Cimetidine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Oral, as hydrochloride [strength expressed as base]:

Generic: 300 mg/5 mL (237 mL)

Tablet, Oral:

Cimetidine Acid Reducer: 200 mg

Generic: 200 mg, 300 mg, 400 mg, 800 mg

Pharmacology

Mechanism of Action

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

Pharmacokinetics/Pharmacodynamics

Absorption

Rapid

Distribution

Children and Adolescents: 1.23 ± 0.45 L/kg (Lloyd 1985b); Adults: 1 to 1.5 L/kg (Somogyi 1983)

Metabolism

Partially hepatic, forms metabolites (Somogyi 1983)

Excretion

Primarily urine (48% as unchanged drug); feces (2%) (Somogyi 1983)

Onset of Action

1 hour

Time to Peak

Serum: Oral: 0.75 to 1.5 hours

Duration of Action

80% reduction in gastric acid secretion for 4 to 5 hours after 300 mg dose

Half-Life Elimination

Half-life elimination: Neonates: 3.6 hours (Lloyd 1985a); Children and Adolescents: 1.39 ± 0.25 hours (Lloyd 1985b); Adults: ~2 hours

Protein Binding

20% (Somogyi 1983)

Use in Specific Populations

Special Populations: Renal Function Impairment

Drug accumulation may occur in patients with severe renal failure.

Use: Labeled Indications

Duodenal ulcer: Short-term treatment of active duodenal ulcer and maintenance therapy after the healing of active ulcer.

Gastric ulcer: Short-term treatment of active, benign gastric ulcer.

Gastroesophageal reflux disease: Treatment of erosive gastroesophageal reflux disease (GERD).

Pathological hypersecretory conditions: Treatment of pathological hypersecretory conditions (eg, Zollinger-Ellison syndrome, systemic mastocytosis, multiple endocrine adenomas).

Heartburn (OTC only): Relief and prevention of heartburn associated with acid indigestion and sour stomach.

Use: Off Label

Interstitial cystitis (bladder pain syndrome)cyes

Cimetidine in the management of interstitial cystitis/bladder pain syndrome has been studied in a limited number of controlled and noncontrolled trials demonstrating moderate to complete relief of symptoms. American Urological Association guidelines recommend oral cimetidine as a second-line treatment option that may provide benefit without significant risk of adverse events; data are limited by small sample size, lack of long-term follow-up, and the potential for drug interactions.

Stress ulcer prophylaxis in critically-ill patientsyes

The American Society of Health-System Pharmacists (ASHP) recommends and supports the use of histamine H₂-receptor antagonists for stress ulcer prophylaxis in critically ill patients, although there was limited data on the use of proton pump inhibitors for stress ulcer prophylaxis at the time of publication ASHP 1999.

Based on the Surviving Sepsis Campaign International Guidelines for the Management of Severe Sepsis and Septic Shock, stress ulcer prophylaxis using a histamine H₂-receptor antagonist or a proton pump inhibitor is recommended in sepsis or septic shock patients who have GI bleeding risk factors.

Contraindications

Hypersensitivity to cimetidine or any component of the formulation

OTC labeling: When used for self-medication (OTC), do not use if trouble or pain when swallowing food, vomiting with blood, or bloody or black stools, allergic to cimetidine or other acid reducers. Do not use with other acid reducers.

Documentation of allergenic cross-reactivity for histamine H₂ antagonists is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Duodenal ulcer, active: Oral: 300 mg 4 times daily or 800 mg at bedtime or 400 mg twice daily for up to 8 weeks

Note: Higher doses of 1,600 mg at bedtime for 4 weeks may be beneficial for a subpopulation of patients with larger duodenal ulcers (>1 cm defined endoscopically) who are also heavy smokers (≥1 pack/day).

Duodenal ulcer, prophylaxis: Oral: 400 mg at bedtime

Gastric ulcer, active: Oral: 300 mg 4 times daily or 800 mg at bedtime for up to 8 weeks

Gastroesophageal reflux disease: Oral: 400 mg 4 times daily or 800 mg twice daily for 12 weeks

Heartburn (OTC labeling):

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.

