TechneLite

Dosage Form: injection

DESCRIPTION: Sodium Pertechnetate Tc 99m Injection, as eluted according to the elution instructions with Bristol-Myers Squibb Medical Imaging, Inc. TechneLite®, Technetium Tc 99m Generator, is in Sodium Chloride 0.9% as a sterile, non-pyrogenic, diagnostic radiopharmaceutical suitable for intravenous injection, oral administration, and direct instillation. The pH is 4.5-7.5. The eluate should be clear, colorless, and free from visible foreign material. Each eluate of the TechneLite®, Technetium Tc 99m Generator should not contain more than 0.0056MBq (0.15 microcuries) of Molybdenum Mo99 per 37MBq (1 millicurie) of Technetium Tc 99m per administered dose at the time of administration, and not more than 10 micrograms of aluminum per milliliter of the Technetium Tc 99m Generator eluate, both of which must be determined by the user before administration. Since the eluate does not contain an antimicrobial agent, it should not be used later than one (1) working day after the elution (12 hours).

Bristol-Myers Squibb Medical Imaging, Inc. TechneLite®, Technetium Tc 99m Generator consists of a column containing fission produced Molybdenum Mo99 adsorbed on alumina. The terminally sterilized and sealed column is enclosed in a lead shield; the shield and other components are sealed in a cylindrical plastic container with an attached handle. Built into the top surface are two recessed wells marked CHARGE and COLLECT. Needles protruding from these two wells accommodate supplied sterile eluant charge vials and sterile eluate collection vials. The eluting solvent consists of Sodium Chloride 0.9%, prepacked into septum-sealed vials.

The eluate collection vial is evacuated, sterile and non-pyrogenic. A sterile 0.22 micrometer bacteriological filter is incorporated between the column outlet and the collection vials. During and subsequent to elution, the eluate collection vial should be kept in a radiation shield. The Generator is shipped with a silicone needle seal over the charge needle and a vented needle cover over the collect needle. A sterile vial containing bacteriostat is supplied for the customer to aseptically reseal the collect needle after each elution.

PHYSICAL CHARACTERISTICS

Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours.1 Photons that are useful for imaging studies are listed in Table 1.

Table 1. Principal Radiation Emission Data - Technetium Tc 99m

1Kocher, David C., "Radioactive Decay Data Tables," DOE/TIC-11026, 108 (1981).
Radiation	Mean %/Disintegration	Mean Energy (keV)
Gamma-2	89.07	140.5

EXTERNAL RADIATION

The specific gamma ray constant for Technetium Tc 99m is 5.4 microcoulombs/Kg-MBq-hr (0.78 R/mCi-hr) at 1cm. The first half-value thickness is 0.017cm of lead (Pb). To facilitate control of radiation exposure from millicurie amounts of Technetium Tc 99m, for example, the use of a 0.25 cm thick standard radiation elution lead shield will attenuate the radiation emitted by a factor of about 1000. A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of lead is shown in Table 2.

NOTE: Because the generator is well contained and essentially dry, there is little likelihood of contamination due to damage in transit. The most probable source of leakage resulting from damage in transit is the nonradioactive eluant charge vial.

Table 2. Radiation Attenuation of Technetium Tc 99m by Lead Shielding

Shield Thickness lead (Pb) cm	Coefficient of Attenuation
0.017	0.5
0.08	10-1
0.16	10-2
0.25	10-3
0.33	10-4

Molybdenum Mo99 decays to Technetium Tc 99m with a Molybdenum Mo99 half-life of 66 hours. The physical decay characteristics of Molybdenum Mo99 are such that only 88.6% of the decaying Molybdenum Mo99 atoms form Technetium Tc 99m. This means that only 78% of the activity remains after 24 hours; 60% remains after 48 hours, etc. All units have a minimum of 38 mm, 1.5 inches (~ 6 half-value layers) of lead surrounding the activity. Since the Molybdenum Mo99 is constantly decaying to fresh Technetium Tc 99m, it is possible to elute the generator at any time. (See Table 3.)

Table 3. Molybdenum Mo99 Decay Chart Half-Life 66.0 Hours

Days	Percent Remaining	Days	Percent Remaining
0	100	8	13
1	78	9	10
2	60	10	8
3	47	11	6
4	36	12	5
5	28	13	4
6	22	14	3
7	17

Generator elutions may be made at any time, but the amount of Technetium Tc 99m available will depend on the interval from the last elution. Approximately 47% of maximum Technetium Tc 99m is reached after 6 hours and 95% after 24 hours.

The elution vial shield has a wall thickness of 7.9 mm, 0.31 inches, and reduces transmitted Technetium Tc 99m radiation essentially to zero. To correct for physical decay of Tc 99m, the fractions that remain at selected intervals of time are shown in Table 4.

Table 4. Physical Decay Chart: Technetium Tc 99m Half-Life 6.02 Hours

*Calibration Time
Hours	Percent Remaining	Hours	Percent Remaining
0*	100.0	7	44.7
1	89.1	8	39.8
2	79.4	9	35.5
3	70.8	10	31.6
4	63.1	11	28.2
5	56.2	12	25.1
6	50.1

CLINICAL PHARMACOLOGY: The pertechnetate ion distributes in the body similarly to the iodide ion but is not organified when trapped in the thyroid gland. Pertechnetate tends to accumulate in intracranial lesions with excessive neovascularity or an altered blood-brain barrier. It also concentrates in the choroid plexus, thyroid gland, salivary glands, and stomach. However, in contrast to the iodide ion, the pertechnetate ion is released unchanged from the thyroid gland.

After intravascular administration it remains in the circulatory system for sufficient time to permit blood pool, organ perfusion, and major vessel studies. It gradually equilibrates with the extracellular space. A fraction is promptly excreted via the kidneys.

Following the administration of Sodium Pertechnetate Tc 99m Injection as an eye drop, the drug mixes with tears within the conjunctival space. Within seconds to minutes it leaves the conjunctival space and escapes into the inferior meatus of the nose through the nasolacrimal drainage system. During this process the pertechnetate ion passes through the canaliculi, the lacrimal sac and the nasolacrimal duct. In the event of any anatomical or functional blockage of the drainage system there will be a backflow resulting in tearing (epiphora). Thus the pertechnetate escapes the conjunctival space in the tears.

While the major part of the pertechnetate escapes within a few minutes of normal drainage and tearing, it has been documented that there is some degree of transconjunctival absorption with a fractional turnover rate of 0.015/min in normal individuals, 0.021/min in patients without any sac and 0.027/min in patients with inflamed conjunctiva due to chronic dacryocystitis. Individual values may vary but these rates are probably representative and indicate that the maximum possible pertechnetate absorbed will remain below one thousandth of that used in other routine diagnostic procedures.

