W12 (AM) Flashcards
Tolterodine tartrate used to treat?
Developed and Marketed as?
It is an antimuscarinic used in the treatment of “Urge incontinence and/or increased urinary frequency and urgency
Was developed by Pharmacia and marketed as Detrol® (in the US) and Detrusitol® (rest of world) in the 1990s
* Pharmacia was bought out by Pfizer in 2002
What are the principal micturition disorders?
Urinary incontinence and Urinary
retention
Tolterodine tartrate formulations
Detrusitol:
- Detrusitol®/Detrol® originally launched as a standard release formulation with an extended-release (“XL”) capsule formulation following in early-2000s
- Better side-effect profile with the XL formulation
- Tolterodine tartrate currently available in the UK as standard release tablets and XL capsule
Detrusitol® XL capsule:
Tolterodine spheres
Polymer-coated (Surelease®)
Tolterodine tartrate formulations
Surelease® produced by (Colorcon®)
- Ethylcellulose mixture is then emulsified with ammoniated water in a high shear mixer, i.e. homogeniser, → aqueous dispersion
- Drug release is primarily by diffusion through the ethylcellulose membrane – rate is modified by altering the quantity of Surelease applied
- pH changes do not affect drug release
Tolterodine tartrate formulations
Why use small spheres?
- The stomach only empties its contents
periodically – allows time for digestion to
commence - Small particles (2-3 mm) can pass
through the pyloric sphincter (separates
the stomach and duodenum) but large
intact tablets cannot - Small tolterodine spheres can pass
through the pyloric sphincter irrespective of fed/ fasting state
Neditol® XL
Generic equivalents must contain the same amount of drug in the same dosage form and have similar pharmacokinetics
Detrusitol® was the innovator product – the patent is now long-expired
Neditol® XL is another (generic) prolonged-released hard capsule dosage form for tolterodine tartrate
- The capsule contains two coated tolterodine tartrate tablets
- Tablet coating consists of ethylcellulose, triethyl citrate, methacrylic acid - ethyl acrylate copolymer, 1,2-Propylene glycol
Steady-state study under fasting conditions is similar to detrusitol, so it was allowed
Branded generic prescribing
- Branded generics are generic medicines that are given a brand name by the manufacturer
- Manufacturers will then approach prescribers and primary care
organisations, i.e. local health boards in Wales, to encourage prescribing of their brand – which might have a reduced price - Can be good in the short-term but there often longer-term issues,
e.g. long-term price, availability, patient acceptability etc
Oxybutynin formulations
- Oxybutynin hydrochloride is another antimuscarinic used in the treatment of urge incontinence, increased urinary frequency,
urgency and neurogenic bladder instability - Innovator product: Ditropan® (early-1970s)
- Dosage forms in which oxybutynin available:
− Tablet
− Modified-release tablet
− Oral solution
− Transdermal patch
− Transdermal gel (not in the UK) - Oxybutynin transdermal patch (Kentera®) reserved for patients who experience intolerable anticholinergic side effects
Erectile dysfunction definition:
Treatments?
- Erectile dysfunction (impotence) is the inability to get and keep an erection firm enough – and/or for long enough – to have sex
- Treatments: lifestyle changes, phosphodiesterase-5 (PDE-5) inhibitors, e.g. sildenafil and tadalafil, prostaglandin E1 agonists,
e.g. alprostadil, vacuum pumps
Sildenafil discovered serendipitously (for info)
− 1989: Peter Dunn & Albert Wood create a new anti-angina drug: UK-92480
− 1991: new drug patented as sildenafil citrate (Nicholas Terrett)
− Early 1990s: clinical trials show only limited success, but researcher Ian Osterloh notes an unexpected side-effect…
− 1998: approved by FDA (March) and EMA (September
Prostaglandin E1 agonists e.g. alprostadil, are administered by more novel formulations:
(Caverject)
- SmPC: Caverject® (alprostadil) is administered by direct intracavernous injection: 0.5 inch, 27-to-30- gauge needle is generally recommended
- Supplied as a powder and a separate diluent (1 mL) – this is added with a larger 22-gauge needle
- Caverject® Dual Chamber (“Impulse”) in some territories has powder + diluent in one device
MUSE® = medicated urethral system for erection (alprostadil)
- SmPC: sterile, single-use transurethral system for the delivery of alprostadil to the male urethra
- Alprostadil is suspended in macrogol 1450 (polyethylene glycol) and is formed into a urethral stick or suppository (1.4 mm × 3 mm)
which is contained in the tip of the polypropylene applicator - Inserted into urethra 10-30 mins before intercourse (full instructions in SmPC)
- MUSE reported as often less effective than
Caverject®
Macrogol 1450: white to almost white solid with a waxy or paraffin-like appearance
