Ampliton Forte (Tablet kit) Instructions for Use

Marketing Authorization Holder

Makiz-Pharma, LLC (Russia)

ATC Code

C09BB (ACE inhibitors in combination with calcium channel blockers)

Active Substances

Amlodipine (Rec.INN registered WHO)

Cilazapril (Rec.INN registered WHO)

Dosage Form

Ampliton Forte

Set of tablets: 10 or 12 pcs. in blister packaging, 3 or 6 blister packs in a carton; tab. 10 mg: 5 or 7 pcs.; tab., coated, 2.5 mg: 5 or 7 pcs. respectively

Dosage Form, Packaging, and Composition

Tablets white or almost white color, flat-cylindrical shape, with a bevel and a score.

Auxiliary substances : lactose, cellulose microcrystalline, calcium stearate, sodium croscarmellose (primellose), silicon dioxide colloidal (aerosil).

Tablets, coated dull-red color, oval, biconvex, with an engraving on one side “CIL 2,5”, with a score – on the other side.

Auxiliary substances : lactose, starch corn, hydroxypropylmethylcellulose (hypromellose) 3 cPz, talc (sodium hydrosilicate), sodium stearyl fumarate.

Composition of the coating hydroxypropylmethylcellulose (hypromellose) 6 cPz, iron oxide red (E172), iron oxide yellow (E172), titanium dioxide (E171).

10 pcs. – packaging cell contour (3) – packs cardboard.
10 pcs. – packaging cell contour (6) – packs cardboard.

Clinical-Pharmacological Group

Antihypertensive drug

Pharmacotherapeutic Group

Combined antihypertensive agent (CCB + ACE inhibitor)

Indications

• Arterial Hypertension: The drug Ampliton Forte is indicated for the treatment of essential hypertension in patients for whom combination therapy is appropriate. It is not indicated for initial therapy.
• Combination Therapy Rationale: This fixed-dose combination is appropriate when the use of both amlodipine and cilazapril in the same doses as in the kit is considered suitable for an individual patient. The combination provides an additive antihypertensive effect, achieving better blood pressure control than either component alone.
• Target Patient Population: This medication is intended for patients whose blood pressure is not adequately controlled on monotherapy with either an ACE inhibitor or a dihydropyridine calcium channel blocker, or for those who are already receiving both components separately and are stabilized on the same doses present in this kit for improved convenience and adherence.

Contraindications

• Hypersensitivity: Hypersensitivity to cilazapril, amlodipine, other dihydropyridines, any other ACE inhibitor, or to any of the excipients listed in the composition.
• Angioedema: A history of angioedema (hereditary, idiopathic, or previous angioedema associated with ACE inhibitor therapy).
• Hemodynamic Instability: Patients with cardiogenic shock, clinically significant aortic stenosis, or unstable angina (excluding Prinzmetal’s angina).
• Pregnancy and Lactation: The use of Ampliton Forte is contraindicated during the second and third trimesters of pregnancy and is not recommended during the first trimester. It is also contraindicated in women who are breastfeeding.
• Concomitant Use with Aliskiren: In patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²), the concomitant use of Ampliton Forte with aliskiren-containing products is contraindicated.
• Dialysis: Patients undergoing dialysis with high-flux membranes (e.g., AN69).
• Severe Hepatic Impairment: Patients with severe hepatic impairment (Child-Pugh class C).

Dosage Regimen

The dosage of Ampliton Forte must be individualized based on the patient’s therapeutic needs and response. The kit is designed for a single day’s administration, comprising one 10 mg amlodipine tablet and one 2.5 mg cilazapril tablet.

Usual Adult Dose: The recommended dose is one Ampliton Forte kit per day, taken orally. The two different tablets from the kit should be taken together, preferably at the same time each day, with or without food. Consistency in timing is important for maintaining stable blood pressure control.

Dose Titration: This combination is for patients whose blood pressure is not adequately controlled on one of the components alone or for those already stabilized on both amlodipine and cilazapril in the same doses. Dose adjustment should be done under close medical supervision. Clinical response may be delayed; therefore, dosage adjustments should generally not be made more frequently than at 1- to 2-week intervals.

Special Populations: In elderly patients, no initial dosage adjustment is routinely required, but caution is advised due to a greater frequency of decreased hepatic, renal, or cardiac function. In patients with renal impairment, the dose should be carefully titrated. For patients with severe renal impairment (creatinine clearance < 30 ml/min), the use of cilazapril is not recommended, and therefore this combination should be avoided. In patients with hepatic impairment, the clearance of amlodipine is prolonged, and dosage recommendations have not been established; caution and close monitoring are required.

Adverse Reactions

Adverse reactions reported with the use of Ampliton Forte are generally those known for the individual components, amlodipine and cilazapril. The most common adverse reactions are usually mild and transient.