INDICATIONS AND USAGE: Sodium Pertechnetate Tc 99m Injection is used IN ADULTS as an agent for:

 

Brain Imaging (including cerebral radionuclide angiography)

 

Thyroid Imaging

 

Salivary Gland Imaging

 

Placenta Localization

 

Blood Pool Imaging (including radionuclide angiography)

 

Urinary Bladder Imaging (direct isotopic cystography) for the detection of vesico-ureteral reflux.

 

Nasolacrimal Drainage System Imaging

Sodium Pertechnetate Tc 99m Injection is used IN CHILDREN as an agent for:

 

Brain Imaging (including cerebral radionuclide angiography)

 

Thyroid Imaging

 

Blood Pool Imaging

 

Urinary Bladder Imaging (direct isotopic cystography) for the detection of vesico-ureteral reflux.

CONTRAINDICATIONS: None known.

WARNINGS: Radiation risks associated with the use of Sodium Pertechnetate Tc 99m Injection are greater in children than in adults and, in general, the younger the child, the greater the risk owing to greater absorbed radiation doses and longer life-expectancy. These greater risks should be taken firmly into account in all benefit-risk assessments involving children.

PRECAUTIONS:

General

As in the use of any radioactive material, care should be taken to minimize radiation exposure to the patient consistent with proper patient management and to ensure minimum radiation exposure to occupational workers.

Since the eluate does not contain an antimicrobial agent, it should not be used after 12 hours from the time of TechneLite®, Technetium Tc 99m Generator elution.

After the termination of the nasolacrimal imaging procedure, blowing the nose and washing the eyes with sterile distilled water or an isotonic sodium chloride solution will further minimize the radiation dose.

Radiopharmaceuticals should be used only by physicians who are qualified by training and experience in the safe handling of radionuclides and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No animal studies have been performed to evaluate carcinogenic potential or whether Sodium Pertechnetate Tc 99m affects fertility in males or females.

Pregnancy Category C

Animal reproductive studies have not been conducted with Sodium Pertechnetate Tc 99m. It is also not known whether Sodium Pertechnetate Tc 99m can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sodium Pertechnetate Tc 99m Injection should be given to a pregnant woman only if clearly needed.

Ideally examinations using radiopharmaceuticals, especially those elective in nature, of a woman of childbearing capability should be performed during the first few (approximately 10) days following the onset of menses.

Nursing Mothers

Sodium Pertechnetate Tc 99m is excreted in human milk during lactation; therefore formula feedings should be substituted for breast feeding.

This radiopharmaceutical preparation should not be administered to pregnant or lactating women unless expected benefits to be gained outweigh the potential risks.

Pediatric Use

See INDICATIONS and DOSAGE AND ADMINISTRATION sections. Also see the description of additional risks under WARNINGS.

Geriatric Use

Clinical studies of TechneLite® did not include sufficient numbers 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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS: Allergic reactions including anaphylaxis have been reported infrequently following the administration of Sodium Pertechnetate Tc 99m Injection.

DOSAGE AND ADMINISTRATION: Sodium Pertechnetate Tc 99m Injection is usually administered by intravascular injection but can be given orally. For imaging the urinary bladder and ureters (direct isotopic cystography), the Sodium Pertechnetate Tc 99m Injection is administered by direct instillation aseptically into the bladder via a urethral catheter, following which the catheter is flushed with approximately 200 mL of sterile saline directly into the bladder. The dosage employed varies with each diagnostic procedure. If the oral route is elected, the patient should fast for at least six (6) hours before and two (2) hours after administration. When imaging the nasolacrimal drainage system, instill the Sodium Pertechnetate Tc 99m Injection by the use of a device such as a micropipette or similar method which will ensure the accuracy of the dose.

The suggested dose range employed for various diagnostic indications in the average ADULT PATIENT (70kg) is:

Vesico-ureteral Imaging	18.5 to 37MBq (0.5 to 1mCi)
Brain Imaging	370 to 740MBq (10 to 20mCi)
Thyroid Gland Imaging	37 to 370MBq (1 to 10mCi)
Salivary Gland Imaging	37 to 185MBq (1 to 5mCi)
Placenta Localization	37 to 111 MBq (1 to 3mCi)
Blood Pool Imaging	370 to 1110MBq (10 to 30mCi)
Nasolacrimal Drainage System	Max. 3.7MBq (100μCi)

The recommended dosage range in PEDIATRIC PATIENTS is:

Vesico-ureteral Imaging	18.5 to 37MBq (0.5 to 1mCi)
Brain Imaging	5.18 to 10.36MBq (140 to 280μCi)/kg body weight
Thyroid Gland Imaging	2.22 to 2.96MBq (60 to 80μCi)/kg body weight
Blood Pool Imaging	5.18 to 10.36MBq (140 to 280μCi)/kg body weight

A minimum dose of 111 to 185MBq (3 to 5 mCi) should be employed if radionuclide angiography is performed as part of the blood pool or brain imaging procedure.

NOTE: Up to one (1) gram of pharmaceutical grade potassium perchlorate in a suitable base or capsule may be given prior to administration of Sodium Pertechnetate Tc 99m Injection. When Sodium Pertechnetate Tc 99m Injection is used in children for brain or blood pool imaging, the administration of potassium perchlorate is especially important in order to minimize the absorbed radiation dose to the thyroid gland.

The patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration of the dose.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The solution to be administered as the patient dose should be clear and contain no particulate matter. Do not use an eluate of the TechneLite®, Technetium Tc 99m Generator later than one (1) working day after elution (12 hours).

RADIATION DOSIMETRY

The estimated absorbed radiation doses2 to an average ADULT patient (70 kg) from an intravenous injection of a maximum dose of 1110MBq (30 millicuries) of Sodium Pertechnetate Tc 99m Injection distributed uniformly in the total body of subjects not pretreated with blocking agents such as pharmaceutical grade potassium perchlorate are shown in Table 5. For placenta localization studies, when a maximum of 111MBq (3 millicuries) is used, it is assumed to be uniformly equilibrated between maternal and fetal tissues.

