Cimetidine

Cimetidine belongs to the Gastrointestinal Agent acts as a Histamine H₂ Receptor Antagonist.

Cimetidine is a histamine H2 receptor antagonist used to manage GERD, peptic ulcer disease, and indigestion.

In healthy patients, the absolute bioavailability of cimetidine is approximately 60%; however, the bioavailability can be as high as 70% in patients with peptic ulcer disease. Overall, rates of bioavailability are much more variable in patients with peptic ulcer disease. The volume of distribution of cimetidine is reported to be 1 L/kg. In humans, approximately 22.5% of cimetidine is plasma protein bound. After intravenous administration of cimetidine, much of the parent drug (58-77%) is eliminated unchanged in the urine. Cimetidine’s primary metabolite is cimetidine sulfoxide and represents an estimated 10-15% of total elimination.

Cimetidine shows side effects like Headache, Diarrhea, Dizziness, Drowsiness, Breast enlargement.

Cimetidine is available in the form of Oral Tablet, Oral liquid, Injectable solution.

Cimetidine is available in India, US, Germany, UK, Spain, Australia, China, Canada, Japan, Switzerland, and Italy.

Cimetidine belongs to the Gastrointestinal Agent acts as a Histamine H₂ Receptor Antagonist.

Cimetidine binds to an H₂-receptor located on the basolateral membrane of the gastric parietal cell, blocking histamine effects. This competitive inhibition results in reduced gastric acid secretion and a reduction in gastric volume and acidity.

The onset of action of Cimetidine can be observed in less than 1 hour after an oral dose and less than 30 minutes after an intravenous dose.

The duration of action of Cimetidine lasts for an average duration of 4 to 5 hours after an intravenous dose and 4 to 8 hours after an oral dose.

Cimetidine is available in the form of Oral Tablet, Oral liquid, Injectable solution.

Cimetidine Tablet and liquid is taken orally, usually in divided dose.

Cimetidine is a very effective medicine to reduce the amount of acid produced in the stomach. Cimetidine should be taken 30 minutes before food to relieve symptoms of heartburn.

Cimetidine belongs to the Gastrointestinal Agent acts as a Histamine H₂ Receptor Antagonist.

Cimetidine competitive inhibition of histamine at H₂ receptors of the gastric parietal cells resulting in reduced gastric acid secretion, gastric volume and hydrogen ion concentration reduced.

Cimetidine is approved for use in the following clinical indications

Adult indication

• Gastroesophageal reflux disease
• Heartburn
• Interstitial cystitis
• Stress ulcer prophylaxis in critically ill patients

Pediatric indication

• Duodenal ulcer, treatment, and maintenance
• Gastric ulcer, active
• Gastroesophageal reflux disease
• Pathological hypersecretory conditions
• Sour stomach/Heartburn

Adult Dose

• Gastroesophageal reflux disease

Oral: 400 mg 4 times daily or 800 mg twice daily for 12 weeks.

• Heartburn

Prevention: Oral: 200 mg daily up to 30 minutes prior to eating foods or beverages that cause heartburn (maximum: 400 mg per 24 hours).

Relief of symptoms: Oral: 200 mg daily; maximum: 400 mg per 24 hours.

• Interstitial cystitis

Oral: 200 mg 3 times daily or 300 to 400 mg twice daily.

• Stress ulcer prophylaxis in critically ill patients

Oral: 300 mg 4 times daily.

Paediatric Dose

• Duodenal ulcer, treatment, and maintenance

Children ≥5 years and Adolescents <16 years: Oral: 20 to 40 mg/kg/day in 3 to 4 divided doses for 4 to 8 weeks (maximum dose: 300 mg/dose), followed by 5 to 8 mg/kg/dose once daily at bedtime (maximum dose: 400 mg/dose).

Adolescents ≥16 years: Oral: 800 mg at bedtime or 400 mg twice daily or 300 mg 4 times daily for up to 8 weeks, followed by maintenance therapy of 400 mg once daily at bedtime.

• Gastric ulcer, active

Adolescents ≥16 years: Oral: 800 mg at bedtime or 300 mg 4 times daily for up to 8 weeks.

• Gastroesophageal reflux disease

Infants, Children, and Adolescents <16 years: Oral: 30 to 40 mg/kg/day in 4 divided doses; maximum dose: 400 mg/dose.

