Pronunciation
(trip toe REL
in)
Index Terms
AY-25650
CL-118,532
D-Trp(6)-LHRH
Detryptoreline
Triptodur
Triptorelin Embonate
Triptorelin Pamoate
Tryptoreline
Dosage Forms
Excipient
information presented when available (limited, particularly for generics);
consult specific product labeling. [DSC] = Discontinued product
Suspension
Reconstituted, Intramuscular:
Trelstar: 3.75
mg (1 ea [DSC]); 11.25 mg (1 ea [DSC]) [contains polysorbate 80]
Trelstar
Mixject: 3.75 mg (1 ea); 11.25 mg (1 ea); 22.5 mg (1 ea) [contains polysorbate
80]
Suspension
Reconstituted ER, Intramuscular:
Triptodur: 22.5
mg (1 ea) [contains polysorbate 80]
Brand Names:
U.S.
Trelstar Mixject
Trelstar [DSC]
Triptodur
Pharmacologic
Category
Gonadotropin
Releasing Hormone Agonist
Pharmacology
Triptorelin is
an agonist analog of gonadotropin releasing hormone (GnRH) and causes
suppression of ovarian and testicular steroidogenesis due to decreased levels
of LH and FSH with subsequent decrease in testosterone (male) and estrogen
(female) levels. After chronic and continuous administration, usually 2 to 4
weeks after initiation, a sustained decrease in LH and FSH secretion occurs.
When used for ART, prevents premature LH surge in women undergoing controlled
ovarian hyperstimulation.
Distribution
Vd:
30 to 33 L
Metabolism
Unknown;
unlikely to involve CYP; no known metabolites
Excretion
Urine (42% as
intact peptide); hepatic
Time to Peak
Trelstar: 1 to 3
hours; Triptodur: 4 hours
Half-Life
Elimination
2.8 ± 1.2 hours
Moderate-to-severe
renal impairment: 6.6 to 7.7 hours
Hepatic
impairment: 7.6 hours
Protein Binding
None
Special
Populations: Renal Function Impairment
There is a
decrease in total Cl proportional to decrease in CrCl and increased Vd and
half-life. Patients with renal impairment had 2- to 4-fold higher exposure
(AUC) values than younger healthy men.
Special
Populations: Hepatic Function Impairment
The decrease in
triptorelin Cl is more pronounced. Triptorelin half-life increase is similar to
renal impairment. Patients with hepatic impairment had 2- to 4-fold higher
exposure (AUC) values than younger healthy men.
Special
Populations: Elderly
Triptorelin
clearance is partly correlated to total CrCl, which is well known to decrease
with age.
Use: Labeled
Indications
Advanced
prostate cancer: Palliative treatment of advanced prostate cancer
Assisted reproductive
technologies: Decapeptyl [Canadian product]: Adjunctive therapy in women
undergoing controlled ovarian hyperstimulation for assisted reproductive
technologies (ART)
Off Label Uses
Paraphilia/hypersexuality
Based on The World Federation of Societies of Biological
Psychiatry (WFSBP) Guidelines for the Biological Treatment of Paraphilias, triptorelin
given for paraphilia/hypersexuality is an effective and recommended treatment
option in the management of this condition.
Additional
Off-Label Uses
Endometriosis; In
vitro fertilization; Uterine sarcoma
Contraindications
Hypersensitivity
to triptorelin or any component of the formulation, other GnRH agonists or
GnRH; pregnancy
Canadian
labeling: Additional
contraindications (not in US labeling): Breast-feeding women
Dosing: Adult
Advanced
prostate carcinoma: IM:
3.75 mg once
every 4 weeks or
11.25 mg once
every 12 weeks or
22.5 mg once
every 24 weeks
Controlled
ovarian hyperstimulation for assisted reproductive technologies (ART)
(adjunctive therapy): Decapeptyl [Canadian product]): Females:
SubQ: Usual dose: 0.1 mg once daily initiated on day 2 or 3 or days 21 to 23 of
menstrual cycle (or 5 to 7 days prior to expected onset of menses). Dose may be
adjusted according to ovarian response as measured by ovarian ultrasound with
or without serum estradiol levels. Treatment is continued until follicles achieve
suitable size (typically 4 to 7 weeks).
