Vanatex®: composition and dosage form
One film-coated tablet contains 80 mg or 160 mg of valsartan. This is plain valsartan, and that is the point of the medicine: it has three different indications, whereas the combined forms with a diuretic are used for only one of them. The starting dose after a heart attack — 20 mg twice a day — is provided by the divisible 40 mg tablet.
The tablet is taken independently of meals, with water. The composition includes lactose monohydrate, and that is the only restriction: in the rare hereditary disorders — galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption — the medicine is not suitable.
How Vanatex® works
Valsartan is a potent and specific angiotensin II receptor antagonist, active by mouth. It acts on the AT1 subtype, which is responsible for the known effects of angiotensin II: its affinity for AT1 is about 20 000 times greater than for AT2, and it shows not even partial agonist activity at AT1. The angiotensin II concentration raised after AT1 blockade may stimulate the unblocked AT2 receptor, which, judging by the data, acts antagonistically towards AT1.
The main practical difference from the ACE inhibitors follows from what valsartan does not do: it does not inhibit the activity of the angiotensin-converting enzyme, also known as kininase II, which converts angiotensin I into angiotensin II and breaks down bradykinin. Not acting on ACE and not potentiating the action of bradykinin or substance P, angiotensin II receptor antagonists rarely cause a cough: in trials a dry cough occurred significantly less often on valsartan than on an ACE inhibitor — 2.6% against 7.9%. And among people with a history of cough on an ACE inhibitor, 19.5% complained of it on valsartan and 19.0% on a thiazide diuretic, against 68.5% on the ACE inhibitor.
Indications
There are three indications and they differ fundamentally — from years of treating blood pressure to an intervention in the first hours after a heart attack. Each has its own dosing schedule and its own group of patients.
| Indication | For whom | Detail |
| Arterial hypertension | adults, and also children and adolescents aged 6–18 | treatment of essential hypertension |
| After a recent myocardial infarction | adults in a clinically stable condition | with symptomatic heart failure or asymptomatic left ventricular systolic dysfunction, from 12 hours to 10 days |
| Heart failure | adults with the symptomatic form | when ACE inhibitors are not tolerated; or as an addition to them in patients who cannot tolerate beta-blockers, if mineralocorticoid receptor antagonists cannot be given |
Note the wording of the last two indications: there valsartan is not the first choice but a replacement or an addition, when standard therapy is not tolerated. The assessment of such a patient always includes kidney function.
Method of administration and dosage
In hypertension the starting dose is 80 mg once a day. The effect is clearly noticeable within 2 weeks and reaches its maximum by 4 weeks, so it is not worth judging it earlier. If control is insufficient, the dose is raised to 160 mg and at most to 320 mg; the medicine combines with other antihypertensives, and hydrochlorothiazide strengthens the effect.
- after a heart attack treatment may start 12 hours after the diagnosis with 20 mg twice a day and be raised over several weeks to 40, 80 and 160 mg twice a day; for the first 2 weeks 80 mg twice a day is usual, and the target 160 mg twice a day is introduced over 3 months according to tolerance, while with symptomatic hypotension or impaired kidney function the dose is reduced;
- in heart failure the dose is increased at intervals of at least 2 weeks up to the highest tolerated; the maximum in the trials was 320 mg a day in divided doses;
- children aged 6–18 with hypertension: start at 40 mg once a day below 35 kg of body weight and 80 mg from 35 kg, with the ceiling depending on weight — 80 mg at 18–35 kg, 160 mg at 35–80 kg, 320 mg at 80–160 kg;
- in the elderly and in adults with a creatinine clearance above 10 ml/min no adjustment is needed, and in mild to moderate liver impairment without cholestasis the dose does not exceed 80 mg a day.
No less important is what should not be done. After a heart attack valsartan combines with thrombolytics, acetylsalicylic acid, beta-blockers, statins and diuretics, but not with an ACE inhibitor, and in heart failure the triple regimen of an ACE inhibitor, valsartan and a beta-blocker or a potassium-sparing diuretic is not recommended. In children under 6 efficacy has not been established, and after a recent infarction and in heart failure the medicine is not recommended for anyone under 18.
