Histrelin - Indications, Contraindications, Warnings, and Precautions

Overview

Histrelin is a widely advised treatment strategy to tackle the manifestations and progression of prostate cancer. It falls under the category of gonadotropin-releasing hormone agonist. It is a laboratory-made hormone-like medicine that hampers the normal production of certain bodily hormones. Food and Drug Administration, the drug regulatory body in the United States, authorizes the use of Histrelin implants for symptomatic prostate cancer cases in October 2004. Unlike other medicine, it is made available in the body by placing it under the skin.

How Does Histrelin Work?

Histrelin checks the extension and ballooning of the cancerous mass associated with the prostate gland. In prostate cancer, the cancerous cells present in the prostate gland are in constant need of a male hormone, medically known by the name testosterone, for development and multiplication. Histrelin works by interfering with the availability of the male hormone for the cancer cells by hampering its production in the body. As a result of the lack of required hormonal support, the cancerous cells undergo regression in growth and eventually die out. In this way, Histrelin works to restrict the further extension of cancer and its associated symptoms.

Available Doses and Dosage Forms:

Contrary to other medicines, which are administered orally or via a vein, Histrelin is employed in implant form.

• Dosage Forms: Histrelin is marketed in implant form, which is advised to be embedded within the skin layers. The placement of the implant is routinely done on the non-dominant hand of the person.

• Available Doses: Each implant encompasses 50 milligrams (mg) of the Histrelin acetate compound, which is capable of releasing 41 mg of Histrelin through the lifetime of an implant. 50 micrograms of Histrelin is liberated from the implant daily for up to a period of one year. After the stipulated time frame, the Histrelin gets exhausted, and the implant needs to be replaced with a new one.

Warnings and Precautions:

• Immediate Worsening of Manifestations: Following the initiation of treatment, particularly in the initial days, the person may experience a magnification of the symptoms. At times, the person may elicit advanced manifestations like bone and joint pain and trouble passing urine. It is due to treatment-induced sudden fluctuations in the testosterone level. However, these manifestations are transient and settle once the treatment process is on track.

• Yearly Replacement of Implant: As the implant is functional only for one year period, it needs to be taken out. During the removal, sometimes there will be challenges in identifying the exact spot.

• Blockage in the Urinary Tract: Being a gonadotropin-releasing hormone agonist, it is capable of precipitating blockages in the urinary tract. Hindered urinary flow creates a burden on kidney functions and induces considerable impairments.

• Compression of the Spinal Cord: Histrelin is known to create compressive pressure over the spinal cord, which entails immediate medical attention. If not attended promptly, it may progress into further complications like paralysis (inability to control the affected part).

• Sugar Level Elevation: Histrelin is reported to interrupt the processing of sugar in the body and thus accelerate the blood sugar level. Thereby potentially raising the probability of developing diabetes (pronounced blood sugar level). In addition, it also hampers the sugar level of diabetic patients, thus necessitating the dose alteration of diabetic medicines.

• Heart Diseases: The therapy using Histrelin increases the likelihood of developing various complications, like cardiac arrest (the heart stops its functions), strokes (hampered blood flow to the brain), and blocked blood vessels in the heart.

For Patients:

What Is Prostate Cancer?

Cancer is quite a familiar and alarming disease condition that can arise in any part of the body. When it develops in association with the prostate gland, it is medically coined as prostate cancer. These glands are specifically present in an anatomically male body and release seminal fluid, which enhances the movement of sperm. When the cells that form the prostate gland exhibit cancerous changes, the affected person notices certain symptoms like compromised urinary flow, difficulty in passing urine, presence of blood streaks in the semen and urine. As the disease progresses, further manifestations in the form of abrupt weight loss, general weakness, and bone pain do develop. Though it is a malignant (dangerous) condition, a timely diagnosis aids in prompt recovery. It offers an average survival rate of ten years and is mostly encountered in men above the 50 years of age category. An in-depth analysis of the medical history, clinical findings, rectal examination, and blood test to identify specific antigens helps in figuring out the cancerous condition.

When and Why Is Histrelin Prescribed?

Prostate cancer poses diverse manifestations in the affected patients. These manifestations considerably impact the life of a person, and that is why Histrelin is advised. It alleviates and calms down the symptoms. Histrelin effectively controls the progesterone hormone level and thereby makes the cancer cells starve, which in turn negatively impacts the cancer progression. However, it is not a curative therapy and is incapable of completely settling the cancer.