Treatment of
paraphilia/hypersexuality (off-label use; Guay, 2009; Thibaut, 1993): Males:
Note: May cause
an initial increase in androgen concentrations which may be treated with an
antiandrogen (eg, flutamide, cyproterone) for 1 to 2 months (Guay, 2009). Avoid
use in patients with osteoporosis or active pituitary pathology.
SubQ: Test dose:
1 mg (observe for hypersensitivity)
IM: 3.75 mg
monthly
Dosing:
Geriatric
Refer to adult
dosing.
Dosing:
Pediatric
Central precocious
puberty: Triptodur:
Children ≥2 years and Adolescents: IM: 22.5 mg once every 24 weeks; discontinue
therapy at appropriate age of onset of puberty.
Dosing: Renal
Impairment
There are no
dosage adjustments provided in the manufacturer's labeling. However, renal
impairment increases systemic exposure to triptorelin.
Dosing: Hepatic
Impairment
There are no
dosage adjustments provided in the manufacturer's labeling. However, hepatic
impairment increases systemic exposure to triptorelin.
Reconstitution
MIXJECT System:
Follow manufacturer's instructions for mixing prior to use.
Trelstar:
Reconstitute with 2 mL sterile water for injection. Shake well to obtain a
uniform suspension. Solution will appear milky. Administer immediately after
reconstitution.
Triptodur:
Reconstitute with 2 mL sterile water for injection. Gently swirl the vial.
Solution will appear milky. Administer immediately after reconstitution.
Administration
Administer by IM
injection into the buttock (Trelstar) or into the buttock or thigh (Triptodur);
alternate injection sites. Administer immediately after reconstitution. Must
administer under the supervision of a health care provider.
Decapeptyl
[Canadian product] is administered by subcutaneous injection into the lower
abdomen; alternate injection sites. If a dose is missed, it can be administered
on the same day; however, do not double doses. Must administer under the
supervision of a health care provider.
Storage
Trelstar: Store
at 20°C to 25°C (68°F to 77°F). Do not freeze MIXJECT system. Administer
immediately after reconstitution.
Triptodur: Store
at 20°C to 25°C (68°F to 77°F). Do not freeze.
Decapeptyl
[Canadian product]: Store at 2°C to 8°C (36°F to 46°F); do not freeze. Protect
from light.
Drug
Interactions
Antidiabetic
Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of
Antidiabetic Agents. Monitor therapy
Choline C 11:
Luteinizing Hormone-Releasing Hormone Analogs may diminish the therapeutic
effect of Choline C 11. Monitor therapy
Corifollitropin
Alfa: Luteinizing Hormone-Releasing Hormone Analogs may enhance the therapeutic
effect of Corifollitropin Alfa. Avoid combination
Indium 111
Capromab Pendetide: Luteinizing Hormone-Releasing Hormone Analogs may diminish
the diagnostic effect of Indium 111 Capromab Pendetide. Avoid
combination
MiFEPRIStone:
May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate
Risk and Risk Modifying). Management: Though the drugs listed here have
uncertain QT-prolonging effects, they all have some possible association with
QT prolongation and should generally be avoided when possible. Consider
therapy modification
QTc-Prolonging
Agents (Highest Risk): QTc-Prolonging Agents (Indeterminate Risk and Risk
Modifying) may enhance the QTc-prolonging effect of QTc-Prolonging Agents
(Highest Risk). Management: Avoid such combinations when possible. Use should
be accompanied by close monitoring for evidence of QT prolongation or other
alterations of cardiac rhythm. Consider therapy modification
QTc-Prolonging
Agents (Moderate Risk): QTc-Prolonging Agents (Indeterminate Risk and Risk
Modifying) may enhance the QTc-prolonging effect of QTc-Prolonging Agents
(Moderate Risk). Monitor therapy
Test
Interactions
Pituitary-gonadal
function may be suppressed with chronic administration and for up to 8 weeks
after triptorelin therapy has been discontinued.
