Histrelin is a synthetic form of gonadotropin-releasing hormone (GnRH), a hormone that regulates the release of other hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary gland. These hormones play a crucial role in the regulation of reproductive function.

Histrelin is primarily used in medicine as a therapeutic agent in the treatment of certain conditions. One common medical application of histrelin is in the management of central precocious puberty (CPP) in children. Central precocious puberty is a condition in which puberty begins earlier than normal, and histrelin can help delay the onset of puberty by suppressing the release of LH and FSH.

Histrelin is available in various formulations, including implants and injections. The implant forms of histrelin are typically placed under the skin, where they slowly release the medication over an extended period. This sustained release helps maintain a consistent therapeutic effect.

A GnRH analog called histrelin (Supprelin LA, Vantas) works on the anterior pituitary's gonadotropin-releasing cells to prevent the release of LH and FSH. It is recommended for the treatment of advanced prostatic cancer and premature puberty.

Histrelin Uses:

• Central precocious puberty (Supprelin LA):
  • It is used to treat central precocious puberty in children.
• Advanced prostate cancer (Vantas):
  • It is indicated as a palliative treatment of advanced prostate cancer

Histrelin (Vantas) Dose in Adults

Histrelin (Vantas) Dose in the treatment of advanced Prostate cancer:

• Histrelin is a medicine used to treat advanced prostate cancer.
• The specific form of histrelin called Vantas is given through a small implant inserted under the skin. This implant has 50 milligrams of histrelin.
• The implant is placed through a surgical procedure, and it only needs to be done once a year (every 12 months).
• This helps in managing the progression of advanced prostate cancer over time.

Histrelin (Vantas) Dose in Children

Histrelin (Supprelin LA, Vantas) Dose in the treatment of central precocious puberty:

Histrelin is also used to treat a condition called central precocious puberty in children aged 2 years and older.

• For this purpose, a specific form called Supprelin LA is used.
• It comes in the form of a 50-milligram implant that is inserted under the skin through a surgical procedure.
• This implant is placed every 12 months, and the treatment is typically stopped when it's deemed appropriate for the normal onset of puberty.
• The implant helps delay the onset of puberty by regulating certain hormones.

Pregnancy Risk Factor X

• Histrelin should not be used if a person is pregnant or might become pregnant.
• Studies in animals showed problems during pregnancy when histrelin was used.
• If histrelin is taken during pregnancy, it could harm the baby or lead to a spontaneous abortion (miscarriage).

Histrelin use during breastfeeding:

• It's unclear whether histrelin is found in breast milk.
• Additionally, these products are not meant for use in women who have already gone through puberty.

Dose in Kidney disease:

• For the medication Vantas, if your kidney function (measured as creatinine clearance or CrCl) is equal to or greater than 15 mL/minute, there's no need to change the dosage.
• For Supprelin LA, the manufacturer's instructions do not mention any specific dosage adjustments. This means that the standard dosage recommendations apply, and there is no need to change the dose based on kidney function.

Dose in Liver disease:

• The manufacturer's instructions do not include any adjustments to the dosage for individuals with liver problems.
• The use of the medication in people with liver impairment has not been studied or specified in the labeling.

Common Side Effects of Histrelin (Supprelin LA, Vantas):

• Dermatologic:
  • Dermatological Reaction

Less Common Side Effects Of Histrelin (Supprelin LA, Vantas):

• Central Nervous System:
  • Emotional Lability
  • Headache
  • Migraine
  • Sensation Of Cold
• Dermatologic:
  • Scarring
  • Pruritus
• Endocrine & Metabolic:
  • Gynecomastia
  • Hypermenorrhea
  • Weight Gain
• Genitourinary:
  • Uterine Hemorrhage
  • Breast Tenderness
  • Dysmenorrhea
  • Precocious Puberty
• Hematologic & Oncologic:
  • Pituitary Neoplasm
• Infection:
  • Localized Infection
• Local:
  • Application Site Pain
• Neuromuscular & Skeletal:
  • Keloid-Like Scar
• Respiratory:
  • Epistaxis
  • Flu-Like Symptoms
• Miscellaneous:
  • Procedural Complications
  • Postoperative Pain

Frequency of Side effects Not Defined:

• Endocrine & Metabolic:
  • Altered Hormone Levels

Prostate Cancer:

Common Side Effects Of Histrelin (Supprelin LA, Vantas):

• Dermatologic:
  • Dermatological Reaction
• Endocrine & Metabolic:
  • Hot Flash

Less Common Side Effects Of Histrelin (Supprelin LA, Vantas):

