Elephant specific information, if available, is in blue.

Chemistry – 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 approximately soluble in 1.5 ml of water or 6 ml of alcohol. The commercially available injection has a pH of 6.7-7.3.

 

Storage/Stability/Compatibility – 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 for up to 48 hours when mixed with the com­monly used IV solutions (including 5% sodium bicarbonate).

 

Pharmacology – 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 3-13 times more potent (on a molar basis) as cimetidine.

 

Ranitidine can cause gastric emptying times to be delayed, but the clinical significance of this effect is not known. Lower esophageal sphincter pressures may be increased by ranitidine. By decreasing the amount of gastric juice produced, ranitidine also 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.

 

Uses/Indications – 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. It has also been employed to treat hypersecretory conditions associated with gastri­nomas and systemic mastocytosis.

 

Pharmacokinetics – Pharmacokinetic data for veterinary species is limited for this prod­uct. In dogs, the oral bioavailability is approximately 81%, serum half-life is 2.2 hours and volume of distribution 2.6 L/kg.

 

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 about 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 of 25-100% of those found in the 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 from 2-3 hours. The duration of action at usual doses is from 8-12 hours.

 

Contraindications/Precautions – 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 in high dose, chronic therapy that serum ALT values be considered for monitoring.

 

Adverse Effects/Warnings – 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.

 

Overdosage – 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; symptoms may be treated symptomatically and supportively if necessary. Hemodialysis and peritoneal dialysis have been noted to remove ranitidine from the body.

 

Drug Interactions – Unlike cimetidine, ranitidine appears to only have minimal effects on the hepatic metabolism of drugs and is unlikely to cause clinically relevant drug interactions via this mechanism.  Propantheline Bromidedelays the absorption, but increases the peak serum level of ran­itidine. The relative bioavailability of ranitidine may be increased by 23% when propantheline is administered concomitantly with ranitidine. Antacids may decrease the absorption of ranitidine; give at separate times (2 hours apart) if used concurrently. Ranitidine may decrease the renal clearance of procainamide, but the clinical relevance of this interaction is unclear at this time.  The manufacturer states that ranitidine may alter the bioavailability of certain drugs through pH-dependent effects, changes in volume of distribution or an unknown effect. Further information is pending.

 

Drug/Laboratory Interactions – 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.

 

Doses –

Horses:

a)   0.5 mg/kg bid PO (Robinson 1987)

b)   Foals: 150 mg PO bid (Clark and Becht 1987)

c)   1 mg/kg q8h IV (Duran 1992)  

 

Monitoring Parameters –

1)   Clinical efficacy (dependent on reason for use); monitored by decrease in symptomatology, endoscopic examination, blood in feces, etc.

 

Client Information – To maximize the benefit of this medication, it must be administered as prescribed by the veterinarian; symptoms may reoccur if dosages are missed.

 

Dosage Forms/Preparations/FDA Approval Status/Withholding Times –

 

Veterinary-Approved Products: None

 

Human-Approved Products:

Ranitidine HCl Tablets  75 mg, 150 mg, 300 mg (as base); Zantac®  (Glaxo Wellcome); (Rx); Zantac 75® (Glaxo Wellcome) (OTC)

 

Rantidine HCl Effervescent Tablets & Granules:  150 mg; Zantac EFFERdose® (Glaxo Wellcome) (Rx)

 

Rantidine Capsules:  150 mg, 300 mg; Zantac GELdose® (Glaxo Wellcome) (Rx)

 

Ranitidine HCl Oral Syrup 15 mg/ml in UD 10 ml and 480 ml; Zantac® (Glaxo Wellcome); (Rx); Rantidine HCl (UDL) (Rx)

 

Ranitidine HCl Injection:  0.5 mg/ml, 25 mg/ml in 100 ml single dose containers and 2, 10, & 40 ml vials and 2 ml syringes; Zantac® (Glaxo Wellcome) (Rx)

 

Ranitidine HCl 0.5 mg/ml (preservative free in 100ml single dose containers & 25 mg/ml (as HCl) in 2 ml, 10 ml, & 40 ml vials; Zantac® (Glaxo); (Rx)

 

 

Ranitidine HCl 0.5 mg/ml (preservative free in 100ml single dose containers & 25 mg/ml (as HCl) in 2 ml, 10 ml, & 40 ml vials; Zantac® (Glaxo); (Rx)