Ketoconazole Antihistamines

Drugs that may affect antihistamines include aluminum/magnesium-containing acids, cimetidine, erythromycin, ketoconazole, MAO inhibitors, and rifamycins (eg, rifampin). Drugs that may be affected by antihistamines include alcohol and CNS depressants, beta-blockers, MAO inhibitors, metyrapone, nefazodone, selective serotonin reuptake inhibitors (SSRIs), and venlafaxine. 

Flurazepam (Dalmane) [C-IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia Action Benzodiazepine Dose Adults Beds >15 y. 15-30 mg PO qhs PRN X in elderly Caution [X, /-] Elderly, low albumin, hepatic impair Contra NAG PRG Disp Caps SE Hangover d/t accumulation of metabolites, apnea, anaphylaxis, angioedema, amnesia Interactions T CNS depression W/ antidepressants, antihistamines, opioids, EtOH T effects OF digoxin, phenytoin T effects W/ cimetidine, disulfiram, fluoxetine, iso-niazid, ketoconazole, metoprolol, OCPs, propranolol, SSRIs, valproic acid. 

Dicyclomine (Bentyl) [Anrimuscarinic, GI Anrispasmodic/ Anticholinergic] Uses Functional IBS Action Smooth-muscle relaxant Dose Adults. 20 mg PO qid T to 160 mg/d max or 20 mg EM q6h, 80 mg/d - qid then T to 160 mg/d, max 2 wk Feds. Infants >6 mo 5mg/dose tid-qid Children 10 mg/dose tid-qid Caution [B, -] Contra Infants <6 mo, NAG, MyG, severe UC, BOO Disp Caps, tabs, syrup, inj SE Anticholinergic SEs may limit dose Interactions T Anticholinergic effects W/ anticholinergics, antihistamines, amantadine, MAOIs, TCAs, phenothiazides T effects OF atenolol, digoxin X effects H7 antacids X effects OF haloperidol, ketoconazole, levodopa, phenothiazines EMS Avoid procainamide usage, may T adverse effects may T effects of digoxin, monitor... 

Non-sedating antihistamines (e.g. loratidine, e.g. Clarityn cetirizine, e.g. Benadryl, Piriteze, Zirtek clemastine), which can cause dangerous arrhythmias with antifungal agents (itraconazole, ketoconazole), antibiotics (erythromycin, clarithromycin) and drugs used to counteract acidity... 

Ketoconazole affects plasma concentrations of lorata-dine, a non-sedating antihistamine, but appears to be devoid of any electrocardiographic effects (31). In a randomized, single-bhnd, multiple-dose, three-way, crossover study, concomitant administration of loratadine 10 mg qds and ketoconazole 200 mg bd resulted in significantly increased mean loratadine plasma... 

Clinically important, potentially hazardous interactions with alcohol, antihistamines, azatadine, azelastine, brompheniramine, buclizine, chlorpheniramine, cimetidine, clemastine, dexchlorpheniramine, erythromycin, ketoconazole, meclizine, pizotifen, rifampicin, ritonavir... 

Potentially harmful drug interactions may not be identified during controlled clinical trials, due to the exclusion of patients taking concomitant medications, which are not allowed to be taken during a study. For example, terfenadine, a novel nonsedating antihistamine which was found to cause a serious and potentially fatal cardiac arrhythmia, torsades de pointes, when administered with keto-conazole or erythromycin, and this could not realistically have been expected to be identified in the clinical trial setting. The mechanism of this adverse drug interaction was found to be due to cumulation of unmetabolized terfenadine, due to inhibition of cytochrome P-450 (CYP) by ketoconazole or erythromycin the parent terfenadine molecule is usually cleared very rapidly when there is no concomitant CYP inhibitor. 

Many Hj antihistamines are metabolized by CYPs. Thus, inhibitors of CYP activity such as macrolide antibiotics (e.g., erythromycin) or imidazole antifungals (e.g.,ketoconazole) can increase Hj antihistamine levels, leading to toxicity. Some newer antihistamines, such as cetirizine, fexofenadine, levocabastine, and acrivastine, are not subject to these drug interactions. 

Use of antihistamines by persons of Asian background A genetic predisposition to metabolize succinylcholine slowly Treatment of these patients with ketoconazole. an antifungal agent Which of the following drugs is associated with slower metabolism in Caucasians and African-Americans than in most Asians ... 

Cardiotoxicity occurred when ketoconazole was used by patients taking astemizole or terfena-dine, a drug interaction that led to the withdrawal of the two nonsedating antihistamines in the United States. The same type of drug interaction has been reported between ketoconazole and cisapride as a result of the ability of ketoconazole to inhibit hepatic drug-metaholizing enzymes. The answer is (D). 

Cisapride is metabolized by a cytochrome P450 isozyme that is inhibited by erythromycin and by ketoconazole. Decreased clearance of the antihistaminic drugs astemizole and terfenadine (now withdrawn) may also result in cardiotoxicity. The answer is (E). 

---