ranitidine hydrochloride

H2 Antagonists

All oral dosage forms: May be administered without regard to meals. May administer with food, water, or milk to minimize gastric irritation.

Oral Solution (Syrup): Measure with calibrated oral syringe or cup prior to administration to give an accurate dosage. Alternatively, ranitidine oral solution may be administered via feeding tube in patients requiring enteral feeding. In vitro stability analysis demonstrates that > 90% of ranitidine syrup is recovered at 24 hours after mixing with eight different enteral feedings. No interaction with food was noted, thus, no medication administration changes are necessary.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit; undiluted ranitidine tends to exhibit a yellow color that may intensify over time that does not adversely affect potency.
Administer via the intramuscular (IM) or intravenous (IV) routes.
Compatible solutions for dilution include D5W, D10W, NS, lactated ringers, or 5% sodium bicarbonate.
Pharmacy bulk vial package is only available for preparing admixtures; the pre-mixed infusion bags are only for slow IV infusion administration.
Storage of diluted injection: Diluted solutions are stable for up to 48 hours at room temperature.

IV Push
Dilute to a maximum of 2.5 mg/ml (50 mg/20 ml) using non-preserved NS or other compatible IV solution.
Inject at a rate no greater than 4 ml/minute (i.e., 50 mg/20 ml dose should be pushed over 5 minutes).
 
Intermittent IV infusion
Dilute to a maximum of 0.5 mg/ml using D5W, NS, or other compatible IV solution. Infuse over 15—20 minutes (5—7 ml/minute).
Pre-mixed ready-to-use infusion bags are available as 1 mg/ml ranitidine (i.e., 50 mg/50 ml). Premixed ready-to-use bags are for slow IV administration only; infuse over 15—20 minutes.
 
Continuous 24-hour IV infusion
For adults, dilute 150 mg in 250 ml of D5W or NS or another compatible solution. The diluted solution is stable for up to 48 hours at room temperature. Infuse over 24 hours at a rate of 6.25 mg/hr or as specified by physician. For Zollinger-Ellison patients, dilute in D5W or NS or another compatible solution up to a maximum concentration of 2.5 mg/ml.
Use a controlled-rate infusion device.
Alternatively, the dosage may be added to a compatible TPN solution for administration over 24 hours.

No dilution necessary.
Inject into a large muscle mass. Aspirate prior to injection to avoid injection into a blood vessel.

pancreatitis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
interstitial nephritis / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
vasculitis / Delayed / Incidence not known
bradycardia / Rapid / Incidence not known
AV block / Early / Incidence not known
atrophic gastritis / Delayed / Incidence not known

constipation / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
depression / Delayed / Incidence not known
confusion / Early / Incidence not known
blurred vision / Early / Incidence not known
hallucinations / Early / Incidence not known
impotence (erectile dysfunction) / Delayed / Incidence not known
galactorrhea / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
premature ventricular contractions (PVCs) / Early / Incidence not known
vitamin B12 deficiency / Delayed / Incidence not known
pernicious anemia / Delayed / Incidence not known

headache / Early / 6.0-7.7
nausea / Early / 4.1-4.1
dizziness / Early / 2.6-2.6
infection / Delayed / 2.6-2.6
diarrhea / Early / 2.1-2.1
abdominal pain / Early / 2.1-2.1
vomiting / Early / 1.5-1.5
asthenia / Delayed / 1.5-1.5
cough / Delayed / 1.5-1.5
paranoia / Early / Incidence not known
drowsiness / Early / Incidence not known
vertigo / Early / Incidence not known
malaise / Early / Incidence not known
insomnia / Early / Incidence not known
agitation / Early / Incidence not known
gynecomastia / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
fever / Early / Incidence not known
rash / Early / Incidence not known
alopecia / Delayed / Incidence not known
myalgia / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
pruritus / Rapid / Incidence not known

Acid Reducer, Ranitidine, Taladine, Wal-Zan, Zantac, Zantac 150, Zantac 75

Rx, OTC

Oral and parenteral histamine type 2-receptor antagonist; ranitidine products withdrawn from U.S. market due to NDMA impurity
Used for gastrointestinal disorders such as peptic ulcer and gastroesophageal reflux disease
More potent histamine antagonist than cimetidine; less affinity for CYP450 enzymes

75 to 150 mg PO immediately before eating or up to 60 minutes before consuming food and beverages that may cause heartburn. Tablets can be taken up to twice daily (maximum daily dose of 300 mg PO). Patients should not take for more than 2 weeks without consulting a physician.

OTC use is not recommended unless advised by a qualified health care prescriber.

75 to 150 mg PO once or twice daily. Patients should not take for more than 2 weeks without consulting a physician.

OTC use is not recommended unless advised by a qualified health care prescriber.

150 mg PO twice daily. Symptomatic relief usually occurs within 24 hours after starting therapy. Although higher doses of ranitidine have been studied (300 mg PO twice daily), doubling the standard dose not improve efficacy; if a standard dose is not effective, consider alternate therapy (e.g., PPI). While ranitidine may be effective in patients with less severe GERD, proton pump inhibitors (PPIs) offer more rapid symptom relief and better healing.

5 to 10 mg/kg/day PO divided 2 to 3 times per day (Max: 300 mg/day). Continue therapy for 6 to 8 weeks if improvement in symptoms is noted. While ranitidine may be effective in patients with less severe GERD, proton pump inhibitors (PPIs) offer more rapid symptom relief and better healing.

4 to 8 mg/kg/day PO divided 2 to 3 times per day has been studied. Gastric pH was monitored over 24 hours after administration of varying doses of ranitidine in preterm and term neonates (n = 25, postnatal age 7 days to 8 months). The time gastric pH was less than 4 was decreased significantly compared to controls in patients receiving doses of 3 to 4 mg/kg PO 2 times daily and 2 mg/kg PO 3 times daily; more frequent dosing (3 times daily) also led to significantly longer times of elevated pH compared to less frequent dosing (2 times daily). While ranitidine may be effective in patients with less severe GERD, proton pump inhibitors (PPIs) offer more rapid symptom relief and better healing.

150 mg PO twice daily. The American College of Gastroenterology recommends that treatment be continued for as long as necessary to control symptoms and prevent complications.

150 mg PO 4 times per day for up to 12 weeks. Symptomatic relief may begin within 24 hours of initiation of treatment.

5 to 10 mg/kg/day PO divided 2 to 3 times per day (Max: 600 mg/day).

