Ranitidine (Page 2 of 5)

2. Effects on Other Gastrointestinal Secretions:

Pepsin: Oral ranitidine does not affect pepsin secretion. Total pepsin output is reduced in proportion to the decrease in volume of gastric juice.

Intrinsic Factor: Oral ranitidine has no significant effect on pentagastrin-stimulated intrinsic factor secretion.

Serum Gastrin: Ranitidine has little or no effect on fasting or postprandial serum gastrin.

Other Pharmacologic Actions:

1.

Gastric bacterial flora – increase in nitrate-reducing organisms, significance not known.

2.

Prolactin levels – no effect in recommended oral or intravenous (IV) dosage, but small, transient, dose-related increases in serum prolactin have been reported after IV bolus injections of 100 mg or more.

3.

Other pituitary hormones – no effect on serum gonadotropins, TSH, or GH. Possible impairment of vasopressin release.

4.

No change in cortisol, aldosterone, androgen, or estrogen levels.

5.

No antiandrogenic action.

6.

No effect on count, motility, or morphology of sperm.

Pediatrics:

Oral doses of 6 to 10 mg/kg/day in 2 or 3 divided doses maintain gastric pH>4 throughout most of the dosing interval.

Clinical Trials

Active Duodenal Ulcer:

In a multicenter, double-blind, controlled, US study of endoscopically diagnosed duodenal ulcers; earlier healing was seen in the patients treated with ranitidine as shown in Table 3.

Table 3. Duodenal Ulcer Patient healing Rates

* All patients were permitted antacids as needed for relief of pain. † p < 0.0001.
	Ranitidine *		Placebo *
	Number Entered	Healed/Evaluable	Number Entered	Healed/Evaluable
Outpatients	195	69/182 (38%) †	188	31/164 (19%)
Week 2
Week 4			137/187 (73%)†	76/168 (45%)

In these studies, patients treated with ranitidine reported a reduction in both daytime and nocturnal pain, and they also consumed less antacid than the placebo-treated patients.

Table 4. Mean Daily Doses of Antacid

	Ulcer Healed	Ulcer Not Healed
Ranitidine	0.06	0.71
Placebo	0.71	1.43

Foreign studies have shown that patients heal equally well with 150 mg twice daily and 300 mg at bedtime (85% versus 84%, respectively) during a usual 4-week course of therapy. If patients require extended therapy of 8 weeks, the healing rate may be higher for 150 mg twice daily as compared to 300 mg at bedtime (92% versus 87%, respectively).

Studies have been limited to short-term treatment of acute duodenal ulcer. Patients whose ulcers healed during therapy had recurrences of ulcers at the usual rates.

Maintenance Therapy in Duodenal Ulcer:

Ranitidine has been found to be effective as maintenance therapy for patients following healing of acute duodenal ulcers. In 2 independent, double-blind, multicenter, controlled trials, the number of duodenal ulcers observed was significantly less in patients treated with ranitidine (150 mg at bedtime) than in patients treated with placebo over a 12-month period.

Table 5. Duodenal Ulcer Prevalence

% = Life table estimate. RAN = ranitidine (ranitidine tablets USP) PLC = placebo
* p < 0.05 (ranitidine tablets USP versus comparator)
Double-Blind, Multicenter, Placebo-Controlled Trials
Multicenter trial	Drug	Duodenal Ulcer Prevalence			No. of Patients
		0 — 4 Months	0 — 8 Months	0 — 12 Months
USA	RAN	20%*	24%*	35%*	138
	PLC	44%	54%	59%	139
Foreign	RAN	12%*	21%*	28%*	174
	PLC	56%	64%	68%	165

As with other H₂ -antagonists, the factors responsible for the significant reduction in the prevalence of duodenal ulcers include prevention of recurrence of ulcers, more rapid healing of ulcers that may occur during maintenance therapy, or both.

Gastric Ulcer:

In a multicenter, double-blind, controlled, US study of endoscopically diagnosed gastric ulcers, earlier healing was seen in the patients treated with ranitidine as shown in Table 6.

Table 6. Gastric Ulcer Patient Healing Rates

* All patients were permitted antacids as needed for relief of pain. † p = 0.009.
	Ranitidine *		Placebo *
	Number Entered	Healed/Evaluable	Number Entered	Healed/Evaluable
Outpatients	92	16/83 (19%)	94	10/83 (12%)
Week 2
Week 6			50/73 (68%)†	35/69 (51%)

In this multicenter trial, significantly more patients treated with ranitidine became pain free during therapy.