Efnocar T 40-40 Tablets

Efonidipine Hydrochloride Ethanolate and Telmisartan Tablets

Efnocar T 20/40

Each uncoated bilayered tablet contains :

Efonidipine Hydrochloride Ethanolate 20 mg

Telmisartan IP 40 mg

Excipients q.s.

Efnocar T 40/40

Each uncoated bilayered tablet contains :

Efonidipine Hydrochloride Ethanolate 40 mg

Telmisartan IP 40 mg

Excipients q.s.

Tablet Efonidipine Hydrochloride [20/40 mg] and Telmisartan [40/40 mg]

4.1 Therapeutic indication

For the management of stage II hypertension.

4.2 Posology and method of administration

Adult

The usual recommended dose is 1 tablet daily. It may be increased to 2 tablets per day depending upon the blood pressure control or as directed by the Physician.

Efonidipine

Essential hypertension : 20 - 40 mg orally once daily. A dose of up to 80 mg/day has been reported to be safe and effective in clinical trials.

Telmisartan

Essential hypertension : The usually effective dose is 40 mg once daily. In cases where the target blood pressure is not achieved, the dose of Telmisartan can be increased to a maximum of 80 mg once daily.

Use in special populations

Pediatric

The combination of Efonidipine and Telmisartan is not recommended in infants and children.

Geriatric

Efonidipine should be started at low dose (20 mg/day) in elderly. Patient should be carefully observed for development of hypotension. Dose may be halved if there is intolerance to the 20 mg/day dosage regimen. The pharmacokinetics of Telmisartan does not differ in young and elderly patients.

Hepatic impairment

Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute bioavailability of Telmisartan up to nearly 100%. Patients with hepatic impairment should be carefully monitored and dose should be slowly up titrated. Hence, caution should be exercised while administering FDC of Efonidipine and Telmisartan in patients with mild to moderate hepatic impairment.

Renal impairment

In Telmisartan limited experience is available in patients with severe renal impairment or haemodialysis. A lower starting dose of 20 mg is recommended in these patients. No dose adjustment is required for patients with mild to moderate renal impairment. Hence, caution should be exercised while administering FDC of Efonidipine and Telmisartan in patients with severe renal impairment or haemodialysis.

4.3 Contraindications

The combination of Efonidipine and Telmisartan is contraindicated in the following situations :

• Known hypersensitivity to the active substance Efonidipine and Telmisartan or any other component of the formulation.
• In pregnant women
• Severe hepatic impairment.
• Concomitant use of ACE inhibitors

4.4 Warning and precautions

Should be administered with caution in patients with hepatic impairment.

The drug may worsen clinical condition in patients with sinus bradycardia, sinus arrest or sinus node dysfunction.

Should not be taken with grapefruit juice as there may be excessive lowering of blood pressure.

Administration of the drug may cause hypotension. Under such circumstance appropriate measures should be taken to either reduce the dose or withdraw the drug

Dizziness may occur while taking the antihypertensive agents. Hence, working on aerial platform, working with machinery and/or driving should be avoided.

4.5 Drug interactions

Efonidipine

Concomitant administration of other antihypertensive agent/s may enhance the antihypertensive effect of Efonidipine.

Administration of Calcium channel blockers (CCBs) with cimetidine may cause elevated levels of CCBs.

Increased levels of CCBs observed when taken concomitantly with grapefruit juice which may result in excessive lowering of blood pressure.

Efonidipine when taken along with Tacrolimus may cause increased blood levels of Tacrolimus.

Telmisartan

• Concomitant administration of Digoxin may increase peak plasma concentration of Digoxin. When initiating, adjusting, and discontinuing Telmisartan, monitor Digoxin levels in order to maintain levels within the therapeutic range.
• Telmisartan may cause hyperkalaemia with other medicinal products acting on the renin-angiotensin-aldosterone system.
• Angiotensin II receptor antagonists such as Telmisartan, attenuate diuretic induced potassium loss.
• NSAIDs (i.e. Acetylsalicylic Acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists and increase risk of renal impairment.
• Co-administration of Telmisartan and Ramipril led to an increase of up to 2.5 fold in the AUC0-24 and Cmax of Ramipril and Ramiprilat.
• Prior treatment with high dose diuretics such as Furosemide (loop diuretic) and Hydrochlorothiazide (Thiazide diuretic) may result in volume depletion, and there is a risk of hypotension when initiating therapy with Telmisartan.
• The blood pressure lowering effect of Telmisartan can be increased by concomitant use of other antihypertensive medicinal products.
• Based on their pharmacological properties it can be expected that the following medicinal products may potentiate the hypotensive effects of all antihypertensives including Telmisartan : Baclofen, Amifostine. Furthermore, orthostatic hypotension may be aggravated by Alcohol, Barbiturates, Narcotics, or Antidepressants.