150 mg PO twice daily. NOTE: Single doses administered prior to bedtime (i.e., 300 mg PO at bedtime) have been less effective than 150 mg PO twice daily. Placebo-controlled studies have been carried out for 48 weeks.

Initially, 150 mg PO twice daily; however, larger doses are usually necessary; in some patients, more frequent dosing may be necessary. Maximum dose for this condition is 6 g/day PO, administered in divided doses. Continue as long as clinically indicated.

Initially, 150 mg PO twice daily; however, larger doses are usually necessary; in some patients, more frequent dosing may be necessary. Maximum dose for this condition is 6 g/day PO, administered in divided doses. Continue as long as clinically indicated.

50 mg IV (intermittent infusion) or IM every 6 to 8 hours; however, larger doses may be necessary. In general, do not exceed 400 mg/day IV, administered in divided doses.

50 mg IV (intermittent infusion) or IM every 6 to 8 hours; however, larger doses may be necessary. In general, do not exceed 400 mg/day IV, administered in divided doses.

For patients with Zollinger-Ellison syndrome, begin infusion at 1 mg/kg/hour. After 4 hours, if the measured gastric acid output is greater than 10 mEq/hour or the patient is symptomatic, adjust the dose upward in 0.5 mg/kg/hour increments, and remeasure the acid output. Dosages up to 2.5 mg/kg/hour or infusion rates up to 220 mg/hour have been used.

For patients with Zollinger-Ellison syndrome, begin infusion at 1 mg/kg/hour. After 4 hours, if the measured gastric acid output is greater than 10 mEq/hour or the patient is symptomatic, adjust the dose upward in 0.5 mg/kg/hour increments, and remeasure the acid output. Dosages up to 2.5 mg/kg/hour or infusion rates up to 220 mg/hour have been used.

150 mg PO twice daily or 300 mg PO once daily after the evening meal or at bedtime. Most duodenal ulcers heal within 4 weeks, most gastric ulcers heal within 6 weeks. Per the manufacturer, many foreign trials have shown that 100 mg PO twice daily has been as effective as 150 mg PO twice daily for duodenal ulcer. Safety of therapy beyond 8 weeks for uncomplicated duodenal ulcer or beyond 6 weeks for benign gastric ulcer has not been assessed.

150 mg PO twice daily or 300 mg PO once daily after the evening meal or at bedtime. Most duodenal ulcers heal within 4 weeks, most gastric ulcers heal within 6 weeks. Per the manufacturer, many foreign trials have shown that 100 mg PO twice daily has been as effective as 150 mg PO twice daily for duodenal ulcer. Safety of therapy beyond 8 weeks for uncomplicated duodenal ulcer or beyond 6 weeks for benign gastric ulcer has not been assessed.

2 to 4 mg/kg/dose PO twice daily (Max: 300 mg/day).

50 mg IV (intermittent infusion) or IM every 6 to 8 hours.

50 mg IV (intermittent infusion) or IM every 6 to 8 hours.

2 to 4 mg/kg/day IV (intermittent infusion) divided and administered every 6 to 8 hours (Max: 50 mg/dose).

6.25 mg/hour via continuous IV infusion (i.e., total daily dosage will equal 150 mg/24 hours).

6.25 mg/hour via continuous IV infusion (i.e., total daily dosage will equal 150 mg/24 hours).

150 mg PO once daily at bedtime. No placebo-controlled studies have lasted for longer than 1 year.

150 mg PO once daily at bedtime. No placebo-controlled studies have lasted for longer than 1 year.

2 to 4 mg/kg/day PO once daily at bedtime (Max: 150 mg/day).

NOTE: This drug is discontinued in the U.S. A dose of 50 mg IV once in combination with an H1-blocker (e.g., diphenhydramine) has been used. Ranitidine has also been used to premedicate against these reactions for patients receiving selected chemotherapy agents.[33365] Per treatment guidelines, the use of H2-blockers provides uncertain adjunctive benefit in prevention of treatment of anaphylaxis.

NOTE: This drug is discontinued in the U.S. A dose of 1 mg/kg IV (Max: 50 mg/dose), then 2 to 4 mg/kg/day, divided every 6 to 8 hours (Max: 200 mg/day), has been used, but per guidelines the benefit as adjunctive therapy for anaphylaxis is uncertain.

NOTE: This drug is discontinued in the U.S. A dose of 4 to 8 mg/kg/day PO divided twice daily (Max: 300 mg/day) has been used, but per guidelines the benefit as adjunctive therapy for anaphylaxis is uncertain.

†Indicates off-label use

In patients with compensated cirrhosis, there are minor but clinically insignificant alterations in ranitidine half-life and clearance. It appears that no dosage adjustment is needed in patients with hepatic impairment.

FDA-approved dose adjustments (Adults and Adolescents older than 16 years receiving adult dosage)
CrCl 50 mL/minute or more: No dosage adjustment needed.
CrCl less than 50 mL/minute: Reduce recommended dose by 50% (or extend dosing interval). For example, the manufacturer recommends a dosage of 150 mg PO every 24 hours or 50 mg IV every 18 to 24 hours. Depending upon the patient's condition, the PO or IV dosage may be cautiously increased to every 12 hours if required.
 
Pediatric dose adjustments
The following dose adjustments are based on the usual dose of ranitidine in pediatric patients of 2 to 6 mg/kg/day PO divided every 8 to 12 hours or 2 to 4 mg/kg/day IV divided every 6 to 24 hours :
CrCl 30 to 50 mL/minute/1.73 m2: 2 mg/kg/dose PO every 12 hours; 1 mg/kg/dose IV every 12 hours.
CrCl 10 to 29 mL/minute/1.73 m2: 1 mg/kg/dose PO every 12 hours; 0.5 mg/kg/dose IV every 12 hours.
CrCl less than 10 mL/minute/1.73 m2: 1 mg/kg/dose PO every 24 hours; 0.5 mg/kg/dose IV every 24 hours.
 
Intermittent hemodialysis
Ranitidine is removed to some degree by hemodialysis. The patient's normal dosage schedule based on CrCl should be adjusted, when possible, so that the timing of a regularly scheduled dose coincides with the end of a hemodialysis session. 1 mg/kg/dose PO every 24 hours or 0.5 mg/kg/dose IV every 24 hours is recommended for pediatric patients.
 
Peritoneal dialysis
Adults: 75 to 150 mg PO every 24 hours; 50% to 75% dose reduction for IV.
Pediatrics: 1 mg/kg/dose PO every 24 hours or 0.5 mg/kg/dose IV every 24 hours.
 