Pathological hypersecretory conditions: Oral: 300 mg 4 times daily; adjust dose to patient response; maximum 2,400 mg/day

Interstitial cystitis (bladder pain syndrome) (off-label use): Oral: 200 mg 3 times daily or 300 to 400 mg twice daily (Dasgupta 2001; Seshadri 1994; Thilagarajah 2001)

Stress ulcer prophylaxis in critically ill patients (off-label use): Oral or NG tube: 300 mg 4 times daily (ASHP 1999). Note: Intended for patients with associated risk factors (eg, coagulopathy, mechanical ventilation for >48 hours, sepsis/septic shock); discontinue use once risk factors have resolved (Rhodes 2017).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Gastroesophageal reflux disease (GERD):

Infants, Children, and Adolescents <16 years: Limited data available: Oral: 20 to 40 mg/kg/day in 3 to 4 divided doses; maximum dose: 400 mg/dose (Cucchiara 1984; Cucchiara 1989; Lightdale 2013; NASPGHAN/ESPGHAN [Vandenplas 2009]). A pharmacokinetic modeling study suggests that the optimal dose for acid suppression is 10 mg/kg/dose every 6 hours and that some patients may need doses as high as 15 mg/kg/dose (Lambert 1992).

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

Duodenal ulcer, treatment and maintenance:

Children ≥5 years and Adolescents <16 years: Limited data available, efficacy results variable: Oral: 20 to 40 mg/kg/day in 3 to 4 divided doses for 4 to 8 weeks, followed by 5 to 8 mg/kg/dose once daily at bedtime (Chiang 1989; Thomson 1983). In the largest trail, 33 patients (ages 8 to 15 years) with duodenal ulcer were allocated to receive cimetidine 20 mg/kg/day (n=8), an antacid (n=12), or sucralfate (n=17) for 8 weeks followed by maintenance therapy with once daily bedtime doses of cimetidine 5 mg/kg/dose, antacid, or sucralfate. Short-term improvement occurred in all three groups with no significant difference (Chiang 1989).

Adolescents ≥16 years: Oral: 300 mg 4 times daily or 800 mg at bedtime or 400 mg twice daily for up to 8 weeks

Duodenal ulcer, prophylaxis: Adolescents ≥16 years: Oral: 400 mg at bedtime

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

Pathological hypersecretory conditions (eg, Zollinger-Ellison syndrome): Adolescents ≥16 years: Oral: 300 mg 4 times daily; adjust dose to patient response; maximum daily dose: 2,400 mg/day

Sour stomach/Heartburn (OTC labeling):

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

Extemporaneously Prepared

Note: Commercial oral solution is available (strength expressed as base: 60 mg/mL)

A 60 mg/mL oral suspension may be made with tablets. Place twenty-four 300 mg tablets in 5 mL of sterile water for ~3-5 minutes to dissolve film coating. Crush tablets in a mortar and reduce to a fine powder. Add 10 mL of glycerin and mix to a uniform paste; mix while adding Simple Syrup, NF in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well" and "refrigerate". Stable for 17 days.

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Administration

Administer with meals. For stress ulcer prophylaxis in critically-ill patients (off-label use), may administer via NG tube (Rhodes 2017).

Storage

Store at room temperature. Protect from light.

Drug Interactions

Acalabrutinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Acalabrutinib. Management: To minimize the potential for a significant interaction, separate administration of these agents by giving acalabrutinib 2 hours before ingestion of a histamine-2 receptor antagonist. Consider therapy modification

Alfentanil: Cimetidine may increase the serum concentration of Alfentanil. Monitor therapy

Amiodarone: Cimetidine may increase the serum concentration of Amiodarone. Management: Consider alternatives to cimetidine. If this combination cannot be avoided, monitor for increased amiodarone concentrations/effects with cimetidine initiation/dose increase or decreased concentrations/effects with cimetidine discontinuation/dose decrease. Consider therapy modification

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

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. Consider therapy modification

AtorvaSTATin: May enhance the adverse/toxic effect of Cimetidine. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Monitor therapy

Azelastine (Systemic): Cimetidine may increase the serum concentration of Azelastine (Systemic). Monitor therapy

Bosutinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Bosutinib. Management: Administer histamine H2 receptor antagonists more than 2 hours before or after bosutinib. Consider therapy modification

Bromazepam: Cimetidine may increase the serum concentration of Bromazepam. Monitor therapy

Calcium Channel Blockers: Cimetidine may increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. Exceptions: AmLODIPine; Clevidipine; NiCARdipine. Consider therapy modification

