So you have the complete information, here's the monograph on ranitidine (Zantac)
- H2 Receptor Antagonist; Prokinetic
- H2 receptor antagonist similar to cimetidine, but fewer drug interactions; used to reduce acid output in stomach; also has prokinetic activity.
- Contraindications: Hypersensitivity. Caution: Geriatric patients, hepatic or renal insufficiency.
- Adverse Effects: Rare. IV boluses may cause vomiting. Potentially: Mental confusion, agranulocytosis, & transient cardiac arrhythmias (too rapid IV injection). Pain at the injection site after IM administration.
In veterinary medicine, ranitidine has been used for the treatment and/or prophylaxis of gastric, abomasal and duodenal ulcers, uremic gastritis, stress-related or drug-induced erosive gastritis, esophagitis, duodenal gastric reflux and esophageal reflux. One study did not demonstrate any reduction in the incidence of gastroesophageal reflux in anesthetized dogs from either ranitidine or metoclopramide (Favarato et al. 2012). Ranitidine has also been employed to treat hypersecretory conditions associated with gastrinomas and systemic mastocytosis. Because of its effects on gastric motility, ranitidine may be useful in increasing gastric emptying, particularly when delayed gastric emptying is associated with gastric ulcer disease. Ranitidine may also be useful to stimulate colonic activity in cats via its prokinetic effects.
At the H2 receptors of the parietal cells, ranitidine competitively inhibits histamine, thereby reducing gastric acid output both during basal conditions and when stimulated by food, amino acids, pentagastrin, histamine, or insulin. Ranitidine is between 3-13X more potent (on a molar basis) as cimetidine.
Ranitidine may stimulate GI motility, especially in the stomach by inhibiting acetylcholinesterase (thereby increasing acetylcholine at muscarinic receptors). Lower esophageal sphincter pressures may be increased by ranitidine. By decreasing the amount of gastric juice produced, ranitidine decreases the amount of pepsin secreted.
Ranitidine, unlike cimetidine, does not appear to have any appreciable effect on serum prolactin levels, although it may inhibit the release of vasopressin.
In dogs, the oral bioavailability is approximately 81%, serum half-life is 2.2 hours and volume of distribution is 2.6 L/kg.
In horses, oral ranitidine has a bioavailability of ≈ 27% in adults and 38% in foals. Peak levels after oral dosing occur in ≈ 100 minutes in adults and 60 minutes in foals. Apparent volume of distribution is ≈ 1.1 L/kg and 1.5 L/kg in adults and foals, respectively. Clearance in adults is ≈ 10 mL/min/kg and 13.3 mL/min/kg in foals.
In humans, ranitidine is absorbed rapidly after oral administration, but undergoes extensive first-pass metabolism with a net systemic bioavailability of approximately 50%. Peak levels occur at ≈ 2-3 hours after oral dosing. Food does not appreciably alter the extent of absorption or the peak serum levels attained.
Ranitidine is distributed widely throughout the body and is only 10-19% bound to plasma proteins. Ranitidine is distributed into human milk at levels 25-100% of those found in plasma.
Ranitidine is both excreted in the urine by the kidneys (via glomerular filtration and tubular secretion) and metabolized in the liver to inactive metabolites; accumulation of the drug can occur in patients with renal insufficiency. The serum half-life of ranitidine in humans averages 2-3 hours. The duration of action at usual doses is from 8-12 hours.
Ranitidine is contraindicated in patients who are hypersensitive to it. It should be used cautiously and possibly at reduced dosage in patients with diminished renal function. Ranitidine has caused increased serum ALT levels in humans receiving high IV doses for longer than 5 days. The manufacturer recommends that with high-dose chronic therapy, serum ALT values be considered for monitoring.
Adverse effects appear to be very rare in animals at the dosages generally used. Potential adverse effects (documented in humans) that might be seen include mental confusion and headache. Rarely, agranulocytosis may develop and, if given rapidly IV, transient cardiac arrhythmias may be seen. Pain at the injection site may be noted after IM administration. IV boluses have been associated with vomiting in small animals and transient hypotension in cats.
In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, but there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, but adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as class: B (Safe for use if used cautiously. Studies in laboratory animals may have uncovered some risk, but these drugs appear to be safe in dogs and cats or these drugs are safe if they are not administered when the animal is near term.)
Ranitidine is excreted in human breast milk with milk:plasma ratios of approximately 5:1 to 12:1. The drug is not recommended to be used in nursing humans; use with caution in nursing veterinary patients.
Clinical experience with ranitidine overdosage is limited. In laboratory animals, very high dosages (225 mg/kg/day) have been associated with muscular tremors, vomiting and rapid respirations. Single doses of 1 gram/kg in rodents did not cause death.
Treatment of overdoses in animals should be handled using standard protocols for oral ingestions of drugs; clinical signs may be treated symptomatically and supportively if necessary. Hemodialysis and peritoneal dialysis have been noted to remove ranitidine from the body.
Unlike cimetidine, ranitidine appears to have much less effect on the hepatic metabolism of drugs and is unlikely to cause clinically relevant drug interactions via this mechanism. The following drug interactions have either been reported or are theoretical in humans or animals receiving ranitidine and may be of significance in veterinary patients. Unless otherwise noted, use together is not necessarily contraindicated, but weigh the potential risks and perform additional monitoring when appropriate.
- Acetaminophen: Ranitidine (dose-dependent) may inhibit acetaminophen metabolism.
- Antacids (high doses): May decrease the absorption of ranitidine; give at separate times (2 hours apart) if used concurrently.
