Adpaxil

Indications

• Adjuvant treatment of operable node-positive and node-negative breast cancer
• Treatment of hormone-refractory metastatic prostate cancer
• Initial chemotherapy for metastatic breast cancer
• Treatment of advanced ovarian cancer in combination with cisplatin
• Initial chemotherapy of non-small cell lung cancer with cisplatin
• Treatment of metastatic gastric adenocarcinoma
• Treatment of locally advanced squamous cell carcinoma of the head and neck

Dosage

Children: Refer to the BNF for Children for detailed paediatric dosing guidelines.

Adults: Refer to product literature or local protocols for specific dosing information.

Mechanism of action

Paclitaxel interferes with the normal function of microtubule growth by hyper-stabilizing their structure. It binds to the beta subunit of tubulin, locking the microtubule structure in place and preventing disassembly. This disrupts the dynamic instability necessary for essential cellular functions, including mitosis, and promotes apoptosis in cancer cells by inhibiting the function of the apoptosis regulator Bcl-2.

Pharmacodynamics

Paclitaxel acts as an antineoplastic agent by promoting the assembly of microtubules and preventing their depolymerization. This results in the formation of abnormal microtubule structures and inhibits cellular processes essential for cell division and function. It is indicated for first-line and subsequent therapy in advanced ovarian carcinoma and other malignancies, demonstrating a significant ability to induce programmed cell death in cancer cells.

Pharmacokinetics

Paclitaxel is administered intravenously and exhibits a multi-compartment pharmacokinetic profile. It is extensively metabolized by the liver, primarily through cytochrome P450 enzymes. Its half-life can vary widely due to extensive protein binding and distribution in tissues. The drug's clearance is affected by hepatic function, necessitating monitoring in patients with liver impairment.

Contra-indications

• Severe hypersensitivity to paclitaxel or any excipients
• Severe hepatic impairment
• Pregnancy

Adverse effects

• Abdominal pain
• Alopecia
• Anaemia
• Appetite decreased
• Arrhythmia
• Arthralgia
• Asthenia
• Constipation
• Diarrhoea
• Dyspnoea
• Fluid imbalance
• Haemorrhage
• Hypersensitivity
• Hypertension
• Hypotension
• Increased risk of infection
• Myalgia
• Nausea
• Neutropenia
• Pain
• Peripheral neuropathy
• Sepsis
• Skin reactions
• Stomatitis
• Taste altered
• Thrombocytopenia
• Vomiting

Interactions

• Dabrafenib (severe - decreases exposure)
• Bosentan (severe - decreases exposure)
• Mitotane (severe - decreases exposure)
• Rifampicin (severe - decreases exposure)
• Selpercatinib (severe - increases exposure)
• St John's Wort (severe - decreases exposure)
• Berotralstat (moderate - increases concentration)
• Eliglustat (moderate - increases exposure)
• Sotorasib (moderate - increases exposure)
• Tucatinib (moderate - increases exposure)

Precautions

• Monitor liver function in hepatic impairment
• Caution in patients with acute porphyrias
• Caution in patients with pre-existing heart conditions

Pregnancy

Paclitaxel is contraindicated in pregnancy due to potential harm to the fetus.

Breast-feeding

Breastfeeding is not recommended during treatment with paclitaxel due to potential adverse effects on the infant.

Storage

Store in a refrigerator (2°C to 8°C). Protect from light. Do not freeze.

Formulations

• Paclitaxel 80mg/8ml concentrate for solution for infusion

Indications

• Constipation
• Labor induction
• Topical treatment for skin conditions

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing guidelines, as no specific doses are provided.

Adults: Refer to specific guidelines for adult dosing based on the formulation used and the condition being treated, as no standardized dose is provided.

Mechanism of action

Ricinoleic acid, the main active component of castor oil, acts as a stimulant laxative. It works by increasing the peristaltic movement of the intestines, which aids in the evacuation of stool. Additionally, it may inhibit the absorption of water in the intestines, resulting in softer stools. The oil is also believed to have anti-inflammatory properties, which can be beneficial in treating certain skin conditions.

Pharmacodynamics

The pharmacodynamic properties of castor oil include its ability to stimulate intestinal motility and increase the secretion of intestinal fluids. This leads to a faster transit time for stool through the bowel. In topical applications, castor oil exhibits emollient and moisturizing effects, promoting healing and soothing irritated skin. Its anti-inflammatory effects may also contribute to the reduction of swelling and pain in inflamed tissues.

