Generic Name: Triptorelin Pamoate
Class: Antineoplastic Agents
VA Class: AN500
Chemical Name: 6-d-Tryptophan luteinizing hormone-releasing factor (pig)
Molecular Formula: C64H82N18O13
CAS Number: 57773-63-4
Special Alerts:
[Posted 10/20/2010] ISSUE: Gonadotropin-Releasing Hormone (GnRH) agonists will have new safety information added to the Warnings and Precautions section of the drug labels. This new information warns about increased risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, stroke) in men receiving these medications for the treatment of prostate cancer.
BACKGROUND: GnRH agonists are approved to treat the symptoms (palliative treatment) of advanced prostate cancer. The benefits of GnRH agonist use for earlier stages of prostate cancer that have not spread (non-metastatic prostate cancer) have not been established. FDA’s notification to manufacturers of GnRH agonists to add this safety information is based on the Agency’s review of several published studies. Most of the studies reviewed by FDA reported small but statistically significant increased risks of diabetes and/or cardiovascular events in patients receiving GnRH agonists.
RECOMMENDATIONS: Healthcare professionals should evaluate patients for risk factors for these diseases and carefully weigh the benefits and risks of using GnRH agonists before determining appropriate treatment for prostate cancer. Patients who are receiving treatment with GnRH agonists should undergo periodic monitoring of blood glucose and/or glycosylated hemoglobin (HbA1c). Healthcare professionals should also monitor patients for signs and symptoms suggestive of development of cardiovascular disease and manage according to current clinical practice. For more information visit the FDA website at: and .
[Posted 05/03/2010] FDA notified healthcare professionals and patients of FDA’s preliminary and ongoing review which suggests an increase in the risk of diabetes and certain cardiovascular diseases in men treated with GnRH agonists, drugs that suppress the production of testosterone, a hormone that is involved in the growth of prostate cancer.
Most of the studies reviewed by FDA reported small, but statistically significant increased risks of diabetes and/or cardiovascular events in patients receiving GnRH agonists. FDA’s review is ongoing and the agency has not made any conclusions about GnRH agonists and whether they increase the risk of diabetes and cardiovascular disease in patients receiving these medications for prostate cancer.
Healthcare professionals and patients should be aware of these potential safety issues and carefully weigh the benefits and risks of GnRH agonists when determining treatment choices. FDA recommends that patients receiving GnRH agonists should be monitored for development of diabetes and cardiovascular disease. Patients should not stop their treatment with GnRH agonists unless told to do so by their healthcare professional.
Some GnRH agonists are also used in women and in children for other indications than those above. There are no known comparable studies that have evaluated the risk of diabetes and heart disease in women and children taking GnRH agonists. For more information visit the FDA website at: and .
Introduction
Antineoplastic agent; synthetic decapeptide analog of gonadotropin-releasing hormone (GnRH, luteinizing hormone-releasing hormone, gonadorelin);1 7 structurally related to leuprolide and goserelin.1 2 3 4 6 7
Uses for Trelstar
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Prostate Cancer
Palliative treatment of advanced prostate cancer; considered alternative therapy when orchiectomy or estrogen therapy is not appropriate or is unacceptable to the patient.1 7
Trelstar Dosage and Administration
Administration
IM Administration
Administer by IM injection once monthly (every 28 days) as a depot 1-month formulation or every 84 days (12 weeks) as a long-acting 3-month formulation.1 7
Inject IM into buttock; rotate injection sites periodically.1 7
Administer under the supervision of a qualified clinician.1 7
Reconstitution
Reconstitute powder just prior to administration.1 7 Discard suspension if not used immediately after reconstitution.1 7
Using a syringe with 20-gauge needle, add 2 mL of sterile water for injection to vial containing the powder (1- or 3-month formulation); do not reconstitute with other diluents.1 7 Shake well to disperse particles and obtain a uniform, milky suspension.1 7
If using the single-dose delivery system, add contents of the prefilled syringe (2 mL of sterile water for injection) to vial containing the powder according to the manufacturer’s instructions.1 7 Mix well.1 7
Withdraw entire contents of vial and use immediately.1 7
Dosage
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Available as triptorelin pamoate; dosage is expressed in terms of triptorelin.1 7
Adults
Prostate Cancer
IM
3.75 mg every 28 days (monthly) as the 1-month formulation or 11.25 mg every 84 days (12 weeks) as the 3-month formulation.1 7
Special Populations
Hepatic Impairment
Potential need for dosage adjustment not determined.1
Renal Impairment
Potential need for dosage adjustment not determined.1
Cautions for Trelstar
Contraindications
Known hypersensitivity to triptorelin or any other ingredient in the formulation, other GnRH agonists, or GnRH.1 7
Known or suspected pregnancy.1 7
Warnings/Precautions
Warnings
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Endocrine Effects
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Possible worsening of signs and/or symptoms of prostate cancer and/or development of new manifestations (e.g., bone pain, neuropathy, hematuria, urethral or bladder outlet obstruction) due to increases in serum testosterone concentrations during initial weeks of therapy.1 2 3 5 7
Possible spinal cord compression contributing to paralysis; possibly fatal.1 2 5 7
Increased risk of neurologic and/or genitourinary complications during initial therapy in patients with prostate cancer and metastatic vertebral lesions and/or urinary tract obstruction.1 7 Observe such patients closely during initial weeks of therapy.1 5 7
If spinal cord compression or renal impairment develops, institute standard treatment of these complications; consider immediate orchiectomy in extreme cases.1 7
Sensitivity Reactions
Hypersensitivity Reactions
Anaphylactic shock and angioedema reported rarely.1 7 If such reactions occur, discontinue immediately and provide supportive and symptomatic care.1 7
Major Toxicities
Pituitary Apoplexy
Pituitary apoplexy, a clinical syndrome resulting from infarction of the pituitary gland, reported rarely.1 7 Most cases occur within 2 weeks of the first dose, sometimes within the first hour.1 7 If manifestations occur (e.g., sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, sometimes cardiovascular collapse), immediate medical attention required.1 7 In most cases, pituitary adenoma diagnosed.1
General Precautions
Laboratory Monitoring
Periodically determine serum testosterone and prostate-specific antigen concentrations to monitor therapeutic response.1 7
Specific Populations
Pregnancy
Category X.1 7 (See Contraindications under Cautions.)
