recommended, because may induce skin rash and thyroid suppression in nursing infant |
|
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| Use in children— Increased susceptibility to anticholinergic effects |
|
|
|||||
| Increased susceptibility to vasopressor effects of sympathomimetic amines |
|
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| Paradoxical reaction (hyperexcitability) |
|
|
|
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| Increased susceptibility to toxic effects of salicylates, especially if fever and dehydration present |
2 |
||||||
| Possible association between aspirin usage and Reye's syndrome |
2 |
||||||
| Increased susceptibility to goitrogenic effects of iodides |
3 |
||||||
| Increased susceptibility to respiratory depressant effects of opioids in children up to 2 years of age |
|
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| Use in the elderly— Anticholinergic effects more likely to occur |
|
|
|||||
| Increased sensitivity to CNS and vasopressor effects of sympathomimetic amines |
|
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| Increased susceptibility to toxic effects of salicylates |
2 |
||||||
| Increased susceptibility to respiratory depressant effects of opioids |
|
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| Other medications, especially: Alcohol |
|
|
4 |
|
|||
| Alkalizers, urinary |
2 |
||||||
| Anticholinergics |
|
|
|||||
| Anticoagulants |
2 |
||||||
| Antidepressants, tricyclic |
|
|
|||||
| Antidiabetic agents, oral |
2 |
||||||
| Antihypertensives |
|
||||||
| Anti-inflammatory drugs, nonsteroidal |
2 |
||||||
| Antithyroid agents |
3 |
||||||
| Beta-adrenergic blocking agents, oral |
|
||||||
| CNS depressants |
|
4 |
|||||
| CNS stimulants |
|
||||||
| Heparin |
2 |
||||||
| Lithium |
3 |
||||||
| Methotrexate |
2 |
||||||
| Monoamine oxidase (MAO) inhibitors |
|
|
4 |
|
|||
| Platelet aggregation inhibitors |
2 |
||||||
| Probenecid |
2 |
||||||
| Rauwolfia alkaloids |
|
||||||
| Sulfinpyrazone |
2 |
||||||
| Thrombolytic agents |
2 |
||||||
| Vancomycin |
|
||||||
| Zidovudine |
|
||||||
| Other medical problems, especially: |
|||||||
| Alcoholism, active 9 |
8 |
||||||
| Asthma |
|
4 |
2 |
||||
| Bleeding problems |
2 |
||||||
| Cardiovascular disease |
|
||||||
| Diabetes |
|
||||||
| Diarrhea |
|
||||||
| Gastritis or peptic ulcer |
2 |
||||||
| Glaucoma |
|
|
|||||
| Hypertension |
|
||||||
| Inflammatory bowel disease |
|
||||||
| Prostatic hypertrophy |
|
|
|||||
| Thyroid disease |
|
||||||
| Proper use of this medication Taking with food, water, or milk to minimize gastric irritation |
|
2 |
|||||
| » Importance of drinking a glass of water after each dose of medication to help loosen mucus in lungs |
|
|
|
|
|
|
|
| » Importance of not taking more medication than the amount recommended |
|
|
5 |
|
|
5 |
|
| Swallowing extended-release dosage form whole |
|
|
|
|
|
|
|
| » Not taking combinations containing aspirin if a strong vinegar-like odor is present |
|
||||||
| Missed dose: If on scheduled dosing regimen—Taking as soon as possible; not taking if almost time for next dose; not doubling doses |