Continuous renal replacement therapy
Adults: 150 mg PO every 12 to 24 hours; 50% dose reduction for IV.
Pediatrics: 2 mg/kg/dose PO every 12 hours or 1 mg/kg/dose IV every 12 hours.

Acalabrutinib: (Moderate) Separate the administration of acalabrutinib and H2-blockers if these agents are used together; administer acalabrutinib 2 hours before the H2-blocker. Acalabrutinib solubility decreases with increasing pH values; therefore, coadministration may result in decreased acalabrutinib exposure and effectiveness.
Acetohexamide: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion; coadministration of adefovir with drugs that reduce renal function or compete for active tubular secretion, such as ranitidine may decrease adefovir elimination by competing for common renal tubular transport systems; therefore increasing serum concentrations of either adefovir and/or ranitidine may occur.
Alendronate: (Moderate) Although the clinical significance has not been determined, the bioavailability of oral alendronate is doubled by concomitant administration of intravenous ranitidine. Investigations have not been undertaken to determine if other H2-antagonists have a similar effect on bioavailability. Patients should be closely monitored when H2-blockers are coadministered as they may affect the bioavailability of alendronate, possibly leading to a higher likelihood of developing adverse effects while taking alendronate.
Alendronate; Cholecalciferol: (Moderate) Although the clinical significance has not been determined, the bioavailability of oral alendronate is doubled by concomitant administration of intravenous ranitidine. Investigations have not been undertaken to determine if other H2-antagonists have a similar effect on bioavailability. Patients should be closely monitored when H2-blockers are coadministered as they may affect the bioavailability of alendronate, possibly leading to a higher likelihood of developing adverse effects while taking alendronate.
Alogliptin; Pioglitazone: (Minor) Concentrations of pioglitazone may be decreased with concomitant use of ranitidine. The effect of capistration on the systemic exposure of pioglitazone was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with ranitidine 150 mg twice daily for 4 days resulted in a 13% and 16% reduction in pioglitazone AUC and Cmax, respectively. Close monitoring of blood glucose is recommended; dosage adjustments in pioglitazone may be needed.
Amphetamine; Dextroamphetamine Salts: (Moderate) The use of H2-blockers with amphetamine therapy may change the onset of action of amphetamine or dextroamphetamine due to the increase in gastric pH. The time to maximum concentration (Tmax) of these amphetamines is decreased compared to when administered alone, thus increasing stimulant concentrations, which may be of particular significance with extended-release dosage forms. Monitor clinical response and adjust if needed.
Atazanavir: (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Atazanavir; Cobicistat: (Major) Coadministration of H2-blockers with atazanavir reduces serum atazanavir concentrations; however, H2-blockers can be used under specific administration restrictions. Although data are insufficient to recommend atazanavir dosing in children < 40 kg receiving concomitant H2-blockers, the same recommendations regarding timing and maximum doses of concomitant H2-blockers should be followed. In treatment-naive patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 40 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. If a treatment-naive adult or adolescent (>= 40 kg) cannot tolerate ritonavir, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and the atazanavir dose should be increased to 400 mg once daily with food given at least 2 hours before or 10 hours after the H2- blocker. Data are insufficent to recommend atazanavir dosing in children or adolescents < 40 kg not receiving ritonavir boosting. In treatment-naive patients on a cobicistat-boosted regimen, cobicistat and atazanavir may be administered without dosage adjustment if given at the same time or a minimum of 10 hours after dosing of the H2-blocker. The H2-blocker dose should not exceed a dose that is comparable to 40 mg/day of famotidine in treatment-naive patients. In treatment-experienced patients >= 40 kg, do not exceed an H2- blocker dose equivalent to famotidine 20 mg twice daily, and give atazanavir 300 mg with ritonavir 100 mg once daily with food. Give atazanavir simultaneously with and/or at least 10 hours after the H2- blocker. In treatment-experienced patients >= 40 kg receiving H2-antagonists and tenofovir, atazanavir should be dosed 400 mg with ritonavir 100 mg once daily with food. In antiretroviral-experienced patients on a cobicistat-boosted regimen, the dosage of cobicistat with atazanavir needs to be increased if administered with H2-blockers; the recommended dose is cobicistat 150 mg/day with atazanavir 400 mg/day and 20 mg/day or less of famotidine or other comparably dosed H2-blocker. Significant reductions in atazanavir serum concentrations may lead to therapeutic failure and the development of HIV resistance. Closely monitor patients for antiretroviral therapeutic failure and resistance development during treatment with an H2- blocker.
Atracurium: (Moderate) Ranitidine may cause resistance to atracurium-induced neuromuscular blockade, due to pharmacodynamic alterations at the acetylcholine receptor. In vitro studies demonstrate that therapeutic serum concentrations of ranitidine inhibit acetylcholinesterase, thus increasing the amount of acetylcholine available to compete at the neuromuscular junction and reverse the neuromuscular blockade. The inhibition of acetylcholinesterase is likely dose-related. Resistance to nondepolarizing neuromuscular blockers was reported occasionally with intravenous ranitidine dosages that were slightly higher than those given clinically, but not frequently with oral therapy.
Bisacodyl: (Minor) The concomitant use of bisacodyl tablets with H2-blockers can cause the enteric coating of the bisacody tablet to dissolve prematurely, leading to possible gastric irritation or dyspepsia. Avoid H2-blockers within 1 hour before or after the bisacodyl dosage.
Bismuth Subsalicylate: (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) H2-blockers may increase the systemic absorption of bismuth from bismuth-containing compounds like bismuth subsalicylate.
Bosutinib: (Moderate) Bosutinib displays pH-dependent aqueous solubility; therefore, concomitant use of bosutinib and H2-blockers may result in decreased plasma exposure of bosutinib. Separate the administration of bosutinib and H2-blockers by more than 2 hours.
Budesonide: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression.
Budesonide; Formoterol: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for altered response to budesonide in patients receiving H2-blockers with enteric-coated or extended-release formulations of oral budesonide. Enteric-coated budesonide granules (Entocort EC) dissolve at a pH > 5.5. Likewise, the dissolution of the coating of extended-release budesonide tablets (Uceris) is pH dependent. Concomitant use of oral budesonide and antacids, milk, or other drugs that increase gastric pH levels can cause these products to dissolve prematurely, possibly affecting release properties and absorption of the drug in the duodenum. When cimetidine (1 gram/day PO) is administered with an uncoated formulation of oral budesonide, a slight increase in absorption and peak plasma concentrations occur, resulting in significant cortisol suppression.
Cabotegravir; Rilpivirine: (Moderate) Coadministration with ranitidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of ranitidine for at least 12 hours before and at least 4 hours after administering rilpivirine.
Calcium Carbonate; Risedronate: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
Cefditoren: (Moderate) Cefditoren pivoxil absorption may be decreased by H2-blockers. Coadministration is not recommended. A reduction in mean Cmax (by 27%) and AUC (by 22%) were seen for oral cefditoren pivoxil (single dose, 400 mg after a meal) when a single intravenous dose of an H2-blocker (famotidine) was given. The clinical significance of this interaction is not known.
Cefpodoxime: (Moderate) H2-blockers should be avoided during treatment with cefpodoxime. Coadministration could result in antibiotic failure. H2-blockers increase gastric pH. Cefpodoxime proxetil requires low gastric pH for dissolution. While the rate of absorption is not affected, coadministration reduces cefpodoxime AUC, peak plasma concentration (by 42%), and extent of absorption (by 32%).
Ceftibuten: (Minor) H2-blockers can affect the pharmacokinetics of some orally-administered cephalosporins. The oral bioavailability of ceftibuten was reported to be increased by the administration of 150 mg of ranitidine PO every 12 hours for 3 days, but this interaction is of unknown clinical relevance.
