Cimetidine dosing

Cimetidine, an H2 antagonist used therapeutically in patients with ulcers, inhibits activity of hepatic microsomal enzymes. When rats or mice were pretreated with cimetidine, dose-related lethality of methyl parathion was reduced, and cholinergic signs of toxicity were delayed. Simultaneous administration with methyl parathion did not reduce toxicity (Joshi and Thornburg 1986). 

Pharmacokinetics" the label indicates that "following I.V. or I.M. administration, approximately 75% of the drug is recovered from the urine after 24 hours as the parent compound" (14). Since only one-fourth of the dose is eliminated by nonrenal mechanisms, it can be expected that functionally anephric patients who receive half the usual cimetidine dose, such as the man in the case presented at the beginning of this chapter, will have potentially toxic blood levels that are twice those recommended for patients with normal renal function. 

Thrombocytopenia has been attributed to cimetidine, with recurrence on rechallenge, and neutropenia has also been documented as an occasional adverse effect, possibly related to inhibition of granulocyte colony growth (SEDA-10, 325). These effects appear to occur with aU H2 receptor antagonists in an incidence roughly proportional to their sales. Exceptionally, thrombocytopenia and leukopenia have occurred together (SEDA-17, 417). In one case of pancytopenia there was cimetidine dose-related inhibition of normal human CFU-GM colon formation (SEDA-16, 422). 

Importantly, it exhibits relatively higher oral bioavailability (60-70%), and a plasma half-life of - 2 hour that gets enhaneed particularly either in agedsubjects or those having a renal and hepatic impairment. However, it has been observed that nearly 30 to 40% of a cimetidine dose gets metabolized either as S-oxidation or a 5-CH3 hydroxylation. Finally, the parent drug and the metabolites are virtually eliminated primarily by the renal excretion. 

Cohen, I. A. et al., Cimetidine-theophylline interaction effects of age and cimetidine dose, Ther. Drug Monit., 7(4) 426 34, 1985. 

A study in patients with suspected myocardial infarction given two 300-mg oral doses of cimetidine 4 hours apart, starting 11 to 20 hours after a 2 mg/minute infusion of lidoeaine began, showed that total lidoeaine serum levels had risen by 28%, and unbound levels by 18%, 24 hours after the initial cimetidine dose. In three of these patients whose diagnosis of myocardial infarction was subsequently confirmed, rises in total and unbound lidoeaine... 

In a preliminary report of a study, 4 days of treatment with cimetidine [dose not stated] in 11 healthy subjects had a small effect on the pharmacokinetics of tocainide 500 mg given intravenously over 15 minutes, whieh was not considered elinieally important. In another study, cimetidine 300 mg four times daily for 2 days reduced the AUC of a single 400-mg oral dose of toeainide in 7 healthy subjects by about one-third. The peak... 

This interaction has been described in many reports and studies involving patients and healthy subjects. "" Phenytoin toxicity has developed in some individuals. The extent of the rise in serum levels is very variable being quoted as 13 to 33% over about 6 days in one report and 22 to 280% over 3 weeks in others." There is some evidence that the effect may be dependent on cimetidine dose. One study found that the effect of cimetidine 2.4 g daily was greater than that of 1.2 g daily or 400 mg daily, which did not differ from each other. In another study, cimetidine 200 mg twice daily for 2 weeks had no effect on serum phenytoin levels in 9 patients taking stable doses of phenytoin. ... 

Asghamejad M, Powell JR, Donn KH, Danis M The effect of cimetidine dose tim ing on oral... 

In this study patients were treated for up to 83 days with these intravenous cimetidine doses without side-effects or loss of efficacy. Another recent study [68] demonstrated that continuous intravenous infusion of ranitidine at 100% of the previously effective oral equivalent dose will effectively control acid output in 95 % of patients with ZES, thus limiting the need for repeated dose adjustments and gastric output assessment in patients who require parenteral therapy. It must be stressed, however, that the adequacy of the administered dose should be checked by measuring acid output after a few hours to ensure that acid output is less than 10 mEq/h. It was recommended [14, 35, 66] that acid output be rechecked... 

The development of easy-to-use assays for determining theophylline blood levels afforded a handle on maintenance of effective but nontoxic levels. The relatively good availabihty of such assays in the United States probably contributed to the historical preference for theophylline treatment by U.S. physicians. Careful titration of the dose must be done on a patient-by-patient basis because individual rates of metaboHsm vary widely. Most ( 85%) of an oral dose of theophylline is metabolized by Hver microsomal enzymes. As a result many dmgs, eg, cimetidine [51481-61-9], anticonvulsants, or conditions, eg, fever, cigarette smoking, Hver disease, which affect Hver function alter theophylline blood levels. 

HISTAMINE H2 ANTAGONISTS. The nurse administers ranitidine and oral cimetidine before or with meals and at bedtime Nizatidine and famotidine are given at bedtime or, if twice-a-day dosing is prescribed, in the morning and at bedtime. These drugp are usually given concurrently with an antacid to relieve the pain. In certain situations or disorders, cimetidine and ranitidine may also be given by intermittent IV infusion or direct IV injection. 

