Talha Shafique

CYP 450 Substrate Inducers Inhibitors

3A4 (2C9, 2D6, P glycoproteins, etc.)
PS PROCS G PACMAN (aggressive angry guy)
Phenytoin, Smoking, Phenobarbital Grapefruit, Protease Inhibitors
Rifampin (Rifabutin, Rifapentine) Azoles, Cyclosporine & cimetidine
Oxcarbazepine, Carbamazepine Macrolides Clarithro, Erythro &
S.t John Wort Telithrom
Amiodarone & Dronedarone
Non DHPCCB  Diltiazem & Verapamil

 Decrease the dose 30-50 % of the following drugs when administering with Amiodarone
Digoxin, Warfarin, Statins, Procainamide and Quinidine

 Digoxin levels can be increased due to  Decrease Renal function, Hypokalemia and CYP-Inhibitors
 Caution with other drugs that decrease Heart Rate (< 60 BPM)  ‘Non ABCO’ – Non-DHP CCBs,
Amiodarone, Beta-Blockers, Clonidine and Opioids/Organophosphates

Contraindicated with

 NSAIDs, Aspirin, APAP and other Antiplatelets  Increased bleeding risk and Increase INR
 Antibiotics (Cipro, Clarithro, Metronidazole, Sulfa/Trimeth (Bactrim)  Increased effect of Warfarin
 Herbal drugs  Ginkgo biloba, Feverfew, Ginger, Garlic  Increased bleeding risk

– If given together they can increase the Risk of Severe Rash

– Risk of Serotonin Syndrome / Hypertensive crisis (Fever, Diarrhea,

Agitation, Sweating and Tremors) - Contraindicated with
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 Drugs  SSRI, SNRI, TCA, Ephedrine & Pseudoephedrine, Tramadol, Meperidine, Dextromethorphan,
Bupropion, Lithium, Cyclosporine, Muscle relaxants, Methylene Blue, Linezolid, Levodopa, Triptans
 Herbal supplements  St. john’s wort
Monoamines  Epinephrine, NE, Dopamine, Serotonin, Tyramine

– Both metabolize with 2D6 Enzymes

 Patients without 2D6 or 2D6-Inhibitors will have increase concentrations and lead to Respiratory
depression

– Prodrug of Morphine which is converted by 2D6

 Patients with increased 2D6 enzymes can lead to Increase Morphine and Vice-versa

– All metabolized by 3A4 (Avoid 3A4

Inhibitors)

 Antacids, Bile-acid Resins, Sucralfate and Minerals (Mg, Ca, Al, Zinc, Iron) and Multivitamins

– Increase doses can lead to Muscle toxicity and Rhabdomyolysis

 Statin with increased 3A4 activity  ‘SAL’ – Simvastatin, Atorvastatin and Lovastatin
 Avoid with CYP-Inhibitors

– All azoles are Inhibitors

 Ketoconazole & Itraconazole  Both have pH-dependent absorption

 NSAIDS including COX-inhibitors, all increase BP (APAP is safer)

 Triptans, Stimulants, Amphetamines, TKIs, ESAs, COX-2, Antidepressants, Dihydro-Ergotamine

– RAAS (ACEi, ARBs, Aldosterone) and K-sparing Diuretics

– Increased lithium levels when used with NSAID or Diuretics

 Decreased Effectiveness with  CYP-Inducers and Antibiotics

 Mostly are CYP-3A4 substrate (Caution with CYP inhibitors and inducers)
 With Alpha-blockers  Additive vasodilation = Reduction in BP
 With Nitrates  Both increases cGMP = Reduction in BP
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– Increase the concentration of others

 Increase Bleeding risk with Anticoagulants and can increase risk of QT-Prolongation
 Muscle weakness/Rhabdomyolysis & Leg pain if used with Statins (Atorvastatin, Lovastatin)

 Eating too much vit. K rich foods can interact with Blood thinning drugs, especially Warfarin and can
decrease the ability of these drugs to prevent clotting
 Examples of Vitamin-K Foods  Kale, Spinach, Broccoli, Turnip, Parsley, Cabbage, Banana, etc.