Table 5. Absorbed Radiation Doses (Adults)

mGy/1110MBq (rads/30 millicuries)
Tissue	Resting Population	Active Population	mGy/111MBq (rads/3mCi)
Bladder Wall	15.9 (1.59)	25.5 (2.55)	-
Gastrointestinal Tract:
Stomach Wall	75.0 (7.50)	15.3 (1.53)	-
Upper Large Intestine Wall	20.4 (2.04)	36.0 (3.60)	-
Lower Large Intestine Wall	18.3 (1.83)	33.0 (3.30)	-
Red Marrow	5.7 (0.57)	5.1 (0.51)	-
Testes	2.7 (0.27)	2.7 (0.27)	-
Ovaries	6.6 (0.66)	9.0 (0.90)	-
Thyroid	39.0 (3.90)	39.0 (3.90)	-
Brain	4.2 (0.42)	3.6 (0.36)	-
Whole-Body	4.2 (0.42)	3.3 (0.33)	-
Placenta	-	-	0.5(0.05)
Fetus	-	-	0.5(0.05)

In pediatric patients, the maximum radiation doses of 185MBq (5 millicuries) of Sodium Pertechnetate Tc 99m Injection administered to a neonate (3.5 kg) for brain or blood pool imaging with radionuclide angiography are shown in Table 6. In pediatric patients, an average 30 minute exposure to 37MBq (1 millicurie) of Sodium Pertechnetate Tc 99m Injection following instillation for direct cystography, results in an estimated absorbed radiation dose of approximately 0.30mGy (30 millirads) to the bladder wall and 0.04 to 0.05mGy (4 to 5 millirads) to the gonads.3

Table 6. Absorbed Radiation Doses (Pediatric)

	Absorbed Radiation Doses
Tissue	mGy/ 37MBq	(rads/ 1mCi)	mGy/ 185MBq	(rads/ 5mCi)
2 Modified from: Summary of Current Radiation Dose Estimates to Normal Humans from 99m-Tc as Sodium Pertechnetate.  MIRD Dose Estimates Report No. 8. J. Nucl. Med. 17(1): 74-77, 1976.
3 Conway, JJ, et al: Direct and Indirect radionuclide cystography.  J. Urol. 113: 689-693 May 1975.
Thyroid (without perchlorate)	46.0	(4.6)	230.0	(23.0)
Thyroid (with perchlorate)	9.7	(1.0)	48.5	(4.9)
Large Bowel (with perchlorate)	19.0	(1.9)	95.5	(9.6)
Testes	1.0	(0.1)	5.1	(0.5)
Ovaries	2.2	(0.2)	11.0	(1.1)
Whole-Body	1.5	(0.2)	7.6	(0.8)

Table 7. Absorbed Radiation Dose from Dacryoscintigraphy Using Sodium Pertechnetate Tc 99m

	Absorbed Dose
Target Organ	mGy/ 3.7MBq	(mrad/ 100μCi)
* Assuming no blockage of drainage system. MIRD Dose Estimate Report No. 8, J. Nucl Med. 17: 74-77, 1976.
Eye Lens:   If lacrimal fluid turnover is 16%/min   If lacrimal fluid turnover is 100%/min   If drainage system is blocked Total Body* Ovaries* Testes* Thyroid*	0.140 0.022 4.020 0.011 0.030 0.009 0.130	14.0 2.2 402.0 1.1 3.0 0.9 13.0

HOW SUPPLIED: Bristol-Myers Squibb Medical Imaging TechneLite®, Technetium Tc 99m Generator is available in the following quantities of radioactivity: 37.0 (NDC #11994-090-36), 74.0 (NDC #11994-090-73), 92.5 (NDC #11994-090-92), 111.0 (NDC #11994-090-01), 148.0 (NDC #11994-090-03), 166.5 (NDC #11994-090-04), 185.0 (NDC #11994-090-05), 222.0 (NDC #11994-090-06), 277.5 (NDC #11994-090-07), 370.0 (NDC #11994-090-09), 462.5 (NDC #11994-090-10), 555.0 GBq(NDC #11994-090-11), 666.0 GBq (NDC #11994-090- 12) (1000, 2000, 2500, 3000, 4000, 4500, 5000, 6000, 7500, 10,000, 12,500, 15,000 18,000 mCi) of Mo99 on the calibration date (date of manufacture) as specified on the product lot identification label affixed to the generator. Each generator is supplied with the following standard components:

 

1 Collect Needle Seal Vial

 

6 Eluant Charge Vials (may be supplied separately)

 

6 Eluate Collection Vials (may be supplied separately)

 

1 Package Insert

 

6 Radiation Labels (Collection Vial)

 

6 Radiation Labels (Eluting Shield)

 

1 Molybdenum Mo99 Activity Record (optional)

First order generators are shipped with the following accessory components:

 

2 Eluting Shields

Extra quantities of these components may be obtained at the customer's request.

STORAGE: Controlled room temperature 20° to 25°C (68° to 77°F) [See USP].

EXPIRATION: The expiration time of the Sodium Pertechnetate Tc 99m Injection is not later than 12 hours after elution. (If the eluate is to be used to reconstitute a kit for the preparation of a Technetium Tc 99m radiopharmaceutical, the kit should not be used after 12 hours from time of Generator elution or after six hours from the time of reconstitution of the kit.)

The expiration date of the TechneLite®, Technetium Tc 99m Generator is fourteen days post-manufacture.

ELUTION INSTRUCTIONS - TOTAL ELUTION METHOD

1. Waterproof gloves should be worn during elution.


2. Remove dust (clear plastic) cover of generator.


3. Perform all subsequent operations aseptically.


4. Remove silicone needle seal from eluant charge well. Discard as radioactive waste.


5. Remove flip-off seal and swab septum of eluant charge vial with a bactericide (such as 70% isopropyl alcohol), allow to dry, and insert the vial into charge well. Vial should be firmly inserted to assure puncture of septum.


6. Open elution shield base and insert an eluate collection vial from which the flip-off seal has been removed. Screw base back on securely. Swab the exposed vial septum with a bactericide.


7. Remove vented needle cover from collect well. Discard as radioactive waste.


8. Insert shielded eluate collection vial in collect well. Elution should commence within 30 seconds and can be visually checked by the appearance of bubbles in the eluant charge vial.**
   
   **NOTE: If bubbles do not appear in the eluant charge vial within 30 seconds, either one of the vials has not been properly placed on its needle or the eluate vial has no vacuum. Remove the eluate collection vial to prevent vacuum loss; then remove and reinsert the charge vial. Reinsert the eluate collection vial and if elution does not commence, use a second shielded collection vial.
   
   Caution: Tampering with the internal components could compromise sterility and present a radiation hazard. This generator should not be dismantled.


9. To assure proper yield and functioning, elution must proceed to completion as evidenced by emptying of the charge vial. Allow generator to elute for at least 3 minutes after the charge has been drained, or for a total of 6 minutes.


10. After elution has been completed, remove shield containing the collection vial. Obtain the collect needle seal vial, and using a bactericide, swab the septum of the collect needle seal vial and insert over the collect needle. The eluant vial is sterile and should stay in place until the next elution, functioning as a seal for the needles within the charge well. Upon initiating the next elution, discard the empty eluant vial as radioactive waste.


