INFOGRAPHIC INFOGRAPHIC

THREE DECADES OF VIAGRA

Sildenafil (Viagra) — the first oral drug for erectile dysfunction to hit the market

64.0m
37.0m
in 1998 — has been prescribed for more than 64 million men worldwide,

5.4bn
2008 2016 2016
By 2008, Viagra had been By 2016, Viagra had been 5.4 billion Viagra tablets
and may soon be reclassified as a pharmacy medicine in the UK. prescribed for more than 37 million prescribed for more than 64 million had been dispensed
men worldwide men worldwide worldwide by 2016
BY DAWN CONNELLY  ALISDAIR MACDONALD

Sildenafil, a drug that
selectively targets and
powerfully inhibits the
enzyme phosphodiesterase
type 5 (PDE5), is first
synthesised and tested in
Pfizer’s UK laboratories.
The first trial of Pivotal phase III trial Sildenafil (Viagra; Pfizer) is Pfizer withdraws an application Boots becomes Tesco breaks into The UK patent Generic sildenafil can now The Medicines and
sildenafil for of sildenafil for ED approved by the US Food and to the EMA to market Viagra the first UK the Viagra market on Viagra be prescribed on the NHS Healthcare products
coronary heart is published in Drug Administration (FDA) over the counter for ED after pharmacy to and offers the drug expires, for any male with ED, Regulatory Agency
disease shows it is The New England in March and the European the regulator expresses offer Viagra to customers opening the whereas previously it was (MHRA) recommends
ineffective but penile Journal of Medicines Agency (EMA) concerns that there would be without a without a way for generic restricted to those with ED sildenafil 50mg (Pfizer)
erection is noticed Medicine. in September as the first oral no medical supervision, which prescription prescription under versions of because of an underlying should be available as a
as a side effect. treatment for men with ED. could delay diagnosis of under a patient a patient group sildenafil to be health condition, such as pharmacy medicine, and
possible cardiovascular group direction. direction. launched. diabetes or prostate launches a consultation
disease. cancer. that closes in April.

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

DRUG APPROVALS AND MARKET DEVELOPMENTS Tadalafil (Cialis; Eli Lilly) is Vardenafil (Levitra; Bayer) The European Vardenafil Avanafil Manufacturer of Cialis, Lilly,
Sildenafil showed promise as an oral treatment for erectile dysfunction (ED) in the approved for the is approved by the Commission (10mg) is the first (Spedra; Vivus) agrees a deal with Sanofi to allow
early 1990s and was launched by Pfizer as Viagra in 1998. Since then three more treatment of ED by the EMA for the approves low-dose PDE5 inhibitor is approved for the French firm to buy exclusive
PDE5 inhibitors have been launched in the UK. Sildenafil events are shown on the EMA in November, and by treatment of ED (2.5mg and 5.0mg) introduced treatment of ED rights to apply to sell Cialis as a
top of the timeline and other PDE5 inhibitor events are below the line. the US FDA in November in March and tadalafil as for ED in an by the US FDA in non-prescription medicine in Europe,
the following year. the US FDA in single-daily ED orodispersible April and by the the United States, Canada and
August. therapy. tablet. EMA in June 2013. Australia after certain patents expire.

Sildenafil Tadalafil
3.0m
USAGE AND Number of prescription items dispensed in England EFFICACY: EFFICACY: PDE5
COST DATA 69% 75% INHIBITORS:
FOR THE PDE5 2.5m KEY FACTS
Branded tadalafil, vardenafil and avanafil, and Viagra,
INHIBITORS continue to be restricted on the NHS, so as prescriptions for } Recommended dose: 50mg, 1 hour before } Recommended dose: 10mg, 30 minutes before
PDE5 inhibitors work by
The number of 2.0m sildenafil rose, those for tadalafil and vardenafil began to fall. sexual activity, may be adjusted to 100mg or 25mg sexual activity, may be adjusted to 20mg; or increasing blood flow to
prescription items Introduction of low-price generic sildenafil and } Bioavailability: 41% 2.5–5.0mg daily the penis during sexual
removal of prescribing restrictions led to a stimulation. Although all
dispensed in England steep rise in the number of prescription items } Time to peak plasma levels: 60 minutes } Bioavailability: not determined
for the four PDE5 1.5m
dispensed in England, from 1.3 million in } Half-life: 3–5 hours } Time to peak plasma levels: 120 minutes PDE5 inhibitors are
inhibitors has been 2012-2013 to 2.7 million in 2015-2016. } Onset of action: 25 minutes } Half-life: 17.5 hours effective, there are
influenced by their } Duration of action: up to 4 hours } Onset of action: 15–30 minutes differences in their onset
1.0m
cost and restrictions } Food: high-fat meals delay the time to peak plasma } Duration of action: up to 36 hours and duration of action.
concentration by 60 mins and reduce peak plasma } Food: rate and extent of absorption are not There are also differences
on prescribing them Avanafil levels by 29% influenced by food
within the NHS. 0.5m (2015-2016): in how their absorption is
} Common side effects: headache, dizziness, flushing, nasal } Common side effects: headache, flushing, nasal
6,765
congestion, nausea, dyspepsia, visual abnormalities congestion, dyspepsia, myalgia and back pain affected by food, and in
their side effect profiles.
0
1999 2016
Slidenafil Vardenafil Avanafil
Tadalafil £50m
Net ingredient cost of prescription items dispensed Efficacy = successful
EFFICACY: EFFICACY:
Vardenafil intercourse for general
7180% 4759%
ED population
Avanafil £40m

} Recommended dose: 10mg, 25–60 minutes before sexual } Recommended dose: 100mg, 15 to 30 minutes before
activity. May be adjusted to 20mg or 5mg (film-coated only) sexual activity, may be adjusted to 200mg or 50mg
£30m } Bioavailability: 15%, (film-coated), 19% (orodispersible) } Bioavailability: not determined
} Time to peak plasma levels: 60 minutes (film-coated), } Time to peak plasma levels: 30–45 mins
The net ingredient cost for sildenafil fell from 45–90 minutes (orodispersible) } Half-life: 6–17 hours
£40.2m in 2012-2013 to £5.8m in 2015-2016, } Half-life: 4-5 hours } Onset of action: 15-30 minutes
£20m reflecting a fall in the cost per prescription } Onset of action: 25 minutes } Duration of action: up to 6 hours
item from £31.22 to £2.20
} Duration of action: up to 12 hours } Food: high-fat meals delay the time to peak plasma
Sources: NHS Digital, MHRA, EMA,
} Food: high-fat meals delay the time to peak plasma concentration concentration by 75 mins and reduce peak plasma levels summaries of product characteristics,
£10m by 60 mins (film-coated) and reduce peak plasma levels by 20% by 39% Pfizer, Bayer, Menarini
Avanafil (2015-2016): £148,113 (film-coated) or 35% (orodispersible) } Common side effects: headache, flushing, nasal congestion Editorial advisers: Ian Pearce,
} Common side effects: headache, dizziness, flushing, nasal consultant urological surgeon, Central
congestion, dyspepsia. Inhibits PDE6, which can cause transient Manchester University Hospitals NHS
0 Foundation Trust, and honorary senior
1999 2016 visual abnormalities. Can prolong QTc interval lecturer, University of Manchester
Graphics: alisdairmacdonald.co.uk

286 THE PHARMACEUTICAL JOURNAL VOL 298 NO 7901 MAY 2017 MAY 2017 NO 7901 VOL 298 THE PHARMACEUTICAL JOURNAL 287