CONTILIN

Indications

• Urinary frequency
• Urinary urgency
• Urinary incontinence
• Neurogenic bladder instability
• Nocturnal enuresis associated with overactive bladder

Dosage

Adults: Initially 5 mg 2–3 times a day, increased if necessary up to 5 mg 4 times a day. For modified-release tablets, start at 5 mg once daily, with adjustments in steps of 5 mg weekly, maximum 20 mg per day. For transdermal patches, apply 1 patch twice weekly to clean

Mechanism of action

Oxybutynin acts as a competitive antagonist of the muscarinic receptors, specifically M1, M2, and M3 subtypes. By blocking acetylcholine's action at these receptors, it reduces involuntary contractions of the bladder detrusor muscle, thus increasing bladder capacity and decreasing urinary urgency and frequency.

Pharmacodynamics

Oxybutynin exhibits dose-dependent effects on bladder function. By reducing detrusor muscle contractions, it leads to an increase in bladder storage capacity and a decrease in the frequency of involuntary urination. Its efficacy in controlling overactive bladder symptoms is typically observed within a few weeks of treatment initiation. Additionally, oxybutynin has central nervous system effects, which may contribute to its overall efficacy and side effect profile.

Pharmacokinetics

Oxybutynin is well-absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours for immediate-release formulations. It undergoes extensive first-pass metabolism in the liver, primarily via cytochrome P450 3A4. The elimination half-life is roughly 2 hours, but this may be extended in elderly patients or those with hepatic impairment. Oxybutynin is excreted mainly in the urine as metabolites, with less than 1% of the unchanged drug found in urine.

Contra-indications

• Hypersensitivity to oxybutynin or any of its components
• Acute porphyrias
• Uncontrolled narrow-angle glaucoma
• Severe gastrointestinal obstruction
• Myasthenia gravis

Adverse effects

• Dry mouth
• Constipation
• Blurred vision
• Urinary retention
• Dizziness
• Somnolence
• Nausea
• Vomiting

Interactions

• Anticholinergic agents may increase the effects of oxybutynin
• CYP3A4 inhibitors may increase levels of oxybutynin
• CYP3A4 inducers may decrease levels of oxybutynin
• Concurrent use with other medications that cause anticholinergic effects may increase the risk of adverse effects

Precautions

• Use with caution in patients with bladder outlet obstruction
• Caution in patients with a history of seizures or epilepsy
• Use with caution in the elderly due to increased risk of side effects
• Monitor for signs of urinary retention

Pregnancy

Oxybutynin should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Limited data is available regarding its safety during pregnancy.

Breast-feeding

Oxybutynin is excreted in breast milk. Caution should be exercised when oxybutynin is administered to nursing mothers.

Storage

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

Formulations

• Oxybutynin hydrochloride 2.5 mg tablets
• Oxybutynin hydrochloride 5 mg tablets
• Oxybutynin hydrochloride 10 mg modified-release tablets
• Oxybutynin hydrochloride oral solution
• Oxybutynin transdermal patch

Indications

• Constipation
• Dietary fiber supplementation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Adults: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Mechanism of action

Cellulose acts primarily as a bulk-forming laxative. It absorbs water in the intestines, which increases stool bulk and stimulates peristalsis, thus facilitating bowel movements. Additionally, cellulose is not digestible by human enzymes, leading to fermentation by gut bacteria, which may enhance gut health and alter gut microbiota composition.

Pharmacodynamics

Cellulose increases stool weight and frequency of bowel movements. It works by retaining water in the intestines, leading to softer stools and improved passage through the gastrointestinal tract. The bulking effect of cellulose can help alleviate constipation and promote overall digestive health. It may also play a role in cholesterol reduction and glycemic control through its effects on digestion and absorption of nutrients.

Pharmacokinetics

Cellulose is not absorbed into the bloodstream due to its indigestible nature. Instead, it passes through the gastrointestinal tract, where it adds bulk to the stool. Its fermentation by colonic bacteria produces short-chain fatty acids, which may have beneficial effects on colon health. The onset of action for cellulose as a laxative can vary but is generally within 24 to 72 hours after ingestion.

Adverse effects

• Bloating
• Flatulence
• Diarrhea
• Abdominal discomfort

Precautions

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

Pregnancy

Cellulose is generally considered safe during pregnancy as it is a non-toxic, indigestible fiber.

Breast-feeding

Cellulose is also considered safe during breastfeeding; it is excreted in breast milk in negligible amounts.

Storage

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

Formulations

• Powder
• Capsules
• Tablets
• Granules

Indications

• Lactose intolerance
• As a filler or excipient in pharmaceutical formulations

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and clinical context.

Adults: Refer to the BNF for specific dosing information based on clinical context.

Mechanism of action

Lactose is metabolized in the intestine by the enzyme lactase into its constituent monosaccharides, glucose and galactose. In individuals with lactase deficiency, unabsorbed lactose passes into the colon, where it is fermented by bacteria, leading to gas production and osmotic effects that contribute to diarrhea.

Pharmacodynamics

The pharmacodynamics of lactose are primarily related to its effects on gastrointestinal function. In healthy individuals, lactose is effectively broken down into glucose and galactose, which are absorbed and utilized for energy. In individuals with lactose intolerance, the unabsorbed lactose can cause osmotic diarrhea and colonic fermentation, leading to discomfort and symptoms associated with lactose intolerance.

Pharmacokinetics

Lactose is not absorbed in the gastrointestinal tract until it is hydrolyzed into glucose and galactose by lactase. The absorption of glucose and galactose occurs in the small intestine. The half-life is not applicable as lactose is not typically administered as a medication but is rather ingested as a natural component of food. Its metabolism primarily occurs in the intestine.