|
|
|
|
|
|
|
| » Proper storage |
|
|
|
|
|
|
|
| Precautions while using this medication » Checking with physician if symptoms persist after medication has been used for 7 days or if high fever, skin rash, or continuing headache is present with cough |
|
|
|
|
|
|
|
| Possible interference with skin tests using allergens; need to inform physician of use of medication |
|
||||||
| » Avoiding use of alcohol or other CNS depressants |
|
|
|||||
| » Caution if drowsiness or dizziness occurs |
|
6 |
|||||
| Lying down if nausea occurs |
|
||||||
| Possible dryness of mouth; using sugarless candy or gum, ice, or saliva substitute for relief; checking with physician or dentist if dry mouth continues for more than 2 weeks |
|
|
|||||
| May mask ototoxic effects of large doses of salicylates |
|
||||||
| » Caution if taking appetite suppressants |
|
||||||
| » Possible insomnia; taking the medication a few hours before bedtime |
7 |
||||||
| » Caution during exercise and hot weather; overheating may result in heat stroke |
|
||||||
| Caution when getting up suddenly from a lying or sitting position |
|
||||||
| Need to inform physician or dentist of use of medication if any kind of surgery (including dental surgery) or emergency treatment is required |
|
|
|||||
| » Caution if other medications containing acetaminophen, aspirin, or other salicylates (including diflunisal) are used |
|
||||||
| Diabetics: Salicylates present in some of these combinations may cause false urine sugar tablet test results with use of larger doses |
|
||||||
| Not taking products containing aspirin for 5 days prior to any kind of surgery, unless otherwise directed by physician |
|
||||||
| Side/adverse effects Signs of potential side effects, especially: Allergic reactions |
|
|
|
|
|
|
|
| Anemia |
|
||||||
| Anticholinergic effects |
|
|
|||||
| Blood dyscrasias |
|
||||||
| Gastrointestinal irritation or bleeding |
2 |
||||||
| Jaundice |
8 |
||||||
| Parotitis, acute |
3 |
||||||
2 Applies to salicylates only, particularly aspirin.
3 Applies to iodides (e.g., calcium iodide, iodinated glycerol, potassium iodide) only.
4 Applies to dextromethorphan.
5 Danger of overdose of acetaminophen, salicylates, or opioid (narcotic) antitussives; also, acetaminophen may cause liver damage with long-term or high-dose use.
6 In addition to drowsiness and dizziness, a false sense of well-being may also occur with the opioid (narcotic) antitussives.
7 The possibility of insomnia may be minimized with preparations containing an antihistamine or an opioid (narcotic) antitussive.
8 Applies to acetaminophen only.
9 Caution should be exercised whether alcoholism is active or in remission with all alcohol-containing products.
Oral Dosage Forms
Note: Products containing phenylpropanolamine were removed from the U.S. and Canadian Markets in November 2000.{61}
Table 3. Oral Dosage Forms
Note: Content per capsule, tablet, or 5 mL, unless otherwise stated.
| Brand or generic name [availability] |
Antihistamines |
Decongestants |
Antitussives |
Expec- torants |
Analgesics |