Lactation
Not known whether distributed into milk; not recommended for use in nursing women.1 7
Pediatric Use
Safety and efficacy not established in children.1 7
Geriatric Use
Studies conducted principally in patients ≥65 years of age, since prostate cancer occurs mainly in an older patient population.1 7
Common Adverse Effects
Temporary worsening of disease manifestations, hot flushes (flashes), skeletal pain, impotence, headache, pain at injection site, leg pain and edema, dysuria, hypertension.1 7
Also observed with 3-month formulation: decreased hemoglobin and erythrocyte counts, increased BUN, increased serum concentrations of glucose, AST, ALT, and alkaline phosphatase.7
Interactions for Trelstar
Metabolism unlikely to involve CYP enzymes; effect of triptorelin on other drug-metabolizing enzymes unknown.7
Drugs That Induce Hyperprolactinemia
Potential pharmacologic interaction (possible decrease in triptorelin efficacy due to decreased number of GnRH receptors) with drugs such as antipsychotic agents, methyldopa, metoclopramide, and reserpine.1 6 7
Trelstar Pharmacokinetics
Absorption
Bioavailability
Not active when administered orally.1 7
Following IM administration as Trelstar Depot or Trelstar LA, peak plasma concentrations usually are attained within 1 or 3 hours, respectively.1 7
Duration
Following IM injection of Trelstar Depot or Trelstar LA in males, therapeutic plasma concentrations persist for 1 or 3 months, respectively.1 7
Distribution
Extent
Not known whether triptorelin is distributed into milk.1 7
Plasma Protein Binding
No evidence that triptorelin binds to plasma proteins.1 7
Elimination
Metabolism
Metabolism is unknown; involvement of CYP enzymes is unlikely.1 7 No metabolites identified to date.1 7
Elimination Route
Hepatic and renal elimination.1 7
Half-life
Approximately 3 hours.1 7
Special Populations
In males with hepatic impairment or moderate or severe renal impairment, AUC increased 2- to 4-fold compared with healthy males.1 7
Stability
Storage
Parenteral
Powder for Injection
20–25°C (may be exposed to 15–30°C).1 7 Do not freeze.7
Discard suspension if not used immediately after reconstitution.1 7
ActionsActions
Potent inhibitor of gonadotropin secretion when given continuously in therapeutic doses; greater activity than naturally occurring GnRH.1 7
Transient surge in circulating levels of LH, FSH, testosterone, and estradiol observed after initial administration.1 7 Sustained decreases in LH and FSH secretion and reduced testicular and ovarian steroidogenesis observed following chronic, continuous administration (generally 2–4 weeks after initiation of therapy).1 4 7
Reduction of serum testosterone in males comparable to effects achieved after surgical castration; results in inactivation of physiologic functions and tissues dependent on testosterone.1 2 4 7 These effects usually are reversible after cessation of therapy.1 7
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.
Risk of worsening manifestations of prostate cancer during initial weeks of therapy.1 7
Importance of promptly reporting weakness or paresthesia of lower limbs and/or worsening of urinary signs and symptoms to clinicians.6
Importance of promptly reporting sudden onset of headache, vomiting, or visual changes to clinicians.1 7
Risk of anaphylactoid and other sensitivity reactions.1 7
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 7
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 7 If used during pregnancy, apprise of potential fetal hazard.7
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | For injection, for IM use only | 3.75 mg (of triptorelin) | Trelstar Depot | Watson |
Trelstar Depot Clip’n’Ject | Watson | |||
11.25 mg (of triptorelin) | Trelstar LA | Watson | ||
Trelstar LA Clip’n’Ject | Watson |
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
1. Watson Pharma. Trelstar Depot 3.75 mg (triptorelin pamoate for injectable suspension) prescribing information. Corona, CA; 2006 Aug.
2. Parmar H, Phillips RH, Lightman SL et al. Randomised controlled study of orchidectomy vs long-acting D-Trp-6-LHRH microcapsules in advanced prostatic carcinoma. Lancet. 1985; 2:1201-5. [PubMed 2866289]
3. Mahler C. Is disease flare a problem? Cancer. 1993; 72:3799-802.
4. Rolandi E, Martorana G, Franceschini R et al. Treatment of prostatic cancer with a depot preparation of an LHRH analogue: endocrine effects. Curr Ther Res. 1985; 38:670-5.
5. Kahan A, Delrieu F, Amor B et al. Disease flare induced by D-Trp6-LHRH analogue in patients with metastatic prostatic cancer. Lancet. 1984; 1:971-2. [IDIS 184509] [PubMed 6143912]
6. Pharmacia & Upjohn, Kalomazoo, MI: Personal communication.
7. Watson Pharma. Trelstar LA 11.25 mg (triptorelin pamoate for injectable suspension) prescribing information. Corona, CA: 2006 Aug.
8. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52.
More Trelstar resources
- Trelstar Side Effects (in more detail)
- Trelstar Use in Pregnancy & Breastfeeding
- Trelstar Drug Interactions
- Trelstar Support Group
- 0 Reviews for Trelstar - Add your own review/rating
Compare Trelstar with other medications
- Prostate Cancer
No comments:
Post a Comment