Contraindications
There are four prohibitions. Hypersensitivity to the active substance or to an excipient. Severe impairment of liver function, biliary cirrhosis and cholestasis. The second and third trimesters of pregnancy. And taking products containing aliskiren in patients with diabetes or with renal impairment at a glomerular filtration rate below 60 ml/min/1.73 m2.
The liver contraindications apply to children as well: with severe impairment, biliary cirrhosis and cholestasis valsartan is forbidden to them just as to adults, and in mild to moderate impairment experience is limited and the dose does not exceed 80 mg. The first trimester of pregnancy is not on the list, but that is not permission: use in it is not recommended.
Special warnings and precautions
The main things watched on valsartan are potassium and circulating blood volume. The medicine is not recommended together with potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes and other drugs capable of raising potassium, heparin for instance. In rare cases at the start of treatment, in patients with a marked sodium deficit or dehydration — say on large doses of diuretics — symptomatic hypotension may occur, so the sodium deficit and the blood volume are corrected beforehand by reducing the diuretic dose.
- kidneys: there is no experience at a creatinine clearance below 10 ml/min or on dialysis, and in children with a clearance below 30 ml/min the medicine is not recommended;
- renal artery stenosis: in bilateral stenosis and in stenosis of the artery of a single working kidney safety has not been established; in unilateral stenosis kidney function must be monitored;
- there is no experience after a recent kidney transplant; in primary hyperaldosteronism the medicine is not used — the renin-angiotensin system in such patients is suppressed;
- if kidney function depends on the renin-angiotensin system, as in severe congestive heart failure, treatment with ACE inhibitors was associated with oliguria and azotaemia and, rarely, acute renal failure; with valsartan this cannot be ruled out.
Like other vasodilators, valsartan calls for particular caution in aortic or mitral valve stenosis and in hypertrophic cardiomyopathy with outflow tract obstruction. Starting treatment after a heart attack and in heart failure also calls for caution: the blood pressure usually falls somewhat, but withdrawing the medicine because of persistent symptomatic hypotension is not usually necessary, provided the dosing schedule is followed. In children kidney function and potassium are monitored strictly, especially with fever and dehydration. The effect on driving has not been studied, but at the wheel dizziness and tiredness should be borne in mind.
Interaction with other medicines
The first interaction concerns the whole class. Dual blockade of the renin-angiotensin-aldosterone system — the simultaneous use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren — according to clinical trial data leads more often to hypotension, hyperkalaemia and impaired kidney function, including acute renal failure, than monotherapy.
| With what | What happens | What to do |
| Lithium | for ACE inhibitors a reversible rise in serum lithium and its toxicity has been described; there is no experience with valsartan | not recommended; if necessary, strict monitoring of lithium |
| Potassium-sparing diuretics, potassium supplements, potassium salt substitutes | a rise in potassium | monitoring of plasma potassium |
| NSAIDs, including COX-2 inhibitors and acetylsalicylic acid above 3 g a day | weakening of the antihypertensive effect, risk of worsening kidney function and rising potassium | kidney monitoring at the start of treatment and adequate hydration |
The list of safe combinations is shorter: no clinically significant interactions were found with cimetidine, warfarin, furosemide, digoxin, atenolol, indometacin, hydrochlorothiazide, amlodipine and glibenclamide. One more mechanism, though, did not make it into the table: valsartan is a substrate of the hepatic transporters OATP1B1/OATP1B3 and MRP2, so rifampicin, ciclosporin and ritonavir may increase its systemic exposure, and caution is needed when starting and ending such therapy. In children with hypertension kidney impairment is often present, so combining it with other agents that inhibit the renin-angiotensin-aldosterone system calls for strict monitoring. And one thing more: captopril with valsartan added no clinical benefit and did increase the risk of adverse reactions.