Adverse
Reactions
Prostate cancer: As
reported with all strengths; frequency of effect may vary by strength:
>10%:
Endocrine &
metabolic: Hot flash (59% to 72%), increased serum glucose, increased
testosterone (peak: days 2-4; decline to low levels by weeks 3-4)
Hematologic
& oncologic: Decreased hemoglobin, decreased red blood cells
Hepatic:
Increased serum alkaline phosphatase (2% to >10%), increased serum ALT,
increased serum AST
Neuromuscular
& skeletal: Musculoskeletal pain (12% to 13%)
Renal: Increased
blood urea nitrogen
1% to 10%:
Cardiovascular:
Lower extremity edema (6%), hypertension (≤4%), chest pain (2%), dependent edema
(2%), peripheral edema (≤1%)
Central nervous
system: Headache (2% to 7%), pain (2% to 3%), dizziness (1% to 3%), fatigue
(2%), insomnia (1% to ≤2%), emotional lability (1%)
Dermatologic:
Skin rash (2%), pruritus (1%)
Endocrine &
metabolic: Decreased libido (2%), gynecomastia (2%)
Gastrointestinal:
Nausea (3%), anorexia (2%), constipation (2%), dyspepsia (2%), mastalgia (2%),
vomiting (2%), abdominal pain (1%), diarrhea (1%)
Genitourinary:
Erectile dysfunction (10%), testicular atrophy (8%), impotence (2% to 7%),
dysuria (5%), urinary retention (≤1%), urinary tract infection (≤1%)
Hematologic
& oncologic: Anemia (1%)
Local: Pain at
injection site (4%)
Neuromuscular
& skeletal: Leg pain (2% to 5%), back pain (≤3%), leg cramps (2%),
arthralgia (≤2%), myalgia (1%), weakness (1%)
Ophthalmic:
Conjunctivitis (1%), eye pain (1%)
Respiratory:
Cough (2%), dyspnea (1%), pharyngitis (1%)
Reproductive
studies:
>10%:
Central nervous
system: Headache (4% to 27%)
Gastrointestinal:
Abdominal pain (9% to 15%)
Genitourinary:
Vaginal hemorrhage (2% to 24%)
Local:
Inflammation at injection site (10% to 12%)
1% to 10%:
Cardiovascular:
Flushing (4%)
Central nervous
system: Dizziness (4% to 5%), fatigue (3% to 4%), malaise (2%)
Endocrine &
metabolic: Spontaneous abortion (7%), dysmenorrhea (2% to 6%), ovarian
hyperstimulation syndrome (3%), hot flash (2%), ovarian cyst (1%)
Gastrointestinal:
Nausea (3% to 10%), vomiting (3%), abdominal distension (2%), diarrhea (2%)
Genitourinary:
Pelvic pain (6%), gynecological pain (adnexa uteri, 2%), leukorrhea (2%)
Local: Pain at
injection site (4% to 7%), bruising at injection site (3%), injection site
reaction (2% to 3%)
Neuromuscular
& skeletal: Postoperative pain (3% to 4%), back pain (3%)
Respiratory:
Upper respiratory tract infection (4%), flu-like symptoms (3%), pharyngitis
(3%), dyspnea (2%), rhinitis (2%)
Postmarketing
and/or case reports (all indications; limited to important or
life-threatening): Anaphylactic shock, anaphylaxis, angioedema, bladder outflow
obstruction, blurred vision, cerebrovascular accident, circulatory shock, deep
vein thrombosis, dyspareunia, exacerbation of depression, hematuria,
hypersensitivity reaction, increased appetite, myocardial infarction,
neuropathy, pituitary apoplexy, prolonged Q-T interval on ECG, pulmonary
embolism, renal insufficiency, seizure, sleep disorder, spinal cord
compression, thrombophlebitis, tissue necrosis at injection site, transient
ischemic attacks, tumor flare, urethral obstruction, vaginal dryness
Warnings/Precautions
Concerns related
to adverse effects:
• Cardiovascular
effects: Androgen-deprivation therapy (ADT) may increase the risk for
cardiovascular disease (Levine, 2010). Myocardial infarction, sudden cardiac
death and stroke have been reported in men receiving GnRH agonists. ADT may
prolong the QT/QTc interval; consider the benefits of ADT versus the risk for
QT prolongation in patients with a history of QTc prolongation, congenital long
QT syndrome, heart failure, frequent electrolyte abnormalities, and in patients
with medications known to prolong the QT interval. Consider periodic monitoring
of electrocardiograms and electrolytes in at-risk patients.