Adolescents ≥16 years: Oral: 400 mg 4 times daily or 800 mg twice daily for 12 weeks.

• Pathological hypersecretory conditions

Adolescents ≥16 years: Oral: 300 mg 4 times daily; adjust dose to patient response; maximum daily dose: 2,400 mg/day.

• Sour stomach/Heartburn

Prevention: Children ≥12 years and Adolescents: Oral: 200 mg daily up to 30 minutes prior to eating foods or beverages that cause heartburn (maximum daily dose: 400 mg/24 hours).

Relief of symptoms: Children ≥12 years and Adolescents: Oral: 200 mg daily; maximum daily dose: 400 mg/24 hours.

Cimetidine is available in various strengths as 300 mg; 400 mg; 800 mg; 300 mg/5 mL; 900 mg-0.9%/250 mL; 480 mg/100 mL-0.9%; 900 mg-0.9%/500 mL; 1200 mg-0.9%/500 mL; 900 mg-0.9%/1000 mL; 1200 mg-0.9%/1000 mL; 150 mg/mL; 300 mg/50 mL-NaCl 0.9%; 200 mg; 100 mg; 200 mg/20 mL.

• Dosage Adjustment in Kidney Patient

GFR >50 mL/minute: No dosage adjustment necessary.

GFR 10 to 50 mL/minute: Administer 50% of normal dose.

GFR <10 mL/minute: 300 mg every 8 to 12 hours.

Cimetidine is contraindicated in patients with

• Hypersensitivity to cimetidine or any component of the formulation.

• Confusion: Rare cases of reversible confusion have been associated with cimetidine; usually in older or severely ill patients, or in patients with kidney or hepatic impairment.
• Vitamin B₁₂ deficiency: Prolonged treatment (≥2 years) may lead to vitamin B₁₂ malabsorption and subsequent vitamin B₁₂ deficiency. The magnitude of the deficiency is dose-related and the association is stronger in females and those younger in age (<30 years); prevalence is decreased after discontinuation of therapy.

Consumption of alcohol is not recommended in patients receiving Cimetidine. Dizziness, difficulty in breathing are the common adverse effects observed while consuming alcohol.

Cimetidine is known to excreted through the breastmilk. Cimetidine is not recommended for breastfeeding women.

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Common

• Headache, dizziness, drowsiness, Gynecomastia, Diarrhea.

Rare

• Agitation, agranulocytosis, alopecia, anaphylaxis, anxiety, aplastic anemia, arthralgia, confusion, decreased white blood cell count, depression, disorientation, fever, hallucination, hemolytic anemia (immune-based), hepatic fibrosis, hypersensitivity angiitis, hypersensitivity reaction, hypotension, impotence, increased serum transaminases, interstitial nephritis, myalgia, pancreatitis, pancytopenia, polymyositis, psychosis, urinary retention, thrombocytopenia.

• Acalabrutinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Acalabrutinib. Management: Give acalabrutinib capsules 2 hours before a histamine H2 receptor antagonist (H2RA). No action is required if acalabrutinib tablets are coadministered with H2RAs.
• Atazanavir: Histamine H2 Receptor Antagonists may decrease the serum concentration of Atazanavir. Management: Specific dose limitations and administration guidelines exist; consult full interaction monograph or atazanavir prescribing information.
• Carmustine: Cimetidine may enhance the myelosuppressive effect of Carmustine. Management: Consider alternatives to cimetidine in patients receiving carmustine. If the combination cannot be avoided, monitor for enhanced carmustine myelotoxicity.
• Citalopram: Cimetidine may increase the serum concentration of Citalopram. Management: Limit citalopram dose to a maximum of 20 mg/day if used with cimetidine. Patients using this combination should be monitored closely for evidence of citalopram toxicity (eg, serotonin syndrome, QT prolongation).
• Dacomitinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Dacomitinib. Management: Administer dacomitinib at least 6 hours before or 10 hours after a histamine H2-receptor antagonist (H2RA).

• Erlotinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Erlotinib. Management: Avoid H2-antagonists in patients receiving erlotinib when possible. If concomitant treatment cannot be avoided, erlotinib should be dosed once daily, 10 hours after and at least 2 hours before H2-antagonist dosing.

