Sildenafil

Products

Sildenafil is commercially available in the form of film-coated tablets and as a solution for injection (Viagra, Revatio, generics). It has been approved in many countries since 1998. Generics went on sale July 22, 2013, and the patent expired June 21. Pfizer launched auto-generic sildenafil Pfizer, identical to the original, back in May. In 2016, the melting film Silvir was additionally released in many countries. Sildenafil was originally to be developed at Pfizer for the treatment of angina. In 1992, erection-promoting effects were discovered as a side effect in a clinical trial. In 1993, the first trials were conducted for erectile dysfunction.

Structure and properties

Sildenafil (C22H30N6O4S, Mr = 474.6 g/mol) is present in drugs as sildenafil citrate, a white, crystalline, slightly hygroscopic powder that is sparingly soluble in water. It is a pyrazole pyrimidine and a piperazine derivative. The blue color of the tablets and meltable tablets is from the added dye indigocarmine (E 132).

Effects

Sildenafil (ATC G04BE03) has vasodilator and antihypertensive properties. It causes relaxation of smooth muscle in the corpus cavernosum and an increase in blood flow to the penis during sexual stimulation. The effects are due to inhibition of cGMP-specific phosphodiesterase type 5 (PDE-5), leading to an increase in cGMP, which mediates these effects as a second messenger of nitric oxide (NO). Sildenafil has a medium-long half-life of 3 to 5 hours.

Indications

For the treatment of men with erectile dysfunction (erectile dysfunction, Viagra). Sildenafil is also approved for the treatment of pulmonary arterial hypertension (Revatio). Another potential use is pulmonary edema associated with altitude sickness (off-label). This article refers to its use in erectile dysfunction.

Dosage

According to the SmPC. Medicines are taken about one hour before sexual intercourse and no more than once daily. The dose range is 25 to 100 mg; 50 mg is generally recommended. With food, the onset of action is delayed.

Contraindications

  • Hypersensitivity
  • Patients who are advised against sexual activity.
  • Sildenafil should not be co-administered with nitrates, NO donors, or amyl nitrite.

Full details of precautions and interactions can be found in the drug label.

Interactions

Sildenafil is metabolized primarily by CYP3A4 and to a lesser extent by CYP2C9. Corresponding drug-drug interactions are possible. It potentiates the antihypertensive properties of nitrates and NO donors, which may lead to a severe and dangerous drop in blood pressure. The combination is therefore contraindicated. With other antihypertensives, lowering of blood pressure may also be possible. Interactions with anticoagulants (phenprocoumon, acenocoumarol) cannot be ruled out.

Adverse effects

The most common possible adverse effects include headache, visual disturbances, dizziness, changes in color vision, flushing, nasal congestion, and indigestion. Very rarely, serious side effects such as stroke, cardiac arrhythmias, myocardial infarction, sudden cardiac death, and seizures are possible.