Effect on Cost of Renal Dosing Adjustments for Nizatidine and Cimetidine

Augusto Miyashiro Jack M. Rosenberg Lorraine A. Cicero

Design: Cost comparison of cimetidine and nizatidine dosed with and without regard to residents' CL_cr.

Setting: A 271-bed, not-for-profit nursing home.

Subjects: 38 residents receiving nizatidine were divided into two groups: group 1 (n = 9) received nizatidine as acute therapy and group 2 (n = 29) received nizatidine as maintenance therapy.

Interventions: Cost was based on a 30-day supply for each medication as charged to the facility by the vendor pharmacy. CL_cr was estimated using the Cockcroft-Gault formula.

Main Outcome Measures: Actual cost difference was calculated for each drug dosed per official labeling, with and without regard to resident's CL_cr.

Results: Mean age of the study groups was 88 years. The total monthly cost of nizatidine dosed without regard for CL_cr was $2,170. With dose reductions for decreased renal function, monthly cost was $1,053, a savings of 48%. For cimetidine, the total monthly cost based on dosing without regard to CL_cr $1,371. Using a decreased dose of cimetidine based on the resident's CL_cr, the monthly cost was reduced to $1,083, a savings of 21%. When dose reductions for decreased renal function were employed, nizatidine was less expensive than cimetidine at our facility.

Conclusions: The study shows a reduced cost for each drug when dosed according to the package insert recommendations for decreased renal function. Besides reduced cost, the different dosing guidelines based on renal function for each drug made nizatidine a more cost-effective choice of histamine H₂ antagonist in our nursing home.

Key Words: Histamine H₂ receptor antagonists, Nizatidine, Cimetidine, Dosing, Costs, Consultant Pharmacists, Cockcroft-Gault Equation.

Abbreviations Used: H₂RAs: = Histamine H₂ receptor antagonists; CL_cr = Creatinine clearance.

Consult Pharm 1996; 11:585-89.

At the Sephardic Home, we are making much progress at reducing the cost of medications without compromising quality of care. The histamine H₂ receptor antagonists have been the focus of much scrutiny at this and other institutions. In addition to their actual acquisition cost, cost of H₂RAs is influenced by proper dosing. Dosing guidelines concerning each drug in this class are determined by the patient's renal function, the condition being treated, and whether the H₂RA is being used for acute or maintenance therapy (Table 1).¹

Table 1. FDA-Approved Dosing Guidelines for Cimetidine and Nizatidine

Indication	Cimetidine	Nizatidine
Active Duodenal Ulcer
a. Treatment	800 mg h.s.	300 mg h.s.
b. Maintenance	400 mg h.s.	150 mg h.s.
Benign Gastric Ulcer
a. Treatment	800 mg h.s.	300 mg h.s.
b. Maintenance	Treatment limited to six weeks or less.	150 mg h.s.
GERD
a. Treatment	800 mg b.i.d.	150 mg b.i.d.
b. Maintenance	Treatment limited to 12 weeks or less.	150 mg h.s.
Renal Impairment
a. Treatment	300 mg b.i.d.	150 mg h.s.
	CLcr < 30mL/min	CLcr = 20-50 mL/min
		150 mg q2d.
		CLcr < 20 mL/min
b. Maintenance	200 mg h.s.	150 mg q2d.
	CLcr < 30mL/min	CLcr 20-50 mL/min
		150 mg q3d.
		CLcr < 20 mL/min

When reduced renal function, as reflected in creatinine clearance is ignored, higher serum drug concentrations, increased adverse effects, and increased cost of therapy result. The relationship between adverse effects of cimetidine (Tagamet, SmithKline Beecham) and high plasma levels is well established. A reduced dose of cimetidine has been shown to correlate with a decreased incidence of confusion, depression, and disorientation.² Both cimetidine and nizatidine (Axid, Lilly) are eliminated by a combination of hepatic and renal routes; additionally, nizatidine has an active metabolite eliminated primarily via the kidneys.³ In our area, some prescribers of these H₂RAs were not following manufactures' official labeling for dose reductions based on renal function.

