Drug Interactions of Antihypertensives (Part 4):

Drug Interactions of Dihydropyridines (Calcium Channel Blockers):

More presentations from Naina Mohamed Pakkir Maideen

©   The most common Dihydropyridine Calcium Channel blockers include Amlodipine, Nifidepine, Nicardipine, Felodipine, Nisoldipine, Isradipine and Clevidipine.

©   Dihydropyridines are useful in the management of hypertension and coronary artery disease.

©   Dihydropyridines inhibit calcium ion influx across cell membranes of vascular smooth muscle cells and cardiac muscle cells. Dihydropyridines are peripheral arterial vasodilators which act directly on vascular smooth muscle to reduce peripheral vascular resistance and reduction of blood pressure.

©   Dihydropyridines can interact significantly with many drugs including Primidone, Colchicine, Ketoconazole, Itraconazole, Clopidogrel, CYP3A4 Inhibitors, CYP3A4 Inducers and CYP3A4 Substrates.

©   It is contraindicated to use Felodipine or Nisoldipine along with Ketoconazole or Itraconazole, due to the potential for cardiotoxicity.

©   Concomitant use of Dihydropyridines and Primidone is contraindicated.

©   Coadministration of Dihydropyridines and Colchicine is contraindicated in patients with renal or hepatic impairment, due to increased risk of colchicine toxicity.

©   The risk of thrombotic events is elevated when dihydropyridines and Clopidogrel are used concurrently.

©   The risk of adverse effects of dihydropyridines is increased in patients taking CYP3A4 Inhibitors such as Clarithromycin, Telaprevir, Ritonavir, Ceritinib, Nilotinib,  Conivaptan, etc.

©   CYP3A4 Inducers like Carbamazepine, Eslicarbazepine acetate, St. John’s wort, Dabrafenib, etc. might decrease the exposure of dihydropyridines.

©   The risk of toxicity of CYP3A4 substrates such as Domperidone, Fentanyl, Eliglustat, etc. might be elevated by the coadministration of dihydropyridines.

Pregnancy:

©   Dihydropyridines could be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast Feeding:

©   It is recommended to discontinue breast feeding, when dihydropyridines are administered to nursing women.

Drug Interactions of Antihypertensives (Part 3):

Drug Interactions of Direct Renin Inhibitor (Aliskiren):

More presentations from Naina Mohamed Pakkir Maideen

©   Aliskiren is a Direct Renin Inhibitor (DRI) and is useful in the treatment of Hypertension.

©   Aliskiren inhibits Renin which is essential for the conversion of Angiotensinogen to Angiotensin I. Hence the formation of Angiotensin II is limited.  Angiotensin II can increase the blood pressure by vasoconstriction and by stimulating the production of aldosterone from the adrenal cortex, which increases the reabsorption of sodium.

©   Aliskiren can interact significantly with many drugs including ACE Inhibitors (ACEIs), Angiotensin Receptor Blockers (ARBs), Cyclosporine, Itraconazole, P-gp Inhbitors and Potassium sparing diuretics.

©   It is contraindicated to use Aliskiren with ACEIs (Captopril, Lisinopril, Perindopril, etc.) or ARBs (Losartan, Candesartan, Valsartan, etc.) in diabetes patients, due to increased risk of Hyperkalemia, Renal impairment and Hypotension.

©   The blood concentrations of Aliskiren might be elevated by the drugs such as Cyclosporine, Itraconazole and P-gp Inhbitors (Simeprevir, Lomitapide, Ulipristal, Nilotinib, Eliglustat, Tocofersolan, etc.).

©   Severe arrhythmias may occur in patients taking Aliskiren and Potassium Sparing Diuretics (Spiranolactone, Amiloride, Triamterene, etc.), due to increased risk of Hyperkalemia.

Pregnancy:

©   Aliskiren should be discontinued as soon as possible, if pregnancy occurs during use.

Breast Feeding:

©   It is recommended to discontinue either Aliskiren or breast feeding.

Drug Interactions of Antihypertensives (Part 2):

Drug Interactions of Angiotensin Receptor Blockers:

More presentations from Naina Mohamed Pakkir Maideen

©    Angiotensin Receptor Blockers (ARBs) are useful in the treatment of Hypertension, Congestive Heart Failure and Diabetic Nephropathy.