Adverse effects

• Bloating
• Diarrhea
• Abdominal pain
• Flatulence

Precautions

• Use with caution in patients with lactose intolerance.
• Consider potential for gastrointestinal upset in sensitive individuals.

Pregnancy

Lactose is generally considered safe for use during pregnancy. However, consult a healthcare professional for individual advice.

Breast-feeding

Lactose is safe to use while breastfeeding, as it is a natural sugar present in breast milk.

Storage

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

Formulations

• Powder
• Granules
• Tablets
• Syrup

Indications

• Used as an excipient in tablet formulations
• Used as a bulking agent in capsule formulations
• Used in food products as a thickener or stabilizer

Dosage

Children: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Adults: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Mechanism of action

Microcrystalline cellulose acts as a non-digestible filler that enhances the flow properties of powders during the manufacturing of tablets and capsules. It does not have a direct pharmacological action on the body but ensures that the active ingredients are effectively delivered to the patient.

Pharmacodynamics

As a non-active ingredient, microcrystalline cellulose does not exert pharmacodynamic effects typical of active pharmaceutical ingredients. Its primary role is to provide a stable and consistent matrix for the drug, facilitating the release of the active compound once ingested.

Pharmacokinetics

Microcrystalline cellulose is not absorbed in the gastrointestinal tract; it passes through the digestive system largely unchanged. It adds bulk to the stool, which may aid in promoting regular bowel movements. The substance is excreted in feces, where it contributes to dietary fiber intake.

Pregnancy

Data regarding the use of microcrystalline cellulose during pregnancy is limited. It is advisable to consult with healthcare professionals before use.

Breast-feeding

Microcrystalline cellulose is considered safe during breastfeeding, as it is not absorbed systemically.

Storage

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

Indications

• Overactive bladder syndrome
• Urinary urgency
• Urinary frequency
• Urinary incontinence

Dosage

Children: Refer to the BNF for Children for specific dosing guidance.

Adults: Refer to the BNF for specific dosing guidance.

Mechanism of action

Oxybutynin acts to relax the bladder by competitively inhibiting the muscarinic receptors (types 1, 2, and 3) in the bladder smooth muscle. This inhibition reduces the effects of acetylcholine, resulting in increased bladder capacity and a decrease in urinary urgency and frequency. It also delays the initial desire to void.

Pharmacodynamics

Oxybutynin exhibits antispasmodic effects on the bladder, alleviating symptoms associated with overactive bladder. Its anticholinergic activity can lead to side effects such as confusion, hallucinations, and drowsiness. Caution is advised when operating heavy machinery until the individual's response to the medication is understood. Angioedema, though rare, may occur and requires immediate discontinuation of the drug.

Pharmacokinetics

Oxybutynin is well absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism, primarily to its active metabolite, N-desethyloxybutynin. It has a half-life that allows for once or twice-daily dosing, depending on the formulation. The drug is primarily excreted in urine, both as unchanged drug and metabolites.

Adverse effects

• Angioedema
• Hallucinations
• Confusion
• Agitation
• Drowsiness

Interactions

• oxybutynin + antiepileptics: Severe (increases risk of overheating and dehydration)
• oxybutynin + zonisamide: Unknown (increases risk of overheating and dehydration)
• clozapine + oxybutynin: Unknown (additive effect)
• cobicistat + oxybutynin: Unknown (increases exposure)
• idelalisib + oxybutynin: Unknown (increases exposure)
• clarithromycin + oxybutynin: Unknown (increases exposure)
• antipsychotics, second generation + oxybutynin: Unknown (additive effect)

Precautions

• Monitor for symptoms of angioedema and discontinue if suspected
• Be cautious with activities requiring alertness until response to oxybutynin is evaluated
• Dose adjustments may be necessary

Pregnancy

Oxybutynin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult healthcare providers for guidance.

Breast-feeding

It is not known whether oxybutynin is excreted in human milk. Caution is advised when administering to nursing women.

Storage

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

Formulations

• Tablets
• Extended-release tablets
• Syrup
• Transdermal patch

Mechanism of action

Oxybutynin acts to relax the bladder by inhibiting the muscarinic action of acetylcholine on smooth muscle, and not skeletal muscle. The active of oxybutynin is metabolite is N-desethyloxybutynin. It competitively inhibits the postganglionic type 1, 2 and 3 muscarinic receptors. The above actions lead to increased urine capacity in the bladder, decreasing urinary urgency and frequency. In addition, oxybutynin delays the initial desire to void. RESULTS OF CYSTOMETRIC STUDIES SHOWED THAT THE DRUG INCR BLADDER CAPACITY @ ONSET OF FIRST CONTRACTION & FIRST DESIRE TO VOID, AS WELL AS @ END OF CYSTOMETRY. /CHLORIDE/

Pharmacodynamics

Oxybutynin exerts antispasmodic actions on the bladder, relieving the uncomfortable symptoms of overactive bladder, including urinary urgency and frequency. These actions occur through the inhibition of muscarinic receptors. **A note on angioedema and anticholinergic effects** Symptoms of angioedema may occur with oxybutynin therapy. If angioedema is suspected, discontinue oxybutynin immediately and provide appropriate medical treatment. In addition, anticholinergic effects may occur with the administration of this drug. Some symptoms may include hallucinations, confusion, agitation, and drowsiness. It is advisable to avoid operating heavy machinery before the response to oxybutynin has been monitored. Dose adjustments may be required.