CarBAMazepine: Cimetidine may increase the serum concentration of CarBAMazepine. The serum carbamazepine concentration might return to normal within one week of starting cimetidine. Monitor therapy

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. Consider therapy modification

Carvedilol: Cimetidine may increase the serum concentration of Carvedilol. Monitor therapy

Cefditoren: Histamine H2 Receptor Antagonists may decrease the serum concentration of Cefditoren. Management: Concomitant use of cefditoren with H2-antagonists and antacids is not recommended. Consider alternative methods to control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided. Consider therapy modification

Cefpodoxime: Histamine H2 Receptor Antagonists may decrease the absorption of Cefpodoxime. Separate oral doses by at least 2 hours. Monitor therapy

Cefuroxime: Histamine H2 Receptor Antagonists may decrease the absorption of Cefuroxime. Separate oral doses by at least 2 hours. Avoid combination

Chlormethiazole: Cimetidine may increase the serum concentration of Chlormethiazole. Monitor therapy

Chloroquine: Cimetidine may increase the serum concentration of Chloroquine. Monitor therapy

Cisapride: Cimetidine may increase the serum concentration of Cisapride. Management: Consider alternatives to cimetidine. If this combination cannot be avoided, monitor for toxic effects of cisapride if cimetidine is initiated/dose increased, or decreased efficacy if cimetidine is discontinued/dose decreased. Consider therapy modification

Citalopram: Cimetidine may increase the serum concentration of Citalopram. Monitor therapy

CloZAPine: Cimetidine may increase the serum concentration of CloZAPine. Management: Consider use of an alternative H2 antagonist. Monitor for increased toxic effects of clozapine if cimetidine is initiated/dose increased, or decreased effects if cimetidine is discontinued/dose decreased. Consider therapy modification

Cysteamine (Systemic): Histamine H2 Receptor Antagonists may diminish the therapeutic effect of Cysteamine (Systemic). Monitor therapy

Dacomitinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Dacomitinib. Management: Administer dacomitinib at least 6 hours before or 10 hours after an histamine H2-receptor antagonist (H2RA). Consider therapy modification

Dalfampridine: Cimetidine may increase the serum concentration of Dalfampridine. Management: Recommendations differ significantly between international labelings in regards to the concomitant use of dalfampridine (referred to as fampridine in Canada) and cimetidine. Consult appropriate product labeling. Monitor therapy

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. Avoid combination

Delavirdine: Histamine H2 Receptor Antagonists may decrease the serum concentration of Delavirdine. Management: Chronic therapy with H2-antagonists should be avoided in patients who are being treated with delavirdine. The clinical significance of short-term H2-antagonist therapy with delavirdine is uncertain, but such therapy should be undertaken with caution. Avoid combination

Dexmethylphenidate: Histamine H2 Receptor Antagonists may increase the absorption of Dexmethylphenidate. Specifically, H2-antagonists may interfere with the normal release of drug from the extended-release capsules (Focalin XR brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Dofetilide: Cimetidine may increase the serum concentration of Dofetilide. This is likely via inhibition of dofetilide renal tubular secretion (primarily) and inhibition of dofetilide metabolism. Avoid combination

Doxofylline: Cimetidine may increase the serum concentration of Doxofylline. Monitor therapy

EpiRUBicin: Cimetidine may increase the serum concentration of EpiRUBicin. Avoid combination

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Erdafitinib: May increase the serum concentration of OCT2 Substrates. Monitor therapy

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. Consider therapy modification

Escitalopram: Cimetidine may increase the serum concentration of Escitalopram. Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Flunitrazepam: Cimetidine may increase the serum concentration of Flunitrazepam. Monitor therapy

Fluorouracil Products: Cimetidine may increase the serum concentration of Fluorouracil Products. Monitor therapy

FLUoxetine: Cimetidine may increase the serum concentration of FLUoxetine. Monitor therapy

Fosamprenavir: Histamine H2 Receptor Antagonists may decrease the serum concentration of Fosamprenavir. Cimetidine may also inhibit the metabolism of the active metabolite amprenavir, making its effects on fosamprenavir/amprenavir concentrations difficult to predict. Monitor therapy

Fosphenytoin-Phenytoin: Cimetidine may enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Cimetidine may increase the serum concentration of Fosphenytoin-Phenytoin. Management: Consider using an alternative H₂-antagonist to avoid this interaction. Monitor for toxic effects of hydantoin anticonvulsants if cimetidine is initiated/dose increased. Consider therapy modification

Gefitinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Gefitinib. Management: Administer gefitinib at least 6 hours before or after administration of a histamine H2-antagonist, and closely monitor clinical response to gefitinib. Consider therapy modification

Indinavir: Histamine H2 Receptor Antagonists may decrease the serum concentration of Indinavir. Monitor therapy

Iron Preparations: Histamine H2 Receptor Antagonists may decrease the absorption of Iron Preparations. Exceptions: Ferric Carboxymaltose; Ferric Citrate; Ferric Derisomaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Monitor therapy

Itraconazole: Histamine H2 Receptor Antagonists may increase the serum concentration of Itraconazole. Histamine H2 Receptor Antagonists may decrease the serum concentration of Itraconazole. Management: Administer Sporanox brand itraconazole at least 2 hours before or 2 hours after administration of any histamine H2 receptor antagonists (H2RAs). Exposure to Tolsura brand itraconazole may be increased by H2RAs; consider itraconazole dose reduction. Consider therapy modification

Ketoconazole (Systemic): Histamine H2 Receptor Antagonists may decrease the serum concentration of Ketoconazole (Systemic). Management: Administer oral ketoconazole at least 2 hours prior to use of any H2-receptor antagonist. Monitor patients closely for signs of inadequate clinical response to ketoconazole. Consider therapy modification

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination

Ledipasvir: Histamine H2 Receptor Antagonists may decrease the serum concentration of Ledipasvir. Consider therapy modification

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. Consider therapy modification

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

Lumacaftor and Ivacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor and Ivacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Mebendazole: Cimetidine may increase the serum concentration of Mebendazole. Monitor therapy

Melatonin: Cimetidine may increase the serum concentration of Melatonin. Monitor therapy

Meperidine: Cimetidine may increase the serum concentration of Meperidine. Monitor therapy

Mesalamine: Histamine H2 Receptor Antagonists may diminish the therapeutic effect of Mesalamine. Histamine H2-Antagonist-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Consider avoiding concurrent administration of high-dose histamine H2-receptor antagonists with sustained-release mesalamine products. Consider therapy modification

MetFORMIN: Cimetidine may increase the serum concentration of MetFORMIN. Management: Consider alternatives to cimetidine in patients receiving metformin due to a potential for increased metformin concentrations and toxicity (including lactic acidosis). Consider therapy modification

Methylphenidate: Histamine H2 Receptor Antagonists may increase the absorption of Methylphenidate. Specifically, H2-antagonists may interfere with the normal release of drug from the extended-release capsules (Ritalin LA brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Mirtazapine: Cimetidine may increase the serum concentration of Mirtazapine. Monitor therapy

Moclobemide: Cimetidine may decrease the metabolism of Moclobemide. Management: Consider using alternative agents to lower gastric pH in order to avoid this interaction. If combined, a moclobemide dose reduction of 50% is recommended and patients should be monitored for increased moclobemide effects/toxicities. Consider therapy modification

Multivitamins/Minerals (with ADEK, Folate, Iron): Histamine H2 Receptor Antagonists may decrease the serum concentration of Multivitamins/Minerals (with ADEK, Folate, Iron). Specifically, the absorption of iron may be impaired by H2-antagonists. Monitor therapy

Nelfinavir: Histamine H2 Receptor Antagonists may decrease the serum concentration of Nelfinavir. Concentrations of the active M8 metabolite may also be reduced. Monitor therapy

Neratinib: Cimetidine may increase the serum concentration of Neratinib. Cimetidine may decrease the serum concentration of Neratinib. Specifically, cimetidine may reduce neratinib absorption. Management: Avoid concomitant use of neratinib and cimetidine. Avoid combination

Nicotine: Cimetidine may increase the serum concentration of Nicotine. Monitor therapy

Nilotinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Nilotinib. Management: The nilotinib dose should be given 10 hours after or 2 hours before the H2 receptor antagonist in order to minimize the risk of a significant interaction. Consider therapy modification

Nitisinone: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

PARoxetine: Cimetidine may increase the serum concentration of PARoxetine. Monitor therapy

PAZOPanib: Histamine H2 Receptor Antagonists may decrease the serum concentration of PAZOPanib. Management: Avoid the use of histamine H2-antagonists in combination with pazopanib. Strategies to minimize the expected interaction between these agents (eg, dose separation) have not been investigated. Avoid combination