Cefuroxime: (Major) Avoid the concomitant use of H2-blockers and cefuroxime. Drugs that reduce gastric acidity, such as H2-blockers, can interfere with the oral absorption of cefuroxime axetil and may result in reduced antibiotic efficacy.
Chlorpropamide: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
Cisatracurium: (Moderate) Ranitidine may cause resistance to cisatracurium-induced neuromuscular blockade, due to pharmacodynamic alterations at the acetylcholine receptor. In vitro studies demonstrate that therapeutic serum concentrations of ranitidine inhibit acetylcholinesterase, thus increasing the amount of acetylcholine available to compete at the neuromuscular junction and reverse the neuromuscular blockade. The inhibition of acetylcholinesterase is likely dose-related. Resistance to nondepolarizing neuromuscular blockers was reported occasionally with intravenous ranitidine dosages that were slightly higher than those given clinically, but not frequently with oral therapy.
Cyclosporine: (Minor) Although data are conflicting, cautious use of ranitidine and cyclosporine is warranted; cyclosporine can cause nephrotoxicity, and ranitidine is substantially excreted by the kidney. The risk of toxic reactions to ranitidine may be greater in patients with impaired renal function; ranitidine dose reduction is needed for renal impairment.
Cysteamine: (Major) Monitor white blood cell (WBC) cystine concentration closely when administering delayed-release cysteamine (Procysbi) with H2-blockers. Drugs that increase the gastric pH may cause the premature release of cysteamine from delayed-release capsules, leading to an increase in WBC cystine concentration.
Dacomitinib: (Major) Administer dacomitinib at least 6 hours before or 10 hours after taking ranitidine due to the risk of decreased plasma concentrations of dacomitinib which may impact efficacy. Although the effect of H2-blockers on dacomitinib pharmacokinetics has not been studied, coadministration with a proton pump inhibitor decreased the dacomitinib Cmax and AUC by 51% and 39%, respectively.
Darunavir: (Minor) No change in darunavir concentrations was observed when coadministered with ranitidine. Darunavir can be coadministered with H2-blockers without any dosage adjustments.
Darunavir; Cobicistat: (Minor) No change in darunavir concentrations was observed when coadministered with ranitidine. Darunavir can be coadministered with H2-blockers without any dosage adjustments.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Minor) No change in darunavir concentrations was observed when coadministered with ranitidine. Darunavir can be coadministered with H2-blockers without any dosage adjustments.
Dasatinib: (Major) Do not administer H2-blockers with dasatinib due to the potential for decreased dasatinib exposure and reduced efficacy. Consider using an antacid if acid suppression therapy is needed. Administer the antacid at least 2 hours prior to or 2 hours after the dose of dasatinib. Concurrent use of an H2-blocker reduced the mean Cmax and AUC of dasatinib by 63% and 61%, respectively.
Delavirdine: (Major) Coadministration of delavirdine with H2-blockers results in decreased absorption of delavirdine. Administration of delavirdine and H2-blockers should be separated by at least 1 hour. Chronic use of H2-blockers with delavirdine is not recommended.
Diphenhydramine; Naproxen: (Moderate) The enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or greater. Concomitant use of this particular naproxen product with H--blockers is not recommended due to the gastric pH alteration.
Dolutegravir; Rilpivirine: (Moderate) Coadministration with ranitidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of ranitidine for at least 12 hours before and at least 4 hours after administering rilpivirine.
Donepezil; Memantine: (Minor) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as ranitidine, could result in elevated serum concentrations of one or both drugs.
Eliglustat: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of ranitidine and eliglustat is not recommended. Ranitidine is a weak CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Because CYP3A plays a significant role in the metabolism of eliglustat in CYP2D6 PMs, coadministration with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias) in these patients.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration with ranitidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of ranitidine for at least 12 hours before and at least 4 hours after administering rilpivirine.
Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Coadministration with ranitidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of ranitidine for at least 12 hours before and at least 4 hours after administering rilpivirine.
Entecavir: (Moderate) Both entecavir and ranitidine are secreted by active tubular secretion. In theory, coadministration of entecavir with ranitidine may increase the serum concentrations of either drug due to competition for the drug elimination pathway. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
Erlotinib: (Major) If concomitant use of erlotinib with ranitidine is necessary, erlotinib must be taken 10 hours after the last dose of ranitidine and at least 2 hours before the next dose. Erlotinib displays pH-dependent solubility with decreased solubility at a higher pH; the increased gastric pH resulting from ranitidine therapy may reduce the bioavailability of erlotinib. Increasing the dose of erlotinib without modifying the administration schedule is unlikely to compensate for loss of exposure. Erlotinib exposure was decreased by 33% and the Cmax by 54% when erlotinib was administered 2 hours after a 300-mg dose of ranitidine. When administered at least 10 hours after an evening dose of ranitidine and 2 hours before the morning dose, erlotinib exposure was decreased by 15% and Cmax by 17%.
Ethanol: (Minor) Some studies have suggested that H2-receptor antagonists inhibit gastric alcohol dehydrogenase and thus decrease the first pass metabolism of alcohol, and some studies have suggested an interaction may not always occur. A meta-analysis evaluating the effects of H2-blockers on blood alcohol concentrations reported that only cimetidine and ranitidine, but not other H2-blockers, caused small elevations in serum alcohol levels. However, it was reported that larger studies were less likely to show an effect and that these elevations were not likely to be clinically relevant.
Flibanserin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including ranitidine, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the risks of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Fluvastatin: (Moderate) Concomitant administration of ranitidine with fluvastatin can decrease fluvastatin clearance by 18 to 23%, and increase AUC by 24 to 33%.
Fosamprenavir: (Moderate) The coadministration of fosamprenavir with H2-blockers decreases amprenavir plasma concentrations. Use these drugs together with caution as amprenavir plasma concentrations may be decreased, which could lead to loss of virologic response and possible viral resistance to fosamprenavir.
Gefitinib: (Major) Avoid coadministration of ranitidine with gefitinib if possible due to decreased exposure to gefitinib, which may lead to reduced efficacy. If concomitant use is unavoidable, take gefitinib 6 hours after the last dose or 6 hours before the next dose of ranitidine. Gefitinib exposure is affected by gastric pH. Coadministration of high doses of ranitidine with sodium bicarbonate to maintain gastric pH above 5 decreased gefitinib exposure by 47%.
Glimepiride: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
Glimepiride; Rosiglitazone: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
Glipizide: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
Glipizide; Metformin: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
Glyburide: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
Glyburide; Metformin: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
Infigratinib: (Moderate) Separate the administration of infigratinib and H2-receptor antagonists if concomitant use is necessary. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Administer infigratinib two hours before or ten hours after an H2-receptor antagonist.
Iron: (Minor) The bioavailability of oral iron salts is influenced by gastric pH, and the concomitant administration of H2-blockers can decrease iron absorption. The non-heme ferric form of iron needs an acidic intragastric pH to be reduced to ferrous and to be absorbed. Iron salts and polysaccharide-iron complex provide non-heme iron. H2-blockers have long-lasting effects on the secretion of gastric acid and thus, increase the pH of the stomach. The increase in intragastric pH can interfere with the absorption of iron salts.