11. Fill out and attach the appropriate supplied pressure sensitive radioactivity labels to the elution shield containing the filled eluate collection vial. Do not use an eluate of the Technetium Tc 99m Generator later than 1 working day after the time of elution (12 hours).


12. Use a shielded syringe when introducing the Sodium Pertechnetate Tc 99m solution into mixing vials.


13. Maintain adequate shielding during the life of the radioactive preparation by using a lead vial shield and cover, and use a shielded syringe for withdrawing and injecting the preparation.

ASSAY INSTRUCTIONS FOR THE TechneLite®, TECHNETIUM Tc 99m GENERATOR ELUATE

The TechneLite®, Technetium Tc 99m Generator Eluate may be assayed using an ionization chamber dose calibrator. The manufacturer's instructions for operation of the dose calibrator should be followed for measurement of Technetium Tc 99m and Molybdenum Mo99 activity in the generator eluate. The Molybdenum 99/Technetium 99m ratio should be determined at the time of elution prior to administration, and from that ratio, the expiration time (up to 12 hours) of the eluate mathematically determined. Each eluate should meet or exceed the purity requirements of the current United States Pharmacopeia; that is, not more than 0.0056MBq (0.15 microcurie) of Molybdenum 99 per 37MBq (1 millicurie) of Technetium 99m per administered dose at the time of administration.

RADIOMETRIC MOLYBDENUM TEST PROCEDURE

This method is based on the fact that most Technetium Tc 99m radiation can be readily shielded and only the more energetic gamma rays from Molybdenum Mo99 (739KeV and 778KeV) are counted in the 550-850KeV energy range. The entire eluate may be assayed for Molybdenum Mo99 activity as follows:

1. A Cesium Cs 137 reference source which has the same geometry as the generator eluate must be used to standardize the well counter.


2. Determine the background after setting the window to the 550-850KeV energy range.


3. Count the Technetium Tc 99m eluate in its lead shield (thereby shielding out Technetium Tc 99m) by placing over the well or probe.


4. Count the Cs 137 reference source in the same shield geometry for the same time period.


5. Compute Molybdenum Mo99 activity in the eluate as follows:
   
   
   μCi Molybdenum      =        μCi simulated Mo99 x net cpm Eluate  
   
   Mo99 (total)                        net cpm simulated Mo99 reference source

Divide this number by the mCi of Technetium Tc 99m. This result (μCi Mo99/mCi Tc 99m) can be converted to MBq Mo99/MBq Tc 99m by multiplying by 10-3. The U.S. Pharmacopeia and the U.S. Nuclear Regulatory Commission or equivalent Agreement State regulations specify a limit of 0.00015MBq Molybdenum Mo99 per MBq of Technetium Tc 99m (0.15μCi Mo99/mCi Tc 99m) at the time of administration to each patient.

COLORIMETRIC ALUMINUM ION TEST PROCEDURE

Bristol-Myers Squibb Medical Imaging, Inc. offers an Aluminum Ion Indicator Kit as an accessory to permit monitoring the aluminum ion in each eluate. It is based on a colorimetric reaction performed on a paper strip impregnated with indicator. A bottle of aluminum ion standard is included. Complete information is available on request.

DISPOSAL: All components shipped with the TechneLite®, Technetium Tc 99m Generator should be monitored for contamination prior to disposing into routine trash systems. The Technetium Tc 99m should not be disposed of into routine trash systems. The generator should be disposed through a USNRC or Agreement State licensed disposal agency or by a method approved by the appropriate regulatory authority. Spent generators may be returned; complete return instructions are provided regularly with generator shipments and are also available on request.

This radioactive drug is approved for distribution to persons licensed pursuant to the Code of Massachusetts Regulations 105 CMR 120.500 for the uses listed in 105 CMR 120.533 or under equivalent licenses of the U.S. Nuclear Regulatory Commision, an Agreement State or a Licensing State.

Bristol-Myers Squibb

Medical Imaging

331 Treble Cove Road

N. Billerica, MA 01862 USA

For Ordering Call Toll-Free: 800-225-1572 All other business: 800-362-2668

(In Massachusetts and International, call 978-667-9531)

U.S. Patent 5,109,160

Bristol-Myers Squibb

Medical Imaging


Printed in U.S.A.


513160-0205

February 2005

TechneLite  molybdenum mo-99  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 11994-090 Route of Administration INTRAVENOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Molybdenum Mo-99 (Technetium Tc-99m cation) Active 1000 MILLICURIE  In 1 GENERATOR

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 11994-090-36 1 GENERATOR In 1 CARTON None

TechneLite  molybdenum mo-99  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 11994-090 Route of Administration INTRAVENOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Molybdenum Mo-99 (Technetium Tc-99m cation) Active 2000 MILLICURIE  In 1 GENERATOR

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 11994-090-73 1 GENERATOR In 1 CARTON None

TechneLite  molybdenum mo-99  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 11994-090 Route of Administration INTRAVENOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Molybdenum Mo-99 (Technetium Tc-99m cation) Active 2500 MILLICURIE  In 1 GENERATOR

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 11994-090-92 1 GENERATOR In 1 CARTON None

TechneLite  molybdenum mo-99  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 11994-090 Route of Administration INTRAVENOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Molybdenum Mo-99 (Technetium Tc-99m cation) Active 3000 MILLICURIE  In 1 GENERATOR

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 11994-090-01 1 GENERATOR In 1 CARTON None

TechneLite  molybdenum mo-99  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 11994-090 Route of Administration INTRAVENOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Molybdenum Mo-99 (Technetium Tc-99m cation) Active 4000 MILLICURIE  In 1 GENERATOR

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 11994-090-03 1 GENERATOR In 1 CARTON None

TechneLite  molybdenum mo-99  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 11994-090 Route of Administration INTRAVENOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Molybdenum Mo-99 (Technetium Tc-99m cation) Active 4500 MILLICURIE  In 1 GENERATOR

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 11994-090-04 1 GENERATOR In 1 CARTON None

TechneLite  molybdenum mo-99  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source)

Testosterone Cypionate

Class: Androgens
Note: This monograph also contains information on Testosterone, Testosterone Enanthate
VA Class: HS100
CAS Number: 58-22-0
Brands: Androderm, AndroGel, Delatestryl, Striant, Testim

• 
  

  Risk of virilization in children and women following secondary exposure to testosterone in topically administered testosterone gel.^{157 166 170 171} Advise children and women to avoid contact with application sites of men using testosterone gel.^{166 170 171} (See Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.)

  
  


• 
  

  Advise men using testosterone gel to strictly adhere to recommended instructions for use.^{170 171} (See Administration under Dosage and Administration.)