At this facility nizatidine is the sole H₂RA used. We were asked to determine the economic consequences of switching to cimetidine when this drug became available generically at a cost about 40% less than that of nizatidine. Medications supplied to our facility from our pharmacy vendor are purchased at cost (average wholesale cost for brand name products or maximum allowable cost for multisource items) plus a fixed fee of $1.20.

Methods

A total of 38 nursing home residents (average age 88 years) currently receiving nizatidine were admitted to the study. Each resident's age, weight, and serum creatinine were determined. CL_cr was determined using the Cockcroft and Gault formula which incorporates age, weight, gender, and serum creatinine in the calculation as follows⁴:

CL_cr = (140 - age)(body wt in kg) / (serum creatinine)(72kg)

For women, multiply value times 0.85. Each resident's medical record was reviewed to learn if the resident was receiving nizatidine as acute or maintenance therapy.

The cost of nizatidine versus cimetidine was calculated according to the manufacturers' recommended dose with and without consideration of each resident's CL_cr. These costs were then compared to determine the economic consequences of proper dosing and whether cimetidine would be a cost-effective alternative to nizatidine.

Results

Of the 38 residents, 37 (97%) had a CLcr of ² 50 ml/min and 53% (20/38) had a CL_cr of < 30 mL/min. Two residents had CL_cr < 20 mL/min. Only one resident had a CL_cr > 50 mL/min and did not require a dose reduction for either drug (Figure 1). Nine residents were receiving nizatidine as acute therapy, while 29 residents were on maintenance doses of nizatidine.

Figure 1. About 97% of residents have a creatinine clearance less than 50 mL/min. These people require a dosage reduction for nizatidine. The dose of cimetidine requires reduction in the 30% of residents with creatinine clearance less than 30 mL/min.

The total monthly cost of nizatidine when prescribed without regard to the resident's CL_cr was $2,170. If cimetidine were prescribed for these residents without regard to their CL_cr the cost was $1,371. A cost savings of $799 was thus possible if nizatidine were switched to generic cimetidine and dosing recommendations were ignored (Table 2).

Table 2. Monthly Cost Of Cimetidine and Nizatidine with and without Dosing per Creatinine Clearance Adjustments^a

		CLcr Not Considered		CLcr Considered
Patient No.	Type of Therapyb	Nizatidine	Cimetidine	Nizatidine	Cimetidine
1	M	46.16	29.78	23.08	17.34
2	M	46.16	29.78	23.08	17.34
3	M	46.16	29.78	23.08	17.34
4	M	46.16	29.78	46.16	29.78
5	M	46.16	29.78	23.08	17.34
6	M	46.16	29.78	23.08	17.34
7	M	46.16	29.78	14.87	17.34
8	M	46.16	29.78	23.08	17.34
9	M	46.16	29.78	23.08	17.34
10	A	92.31	56.33	46.16	56.33
11	A	92.31	56.33	46.16	56.33
12	M	46.16	29.78	23.08	17.34
13	A	92.31	56.33	23.08	34.20
14	M	46.16	29.78	23.08	29.78
15	A	92.31	56.33	23.08	34.20
16	M	46.16	29.78	23.08	29.78
17	M	46.16	29.78	23.08	17.34
18	M	46.16	29.78	23.08	29.78
19	M	46.16	29.78	23.08	17.34
20	A	92.31	56.33	46.16	56.33
21	A	92.31	56.33	46.16	34.20
22	M	46.16	29.78	23.08	29.78
23	M	46.16	29.78	23.08	29.78
24	M	46.16	29.78	23.08	29.78
25	M	46.16	29.78	23.08	17.34
26	A	92.31	56.33	46.16	56.33
27	M	46.16	29.78	23.08	29.78
28	M	46.16	29.78	23.08	17.34
29	A	92.31	56.33	46.16	56.33
30	M	46.16	29.78	23.08	17.34
31	M	46.16	29.78	23.08	29.78
32	A	92.31	56.33	46.16	34.20
33	M	46.16	29.78	23.08	17.34
34	M	46.16	29.78	23.08	29.78
35	M	46.16	29.78	23.08	17.34
36	M	46.16	29.78	23.08	29.78
37	M	46.16	29.78	23.08	29.78
38	M	46.16	29.78	23.08	29.78
Total		$2169.43	$1370.59	$1053.47	$1083.03