Itraconazole: (Moderate) When administering H2-blockers with the 100 mg itraconazole capsule and 200 mg itraconazole tablet formulations, systemic exposure to itraconazole is decreased. Conversely, exposure to itraconazole is increased when H2-blockers are administered with the 65 mg itraconazole capsule. Administer H2-blockers at least 2 hours before or 2 hours after the 100 mg capsule or 200 mg tablet. Monitor for increased itraconazole-related adverse effects if H2-blockers are administered with itraconazole 65 mg capsules.
Ketoconazole: (Major) Avoid use of H2-blockers with ketoconazole. Medications that increase gastric pH may impair ketoconazole absorption.
Lansoprazole; Naproxen: (Moderate) The enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or greater. Concomitant use of this particular naproxen product with H--blockers is not recommended due to the gastric pH alteration.
Ledipasvir; Sofosbuvir: (Major) Solubility of ledipasvir decreases as gastric pH increases; thus, coadministration of ledipasvir; sofosbuvir with H2-blockers may result in lower ledipasvir plasma concentrations. Ledipasvir; sofosbuvir can be administered with H2-blockers if given simultaneously or separated by 12 hours. The H2-blocker dose should not exceed a dose that is comparable to famotidine 40 mg twice daily.
Lemborexant: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with ranitidine as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ranitidine is a weak CYP3A4 inhibitor. Consider if an alternative to ranitidine would be appropriate for the patient. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Levoketoconazole: (Major) Avoid use of H2-blockers with ketoconazole. Medications that increase gastric pH may impair ketoconazole absorption.
Lomitapide: (Major) Concomitant use of lomitapide and ranitidine may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Ranitidine is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Loperamide: (Moderate) Due to the risk for adverse effects, caution is advised when administering loperamide with ranitidine. Taking these drugs together may increase the serum concentration of loperamide. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
Loperamide; Simethicone: (Moderate) Due to the risk for adverse effects, caution is advised when administering loperamide with ranitidine. Taking these drugs together may increase the serum concentration of loperamide. If these drugs are used together, monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest).
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may alter the systemic exposure of ranitidine. If used together, ranitidine may require a dosage adjustment to obtain the desired therapeutic effect.
Mefloquine: (Moderate) H2-blockers may increase plasma concentrations of mefloquine. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially patients with a neurological or psychiatric history. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO twice daily. In both healthy subjects and peptic ulcer patients, Cmax was increased 42.4% and 20.5%, respectively. The AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted.
Memantine: (Minor) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as ranitidine, could result in elevated serum concentrations of one or both drugs.
Midazolam: (Moderate) Although conflicting data exist regarding an interaction between ranitidine and midazolam, it may be prudent to monitor patients taking both ranitidine and midazolam for increased sedation. The manufacturer of ranitidine warns that the absorption of midazolam may be increased in patients taking ranitidine due to alterations in pH.
Midodrine: (Minor) Although the exact mechanism is uncertain, midodrine may be excreted by the same base-secreting pathway of the kidneys responsible for secretion of other basic drugs like ranitidine. By this pathway, midodrine may potentially interact with ranitidine; however, no drug interactions of this kind have been reported.
Mivacurium: (Moderate) Ranitidine may cause resistance to mivacurium-induced neuromuscular blockade, due to pharmacodynamic alterations at the acetylcholine receptor. In vitro studies demonstrate that therapeutic serum concentrations of ranitidine inhibit acetylcholinesterase, thus increasing the amount of acetylcholine available to compete at the neuromuscular junction and reverse the neuromuscular blockade. The inhibition of acetylcholinesterase is likely dose-related. Resistance to nondepolarizing neuromuscular blockers was reported occasionally with intravenous ranitidine dosages that were slightly higher than those given clinically, but not frequently with oral therapy.
Naproxen: (Moderate) The enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or greater. Concomitant use of this particular naproxen product with H--blockers is not recommended due to the gastric pH alteration.
Naproxen; Esomeprazole: (Moderate) The enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or greater. Concomitant use of this particular naproxen product with H--blockers is not recommended due to the gastric pH alteration.
Naproxen; Pseudoephedrine: (Moderate) The enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or greater. Concomitant use of this particular naproxen product with H--blockers is not recommended due to the gastric pH alteration.
Neratinib: (Major) Take neratinib at least 2 hours before the next dose of an H2-blocker or 10 hours after the last dose of an H2-blocker due to decreased absorption and systemic exposure of neratinib; the solubility of neratinib decreases with increasing pH of the GI tract. The Cmax and AUC of neratinib were reduced by 57% and 48%, respectively, when administered 2 hours after a daily dose of ranitidine 300 mg. The Cmax and AUC of neratinib were reduced by 44% and 32%, respectively, when administered 2 hours before ranitidine 150 mg twice daily (given approximately 12 hours apart).
Nicardipine: (Moderate) Ranitidine may increase nicardipine AUC by inhibiting hepatic metabolism of nicardipine. Clinicians should be alert for exaggerated nicardipine effects if ranitidine is added to the regimen.
Nifedipine: (Moderate) Cimetidine can increase nifedipine exposure by inhibiting hepatic metabolism of nifedipine. Ranitidine has been shown to have a similar, but lesser, effect on nifedipine pharmacokinetics. Clinicians should be alert for exaggerated nifedipine effects if ranitidine is coadministered.
Nilotinib: (Moderate) If concomitant use of these agents is necessary, administer the H2-blocker approximately 10 hours before and approximately 2 hours after the nilotinib dose. Nilotinib displays pH-dependent solubility with decreased solubility at a higher pH. The concomitant use of nilotinib and H2-blockers that elevate the gastric pH may reduce the bioavailability of nilotinib. In a study in healthy subjects, there was no significant change in nilotinib pharmacokinetics when a single 400-mg nilotinib dose was given 10 hours after and 2 hours prior to famotidine.
Octreotide: (Moderate) Coadministration of oral octreotide with H2-blockers may require increased doses of octreotide. Coadministration of oral octreotide with drugs that alter the pH of the upper GI tract, including H2-blockers, may alter the absorption of octreotide and lead to a reduction in bioavailability.
Pancuronium: (Moderate) Ranitidine may cause resistance to pancuronium-induced neuromuscular blockade, due to pharmacodynamic alterations at the acetylcholine receptor. In vitro studies demonstrate that therapeutic serum concentrations of ranitidine inhibit acetylcholinesterase, thus increasing the amount of acetylcholine available to compete at the neuromuscular junction and reverse the neuromuscular blockade. The inhibition of acetylcholinesterase is likely dose-related. Resistance to nondepolarizing neuromuscular blockers was reported occasionally with intravenous ranitidine dosages that were slightly higher than those given clinically, but not frequently with oral therapy.
Pazopanib: (Major) Avoid coadministration of pazopanib with H2-blockers due to decreased absorption of pazopanib, which may decrease efficacy. If concomitant administration with a gastric acid-reducing agent is unavoidable, consider the use of a short-acting antacid in place of an H2-blocker; separate administration of the short-acting antacid and pazopanib by several hours to avoid a reduction in pazopanib exposure. Concomitant use of pazopanib with a proton pump inhibitor decreased pazopanib exposure (AUC and Cmax) by approximately 40%.
Pexidartinib: (Moderate) Administer pexidartinib 2 hours before or 10 hours after H2-blockers as concurrent administration may reduce pexidartinib exposure. Although the effects of H2-blockers on pexidartinib pharmacokinetics have not been studied, other acid-reducing agents have been shown to decrease pexidartinib exposure by 50%.
Pioglitazone: (Minor) Concentrations of pioglitazone may be decreased with concomitant use of ranitidine. The effect of capistration on the systemic exposure of pioglitazone was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with ranitidine 150 mg twice daily for 4 days resulted in a 13% and 16% reduction in pioglitazone AUC and Cmax, respectively. Close monitoring of blood glucose is recommended; dosage adjustments in pioglitazone may be needed.