  
  

REMS:

FDA approved a REMS for testosterone to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of testosterone and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Androgenic anabolic steroid hormone; the principal endogenous androgen.^a

Uses for Testosterone Cypionate

Male Hypogonadism

Management of congenital or acquired primary hypogonadism such as that resulting from orchidectomy or from testicular failure caused by cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals.^{117 133 135 157 161 162 a}

Management of congenital or acquired hypogonadotropic hypogonadism such as that resulting from idiopathic gonadotropin or gonadotropin-releasing hormone (luteinizing hormone-releasing hormone) deficiency or from pituitary-hypothalamic injury caused by tumors, trauma, or radiation.^{117 133 135 157 161 162 a} Should be used in the treatment of hypogonadotropic hypogonadism only in patients uninterested in or unable to achieve fertility.^f

Considered the androgen of choice for the treatment of androgen deficiency (e.g., hypogonadism) and AIDS wasting in HIV-infected men.¹²⁶

May be used to stimulate puberty when the diagnosis is well established in carefully selected males with delayed puberty (designated an orphan drug by FDA for this use).^{a 162}

Some experts (e.g., American College of Rheumatology) recommend that men who develop low serum testosterone concentrations (<300 ng/mL) while receiving long-term corticosteroid therapy receive testosterone replacement therapy in an attempt to treat hypogonadism and possibly reduce the risk of corticosteroid-induced osteoporosis†.¹²²

Clinical evidence to date regarding testosterone therapy in aging men suggests some beneficial effects (e.g., on body composition, strength, bone density, frailty, cognitive function, mood, sexual function, quality of life), but risks relating to benign prostatic hyperplasia and prostate cancer need to be quantified.¹⁵⁶ The Institute of Medicine states that the nature and extent of therapeutic benefits in older men require additional study.¹⁵⁶

Not indicated for the treatment of erectile dysfunction† in men with normal testosterone concentrations.¹⁵⁸

Breast Cancer

Palliative treatment of androgen-responsive, advanced, inoperable, metastatic (skeletal) breast cancer in women who are 1–5 years postmenopausal and in premenopausal women who have benefited from oophorectomy.^{a 162}

Poorly tolerated (see Virilization under Cautions); other hormonal agents (e.g., tamoxifen, anastrozole, letrozole, exemestane) currently are preferred for this use.^{d e}

Misuse and Abuse

Has been misused and abused by athletes, bodybuilders, weight lifters, and others to enhance athletic performance or physique†.^{100 101 102 103 104 105 106 107 108 109 110 111 112 114 115 116 120}

Medical and sports experts (e.g., International Olympic Committee) consider such use to be inappropriate and unacceptable because of known adverse effects and potential long-term sequelae and because such use by athletes is contrary to the rules and ethical principles of athletic competition.^{101 102 107 114 115 116}

Testosterone Cypionate Dosage and Administration

General

Male Hypogonadism

• 
  

  Individualize dosage according to the condition being treated; the severity of symptoms; the patient’s age, gender, and history of prior androgenic therapy; and the specific testosterone preparation being used.^a

  
  


• 
  

  Monitor every 3–4 months during the first year of testosterone replacement and periodically thereafter (e.g., every 4–6 months) for response and tolerance.¹²³

  
  

Delayed Puberty

• 
  

  Prior to initiation of therapy, fully discuss the potential risk of therapy with the patient and his parents.^{a 162}

  
  


• 
  

  Take into consideration the chronological and skeletal ages of the patient, both in determining the initial dosage and in adjusting the dosage.^{117 162 a}

  
  


• 
  

  Perform radiographic examination of the hand and wrist at 6-month intervals to determine the rate of bone maturation and to assess the effect of therapy on the epiphyseal centers.^{117 162 a} (See Pediatric Use under Cautions.)

  
  

Breast Cancer

• 
  

  Administer only under supervision of a qualified clinician experienced in the treatment of breast cancer.^{162 a}

  
  


• 
  

  May occasionally appear to accelerate progression of the disease;^{162 a} monitor patients closely.¹⁶²

  
  


• 
  

  Discontinue the drug if hypercalcemia occurs, since this may indicate progression of metastases to the bone.¹⁶²

  
  

Administration

Administer testosterone topically or intrabuccally.^{133 157 161 166}

Administer testosterone cypionate and testosterone enanthate by deep IM injection;^{117 162} not for IV administration.¹¹⁷

IM Administration

Administer by deep IM injection into the upper outer quadrant of the gluteus maximus.^{117 162}

Topical Administration

Gel

AndroGel: Apply gel topically once daily, preferably in the morning, to clean, dry, intact skin on the shoulders and upper arms and/or abdomen.¹⁶⁶ Do not apply to the genitals.¹⁶⁶

AndroGel unit-dose packet: Upon opening the unit-dose packet, squeeze the entire contents into the palm of the hand and immediately apply to the application site.¹³⁵ Alternatively, squeeze a portion of the contents into the palm of the hand and immediately apply to application site; repeat procedure until entire contents of the packet has been applied.¹³⁵

AndroGel metered-dose pump: Collect gel in the palm of the hand by pressing the pump firmly and fully; apply to application site.¹³⁵ This can be done one pump actuation at a time or after completion of all pump actuations needed for the daily dose.¹³⁵ Alternatively, apply the gel directly to application site (direct application prevents loss of gel during transfer to hand).¹³⁵ Prime pump by depressing 3 times before using the pump for the first dose; discard gel so that household members or pets are not exposed to the gel (i.e., rinse down sink).¹³⁵

Testim: Apply gel topically once daily, preferably in the morning, to clean, dry, intact skin on the shoulders and/or upper arms¹⁵⁷ Do not apply to abdomen or genitals.¹⁵⁷ Upon opening the unit-dose tube, squeeze the entire contents into the palm of the hand and immediately apply to the application site.¹⁵⁷

Immediately wash hands with soap and water after application of the gel.^{157 166 170 171}

Allow the application site to dry for a few minutes after application of gel.^{166 170 171} After the gel has dried, cover site with clothing (e.g., a shirt) to prevent transfer to another individual.^{157 166}

Manufacturer of AndroGel recommends waiting ≥5–6 hours¹⁶⁶ and the manufacturer of Testim recommends waiting ≥2 hours after application before showering or swimming.¹⁵⁷ However, showering or swimming after the elapse of just 1 hour should have a minimal effect on the amount of testosterone gel absorbed if done very infrequently.¹³⁵

Wash the application site(s) thoroughly with soap and water to remove any testosterone residue prior to situations in which skin-to-skin contact with other individuals is anticipated at the site of testosterone gel application.^{170 171} If unwashed or unclothed skin at the site of testosterone gel application comes in contact with the skin of another individual, wash the general area of contact with soap and water as soon as possible.^{157 166 170 171}

Consider the possibility of secondary exposure to testosterone topical gel.^{157 166 170 171} (See Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.)