- Ketoconazole, Itraconazole: Absorption may be reduced secondary to increased gastric pH.
- Metoprolol: Ranitidine may increase metoprolol half-life, and peak levels.
- Nifedipine: Ranitidine may increase nifedipine AUC by 30%.
- Probenecid: May reduce the excretion of ranitidine.
- Propantheline: Delays the absorption but increases the peak serum level of ranitidine; relative bioavailability of ranitidine may be increased by 23% when propantheline is administered concomitantly with ranitidine.
- Vitamin b-12: Long-term ranitidine use may reduce oral absorption of B-12.
- Ranitidine may cause a false-positive urine protein reading when using Multistix®. The sulfosalicylic acid reagent is recommended for determining urine protein when the patient is concomitantly receiving ranitidine.
- For esophagitis, ulcer disease, gastritis, or gastric prokinetic (extra-label): Common anecdotal dosages generally range from 1 – 2 mg/kg PO, SC, IM or slow IV q8-12h, but one study (Bersenas et al. 2005) found that ranitidine at 2 mg/kg IV q12h did not significantly increase gastric pH when compared to saline. One source (Spillman 2012) states: “Therefore, current dose recommendations (0.5 – 2 mg/kg q8–12h) seem to be too low to be of any effect. Currently, clinical studies on the effect of ranitidine on gastric disorders in dogs and cats are lacking.”
- For ulcer disease, esophagitis, or as a prokinetic agent to stimulate colonic motility (extra-label): Based on pharmacokinetic data: 2.5 mg/kg slow IV twice daily or 3.5 mg/kg PO twice daily. (Trepanier 2010)
- For Helicobacter mustelae (extra-label): Ranitidine bismuth citrate (Note: Not available commercially in USA; must be compounded) at 24 mg/kg PO q8-12h and clarithromycin (12.5 mg/kg PO q8-12h). Treat with both for 14 days. (Johnson-Delaney 2008)
Horses: (Note: ARCI UCGFS Class 5 Drug)
- As a gastroprotectant/reduce stomach acid (extra-label): 1.5 – 2 mg/kg IV q8h or 6.6 – 10 mg/kg PO q8h.
- Rabbits: As a prokinetic: 0.5 mg/kg IV q24 with cisapride (0.5 mg/kg PO q8h) (Lichtenberger 2008). For suspected gastric ulceration: 2 – 5 mg/kg PO twice daily. (Bryan 2009)
- Clinical efficacy (dependent on reason for use); monitored by decrease in clinical signs, endoscopic examination, blood in feces, etc.
- Used to treat or prevent stomach ulcers.
- Works best if given before the first meal of the day.
- Ranitidine is available OTC (over the counter; without a prescription), but only give it to your animal if your veterinarian recommends.
An H2 receptor antagonist, ranitidine HCl occurs as a white to pale-yellow granular substance with a bitter taste and a sulfur-like odor. The drug has pKas of 8.2 and 2.7. One gram is soluble in approximately 1.5 mL of water or 6 mL of alcohol. The commercially available injection has a pH of 6.7-7.3.
Ranitidine HCl may also be known as: AH-19065, ranitidini hydrochloridum. Many trade names are available; a common trade name is Zantac®.
Ranitidine tablets should be stored in tight, light-resistant containers at room temperature. The injectable product should be stored protected from light and at a temperature less than 30°C. A slight darkening of the injectable solution does not affect the potency of the drug.
Ranitidine injection is reportedly stable up to 48 hours when mixed with the commonly used IV solutions (including 5% sodium bicarbonate).
Dosage Forms/Regulatory Status
Veterinary-Labeled Products: None.
The ARCI (Racing Commissioners International) has designated this drug as a class 5 substance. See the appendix for more information.
Ranitidine HCl Oral Tablets: 75 mg, 150 mg & 300 mg; Zantac®, generic; (Rx or OTC)
Ranitidine HCl Oral Solution: 15 mg/mL in 473 mL & 480 mL; generic; (Rx)
Ranitidine HCl Injection: 25 mg/mL; Zantac®, generic; (Rx)
Monograph revised/updated August 2014.
Bersenas, A., et al. (2005). Effects of ranitidine, famotidine, pantoprazole, and omeprazole on intragastric pH in dogs. AJVR 66(3): 425-31.
Bryan, J. (2009). Rabbit GI Physiology: What do I do now? Proceedings: WVC. accessed via Veterinary Information Network; vin.com
Favarato, E. S., et al. (2012). Evaluation of metoclopramide and ranitidine on the prevention of gastroesophageal reflux episodes in anesthetized dogs. Research in Veterinary Science 93(1): 466-7.
Johnson-Delaney, C. (2008). Gastrointestinal Diseases in Ferrets. Proceedings: WVC. accessed via Veterinary Information Network; vin.com
Lichtenberger, M. (2008). What's new in small mammal critical care. Proceedings: AAV. accessed via Veterinary Information Network; vin.com
Papich, M. (1989). Effects of drugs on pregnancy. Current Veterinary Therapy X: Small Animal Practice. R. Kirk. Philadelphia, Saunders: 1291-9.
Spillman, T. (2012). Antiemetics and Gastroprotective Drugs in Dogs: Fact and Fiction. Proceedings: WSAVA/FECAVA/BSAVA World Congress 2012. accessed via Veterinary Information Network; vin.com
Trepanier, L. (2010). Acute Vomiting in Cats: Rational treatment selection. Journal of Feline Medicine and Surgery 12(3): 225-30.