4.6 Special populations

Pregnancy

Efonidipine should not be administered to pregnant women and women suspected of being pregnant. Clinical experience with ACE inhibitors has shown increased risk of fetal and neonatal toxicity and death (“ACE inhibitor fetopathy”) when women are exposed to RAAS-active drugs during the last two trimesters of pregnancy. Since this may be a class effect of drugs acting on the RAAS, Telmisartan is contraindicated during pregnancy.

Lactation

Administration to lactating women should be avoided unless benefit significantly surpasses the risk to the child. Mothers on Efonidipine treatment should avoid breast feeding. It is not known whether Telmisartan is excreted in human milk, but Telmisartan was shown to be present in the milk of lactating rats. Because of the potential for adverse effects on the nursing infant, decide either drug or nursing should be discontinued, taking into account the importance of the drug to the mother.

4.7 Effects on ability to drive and use machines

Efonidipine / Telmisartan can have influence on the ability to drive and use machines. Dizziness or drowsiness may occasionally occur when taking Efonidipine/Telmisartan.

4.8 Undesirable effects

Efonidipine

Common side effects

The common side effects are hot flushes, palpitations, facial flushing and headache. In addition, elevation in serum total cholesterol, ALT (SGPT), AST (SGOT) and BUN may occur.

Uncommon side effects

Hepatobiliary disorders : LDH and alkaline phosphatase, Increase in bilirubin.

Renal and urinary disorders : serum creatinine rise, Proteinuria, Frequent urination.

Blood and lymphatic system disorders : Decreased hemoglobin, Decreased hematocrit, Decreased red blood cells,

Eosinophilia, Leukopenia, Thrombocytopenia.

Hypersensitivity : Rash, Itching

Cardiac disorders : Palpitations, Chest pain, Decreased blood pressure, Bradycardia, Tachycardia, Atrial fibrillation,

Premature ventricular contraction, Sick sinus syndrome, Atrioventricular junctional rhythm, Atrioventricular block, Shock

Nervous system disorders : Sluggishness and light-headedness, Drowsiness, Numbness

Gastrointestinal disorders : Nausea, Stomach discomfort, Abdominal pain, Vomiting, Constipation, Diarrhea, Gingival hyperplasia

Ear and labyrinth disorders : Tinnitus

Investigations : Increased CK (CPK), Increased uric acid and hypokalemia, Increased triglycerides

General : Malaise, Sweating, Edema

Telmisartan

Common side effects

The most frequent spontaneously reported events are Headache, Dizziness, Asthenia, Coughing, Nausea, Fatigue, Weakness, Edema, Face edema, Lower limb edema, Angioneurotic edema, Urticaria, Hypersensitivity, Sweating increased, Erythema, Chest pain, Atrial fibrillation, Congestive heart failure, Myocardial infarction, Blood pressure increased, Hypertension aggravated, Hypotension (including Postural hypotension), Hyperkalemia, Syncope, Dyspepsia, Diarrhea, Pain, Urinary tract infection, Erectile dysfunction, Back pain, Abdominal pain, Muscle cramps (including Leg cramps), Myalgia, Bradycardia, Eosinophilia, Thrombocytopenia, Uric acid increased, Abnormal hepatic function/liver disorder, Renal impairment including acute renal failure, Anemia, increased CPK, Anaphylactic reaction, Tendon pain (including Tendonitis, Tenosynovitis), Drug eruption (Toxic skin eruption mostly reported as Toxicoderma, Rash and Urticaria), Hypoglycemia (in Diabetic patients), and Angioedema (with Fatal outcome).

Uncommon side effects

Infections : Upper respiratory tract infection including pharyngitis and sinusitis, Sepsis

including fatal outcome

Psychiatric disorders : Insomnia, Depression, Anxiety

Nervous system disorders : Somnolence

Eye disorders : Visual disturbance

Ear and labyrinth disorders : Vertigo

Cardiac disorders : Tachycardia

Respiratory, thoracic and mediastinal disorders : Dyspnoea, Interstitial lung disease

Gastrointestinal disorders : Flatulence, Vomiting, Dry mouth, Stomach discomfort, Dysgeusia

Hepato-biliary disorders : Abnormal hepatic function /liver disorder

Skin and subcutaneous tissue disorders : Pruritus, Hyperhidrosis, Eczema, Erythema,

Muscoloskeletal and connective tissue disorders: arthralgia, pain in extremity

General disorders and administration site conditions : Chest pain, Influenza-like illness

Investigations : Blood creatinine increased, Haemoglobin decreased, Blood uric acid increased,

