Histrelin - Indications, Contraindications, Warnings, and Precautions

Overview

Histrelin is a medicine commonly used to treat prostate cancer in men. It belongs to a group of drugs called gonadotropin-releasing hormone agonists. Histrelin is made in a lab and works by reducing certain hormones in the body, which helps control the growth and symptoms of prostate cancer. The Food and Drug Administration (FDA), the drug regulatory body in the United States (US), authorized the use of Histrelin implants for symptomatic prostate cancer cases in October 2004. Unlike other medicines, it is made available in the body by placing it under the skin.

Drug group:

Gonadotropin-releasing hormone (GnRH) agonist.

For Patients:

How Does Histrelin Work in Prostate Cancer?

Histrelin treats the symptoms of advanced prostate cancer. Prostate cancer cells need testosterone (a male hormone) to grow and multiply. They are basically fueled by it. Histrelin blocks your body's production of testosterone. No testosterone means no fuel for the cancer cells. Without hormonal support, the cancer cells cease to grow. Eventually, they die off. That is how Histrelin keeps cancer from spreading and reduces symptoms. It cuts off what cancer needs to survive.

Available doses and dosage forms:

Unlike other medications, which are administered orally or intravenously, Histrelin is used 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 person's non-dominant hand.

• Available doses: Each implant contains 50 milligrams (mg) of the Histrelin acetate compound, which can release 41 mg of Histrelin over its lifetime. 50 micrograms (mcg) of Histrelin can be liberated from the implant daily for up to one year (12 months). After the stipulated time frame, the Histrelin will be exhausted, and the implant will need to be replaced.

Histrelin: placement and care

Histrelin comes as a small, thin implant that a doctor places under the skin of the upper arm. The doctor will numb the area, make a tiny cut, and insert the implant just under the skin. The cut will be closed with stitches or surgical strips and covered with a bandage. The implant is usually replaced every 12 months to continue treatment. After insertion, keep the area clean and dry for 24 hours and avoid swimming or bathing. Keep the bandage in place for at least 24 hours, and leave the surgical strips in place until they fall off naturally. Avoid heavy lifting, exercise, or bumping the arm for several days after the implant is placed.

What to Tell Your Doctor Before Getting Histrelin?

• Allergies: Inform the doctor if the patient has experienced allergic reactions to Histrelin or similar medications. The implant procedure uses anesthetic agents to numb the area; please mention any allergies to these as well.

• Medical history: Share full medical history. Histrelin can cause heart issues and urinary problems. If a patient already has these conditions, the doctor must be extra cautious.

• All medications: Inform the doctor about everything the patient takes, including prescriptions, Ayurvedic remedies, herbal supplements, and all other substances. Mixing Histrelin with other medications can cause interactions. The doctor might need to adjust doses.

• Pregnancy and breastfeeding: If you are planning to become pregnant, please inform your doctor. Histrelin is not safe during early pregnancy. If the patient is breastfeeding, mention this as well. Breastfeeding women should be notified 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 an impact on kidney function.

• 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 reflects 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 monitor the site where the Histrelin implant is placed. Although the implant is surgically embedded within the skin layers, it may occasionally become exposed and fall out. In such instances, the patient should inform the doctor regarding the removal 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 prevent unplanned conception.

Histrelin implant’s side effects:

• Common side effects: Patients might experience hot flashes, fatigue, or weight gain. Headaches and constipation can occur. Some notice changes in sex drive or performance. At the insertion spot, bruising, soreness, tingling, itching, or scars may develop.

• Serious problems: Severe pain, swelling, or redness at the implant site, difficulty breathing or swallowing, hives or rashes, bone pain, weakness or numbness in limbs, chest pain, urinary problems, unusual bleeding or bruising, extreme exhaustion, yellowing of skin or eyes, depression or suicidal thoughts.

• Long-term risks: The extended use of Histrelin can weaken bones or increase the risk of fractures.

• Other possible effects: Breast enlargement can happen. Testicles might shrink. Mood swings are common.

• For children: Histrelin affects puberty; early puberty signs might temporarily worsen at the beginning of treatment. Any unexpected or persistent problems should be reported to a doctor.

Missing dose:

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 expelled from the body at the site of placement or when the patient fails to replace the implant after its one-year action period has expired. 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 expels itself from the body.

Overdosing: The probability of developing a Histrelin overdose is relatively low, 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 right time.

For Doctors:

Indications:

• Prostate cancer (advanced stage).

Contraindications:

• Histrelin implant should never be placed in a person who has 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 and removal are performed surgically and require specialized tools. It is carried out under local anesthesia. Implant placement is performed using an insertion tool provided with the Histrelin implant kit. The kit should be stored at a temperature of 2 °C to 8 °C. Approximately one week before the placement procedure, the kit should be removed without opening its seal and kept at a room temperature of 20 to 25 degrees Celsius.

• The patient's non-dominant hand should be chosen for implant placement. The patient should be positioned appropriately so that the doctor can 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 a specific cannula into which the implant can be loaded. Utmost care should be taken when handling the implant, and the sterility of the implant should be promptly maintained to prevent microbial infection at 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 maintain a healthy and clean surgical site.

What Are the Pharmacological Aspects of Histrelin?

Histrelin’s mechanism of action:

Histrelin works as a gonadotropin-releasing hormone agonist, thereby inhibiting 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. Thus, low levels of testosterone can have a direct effect on the progression of prostate cancer. Histrelin works by reducing the availability of testosterone to cancer cells, which forces them 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 levels.

Pharmacokinetics:

• Absorption: Once the Histrelin implant is embedded subcutaneously, it slowly gets absorbed into the bloodstream, and the highest Histrelin level is attained after 12 hours. As the Histrelin is implanted in the body, it will sustain a release of the medicine over 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 studies 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:

• 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 exhibit advanced manifestations, such as bone and joint pain and difficulty urinating. 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 the implant: Since the implant has been functional for only one year, it needs to be removed. During removal, there may be challenges in identifying the exact spot.

• 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 a testosterone surge.

• Hyperglycemia: Treatment with Histrelin is reported to be a trigger for inducing changes in the patient's glycemic status. Disturbance in glycemic control eventually leads to the development of diabetes mellitus. It not only causes 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 result in paralysis.

• Obstructed urinary tract: In addition to compression of the spinal cord, gonadotropin-releasing hormone can also cause obstructions in urine flow and impair renal function.

• 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 infarction, 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. Additionally, low birth weights and stillbirths have also been reported in animal studies.

• Histrelin during breastfeeding: There is insufficient 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.