Products

Molivart 5/320

Amlodipine Besylate 7 mg
& Valsartan 320 mg

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Active ingredient

  • Amlodipine Besylate 7 mg( eq. to 5.0 mg Amlodipine ).
  • Valsartan 320 mg

Indications

  • Treatment of essential hypertension.
  • Molivart is indicated in patients whose blood pressure is not adequately controlled on amlodipine or valsartan monotherapy.

Dosage and Administration

• General Considerations:
Amlodipine is an effective treatment of hypertension in once daily doses of 2.5 mg to 10 mg while valsartan is effective in doses of 80 mg to 320 mg. In clinical trials with once daily Molivart (amlodipine and valsartan) using amlodipine doses of 5 mg to 10 mg and valsartan doses of 160 mg to 320 mg, the antihypertensive effects increased with increasing doses.
The hazards of valsartan are generally independent of dose; those of amlodipine are a mixture of dose-dependent phenomena (primarily peripheral edema) and dose-independent phenomena, the former much more common than the latter.
The majority of the antihypertensive effect is attained within 2 weeks after initiation of therapy or a change in dose. The dosage can be increased after 1 to 2 weeks of therapy to a maximum of one 10/320 mg tablet once daily as needed to control blood pressure.
• Molivart may be administered with or without food.
• Molivart may be administered with other antihypertensive agents.
• Elderly patients: Because of decreased clearance of amlodipine, therapy should usually be initiated at 2.5 mg.
• Renal Impairment: No initial dosage adjustment is required for patients with mild or moderate renal impairment. Titrate slowly in patients with severe renal impairment.
• Hepatic Impairment: No initial dosage adjustment is required for patients with mild or moderate liver insufficiency. Titrate slowly in patients with hepatic impairment.
• Add-on Therapy:
A patient whose blood pressure is not adequately controlled with amlodipine (or another dihydropyridine calcium-channel blocker) alone or with valsartan (or another angiotensin II receptor blocker) alone may be switched to combination therapy with Molivart 5/160 /Molivart 5/320
A patient who experiences dose-limiting adverse reactions on either component alone may be switched to Molivart containing a lower dose of that component in combination with the other to achieve similar blood pressure reductions. The clinical response to Molivart should be subsequently evaluated and if blood pressure remains uncontrolled after 3 to 4 weeks of therapy, the dose may be titrated up to a maximum of 10/320 mg.

Contraindication

  • Hypersensitivity to the active substances, to dihydropyridine derivatives, or to any of the excipients.
  • Severe hepatic impairment, biliary cirrhosis or cholestasis.
  • Severe renal impairment (GFR <30 ml/min/1.73 m2) and patients undergoing dialysis.
  • Second and third trimesters of pregnancy.

Side effects

• The safety of amlodipine /valsartan has been evaluated in the controlled clinical studies with 5,175 patients, 2,613 of whom received valsartan in combination with amlodipine. (See insert leaflet)
• Additional information on the combination:
Peripheral edema, a recognized side effect of amlodipine, was generally observed at a lower incidence in patients who received the amlodipine/valsartan combination than in those who received amlodipine alone. The incidence of peripheral edema by dose is stated in the insert leaflet.
• Additional information on the individual components:
Adverse drug reactions previously reported with one of the individual components (amlodipine or valsartan) may be potential undesirable effects with amlodipine / valsartan combination as well, even if not observed in clinical trials or during the post-marketing period(see insert leaflet).

