Chapter 2The Pre-Travel Consultation
Drug-Vaccine & Drug-Drug Interactions
Vaccines and medications are prescribed frequently in pre-travel consultations, and potential interactions between vaccines and medications, including those already taken by the patient, must be considered. Although a comprehensive list of interactions is beyond the scope of this section, some of the more significant interactions of commonly used vaccines and medications are discussed here.
INTERACTIONS BETWEEN TRAVEL VACCINES AND DRUGS
Oral Typhoid Vaccine
Sulfonamides and antibiotics may be active against the vaccine strain in the oral typhoid vaccine and prevent an adequate immune response to the vaccine. Therefore, oral typhoid vaccine should not be given to people taking sulfonamides or other antibiotics, including doxycycline. Vaccination with oral typhoid vaccine should be delayed for >72 hours after the administration of any antibacterial agent. Parenteral typhoid vaccine may be a more appropriate choice for these people.
Mefloquine and chloroquine can be given concurrently with the oral typhoid vaccine. Atovaquone-proguanil, at prophylaxis doses, can be given concurrently with the oral typhoid vaccine. Ideally, however, the oral typhoid vaccine should be completed 14 days before travel, limiting the need to administer it concurrently with atovaquone-proguanil. (Updated July 6, 2011)
Concomitant use of chloroquine may reduce antibody response to intradermal rabies vaccine administered for preexposure vaccination. The intramuscular route should be used for people taking chloroquine concurrently (the intradermal route is not approved for use in the United States at this time); ideally, the rabies preexposure vaccination series should be completed before beginning chloroquine.
INTERACTIONS BETWEEN ANTIMALARIALS AND OTHER DRUGS
Mefloquine may interact with several categories of drugs, including other antimalarials, drugs that alter cardiac conduction, and anticonvulsants. Although the antimalarial halofantrine is not available in the United States, travelers who might be offered treatment with this drug outside the United States should be informed about interactions with mefloquine. Potentially fatal prolongation of the QTc interval may occur if halofantrine is given after mefloquine. Halofantrine should be avoided, if at all possible. If halofantrine is given to treat malaria, mefloquine for prophylaxis should not be resumed until ≥12 hours after the last halofantrine dose. Although no conclusive data are available with regard to coadministration of mefloquine and other drugs that may affect cardiac conduction, these drugs should not be used concurrently with mefloquine. These drugs include antiarrhythmic or β-blocking agents, calcium-channel blockers, antihistamines, H1-blocking agents, tricyclic antidepressants, or phenothiazines.
Mefloquine used with the anticonvulsants, such as valproic acid, carbamazepine, phenobarbital, or phenytoin, may lower anticonvulsant plasma levels, thus lowering seizure threshold. Monitoring anticonvulsant levels would be appropriate in people for whom mefloquine must be used concomitantly with these drugs.
Chloroquine absorption may be reduced by antacids or kaolin; ≥4 hours should elapse between doses of these medications. Concomitant use of cimetidine and chloroquine should be avoided, as cimetidine can inhibit the metabolism of chloroquine and may increase drug levels. Chloroquine inhibits bioavailability of ampicillin; 2 hours should elapse between doses.
Tetracycline, rifampin, and rifabutin may reduce plasma concentrations of atovaquone and should not be used concurrently with atovaquone-proguanil. Metoclopramide may reduce bioavailability of atovaquone; unless no other antiemetics are available, this antiemetic should not be used to treat the vomiting that may accompany use of atovaquone at treatment doses. Atovaquone-proguanil should not be used with other medications that contain proguanil. Patients on anticoagulants may need to reduce their anticoagulant doses or monitor their prothrombin time more closely while taking atovaquone-proguanil, although coadministration of these drugs is not contraindicated.
Phenytoin, carbamazepine, and barbiturates may decrease the half-life of doxycycline. Patients on anticoagulants may need to reduce their anticoagulant doses while taking doxycycline because of its ability to depress plasma prothrombin activity. Absorption of tetracyclines may be impaired by bismuth subsalicylate, preparations containing iron, and antacids containing calcium, magnesium, or aluminum; these preparations should not be taken within 3 hours of doxycycline. Doxycycline may interfere with the bactericidal activity of penicillin, so these drugs, in general, should not be taken together.
INTERACTIONS WITH ANTIDIARRHEAL DRUGS
Increase in the international normalized ratio has been reported when levofloxacin and warfarin are used concurrently. Concurrent administration of ciprofloxacin and antacids that contain magnesium or aluminum hydroxide may reduce bioavailability of ciprofloxacin. Ciprofloxacin decreases clearance of theophylline and caffeine; theophylline levels should be monitored when ciprofloxacin is used concurrently. Ciprofloxacin should not be used with tizanidine.
Close monitoring for side effects of azithromycin is recommended when azithromycin is used with nelfinavir. Increased anticoagulant effects have been noted when azithromycin is used with warfarin; monitoring of prothrombin time is recommended for people taking these drugs concomitantly.
No clinically significant drug interactions have been reported to date with rifaximin. Although the drug induces cytochrome P450 3A4 enzymes, studies of concurrent administration of rifaximin with midazolam, and with a single dose of the oral contraceptive ethinyl estradiol and norgestimate, did not show changes in the pharmacokinetics of these drugs.
INTERACTIONS WITH DRUGS USED FOR TRAVEL TO HIGH ALTITUDES
Acetazolamide produces alkaline urine that can increase the rate of excretion of barbiturates and salicylates and may potentiate salicylate toxicity. Decreased excretion of dextroamphetamine, anticholinergics, mecamylamine, ephedrine, mexiletine, or quinidine may also occur. Hypokalemia caused by corticosteroids may be potentiated by concurrent use of acetazolamide.
Dexamethasone interacts with multiple classes of drugs. Using this drug to treat altitude illness may, however, be life saving. Interactions may occur with the following drugs and drug classes: macrolide antibiotics, anticholinesterases, anticoagulants, hypoglycemic agents, isoniazid, digitalis preparations, oral contraceptives, and phenytoin.
- CDC. Sudden death in a traveler following halofantrine administration—Togo, 2000. MMWR Morb Mortal Wkly Rep. 2001 Mar 9;50(9):169–70, 79.
- Horowitz H, Carbonaro CA. Inhibition of the Salmonella typhi oral vaccine strain, Ty21a, by mefloquine and chloroquine. J Infect Dis. 1992 Dec;166(6):1462–4.
- Kollaritsch H, Que JU, Kunz C, Wiedermann G, Herzog C, Cryz SJ Jr. Safety and immunogenicity of live oral cholera and typhoid vaccines administered alone or in combination with antimalarial drugs, oral polio vaccine, or yellow fever vaccine. J Infect Dis. 1997 Apr;175(4):871–5.
- Matson PA, Luby SP, Redd SC, Rolka HR, Meriwether RA. Cardiac effects of standard-dose halofantrine therapy. Am J Trop Med Hyg. 1996 Mar;54(3):229–31.
- Pappaioanou M, Fishbein DB, Dreesen DW, Schwartz IK, Campbell GH, Sumner JW, et al. Antibody response to preexposure human diploid-cell rabies vaccine given concurrently with chloroquine. N Engl J Med. 1986 Jan 30;314(5):280–4.