CONTRAINDICATIONS, WARNINGS, AND INTERACTIONS

Topiramate is contraindicated in those hypersensitive to the drug. Topiramate should

be used with caution in those who have a history of urolithiasis, paresthesias,

secondary angle closure glaucoma, renal or hepatic impairment, and conditions or

therapies that predispose to acidosis (e.g., renal disease, severe respiratory

disorders, status epilepticus, diarrhea, surgery, ketogenic diet, or drugs). Monitoring

for hyperchloremic non–ionic-gap metabolic acidosis is essential, and therefore

baseline chemistry (e.g., HCO3

− and pH) should be assessed and monitored regularly

thereafter. Metabolic acidosis can cause symptoms such as tiredness and loss of

appetite, or more serious conditions including arrhythmia or coma. Topiramate has

been found to be teratogenic in animal studies and is a pregnancy category C

medication.

264

Concomitant use of oral contraceptives, phenytoin, carbamazepine, and valproic

acid has been found to interact with topiramate.

220 Coadministration of another

carbonic anhydrase inhibitor, such as acetazolamide, may increase the possibility of

renal stone formation and should be avoided.

COMORBIDITIES IN ALCOHOL USE DISORDER

It is quite common for patients who are involved in harmful drinking to have

comorbid medical issues. Alcohol has significant drug interactions with many

medications (Table 90-8). Clinicians must also consider the potential for comorbid

psychiatric disorders, (also known as dual diagnosis, e.g., depression, bipolar

disorder, or schizophrenia) combined with a substance use disorders. Tobacco and

caffeine dependence are common.

265

Increased comorbid conditions lead to a poorer

treatment prognosis for both medical and psychiatric conditions.

p. 1901

p. 1902

Table 90-8

Ethanol–Drug Interactions

Acetaminophen Chronic excessive alcohol consumption increases susceptibility to acetaminophen-induced

hepatotoxicity. Acute intoxication theoretically protects against acetaminophen toxicity

because less hepatotoxic metabolite is generated.

Anticoagulants (oral) Chronic ethanol consumption induces hepatic metabolism of warfarin, decreasing

hypoprothrombinemic effect. Very large acute ethanol doses (>3 drinks/day) may impair

the metabolism of warfarin and increase hypothrombinemic effect. Vitamin K-dependent

clotting factors may be reduced in alcoholics with liver disease, also affecting coagulation.

Antidepressants Enhanced sedative effects of alcohol and psychomotor impairment are possible. Acute

ethanol impairs metabolism. Fluoxetine, paroxetine, fluvoxamine, and probably other

serotonin reuptake inhibitors (SSRIs) do not interfere with psychomotor or subjective

effects of ethanol.

Ascorbic acid Ascorbic acid increases ethanol clearance and serum triglyceride levels and improves

motor coordination and color discrimination after ethanol consumption. Barbiturates Phenobarbital decreases blood ethanol concentration; acute intoxication inhibits

pentobarbital metabolism; chronic intoxication enhances hepatic pentobarbital metabolism.

Benzodiazepines Psychomotor impairment increases with the combination.

Bromocriptine Ethanol increases gastrointestinalside effects of bromocriptine.

Caffeine Caffeine has no effect on ethanol-induced psychomotor impairment.

Calcium-channel

blockers

Verapamil inhibits ethanol metabolism and increases intoxication.

Cephalosporin

antibiotics

Ethanol produces flushing, nausea, headaches, tachycardia, and hypotension.

Cephalosporin antibiotics that have an ethyl tetrazole thiolside chain produce this

disulfiram-like reaction (e.g., cefoperazone, cefamandole, cefotetan).

Chloral hydrate Elevation of plasma trichloroethanol (a chloral hydrate metabolite) and blood ethanol may

occur. Combined central nervous system (CNS) depression. Vasodilation, tachycardia,

headache.

Chloroform Ethanol increases chloroform hepatotoxicity.

Doxycycline Chronic consumption of ethanol induces hepatic metabolism of doxycycline and may

lower serum concentration of the antibiotic.