Transdermal System

Apply the transdermal system to clean, dry area of skin on the back, abdomen, upper arm, or thigh by firmly pressing the system with the adhesive side touching the skin.¹³³ Do not apply to the scrotum or to oily, damaged, or irritated areas of the skin.^{133 134}

To avoid burn-like blisters, do not apply systems over bony prominences or on a part of the body that may be subject to prolonged pressure during sleep or sitting (e.g., the deltoid region of the upper arm, the greater trochanter of the femur, the ischial tuberosity).¹³³

Apply once daily at night (e.g., 10 p.m.).¹³³ Leave transdermal system in place for 24 hours; after 24 hours, remove system and apply a new system.¹³³ Apply system immediately after removal from its protective pouch and removal of the protective liner.¹³³

To minimize and/or prevent potential skin irritation, apply each transdermal system at a different site, with ≥1 week between applications to a particular site.¹³³

Mild skin irritation may be ameliorated with topical hydrocortisone 0.5 or 1% cream after system removal; alternatively, apply a small amount of triamcinolone acetonide 0.1% cream to the skin under the drug reservoir (do not use ointment formulations because they may reduce testosterone absorption).^{133 143}

Transdermal system does not need to be removed during sexual intercourse or while showering or bathing.¹³³

Intrabuccal Administration

Press the extended-release buccal (transmucosal) tablet against the gum above the upper left or right incisor twice daily (morning and evening) about 12 hours apart.¹⁶¹ These tablets will adhere to the gum and do not dissolve completely; do not chew or swallow.¹⁶¹ Dislodge and remove the tablet after 12 hours.¹⁶¹ Alternate application sites above the left and right upper incisors.¹⁶¹

Consult manufacturer’s patient information for instructions on proper intrabuccal administration and removal of the tablet.¹⁶¹

If the tablet fails to properly adhere to the gum or falls off within the first 8 hours, replace the old tablet with a new one.¹⁶¹ The new tablet may remain in place until the time of the next regularly scheduled dose (i.e., 12 hours after the original buccal tablet was administered).¹⁶¹ If the buccal tablet falls off after 8 hours but before 12 hours, replace the original tablet with one that can serve as the second dose for that day.¹⁶¹

Dosage

Available as testosterone; dosage expressed in terms of testosterone.^{133 135 157 161} Also available as testosterone enanthate or testosterone cypionate; dosage expressed in terms of the salts.^{117 162}

AndroGel unit-dose packets contain 2.5 or 5 g of gel (25 or 50 mg of testosterone).¹³⁵ Each depression of the metered-dose pump delivers 1.25 g of gel (12.5 mg of testosterone) after priming.¹³⁵

Testim unit-dose tubes contain 5 g of gel (50 mg of testosterone).¹⁵⁷

Pediatric Patients

Male Hypogonadism

Delayed Puberty

IM

Dosage regimens vary.^{117 162 a} Some clinicians recommend that lower dosages be used initially, followed by gradual increases in dosage as puberty progresses; subsequently, the dosage may be decreased to maintenance levels.^{117 162 a} Other clinicians state that higher dosages are required initially to induce pubertal changes and lower dosages can then be used for maintenance therapy after puberty.^{117 162 a}

Usual dosage of testosterone enanthate: 50–200 mg every 2–4 weeks for a limited period of time (e.g., 4–6 months).^{a 162}

Adults

Male Hypogonadism

IM

Usual dosage: 50–400 mg of testosterone cypionate or testosterone enanthate every 2–4 weeks.^{117 162}

Some clinicians recommend testosterone cypionate or testosterone enanthate dosage of 50–100 mg every 7–10 days or 100–150 mg every 2 weeks.^f While dosage of 300 mg every 3 weeks also may be considered for convenience, such dosing is associated with wider testosterone fluctuations and generally is inadequate to ensure a consistent clinical response.¹²³ Serum total testosterone concentrations generally should exceed lower limit of normal (in the range of 250–300 ng/dL) just before the next dose.¹²³

Adult males with prepubertal onset of hypogonadism who are going through puberty for the first time with testosterone replacement: Initially, 50 mg every 3–4 weeks;^f increase dosage gradually in subsequent months as tolerated up to full replacement within 1 year.¹²³

Attainment of full virilization may require up to 3–4 years of IM testosterone replacement.¹²³

Topical (Gel)

AndroGel and Testim: Apply 50 mg of testosterone (5 g of 1% gel) once daily, preferably in the morning; this dose delivers about 5 mg of testosterone systemically.^{135 157} Adjust dosage according to serum testosterone concentrations obtained at regular intervals after initiating daily application of AndroGel¹⁶⁶ and approximately 14 days after initiating Testim.¹⁵⁷

AndroGel: If serum testosterone concentrations are below the normal range or the clinical response is inadequate, the dosage can be increased initially to 75 mg of testosterone (7.5 g of 1% gel) and, if necessary, subsequently to 100 mg of testosterone (10 g of 1% gel).¹³⁵ If serum testosterone concentrations exceed the normal range, the daily dosage may be decreased.¹⁶⁶ If serum testosterone concentrations consistently exceed the normal range at a daily dosage of 50 mg of testosterone (5 g of 1% gel), discontinue application of the gel.¹⁶⁶

Testim: If serum testosterone concentrations are below the normal range or the clinical response is inadequate, may increase dosage to 100 mg of testosterone (10 g of 1% gel).¹⁵⁷

Topical (Transdermal System)

Usual initial dosage is 1 system delivering 5 mg/24 hours or 2 systems delivering 2.5 mg/24 hours applied to the skin nightly.¹³³

Adjust dosage according to morning serum testosterone concentrations.¹³³ Depending on requirements, increase dosage to 7.5 mg once daily (administered nightly as 1 system delivering 5 mg/24 hours plus 1 system delivering 2.5 mg/24 hours or as 3 systems delivering 2.5 mg/24 hours) or decrease dosage to 2.5 mg once daily (administered nightly as 1 system delivering 2.5 mg/24 hours).¹³³

Intrabuccal

30 mg (1 extended-release transmucosal tablet) twice daily (morning and evening) about 12 hours apart.¹⁶¹ Serum testosterone concentration may be determined just prior to the morning dose at 4–12 weeks after initiation of intrabuccal therapy; if total serum testosterone concentration is excessive, discontinue intrabuccal therapy and consider alternative treatments.¹⁶¹

Breast Cancer

IM

200–400 mg of testosterone cypionate or testosterone enanthate every 2–4 weeks.^{162 a}

Special Populations

No special population dosage recommendations at this time.^{157 166}

Cautions for Testosterone Cypionate

Contraindications

• 
  

  Men with breast cancer or known or suspected prostate cancer.^{117 133 157 161 162 166}