 Can increase Blood pressure and should be avoided with drugs that Interfere with the breakdown of
Tyramine, such as Monoamine-Oxidase Inhibitors and Anti-Parkinson’s drugs. If used together, there is
increased risk of Hypertensive Crisis and Serotonin syndrome
 Examples of Tyramine-containing Foods  Aged cheese, Dried/Fermented meat, Wine/Bear, Dried
Pickle, Chocolate or smoked food

 Patients taking Digoxin for Heart failure or ACEi / K-sparing diuretics for Blood pressure should be
careful with salts substitutes that replace Sodium with Potassium
 Increased Potassium can decrease the effectiveness of Digoxin
 Taking potassium supplements with drugs that increase potassium in the body, can lead to too much
potassium in the blood, which can cause abnormal heart rhythms (Arrhythmia)
Examples of Foods rich in Potassium  Banana, Oranges, Green-leafy vegetables
 Taking Salts high in Sodium can lead to Increase Blood pressure
 It is important to know that both Sodium & Potassium have opposite effects – Sodium increases blood
pressure whereas potassium decreases blood pressure by relaxing blood vessels and excreting sodium =
So there should be a balance in the body as too much of either can be dangerous

 Can lead to additive Drowsiness if used with following drugs  Antihistamines (Diphenhydramine,
Brompheniramine, Chlorpheniramine, Cetirazine, etc.), Anti-depressants, Benzodiazepines, Stimulants,
Antipsychotics
 Can lead to Stomach Ulcer/Bleeding and Liver damage if used with  NSAIDs, APAP, Atomoxetine,
Statins,
 Can lead to Impaired concentration and risk of Heart Problems if used with  Stimulants
(Methylphenidate, Amphetamines)
 Can lead to additive/abnormally low levels of Hypoglycemia with Antidiabetics
 Can lead to dangerous side effects including Coma & Death if used with  Narcotic Analgesics/Opioids
(Codeine, Morphine, Hydrocodone, Oxycodone)
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– used for indigestion/heartburn

 Glycyrrhizin, a component of black licorice, can cause irregular heartbeat or even death when combined
with digoxin
 Licorice also appears to make certain drugs less effective  blood-pressure medications, blood
thinners, pain relievers, and birth-control pills

 Don’t mix with Tetracyclines / Fluoroquinolones  Can prevent the body from absorbing the drug. In
general, tetracycline works better if taken one hour before or two hours after eating

 Just like Calcium, fiber can also bind to other drugs and Decreases their concentration
 For example, patients with diabetes who try to decrease their cholesterol levels by eating oatmeal after
taking metformin might be worsening their diabetic control. Metformin blood levels are decreased when
taken with large amounts of fiber. Levothyroxine is another drug that is altered when taken with fiber.
Digoxin and penicillin are also affected by this food–drug interaction
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Drugs causing Lactic Acidosis

 ‘MINA’ – Metformin, INSTI, NRTI, ARTs

Drugs causing PML-Progressive Multifactorial Leukoencephalopathy

 ‘DiNa likes BeRi’ – Dimethyl fumarate, Natalizumab, Belimumab and Rituximab

Drugs needing Refrigeration after Reconstitution

 Penicillins (Augmentin/Penicillin/Ampicillin), Cephalosporins (Except Cefdinir), Erythromycin and
Vancomycin/Valacyclovir

Drugs needing 2 Forms of Birth control / Great Caution to not get Pregnant
 ‘LeRI’ – Lefluminide (Stay in the body until 6 months later), Ribavarin (Stay until 2 years later) and
Isotretinoin (IPLEDGE program)

Drugs Requiring Acidic pH for Adequate Absorption

 ‘CIA’ – Calcium carbonate, Iron and Azoles (Ketoconazole, Itraconazole, etc.)

Drugs causing Pulmonary Fibrosis

 ‘BNMAS’ – Bleomycin, Nitrofurantoin, Methotrexate, Amiodarone and Sulfasalazine

Drugs Increasing Uric Acid

 ‘DAT PRN’ – Diuretics, Aspirin (increase doses), Tacrolimus, Pyrazinamide, Ribavarin and Niacin

Drugs causing Gingival Hyperplasia

 ‘CPC’ – Calcium-channel blockers (Nifedipine, Verapamil, Diltiazem), Phenytoin and Cyclosporine

Drugs causing QT-Prolongation

 ‘4As & QM’ – Antipsychotics, Antidepressants, Antihistamines, Antiarrhythmic & Quinolones, Macrolides

Drugs Increasing PR-interval

 ‘BCD PL’ – Beta-blockers, Calcium channel blockers, Digoxin and Protease inhibitors, Lacosamide