R-Gene
®
10
Arginine Hydrochloride Injection, USP
For Intravenous Use
DESCRIPTION
Each 100 mL of R-Gene
®
10 (Arginine Hydrochloride Injection, USP) for intravenous
use contains 10 g of L-Arginine Hydrochloride, USP in Water for Injection, USP
(equivalent to a 10% solution). L-arginine is a naturally occurring amino acid.
R-Gene
®
10 is hypertonic (950 mOsmol/liter) and contains 47.5 mEq of chloride ion per
100 mL of solution. The pH is adjusted to 5.6 (5.0-6.5) with arginine base or
hydrochloric acid.
CLINICAL PHARMACOLOGY
Intravenous infusion of R-Gene
®
10 often induces a pronounced rise in the plasma level
of human growth hormone (HGH) in subjects with intact pituitary function. This rise is
usually diminished or absent in patients with impairment of this function.
Expected Plasma Levels of HGH in ng/mL
Range of
Patient
Normal
Control Range
0-6
Peak Response
to Arginine
10-30
Pituitary
deficient 0-4 0-10
These ranges are based on the mean values of plasma HGH levels calculated from the
data of several clinical investigators and reflect their experiences with various methods of
radioimmunoassay. Upon gaining experience with this diagnostic test, each clinician will
establish his/her own ranges for control and peak levels of HGH.
L-arginine is a normal metabolite in animals and man and has a low order of toxicity.
INDICATIONS AND USAGE
R-Gene
®
10 is indicated as an intravenous stimulant to the pituitary for the release of
human growth hormone in patients where the measurement of pituitary reserve for HGH
can be of diagnostic usefulness. It can be used as a diagnostic aid in such conditions as
panhypopituitarism, pituitary dwarfism, chromophobe adenoma, postsurgical
craniopharyngioma, hypophysectomy, pituitary trauma, acromegaly, gigantism and
problems of growth and stature.
If the insulin hypoglycemia test has indicated a deficiency of pituitary reserve for HGH, a
test with R-Gene
®
10 is advisable to confirm the negative response. This can be done
after a waiting period of one day. As patients may not respond to R-Gene
®
10 (Arginine
Hydrochloride Injection, USP) during the first test, the unresponsive patient should be
This label may not be the latest approved by FDA.
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tested again to confirm the negative result. A second test can be performed after a waiting
period of one day. Some patients who respond to R-Gene
®
10 do not respond to insulin
and vice versa. The rate of false positive responses for R-Gene
®
10 is approximately
32%, and the rate of false negatives is approximately 27%.
CONTRAINDICATIONS
The administration of R-Gene
®
10 is contraindicated in persons having known
hypersensitivity to any ingredient in this product.
WARNINGS
There have been reports of overdosage of R-Gene
®
10 in pediatric patients leading to
death. EXTREME CAUTION MUST BE EXERCISED WHEN INFUSING R-GENE
®
10 INTO PEDIATRIC PATIENTS. OVERDOSAGE OF R-GENE
®
10 IN PEDIATRIC
PATIENTS CAN RESULT IN HYPERCHLOREMIC METABOLIC ACIDOSIS,
CEREBRAL EDEMA, OR POSSIBLY DEATH.
Hypersensitivity reactions, including anaphylaxis have been reported. Appropriate
medical support should be available during R-Gene 10 administration. If anaphylaxis or
other serious hypersensitivity reaction occurs, R-Gene 10 should be discontinued and
appropriate medical treatment initiated.
R-Gene
®
10 should always be administered by intravenous infusion because of its
hypertonicity.
R-Gene
®
10 is a diagnostic aid and is not intended for therapeutic use.
PRECAUTIONS
General
R-Gene
®
10 is a hypertonic (950 mOsmol/liter) and acidic (average pH of 5.6) solution
that can cause irritation and damage to tissues. Care should be used to ensure
administration of R-Gene
®
10 through a patent catheter within a patent vein. Excessive
rates of infusion may result in local irritation and in flushing, nausea, or vomiting.
