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Ranitidine Hydrochloride

H2 blocker, Prokinetic

Generic name: Ranitidine Hydrochloride (rah-nit’ih-deen hye-droe-klor’ide)
Brand names: Tab Rantac 150,300mg, Syrup Rantac 15mg/mL
Dosage form: Ranitidine is available in 75-, 150-, and 300-mg tablets; 150- and 300-mg capsules; and 25-mg/mL injection.
Drug class: H2 Receptor Antagonist; Prokinetic

Pharmacology and Mechanism of Action: Ranitidine is a  H2 blockers, ranitidine competitively inhibits histamine reduces gastric acid secretion by inhibiting histamine stimulation of gastric parietal cells, which leads to an increase in stomach pH. Ranitidine may stimulate stomach emptying and colon motility via anticholinesterase action. It is more likely to stimulate gastrointestinal motility by inhibiting acetylcholinesterase, which increases acetylcholine at muscarinic receptors. Ranitidine may also elevate lower esophageal sphincter pressure. Additionally, by reducing gastric acid production, ranitidine decreases the secretion of pepsin. It has a longer duration of action and is 4 to 10 times more potent than cimetidine. Due to its longer half-life, ranitidine requires less frequent dosing compared to cimetidine. But It does not produce as much of a sustained increase in stomach pH as proton pump inhibitors (omeprazole).

Pharmacokinetics: In horses, the half-life after IV and oral administration is 2.8 and 1.4 hours, respectively, with oral absorption at 27%. In dogs, the half-life is 2.3 hours after oral administration and 2.2 hours after IV administration, with 95% oral absorption. In contrast, cimetidine has a half-life of 1.4 hours in dogs. When adjusting doses, ranitidine hydrochloride contains 81% ranitidine.

Route of elimination: Ranitidine is excreted through the kidneys in the urine via glomerular filtration and tubular secretion, and it is also metabolized in the liver into inactive metabolites. In patients with renal insufficiency, there may be an accumulation of the drug.

Indications and Clinical Uses: Meloxicam is used to decrease pain, inflammation, and fever. -osteoarthritis, pain associated with surgery. Use in cats is limited to either short-term use or long-term use at low doses.

Uses/Indications
In veterinary medicine, ranitidine is used to treat and/or prevent gastric, abomasal, and duodenal ulcers, uremic gastritis, stress-related or drug-induced erosive gastritis, esophagitis, duodenal gastric reflux, and esophageal reflux.Due to its impact on gastric motility, ranitidine can be helpful in promoting gastric emptying, especially when delayed gastric emptying is linked to gastric ulcer disease. Additionally, ranitidine may aid in stimulating colonic activity in cats through its prokinetic effects.

Drug Interactions: Ketoconazole, Itraconazole, iron supplements-The absorption of these medications may be reduced secondary to increased gastric pH. Long-term ranitidine use may reduce oral absorption of Vitamin B-12.

Precautions: Kidney injury, especially in dehydrated animals or animals with preexisting renal disease. Gastrointestinal ulceration has been observed when dogs were administered doses slightly higher than registered doses. In cats at high doses (five times the dose), vomiting and other gastrointestinal problems were reported.

DOGS:

  • For esophagitis:
    a) 1–2 mg/kg PO q12h (Watrous 1989)
  • For chronic gastritis:
    a) 0.5 mg/kg PO q12h (Hall, J.A. & Twedt 1989)
  • For ulcer disease:
    a) 0.5–2 mg/kg PO, IV, or IM q8–12h (Haskins 2000)
    b) 2 mg/kg PO, IV q8h (Matz 1995)
    c) 1–2 mg/kg PO, IV, SC q12h (Sellon 2007)
  • For gastrinoma:
    a) 1–2 mg/kg PO, SC, IV q8–12h (Zerbe & Washabau 2000)
    b) 0.5 mg/kg PO, IV, or SC q12h (Kay & Richter 1988)
  • To treat hyper-gastrinemia secondary to chronic renal failure:
    a) 1–2 mg/kg PO bid (Morgan 1988)
  • To treat hyper-histaminemia secondary to mast cell tumors:
    a) 2 mg/kg q12h (Fox 1995)
  • As a prokinetic agent to stimulate gastric contractions:
    a) 1–2 mg/kg PO q12h (Hall, J. & Washabau 2000)

CATS:

  • For ulcer disease/esophagitis:
    a) 2.5 mg/kg IV q12h or 3.5 mg/kg PO q12h (Matz 1995), (Johnson 1996)
    b) 1–2 mg/kg PO, IV, SC q12h (Sellon 2007)
    c) 2 mg/kg PO, IV q12h (Waddell 2007)
  • As a prokinetic agent to stimulate colonic motility:
    a) 1–2 mg/kg PO q8–12h (Washabau & Holt 2000)
    b) 1–2 mg/kg PO q12h (Scherk 2003)

HORSES:
(Note: ARCI UCGFS Class 5 Drug)

• 2.2-6.6 mg/kg q6-8h PO. The higher dose (6.6 mg/kg) is more effective at
suppressing stomach acid.
• 2 mg/kg q6-8h IV.