Hepatic enzyme

increased, Blood phosphokinase increased

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is

important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to : medico@zuventus.com

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

In humans, experience with intentional overdose is limited. Dizziness, nausea, somnolence, hypovolaemia, hypotension and electrolyte disturbances associated with cardiac arrhythmias and muscle spasms are some of the signs and symptoms associated with drug overdose. Gastric lavage, emesis or activated charcoal should be employed to reduce absorption. Blood pressure and fluid and electrolyte balance should be monitored and appropriate corrective measures taken. Intravenous fluid and electrolyte replacement may be indicated. Clinically significant hypotension due to drug over dosage calls for active cardiovascular support including frequent monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in restoring vascular tone and blood pressure, provided that there is no contraindication to its use. Intravenous Calcium Gluconate may be beneficial in reversing the effects of Calcium channel blockade.

5.1 Mechanism of action

Efonidipine, a new generation Dihydropyridine (DHP) Calcium channel blocker, inhibits both L-type and T-type Calcium channels.

Telmisartan blocks the vasoconstriction and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor.

5.2 Pharmacodynamic properties

Efonidipine

• Efonidipine exhibits antihypertensive effect through vasodilatation by blocking L-type and T-type Calcium channels.
• Efonidipine has a negative chronotropic effect. Working on sino atrial node cells by inhibiting T-type Calcium channel activation, Efonidipine prolongs the late phase-4 depolarization of the sino atrial node action potential and suppresses an elevated HR. The negative chronotropic effect of Efonidipine decreases heart rate, myocardial oxygen demand and increases coronary blood flow.
• Efonidipine increases coronary blood flow by blocking L & T-type Calcium channels and attenuates myocardial ischemia.
• By reducing synthesis and secretion of aldosterone, Efonidipine prevents hypertrophy and remodeling of cardiac myocytes.
• Efonidipine increases glomerular filtration rate without increasing intra-glomerular pressure and filtration fraction. This prevents hypertension induced renal damage
• Efonidipine prevents Rho-kinase and NF B induced renal parenchymal fibrosis and provides long term renal protection.
• Efonidipine suppresses renin secretion from the juxta glomerular apparatus in the kidneys.
• Efonidipine enhances sodium excretion from the kidneys by suppressing aldosterone synthesis and secretion from the adrenal glands. Aldosterone induced renal parenchymal fibrosis is suppressed by Efonidipine.
• Efonidipine prevents NF B induced hypertrophy and inflammation in the renal vasculature and protects the kidneys.
• Efonidipine protects against endothelial dysfunction due to its anti-oxidant activity and by restoring NO bioavailability.
• Efonidipine has anti-atherogenic activity and protects the blood vessels from atherosclerosis.
• Efonidipine lowers blood pressure in cerebral resistance vessels and prevents hypertension induced brain damage.

Telmisartan

• Telmisartan is an orally active and specific angiotensin II receptor (type AT1) antagonist. Telmisartan displaces angiotensin II with very high affinity from its binding site at the AT1 receptor subtype, which is responsible for the known actions of angiotensin II.
• Telmisartan does not exhibit any partial agonist activity at the AT1 receptor. Telmisartan selectively binds the AT1 receptor. The binding is long-lasting.
• Telmisartan does not show affinity for other receptors, including AT2 and other less characterized AT receptors. The functional role of these receptors is not known, nor is the effect of their possible overstimulation by angiotensin II, whose levels are increased by Telmisartan. Plasma aldosterone levels are decreased by Telmisartan
• Telmisartan does not inhibit human plasma renin or block ion channels. Telmisartan does not inhibit angiotensin converting enzyme (kininase II), the enzyme which also degrades bradykinin. Therefore, it is not expected to potentiate bradykinin-mediated adverse effects.

5.3 Pharmacokinetic properties

Efonidipine

Peak plasma concentration is achieved in about 1.5 to 3.67 hours after administration. The bioavailability of Efonidipine is ~25% and half-life is approximately 4 hours. Efonidipine is primarily metabolized in liver. The important metabolites are N-dephenylated Efonidipine (DPH), deaminated Efonidipine (AL) and N-debenzylated Efonidipine (DBZ). DBZ and DPH exhibit activity as Calcium antagonists. The vasodilating properties of DBZ and DPH are about two-third and one-third respectively than that of parent compound. Biliary route is the main route of excretion. No significant amount of unchanged drug is excreted in urine. In the urine collected for 24 hours after an oral dosing, 1.1% of the dose was excreted as deaminated Efonidipine and 0.5% as a pyridine analogue of deaminated.