©    ARBs block the action of Angiotensin II by preventing the binding of angiotensin II angiotensin receptors on the muscles surrounding blood vessels. Inhibited binding of Angiotensin II, results in to vasodilation causing reduction of blood pressure. The function of a failing heart could be improved by lowered blood pressure making it easier for the heart to pump blood.

©    ARBs can interact significantly with many drugs including Aliskiren, ACE Inhibitors, Lithium, CYP2C9 Inhibitors, CYP3A4 Inhibitors, CYP3A4 Inducers, Potassium sparing diuretics, Trimethoprim, NSAIDs and Insulin.

©    It is contraindicated to use ARBs along with Aliskiren concomitantly in diabetes patients, due to increased risk of Hyperkalemia, Renal impairment and Hypotension.

©    Coadministration of ARBs and ACE Inhibitors (Captopril, Lisinopril, Perindopril, etc.) may result in to increased risk of adverse events (Hypotension, syncope, hyperkalemia, changes in renal function, acute renal failure).

©    Concomitant use of ARBs and Lithium may result in to Lithium toxicity (weakness, tremor, excessive thirst, confusion).

©    The risk of toxicity of ARBs may be elevated by the concomitant use of ARBs and CYP2C9 Inhbitors (Entacapone, Ceritinib, etc.) or CYP3A4 Inhibitors (Darunavir, Clarithromycin, Cobicistat, Nilotinib, Crizotinib, Ceritinib, Piperaquine, etc.).

©    Loss of therapeutic efficacy of ARBs may occur in patients taking CYP3A4 Inducers (Carbamazepine, Dabrafenib, etc.).

©    Severe arrhythmias may occur in patients taking ARBs and Potassium Sparing Diuretics (Spiranolactone, Amiloride, Triamterene, etc.) or Trimethoprim, due to increased risk of Hyperkalemia.

©    Use of NSAIDs in patients taking ARBs may result in to renal dysfunction or decreased antihypertensive efficacy.

©    Increased risk of Hypoglycemia noted in patients taking ARBs along with Insulin.

©    Concomitant use of Telmisartan and Digoxin may result in to digoxin toxicity (Slow pulse, Irregular heartbeats, Nausea, Loss of appetite, Visual changes, etc.).

©    Use of ARBs during pregnancy is strongly discouraged.

©    It is recommended to discontinue either ARBs or breast feeding.

Drug Interactions of Antihypertensives (Part 1):

Drug Interactions of ACE Inhibitors:

Drug Interactions of ACE Inhibitors

More presentations from Naina Mohamed Pakkir Maideen 

©   Angiotensin Converting Enzyme Inhibitors (ACEIs) are useful in the treatment of Hypertension, Congestive Heart Failure, Acute Myocardial Infarction and Diabetic Nephropathy.

©   ACEIs decrease the production of Angiotensin II through the inhibition of Angiotensin Converting Enzyme. Decreased production of Angiotensin II, results in to vasodilation causing reduction of blood pressure. The function of a failing heart could be improved by lowered blood pressure making it easier for the heart to pump blood.

©   ACEIs can interact significantly with many drugs including Aliskiren, Potassium sparing diuretics, Potassium supplements, Cyclosporine, Trimethoprim, Angiotensin Receptor Blockers (ARBs), mTOR Inhibitors, Alteplase, Lithium, Azathioprine, Antidiabetics and NSAIDs.

©   It is contraindicated to use ACEIs along with Aliskiren concomitantly, due to increased risk of Hyperkalemia, Renal impairment and Hypotension.

©   Severe arrhythmias may occur in patients taking ACEIs and Potassium Sparing Diuretics (Spiranolactone, Amiloride, Triamterene, etc.), Potassium Suplements, Cyclosporine or Trimethoprim, due to increased risk of Hyperkalemia.

©   Coadministration of ACEIs and Angiotensin receptor blockers (ARBs) (Losartan, Valsartan, Candesartan, etc.) results in increased risk of adverse events (Hypotension, syncope, hyperkalemia, changes in renal function, acute renal failure).

