[Federal Register Volume 65, Number 77 (Thursday, April 20, 2000)]
[Notices]
[Pages 21200-21201]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-9848]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 79N-0113; DESI 2847]


Parenteral Multivitamin Products; Drugs for Human Use; Drug 
Efficacy Study Implementation; Amendment

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is amending the 
conditions for marketing an effective adult parenteral multivitamin 
drug product that published in the Federal Register of September 17, 
1984 (49 FR 36446). The agency is notifying manufacturers of 
modifications in the adult formulation and certain portions of the 
labeling for the products.

DATES: Supplements to approved new drug applications (NDA's) and 
abbreviated new drug applications (ANDA's) are due on or before June 
19, 2000.

ADDRESSES: Communication in response to this notice should be 
identified with the reference number DESI 2847 and directed to the 
attention of the appropriate office named below.
    Supplements to full NDA's (identify with NDA number): Division of 
Metabolic and Endocrine Drug Products (HFD-510), Center for Drug 
Evaluation and Research, Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857.
    Original ANDA's: Office of Generic Drugs (HFD-600), Center for Drug 
Evaluation and Research, Food and Drug Administration, 7500 Standish 
Pl., Rockville, MD 20855.
    Requests for opinion of the applicability of this notice to a 
specific product: Division of Prescription Drug Compliance and 
Surveillance (HFD-330), Food and Drug Administration, 7500 Standish 
Pl., Rockville, MD 20855.

FOR FURTHER INFORMATION CONTACT: Mary E. Catchings, Center for Drug 
Evaluation and Research (HFD-7), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-2041.

SUPPLEMENTARY INFORMATION: In a notice published in the Federal 
Register of September 17, 1984 (49 FR 36446), FDA announced the 
conditions for marketing an effective parenteral multivitamin 
preparation. The effective 12-vitamin formulation set forth in the 
notice was based on the clinical evaluation of a guideline formulation 
recommended in 1975 by the American Medical Association (AMA). The 
notice also stated that, because parenteral multivitamin products are 
used and evaluated in patients with a variety of disease conditions, 
future adjustments to the formulation may be necessary.
    On August 21, 1985, FDA's Division of Metabolic and Endocrine Drug 
Products and the AMA's Division of Personal and Public Health Policy 
sponsored a public workshop on ``Multivitamin Preparations for 
Parenteral Use.'' At the workshop, additional data from clinical 
testing of the 1975 AMA formulation and a variety of other data were 
presented and discussed in light of available information on parenteral 
vitamin therapy. After examining the data, the AMA-FDA workshop 
committee recommended that the dosage of vitamins B1, 
B6, C, and folic acid be increased and that vitamin K be 
added to the formulation. Based on a review of the committee's 
recommendations, the Director of the Center for Drug Evaluation and 
Research has concluded that the 1975 AMA formulation for parenteral 
multivitamins should be modified to reflect the advice of the 
committee.
    Accordingly, this notice amends portions of the section Conditions 
for Approval and Marketing in the September 17, 1984, notice as follows 
(in accordance with current labeling practice, amounts previously 
listed in international units (IU) have been converted to weights):
    Paragraph 1(a)(i) is revised as follows:
    1. Adult formulation (intended for ages 11 and older)

 
------------------------------------------------------------------------
             Ingredient                      Amount per Unit Dose
------------------------------------------------------------------------
Fat Soluble Vitamins
 
A (retinol)                          1 milligram (mg)
D (ergocalciferol or                 5 micrograms (g)
 cholecalciferol)
E (alpha-tocopherol)                 10 mg
K (phylloquinone)                    150 g
 
Water-Soluble Vitamins
 
C (ascorbic acid)                    200 mg
Folic acid                           600 g
Niacin                               40 mg
B2 (riboflavin)                      3.6 mg
B1 (thiamine)                        6.0 mg
B6 (pyridoxine)                      6.0 mg
B12 (cyanocobalamin)                 5 g
Pantothenic acid                     15.0 mg
Biotin                               60 g
------------------------------------------------------------------------

    2. Labeling conditions.
    (a) The label must bear the statement ``Rx only.''
    (b) Indication. Paragraph 2(b)(i)(a) is revised as follows (This 
language may be editorially adapted to a specific product's labeling, 
as appropriate.):
    Adult. This formulation is indicated as a daily multivitamin 
maintenance dosage for adults and for children age 11 and above 
receiving parenteral

[[Page 21201]]

nutrition. It is also indicated in other situations where intravenous 
administration is required. Such situations include surgery, extensive 
burns, fractures and other trauma, severe infectious diseases, and 
comatose states, which may provoke a stress situation with profound 
alterations in the body's metabolic demands and consequent tissue 
depletion of nutrients. This product (administered in intravenous 
fluids under proper dilution) contributes intake of these vitamins that 
are necessary toward maintaining the body's normal resistance and 
repair processes.
    The physician should not await the development of clinical signs of 
vitamin deficiency before initiating vitamin therapy.
    Patients with multiple vitamin deficiencies or with markedly 
increased requirements may be given multiples of the daily dosage for 2 
or more days, as indicated by the clinical status. Clinical testing 
indicates that some patients do not maintain adequate levels of certain 
vitamins when this formulation in recommended amounts is the sole 
source of vitamins.
    (c) Contraindications:
    Known hypersensitivity to any of the vitamins or excipients in this 
product or a preexisting hypervitaminosis. Allergic reaction has been 
known to occur following intravenous administration of thiamine and 
vitamin K. The formulation is contraindicated prior to blood sampling 
for detection of megaloblastic anemia, as the folic acid and the 
cyanocobalamin in the vitamin solution can mask serum deficits.
    In addition, the following sections required by 21 CFR 201.57 
should read as follows:
    1. Precautions: (The following paragraph should be added and should 
appear in bold type.)
    Caution should be exercised when administering this multivitamin 
formulation to patients on warfarin sodium-type anticoagulant therapy. 
In such patients, periodic monitoring of prothrombin time is essential 
in determining the appropriate dosage of anticoagulant therapy.
    2. Drug Reactions: This section is revised to read ``Drug 
Interactions'' and to add aminophylline 125 mg and ampicillin 500 mg to 
this list.
    Supplements to approved NDA's or ANDA's providing for appropriate 
revision of the labeling of drug products affected by this notice 
should be submitted on or before June 19, 2000.
    This notice is issued under the Federal Food, Drug, and Cosmetic 
Act (secs. 201(n), 502, 505, 52 Stat. 1041, 1050-1053, as amended (21 
U.S.C. 321(n), 352, 355)) and under the authority delegated to the 
Director of the Center for Drug Evaluation and Research (21 CFR 5.70).

    Dated: March 28, 2000.
Janet Woodcock,
Director, Center for Drug Evaluation and Research.
[FR Doc. 00-9848 Filed 4-19-00; 8:45 am]
BILLING CODE 4160-01-F