Sildenafil Actavis - (IR): composition and pharmaceutical form
This version of the medicine comes in a single strength: the film-coated tablet contains 100 mg of sildenafil in the form of the citrate. One hundred milligrams is the maximum recommended dose, so there is no need to split the dose across more tablets.
The medicine is intended only for adult men. If tolerance or efficacy calls for a smaller dose, the doctor selects another strength from the range.
How Sildenafil Actavis - (IR) works
An erection comes about thanks to the release of nitric oxide in the corpora cavernosa during sexual arousal. Nitric oxide activates guanylate cyclase, the level of cyclic guanosine monophosphate (cGMP) rises, the smooth muscles of the corpora cavernosa relax and the flow of blood to the penis increases.
Sildenafil is a selective inhibitor of phosphodiesterase type 5, the enzyme that breaks down cGMP specifically in the corpora cavernosa. On its own it does not relax isolated corpus cavernosum tissue, but it markedly enhances the action of nitric oxide, and it does so at the peripheral level. The practical conclusion is that without sexual stimulation the chain is not set in motion and the medicine does not work.
Indications
The indication is disturbances of erection in adult men, that is, the inability to achieve or maintain an erection sufficient for sexual intercourse.
The essential condition for efficacy is sexual stimulation. Before drug treatment begins the doctor establishes the cause of the disturbance: an erectile disorder can be a symptom of vascular, endocrine and psychological problems, and the treatment is chosen with the cause in mind.
Method of use and dosage
The tablet is taken about an hour before the planned sexual activity, as required, but no more than once a day. If the medicine is taken with food, the action may begin later than when it is taken on an empty stomach. The 100 mg strength is the upper limit: it must not be exceeded, since efficacy does not grow from that while undesirable reactions become more frequent.
| Situation | What the doctor takes into account |
|---|---|
| Age 65 and over | No dose adjustment for age is required |
| Mild and moderate impairment of kidney function | Dosing as for other patients |
| Severe impairment of kidney function (creatinine clearance below 30 ml/min) | The clearance of sildenafil is reduced: one starts with 25 mg |
| Hepatic failure, for example cirrhosis | One starts with 25 mg because of the reduced clearance |
| Use of CYP3A4 inhibitors | A starting dose of 25 mg; combination with ritonavir is not recommended |
| Use of alpha blockers | One starts with 25 mg after the patient's condition has been stabilised |
In all these situations the 100 mg strength is not the starting one: the doctor begins with a smaller dose and raises it gradually, guided by the effect and the tolerance. The medicine is not prescribed to people under 18.
Contraindications
The medicine is not used in the following cases:
- hypersensitivity to sildenafil or to any excipient;
- use of nitrates in any form and of agents that release nitric oxide, for example amyl nitrite: sildenafil enhances their hypotensive action;
- use of guanylate cyclase stimulators, including riociguat — the risk of symptomatic hypotension;
- conditions in which sexual activity is inadvisable, including unstable angina and severe heart failure;
- a previous loss of vision in one eye due to non-arteritic anterior ischaemic optic neuropathy;
- severe hepatic failure, blood pressure below 90/50 mm Hg, a recent stroke or myocardial infarction;
- hereditary degenerative diseases of the retina, for example retinitis pigmentosa.
Special warnings and precautions
Sexual activity in itself places a load on the heart, so before any medicine for erectile disturbances is prescribed the state of the cardiovascular system is assessed. Sildenafil dilates the vessels and slightly lowers blood pressure for a short time. Particularly sensitive to this are patients with an obstructed outflow of blood from the left ventricle — with aortic stenosis or hypertrophic cardiomyopathy with obstruction — and those with the rare syndrome of multiple system atrophy, in which the autonomic control of blood pressure is disturbed.
