Sildenafil Actavis: composition and pharmaceutical form
Sildenafil Actavis comes as film-coated tablets. One tablet contains 50 mg or 100 mg of sildenafil in the form of the citrate.
The two strengths are there for adjusting the dose: 50 mg is considered standard, but depending on efficacy and tolerance the doctor may recommend 25 mg or 100 mg. The medicine is intended only for adult men.
How Sildenafil Actavis works
The physiological mechanism of erection is linked to the release of nitric oxide in the corpora cavernosa during sexual arousal. Nitric oxide activates the enzyme guanylate cyclase, because of which the level of cyclic guanosine monophosphate (cGMP) rises, the smooth muscles of the corpora cavernosa relax and blood flows into the penis.
Sildenafil is a potent selective inhibitor of phosphodiesterase type 5, which is specific for cGMP and responsible for breaking it down in the corpora cavernosa. It has no direct relaxant action on isolated corpus cavernosum tissue, but it markedly enhances the relaxant influence of nitric oxide. That is precisely why the medicine works only with sexual arousal: without it the "nitric oxide – cGMP" chain is not set in motion, and the inhibition of the phosphodiesterase achieves nothing.
Indications
The medicine is indicated in adult men with disturbances of erection — the inability to achieve or maintain an erection sufficient for sexual intercourse.
For the medicine to work, sexual stimulation is needed. Before drug treatment is started the doctor takes a history and performs an examination in order to establish the fact of the erectile disturbance itself and to work out its causes.
Method of use and dosage
The recommended dose is 50 mg about an hour before the planned sexual activity, as required. Depending on efficacy and tolerance the dose is increased to 100 mg or reduced to 25 mg; 100 mg is the maximum recommended dose. Taking the medicine more than once a day is not recommended. If the tablet is taken with food, the action may begin later than when it is taken on an empty stomach.
| Group of patients | Particulars of dosing |
|---|---|
| Men aged 65 and over | No dose adjustment is required |
| Mild and moderate impairment of kidney function (creatinine clearance 30–80 ml/min) | The usual doses |
| Severe impairment of kidney function (creatinine clearance below 30 ml/min) | One starts with 25 mg and, if necessary, raises it to 50 and at most 100 mg |
| Impairment of liver function, for example cirrhosis | One starts with 25 mg, with a possible gradual increase |
| Use of CYP3A4 inhibitors | A starting dose of 25 mg; combination with ritonavir is not recommended |
| Use of alpha blockers | The patient's condition is stabilised before treatment begins, starting with 25 mg |
| Age under 18 | The medicine is not indicated |
Contraindications
The medicine is not used in the following cases:
- hypersensitivity to sildenafil or to any excipient;
- concomitant use of nitrates in any form and of medicines that release nitric oxide, for example amyl nitrite — sildenafil enhances their hypotensive action;
- concomitant use of guanylate cyclase stimulators, such as riociguat — symptomatic arterial hypotension is possible;
- conditions in which sexual activity is inadvisable: severe cardiovascular diseases, including unstable angina and severe heart failure;
- loss of vision in one eye due to non-arteritic anterior ischaemic optic neuropathy, regardless of whether it was linked to the use of phosphodiesterase type 5 inhibitors;
- severe hepatic failure, arterial hypotension with a pressure below 90/50 mm Hg, a recent stroke or myocardial infarction — safety in these situations has not been studied;
- hereditary degenerative diseases of the retina, for example retinitis pigmentosa.
Special warnings and precautions
Since sexual activity itself places a load on the heart, before starting any treatment for erectile disturbances the state of the cardiovascular system is assessed. Sildenafil dilates the vessels and causes a small transient fall in blood pressure, so the doctor assesses in advance how sensitive the patient is to the vasodilatory action. Increased sensitivity occurs where the outflow of blood from the left ventricle is obstructed — aortic stenosis, hypertrophic cardiomyopathy with obstruction of the outflow tract — and also in the rare syndrome of multiple system atrophy with marked disturbance of the autonomic control of blood pressure.