• Dalfampridine: OCT2 Inhibitors may increase the serum concentration of Dalfampridine. Management: Consider alternatives to this combination. Carefully weigh the risk of seizures against the benefit of combining OCT2 inhibitors with dalfampridine.

• Dasatinib: Histamine H2 Receptor Antagonists may decrease the absorption of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of H2-antagonists if some acid-reducing therapy is needed.

• Ketoconazole (Systemic): Histamine H2 Receptor Antagonists may decrease the serum concentration of Ketoconazole (Systemic). Management: Administer ketoconazole with an acidic beverage (eg, non-diet cola) and monitor for reduced efficacy if concomitant use with a H2RA is required. Increases in ketoconazole dose may be required.

• Ledipasvir: Histamine H2 Receptor Antagonists may decrease the serum concentration of Ledipasvir. Management: Administer H2 receptor antagonist doses less than or comparable to famotidine 40 mg twice daily simultaneously or 12 hours prior to ledipasvir. The effect of administering H2 receptor antagonists at other time intervals is unknown and not recommended.

• Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors.

• Roflumilast-Containing Products: Cimetidine may increase serum concentrations of the active metabolite(s) of Roflumilast-Containing Products. Cimetidine may increase the serum concentration of Roflumilast-Containing Products.

• Saquinavir: Histamine H2 Receptor Antagonists may increase the serum concentration of Saquinavir. Management: Consider alternatives to this combination for patients taking the Invirase formulation of saquinavir. No action beyond standard clinical care measures is required for patients taking the Fortovase formulation of saquinavir.

• Secretin: Histamine H2 Receptor Antagonists may diminish the diagnostic effect of Secretin. Specifically, use of H2-Antagonists may cause a hyperresponse in gastrin secretion in response to secretin stimulation testing, falsely suggesting gastrinoma. Management: Avoid concomitant use of histamine H2-antagonists (H2RAs) and secretin. Discontinue H2RAs at least 2 days prior to secretin administration.

The common side effects of Cimetidine include the following

Common side effects

• Headache, Diarrhea, Dizziness, Drowsiness, Breast enlargement.

Rare side effects

• Confusion, Excitement, Depression, Nervousness, hallucinating.

• Pregnancy

Pregnancy Category B

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

• Nursing Mothers

Cimetidine is known to excreted through the breastmilk. Cimetidine is not recommended for breastfeeding women.

Symptoms: CNS symptoms (e.g. unresponsiveness).

Management: Supportive and symptomatic therapy. Administer activated charcoal if ingestion is within 1 hour. Induce vomiting or perform gastric lavage.

Pharmacodynamic

Cimetidine is a histamine H₂-receptor antagonist. It reduces basal and nocturnal gastric acid secretion and a reduction in gastric volume, acidity, and amount of gastric acid released in response to stimuli including food, caffeine, insulin, betazole, or pentagastrin. It is used to treat gastrointestinal disorders such as gastric or duodenal ulcer, gastroesophageal reflux disease, and pathological hypersecretory conditions. Cimetidine inhibits many of the isoenzymes of the hepatic CYP450 enzyme system. Other actions of Cimetidine include an increase in gastric bacterial flora such as nitrate-reducing organisms.

Pharmacokinetics

• Absorption

In healthy patients, the absolute bioavailability of cimetidine is approximately 60%; however, the bioavailability can be as high as 70% in patients with peptic ulcer disease. Overall, rates of bioavailability are much more variable in patients with peptic ulcer disease.

• Distribution

The volume of distribution of cimetidine is reported to be 1 L/kg. In humans, approximately 22.5% of cimetidine is plasma protein bound.

• Metabolism and Excretion

After intravenous administration of cimetidine, the majority of the parent drug (58-77%) is eliminated unchanged in the urine. Cimetidine’s primary metabolite is cimetidine sulfoxide and represents an estimated 10-15% of total elimination.

• https://www.rxlist.com/tagamet-drug.htm#clinpharm
• https://www.drugs.com/dosage/cimetidine.html#Usual_Adult_Dose_for_Duodenal_Ulcer
• https://www.practo.com/medicine-info/cimetidine-387-api
• https://www.uptodate.com/contents/cimetidine-drug-information#F151475
• https://go.drugbank.com/drugs/DB00501