Ranitidine

A02B - Drugs for peptic ulcer and GORD ATC A02BA02 Small molecule approved 1983 Oral Parenteral Natural product

JFDA label: Zydac

Mechanism of Action

Antagonist of Histamine H2 receptor — Histamine H2 receptor antagonist

Target	Action	Gene / class
Histamine H2 receptor efficacy	ANTAGONIST	HRH2

Indications

Approved

Duodenal ulcer
Duodenal ulcers
Erosive esophagitis
Gastric ulcer
Gastroesophageal reflux disease
Heartburn (OTC only)
Injection
Oral
Pathological hypersecretory conditions
Patients not able to take oral medication

Off-label

Anaphylaxis, adjunct therapy
Premedication to prevent taxane hypersensitivity
Stress ulcer prophylaxis in critically-ill patients

Contraindications

Source: Lexicomp

Hypersensitivity to ranitidine 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 ranitidine or other acid reducers. Do not use with other acid reducers. Do not use 150 mg tablet with kidney disease without medical advice. Documentation of allergenic cross-reactivity for histamine H2 antagonists is limited. However, because of similarities in che Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (6)

Not Known Asystole · atrioventricular block · bradycardia (with rapid IV administration) · tachycardia · vasculitis · ventricular premature contractions

Nervous system disorders (11)

Not Known Agitation · confusion · depression · dizziness · drowsiness · hallucination · headache · insomnia · involuntary motor activity · malaise · vertigo

Hepatobiliary disorders (4)

Not Known Cholestatic hepatitis · hepatic failure · hepatitis · jaundice

Renal and urinary disorders (2)

Not Known Acute interstitial nephritis · increased serum creatinine

Blood and lymphatic system disorders (7)

Not Known Agranulocytosis · aplastic anemia · granulocytopenia · hemolytic anemia (immune; acquired) · leukopenia · pancytopenia · thrombocytopenia

Immune system disorders (3)

Not Known Anaphylaxis · angioedema · hypersensitivity reaction (eg, bronchospasm, eosinophilia, fever)

Metabolism and nutrition disorders (2)

Not Known Acute porphyria · increased serum prolactin

Gastrointestinal disorders (8)

Not Known Abdominal distress · abdominal pain · constipation · diarrhea · nausea · necrotizing enterocolitis (very low weight neonates; Guillet 2006) · pancreatitis · vomiting

Skin and subcutaneous tissue disorders (4)

Not Known Alopecia · erythema multiforme · injection site pruritus (transient) · skin rash

Musculoskeletal and connective tissue disorders (2)

Not Known Arthralgia · myalgia

Eye disorders (1)

Not Known Blurred vision

General disorders and administration site conditions (2)

Not Known Burning sensation at injection site (transient) · pain at injection site (transient)

Respiratory, thoracic and mediastinal disorders (1)

Not Known Pneumonia (causal relationship not established)

Dosing

Source: Lexicomp

Duodenal ulcer: Oral: Treatment: 150 mg twice daily, or 300 mg once daily after the evening meal or at bedtime; maintenance of healing: 150 mg once daily at bedtime IM: 50 mg every 6 to 8 hours IV: Intermittent bolus or infusion: 50 mg every 6 to 8 hours (if increased doses are necessary utilize more frequent administration up to a maximum of 400 mg/day). Continuous IV infusion: 6.25 mg/hour Erosive esophagitis: Oral: Treatment: 150 mg 4 times daily; maintenance of healing: 150 mg twice daily Gastric ulcer, benign: Oral: 150 mg twice daily; maintenance of healing: 150 mg once daily at bedtime Gastroesophageal reflux disease (GERD): Oral: 150 mg twice daily Heartburn prevention or relief (OTC labeling): Oral: Prevention: 75 to 150 mg 30 to 60 minutes before eating food or drinking beverages that cause heartburn (maximum: 2 doses/day); do not use for more than 14 days Relief of symptoms: 75 mg to 150 mg up to twice daily (maximum: 2 doses/day); do not use for more than 14 days Pathological hypersecretory conditions: Oral: 150 mg twice daily; adjust dose or frequency as clinically indicated; doses of up to 6 g/day have been used in patients with severe disease IM: 50 mg every 6 to 8 hours IV: Continuous IV infusion: 6.25 mg/hour Continuous infusion for Zollinger-Ellison: Initial: 1 mg/kg/hour; measure gastric acid output at 4 hours, if >10 mEq or if patient is symptomatic, increase dose in increments of 0.5 mg/kg/hour; doses of up to 2.5 mg/kg/hour (or 220 mg/hour) have been used Intermittent bolus or infusion: 50 mg every 6 to 8 hours (if increased doses are necessary utilize more frequent administration up to a maximum of 400 mg/day). Patients not able to take oral medication: IM: 50 mg every 6 to 8 hours IV: Intermittent bolus or infusion: 50 mg every 6 to 8 hours (if increased doses are necessary utilize more frequent administration up to a maximum of 400 mg/day) Continuous IV infusion: 6.25 mg/hour Anaphylaxis, adjunct therapy (off-label use): IV: 50 mg/dose; should not be used as monotherapy or as first line therapy (AAAAI/ACAAI [Lieberman 2010]) Premedication to prevent taxane hypersensitivity (off-label use): IV: 50 mg administered 30 minutes prior to paclitaxel administration (along with dexamethasone and diphenhydramine) (Lee 2009) Stress ulcer prophylaxis in critically ill patients (off-label use): Note: Intended for patients with associated risk factors (eg, coagulopathy, mechanical ventilation for >48 hours, severe sepsis); discontinue use once risk factors have resolved (ASHP 1999; Rhodes 2017). Oral, nasogastric (NG) tube: 150 mg twice daily; may administer a 300 mg loading dose prior to maintenance dosing (ASHP 1999; Pemberton 1993) IV: Intermittent bolus: 50 mg every 6 to 8 hours (ASHP 1999; Cook 1998; Geus 1993)