Erythromycin Ethanol may interfere with absorption of the ethylsuccinate salt. Effects on other

formulations are unknown.

Furazolidone When ethanol is ingested, nausea, flushing, light-headedness, and dyspnea may occur (i.e.,

a disulfiram-like reaction).

H2

antagonists Cimetidine potentiates ethanol effects. Increases peak plasma ethanol concentrations and

area under the plasma ethanol concentration–time curve. CNS toxicity from increased

cimetidine serum concentration. Nizatidine and ranitidine may also increase blood alcohol

levels (BALs) slightly by inhibiting gastric alcohol dehydrogenase. Famotidine does not

affect BALs.

Isoniazid Consumption of ethanol with isoniazid increases risk of hepatotoxicity. Tyraminecontaining alcoholic beverages may cause hypertensive reaction.

Ketoconazole and

metronidazole

When ethanol is ingested, nausea, flushing, light-headedness, and dyspnea may occur (i.e.,

a disulfiram-like reaction may occur with metronidazole). A sunburn-like rash has been

reported with ethanol consumption and ketoconazole. A similar reaction may occur with

itraconazole, although no reports exist.

Meprobamate Synergistic CNS depression may occur.

Metoclopramide Enhances sedative effects of ethanol.

Monoamine oxidase

inhibitors

Tyramine-containing alcoholic beverages (e.g., wines, beer) may cause a hypertensive

crisis. Pargyline may inhibit aldehyde dehydrogenase and cause a disulfiram-like

interaction with ethanol.

Narcotic analgesics Volume of distribution of intravenous meperidine increases with increasing ethanol

consumption. Clinicalsignificance unknown. Potential for enhanced CNS depression.

Oral hypoglycemic

agents

Chlorpropamide, tolbutamide, and tolazamide may cause flushing, light-headedness,

nausea, and dyspnea if alcohol is ingested (i.e., a disulfiram-like reaction).

Paraldehyde Possible metabolic acidosis may occur.

Phenothiazines Potentiates psychomotor effects of ethanol.

Quinacrine Possibly inhibits acetaldehyde oxidation.

Salicylates Increases gastric bleeding associated with aspirin; may increase chance of gastrointestinal

hemorrhage.

Tetrachloroethylene Combined CNS depression may occur.

Trichloroethylene Flushing, lacrimation, blurred vision, and tachypnea may occur when patients exposed to

trichloroethylene drink alcohol.

Adapted from Ciraulo D, Shader RI, Greenblatt DJ, Creelman WL. Drug Interactions in Psychiatry. 3rd ed.

Philadelphia, PA: Lippincott Williams & Wilkins; 2006, with permission.

Principles for the optimal treatment of patients with a dual diagnosis include the

following: (a) flexibility (e.g., although the goal of treatment may be abstinence, for

some patents, movement in the right direction is just as important to keep the person

engaged in treatment); (b) repetition (e.g., a constant refocusing of attention for

avoiding alcohol and for confronting their psychiatric symptoms is a priority); and

(c) counseling (e.g., matching patients to the appropriate intervention). These factors

are all fundamental to long-lasting treatment success. Medications, when appropriate

(e.g., early and vigorous drug intervention with nonaddictive medications), may also

help the patient stay in treatment; however, every effort must be made to use

medications that do not induce euphoria or cause dependence, and are effective and

safe even during relapse.

2,3

Patients with both drug use and psychiatric disorders constitute a substantial and

challenging subpopulation. Treating the alcohol use disorder alone predicts a poorer

outcome for other disorders including early relapse. Early and aggressive treatment

for each condition should be implemented. Furthermore, care must be taken to ensure

that the medications prescribed are safe if combined with alcohol.

3

ACKNOWLEDGMENT

The author acknowledges the authors for their contributions to the following chapters

in previous versions of the textbook: Wendy O. Zizzo and Paolo V. Zizzo for their

chapter on Drug Abuse and George A. Kenna for his chapter on Alcohol Use

Disorders.

KEY REFERENCES AND WEBSITES

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