Inadequate dosing or prolongation of the infusion period may diminish the stimulus to the
pituitary and nullify the test.
The arginine in R-Gene
®
10 can be metabolized resulting in nitrogen-containing products
for excretion. The effect of an acute amino acid or nitrogen burden upon patients with
impairment of renal function should be considered when R-Gene
®
10 is to be
administered.
The chloride content of R-Gene
®
10 is 47.5 mEq per 100 mL of solution, and the effect
of infusing this amount of chloride into patients with electrolyte imbalance should be
evaluated before the test is undertaken.
It should be noted that the basal and post stimulation levels of growth hormone are
elevated in patients who are pregnant or are taking oral contraceptives.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
Carcinogenesis, mutagenesis, and impairment of fertility
Long term animal studies have not been performed to evaluate the carcinogenic potential,
the mutagenic potential or the effect on fertility of intravenously administered R-Gene
®
10.
Pregnancy Category B
Reproduction studies have been performed in rabbits and mice at doses 12 times the
human dose and have revealed no evidence of impaired fertility or harm to the fetus due
to R-Gene
®
10 (10% Arginine Hydrochloride Injection, USP). There have been no
adequate or well controlled studies for the use of R-Gene
®
10 in pregnant women.
Because animal reproduction studies are not always predictive of human response, this
drug should not be used during pregnancy.
Nursing Mothers
It is not known whether intravenous administration of R-Gene
®
10 could result in
significant quantities of arginine in breast milk. Systemically administered amino acids
are secreted into breast milk in quantities not likely to have a deleterious effect on the
infant. Nevertheless, caution should be exercised when R-Gene
®
10 is to be administered
to nursing women.
Geriatric Use
Clinical studies of arginine did not include a sufficient number of subjects aged 65 and
over to determine whether they respond differently from younger subjects. Other reported
clinical experience has not identified differences in responses between the elderly and
younger patients.
ADVERSE REACTIONS
Adverse reactions associated with 1670 infusions in premarketing studies were as
follows:
Non-specific side effects consisting of nausea, vomiting, headache, flushing, numbness
and local venous irritation were reported in approximately 3% of the patients.
One patient had an allergic reaction which was manifested as a confluent macular rash
with reddening and swelling of the hands and face. The rash subsided rapidly after the
infusion was terminated and 50 mg of diphenhydramine were administered. One patient
had an apparent decrease in platelet count from 150,000 to 60,000. One patient with a
history of acrocyanosis had an exacerbation of this condition following infusion of R-
Gene
®
10.
Post Marketing Experience:
The following adverse events have been reported during post-marketing use:
extravasation leading to burn-like reaction and/or skin necrosis requiring surgical
intervention, hypersensitivity reactions including anaphylaxis, and hematuria that in some
cases occurred 1-2 days after an R-Gene 10 administration. Because these adverse events
This label may not be the latest approved by FDA.
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are reported voluntarily from a population of uncertain size, it is not always possible to
reliably estimate their frequency or establish a causal relationship to drug exposure.
OVERDOSAGE
An overdosage may cause a transient metabolic acidosis with hyperventilation which
could lead to death (See “WARNINGS”). In most cases the acidosis will self-compensate
and the base deficit will return to normal following completion of the infusion. If the
condition persists, the deficit should be determined and corrected by a calculated dose of
an alkalizing agent.
DOSAGE AND ADMINISTRATION
Adult Dosage
The recommended adult dose is 30 g arginine hydrochloride (300 mL of R-Gene
®
10)
administered by intravenous infusion over 30 minutes. The total dose should not exceed
30 g arginine hydrochloride. See Directions for Use for preparation instructions.
Pediatric Dosage
The recommended pediatric dose is 0.5 g/kg arginine hydrochloride (5 mL/kg of R-
Gene
®
10) administered by intravenous infusion over 30 minutes. The total dose should
not exceed 30 g arginine hydrochloride.