©   The risk of Angioedema might be elevated by concomitant use of ACEIs and Mammalian Target of Rapamycin (mTOR) inhibitors (Sirolimus, Everolimus, Deforolimus, etc.).

©   Administration of Alteplase in patients taking ACEIs increases the bradykinin levels and elevates the risk of Orolingual angioedema.

©   Concomitant use of ACEIs and Lithium may result in to Lithium toxicity (weakness, tremor, excessive thirst, confusion).

©    Anemia or Leukopenia may occur in patients taking ACEIs and Azathioprine due to myelosuppression.

©   Increased risk of Hypoglycemia noted in patients taking ACEIs along with Antidiabetics.

©   Use of NSAIDs in patients taking ACEIs may result in to renal dysfunction or decreased antihypertensive efficacy.

©   Use of ACEIs during pregnancy is strongly discouraged.

©   Caution should be used when administering ACEIs to a nursing mother.

Clinically Important Drug Interactions in Diabetes:

©  Diabetes patients may take a large number of medications to manage blood glucose, cholesterol, blood pressure, etc. which may increase the probability of Drug interactions.

©  Most of the clinically important drug-drug interactions of anti-diabetic agents are related to their metabolic pathways.

©  Gemfibrozil inhibits CYP2C8 mediated metabolism of Repaglinide and increases its plasma concentrations. It is contraindicated to use Repaglinide and Gemfibrozil together due to potential interaction which may proceed to hypoglycemic complications.

©  The risk of Lactic acidosis and acute renal failure is increased by the concomitant use of Metformin and Injection of iodinated contrast materials (Iocetamic acid, Iopronic acid, Ioxitalamic acid, Iodoxamic acid, Acetrizoic acid, Metrizoic acid, Ioglycemic acid, Iopanoic acid, Iodohippuric acid, Ioseric acid, Iobenzamic acid, Ioglycic acid, Iocarmic acid, Iotroxic acid, Iobitridol, Iodamide, Ipodate, Iodixanol, Iodopyralet, Iosimide, Ethiodized oil, Metrizamide, Tyroponate sodium, Iopentol, Iodipamide, Iotasul, Iotrolan, Ioxaglate, Diatrizoate, Iothalamate, Iohexol, Iopromide, Iopamidol, Iophendylate, Ioversol and Iomeprol). Concurrent use of metformin is contraindicated in patients receiving intravascular iodinated contrast media.

©  Carbonic anhydrase inhibitors (Topiramate, Acetazolamide, Zonisamide and Dichlorphenamide) may decrease sodium bicarbonate levels and increase the risk of metabolic acidosis while administered along with Metformin. Concomitant use of metformin and topiramate is contraindicated.

©  Metformin is a cationic (positively charged) molecule and may compete for organic cation transporters in the kidneys with other cationic drugs (Cimetidine, Ranitidine, Procainamide, Digoxin, Quinidine, Quinine, Morphine, Triamterene, Amiloride, Dolutegravir, Cephalexin, Trimethoprim, and vancomycin) for renal secretion which leads to the inhibition of renal organic cation transporters. The risk of metformin-associated lactic acidosis (MALA) is elevated due to the inhibition of renal organic cation transporters and increased metformin plasma concentrations.

©  The diabetics should be warned that excessive hypoglycaemia may occur due to the inhibition of CYP2C9 mediated metabolism of sulfonylureas by Azole Antifungals (Fluconazole, Itraconazole, Ketoconazole, Miconazole, Variconazole), Fibrates (Gemfibrozil, Clofibrate, Bezafibrate, Ciprofibrate and Fenofibrate), Sulfonamides (Sulfaphenazole, sulfadiazine, sulfamethizole, sulfafurazole (sulfisoxazole), sulfamethoxazole, sulfapyridine, sulfadimethoxine and sulfamonomethoxine and Macrolide Antibiotics (Erythromycin, Clarithromycin).

©  The metabolism of thiazolidinediones is inhibited by CYP2C8 inhibitors like Abiraterone, Pixantrone, Azole Antifungals (Fluconazole, Ketoconazole, Itraconazole, Miconazole), Fibrates (Gemfibrozil, Fenofibrate) and Teriflunomide which may result into increased risk of hypoglycemia.