Pregnancy and breastfeeding
The practical rule matters here more than the formal ban: treatment with angiotensin II receptor antagonists is not started during pregnancy, and a woman planning a pregnancy is switched in advance to another antihypertensive with an established safety profile. If pregnancy is confirmed, the medicine is stopped immediately and alternative treatment begun where appropriate. Formally: in the first trimester these medicines are not recommended, in the second and third they are contraindicated.
The grounds for that severity differ by stage. For the first trimester the data on the teratogenicity of ACE inhibitors are not conclusive, but a small increase in risk cannot be excluded; there are no controlled data for angiotensin II receptor antagonists, yet a similar risk is possible for the class. For the second and third everything is clearer: exposure is toxic to the fetus — kidney function deteriorates, oligohydramnios develops, skull ossification is delayed — and in newborns renal failure, hypotension and hyperkalaemia have been described. With exposure from the second trimester onwards ultrasound monitoring of kidney function and skull development is recommended, and the children of such mothers are observed for hypotension. For breastfeeding there are no data and the medicine is not recommended.
Adverse effects
In hypertension the profile is quiet: in controlled trials in adults the frequency of adverse reactions was comparable with placebo, and no link with dose, duration of treatment, sex, age or race was seen. Uncommonly there were vertigo of labyrinthine origin, cough, abdominal pain and tiredness. With unknown frequency a fall in haemoglobin and haematocrit, neutropenia and thrombocytopenia, hypersensitivity up to serum sickness, a rise in potassium and hyponatraemia, vasculitis, raised liver enzymes and bilirubin, angioedema, rash, itching, muscle pain and impaired kidney function with a rise in creatinine have been described.
After a heart attack and in heart failure the picture is different, and this is probably connected with the underlying disease. Commonly recorded are dizziness, including postural dizziness, hypotension and orthostatic hypotension, and impaired kidney function. Uncommonly — fainting, headache, heart failure, cough, nausea, diarrhoea, angioedema, hyperkalaemia, acute renal failure and weakness. In children the profile is close to the adult one: in two trials with 561 patients aged 6–18 no differences were found apart from isolated gastrointestinal disorders and dizziness, while with chronic kidney disease hyperkalaemia was seen more often.
Overdose
An overdose of valsartan can cause a considerable fall in blood pressure, and that in turn a lowered level of consciousness, circulatory collapse and shock. The product information describes no other specific symptoms.
Management depends on the time since the medicine was taken and on the severity of the symptoms; the most important thing is to stabilise the circulation. With hypotension the patient is laid on their back and the circulating blood volume is corrected. One limitation is worth knowing in advance: removal of valsartan by haemodialysis is unlikely.
How to get a prescription for Vanatex® online
People usually come to valsartan from an ACE inhibitor, because of the dry cough that in trials plagued 68.5% of those who went back to an ACE inhibitor and only 19.5% of those who switched to valsartan. Changing the drug within blood pressure treatment is an ordinary medical task, and it is convenient to settle it remotely. On e-zdrowie.com you fill in a questionnaire, the doctor reviews the answers and issues an electronic prescription: the code arrives by message, and any Polish pharmacy will dispense the tablets against it.
Begin the questionnaire with kidneys and potassium — they are what determines the safety of renin-angiotensin blockers: give your latest creatinine or estimated filtration rate, your potassium level, and whether you have diabetes, dialysis, a transplanted kidney or renal artery stenosis. Then the medicines: aliskiren is contraindicated with diabetes and reduced filtration, an ACE inhibitor together with valsartan is not recommended, and potassium supplements, potassium-sparing diuretics, lithium and regular NSAIDs require monitoring. Note liver disease: severe impairment, biliary cirrhosis and cholestasis forbid the medicine, mild impairment limits the dose to 80 mg. Say whether you are pregnant or planning a pregnancy. And name what the medicine is for: the dosing schedules of the three indications are different.