Pentoxifylline: Cimetidine may increase the serum concentration of Pentoxifylline. Monitor therapy

Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Monitor therapy

Pexidartinib: Histamine H2 Receptor Antagonists may decrease the serum concentration of Pexidartinib. Management: Administer pexidartinib 2 hours before or 10 hours after histamine H2 receptor antagonists. Consider therapy modification

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Pilsicainide: Cimetidine may increase the serum concentration of Pilsicainide. Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Posaconazole: Histamine H2 Receptor Antagonists may decrease the serum concentration of Posaconazole. Management: Avoid concurrent use of oral suspension with H2-antagonists whenever possible. Monitor patients closely for decreased antifungal effects if this combination is used. Delayed-release posaconazole tablets may be less likely to interact. Consider therapy modification

Pramipexole: Cimetidine may increase the serum concentration of Pramipexole. Monitor therapy

Praziquantel: Cimetidine may increase the serum concentration of Praziquantel. Monitor therapy

Pretomanid: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

Procainamide: Cimetidine may increase the serum concentration of Procainamide. Management: Consider an alternative H2-receptor antagonist in patients taking procainamide. If combined, monitor for increased therapeutic effects/toxicity of procainamide. Consider therapy modification

Propafenone: Cimetidine may increase the serum concentration of Propafenone. Monitor therapy

QuiNIDine: Cimetidine may increase the serum concentration of QuiNIDine. Management: Consider alternatives to cimetidine. If the combination cannot be avoided, monitor for increased quinidine concentrations/toxicity with cimetidine initiation/dose increase, or decreased concentrations/effects with cimetidine discontinuation/dose decrease. Consider therapy modification

QuiNINE: Cimetidine may increase the serum concentration of QuiNINE. Management: Consider using an alternative H2-receptor antagonist (eg, ranitidine) instead of cimetidine due to a lower interaction risk. If combined, monitor patients closely for signs and symptoms of quinine toxicity. Consider therapy modification

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Rilpivirine: Histamine H2 Receptor Antagonists may decrease the serum concentration of Rilpivirine. Management: Administer histamine H2 receptor antagonists at least 12 hours before or 4 hours after rilpivirine. Consider therapy modification

Risedronate: Histamine H2 Receptor Antagonists may increase the serum concentration of Risedronate. This applies specifically to delayed-release risedronate. Avoid combination

Roflumilast: Cimetidine may increase serum concentrations of the active metabolite(s) of Roflumilast. Cimetidine may increase the serum concentration of Roflumilast. Monitor therapy

Saquinavir: Histamine H2 Receptor Antagonists may increase the serum concentration of Saquinavir. Monitor therapy

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. Consider therapy modification

Sulfonylureas: Cimetidine may increase the serum concentration of Sulfonylureas. Monitor therapy

Tafenoquine: May increase the serum concentration of OCT2 Substrates. Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate's labeling. Consider therapy modification

Tamsulosin: Cimetidine may increase the serum concentration of Tamsulosin. Monitor therapy

Teriflunomide: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Tolvaptan: May increase the serum concentration of OAT1/3 Substrates. Management: Patients being treated with the Jynarque brand of tolvaptan should avoid concomitant use of OAT1/3 substrates. Concentrations and effects of the OAT1/3 substrate would be expected to increase with any combined use. Consider therapy modification

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification

Tricyclic Antidepressants: Cimetidine may decrease the metabolism of Tricyclic Antidepressants. Monitor therapy

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (if needed) of ubrogepant should be limited to 50 mg. Consider therapy modification

Urapidil: Cimetidine may enhance the hypotensive effect of Urapidil. Monitor therapy

Varenicline: Histamine H2 Receptor Antagonists may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of cimetidine or other H2-antagonists, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Monitor therapy

Velpatasvir: Histamine H2 Receptor Antagonists may decrease the serum concentration of Velpatasvir. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Cimetidine may enhance the anticoagulant effect of Vitamin K Antagonists. Consider therapy modification

Zaleplon: Cimetidine may increase the serum concentration of Zaleplon. Management: The initial dose of zaleplon should be limited to 5 mg in patients taking cimetidine. Monitor patients for increased zaleplon effects/toxicities (ie, sedation, CNS depression) when these agents are combined. Consider therapy modification