©  Acarbose may decrease the therapeutic efficacy of Digoxin by reducing its absorption.

©  Acarbose may increase the risk of bleeding by increasing the absorption of Warfarin.

©  Concomitant use of DPP4 inhibitors and P-glycoprotein inhibitors such as Tocofersolan, Nilotinib and Lomitapide may result into increased plasma levels of DPP4 inhibitors due to the inhibition of P-glycoprotein-mediated efflux transport of DPP4 inhibitors.

©  The diabetics should bring a list of all of the drugs they are taking including prescription drugs, over-the-counter drugs, and any supplements (Herbs, Vitamins, Minerals, etc.), during their visit to the doctor or pharmacist.

©  The risk of adverse effects could be reduced and the quality of life for diabetics improved by healthcare professionals through the screening, education, and follow up on suspected drug interactions.

More presentations from Naina Mohamed Pakkir Maideen

FDA warns about Potential Varenicline – Alcohol Interaction:

More presentations from Naina Mohamed Pakkir Maideen

§  On 09^th Mar 2015, the U.S. Food and Drug Administration (FDA) warns that Varenicline can interact potentially with Alcohol.

§  Varenicline – Alcohol interaction may decrease tolerance to alcohol characterized by increased drunkenness, unusual or aggressive behavior, or forgetfulness, in some patients.

§  Before taking varenicline, patients should inform their health care professionals if they drink Alcohol, have a history of seizures, or have ever had depression or other mental health problems.

§  Patients should seek medical attention immediately, if they develop a seizure during treatment with Varenicline.

§  Patients should read the Medication Guide which explains the risks associated with the use of Varenicline.

St. John’s Wort – Drug Interactions:

More Presentations from Naina Mohamed Pakkir Maideen

Ø St. John’s wort (SJW) is an herbal supplement used as an Antidepressant inhibiting the uptake of Serotonin, Noradrenaline and Dopamine.

Ø Hypericin and Hyperforin found to be the active ingredients of St. John’s wort.

Ø SJW can interact significantly with certain drugs including…

§  Warfarin

§  Cyclosporine

§  Oral contraceptives

§  Theophylline

§  Digoxin

§  HIV protease inhibitors

§  Selective Serotonin Re-uptake Inhibitors (SSRIs)

§  CYP1A2 Substrates

§  CYP3A4 Substrates

§  CYP2C19 Substrates

§  CYP2C9 Substrates

Ø The risk of clotting might be elevated by the concomitant use of SJW and Warfarin.

Ø Rejection of a transplanted organ may occur due to the interaction of SJW with Cyclosporine (Immunosuppressant).

Ø Treatment failure and drug resistance are expected to occur with Protease Inhibitors such as Indinavir, Amprenavir, Nelfinavir, Ritonavir and Saquinavir due to the inclusion of SJW.

Ø Oral contraceptives may lose their efficacy when they are administered with SJW.

Ø The effectiveness of Digoxin might be reduced by the coadministration of SJW.

Ø Concomitant use of SJW and Theophylline may result into decreased effectiveness of Theophylline.

Ø SJW interact pharmacodynamically with Selective Serotonin Reuptake Inhibitors (SSRIs) and increase the risk of Serotonin syndrome.

Ø Hyperforin of SJW is an inducer of CYP3A4 and hence it can decrease the effectiveness of CYP3A4 Substrates like Alprazolam, Imatinib, Irinotecan, Tacrolimus, etc.

Ø Hypericin of SJW is an inducer of CYP1A2 and hence it can decrease the effectiveness of CYP1A2 substrates such as Theophylline, Warfarin, Paracetamol, Verapamil, etc.

Ø  The efficacy of CYP2C19 Substrates like Phenytoin, Phenobarbital, Mephenytoin, etc. might be decreased by SJW.

Ø SJW is also an inducer of CYP2C9 and it can reduce the efficacy of CYP2C9 Substrates such as Phenytoin, Sulfonylureas, NSAIDs, etc.

Ø The patients should consult their doctor or pharmacist to know about the safety of a supplement or herb.