Things to Inform the Doctor Before Taking Histrelin:

Before placing Histrelin implants, one should ensure that the concerned doctor is aware of certain important patient details. Some of the relevant information to be shared with the doctor include the following:

• In case the patient is having a previous experience of hypersensitivity towards Histrelin or related medicine, it should be priorly discussed with the doctor to prevent exacerbation of allergic reaction. Since the implant placement procedure involves the use of anesthetic agents (which makes the area numb), allergies to these agents can also evoke undesirable reactions during the implant placement.

• The entire medical history of the patient including past disease conditions, should be communicated with the concerned doctors. Histrelin is reported to induce certain heart-related diseases and hindrance to urine flow. Hence patients who are already suffering from such conditions are to be treated with Histrelin cautiously.

• All the details of medication, be it Ayurveda, allopathy, herbal, or dietary supplements, should be conveyed to the doctor before placing Histrelin implants. In case the patient consumes any medicine while the Histrelin implant is on, it can influence the action of either the medication or both. At times, it may entail modification of the dose to counterbalance the drug-drug interaction.

• If the patient is trying to conceive, the doctor should be made aware of it, because Histrelin is not reported to be safe during the initial phases of pregnancy. Similarly, breastfeeding women should inform of the status to make sure that no harm is induced to the child while the Histrelin implant is on.

Things to Consider While Undergoing Histrelin Therapy:

• Severe trouble in passing urine after the onset of Histrelin therapy should be reported to the doctor at the earliest to prevent remarkable impacts on kidney functions.

• Sudden allergic reactions following the Histrelin implant placement necessitate immediate medical attention. Hence it should be promptly reported to the doctor.

• In case the patient conceives while on Histrelin therapy, reach out to the doctor at the earliest to consider the risk for the developing child in the womb.

• Sudden precipitation of chest pain and loss of consciousness on Histrelin treatment reflect heart issues, and the patients should be aware of the complications of the therapy.

What Are the Instructions to Be Followed While on Histrelin?

• Patients are instructed to keep an eye on the site where the Histrelin implant is placed. Though the implant is surgically embedded within the skin layers, at times, the implant may get exposed and thrown out. In such instances, the patient should inform the doctor regarding the eviction of the implant.

• Female patients of reproductive age are advised about the risk of pregnancy with Histrelin and are instructed to have effective birth control measures to check unplanned conception.

What Are the Possible Side Effects of Histrelin?

Histrelin implant is known to cause numerous side effects. Some of the routinely encountered side effects of Histrelin include the following:

• Skin reactions in the form of redness, soreness, stinging, rashes, and scar formation over the skin surface at the site of Histrelin implant placement.

• The person experiences sudden heat waves (enhanced body temperature) and occasionally gets drenched with sweat.

• Behavioral changes like restlessness, loss of temper, sudden emotional outbursts, mood swings, and aggression are also reported with Histrelin therapy.

• Constant fatigue, loss of interest in sex, troubled sleeping, strange increase in body weight, depletion of testicular size, and severe headache are some of the potentially troubling side effects.

• Vaginal bleeding in the form of spotting is occasionally noticed in female patients following Histrelin therapy; on the other hand, men are reported to have swollen feet.

• Seizures, strained breathing, the presence of streaks of blood in the urine, severe bone pain, stomach pain, yellow skin, slurred speech, and inability to pass urine are some of the grave side effects that demand immediate medical assistance.

What Should Be Done if a Dose Is Missed?

As Histrelin is embedded in the skin, there is less chance of missing the dose. However, it does develop in two specific instances; when the implant is thrown out of the body from the site of placement or when the patient fails to replace the implant once its action period of one year is over. In such cases, the medicine dose will be missed. So patients are instructed to keep track of the implant replacement appointments. Similarly, patients should report to the concerned doctor in case the implant gets expelled by itself from the body.

How to Treat Histrelin Overdose?

The probability of developing a Histrelin overdose is quite less as it is placed in the form of an implant with a specific Histrelin release rate. However, the placement of more implants can precipitate overdose issues in the body, which require prompt treatment at the very right time.

For Doctors:

Indications:

• Prostate cancer (advanced stage).

Contraindications:

• Histrelin implant should never be placed in a person who had exaggerated reactions toward gonadotropin-releasing hormone (GnRH) agonists and their analogs.

• Histrelin influences the hormone level and induces alterations. Hence it is strictly contraindicated during pregnancy. Unwanted shifts in the hormone level can precipitate considerable harm to fetal development and can even induce abortions.

Histrelin Implant Placement:

• Histrelin implant placement, as well as removal, are done surgically, and it requires specific tools. It is carried out under local anesthesia. Implant placement is done using an insertion tool that is made available along with the Histrelin implant kit. The kit should be kept under a temperature of two to eight degree Celsius. Approximately one week before the placement procedure, the kit should be taken out without opening its seal and is instructed to be kept at a room temperature of 20 to 25 degree Celsius.

• The non-dominant hand of the patient should be chosen for implant placement. The patient should be positioned appropriately so that the doctor should get adequate visibility and accessibility to the site.

• Ideally, the implant is placed midway between the elbow joint and the shoulder towards the inner aspect. The placement is subcutaneous without unwanted deep penetration.

• The insertion tool has got a specific cannula into which the implant can be loaded. Utmost care should be taken while handling the implant, and sterility of the implant should be promptly maintained to check microbial infection in the surgical site.

• The implant placement is facilitated by creating an incision at the placement site. Once the implant gets into its position, the incision has to be closed with surgical strips or sutures.

• Patients should be given accurate instructions to keep the surgical site healthy and clean.

What Are the Pharmacological Aspects of Histrelin?

Mechanism of Action:

Histrelin works as a gonadotropin-releasing hormone agonist and thereby checks the secretion of gonadotropin hormones. Histrelin acetate, when administered for over a significant period, impairs the activity of pituitary gonadotropin and eventually results in collapsed testosterone production and secretion. Histrelin is employed as a hormonal therapy for cancer involving the prostate gland. Prostate cancer cells are reported to be dependent on the testosterone hormone for their growth and advancement. Therefore, collapsed testosterone levels can have a direct impact on prostate cancer advancement. Histrelin works by holding back the testosterone availability to the cancer cells, which forces the cancer cells to starve and regress.

Pharmacodynamics:

Histrelin alters the hormone profile in the human body. It precipitates an initial transient upsurge in the level of follicle-stimulating hormone (FSH), testosterone, and luteinizing hormone (LH). However, in two to four weeks of the treatment, the upsurge declines and brings about a remarkable collapse in the FSH, testosterone, and LH level.

Pharmacokinetics:

• Absorption: Once the Histrelin implant is embedded subcutaneously, it slowly gets absorbed into the bloodstream and the utmost Histrelin level is attained after 12 hours. As the Histrelin is implanted in the body, there will be a sustained release of the medicine during the one-year life of the Histrelin implant.

• Distribution: Once Histrelin reaches the bloodstream, it is then distributed throughout the body by attaching to plasma proteins.

• Metabolism: Unlike other medicinal drugs, Histrelin is chiefly metabolized on a cellular level rather than in the liver. In the tissue, Histrelin metabolism is done by proteases.

• Excretion: There is no relevant data available concerning the removal of Histrelin from the body.

• Drug Interactions: The absence of reliable study reports to figure out the interaction of Histrelin with other drugs makes it difficult to assess the drug-to-drug association and its impacts on the body following Histrelin implant placement.

Warnings and Precautions Before Advising Histrelin Therapy

• Initial Peaking of Testosterone: Immediately after the initiation of Histrelin therapy, typically in the first week, the patient experiences a temporary and short-term rise in the testosterone level. It is manifested in the form of aggravated symptoms like neuropathy, bone pain, hematuria, and urinary obstructions. At times, even new symptoms may start to precipitate during the first week due to testosterone surge.

• Hyperglycemia: Treatment using Histrelinis reported to be a trigger for inducing changes in the glycemic status of the patient. Disturbance in glycemic control eventually precipitates diabetes mellitus. It not only induces the development of diabetes, but it also worsens the blood sugar level in patients with pre-existing diabetes mellitus.

• Compression of the Spinal Cord: Certain studies have reported that administration of gonadotropin-releasing hormone agonists can give rise to compression of the spinal cord and may eventually end up in paralysis.

• Obstructed Urinary Tract: In addition to compression of the spinal cord, gonadotropin-releasing hormone can also bring in obstructions in the urine flow and hampers renal functions.

• Periodic Monitoring: Prostate-specific antigens and testosterone concentrations in the blood should be tracked periodically throughout the treatment period.

• Cardiovascular Diseases: Persistent administration of Histrelin critically influences heart functions and may give rise to potentially life-threatening cardiac events like stroke, myocardial infarctions, and cardiac arrest.

Other Specifications:

Histrelin During Pregnancy:

Histrelin is potentially toxic during pregnancy and can even bring about spontaneous abortion. Animal studies have precipitated developmental abnormalities in the fetus upon maternal administration. In addition, low birth weights and stillbirth are also reported in animal studies.

Histrelin During Breastfeeding:

There is no sufficient data available concerning the impact of Histrelin on the breastfed child. However, the administration of Histrelin in a lactating mother is made by considering the maternal need for the medicine and the anticipated adverse effect on the breastfed child.