Pioglitazone; Glimepiride: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas. (Minor) Concentrations of pioglitazone may be decreased with concomitant use of ranitidine. The effect of capistration on the systemic exposure of pioglitazone was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with ranitidine 150 mg twice daily for 4 days resulted in a 13% and 16% reduction in pioglitazone AUC and Cmax, respectively. Close monitoring of blood glucose is recommended; dosage adjustments in pioglitazone may be needed.
Pioglitazone; Metformin: (Minor) Concentrations of pioglitazone may be decreased with concomitant use of ranitidine. The effect of capistration on the systemic exposure of pioglitazone was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with ranitidine 150 mg twice daily for 4 days resulted in a 13% and 16% reduction in pioglitazone AUC and Cmax, respectively. Close monitoring of blood glucose is recommended; dosage adjustments in pioglitazone may be needed.
Polyethylene Glycol; Electrolytes; Bisacodyl: (Minor) The concomitant use of bisacodyl tablets with H2-blockers can cause the enteric coating of the bisacody tablet to dissolve prematurely, leading to possible gastric irritation or dyspepsia. Avoid H2-blockers within 1 hour before or after the bisacodyl dosage.
Procainamide: (Moderate) When ranitidine is used in doses more than 300 mg/day, such as those used in the treatment of Zollinger-Ellison syndrome, the renal tubular secretion of procainamide is inhibited; procainamide clearance is reduced leading to elevated procainamide and N-acetyl-procainamide plasma concentrations. It may be prudent to monitor patients for procainamide toxicity if procainamide and high doses of ranitidine are coadministered.
Propantheline: (Minor) Propantheline bromide increases the bioavailability of ranitidine when the drugs are administered concomitantly. Propantheline bromide is believed to delay gastric emptying, increase transit time, and thereby increase the peak plasma concentration of ranitidine.
Ranolazine: (Moderate) Coadminister ranolazine and ranitidine with caution. Ranitidine is a substrate of the OCT2 transporter. Dosage reduction for metformin, another OCT2 transporter substrate, is recommended by the manufacturer of ranolazine. Coadministration of metformin and ranolazine 1000 mg twice daily results in increased plasma concentrations of metformin. Doses of metformin do not require reduction if coadministered with ranolazine 500 mg twice daily. Reductions in the ranitidine dose may be necessary.
Rilpivirine: (Moderate) Coadministration with ranitidine may significantly decrease rilpivirine plasma concentrations, potentially resulting in treatment failure. To decrease the risk of virologic failure, avoid use of ranitidine for at least 12 hours before and at least 4 hours after administering rilpivirine.
Risedronate: (Major) Use of H2-blockers with delayed-release risedronate tablets (Atelvia) is not recommended. Co-administration of drugs that raise stomach pH increases risedronate bioavailability due to faster release of the drug from the enteric coated tablet. This interaction does not apply to risedronate immediate-release tablets.
Risperidone: (Moderate) Although dosage adjustments are not necessary, patients receiving concurrent treatment with risperidone and ranitidine should be monitored for risperidone-induced side effects or extrapyramidal symptoms. Pharmacokinetic data indicate that increased exposure to risperidone and its active metabolite occurs during use of ranitidine. This interaction is thought to be the result of inhibition of CYP3A4, one of the isoenzymes responsible for the metabolism of risperidone.
Rocuronium: (Moderate) Ranitidine may cause resistance to rocuronium-induced neuromuscular blockade, due to pharmacodynamic alterations at the acetylcholine receptor. In vitro studies demonstrate that therapeutic serum concentrations of ranitidine inhibit acetylcholinesterase, thus increasing the amount of acetylcholine available to compete at the neuromuscular junction and reverse the neuromuscular blockade. The inhibition of acetylcholinesterase is likely dose-related. Resistance to nondepolarizing neuromuscular blockers was reported occasionally with intravenous ranitidine dosages that were slightly higher than those given clinically, but not frequently with oral therapy.
Saquinavir: (Minor) The coadministration of saquinavir and ranitidine increases saquinavir plasma concentrations. However, the increase is not thought to be clinically relevant. No dose adjustment of saquinavir is recommended; no dosage information regarding the use of saquinavir enhanced or 'boosted' with ritonavir is available.
Secretin: (Major) Discontinue use of H2-blockers at least 2 days before administering secretin. Patients who are receiving H2-blockers at the time of stimulation testing may be hyperresponsive to secretin stimulation, falsely suggesting gastrinoma.
Selpercatinib: (Major) Avoid coadministration of selpercatinib with ranitidine due to the risk of decreased selpercatinib exposure which may reduce its efficacy. If concomitant use is unavoidable, take selpercatinib 2 hours before or 10 hours after administration of ranitidine. Coadministration with acid-reducing agents decreases selpercatinib plasma concentrations; however, no clinically significant differences in the pharmacokinetics of selpercatinib were observed when given under fasting conditions with multiple daily doses of ranitidine given 10 hours prior to and 2 hours after the selpercatinib dose.
Sofosbuvir; Velpatasvir: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) H2-blockers may be administered simultaneously with or 12 hours apart from velpatasvir. H2-blocker doses should not exceed doses comparable to famotidine 40 mg twice daily. Velpatasvir solubility decreases as pH increases; therefore, drugs that increase gastric pH are expected to decrease the concentrations of velpatasvir, potentially resulting in loss of antiviral efficacy.
Sonidegib: (Moderate) Based on population PK analysis, the concomitant administration of a histamine-2-receptor antagonist such as ranitidine decreases the geometric mean sonidegib steady-state AUC (0-24 hours) value by 34%.
Sotorasib: (Major) Avoid coadministration of sotorasib and gastric acid-reducing agents, such as H2-receptor antagonists. Coadministration may decrease sotorasib exposure resulting in decreased efficacy. If necessary, sotorasib may be administered 4 hours before or 10 hours after a locally acting antacid. Coadministration with an H2-receptor antagonist decreased sotorasib exposure by 38% under fed conditions.
Sulfonylureas: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
Sumatriptan; Naproxen: (Moderate) The enteric-coated, delayed-release naproxen tablets are designed to dissolve at a pH of 6 or greater. Concomitant use of this particular naproxen product with H--blockers is not recommended due to the gastric pH alteration.
Thalidomide: (Moderate) Thalidomide and other agents that slow cardiac conduction such as H2-blockers should be used cautiously due to the potential for additive bradycardia.
Tolazamide: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
Tolbutamide: (Moderate) Ranitidine has been shown to affect the pharmacokinetics of some oral sulfonylureas. Patients receiving sulfonylureas should be observed for evidence of altered glycemic response when ranitidine is instituted or discontinued. The mechanism of this interaction may involve either increasing the absorption or decreasing the clearance of the sulfonylurea. Asymptomatic hypoglycemia has been observed as a result of this interaction. It is unclear at this time if famotidine or nizatidine interact with oral sulfonylureas.
Triazolam: (Minor) Monitor for signs of triazolam toxicity during coadministration with ranitidine. Coadministration may increase the max plasma concentration of triazolam by 30% and the total drug exposure by 27%.
Trospium: (Moderate) Both trospium and ranitidine are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or ranitidine due to competition for the drug elimination pathway. Careful patient monitoring and dosage adjustment of trospium and/or ranitidine is recommended.
Vecuronium: (Moderate) Ranitidine may cause resistance to vecuronium-induced neuromuscular blockade, due to pharmacodynamic alterations at the acetylcholine receptor. In vitro studies demonstrate that therapeutic serum concentrations of ranitidine inhibit acetylcholinesterase, thus increasing the amount of acetylcholine available to compete at the neuromuscular junction and reverse the neuromuscular blockade. The inhibition of acetylcholinesterase is likely dose-related. Resistance to nondepolarizing neuromuscular blockers was reported occasionally with intravenous ranitidine dosages that were slightly higher than those given clinically, but not frequently with oral therapy.