a Cost for cimetidine was maximum allowable cost plus a fixed dispensing fee at $1.20. Cost for nizatidine was average wholesale price plus the $1.20 dispensing fee.
b M = Maintenance; A = Active treatment.

However, when nizatidine was prescribed according to the manufacturer's dosing recommendation, the estimated total monthly cost of was $1,053, a savings of $1,117.

Reduced doses of cimetidine are recommended by the manufacturer for persons with CL_cr <= 30mL/min. Of the 38 residents, 20 would require a dose reduction for cimetidine. Prescribed according to the manufacturer's recommendation, the cost would be $1,083. When compared with the cost of cimetidine prescribed without regard for CL_cr, a savings of $288 was possible (Table 2). Thus, the cost difference between nizatidine and cimetidine dosed according to a resident's creatinine clearance was of no substantial economic consequence. In fact, cimetidine resulted in a slightly higher monthly cost.

Discussion

The results of this study reinforce the concept that the true cost of a medication can be influenced by factors much more important than product acquisition cost. In our facility cimetidine was 37% less expensive than nizatidine. However, when the prescribing recommendations per the FDA-approved labeling was followed, the picture of the total monthly cost for each drug changed dramatically.

Ranitidine has dosing guidelines similar to those of nizatidine, and famotidine dosage is not decreased until CL_cr is 10 mL/min; thus, we did not study these H₂RAs. The recent availability of cimetidine, famotidine, and ranitidine as nonprescription medications in strengths of one-half the lowest prescription dose may further influence the cost and choice of a H₂RA by long-term care facilities. These items, with greater flexibility in dosing, can now be used as floor stock, which may then further influence the cost effectiveness of a chosen H₂RA therapy. Of course, monitoring the residents for clinical effectiveness remains a primary concern, especially if administering one of the lower strength products.

Comparisons of treatment outcomes were not part of our study. The dosing guidelines used for our cost comparison were based on the manufacturer's official recommendations for reduced CL_cr. Based on pharmacokinetic considerations we would not anticipate any change in therapeutic outcomes. In fact, we would expect a decrease in side effects.

Conclusion

Price differential is part of the decision when choosing the most appropriate H₂RA in a long-term care facility. In our facility, although cimetidine is available multisource at a lower acquisition cost, it did not offer an economic advantage over nizatidine when the latter agent was properly dosed based on renal function. Based on our findings, the decision to continue to use nizatidine according to the manufacturer's FDA-approved labeling was supported by factors other than product acquisition cost.

1. Drugs Ther Persp 1993 (Jun 7); 1 (10).

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3. Hadbavny AM, Hoyt JW. Issues for consideration in selecting H₂ antagonists. Phar Ther 1993 (Apr): 388-92.

4. Young YL, Smith GH. Interpretation of clinical laboratory tests. In: Koda-Kimble MA, Young LY, eds. Applied therapeutics: the clinical use of drugs. Vancouver, WA: Applied Therapeutics Inc., 1992: 3-8.

Address for reprints: Augusto Miyashiro, M.D., Sephardic Home for the Aged, 2266 Cropsey Ave., Brooklyn, NY 11214.

Copyright © 1996, American Society of Consultant Pharmacists, Inc. All rights reserved.