- after the medicine was registered, myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmias, cerebral haemorrhage, transient ischaemic attack, and rises and falls in blood pressure have been described — mainly in patients with cardiovascular risk factors, often during sexual intercourse or shortly afterwards;
- an erection lasting longer than 4 hours requires immediate medical help: without treatment priapism damages the tissue of the penis and leads to a permanent loss of potency;
- caution is needed with curvature of the penis, fibrosis of the corpora cavernosa and Peyronie's disease, and also with sickle cell anaemia, multiple myeloma and leukaemia — conditions that predispose to priapism;
- a sudden disturbance of vision is a reason to stop the medicine and see a doctor at once;
- combination with other phosphodiesterase type 5 inhibitors, with sildenafil used for pulmonary arterial hypertension and with other treatments for erectile disturbances has not been studied and is not recommended;
- with alpha blockers symptomatic hypotension is possible, more often in the first 4 hours after the dose, so the patient is told what to do if signs of orthostatic hypotension appear;
- sildenafil enhanced the antiplatelet action of sodium nitroprusside in experiments on human platelets, and there are no safety data in clotting disorders and active peptic ulcer;
- combination with ritonavir is not recommended.
Drug interactions
The medicine is metabolised by cytochrome P450 — mainly by the isoenzyme CYP3A4 and to a lesser extent by CYP2C9. Inhibitors of these enzymes slow the elimination of sildenafil, so with concomitant use of ketoconazole, erythromycin or cimetidine a starting dose of 25 mg is recommended. Erythromycin at steady state increased the AUC of sildenafil by 182%, whereas azithromycin had no influence on its pharmacokinetics.
The strongest interaction is with HIV protease inhibitors. With ritonavir the maximum concentration of sildenafil rose by 300% and the AUC by 1000%, and after a day the concentration remained at about 200 ng/ml instead of roughly 5 ng/ml; that is why this combination is not recommended and, if it is necessary, the dose must not exceed 25 mg in 48 hours. Saquinavir increased the maximum concentration by 140% and the AUC by 210%. From ketoconazole and itraconazole an even more marked influence is expected. Nitrates and riociguat remain absolutely incompatible with the medicine.
Pregnancy and breastfeeding
The medicine is not intended for women, and no controlled studies have been carried out in pregnant or breastfeeding women.
In studies of reproductive function in rats and rabbits no undesirable influence of sildenafil taken by mouth was found. In healthy men a single dose of 100 mg had no effect on the motility or morphology of the spermatozoa.
Adverse effects
The safety data were collected in 9570 patients in 74 double-blind placebo-controlled studies and are supplemented by more than 10 years of observation since the medicine came onto the market.
- very common — headache;
- common — dizziness, reddening of the face and flushes, nasal congestion, dyspepsia, nausea;
- common — disturbances of colour vision, blurred vision, other visual disturbances;
- uncommon — drowsiness, reduced sensation, tachycardia, palpitations, rhinitis, hypersensitivity;
- uncommon — eye pain, photophobia, photopsia, redness of the eyes, conjunctivitis, disturbances of tear production, tinnitus;
- rare — fainting, seizures, stroke, transient ischaemic attack, hearing loss;
- rare — myocardial infarction, ventricular arrhythmias, atrial fibrillation, unstable angina, sudden cardiac death;
- rare — anterior ischaemic optic neuropathy, occlusion of the retinal vessels, retinal haemorrhage, glaucoma, double vision, visual field defects, reduced visual acuity.
The exact frequency of the reactions identified after registration cannot be estimated: by no means all cases are reported to the manufacturer.
Overdose
In healthy volunteers single doses of up to 800 mg gave the same undesirable reactions as the usual ones, but more often and more severely. A dose of 200 mg did not raise efficacy but did increase the frequency of headache, flushes, dizziness, dyspepsia, nasal congestion and visual disturbances.
There is no specific antidote: treatment is supportive, according to the symptoms. Sildenafil is firmly bound to the plasma proteins and is not eliminated with the urine, so dialysis does not speed up its clearance.
How to get a prescription for Sildenafil Actavis - (IR) online
Sildenafil is dispensed on prescription. The 100 mg strength is the maximum, and it is prescribed when smaller doses have proved insufficiently effective with good tolerance.
During the online consultation the doctor will go through the cause of the erectile disturbance, the state of the heart and the list of medicines being taken, above all nitrates, and if there are no contraindications will issue an electronic prescription — the medicine can be collected from a pharmacy using its code.