• Decreased bone
density: Use with caution in patients with risk factors for decreased bone
mineral density; GnRH agonist therapy may increase risk for osteoporosis and
bone fractures particularly with prolonged use.
• Hyperglycemia:
Hyperglycemia and an increased risk of developing diabetes has been reported
with therapy and may manifest as diabetes or worsening of glycemic control in
patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin
(HbA1c) as clinically necessary.
•
Hypersensitivity reactions: Angioedema and anaphylactic shock have occurred;
discontinue use if severe reaction occurs.
• Ovarian hyperstimulation
syndrome: Decapeptyl [Canadian product]: Ovarian hyperstimulation syndrome
(OHSS) is a rare exaggerated response to ovulation induction therapy (Corbett
2014; Fiedler 2012). This syndrome may begin within 24 hours of treatment but
may become most severe 7 to 10 days after therapy (Corbett 2014). Symptoms of
mild/moderate OHSS may include abdominal distention/discomfort, diarrhea,
nausea, and/or vomiting. Severe OHSS symptoms may include severe abdominal
pain, anuria/oliguria, ascites, severe dyspnea, hypotension, or nausea/vomiting
(intractable). Decreased creatinine clearance, hemoconcentration,
hypoproteinemia, elevated liver enzymes, elevated WBC, and electrolyte
imbalances may also be present (ASRM 2016; Corbett 2014; Fiedler 2012). Treatment
is primarily symptomatic and includes fluid and electrolyte management,
analgesics, and prevention of thromboembolic complications (ASRM 2016;
SOGC-CFAS 2011). Therapy with gonadotropins should be stopped.
• Pituitary
apoplexy: Rare cases of pituitary apoplexy (frequently secondary to pituitary
adenoma) have been observed with GnRH agonist administration (onset from 1 hour
to usually <2 weeks); may present as sudden headache, vomiting, visual or
mental status changes, and infrequently cardiovascular collapse; immediate
medical attention required.
• Psychiatric
effects: Symptoms of emotional lability (eg, crying, irritability, anger,
aggression, impatience) have been reported with GnRH agonists, including
triptorelin; monitor for the development or worsening of psychiatric symptoms.
• Seizures:
Seizures have been reported with GnRH agonists, including triptorelin in
patients with or without a history of seizures or other conditions or
concurrent medications associated with seizures.
• Spinal cord
compression: Cases of spinal cord compression, which may contribute to weakness
or paralysis (possible fatal complications), have been reported; observe
patients with metastatic vertebral lesions closely during the first few weeks
of treatment.
• Symptom flare:
Transient initial increases in gonadotropins and sex steroids leading to a
worsening of symptoms may be observed during the first few weeks of therapy or
after subsequent doses. Patients with prostate cancer may experience new or
increased bone pain, neuropathy, hematuria, or urethral or bladder outlet
obstruction. Female patients with central precocious puberty may experience
transient vaginal bleeding.
Disease-related
concerns:
• Urinary tract
obstruction: Observe patients with urinary tract obstruction closely during the
first few weeks of treatment.
Monitoring
Parameters
Glucose and HbA1c (periodically),
signs and symptoms of emerging cardiovascular disease; consider periodic
monitoring of electrocardiograms and electrolytes in at-risk patients;
development/worsening of psychiatric symptoms.