  • Foals:
    a) 1.5 mg/kg IV q8h or 6.6 mg/kg PO q8h, often used with omeprazole (4 mg/kg PO q24h) (Paradis 2008)
    b) 6.6 mg/kg IV q4h or 0.8–2.2 mg/kg IV four times a day; 5–10 mg/kg PO two to four times a day (Wilkins 2004)
    c) 1.5–2 mg/kg IV or IM q6–8h; 6.6 mg/kg PO q8h (Sanchez 2004)

SMALL MAMMALS (Rabbit):

  • As a prokinetic in Rabbits:
    0.5 mg/kg IV q24h with cisapride (0.5 mg/kg PO q8h) (Lichtenberger 2008)
  • For suspected gastric ulceration in rabbits:
    2–5 mg/kg PO twice daily (Bryan 2009)

Calves
• 50 mg/kg q8h PO in milk-fed calves

Patient Monitoring and Laboratory Tests: Ranitidine is contraindicated in patients who are hypersensitive to it. It should be used with caution, and possibly at a reduced dosage, in patients with impaired renal function.

Reproductive Safety: 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.)

Stability and Storage :Store in a tightly sealed container, away from light, and at room temperature. Ranitidine hydrochloride is water-soluble. Crushed tablets mixed with water and syrup remain stable for up to 7 days. Protect from freezing.

Ref:

  • Bryan, J. (2009). Rabbit GI Physiology: What do I do now? Proceedings: WVC. Accessed via: Veterinary Information Network. http://goo.gl/cAD9L
  • Fox, L. (1995). The paraneoplastic disorders. Kirk’s Current Veterinary Therapy: XII. J Bonagura Ed. Philadelphia, W.B. Saunders: 530–542.
  • Hall, J.A. & D.C. Twedt (1989). Diseases of the Stomach. Handbook of Small Animal Practice. RV Morgan Ed. New York, Churchill LIvingstone: 371–384.
  • Hall, J. & R. Washabau (2000). Gastric Prokinetic Agents. Kirk’s Current Veterinary Therapy: XIII Small Animal Practice. J Bonagura Ed. Philadelphia, WB Saunders: 609–617.
  • Haskins, S. (2000). Therapy for Shock. Kirk’s Current Veterinary Therapy: XIII Small Animal Practice. J Bonagura Ed. Philadelphia, WB Saunders: 140–147.
  • Johnson, S. (1996). Nonsteroidal antiinflammatory analgesics to manage acute pain in dogs and cats. Comp CE(October 1996): 1117–1123.
  • Kay, A.D. & K.P. Richter (1988). Diseases of the parathyroid glands. Handbook of Small Animal Practice. RV Morgan Ed. New York, Churchill Livingstone: 521–526.
  • Lichtenberger, M. (2008). What’s new in small mammal critical care. Proceedings: AAV. http://goo.gl/f4wXv
  • Morgan, R.V., Ed. (1988). Handbook of Small Animal Practice. New York, Churchill Livingstone.
  • Paradis, M. (2008). Gastrointestinal Problems in the Equine Neonate. Proceedings: World Veterinary Congress. Accessed via: Veterinary Information Network. http://goo.gl/pZkEx
  • Sanchez, C. (2004). Disorders of the stomach. Equine Internal Medicine, 2nd Ed. S Reed, W Bayly and D Sellon Eds. Philadelphia, Saunders: 863–872.
  • Scherk, M. (2003). Feline megacolon. Proceedings: World Small Animal Veterinary Assoc World Congress. Accessed via: Veterinary Information Network. http://goo.gl/v69lu
  • Sellon, R. (2007). Gastric Ulcers. Proceedings: Western Vet Conf. Accessed via: Veterinary Information Network. http://goo.gl/hW7b9
  • Waddell, L. (2007). Acute renal failure. Proceedings: Western Vet Conference. Accessed via: Veterinary Information Network. http://goo.gl/RlcNc
  • Washabau, R. & D. Holt (2000). Feline Constipation and Idiopathic Megacolon. Kirk’s Current Veterinary Therapy: XIII Small Animal Practice. J Bonagura Ed. Philadelphia, WB Saunders: 648–652.
  • Watrous, B.J. (1989). Diseases of the esophogus. Handbook of Small Animal Practice. RV Morgan Ed. New York, Churchill LIvingstone: 357–370.
  • Wilkins, P. (2004). Disorders of foals. Equine Internal Medicine, 2nd Ed. S Reed, W Bayly and D Sellon Eds. Philadelphia, Saunders: 1381–1431.
  • Zerbe, C. & R. Washabau (2000). Gastrointestinal endocrine disease. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. S Ettinger and E Feldman Eds.