Very Common (≥1/10) and Common (≥1/100 to <1/10) Reactions: Headache, dizziness, somnolence, fatigue, palpitations, flushing, peripheral edema (ankle swelling), nausea, abdominal pain, dyspepsia, diarrhea, constipation, rash, pruritus, muscle cramps, myalgia, asthenia, and cough (a characteristic, persistent, dry cough associated with ACE inhibitors).

Uncommon (≥1/1,000 to <1/100) and Rare (≥1/10,000 to <1/1,000) Reactions: Hypotension, syncope, myocardial infarction, arrhythmia (including bradycardia, tachycardia), vasculitis, pancreatitis, hepatitis, cholestatic jaundice, angioedema (which may involve the face, extremities, lips, tongue, glottis, and/or larynx; requires immediate discontinuation and emergency treatment), urticaria, alopecia, purpura, hyperhidrosis, visual disturbances, tinnitus, taste disturbances (dysgeusia), paresthesia, tremor, impotence, mood changes, anxiety, sleep disorders, increased urinary frequency, renal dysfunction, including acute renal failure, and hematological abnormalities such as neutropenia, agranulocytosis, thrombocytopenia, and anemia.

Laboratory Findings: Increases in blood urea nitrogen (BUN) and serum creatinine, hyperkalemia, hyponatremia, elevations in liver enzymes (transaminases) and serum bilirubin have been observed.

If any serious adverse reaction or any other reaction not listed occurs, the patient should consult a physician.

Drug Interactions

Diuretics and Other Antihypertensive Agents: Concomitant use may lead to an additive hypotensive effect. In patients already on diuretics, particularly those with volume depletion, initiation of cilazapril may cause a pronounced fall in blood pressure. It is recommended to discontinue the diuretic or increase salt intake 2-3 days before starting Ampliton Forte, or initiate therapy under close medical supervision.

Lithium: ACE inhibitors can increase serum lithium concentrations and lithium toxicity. Concurrent use is not recommended. If necessary, monitor serum lithium levels frequently.

Potassium-Sparing Diuretics, Potassium Supplements, Salt Substitutes: Concomitant use with cilazapril can lead to a significant increase in serum potassium levels, which may result in hyperkalemia. Such combinations should be used with caution and with frequent monitoring of serum potassium.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): NSAIDs, including selective COX-2 inhibitors, may reduce the antihypertensive effect of ACE inhibitors and increase the risk of renal impairment, including acute renal failure. The risk is increased in elderly patients, those with volume depletion, or pre-existing renal impairment.

Sympathomimetics: Drugs such as ephedrine, pseudoephedrine, and adrenaline may reduce the antihypertensive effect of Ampliton Forte.

CYP3A4 Inhibitors: Amlodipine is metabolized by the cytochrome P450 3A4 system. Concomitant use with strong inhibitors (e.g., ketoconazole, itraconazole, ritonavir, clarithromycin) may increase the plasma concentration of amlodipine, potentially requiring a dose reduction. Caution is advised with moderate inhibitors (e.g., diltiazem, verapamil, erythromycin).

Inducers of CYP3A4: Drugs like rifampicin, St. John’s Wort, carbamazepine, and phenytoin can decrease the plasma concentrations of amlodipine, potentially reducing its therapeutic effect.

Allopurinol, Cytostatics, Immunosuppressants, Systemic Corticosteroids: Concurrent use with ACE inhibitors may increase the risk of leukopenia.

Gold Injections (Sodium Aurothiomalate): Nitritoid reactions (symptoms including facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients receiving ACE inhibitors and injectable gold.

Alcohol, Barbiturates, Narcotics: Concomitant use may potentiate vasodilation and can lead to an excessive hypotensive effect.

Overdose

Symptoms of Overdose: The most likely manifestation of an overdose with Ampliton Forte is profound hypotension, which may be accompanied by reflex tachycardia. Other symptoms can include dizziness, drowsiness, confusion, shock, electrolyte disturbances, and acute renal failure. The amlodipine component can cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. Significant bradycardia, including third-degree AV block, has been reported in amlodipine overdose. Cilazapril overdose can lead to severe hypotension, circulatory shock, hyperkalemia, hyponatremia, and renal failure.

Management: In case of suspected overdose, immediately discontinue the medication and institute supportive and symptomatic treatment. Gastric lavage and administration of activated charcoal may be considered if ingestion was recent. Close monitoring of cardiac and respiratory function, blood pressure, urine output, and serum electrolytes is essential.

Specific Measures: For severe hypotension, place the patient in a supine position with legs elevated and administer volume expanders (intravenous fluids). Vasopressors (such as dopamine or norepinephrine) may be used if necessary. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade by amlodipine. Atropine can be administered for bradycardia. Hemodialysis is not expected to be effective for removing amlodipine due to its high protein binding, but it may be beneficial for correcting electrolyte imbalances and removing cilazaprilat, the active metabolite of cilazapril.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.