Coveram Drug Interactions

Perindopril: Concomitant Use With the Following is Not Recommended: Potassium-Sparing Diuretics, Potassium Supplements or Potassium-Containing Salt Substitutes: ACE inhibitors attenuate diuretic induced potassium loss. Potassium-sparing diuretics eg, triamterene or amiloride, potassium supplements or potassium-containing salt substitutes may lead to significant increases in serum potassium and are, therefore, not recommended (see Precautions). If the concomitant use in indicated because of documented hypokalemia, it should be cautiously and with frequent monitoring of serum potassium level.
Lithium: Reversible increase in serum lithium concentrations and toxicity (severe toxicity) have been reported during concurrent use of ACE inhibitors. The combination of perindopril with lithium is not recommended. If the combination proves necessary, careful monitoring of serum lithium levels is recommended (see Precautions).
Estramustine: Risk of increased adverse effects eg, angioneurotic edema (angioedema).
Concomitant Use Which Requires Special Care: Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Including Aspirin ≥3 g/day: The administration of a non-steroidal anti-inflammatory drug may lead to an increased risk of worsening of renal function, including possible acute renal failure, and an increase in serum potassium, especially in patients with poor preexisting renal function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy, and periodically thereafter.
Antidiabetic Agents (Insulin, Hypoglycemic Sulfonamides): The use of angiotensin converting enzyme inhibitors may increase the hypoglycemic effects in diabetics receiving treatment with insulin or with hypoglycemic sulfonamides. The onset of hypoglycemic episodes is very rare (there is probably an improvement in glucose tolerance with a resulting reduction in insulin requirements).
Concomitant Use To Be Taken Into Consideration: Diuretics: Patients on diuretics and especially those who are volume and/or salt depleted, may experience excessive reduction in blood pressure after initiation of therapy with an ACE inhibitor. The possibility of hypotensive effects can be reduced by discontinuation of the diuretic, by increasing volume or salt intake prior to initiating therapy with low and progressive doses of perindopril.
Sympathomimetics: Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.
Gold: Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including perindopril.
Amlodipine: Concomitant Use With Dantrolene (Infusion) is Not Recommended: In animals, lethal ventricular fibrillations are observed after administration of verapamil and dantrolene IV by extrapolation, the combination of amlodipine and dantrolene should be avoided.
Concomitant Use With CYP3A4 Inducers and Inhibitors Require Special Care: CYP3A4 inducers (rifampicin, Hypericum perforatum, anticonvulsant agents ie, carbamazepine, phenobarbital, fosphenytoin, primidone): Co-administration with Coveram may lead to reduced plasma concentration of amlodipine due to increased hepatic metabolism by these inducers. Caution should be exercised in combination of amlodipine with CYP3A4 inducers and posology of amlodipine could be adjusted if needed.
CYP3A4 Inhibitors (Itraconazole, Ketoconazole): Co-administration with Coveram may increase the plasma concentration of amlodipine and consequently its adverse effects. Caution should be exercised when combining with itraconazole or ketoconazole and posology of amlodipine should be adjusted if needed.
Concomitant Use To be Taken Into Consideration: β-blockers used in heart failure (bisoprolol, carvedilol, metoprolol) may increase risk of hypotension, heart weakness in patients with cardiac heart failure, be it latent or uncontrolled (addition of negative inotrope effect). Furthermore, the β-blocker may minimize the sympathic reflex in case of excessive hemodynamic repercussion.
Other Combinations: In monotherapy, amlodipine has been safely administered with thiazide diuretics, β-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, antacid medicines (aluminum hydroxide gel, magnesium hydroxide, simethicone), cimetidine, nonsteroidal anti-inflammatory medicines, antibiotics and oral hypoglycemic medicines.
Indeed, specific studies conducted with some drugs have shown no influence on amlodipine: Co-administration of amlodipine with cimetidine did not alter the pharmacokinetics of amlodipine, when sildenafil and amlodipine were used in combination, each one independently exerted its own blood pressure-lowering effect, grapefruit juice: co-administration of 240 mL of grapefruit juice with a single oral dose of 10 mg amlodipine in 20 healthy volunteers had no significant effect on the pharmacokinetics of amlodipine.
Moreover, specific studies conducted with some drugs have shown that amlodipine has no influence on their pharmacokinetics parameters: Atorvastatin: Co-administration of multiple doses of 10-mg amlodipine with 80 mg of atorvastatin resulted in no significant change in the steady-state pharmacokinetics parameters of atorvastatin.
Digoxin: Co-administration of amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers.
Warfarin: In healthy male volunteers, the co-administration of amlodipine did not significantly alter the effect of warfarin on prothrombin response time. Co-administration of amlodipine with warfarin did not change the warfarin prothrombin response time.
Ciclosporin: Pharmacokinetic studies with ciclosporin have demonstrated that amlodipine does not significantly alter the pharmacokinetics of ciclosporin.
Concomitant Use Which Requires Special Care: Baclofen: Potentiation of the antihypertensive effect of Coveram. Monitoring of blood pressure and renal function and dose adaptation of the antihypertensive if necessary.
Concomitant Used To be Taken Into Consideration: Antihypertensive agents (eg, β-blockers) and Vasodilators: Concomitant use with Coveram may increase the hypotensive effects of perindopril and amlodipine. Concomitant use with nitroglycerin and other nitrates or other vasodilators, may further reduce blood pressure and therefore should be considered with caution.
Corticosteroids, Tetracosactide: Reduction in antihypertensive effect (salt and water retention due to corticosteroids).
Alpha-blockers (Prazosin, Alfuzosin, Doxazosin, Tamsulosin, Terazosin): Increased antihypertensive effect and increased risk of orthostatic hypotension.
Amifostine: May potentiate the antihypertensive effect of amlodipine.
Tricyclic Antidepressants/Antipsychotics/Anesthetics: increased antihypertensive effect and increased risk of orthostatic hypotension