Drug Interaction

• Interactions linked to amlodipine
Caution required with concomitant use CYP3A4 inhibitors.
A study in elderly patients has shown that diltiazem inhibits the metabolism of amlodipine, probably via CYP3A4 (plasma concentration increases by approximately 50% and the effect of amlodipine is increased). The possibility that more potent inhibitors of CYP3A4 (i.e. ketoconazole, itraconazole, ritonavir) may increase the plasma concentration of amlodipine to a greater extent than diltiazem cannot be excluded.
CYP3A4 inducers (anticonvulsant agents [e.g. carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone], rifampicin, Hypericum perforatum)
Co-administration may lead to reduced plasma concentrations of amlodipine. Clinical monitoring is indicated, with possible dosage adjustment of amlodipine during the treatment with the inducer and after its withdrawal.
- To be taken into account with concomitant use.
• Others
In monotherapy, amlodipine has been safely administered with thiazide diuretics, beta blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenal, anti-acid medicines (aluminium hydroxide gel, magnesium hydroxide, simeticone), cimetidine, non-steroidal anti-inflammatory medicines, antibiotics and oral hypoglycaemic medicines.
- Interactions linked to valsartan.
- Concomitant use not recommended.
• Lithium
Reversible increases in serum lithium concentrations and toxicity have been reported during concurrent use of ACE inhibitors. Despite the lack of experience with concomitant use of valsartan and lithium, this combination is not recommended. If the combination proves necessary, careful monitoring of serum lithium levels is recommended.
Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substances that may increase potassium levels If a medicinal product that affects potassium levels is to be prescribed in combination with valsartan, monitoring of potassium plasma levels is advised.
- Caution required with concomitant use.
• Non-steroidal anti-inflammatory medicines (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid (>3 g/day), and non-selective NSAIDs
When angiotensin II antagonists are administered simultaneously with NSAIDs attenuation of the antihypertensive effect may occur. Furthermore, concomitant use of angiotensin II antagonists and NSAIDs may lead to an increased risk of worsening of renal function and an increase in serum potassium. Therefore, monitoring of renal function at the beginning of the treatment is recommended, as well as adequate hydration of the patient.
• Others
In monotherapy with valsartan, no interactions of clinical significance have been found with the following substances: cimetidine, warfarin, furosemide, digoxin, atenolol, indometacin, hydrochlorothiazide, amlodipine, glibenclamide. Interactions common to the combination
No drug interaction studies were performed with Molivart and other medicinal products.
- To be taken into account with concomitant use.
• Other antihypertensive agents
Commonly used antihypertensive agents (e.g. alpha blockers, diuretics) and other medicinal products which may cause hypotensive adverse effects (e.g. tricyclic antidepressants, alpha blockers for treatment of benign prostate hyperplasia) may increase the antihypertensive effect of the combination.

Pregnancy and Lactation

Pregnancy: 
Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Antagonists (AIIRAs), similar risks may exist for this class of drugs. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started.
Exposure to AIIRA therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossication retardation) and neonatal toxicity (renal failure, hypotension, and hyperkalaemia).
Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken AIIRAs should be closely observed for hypotension.
Lactation:
Because no information is available regarding the use of Molivart during breastfeeding, Molivart is not recommended and alternative treatments with better established safety proves during breast-feeding are preferable, especially while nursing a new-born or preterm infant.

Warning and Precaution

Pregnancy
Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started.
Sodium- and/or volume-depleted patients
Excessive hypotension was seen in 0.4% of patients with uncomplicated hypertension treated with Amlodipine/ valsartan in placebo-controlled studies. In patients with an activated renin- angiotensin system (such as volume- and/or salt-depleted patients receiving high doses of diuretics) who are receiving angiotensin receptor blockers, symptomatic hypotension may occur. Correction of this condition prior to administration of Amlodipine/ valsartan or close medical supervision at the start of treatment is recommended.
If hypotension occurs with Molivart, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. Treatment can be continued once blood pressure has been stabilised.
Hyperkalaemia
Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other medicinal products that may increase potassium levels (heparin, etc.) should be undertaken with caution and with frequent monitoring of potassium levels.
Renal artery stenosis
No data are available on the use of Molivart in patients with bilateral renal artery stenosis or stenosis to a solitary kidney.
Kidney transplantation
To date there is no experience of the safe use of Molivart in patients who have had a recent kidney transplantation.
Hepatic impairment
Valsartan is mostly eliminated unchanged via the bile, whereas amlodipine is extensively metabolised by the liver. Particular caution should be exercised when administering Molivart to patients with mild to moderate hepatic impairment or biliary obstructive disorders.
In patients with mild to moderate hepatic impairment without cholestasis, the maximum recommended dose is 80 mg valsartan.
Renal impairment
No dosage adjustment of Molivart is required for patients with mild to moderate renal impairment (GFR>30 ml/min/1.73 m2). Monitoring of potassium levels and creatinine is advised in moderate renal impairment.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism should not be treated with the angiotensin II antagonist valsartan as their renin-angiotensin system is affected by the primary disease.
Heart failure
As a consequence of the inhibition of the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotaemia and (rarely) with acute renal failure and/or death. Similar outcomes have been reported with valsartan.
In a long-term, placebo-controlled study (PRAISE-2) of amlodipine in patients with NYHA (New York Heart Association Classification) III and IV heart failure of non-ischaemic aetiology, amlodipine was associated with increased reports of pulmonary oedema despite no significant difference in the incidence of worsening heart failure as compared to placebo.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy
As with all other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Molivart has not been studied in any patient population other than hypertension.

Package and Storage

  • Storage:
    - Store at temperature not exceeding 30ºC in a dry place.
    - Store in the original package in order to protect from moisture.
  • Package: Carton box containing 1, 2 or 3 strips each of 7 film coated tablets and insert leaflet.

Mother Company

Manufactured by Marcyrl