Additional
monitoring (per indication):
Treatment of
precocious puberty: Monitor response to therapy with LH levels after a GnRH or
GnRH agonist stimulation test, basal LH, or serum sex steroid levels beginning
1 to 2 months after initiation of therapy, during therapy, and with each
subsequent dose; height every 3 to 6 months; bone age (periodically)
Treatment of
prostate cancer: Serum testosterone levels, prostate-specific antigen; bone
density.
Assisted
reproductive technologies: Decapeptyl [Canadian product]: Negative pregnancy
test prior to initiation of therapy; signs/symptoms of allergic reaction for 30
minutes after administration; ultrasound and/or estradiol levels to assess
follicle development; ultrasound to assess number and size of follicles
OHSS: Monitoring
of hospitalized patients should include abdominal circumference, albumin,
cardiorespiratory status, electrolytes, fluid balance, hematocrit, hemoglobin,
serum creatinine, urine output, urine specific gravity, vital signs, weight
(daily or as necessary) and liver enzymes (weekly) (SOGC-CFAS 2011).
Treatment of
paraphilia/hypersexuality (off-label use): The following monitoring has been
recommended for other GnRH agonists: CBC (baseline, monthly for 4 months then
every 6 months); serum testosterone (baseline, monthly for 4 months then every
6 months); serum LH (baseline and every 6 months), FSH (baseline), serum BUN
and creatinine (baseline and every 6 months); bone density (baseline and
yearly); ECG (baseline) (Reilly 2000)
Pregnancy Risk
Factor
X
Pregnancy
Considerations
Use is
contraindicated in pregnant women. When used for ART, pregnancy must be ruled
out prior to therapy and nonhormonal contraception should be used until menses
occurs. Due to the short half-life of triptorelin (formulations used for ART),
it is not expected to be present in the maternal serum at the time of embryo
transfer. In case reports, spontaneous abortion, congenital anomalies, and
other adverse events have been reported following triptorelin (Decapeptyl
[Canadian product]) exposure during pregnancy.
Patient
Education
• Discuss
specific use of drug and side effects with patient as it relates to treatment.
(HCAHPS: During this hospital stay, were you given any medicine that you had
not taken before? Before giving you any new medicine, how often did hospital
staff tell you what the medicine was for? How often did hospital staff describe
possible side effects in a way you could understand?)
• Patient may
experience sexual dysfunction, hot flashes, or insomnia. Have patient report
immediately to prescriber signs of pituitary apoplexy (sudden headache,
vomiting, passing out, mood changes, eye weakness, unable to move eyes, or
vision changes), signs of high blood sugar (confusion, fatigue, increased
thirst, increased hunger, polyuria, flushing, fast breathing, or breath that
smells like fruit), signs of a urinary tract infection (hematuria, burning or
painful urination, polyuria, fever, lower abdominal pain, or pelvic pain),
signs of severe cerebrovascular disease (change in strength on one side is
greater than the other, difficulty speaking or thinking, change in balance, or
vision changes), angina, shortness of breath, excessive weight gain, swelling
of arms or legs, difficult urination, severe headache, severe dizziness,
passing out, vision changes, back pain, hematuria, breast pain, burning or
numbness feeling, tachycardia, abnormal heartbeat, chills, pharyngitis,
behavioral changes, mood changes, severe muscle pain, severe joint pain, severe
loss of strength and energy, or bone pain (HCAHPS).
• Educate
patient about signs of a significant reaction (eg, wheezing; chest tightness;
fever; itching; bad cough; blue skin color; seizures; or swelling of face,
lips, tongue, or throat). Note: This is not a comprehensive
list of all side effects. Patient should consult prescriber for additional
questions.
Intended Use and
Disclaimer: Should not be printed and given to patients. This information is
intended to serve as a concise initial reference for health care professionals
to use when discussing medications with a patient. You must ultimately rely on
your own discretion, experience, and judgment in diagnosing, treating, and
advising patients.