Telmisartan

Absorption of Telmisartan is rapid although the amount absorbed varies. The mean absolute bioavailability for Telmisartan is about 50%. When Telmisartan is taken with food, the reduction in the area under the plasma concentration-time curve of Telmisartan varies from approximately 6% (40 mg dose) to approximately 19% (160 mg dose). By 3 hours after administration, plasma concentrations are similar whether Telmisartan is taken fasting or with food. Telmisartan is largely bound to plasma protein (>99.5%), mainly albumin and alpha-1 acid glycoprotein. The mean steady state apparent volume of distribution (Vdss) is approximately 500 L. Telmisartan is metabolised by conjugation to the glucuronide of the parent compound. No pharmacological activity has been shown for the conjugate. Telmisartan is characterised by biexponential decay pharmacokinetics with a terminal elimination half-life of 24 hours.

6.1 Animal toxicology or pharmacology

No known animal toxicology data

8.1 Incompatibilities

Not applicable

8.2 Shelf life

24 Months

8.3 Packaging information

Efnocar T 20/40 : Alu-Alu blister strip of 10 tablets

Efnocar T 40/40 : Alu-Alu blister strip of 10 tablets.

8.4 Storage and handing Instructions

Store protected from moisture at a temperature not exceeding 30°C

Keep out of reach of children.

Who should not take Efnocar T ?

You should not take Efnocar T tablets if you are allergic (hypersensitive) to the active ingredients (Telmisartan or Efonidipine).

For patients with diabetes, if you are taking Efnocar T you should not take aliskiren

What should I tell my doctor before taking Efnocar T tablets ?

Before you take Efnocar T tablets, tell your doctor if you :

• Have liver problems.
• Have kidney problems.
• Have heart problems.
• Have any other medical conditions.
• Are pregnant or are planning to become pregnant.
• Are breast-feeding or plan to breast-feed. It is not known if Efnocar T passes into your breast milk.

You and your doctor should decide if you will take Efnocar T tablets or breast-feed. You should not do both. Talk with your doctor about the best way to feed your baby if you take Efnocar T tablets. Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements.

Efnocar T may affect the way other medicines work, and other medicines may affect how Efnocar Tworks. Especially tell your doctor if you take :

• Aliskiren
• Digoxin
• Lithium
• Medicines used to treat pain and arthritis, called non-steroidal anti-inflammatory drugs (NSAIDs), including COX2 inhibitors.
• Ramipril or other medicines that may be used to treat high blood pressure or a heart problem.
• Simvastatin
• Water pills (diuretics)

Know the medicines you take. Keep a list of them and show it to your doctor or pharmacist when you get a new medicine. How should I take Efnocar T tablets ?

Take Efnocar T tablets exactly as your doctor tells you to take it.

Your doctor will tell you how much Efnocar T to take and when to take it. Your doctor may change your dose if needed.

• Take Efnocar T one time each day at the same time.
• Take Efnocar T tablets with or without food.
• If you miss a dose, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Take the next dose at your regular time.
• If you take too much Efnocar T, call your doctor or go to the nearest hospital emergency room right away.

What are possible side effects of Efnocar T tablets ?

Efnocar T tablets may cause serious side effects, including :

Injury or death to your unborn baby.

Low blood pressure (hypotension) is most likely to happen if you also :

• Take water pills. (diuretics)
• Are on a low-salt diet.
• Get dialysis treatments
• Have heart problems.
• Get sick with vomiting or diarrhea

If you feel faint or dizzy, lie down and call your doctor right away.

• Kidney problems. Kidney problems may get worse if you already have kidney disease. You may have changes in your kidney test results, and you may need a lower dose of Efnocar T tablets. Call your doctor if you get :
• Swelling in your feet, ankles, or hands
• Unexplained weight gain

Call your doctor right away if you get any of the symptoms listed above.

• Heart problems or heart attack. Heart problems may get worse in people that already have heart disease. This may happen when you start Efnocar T tablets or when there is an increase in your dose of Efnocar T. Get emergency help if you get worse chest pain or chest pain that does not go away.
• High potassium in the blood (hyperkalemia). Your doctor may check your potassium levels as needed.
• Muscle rigidity, tremor and/or abnormal muscle movement

Rare, serious allergic reactions may happen. Tell your doctor right away if you get any of these symptoms :

• Swelling of face, tongue, throat.
• Difficulty breathing.
• Skin rash.

The most common side effects of Efnocar T tablets include :

• Swelling in your hands, ankles, or feet.
• Feeling like your heart is pounding or racing
• Flushing or sudden redness of the face and neck.
• Dizziness
• Back pain.
• Feeling tired or sleepy
• Abdominal pain, nausea, or diarrhea.
• Low blood pressure or a sudden drop in blood pressure with fainting.

These are not all the possible side effects of Efnocar T tablets. Tell your doctor if you have any other side effects.

03 January 2022