• For patients weighing 59 kg or less, withdraw a weight based dose from a sealed R-
Gene
®
10 bottle and place in a separate container for intravenous infusion to avoid
the inadvertent delivery and administration of the total volume from the commercially
available container. See Directions for Use for preparation instructions.
• For patients weighing 60 kg or more, the recommended dose is 30 g arginine
hydrochloride (300 mL of R-Gene
®
10). See Directions for Use for preparation
instructions
Test Procedure
The intravenous infusion of R-Gene
®
10 is a part of the test for measurement of pituitary
reserve of human growth hormone and, for successful administration of the test, clinical
conditions and procedures should be as follows:
1. The test should be scheduled in the morning following a normal night’s sleep, and
an overnight fast should continue through the test period.
2. Patients must be placed at bed rest for at least 30 minutes before the infusion
begins. Care should be taken to minimize apprehension and distress. This is
particularly important in children.
3. R-Gene
®
10 (Arginine Hydrochloride Injection, USP) is a hypertonic solution and
should only be infused through an indwelling needle or soft catheter placed in an
antecubital vein or other suitable vein (See PRECAUTIONS). Blood samples
should be taken by venipuncture from the contra-lateral arm.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
4. A desirable schedule for drawing blood samples is at –30, 0, 30, 60, 90, 120 and
150 minutes.
5. R-Gene
®
10 should be infused beginning at zero time at a uniform rate which will
permit the recommended dose to be administered over 30 minutes.
6. Blood samples should be promptly centrifuged and the plasma stored at –20°C
until assayed by one of the published radioimmunoassay procedures.
7. Diagnostic test results showing a deficiency of pituitary reserve for HGH should
be confirmed by a second test with R-Gene
®
10, or one may elect to confirm with
the insulin hypoglycemia test. A waiting period of one day is advised between
tests.
Directions for Use
R-Gene
®
10 is provided as a ready-to-use solution for patients weighing 60 kg (132 lbs)
or more and should not be further diluted. For pediatric patients weighing 59 kg (130
lbs) or less a dose must be placed in a separate container. Follow the preparation
instructions below.
Parenteral drug products should be inspected visually for particulate matter and
discoloration prior to administration whenever solution and container permit.
For Pediatric Patients weighing 59 kg (130 lbs) or less:
Withdraw a weight-based dose from an intact sealed bottle of R-Gene
®
10. The entire
300 mL bottle of R-Gene
®
10 for infusion is not intended for use in patients weighing 59
kg or less. The dose must be placed in a separate container, such as an evacuated sterile
glass container designed for intravenous administration, using aseptic technique.
Additionally, R-Gene
®
10 is stable in polypropylene syringes and plastic containers made
of either polyvinyl chloride (PVC) or ethylene vinyl acetate (EVA).
The post-penetration storage period is not more than 4 hours at room temperature or 24
hours at refrigerated temperature (2-8°C).
The healthcare professional administering the dose should berify the accuracy of the dose
prior to administration.
Use only if the solution is clear. Discard any unused drug product.
For Adults and Pediatric Patients weighing 60kg (132 lbs) or more:
Follow these directions using aseptic technique. As R-Gene
®
10 for intravenous use is
provided in glass containers, a standard air-inletting, air-filtering intravenous infusion set
with a bacterial air filter is required.
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
HOW SUPPLIED
R-Gene
®
10 is supplied as a 300 mL fill in 500 mL glass containers.
Preservative Free: Discard any unused portion.
NDC 0009-0436-24
Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat.
It is recommended that the product be stored at room temperature (25°C); however, brief
exposure up to 40°C does not adversely affect the product. Solution that has been frozen
must not be used.
Rx Only
Manufactured By:
Hospira, Inc.
Lake Forest, IL 60045 USA
LAB-0020-5.0
Revised June 2009
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda