Zoladex

Indications

• Locally advanced prostate cancer
• Metastatic prostate cancer
• Adjuvant treatment to radiotherapy in prostate cancer
• Neoadjuvant treatment prior to radiotherapy in high-risk prostate cancer
• Advanced breast cancer
• Oestrogen-receptor-positive early breast cancer
• Endometriosis
• Uterine fibroids

Dosage

Children: Paediatric dosing information should be referred to in the BNF for Children as specific doses are not

Adults: For adults, the standard dosage is 3.6 mg administered subcutaneously every 28 days.

Mechanism of action

Goserelin acts as a potent inhibitor of pituitary gonadotropin secretion when administered. It initially stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), but with chronic administration, it leads to down-regulation of gonadotropin-releasing hormone receptors. This results in sustained suppression of LH and serum testosterone levels, ultimately causing regression of hormone-sensitive tissues.

Pharmacodynamics

Upon administration, goserelin causes an initial increase in serum LH and FSH levels, which is followed by a sustained decrease in gonadotropins and serum testosterone levels. This pharmacodynamic effect effectively mimics surgical castration, as testosterone levels can fall to castrate levels approximately 21 days after the initiation of therapy. Studies have shown that goserelin can lead to the regression of hormone-sensitive tumors.

Pharmacokinetics

Goserelin is administered as a subcutaneous depot formulation, with pharmacokinetics evaluated in both male and female healthy volunteers. Following a single or multiple doses, goserelin reaches peak serum concentrations, and its effects on gonadotropin suppression are maintained over the duration of therapy. The drug exhibits a sustained release profile, contributing to its effectiveness in long-term treatment settings.

Contra-indications

• Hypersensitivity to goserelin or any of its components
• Pregnancy
• Breastfeeding
• Unhealed lesions from dental or oral surgery

Adverse effects

• Abdominal discomfort
• Altered smell sensation
• Alopecia
• Anxiety
• Appetite change
• Constipation
• Diarrhoea
• Dizziness
• Drowsiness
• Dry eye
• Dysuria
• Fatigue
• Feeling of pressure behind the eyes
• Hypercalcaemia (on discontinuation)
• Increased risk of fracture
• Menopausal symptoms
• Muscle weakness
• Nausea
• Oedema
• Palpitations
• Sexual dysfunction
• Skin reactions
• Vision disorders
• Vomiting
• Weight changes
• QT interval prolongation
• Hyperhidrosis
• Memory loss
• Embolism and thrombosis
• Second primary malignancy
• Osteonecrosis of the jaw
• Atypical femur fracture

Precautions

• Caution in patients with a history of pituitary tumors
• Monitor for symptoms of hypercalcaemia
• Ensure effective non-hormonal contraception during treatment
• Consider temporary interruption of treatment in cases of osteonecrosis of the jaw

Pregnancy

Avoid in pregnancy. Pregnancy should be excluded before treatment initiation.

Breast-feeding

Avoid during breastfeeding.

Storage

Store in a refrigerator (2 to 8 degrees Celsius). Protect from light.

Formulations

• Goserelin acetate 3.6 mg depot injection (Zoladex®)

Indications

• Infections (topical treatment)
• Wound care (as an antiseptic)
• Ear infections (as an ear drop solution)
• Acid-base balance in metabolic acidosis

Dosage

Children: Refer to established guidelines as dosage may vary based on the formulation and indication.

Adults: Refer to established guidelines as dosage may vary based on the formulation and indication.

Mechanism of action

Acetic acid exerts its effects primarily through its ability to lower pH levels, creating an acidic environment which is inhospitable to many pathogens. It can disrupt the integrity of microbial cell membranes, leading to cell lysis and death. Additionally, acetic acid can promote the healing of wounds and enhance the absorption of certain medications when used as a solvent.

Pharmacodynamics

The pharmacodynamics of acetic acid involve its interaction with biological systems, leading to changes in cellular functions. Its acidic nature helps in the denaturation of proteins and disruption of microbial metabolism. This contributes to its antibacterial and antifungal activities, making it effective against a range of pathogens.

Pharmacokinetics

Acetic acid is rapidly absorbed in the gastrointestinal tract when ingested. It is metabolized primarily in the liver, converting to acetyl CoA and subsequently entering various metabolic pathways including the citric acid cycle. The elimination half-life varies but is generally short, with excretion occurring mainly via urine. When applied topically, absorption is minimal, and local effects are predominant.

Pregnancy

The safety of acetic acid during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

There is no specific information available regarding the use of acetic acid during breastfeeding. Caution is advised.

Storage

Store in a cool, dry place away from direct sunlight. Keep tightly closed in a well-ventilated area.

Indications

• Topical treatment of localized infections
• Antiseptic for skin and mucous membrane applications
• Astringent in certain dermatological conditions

Dosage

Children: Refer to professional resources for specific dosing information, as it can vary based on formulation and condition treated.

Adults: Refer to professional resources for specific dosing information, as it can vary based on formulation and condition treated.

Mechanism of action

Glacial acetic acid exerts its effects primarily through its acidic properties, leading to protein denaturation and cell lysis in microbial cells. This action disrupts cellular integrity, promoting the death of bacteria and fungi. Additionally, it can alter the pH of tissues, which may contribute to its antiseptic effects.

Pharmacodynamics

The pharmacodynamic effects of glacial acetic acid are largely attributed to its ability to lower the pH in the local environment, which can inhibit the growth of certain pathogens. Its astringent properties help to reduce secretions and promote tissue contraction, which can be beneficial in managing conditions that involve inflammation or excessive exudation.

