CIMETIDINE

(sye-met'i-deen)

Tagamet, Tagamet HB
Classifications: antisecretory (h₂-receptor antagonist);
Therapeutic: h₂-receptor antagonist; antisecretory
Pregnancy Category: B

Availability

100 mg, 200 mg, 400 mg, 800 mg tablets; 300 mg/5 mL liquid; 150 mg/mL injection

Action

Has high selectivity for histamine H₂-receptors on parietal cells of the stomach. By inhibition of histamine at the H₂-receptor sites, it suppresses all phases of daytime and nocturnal basal gastric acid secretion in the stomach. Indirectly reduces pepsin secretion.

Therapeutic Effect

Blocks the H₂-receptors on the parietal cells of the stomach, thus decreasing gastric acid secretion; raises the pH of the stomach and thereby reduces pepsin secretion.

Uses

Short-term treatment of active duodenal ulcer and prevention of ulcer recurrence (at reduced dosage) after it is healed. Also used for short-term treatment of active benign gastric ulcer, pathologic hypersecretory conditions such as Zollinger-Ellison syndrome, and heartburn.

Unlabeled Uses

Prophylaxis of stress-induced ulcers, upper GI bleeding, and aspiration pneumonitis; gastroesophageal reflux; chronic urticaria; acetaminophen toxicity.

Contraindications

Known hypersensitivity to cimetidine or other H₂-receptor antagonists.

Cautious Use

Older adults or critically ill patients; impaired renal or hepatic function; organic brain syndrome; gastric ulcers; immunocompromised patients, pregnancy (category B).

Route & Dosage

Duodenal Ulcer
Adult: PO 300 mg q.i.d. or 400 mg b.i.d. or 800 mg h.s. IM/IV 300 mg q6–8h
Child: PO/IM/IV 20–40 mg/kg/d in 4 divided doses
Neonate: PO/IM/IV 5–10 mg/kg/d divided q8–12h
Infant: PO/IM/IV 10–20 mg/kg/d divided q6–12h

Duodenal Ulcer, Maintenance Therapy
Adult: PO 400 mg h.s.

Gastric Ulcer
Adult: PO 300 mg q.i.d. with meals and h.s. IM/IV 300 mg q6–8h

Upper GI Bleed
Adult: IV 37.5 mg/h

Heartburn
Adult: PO 200 mg 2–4 times/d

Pathologic Hypersecretory Disease
Adult: PO 300 mg q.i.d. with meals and h.s., may increase up to 2400 mg/d IM/IV 300 mg q6–8h, may increase up to 2400 mg/d

Renal Impairment
Cl_cr <20 mL/min: dose q12h
Hemodialysis: Give scheduled dose after dialysis

Administration

Oral

Give 1 h before or 2 h after an antacid.

Intravenous

IV administration to neonates, infants and children: Verify correct IV concentration and rate of infusion/injection with physician.

PREPARE: Direct: Dilute 300 mg in 18 mL D5W or NS to yield 300 mg/20 mL. Intermittent: Dilute 300 mg in 50 mL D5W or NS. Continuous: Further dilute in up to 1000 mL of selected IV solution.

ADMINISTER: Direct: Give 300 mg or fraction thereof over at least 5 min. Intermittent: Give over 15–20 min. Continuous: Give a loading dose of 150 mg at the intermittent infusion rate; then give continuous infusion equally spaced over 24 h.

INCOMPATIBILITIES Solution/additive: Amphotericin B, cefazolin, chlorpromazine, pentobarbital, phenobarbital, secobarbital. Y-site: Allopurinol, amphotericin B cholesteryl complex, amsacrine, cefepime, indomethacin, lansoprazole, phenytoin, warfarin.

Parenteral solutions are stable for 48 h at room temperature when added to commonly used IV solutions for dilution. Follow manufacturer's directions.
Store all forms of cimetidine at 15°–30° C (59°–86° F) protected from light unless otherwise directed by manufacturer.