  
  


• 
  

  Known hypersensitivity to testosterone, testosterone cypionate, testosterone enanthate, or any ingredient in the formulation.^{117 133 157 161 162 166 a}

  
  


• 
  

  Some manufacturers state that testosterone is contraindicated in patients with serious cardiac, renal, or hepatic disease.¹¹⁷

  
  


• 
  

  Manufacturers of testosterone cypionate and testosterone enanthate injections (preparations indicated for the treatment of breast cancer) state that androgens are contraindicated in women who are or may become pregnant.^{117 162}

  
  


• 
  

  Manufacturers of testosterone gel (AndroGel, Testim) state that testosterone is contraindicated in women who are or may become pregnant, or who are breastfeeding.^{157 166}

  
  


• 
  

  Manufacturers of buccal and transdermal testosterone preparations state that these preparations should not be used in women.^{133 161}

  
  

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity

May cause fetal harm;^{117 133 157 162 166} dose-related virilization of the external genitalia (e.g., clitoral hypertrophy, abnormal vaginal development, fusion of genital folds to form a scrotal-like structure) of female fetus reported, particularly when exposure to androgens occurs during the 1st trimester.^{162 166 a}

Virilization in Children and Women from Secondary Exposure to Testosterone

Virilization in children and women can occur following secondary exposure to testosterone in topically administered gel.^{170 171 172 173} Enlargement of penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age reported in children 9 months to 5 years of age during postmarketing surveillance of testosterone gel.^{167 168 169 170 171 172 173} Direct contact of children with testosterone gel application sites on men's skin reported in most cases.^{170 172 173} Secondary exposure to testosterone also possible from contact with items (e.g., shirts, bed linens) of men receiving testosterone gel.^{170 172 173} Signs and symptoms generally resolved with removal of testosterone exposure.^{169 170 171 172} In some cases, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronologic age.^{169 170 171}

Children and women should avoid contact with application sites on the skin of men using testosterone gel.^{166 170 171} Consider also the possibility of secondary exposure from contact with items (e.g., shirts, bed linens) of men using testosterone gel.^{170 172 173}

Risk of testosterone transfer in some cases increased by lack of adherence to precautions for appropriate use of testosterone gel.¹⁷⁰ Advise men using topical gel to strictly adhere to the recommended instructions for use and appropriate precautions from the manufacturers to minimize the potential for secondary exposure to testosterone in other individuals.^{170 171} (See Administration under Dosage and Administration.)

If unwashed or unclothed skin to which testosterone gel has been applied comes in contact with the skin of another individual, wash the general area of contact with soap and water as soon as possible.^{157 166}

Inform clinicians of inappropriate changes in genital size or development of pubic hair or libido in children, or changes in body hair distribution, substantial increases in acne, or other signs of virilization in women.^{166 170 171} Consider the possibility of secondary exposure to testosterone as the cause of virilization in these patients.^{166 170 171} Discontinue testosterone gel promptly at least until the cause of virilization in such children and women is identified.^{170 171}

Hepatic Effects

Potentially serious and/or life-threatening adverse hepatic effects (e.g., peliosis hepatis, hepatic adenomas, hepatocellular carcinoma, cholestatic hepatitis, jaundice) associated with prolonged use of high dosages of androgens (e.g., testosterone enanthate).^{117 133 134 135 157 161 162} Abnormal liver function tests (e.g., ALT, AST, gamma-glutamyltranspeptidase [GGTP], bilirubin) reported with AndroGel during postmarketing surveillance.¹⁶⁶

If cholestatic jaundice or hepatitis occurs or if liver function test results become abnormal during therapy, discontinue the drug and investigate the etiology of these disorders.¹⁶² Drug-induced jaundice usually is reversible following discontinuance of the drug.¹⁶² Discontinuance of androgen therapy following development of hepatocellular carcinoma does not always result in regression of the tumor.^{117 133 135 157 161 162}

GU Effects

Priapism or excessive sexual stimulation possible, especially in geriatric men.^{117 133 135 a} Oligospermia and decreased ejaculatory volume may also occur in men receiving excessive dosage or prolonged administration of testosterone.^{117 a} If any of these adverse effects occur, discontinue the drug temporarily.^{117 a} If therapy is restarted, use lower dosages.^{117 a}

Possible increased risk for the development of prostatic hyperplasia and prostate cancer, particularly in geriatric patients.^{117 133 134 135 157 161 162} Testosterone therapy has been associated with increases in PSA (of 0.3 ng/mL) in men with hypogonadism.^{135 163} Increased serum PSA concentrations observed in 18% of hypogonadal men receiving AndroGel for up to 42 months; most increases occurred within the first year of therapy.¹⁶⁶ Evaluate geriatric patients and other patients with known clinical or demographic risk factors for prostate cancer for the presence of the disease prior to initiation of testosterone replacement therapy.^{133 135 157 161 162} Perform rectal prostate examinations at baseline and periodically thereafter.¹²³ Baseline and annual determinations of PSA also recommended in older men, particularly in those >50 years of age.¹²³

Acute urethral obstruction possible in patients with benign prostatic hypertrophy who receive IM testosterone cypionate.¹¹⁷

Gynecomastia frequently develops and occasionally persists.^{117 135 157 161 162} Consider concomitant use of an aromatase inhibitor or surgery.¹²³

Postmarketing reports with AndroGel include impaired urination, prostatic enlargement, testicular atrophy, oligospermia, priapism, gynecomastia, and mastodynia.¹⁶⁶

Fluid Retention

Edema, with or without CHF, possible as a result of sodium and water retention and may be a serious complication in patients with preexisting cardiac, renal, and/or hepatic disease.^{117 133 157 161 162 166} (See Contraindications under Cautions.)