Acid Reducer/Ranitidine/Ranitidine Hydrochloride/Wal-Zan/Zantac/Zantac 150/Zantac 75 Oral Tab: 75mg, 150mg, 300mg
Ranitidine Hydrochloride/Taladine Oral Cap: 150mg, 300mg
Ranitidine Hydrochloride/Zantac Intramuscular Inj Sol: 1mL, 25mg
Ranitidine Hydrochloride/Zantac Intravenous Inj Sol: 1mL, 25mg
Ranitidine Hydrochloride/Zantac Oral Sol: 1mL, 15mg

300 mg/day PO or 200 mg/day IV for most indications; up to 6 g/day PO or 220 mg/hour continuous IV for pathologic hypersecretory conditions.

300 mg/day PO or 200 mg/day IV for most indications; up to 6 g/day PO or 220 mg/hour continuous IV for pathologic hypersecretory conditions.

17 years: 300 mg/day PO or 200 mg/day IV for most indications; up to 6 g/day PO or 220 mg/hour continuous IV for pathologic hypersecretory conditions.
13 to 16 years: 10 mg/kg/day PO (Usual Max: 300 mg/day); 4 mg/kg/day IV (Max: 200 mg/day) is FDA-approved maximum dosage; however, doses up to 6 mg/kg/day IV (Max: 200 mg/day) have been used off-label.

