Cimetidine

Pronunciation: (sigh-MET-ih-deen)

Class: Histamine H 2 antagonist

Trade Names:

Cimetidine
- Tablets 300 mg
- Tablets 400 mg
- Tablets 800 mg
- Liquid 300 mg (as hydrochloride) per 5 mL
- Injection 150 mg (as hydrochloride) per mL

Trade Names:

Cimetidine in 0.9% Sodium Chloride
- Injection, premixed 6 mg (as hydrochloride) per mL

Trade Names:

Tagamet HB
- Tablets 200 mg
Apo-Cimetidine (Canada)
Gen-Cimetidine (Canada)
Nu-Cimet (Canada)

Pharmacology

Pharmacokinetics

Absorption

Oral

Rapidly absorbed. T max is 45 to 90 min. 60% to 70% bioavailable.

Distribution

13% to 25% protein bound. Vd is 0.8 to 1.2 L/kg. Crosses the placenta and is excreted in breast milk.

Metabolism

Following oral administration, cimetidine is extensively metabolized with the sulfoxide being the major metabolite.

Elimination

The t ½ is about 2 h.

Oral

48% is excreted unchanged in the urine.

IV/IM

About 75% is excreted unchanged in the urine.

Special Populations

Renal Function Impairment

Drug accumulation may occur in those with severe renal failure. Dosage adjustment may be necessary.

Indications and Usage

Management of duodenal ulcer; treatment of gastroesophageal reflux disease (GERD), including erosive esophagitis; therapy for benign gastric ulcer; treatment of pathologic hypersecretory conditions; prevention of upper GI bleeding.

Unlabeled Uses

Prevention of aspiration pneumonia and stress ulcers; herpes virus infection; chronic idiopathic urticaria; anaphylaxis (relieves dermatologic symptoms only); dyspepsia; used before anesthesia to prevent aspiration pneumonitis; treatment of hyperparathyroidism and control of secondary hyperparathyroidism in chronic hemodialysis patient; treatment of chronic viral warts in children.
Contraindications

Hypersensitivity to cimetidine or other H 2 antagonists.

Drug Interactions


Amiodarone cimetidine increases plasma concentration of amiodarone Amiodarone has a long half-life; there is a potential for drug interactions to occur for several weeks (or even months) after treatment with it has been stopped
Amitriptyline cimetidine inhibits metabolism of amitriptyline (increased plasma concentration)
Amprenavir plasma concentration of cimetidine possibly increased by amprenavir
Antidepressants, Tricyclic cimetidine possibly increases plasma concentration of tricyclics
Antipsychotics cimetidine possibly enhances effects of antipsychotics Increased risk of toxicity with myelosuppressive drugs
Artemether with Lumefantrine avoidance of cimetidine advised by manufacturer of artemether/lumefantrine
Azapropazone cimetidine possibly increases plasma concentration of azapropazone
Benzodiazepines cimetidine inhibits metabolism of benzodiazepines (increased plasma concentration)
Calcium-channel Blockers cimetidine possibly inhibits metabolism of calcium-channel blockers (increased plasma concentration) Dihydropyridine calcium-channel blockers include amlodipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine, and nisoldipine
Carbamazepine cimetidine inhibits metabolism of carbamazepine (increased plasma concentration)
Chloroquine and Hydroxychloroquine cimetidine inhibits metabolism of chloroquine and hydroxychloroquine (increased plasma concentration)
Chlorpromazine cimetidine possibly enhances effects of chlorpromazine
Ciclosporin cimetidine possibly increases plasma concentration of ciclosporin
Cilostazol cimetidine possibly increases plasma concentration of cilostazol —avoid concomitant use
Citalopram cimetidine increases plasma concentration of citalopram
Clomethiazole cimetidine inhibits metabolism of clomethiazole (increased plasma concentration)
Clozapine cimetidine possibly enhances effects of clozapine Avoid concomitant use of clozapine with drugs that have a substantial potential for causing agranulocytosis
Coumarins cimetidine inhibits metabolism of coumarins (enhanced anticoagulant effect) Change in patient's clinical condition, particularly associated with liver disease, intercurrent illness, or drug administration, necessitates more frequent testing. Major changes in diet (especially involving salads and vegetables) and in alcohol consumption may also affect anticoagulant control
Doxepin cimetidine inhibits metabolism of doxepin (increased plasma concentration)
Epirubicin cimetidine increases plasma concentration of epirubicin
Ergotamine and Methysergide increased risk of ergotism when cimetidine given with ergotamine and methysergide —avoid concomitant use
Erythromycin cimetidine increases plasma concentration of erythromycin (increased risk of toxicity, including deafness) Interactions do not apply to small amounts of erythromycin used topically
Escitalopram cimetidine increases plasma concentration of escitalopram
Flecainide cimetidine inhibits metabolism of flecainide (increased plasma concentration)
Fluorouracil cimetidine inhibits metabolism of fluorouracil (increased plasma concentration)
Imipramine cimetidine inhibits metabolism of imipramine (increased plasma concentration)
Labetalol cimetidine increases plasma concentration of labetalol
Levothyroxine (thyroxine) cimetidine reduces absorption of levothyroxine (thyroxine)
Lidocaine (lignocaine) cimetidine increases plasma concentration of lidocaine (lignocaine) (increased risk of toxicity) Interactions less likely when lidocaine used topically
Loratadine manufacturer of loratadine advises cimetidine possibly increases plasma concentration of loratadine
Mebendazole cimetidine possibly inhibits metabolism of mebendazole (increased plasma concentration)
Metformin cimetidine reduces excretion of metformin (increased plasma concentration)
Metoprolol cimetidine increases plasma concentration of metoprolol
Metronidazole cimetidine inhibits metabolism of metronidazole (increased plasma concentration) Interactions do not apply to topical metronidazole preparations
Mirtazapine cimetidine increases plasma concentration of mirtazapine
Moclobemide cimetidine increases plasma concentration of moclobemide (halve dose of moclobemide)
Nortriptyline cimetidine inhibits metabolism of nortriptyline (increased plasma concentration)
Octreotide absorption of cimetidine possibly delayed by octreotide
Opioid Analgesics cimetidine inhibits metabolism of opioid analgesics (increased plasma concentration)
Phenytoin cimetidine inhibits metabolism of phenytoin (increased plasma concentration)
Posaconazole cimetidine reduces plasma concentration of posaconazole
Pramipexole cimetidine reduces excretion of pramipexole (increased plasma concentration)
Procainamide cimetidine increases plasma concentration of procainamide
Propafenone cimetidine increases plasma concentration of propafenone
Propranolol cimetidine increases plasma concentration of propranolol
Quinine cimetidine inhibits metabolism of quinine (increased plasma concentration)
Rifampicin metabolism of cimetidine accelerated by rifampicin (reduced plasma concentration)
Sertindole increased risk of ventricular arrhythmias when cimetidine given with sertindole —avoid concomitant use
Sertraline cimetidine increases plasma concentration of sertraline
Sildenafil cimetidine increases plasma concentration of sildenafil (reduce initial dose of sildenafil)
Sulphonylureas cimetidine enhances hypoglycaemic effect of sulphonylureas
Terbinafine cimetidine increases plasma concentration of terbinafine
Theophylline cimetidine inhibits metabolism of theophylline (increased plasma concentration)
Tolazoline cimetidine antagonises effects of tolazoline
Valproate cimetidine inhibits metabolism of valproate (increased plasma concentration)
Zaleplon cimetidine inhibits metabolism of zaleplon (increased plasma concentration)
Zolmitriptan cimetidine inhibits metabolism of zolmitriptan (reduce dose of zolmitriptan)
Cimetidine belongs to Histamine H2-antagonists and will have the following interactions:

