ranitidine (Discontinued)

FDA Safety Communication

On April 1, 2020, FDA requests removal of all ranitidine products (Zantac) from the market

For more information, see FDA Drug Safety Communication (link https://www.fda.gov/news-events/press-announcements/fda-requests-removal-all-ranitidine-products-zantac-market)

Health care professionals should stop prescribing and dispensing ranitidine to patients

Contact patients currently taking ranitidine, inform them of the reported contaminant N-Nitrosodimethylamine (NDMA) found in several ranitidine products, and request to discontinue medication

Discuss alternative medications approved for the same or similar uses as ranitidine that do not carry the same risks as NDMA

Gastroesophageal Reflux Disease

150 mg PO q12hr or 50 mg IM/IV q6-8hr

Gastric Ulcer, Benign

Treatment: 150 mg PO q12hr or 300 mg PO at bedtime

Maintenance of healing: 150 mg PO at bedtime

Erosive Esophagitis

Treatment: 150 mg PO q6hr or 50 mg IM/IV q6-8hr intermittent bolus or infusion; alternatively, 6.25 mg/hr IV by continuous infusion

Maintenance of healing: 150 mg PO q12hr

Hypersecretory Conditions

150 mg PO q12hr; up to 6 g/day used

Parenteral: 50 mg (2 mL) IM or intermittent IV bolus or infusion q6-8hr; not to exceed 400 mg/day; alternatively, 6.25 mg/hr continuous infusion

Dosing considerations

• More frequent doses may be necessary; individualize dosage, and continue as long as indicated; dosages up to 6 g/day have been used for severe disease
• Zollinger-Ellison syndrome: Start IV infusion at 1 mg/kg/hr, then adjust upward in 0.5 mg/kg/hr increments according to gastric acid output (not to exceed 2.5 mg/kg/hr or 220 mg/hr)  

Stress Ulcer Prophylaxis (Off-label)

150 mg PO or NG q12hr

50 mg (2 mL) IM or intermittent IV bolus or infusion q6-8hr; not to exceed 400 mg/day; alternatively, 6.25 mg/hr continuous infusion

Dosing Modifications

Renal impairment (CrCl <50 mL/min): 50 mg IV/IM q18-24hr or 150 mg PO once daily

Hepatic impairment: Dosage adjustment not necessary

Active Duodenal/Gastric Ulcer

Treatment: 4-8 mg/kg PO q12hr; not to exceed 300 mg/day  

Maintenance: 2-4 mg/kg PO once daily; not to exceed 150 mg/day

Parenteral: 2-4 mg/kg/day IV divided q6-8hr; not to exceed 50 mg/dose or 200 mg/day

Gastroesophageal Reflux Disease

1 month - 16 years

5-10 mg/kg/day PO divided q12hr; not to exceed 300 mg/day  

Parenteral (Off-label): 2-4 mg/kg/day IV divided q6-8hr; not to exceed 50 mg/dose or 200 mg/day; alternatively, infusion at 1mg/kg/dose once followed by continuous infusion of 0.08-0.17 mg/kg/hr or 2-4 mg/kg/day

Erosive Esophagitis

1 month - 16 years

5-10 mg/kg/day PO divided q12hr; not to exceed 300 mg/day  

Parenteral (Off-label): 2-4 mg/kg/day IV divided q6-8hr; not to exceed 200 mg/day; alternatively, 1mg/kg/dose once followed by continuous infusion of 0.08-0.17 mg/kg/hr or 2-4 mg/kg/day

Neonates (Off-label)

Term Neonates (<29 days)

• 2-4 mg/kg/day PO divided q8-12hr or 2 mg/kg/day IV divided q8hr  
• Prophylaxis against dexamethasone associated ulceration: 0.031-1.25 mg/kg/hr during dexamethasone therapy to maintain gastric pH >4
• Prophylaxis against stress ulceration: 2 mg/kg q12hr or 1.5 mg/kg IV q8hr; alternatively, 2 mg/kg over 10 min, followed by continuous infusion of 0.083 mg/kg/hr

Contraindicated (1)

• fezolinetant

  ranitidine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

Serious - Use Alternative (6)

• infigratinib

  ranitidine will decrease the level or effect of infigratinib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer infigratinib 2 hr before or 10 hr after administration of a H2-antagonist.

• levoketoconazole

  ranitidine will decrease the level or effect of levoketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• lonafarnib

  ranitidine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• sotorasib

  ranitidine will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

• sparsentan

  ranitidine decreases effects of sparsentan by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. H2-antagonists may decrease sparsentan exposure which may reduce efficacy of sparsentan.

• trilaciclib

  trilaciclib will decrease the level or effect of ranitidine by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

Monitor Closely (3)

• atogepant

  ranitidine will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• finerenone

  ranitidine will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

• isavuconazonium sulfate

  ranitidine will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

Minor (0)

• atogepant

  Monitor Closely (1)ranitidine will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fezolinetant

  Contraindicated (1)ranitidine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• finerenone

  Monitor Closely (1)ranitidine will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

• infigratinib

  Serious - Use Alternative (1)ranitidine will decrease the level or effect of infigratinib by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer infigratinib 2 hr before or 10 hr after administration of a H2-antagonist.

• isavuconazonium sulfate

  Monitor Closely (1)ranitidine will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)isavuconazonium sulfate will increase the level or effect of ranitidine by Other (see comment). Minor/Significance Unknown. Isavuconazonium sulfate, an OCT2 inhibitor, may increase the effects or levels of OCT2 substrates.

• levoketoconazole

  Serious - Use Alternative (1)ranitidine will decrease the level or effect of levoketoconazole by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

• lonafarnib

  Serious - Use Alternative (1)ranitidine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• sotorasib

  Serious - Use Alternative (1)ranitidine will decrease the level or effect of sotorasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use with an acid-reducing agent cannot be avoided, administer sotorasib 4 hr before or 10 hr after administration of a locally-acting antacid.

• sparsentan

  Serious - Use Alternative (1)ranitidine decreases effects of sparsentan by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. H2-antagonists may decrease sparsentan exposure which may reduce efficacy of sparsentan.

• trilaciclib

  Serious - Use Alternative (1)trilaciclib will decrease the level or effect of ranitidine by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.