- after the medicine came onto the market serious cardiovascular events coinciding in time with its use were described: myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmias, cerebral haemorrhage, transient ischaemic attack, rises and falls in blood pressure; most of these patients had cardiovascular risk factors, and many of the events occurred during sexual intercourse or shortly afterwards;
- caution is needed with anatomical deformities of the penis — curvature, fibrosis of the corpora cavernosa, Peyronie's disease — and in conditions that predispose to priapism: sickle cell anaemia, multiple myeloma, leukaemia;
- with an erection lasting longer than 4 hours medical help must be sought immediately: without timely treatment priapism damages the tissue of the penis and leads to a permanent loss of potency;
- 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 any sudden disturbance of vision the medicine is stopped and a doctor is consulted immediately: cases of non-arteritic anterior ischaemic optic neuropathy have been described;
- with alpha blockers symptomatic hypotension is possible, most often within 4 hours of the dose, so the patient's condition must be haemodynamically stable and treatment starts with 25 mg;
- in in vitro studies sildenafil enhanced the antiplatelet action of sodium nitroprusside; there are no safety data in clotting disorders and active peptic ulcer, and in those cases the medicine is prescribed only after a careful assessment;
- concomitant use with ritonavir is not recommended.
Drug interactions
Sildenafil is metabolised by the cytochrome P450 system, mainly by the isoenzyme CYP3A4 and to a lesser extent by CYP2C9, so inhibitors of these enzymes reduce its clearance. With concomitant use of CYP3A4 inhibitors — ketoconazole, erythromycin, cimetidine — it is recommended to start with a dose of 25 mg. Erythromycin at steady state increased the AUC of sildenafil by 182%, while azithromycin had no influence on the pharmacokinetics of sildenafil.
The interaction with HIV protease inhibitors is especially marked. Ritonavir raised the maximum concentration of sildenafil by 300% and the AUC by 1000%: after 24 hours the concentration remained at about 200 ng/ml against roughly 5 ng/ml with sildenafil alone, so this combination is not recommended and, if it is unavoidable, the dose must not exceed 25 mg in 48 hours. Saquinavir increased the maximum concentration by 140% and the AUC by 210%. From more potent CYP3A4 inhibitors, such as ketoconazole and itraconazole, an even greater effect can be expected. Separately one must remember nitrates and riociguat — these combinations are contraindicated.
Pregnancy and breastfeeding
The medicine is not intended for use by women. No adequate controlled studies have been carried out in pregnant or breastfeeding women.
In studies of reproductive function in rats and rabbits with sildenafil given by mouth no undesirable effects were found. In healthy volunteers a single dose of 100 mg did not change the motility or morphology of the spermatozoa.
Adverse effects
The safety profile is based on data from 9570 patients in 74 double-blind placebo-controlled studies and on more than a decade of observation after the medicine came onto the market.
- very common — headache;
- common — dizziness, reddening of the face, flushes, dyspepsia, nasal congestion, nausea;
- common — disturbances of colour vision, blurred vision and other visual disturbances;
- uncommon — drowsiness, reduced sensation, tachycardia, palpitations, rhinitis, hypersensitivity reactions;
- uncommon — disturbances of tear production, eye pain, photophobia, photopsia, redness of the eyes, a sensation of bright light, conjunctivitis;
- uncommon — dizziness of central origin, tinnitus;
- rare — stroke, transient ischaemic attack, seizures, fainting, hearing loss;
- rare — sudden cardiac death, myocardial infarction, ventricular arrhythmias, atrial fibrillation, unstable angina;
- rare — anterior ischaemic optic neuropathy, occlusion of the retinal vessels, retinal haemorrhage, glaucoma, visual field defects, double vision, reduced visual acuity, swelling of the eyelids and other eye disorders.
Since not all reactions are reported to the manufacturer, it is impossible to estimate their frequency accurately from the data of post-authorisation observation.
Overdose
In studies in healthy volunteers single doses of up to 800 mg caused the same undesirable reactions as smaller doses, but more often and more strongly. A dose of 200 mg did not increase efficacy, but did raise the frequency of headache, flushes, dizziness, dyspepsia, nasal congestion and visual disturbances.
In an overdose standard supportive treatment is given according to the symptoms. Sildenafil binds firmly to the plasma proteins and is not eliminated with the urine, so dialysis should not speed up its elimination.
How to get a prescription for Sildenafil Actavis online
Sildenafil is dispensed on prescription: before prescribing it, the cause of the erectile disturbance must be established, the state of the cardiovascular system assessed and it must be checked that the patient is not taking nitrates or other incompatible medicines.
During the online consultation the doctor will go through your situation and the medicines you take, will choose the dose and, if there are no contraindications, will issue an electronic prescription — the medicine can be collected from a pharmacy using its code.