Pharmacokinetics

Castor oil is absorbed in the gastrointestinal tract, where it is metabolized to ricinoleic acid. The onset of action for its laxative effect typically occurs within 2 to 6 hours after oral administration. The duration of action varies, but effects usually last for several hours. When applied topically, castor oil penetrates the skin and may provide localized effects without significant systemic absorption.

Adverse effects

• Abdominal cramps
• Diarrhea
• Nausea
• Vomiting
• Dehydration

Precautions

• Use with caution in patients with gastrointestinal disorders
• Not recommended for prolonged use
• Monitor for signs of dehydration

Pregnancy

Castor oil is generally not recommended during pregnancy due to potential uterine contractions and risk of premature labor.

Breast-feeding

Castor oil should be used with caution during breastfeeding as it may cause gastrointestinal discomfort in nursing infants.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Liquid
• Capsules

Indications

• Constipation
• Bowel preparation before colonoscopy or surgery

Dosage

Children: Refer to specific product guidelines for dosing instructions.

Adults: Refer to specific product guidelines for dosing instructions.

Mechanism of action

Polyoxyl works by retaining water in the stool, increasing its bulk and consistency. This osmotic effect stimulates bowel movements by softening the stool and promoting peristalsis. The water-retaining properties are attributed to its high molecular weight and hydrophilicity, which allow it to attract and hold water within the gastrointestinal tract.

Pharmacodynamics

The pharmacodynamic profile of polyoxyl includes its ability to enhance stool water content, thereby improving fecal passage through the intestines. This results in increased stool frequency and decreased transit time. Polyoxyl does not significantly affect electrolyte balance, making it a safe option for chronic constipation management.

Pharmacokinetics

Polyoxyl is not absorbed systemically; it remains in the gastrointestinal tract where it exerts its effects. The onset of action can vary but typically occurs within 24 to 72 hours after administration. The elimination of polyoxyl occurs through fecal excretion, with no significant metabolism or renal clearance involved.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal cramps
• Allergic reactions

Precautions

• Use with caution in patients with gastrointestinal disorders.
• Monitor for allergic reactions in patients with a history of hypersensitivity.

Pregnancy

Polyoxyl is generally regarded as safe for use during pregnancy, but specific clinical guidance should be consulted.

Breast-feeding

Polyoxyl is considered safe during breastfeeding, though maternal factors should be assessed.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Oral solution
• Tablet
• Topical cream

Mechanism of action

Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the "building block" of mictotubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function. Evidence suggests that paclitaxel also may induce cell death by triggering apoptosis. In addition, paclitaxel and docetaxel enhance the effects of ionizing radiation, possibly by blocking cells in the G2 phase, the phase of the cell cycle in which cells are most radiosensitive. Paclitaxel is an antimicrotubule antineoplastic agent. Unlike some other common antimicrotubule agents (e.g., vinca alkaloids, colchicine, podophyllotoxin), which inhibit microtubule assembly, paclitaxel and docetaxel (a semisynthetic taxoid) promote microtubule assembly. Microtubules are organelles that exist in a state of dynamic equilibrium with their components, tubulin dimers. They are an essential part of the mitotic spindle and also are involved in maintenance of cell shape and motility, and transport between organelles within the cell. By binding in a reversible, concentration-dependent manner to the beta-subunit of tubulin at the N-terminal domain, paclitaxel enhances the polymerization of tubulin, the protein subunit of the spindle microtubules, even in the absence of factors that are normally required for microtubule assembly (e.g., guanosine triphosphate [GTP]), and induces the formation of stable, nonfunctional microtubules. Paclitaxel promotes microtubule stability even under conditions that typically cause depolymerization in vitro (e.g., cold temperature, the addition of calcium, the presence of antimitotic drugs). While the precise mechanism of action of the drug is not understood fully, paclitaxel disrupts the dynamic equilibrium within the microtubule system and blocks cells in the late G2 phase and M phase of the cell cycle, inhibiting cell replication. ... Taxol induces tubulin polymerization and forms extremely stable and nonfunctional microtubules. Taxol has demonstrated broad activity in preclinical screening studies, and antineoplastic activity has been observed in several classically refractory tumors. These tumors include cisplatin resistant ovarian carcinoma in phase II trials and malignant melanoma and non-small cell lung carcinoma in phase I studies.

Pharmacodynamics

Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.