• Cardiovascular:
  • Flushing
  • Palpitations
  • Peripheral Edema
  • Ventricular Premature Contractions
• Central Nervous System:
  • Fatigue
  • Headache
  • Insomnia
  • Depression
  • Dizziness
  • Irritability
  • Lethargy
  • Malaise
  • Pain
  • Sensation Of Cold
• Dermatologic:
  • Diaphoresis
  • Genital Pruritus
  • Hypotrichosis
  • Night Sweats
  • Pruritus
• Endocrine & Metabolic:
  • Gynecomastia
  • Decreased Libido
  • Weight Gain
  • Fluid Retention
  • Hypercalcemia
  • Hypercholesterolemia
  • Increased Lactate Dehydrogenase
  • Increased Prostatic Acid Phosphatase
  • Increased Serum Glucose
  • Weight Loss
• Gastrointestinal:
  • Constipation
  • Abdominal Distress
  • Food Cravings
  • Increased Appetite
  • Nausea
• Genitourinary:
  • Testicular Atrophy
  • Erectile Dysfunction
  • Breast Tenderness
  • Dysuria
  • Exacerbation Of Gynecomastia
  • Exacerbation Of Hematuria
  • Exacerbation Of Urinary Frequency
  • Hematuria
  • Mastalgia
  • Urinary Frequency
  • Urinary Retention
• Hematologic & Oncologic:
  • Anemia
  • Bruise
  • Hematoma
• Hepatic:
  • Hepatic Disease
  • Increased Serum AST
• Local:
  • Bruising At Injection Site
  • Pain At Injection Site
  • Tenderness At Injection Site
  • Erythema At Injection Site
  • Inflammation At Injection Site
  • Injection Site Infection
• Neuromuscular & Skeletal:
  • Arthralgia
  • Back Pain
  • Exacerbation Of Back Pain
  • Limb Pain
  • Muscle Twitching
  • Myalgia
  • Neck Pain
  • Ostealgia
  • Tremor
  • Weakness
• Renal:
  • Renal Insufficiency
  • Decreased Creatinine Clearance
  • Exacerbation Of Renal Failure
  • Nephrolithiasis
• Respiratory:
  • Dyspnea On Exertion
• Miscellaneous:
  • Stent Occlusion

Contraindications to Histrelin (Supprelin LA, Vantas):

• Histrelin should not be used in individuals who have a known allergy or strong sensitivity to histrelin acetate, gonadotropin-releasing hormone (GnRH), GnRH-agonist analogs, or any ingredient in the medication.
• Additionally, it should be avoided in females who are currently pregnant or might become pregnant.

Warnings and precautions

Cardiovascular effects

• Using androgen-deprivation therapy (ADT) might increase the chances of having heart problems.
• There's a reported higher risk of heart attack, sudden cardiac death, and stroke with the use of certain medications called GnRH agonists in men, so it's important to watch out for signs of heart issues.
• ADT can also affect the time it takes for the heart to recharge between beats (QT/QTc interval), especially in individuals with a history of certain heart conditions or those taking medications that can affect the heart rhythm.

Hyperglycemia:

• Using androgen deprivation therapy (ADT) for prostate cancer can lead to high blood sugar levels, a condition known as hyperglycemia.
• This might result in the development of diabetes or make existing diabetes worse.
• It's important for individuals undergoing this therapy to keep an eye on their blood glucose levels and, if applicable, their HbA1c levels (a measure of long-term blood sugar control).
• Regular monitoring can help manage any changes in blood sugar and allow for timely intervention if needed.

Pituitary apoplexy

• There have been rare cases of a condition called pituitary apoplexy associated with the use of GnRH agonists.
• This condition often happens as a result of a pituitary adenoma (a tumor on the pituitary gland).
• Symptoms can come on suddenly, usually within one hour to less than two weeks after starting the medication.
• Signs of pituitary apoplexy may include a sudden headache, vomiting, changes in vision or mental status, and sometimes a sudden drop in blood pressure.
• If someone experiences these symptoms, it's crucial to seek immediate medical attention.

Psychiatric events

• Use of GnRH agonists like histrelin has been linked to psychiatric events.
• This can include changes in emotions such as mood swings, irritability, impatience, anger, and aggression.
• While these symptoms have been reported after the medication has been used, it's important for individuals taking it to be aware of the possibility of developing or experiencing a worsening of psychiatric symptoms.

Seizures:

• There have been reports of seizures in people using GnRH agonists like histrelin.
• This happened in individuals with a history of seizures, epilepsy, cerebrovascular disorders, or brain tumors.
• Seizures were also reported in people who were taking other medications known to be linked with seizures, such as bupropion and SSRIs. Interestingly, seizures have occurred even in individuals without any pre-existing conditions.