Other content information as per product label |
Usual adult and adolescent dose prn ‡ |
Usual pediatric dose prn |
Packaging, storage and auxiliary labeling § |
|
|---|---|---|---|---|---|---|---|---|---|---|
| Opioid |
Non-opioid |
|||||||||
| Alka-Seltzer Plus Cold and Cough Effervescent Tablets (OTC) [U.S.] |
Chlorpheniramine maleate 2 mg |
Phenylephrine HCL 5 mg |
Dextrometh- orphan HBr 10 mg |
Phenylalanine 11.2 mg Sodium 507 mg |
a, e |
|||||
| Alka-Seltzer Plus Cold & Cough Medicine Liqui-Gels Capsules (OTC) [U.S.] |
Chlorpheniramine maleate 2 mg |
Pseudoephedrine HCl 30 mg |
Dextrometh- orphan HBr 10 mg |
Acetamin- ophen 325 mg |
6–12 yrs: 1 cap q 4 hr (max 4 caps/day) |
a, e |
||||
| Alka-Seltzer Plus Flu & Body Aches Medicine Liqui-Gels Capsules (OTC) [U.S.] |
Pseudoephedrine HCl 30 mg |
Dextrometh- orphan HBr 10 mg |
Acetamin- ophen 250 mg |
2 caps q 4 hr (max 8 caps/day) |
6–12 yrs: 1 cap q 4 hr (max 4 caps/day) |
a, e |
||||
| Alka-Seltzer Plus Night Time Cold Effervescent Tablets (OTC) [U.S.] |
Doxylamine succinate 6.25 mg |
Phenylephrine HCL 5 mg |
Dextrometh- orphan HBr 10 mg |
Aspirin 500 mg |
Sodium 506 mg Phenylalanine 16.2 mg |
a, e |
||||
| Alka-Seltzer Plus Night-Time Cold Liqui-Gels Capsules (OTC) [U.S.] |
Doxylamine succinate 6.25 mg |
Pseudoephedrine HCl 30 mg |
Dextrometh- orphan HBr 15 mg |
Acetamin- ophen 325 mg |
Alcohol free |
b, e |
||||
| Ami-Tex LA Extended-release Tablets (Rx) [U.S.] |
Phenylephrine HCl 30 mg |
Guaifenesin 600 mg |
Scored |
1 tab q 12 hr |
6–12 yrs: 1/2 tab q 12 hr |
a1 , d |
||||
| Anatuss LA Extended-release Tablets (Rx) [U.S.] |
Pseudoephedrine HCl 120 mg |
Guaifenesin 400 mg |
Scored |
1 tab q 12 hr |
6–12 yrs: 1/2 tab q 12 hr |
b |
||||
| Anti-Tuss DM Expectorant Oral Solution (OTC) [U.S.] |
Dextrometh- orphan HBr 15 mg |
Guaifenesin 100 mg |
Alcohol 1.4% |
b, c |
||||||
| Benylin DM-D Syrup (OTC) [Canada] |
Pseudoephedrine HCl 30 mg |
Dextrometh- orphan HBr 15 mg |
Alcohol free Sodium 19 mg Sugar free |
10 mL q 6 hr (max 4 doses/day) |
2–5 yrs: 2.5 mL, 6–11 yrs: 5 mL, q 6 hr (max 4 doses/day) |
a |
||||
| Benylin DM-D for Children Syrup (OTC) [Canada] |
Pseudoephedrine HCl 15 mg |
Dextrometh- orphan HBr 7.5 mg |
Alcohol free Sodium 11.04 mg Sugar free |
2–5 yrs: 5 mL, 6–12 yrs: 10 mL, q 6 hr |
a |
|||||
| Benylin DM-D-E Syrup (OTC) [Canada] |
Pseudoephedrine HCl 30 mg |
Dextrometh- orphan HBr 15 mg |
Guaifenesin 100 mg |
Alcohol 5% Sodium 20.6 mg Sugar free |
10 mL q 6 hr (max 4 doses/day) |
2–5 yrs: 2.5 mL, 6–11 yrs: 5 mL, q 6 hr (max 4 doses/day) |
a |
|||
| Benylin DM-D-E Extra Strength Syrup (OTC) [Canada] |
Pseudoephedrine HCl 30 mg |
Dextrometh- orphan HBr 15 mg |
Guaifenesin 200 mg |
Alcohol 5% Sodium 19.6 mg Sugar free |
10 mL q 6 hr (max 4 doses/day) |
Not recommended |
a |
|||
| Benylin DM-E Syrup (OTC) [Canada] |
Dextrometh- orphan HBr 15 mg |
Guaifenesin 100 mg |
Alcohol 5% Sodium 20.6 mg Sugar free |
10 mL q 6 hr (max 4 doses/day) |
2–5 yrs: 2.5 mL, 6–11 yrs: 5 mL, q 6 hr (max 4 doses/day) |
a |
||||
| Benylin DM-E Extra Strength Syrup (OTC) [Canada] |
Dextrometh- orphan HBr 15 mg |
Guaifenesin 200 mg |