If edema occurs and is considered a serious complication, discontinue the drug and, if necessary, initiate diuretic therapy.^{133 135 157 161 162 a}

Hypercalcemia

Possible hypercalcemia resulting from osteolysis, especially in immobile patients and in women with metastatic breast cancer.^{161 166 a} In patients with cancer, hypercalcemia may indicate progression of metastases to the bone.^{161 a} Monitor urine and serum calcium concentrations frequently during the course of androgen therapy in women with metastatic breast cancer.^{162 166}

If hypercalcemia occurs, discontinue the drug and institute appropriate measures to reduce serum calcium concentrations.^{162 a}

Sleep Apnea

May potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases.^{157 161 166}

If manifestations of sleep apnea occur or worsen during therapy, perform sleep studies.^{123 144} If sleep apnea is confirmed, decrease the dosage or discontinue the drug.^{123 144}

Some clinicians consider a history of sleep apnea to be a relative contraindication to testosterone therapy.¹²³

Misuse and Abuse

Potential for serious adverse effects (e.g., increased aggression,^{100 101 102 104 107 108 109 116} antisocial behavior,^{100 101 102 104 107 108 109 116} manic episode,^{102 104 105 106 107 108 112 114} depression,^{102 104 105 106 107 108 112 114} changes in libido,^{101 102 107 109 116} increased risk of cardiovascular disease,^{100 101 102 104 107 108 111 112 114 116 119} hepatotoxicity^{100 101 102 104 107 108 109 110 112 114 116} ) associated with misuse and abuse of androgens (see Misuse and Abuse under Uses); testosterone preparations currently subject to control under the Federal Controlled Substances Act of 1970, as amended by the Anabolic Steroids Control Act of 1990 and 2004, as schedule III (C-III) drugs.^{113 164}

Flammability

Testosterone gels contain alcohol and are flammable until dry; keep away from open flame.¹⁶⁶

Sensitivity Reactions

Allergic contact dermatitis possible with transdermal systems.^{133 137 142} Topical application of testosterone gel (i.e., AndroGel) is not associated with phototoxicity.¹³⁵ Hypersensitivity reactions (e.g., anaphylactoid reactions, skin manifestations) rarely reported with testosterone.^a

General Precautions

Virilization in Women Receiving Testosterone Therapy

Virilization, including deepening of the voice, hirsutism, and clitoral enlargement, occurs commonly in females receiving testosterone therapy; these changes may not be reversible following discontinuance of the drug.^{162 a}

Monitor women receiving testosterone therapy for signs of virilization (e.g., deepening of the voice, hirsutism, clitoromegaly, menstrual irregularities).¹⁶¹ If virilization occurs, discontinue therapy.¹⁶¹

See Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.

Lipid Abnormalities

Androgens may alter serum cholesterol concentration.^{117 162} Although lipid abnormalities generally do not develop during testosterone replacement therapy because of aromatization of testosterone to estradiol,¹²³ consider the possibility that such changes could occur and use testosterone with caution in patients with a history of MI or CAD.¹⁶²

Perform a lipid profile at baseline and after 6–12 months; adjust therapy accordingly.^{123 135 157 161 162} Changes in serum lipid profiles may require dosage adjustment or discontinuance of testosterone therapy.¹⁶⁶

Hematologic Effects

Supraphysiologic concentrations of testosterone can stimulate erythropoiesis^{123 166} and may increase the risk for a thromboembolic event.¹⁶⁶ Increases in hematocrit may require dosage reduction or discontinuation of testosterone.¹⁶⁶ To detect polycythemia, perform periodic hemoglobin and hematocrit determinations in patients receiving long-term therapy.^{117 123 133 135 157 161 162}

Some clinicians consider hyperviscosity to be a relative contraindication to testosterone therapy.¹²³

Transfer of Topically Administered Testosterone to Other Individuals

Possible transfer of testosterone from patients treated with topical gel to their sexual partners or other individuals in close physical contact.^{157 166} (See Pregnancy and also see Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.)

Androderm transdermal system has an occlusive backing that prevents the partner from coming in contact with testosterone in the system; the system does not need to be removed during sexual intercourse.¹³³ Transfer of the transdermal system itself from the patient’s body to that of his partner is unlikely.¹³³

Specific Populations

Pregnancy

Category X.^{117 133 135 157 161 162} (See Fetal/Neonatal Morbidity and also see Contraindications under Cautions.)

Avoid transfer of testosterone from topical preparations of the drug to pregnant women.^{157 166} (See Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.)

If unwashed or unclothed skin to which testosterone topical gel has been applied comes in direct contact with the skin of a pregnant woman, wash the general area of contact with soap and water as soon as possible.^{157 166}

Lactation

Not known whether testosterone is distributed into milk.¹⁶² Potential for serious adverse reactions in nursing infants.^{162 166} Testosterone also may adversely affect lactation.¹⁶⁶ Discontinue nursing or testosterone enanthate injection taking into account the importance of the drug to the woman.¹⁶² Use of testosterone gel, transdermal system, and buccal tablets not recommended.^{117 133 157 161 166}

Pediatric Use

Safety and efficacy not established for topical testosterone gel ^{157 166} or extended-release buccal (transmucosal) testosterone tablets in children <18 years of age;¹⁶¹ testosterone transdermal systems in males <15 years of age;¹³³ or testosterone cypionate in children <12 years of age.¹¹⁷ Secondary exposure to testosterone in children can occur with use of testosterone gel in other individuals.^{170 171} (See Virilization in Children and Women from Secondary Exposure to Testosterone under Cautions.)

Testosterone enanthate injection may accelerate bone maturation without producing compensatory gain in linear growth, possibly resulting in compromised adult stature.^{162 a} The younger the child, the greater the risk of testosterone compromising final mature stature.^{162 a} Use with extreme caution in children and only under the supervision of a specialist who is aware of the adverse effects of testosterone on bone maturation.^{162 a} Perform radiographic examination of the hand and wrist every 6 months to determine the rate of bone maturation and to assess the effect of treatment on the epiphyseal centers.^{162 a}

Geriatric Use

Possible increased risk of developing prostatic hypertrophy and prostate cancer during androgen therapy.^{117 133 157 166 161 a} (See GU Effects under Cautions.)

Total amount of testosterone delivered over 24 hours in men 65–79 years of age following application of transdermal testosterone system (Androderm) was approximately 20% less than the average amount delivered in younger patients.¹³³

Clinical studies evaluating testosterone enanthate injection (Delatestryl) and topical testosterone gel (AndroGel) have not included sufficient numbers of adults ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^{162 166}

No substantial differences in safety and efficacy of extended-release buccal (transmucosal) testosterone tablets (Striant)in geriatric patients relative to younger adults.¹⁶¹ Pharmacokinetic differences observed between geriatric and younger adults in studies with Striant, but not known whether these differences are clinically important.¹⁶¹

Insufficient long-term safety data with Delatestryl and AndroGel to determine the potential risks of cardiovascular disease, prostate cancer, and prostatic hyperplasia in geriatric adults.^{162 166}

Common Adverse Effects

Acne, flushing of the skin, gynecomastia, increased or decreased libido, habituation, edema,^a local irritation at the site of application (with topical or intrabuccal administration).^{133 137 138 139 140 143 157 161 166}

Interactions for Testosterone Cypionate

Specific Drugs

Drug	Interaction	Comment
Anticoagulants, oral	Testosterone may potentiate the action of oral anticoagulantsa and decrease anticoagulant requirements117 133 162	Monitor INR and prothrombin time closely when androgen therapy is initiated or discontinued in patients receiving oral anticoagulants and adjust anticoagulant dosage as needed133 162 166 a