ZOLMitriptan: Cimetidine may increase the serum concentration of ZOLMitriptan. Management: Limit the maximum single dose of zolmitriptan to 2.5 mg, not to exceed 5 mg in 24 hours, when coadministered with cimetidine. Consider therapy modification

Adverse Reactions

1% to 10%:

Central nervous system: Headache (2% to 4%), dizziness (1%), drowsiness (1%)

Endocrine & metabolic: Gynecomastia (≤4%)

Gastrointestinal: Diarrhea (1%)

Frequency not defined: Renal: Increased serum creatinine

Postmarketing: Agitation, agranulocytosis, alopecia, anaphylaxis, anxiety, aplastic anemia, arthralgia, confusion, decreased white blood cell count, depression, disorientation, fever (Potter 1986), hallucination, hemolytic anemia (immune-based), hepatic fibrosis, hypersensitivity angiitis, hypersensitivity reaction, hypotension, impotence (Jensen 1983), increased serum transaminases, interstitial nephritis, myalgia, pancreatitis, pancytopenia, polymyositis (Watson 1983), psychosis, urinary retention, thrombocytopenia

Warnings/Precautions

Concerns related to adverse effects:

• Confusion: Rare cases of reversible confusion have been associated with cimetidine; usually in elderly or severely ill patients, or in patients with renal 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 (Lam 2013).

Disease-related concerns:

• Gastric malignancy: Relief of symptoms does not preclude the presence of a gastric malignancy.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use caution in this age group due to risk of confusion and other CNS effects. Cimetidine should be avoided in those older adults with, or at risk of, delirium.
• Immunocompromised patients: May have increased risk of hyperinfection of strongyloidiasis.
• Pediatric: Use of gastric acid inhibitors, including proton pump inhibitors and H₂ blockers, has been associated with an increased risk for development of acute gastroenteritis and community-acquired pneumonia in pediatric patients (Canani 2006).

Other warnings/precautions:

• Serum creatinine/creatinine clearance estimates: Cimetidine can cause a transient and reversible rise in serum creatinine and/or decrease in creatinine clearance (when using routine creatinine clearance estimation formulas). This interference is likely due to competitive inhibition of cimetidine with creatinine for active tubular secretion and independent of an actual change in glomerular filtration rate (GFR). In patients with normal renal function, the rise in serum creatinine may not be clinically apparent, but in patients with varying degrees of renal impairment, this rise in serum creatinine may be more significant. Thus, treatment with cimetidine in patients with renal failure may invalidate measurements of serum creatinine and estimates of creatinine clearance (Andreev 1999; Larsson 1980). However, creatinine clearance estimation formulas, such as Cockcroft-Gault, are known to overestimate actual GFR, particularly in patients with renal impairment, and use of cimetidine has been explored clinically to improve the accuracy of creatinine clearance estimates in these patients (Choi 1993; Van Acker 1992).
• OTC labeling: When used for self-medication (OTC), notify health care provider before use if any of the following are present: Frequent chest pain; frequent wheezing particularly with heartburn; nausea/vomiting; unexplained weight loss; stomach pain; heartburn >3 months; heartburn with light-headedness, sweating, or dizziness; chest pain or shoulder pain with shortness of breath; sweating or pain that spreads to arms, neck, or shoulders; light-headedness. Stop use and notify health care provider if heartburn continues or worsens, stomach pain continues, or if use is required >14 days.

Monitoring Parameters

CBC, gastric pH; monitor renal function to correct dose; occult blood with GI bleeding; signs of confusion.

Pregnancy

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Cimetidine crosses the placenta (Howe 1981). Histamine H₂ antagonists have been evaluated for the treatment of gastroesophageal reflux disease (GERD), as well as gastric and duodenal ulcers during pregnancy (Cappell 2003; Richter 2003). Histamine H₂ antagonists may be used for aspiration prophylaxis prior to cesarean delivery (ASA 2007).

Patient Education

What is this drug used for?

• It is used to treat or prevent GI (gastrointestinal) ulcers.
• It is used to treat gastroesophageal reflux disease (GERD; acid reflux).
• It is used to treat heartburn and sour stomach.
• It is used to treat syndromes caused by lots of stomach acid.
• It may be given to you for other reasons. Talk with the doctor.

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Agitation
• Confusion
• Mood changes
• Sensing things that seem real but are not
• Enlarged breasts
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.