Alcohol Sodium 19.6 mg Sugar free |
10 mL q 6 hr (max 4 doses/day) |
Not recommended |
a |
||||
| Benylin Expectorant Oral Solution (OTC) [U.S.] |
Dextrometh- orphan HBr 10 mg |
Guaifenesin 100 mg |
Alcohol free Sugar free |
b, c |
||||||
| Benylin 4 Flu Oral Solution (OTC) [Canada] |
Pseudoephedrine HCl 30 mg/15 mL |
Dextrometh- orphan HBr 15 mg/15 mL |
Guaifenesin 100 mg/ 15 mL |
Acetami- nophen 500 mg/ 15 mL |
Alcohol 5% Sugar free |
30 mL q 6 hr (max 4 doses/day) |
Not recommended |
a, c |
||
| Bromfed-DM Syrup (Rx) [U.S.] |
Brompheniramine maleate 2 mg |
Pseudoephedrine HCl 30 mg |
Dextromethorphan HBr 10 mg |
Alcohol free |
10 mL q 4 hr (max 6 doses/day) |
2–6 yrs: 2.5 mL, 6–12 yrs: 5 mL, q 4 hr (max 6 doses/day) |
a, c, d, e |
|||
| Broncholate Syrup (Rx) [U.S.] |
Ephedrine HCl 6.25 mg |
Guaifenesin 100 mg |
10–20 mL q 4 hr |
2–6 yrs: 2.5–5 mL, 6–12 yrs: 5–10 mL, q 4 hr |
a, c, d |
|||||
| Brontex Oral Solution (Schedule V) [U.S.] |
Codeine PO 4 2.5 mg |
Guaifenesin 75 mg |
20 mL q 4 hr (max 120 mL/day) |
6–12 yrs: 10 mL q 4 hr |
b, e, f |
|||||
| Tablets (Schedule III) [U.S.] |
Codeine PO 4 10 mg |
Guaifenesin 300 mg |
1 tab q 4 hr |
Recommended for use in pediatric patients 12 years of age and older |
b, e, f |
|||||
| Calmydone Syrup (N) [Canada] |
Doxylamine succinate 1.2 mg/mL |
Etafedrine HCl 3.33 mg/mL |
Hydrocodone bitartrate 0.33 mg/mL |
Alcohol 5% Sodium citrate 40 mg/mL |
a, e, f |
|||||
| Calmylin #2 Syrup (OTC) [Canada] |
Pseudoephedrine HCl 30 mg |
Dextrometh- orphan HBr 15 mg |
Alcohol free Sugar free |
5–10 mL q 6–8 hr |
2–5 yrs: 2.5 mL, 6–12 yrs: 5 mL, q 6–8 hr |
a, c, e |
||||
| Calmylin #3 Syrup (OTC) [Canada] |
Pseudoephedrine HCl 30 mg |
Dextrometh- orphan HBr 15 mg |
Guaifenesin 100 mg |
Alcohol 5% Sugar free |
10 mL q 6–8 hr |
2–5 yrs: 2.5 mL, 6–12 yrs: 5 mL, q 6–8 hr |
a, c, e |
|||
| Calmylin #4 Syrup (OTC) [Canada] |
Diphenhydramine HCl 12.5 mg |
Dextrometh- orphan HBr 15 mg |
Ammonium chloride † 125 mg |
Alcohol 5% |
5–10 mL q 6–8 hr |
2–3 yrs: 1.25 mL, 4–12 yrs: 2.5–5 mL, q 6–8 hr |
a, c, e |
|||
| Calmylin Cough & Flu Syrup (OTC) [Canada] |
Pseudoephedrine HCl 30 mg/ 15 mL |
Dextrometh- orphan HBr 15 mg/15 mL |
Guaifenesin 100 mg/ 15 mL |
Acetamin- ophen 325 mg/ 15 mL |
Alcohol free Sugar free |
15–30 mL q 6–8 hr (max 120 mL/day) |
Not recommended |
a, c |
||
| Calmylin DM-D-E Extra Strength Syrup (OTC) [Canada] |
Pseudoephedrine HCl 30 mg |
Dextrometh- orphan HBr 15 mg |
Guaifenesin 200 mg |
Alcohol 5% Sugar free |
10 mL q 6 hr |
Not recommended |
a, c |
|||
| Calmylin Original with Codeine Syrup (N) [Canada] |
Diphenhydramine HCl 12.5 mg |
Codeine PO 4 3.33 mg |
Ammonium chloride † 125 mg |
Alcohol 2.9% |
5–10 mL q 3–4 hr |
b, c, e, f |
||||
| Calmylin Pediatric Syrup (OTC) [Canada] |
Pseudoephedrine HCl 15 mg |
Dextrometh- orphan HBr 7.5 mg |
Alcohol free Sugar free |
1–2 yrs: 2.5 mL 2–6 yrs: 5 mL, 6–12 yrs: 10 mL, q 6–8 hr |
a, c |
|||||
| Carbinoxamine Compound-Drops Oral Solution (Rx) [U.S.] |
Carbinoxamine maleate 2 mg/mL |
Pseudoephedrine HCl 25 mg/mL |
Dextrometh- orphan HBr 4 mg/mL |
Alcohol <0.2% |
1& | |||||