10 mg/kg/day PO (Usual Max: 300 mg/day); 4 mg/kg/day IV (Max: 200 mg/day) is FDA-approved maximum dosage; however, doses up to 6 mg/kg/day IV (Max: 200 mg/day) have been used off-label.

10 mg/kg/day PO; 4 mg/kg/day IV is FDA-approved maximum dosage; however, doses up to 6 mg/kg/day IV have been used off-label.

Safety and efficacy have not been established; however, doses up to 8 mg/kg/day PO or 5 mg/kg/day have been used off-label.

Ranitidine competitively inhibits the binding of histamine to receptors on gastric parietal cells (designated as the H2-receptor), thus reducing basal and nocturnal gastric acid secretion. The drug also decreases the amount of gastric acid released in response to stimuli such as food, betazole, or pentagastrin. Ranitidine reduces the total volume of gastric juice, thereby indirectly decreasing pepsin secretion. Ranitidine has little to no effect on serum gastrin and does not impair intrinsic factor secretion. The drug does not appear to alter gastric motility, gastric emptying, esophageal pressures, biliary secretions, or pancreatic secretions. Ranitidine is not an antimuscarinic anticholinergic. Ranitidine may aid in gastromucosal healing. Other actions of ranitidine include an increase in gastric bacterial flora (e.g., nitrate-reducing organisms). The clinical significance of this effect is not known.
 
After bolus ranitidine doses of 100 mg IV or greater, small and transient increases in prolactin serum concentrations have been noted. Ranitidine does not affect serum concentrations or release of gonadotropin, TSH, or GH. Ranitidine may impair the release of vasopressin. Ranitidine has no effect on serum cortisol, aldosterone, androgen, or estrogen concentrations.
 
In combination with an H1-receptor antagonist, ranitidine can suppress the formation of edema, flare, and pruritus that results from histaminic activity. Human skin mast cells express both H1- and H2-receptors. Stimulation of H2-receptors leads to changes in membrane permeability (activating the cyclic AMP-PKA pathway) causing vasodilation. The resultant dilation develops more slowly and is more sustained, as compared to H1-stimulation. Combination therapy blocks both the initial and delayed histaminic response.

Ranitidine is administered either orally or parenterally. It distributes throughout the body fluids and tissues, and can be found in breast milk and CSF. Using inhibition of pentagastrin-induced acid secretion as an indicator, ranitidine's effects persist for 8 to 12 hours. It ranitidine undergoes partial metabolism (30%) in the liver, and both the unchanged drug and metabolites are excreted in the urine and feces. The half-life is 2 to 3 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: none
Although ranitidine has been reported to bind weakly to cytochrome P-450 in vitro, recommended doses of the drug do not inhibit the action of the cytochrome P-450 enzyme system. However, there have been isolated reports of drug interactions that suggest that ranitidine may affect the bioavailability of certain drugs by some mechanism as yet unidentified (e.g., a pH-dependent effect on absorption or a change in volume of distribution).
 

Due to first-pass elimination, oral bioavailability of ranitidine is about 50% to 60%. The presence of food in the GI tract does not appear to affect the extent or rate of absorption. 
 
Following oral administration, roughly 30% of an administered dose is excreted unchanged in the urine. 

Intramuscular (IM) administration results in a bioavailability of 90% to 100% compared to intravenous (IV) administration. 
 
Following IV injection, roughly 70% of ranitidine is recovered in the urine unchanged.

Intramuscular (IM) administration of ranitidine results in a bioavailability of 90% to 100% compared to intravenous (IV) administration.

There are no adequate and well-controlled studies with ranitidine in pregnant women; animal studies have not demonstrated a risk to the fetus.[29242] [33299] Ranitidine does cross the placenta; mean fetal: maternal ratios are approximately 0.9 after IV administration versus 0.4 for oral dosages. Human epidemiological evidence has not suggested an association between the drug and congenital defects in first-trimester exposure. In 2009, a population-based observational cohort study explored a possible link between gastric acid suppressive therapy (e.g., H2 blockers) during pregnancy and a diagnosis of allergic disease or a prescription for asthma or allergy medications in the exposed child. Among the cohort (n = 585,716), 1% of children exposed to gastric acid-suppressive drugs in pregnancy received a diagnosis of allergic disease. For developing allergy or asthma, an increased OR of 1.43 and 1.51, respectively, were observed regardless of drug used, time of exposure during pregnancy, and maternal history of the disease. Proposed possible mechanisms for a link include: (1) exposure to increased amounts of allergens could cause sensitization to digestion-labile antigens in the fetus; (2) the maternal Th2 cytokine pattern could promote an allergy-prone phenotype in the fetus; (3) maternal allergen-specific immunoglobulin could cross the placenta and sensitize fetal immune cells to food and airborne allergens. Study limitations were present, and confirmation of results are necessary before further conclusions can be drawn from this data.[57770] In general, experts consider ranitidine a preferred H2 blocker when one is necessary in pregnancy, due to more documented data of efficacy and safety in the pregnant population versus other agents.[45899] [57770] Risk versus benefit should be considered before use. Self-medication during pregnancy is not recommended; pregnant patients should see their health care professional for a proper diagnosis and treatment recommendations. Limited use of single dosages of ranitidine for reducing gastric acid during labor and before obstetric delivery, including caesarian section, have not been noted to adversely affect labor or neonatal outcomes.

The manufacturer recommends that caution be used with administering ranitidine to women who are breast-feeding their infants. Ranitidine is excreted into human breast milk. Milk concentrations increase with time after the administration of a maternal oral dose. Mean maternal milk:plasma ratios at 2 and 6 hours after a single oral dose are 1.9 and 6.7, respectively, although higher concentrations have also been reported. In a single-patient study, maternal milk:plasma ratios at 1.5 hours, 5.5 hours, and 12 hours after a ranitidine 150 mg dose were 6.81, 8.44, and 23.77, respectively. Prior to measuring milk and serum concentrations, the patient had previously received 5 doses of 150 mg ranitidine given every 12 hours. The pre-dose milk:plasma concentration was 18.73. Because it appears that milk concentrations are highest approximately 12 hours after a dose, the authors recommend mothers consider nursing within 2 hours after taking ranitidine, if possible. The effect of ranitidine or the resultant decrease in gastric acidity on the nursing infant is not known. However, the American Academy of Pediatrics has considered the use of cimetidine, a related agent that is also excreted into breast milk, to be usually compatible with breast-feeding due to a lack of reported adverse effects in nursing infants. Most experts consider H-2 blockers to be of low-risk to the nursing infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.