Atazanavir histamine H2-antagonists possibly reduce plasma concentration of atazanavir
Cefpodoxime histamine H2-antagonists reduce absorption of cefpodoxime
Itraconazole histamine H2-antagonists reduce absorption of itraconazole
Ketoconazole histamine H2-antagonists reduce absorption of ketoconazole


Dosage and Administration

Duodenal Ulcer (Active)

Adults

PO 800 mg at bedtime for 4 to 6 wk.

Alternate regimens

PO 300 mg 4 times daily with meals and at bedtime or 400 mg twice daily.

Maintenance Therapy

PO 400 mg at bedtime.

Active Benign Gastric Ulcer

Adults

PO 800 mg at bedtime.

GERD

Adults

PO 1600 mg daily in divided doses (800 mg or 400 mg) for 12 wk, although some patients may require chronic therapy.
Pathologic Hypersecretory Conditions

Adults

PO 300 mg 4 times daily w/meals and at bedtime. If needed, 300 mg doses may be given more often (max, 2400 mg/day).
Prevention of Upper GI Bleeding

Adults

Continuous IV infusion of 50 mg/h. For hospitalized patients with pathologic hypersecretory conditions or intractable ulcers, or patients unable to take PO medication.

Usual dose

IM/IV 300 mg every 6 h to 8 h (max 2400 mg/day).

General Advice

* Dilute IV dose (300 mg) in 0.9% normal saline, D5W, or other compatible solution to a total of 20 mL. Inject slowly over at least 5 min.
* For intermittent IV infusion, dilute 300 mg in at least 50 mL of compatible solution; infuse over at least 20 min (continuous IV infusion is usually preceded by a loading dose).
* Do not add drugs or additives to mixture. Stop other inline drugs while administering, and flush lines before and after administration.
* Product may be added to standard TPN solutions.

Storage/Stability

Store premixed products at room temperature. Discard any unused mixed solutions after 48 h. Store oral doseform between 15° to 30°C (59° to 86°F).
Adverse Reactions

Cardiovascular

Cardiac arrhythmias.

CNS

Headache; somnolence; fatigue; dizziness; confusional states; hallucinations

GI

Diarrhea.

Genitourinary

Impotence; loss of libido.

Respiratory

Bronchospasm.

Miscellaneous

Gynecomastia; hypersensitivity reactions; transient pain at injection site; reversible exacerbation of joint symptoms with pre-existing arthritis, including gouty arthritis.

Precautions

Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

May have reduced renal function; decreased Cl may occur.

Hypersensitivity

Rare cases of anaphylaxis have occurred as well as rare episodes of hypersensitivity.

Renal Function

Decreased Cl may occur; reduced dosage may be needed.

Hepatic Function

Use caution; decreased Cl may occur.

Gastric malignancy

Symptomatic relief with cimetidine does not preclude gastric malignancy.

Antiandrogenic effect

Gynecomastia may occur, especially in patients treated for pathologic hypersecretory states.

Rapid IV administration

Has been followed by rare instances of cardiac arrhythmias and hypotension.

Reversible CNS effects

Mental confusion, agitation, psychosis, depression, anxiety, hallucinations, and disorientation have occurred, predominantly in severely ill patients. Advanced age and pre-existing liver or renal disease appear to be contributing factors.
Patient Information

* Counsel patients to stop smoking, since smoking reduces ulcer-healing efficacy of cimetidine.
* Instruct patients to keep appointments for laboratory testing and health care provider follow-up.
* Instruct patients to report to health care provider immediately any black tarry stools, coffee-ground emesis, abdominal pain or confusion.
* Counsel patients regarding need for lifestyle changes, stress reduction programs and dietary modifications (eg, avoid spicy foods and alcohol).