(For additional information see "Ranitidine: Pediatric drug information") Duodenal ulcer: Oral: Treatment: Infants, Children, and Adolescents ≤16 years: 4 to 8 mg/kg/day divided twice daily; maximum: 300 mg/day Adolescents >16 years: Refer to adult dosing Maintenance of healing: Infants, Children, and Adolescents ≤16 years: 2 to 4 mg/kg once daily; maximum: 150 mg/day Adolescents >16 years: Refer to adult dosing. IM: Adolescents >16 years: Refer to adult dosing. IV: Infants, Children, and Adolescents ≤16 years: 2 to 4 mg/kg/day divided every 6 to 8 hours; maximum dose: 50 mg/dose Adolescents >16 years: Refer to adult dosing. Gastric ulcer: Oral: Treatment: Infants, Children, and Adolescents ≤16 years: 4 to 8 mg/kg/day divided twice daily; maximum: 300 mg/day Adolescents >16 years: Refer to adult dosing Maintenance of healing: Infants, Children, and Adolescents ≤16 years: 2 to 4 mg/kg once daily; maximum: 150 mg/day Adolescents >16 years: Refer to adult dosing. Gastroesophageal reflux disease (GERD) or erosive esophagitis: Oral: Infants, Children, and Adolescents ≤16 years: 5 to 10 mg/kg/day divided twice daily; maximum: 300 mg/day Adolescents >16 years: Refer to adult dosing. Heartburn prevention or relief (OTC labeling): Prevention: Children ≥12 years and Adolescents: Oral: 75 to 150 mg 30 to 60 minutes before eating food or drinking beverages that cause heartburn (maximum: 2 doses/day); do not use for more than 14 days Relief of symptoms: Children ≥12 years and Adolescents: Oral: 75 to 150 mg up to twice daily (maximum: 2 doses/day); do not use for more than 14 days Patients not able to take oral medication: Infants, Children, and Adolescents Adolescents ≥16 years: IV: Refer to adult dosing. Pathological hypersecretory conditions: Adolescents >16 years: Refer to adult dosing. Anaphylaxis, adjunct therapy (off-label use): Infants, Children, and Adolescents: IV: 1 mg/kg/dose; maximum dose: 50 mg/dose; Note: Should not be used as monotherapy or as first line therapy (AAAAI/ACAAI [Lieberman 2010])

Refer to adult dosing (use caution with dose selection).

Adults: CrCl ≥50 mL/minute: No dosage adjustment necessary. CrCl Oral: 150 mg every 24 hours; adjust dose cautiously if needed (frequency of dosing may be increased to every 12 hours or further with caution). IV: 50 mg every 18 to 24 hours; adjust dose cautiously if needed Hemodialysis: Adjust dosing schedule so that dose is scheduled to coincide with the end of hemodialysis. Stress ulcer prophylaxis (ASHP 1999): CrCl Oral, nasogastric (NG) tube: 150 mg 1 to 2 times daily IV: Intermittent bolus: 50 mg every 12 to 24 hours Pediatrics (Aronoff 2007): Oral: Based on a usual dose of 2 to 6 mg/kg/day divided every 8 to 12 hours GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary. GFR 30 to 50 mL/minute/1.73 m2: 2 mg/kg/dose every 12 hours GFR 10 to 29 mL/minute/1.73 m2: 1 mg/kg/dose every 12 hours GFR 2: 1 mg/kg/dose every 24 hours Hemodialysis: 1 mg/kg/dose every 24 hours Peritoneal dialysis: 1 mg/kg/dose every 24 hours Continuous renal replacement therapy: 2 mg/kg/dose every 12 hours Parenteral (IV): Based on a usual dose of 2 to 4 mg/kg/day divided every 6 to 24 hours GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary. GFR 30 to 50 mL/minute/1.73 m2: 1 mg/kg/dose every 12 hours GFR 10 to 29 mL/minute/1.73 m2: 0.5 mg/kg/dose every 12 hours GFR 2: 0.5 mg/kg/dose every 24 hours Hemodialysis: 0.5 mg/kg/dose every 24 hours Peritoneal dialysis: 0.5 mg/kg/dose every 24 hours Continuous renal replacement therapy: 1 mg/kg/dose every 12 hours

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Warnings & Precautions

Source: Lexicomp

Confusion

Rare cases of reversible confusion have been associated with ranitidine; usually elderly or severely ill patients, or in patients with renal or hepatic impairment.