Compression of the spinal cord:

• There have been reports of spinal cord compression in individuals using certain treatments, like those for prostate cancer.
• This condition could potentially lead to paralysis.
• It's important for healthcare providers to closely monitor patients who have metastatic vertebral lesions (abnormalities in the spine due to cancer spreading) for signs like weakness or abnormal sensations in the first few weeks of the therapy.
• This close observation helps detect any potential issues early on and allows for appropriate action to be taken.

Tumor flare:

• When men with prostate cancer start certain treatments, there can be a temporary increase in the levels of testosterone in the blood during the first week.
• This brief rise in testosterone might cause a temporary worsening of symptoms related to the prostate cancer, such as bone pain, neuropathy (nerve damage), blood in the urine, blockage in the urinary tract, or spinal cord compression.

Occlusion of the urinary tract:

• When histrelin is used for prostate cancer, there's a chance that it might lead to a blockage in the tubes (ureters) that carry urine from the kidneys to the bladder.

Worsening symptoms

• When histrelin is used for treating central precocious puberty (CPP) in both girls and boys, there might be a temporary rise in estrogen levels in girls or testosterone levels in both girls and boys during the first week of treatment.
• This could lead to a brief worsening of puberty-related symptoms. However, the signs of puberty should start decreasing within about four weeks of starting the treatment.

Monitoring parameters:

Central Precocious Puberty (CPP):

• Hormone Levels Monitoring:
  • Luteinizing hormone
  • Follicle-stimulating hormone
  • Estradiol (for females) or Testosterone (for males)
  • Initially after 1 month, then every 6 months
• Growth Monitoring:
  • Height
  • Bone age (every 6 to 12 months)
• Puberty Stage Assessment:
  • Tanner staging
• Clinical Manifestations:
  • Monitor for signs of CPP suppression
• Psychiatric Symptoms:
  • Watch for the development or worsening of psychiatric symptoms, including depression

Prostate Cancer:

• Hormone and PSA Levels:
  • Serum testosterone levels
  • Prostate-specific antigen (PSA)
• Bone Health:
  • Bone mineral density
• Observation for Physical Symptoms:
  • Weakness
  • Paresthesias
  • Urinary tract obstruction (especially in the first few weeks of therapy)
• Diabetes Screening:
  • Regular screening for diabetes
• Cardiovascular Monitoring:
  • Monitor for symptoms associated with cardiovascular disease
  • Consider periodic monitoring of electrocardiograms and electrolytes

How to administer Histrelin (Supprelin LA, Vantas)?

Subcutaneous Implantation Procedure:

• Surgical Implantation:
  • Using a sterile field
  • Requires the provided implantation device
• Location:
  • Inner portion of the upper arm
  • Use the patient's nondominant arm
  • Halfway between the shoulder and the elbow
  • At the crease between the tricep and the bicep
• Handling Instructions:
  • Do not bend or pinch the implant
• Duration and Replacement:
  • Implant should remain for approximately 12 months
  • Removal process required
  • Replacement implant may be inserted if therapy continues
• Removal Procedure:
  • Palpate the area of incision to locate the implant
  • If not readily palpated, imaging methods like ultrasound, CT, or MRI may be used
  • Plain films are not recommended as the implant is not radiopaque
• Detailed Instructions:
  • Refer to the manufacturer's labeling for comprehensive insertion and removal details.

Mechanism of action of Histrelin (Supprelin LA, Vantas):

• Histrelin is a powerful inhibitor of hormones that control reproductive functions.
• When given continuously, it initially has a phase where it significantly lowers luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to a decrease in testosterone and dihydrotestosterone in males or estrone and estradiol in premenopausal females.
• For males with prostate cancer, testosterone levels drop to very low levels within 2 to 4 weeks.
• In children with central precocious puberty (CPP), the medication slows down the speed at which they grow, increasing the likelihood that they will reach a height close to what is predicted for adults.

Onset of Action:

• Prostate Cancer:
  • Chemical castration begins within 2 to 4 weeks
• Central Precocious Puberty (CPP):
  • Progression of sexual development stops, and growth decreases within 1 month

Duration:

• 12 months, with a few additional weeks of histrelin release

Distribution:

• Adults:
  • Volume of distribution: ~58.4 L ± 7.86 L

Protein Binding:

• Adults:
  • Approximately 70% ± 9%

Metabolism:

• Hepatic Process:
  • Via C-terminal dealkylation and hydrolysis

Bioavailability:

• Adults:
  • Subcutaneous (SubQ): 92%

Half-life Elimination:

• Adults:
  • Terminal half-life: Approximately 4 hours

Time to Peak, Serum:

• Adults:
  • Peaks in the blood approximately 12 hours after administration

International Brand Names of Histrelin:

• Supprelin LA
• Vantas
• Vantasse
• Vantus

Histrelin Brand Names in Pakistan:

Not available.