Adverse Effects (≥1%)

Body as a Whole: Fever. CV (rare): Cardiac arrhythmias and cardiac arrest after rapid IV bolus dose. GI: Mild transient diarrhea; severe diarrhea, constipation, abdominal discomfort. Hematologic: Increased prothrombin time; neutropenia (rare), thrombocytopenia (rare), aplastic anemia. Metabolic: Slight increase in serum uric acid, BUN, creatinine; transient pain at IM site; hypospermia. Musculoskeletal: Exacerbation of joint symptoms in patients with preexisting arthritis. CNS: Drowsiness, dizziness, light-headedness, depression, headache, reversible confusional states, paranoid psychosis. Skin: Rash, Stevens-Johnson syndrome, reversible alopecia. Urogenital: Gynecomastia and breast soreness, galactorrhea, reversible impotence.

Diagnostic Test Interference

Cimetidine may cause false-positive Hemoccult test for gastric bleeding if test is performed within 15 min of oral cimetidine administration.

Interactions

Drug: Cimetidine decreases the hepatic metabolism of warfarin, phenobarbital, phenytoin, diazepam, propranolol, lidocaine, theophylline, thus increasing their activity and toxicity; antacids may decrease absorption of cimetidine.

Pharmacokinetics

Absorption: 70% of PO dose absorbed from GI tract. Peak: 1–1.5 h. Distribution: Widely distributed; crosses blood–brain barrier and placenta. Metabolism: In liver by CYP1A2 and 3A4. Elimination: Most of drug excreted in urine in 24 h; excreted in breast milk. Half-Life: 2 h.

Nursing Implications

Assessment & Drug Effects

Ulcer healing may occur within the first 2 wk of therapy but generally requires at least 4 wk in most patients. Short-term (i.e., 8 wk) therapy of active duodenal ulcer does not prevent ulcer recurrence when drug is discontinued.
Monitor pulse of patient during first few days of drug regimen. Bradycardia after PO as well as IV administration should be reported. Pulse usually returns to normal within 24 h after drug discontinuation.
Monitor I&O ratio and pattern: Particularly in the older adult, severely ill, and in patients with impaired renal function.
Report loss of bowel sounds, absence of bowel movement or flatus, vomiting, crampy pain, abdominal distention. Adynamic ileus has been reported in patients receiving cimetidine to prevent and treat stress ulcers.
Lab tests: Periodic evaluations of blood count and renal and hepatic function are advised during therapy.
Be alert to onset of confusional states, particularly in the older adult or severely ill patient. Symptoms occur within 2–3 d after first dose. Report immediately: drug should be withdrawn. Symptoms usually resolve within 3–4 d after therapy is discontinued.
Check BP and report an elevation to the physician, if patient complains of severe headache.
Cimetidine impairs absorption of protein-bound vitamin B₁₂; therefore patient who takes cimetidine in divided doses to continuously suppress acid gastric secretion is at risk for vitamin B₁₂ deficiency (no risk for patient who takes drug at bedtime to suppress nocturnal acid production).

Patient & Family Education

Cimetidine must be taken exactly as prescribed. Sudden discontinuation of therapy reportedly has caused perforation of chronic peptic ulcer.
Seek advice about self-medication with any OTC drug.
Report breast tenderness or enlargement. Mild bilateral gynecomastia and breast soreness may occur after ≥1 mo of therapy. It may disappear spontaneously or remain throughout therapy.
Report recurrence of gastric pain or bleeding (black, tarry stools or "coffee ground" vomitus) immediately, and notify physician if diarrhea continues more than 1 d.
Avoid driving and other potentially hazardous activities until reaction to drug is known.
Duodenal or gastric ulcer is a chronic, recurrent condition that requires long-term maintenance drug therapy.
Maintenance therapy at reduced dosage after healing of active duodenal ulcer appears to limit recurrence, particularly if patient undertakes other antiulcer therapeutic measures: no smoking, life-style that promotes reduced stress.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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