Paclitaxel Peripheral neuropathy (DLT), nausea/vomiting, alopecia, hypersensitivity reactions Use caution with any elevation in AST (SGOT). Give proper dosing for liver dysfunction. Premedicate dexamethasone, diphenhydramine, and cimetidine. 

Cimetidine 800 mg PO/IV daily during IL-2 therapy (given in single or divided doses)... 

Nwokolo CU, Smith JT, Gavey C, Sawyerr A, Pounder RE Tolerance during 29 days of conventional dosing with cimetidine, nizatidine, famotidine or ranitidine. Aliment Pharmacol Ther 1990 4(suppl 1) 29—45. 

Histamine-2 antagonists (cimetidine, famotidine, nizatidine, ranitidine) may be used in low doses to manage simple nausea and vomiting associated with heartburn or gastroesophageal reflux. 

Sildenafil doses should be decreased when any potent cytochrome P450 3A4 inhibitor is used (e g., cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and saquinavir). Vardenafil doses vary accordingto which agent is used (2.5 mg q 72 h for ritonavir, 2.5 mg q 24 h for indinavir, ketoconazole 400 mg daily, and itraconazole 400 mg daily and 5 mg q 24 h for ketoconazole 200 mg daily, itraconazole200 mg daily, and erythromycin). Tadalafil doses are reduced only when it is used with the most potent cytochrome P450 3A4 inhibitors (e g., ketoconazole or ritonavir). 

In vitro stndies have shown that there are distinct transport systems for both baso-lateral and apical uptake of nicotine (Takami et al. 1998). Nicotine has been shown to be actively transported by kidney cells, most likely by the organic ion transporter OCT2 (Zevin et al. 1998 Urakami et al. 1998). Cimetidine decreases renal clearance of nicotine by 47% in nonsmoking volunteers (Bendayan et al. 1990). This is consistent with the inhibition of basolateral uptake by cimetidine detected in vitro. Mecamylamine reduces renal clearance of nicotine in smokers dosed with intra-venons nicotine when urine is alkalinized, but not when nrine is acidified (Zevin et al. 2000). 

Antagonists. Most of the so-called Hi-antihistamines also block other receptors, including M-cholinoceptors and D-receptors. Hi-antihistamines are used for the symptomatic relief of allergies (e.g., bamipine, chlorpheniramine, clemastine, dimethindene, mebhydroline pheniramine) as antiemetics (meclizine, dimenhydrinate, p. 330), as over-the-counter hypnotics (e.g., diphenhydramine, p. 222). Promethazine represents the transition to the neuroleptic phenothiazines (p. 236). Unwanted effects of most Hi-antihistamines are lassitude (impaired driving skills) and atropine-like reactions (e.g., dry mouth, constipation). At the usual therapeutic doses, astemizole, cetrizine, fexofenadine, and loratidine are practically devoid of sedative and anticholinergic effects. Hj-antihistamines (cimetidine, ranitidine, famotidine, nizatidine) inhibit gastric acid secretion, and thus are useful in the treatment of peptic ulcers. 

Use caution when using tamsulosin in combination with cimetidine, particularly at doses higher than 0.4 mg. 

Concomitant cimetidine- Give an initial dose of 5 mg to patients concomitantly taking cimetidine (see Drug Interactions). 

Cimetidine, erythromycin, and dextropropoxyphene had no effect on the pharmacokinetics of MHD. Results with warfarin show no evidence of interaction with either single or repeated doses of oxcarbazepine. 

Diazepam (Valium, Diastat) [C-IVj [Anxiolytic, Skeletal Muscle Relaxant, Anticonvulsant, Sedative/Hypnotic/ Benzodiazepine] Uses Anxiety, EtOH withdrawal, muscle spasm, status epilepticus, panic disorders, amnesia, preprocedure sedation Action Benzodiazepine Dose Adults. Status epilepticus 5-10 mg IV/IM Anxiety 2-5 mg IM/IV Preprocedure 5-10 mg IV just prior to procedure Peds. Status epilepticus 0.5-2 mg IV/IM Sedation 0.2-0.5 mg/kg IV (onset w/in 5IV and 30 min IM duration about 1 h IV and IM) Caution [D, / -] Contra Coma, CNS depression, resp d es-sion, NAG, severe uncontrolled pain, PRG Disp Tabs 2, 5, 10 mg soln 1, 5 mg/mL inj 5 mg/mL rectal gel 2.5, 5, 10, 20 mg/mL SE Sedation, amnesia, bradycardia, i BP, rash, X resp rate Interactions T Effects W/ antihistamines, azole antifungals, BBs, CNS depressants, cimetidine, ciprofloxin, disulfiram, INH, OCP, omeprazole, phenytoin, valproic acid, verapamil, EtOH, kava kava, valman T effects OF digoxin, diuretics X effects w/ barbiturates, carbamazepine. 

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