Hepatic effects

Elevation in ALT levels has occurred with higher doses (≥100 mg) or prolonged IV therapy (≥5 days); monitor ALT levels daily for the remainder of treatment.

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 ( 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 (ranitidine undergoes hepatic metabolism).

Porphyria

Avoid use in patients with a history of acute porphyria; may precipitate attacks.

Renal impairment

Ranitidine is primarily excreted renally; dosage adjustment is recommended in patients with renal impairment. 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:

Children

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). Dosage form specific issues:

Injection

Rapid administration has been associated with bradycardia (rare), usually in patients with predisposing risk factors for cardiac rhythm disorders. Do not exceed the recommended IV administration rate(s).

Syrup

May contain up to 7.5% alcohol. Other warnings/precautions:

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 longer than 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, worsens, or lasts longer than 14 days.

Pregnancy & Lactation

Pregnancy

FDA category B

Safe

H2 blocker with long safety record in pregnancy. Note: ranitidine was withdrawn in some markets due to NDMA contamination — check product status

Lactation

RID 3.9%

Ranitidine is excreted into breast milk. Notable interpatient variability has been observed with regards to the extent of excretion (Riley 1982); information is limited. The relative infant dose (RID) of ranitidine is 3.9% to 19.6% when calculated using the highest breast milk concentration located and compared to an infant therapeutic dose of 2 to 10 mg/kg/day. In general, breastfeeding is considered unacceptable when the RID is >10% (Anderson 2016; Ito 2000). Using the highest milk concentra

Monitoring

Clinical pearl	AST, ALT, serum creatinine; occult blood with GI bleeding, signs/symptoms of peptic ulcer disease; when used to prevent stress-related GI bleeding, measure the intragastric pH and try to maintain pH >4; when used for Zollinger-Ellison syndrome, monitor gastric acid secretion (goal:

Chemistry & Properties

Formula	C13H22N4O3S
Molecular weight	314.41 g/mol
IUPAC name	(E)-1-N'-[2-[[5-[(dimethylamino)methyl]furan-2-yl]methylsulfanyl]ethyl]-1-N-methyl-2-nitroethene-1,1-diamine
CAS	66357-35-5
PubChem CID	3001055
InChIKey	`VMXUWOKSQNHOCA-UHFFFAOYSA-N`
logP	1.46 (XLogP 0.3)
Polar surface area	83.58 Å²
H-bond acceptors / donors	7 / 2
Drug-likeness (QED)	0.38
Lipinski violations	0

SMILES

CNC(=C[N+](=O)[O-])NCCSCc1ccc(CN(C)C)o1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No (logBB -1.23)

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2C19	Substrate	—
CYP2C9	Substrate	—
CYP2D6	Substrate	—
CYP3A4	Substrate	—

Receptor binding (top 2)

Target	Action	Affinity
HISTAMINE H2 (HRH2)	Binding	pKi 7.1
H2 receptor (HRH2)	Antagonist	pKi 7.1

Transporters

ASBT (Inhibitor)BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MATE2 (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT(unspecified) (Inhibitor)OCT1 (Inhibitor)OCT2 (Inhibitor)OCT3 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)MATE1 (Substrate)MDR1 (Substrate)OAT1 (Substrate)OAT2 (Substrate)OAT3 (Substrate)OCT1 (Substrate)OCT2 (Substrate)OCT3 (Substrate)P-gp (Substrate)Transporter(unspecified) (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Atazanavir	major
Dasatinib	major
Lemborexant	major
Loperamide	major
Neratinib	major
Pazopanib	major
Rilpivirine	major
Selpercatinib	major
Siponimod	major
Acalabrutinib	moderate
Acetohexamide	moderate
Aminophylline	moderate
Bacampicillin	moderate
Bosutinib	moderate
Brigatinib	moderate
Cefditoren	moderate
Cefpodoxime	moderate
Cefuroxime	moderate
Ceritinib	moderate
Chlorpropamide	moderate
Dabrafenib	moderate
Dacomitinib	moderate
Delavirdine	moderate
Dicoumarol	moderate
Donepezil	moderate
Eliglustat	moderate
Entecavir	moderate
Erlotinib	moderate
Fingolimod	moderate
Flibanserin	moderate
Fosamprenavir	moderate
Fosphenytoin	moderate
Galantamine	moderate
Gefitinib	moderate
Glimepiride	moderate
Glipizide	moderate
Glyburide	moderate
Itraconazole	moderate
Ivabradine	moderate
Ketoconazole	moderate

Showing 40 of 100+.

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Zydac	Ampoule 50 mg/2 ml	5 amp	Land Of Medicine Drug Store	3.230