Pharmacokinetics

Glacial acetic acid is absorbed through the skin and mucous membranes when applied topically. Once absorbed, it can be metabolized by the liver, with elimination primarily occurring through urine. The exact pharmacokinetic parameters can vary based on the route of administration and the formulation used, but detailed data on half-life and volume of distribution are not well-characterized in standard references.

Pregnancy

Glacial acetic acid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is classified as a category C drug.

Breast-feeding

It is not known whether glacial acetic acid is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a tightly closed container, in a cool, dry place away from incompatible substances.

Indications

• Heart failure
• Atrial fibrillation
• Atrial flutter
• Supraventricular tachycardia

Dosage

Children: Refer to the BNF for Children for appropriate dosing information, as paediatric doses are based on weight and specific clinical circumstances.

Adults: Refer to specific guidelines for dosing, as it varies based on indication, renal function, and patient characteristics. Regular monitoring of serum levels is essential.

Mechanism of action

Glycosides, particularly cardiac glycosides like digoxin, primarily exert their effects by inhibiting the Na+/K+ ATPase pump in cardiac myocytes. This inhibition leads to an increase in intracellular sodium, which in turn promotes calcium influx via the sodium-calcium exchanger, enhancing cardiac contractility (positive inotropic effect). Additionally, glycosides can have effects on the autonomic nervous system, increasing vagal tone and decreasing heart rate.

Pharmacodynamics

The pharmacodynamic effects of glycosides include increased force of myocardial contraction, decreased heart rate, and improved efficiency of the heart's pumping ability. These effects are particularly beneficial in heart failure and certain types of arrhythmias. The therapeutic window for glycosides is narrow, making monitoring of serum levels important to avoid toxicity.

Pharmacokinetics

Glycosides are typically well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 3 hours after oral administration. They are extensively distributed in body tissues, particularly in the heart, liver, and kidneys. Glycosides are metabolized by the liver, and their elimination half-lives can vary, necessitating individualized dosing. Renal function significantly impacts the clearance of glycosides, requiring dose adjustments in patients with renal impairment.

Contra-indications

• Hypersensitivity to glycosides
• Ventricular fibrillation
• Certain types of heart block
• Severe renal impairment

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Arrhythmias
• Visual disturbances (e.g., yellow-green halos)
• Fatigue
• Dizziness

Interactions

• Diuretics (may increase the risk of hypokalemia)
• ACE inhibitors (can increase the risk of hyperkalemia)
• Antacids (may reduce absorption of glycosides)
• Calcium channel blockers (may increase the risk of bradycardia)
• Beta-blockers (may enhance cardiac effects)

Precautions

• Use with caution in patients with renal dysfunction
• Monitor serum electrolytes, particularly potassium levels
• Regularly assess cardiac function
• Be cautious in the elderly or those with pre-existing heart conditions

Pregnancy

Glycosides should be used in pregnancy only if clearly needed, as they may have adverse effects on the fetus.

Breast-feeding

Glycosides are excreted in breast milk; caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Oral tablets
• Oral solution
• Injectable forms

Dosage

Children: Lactide is not used in pediatric medicine, and therefore, no dosing information is available.

Adults: Lactide is not administered as a medication, and therefore, no dosing information is available.

Mechanism of action

Lactide undergoes polymerization to form polylactic acid, which is a biodegradable polymer. The process involves the opening of the lactide ring, leading to the formation of long chains of lactic acid units. This polymerization is facilitated by heat, catalysts, or enzymes, resulting in materials that degrade in the body over time, which can be advantageous for drug delivery and tissue engineering applications.

Pharmacodynamics

The pharmacodynamics of lactide is primarily related to its role in the formation of polylactic acid. PLA exhibits properties such as biocompatibility and biodegradability, which are crucial for applications in drug delivery and tissue scaffolding. The degradation of PLA occurs via hydrolysis, resulting in lactic acid, which is a naturally occurring substance in the body, thus minimizing potential adverse effects.

Pharmacokinetics

As lactide is not used therapeutically as a drug, traditional pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion do not apply. However, when lactide is polymerized to form PLA, the degradation products (lactic acid) are metabolized in the body through the Krebs cycle, with excretion occurring primarily via urine.

Pregnancy

There is limited data on the use of lactide in pregnancy. Caution is advised.

Breast-feeding

Lactide should be used with caution during breastfeeding due to insufficient data on excretion in human milk.

Storage

Store in a cool, dry place, protected from light.

Mechanism of action

Goserelin is a synthetic decapeptide analogue of LHRH. Goserelin acts as a potent inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. The result is sustained suppression of LH and serum testosterone levels. Zoladex is a synthetic decapeptide analogue of LHRH. Zoladex acts as a potent inhibitor of pituitary gonadotropin secretion when administered in the biodegradable formulation. Following initial administration, ZOLADEX causes an initial increase in serum-luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels with subsequent increases in serum levels of testosterone. Chronic administration of Zoladex leads to sustained suppression of pituitary gonadotropins, and serum levels of testosterone consequently fall into the range normally seen in surgically castrated men approximately 21 days after initiation of therapy. This leads to accessory sex organ regression. In animal and in in vitro studies, administration of goserelin resulted in the regression or inhibition of growth of the hormonally sensitive dimethylbenzanthracene (DMBA)-induced rat mammary tumor and Dunning R3327 prostate tumor. In clinical trials using Zoladex 3.6 mg with follow-up of more than 2 years, suppression of serum testosterone to castrate levels has been maintained for the duration of therapy.

Pharmacodynamics

The pharmacokinetics of goserelin have been determined in both male and female healthy volunteers and patients. In these studies, goserelin was administered as a single 250µg (aqueous solution) dose and as a single or multiple 3.6 mg depot dose by subcutaneous route.