Drug Interaction Report

This report displays the potential drug interactions for the following 5 drugs:
atorvastatin
cilostazol
ramipril
Lantus (insulin glargine)
insulin aspart

Interactions between your drugs

Moderate
ramipril  insulin glargine
Applies to: ramipril, Lantus (insulin glargine)
MONITOR: The hypoglycemic effect of insulin may be potentiated by certain drugs, including ACE inhibitors,
angiotensin receptor blockers (ARBs), amylin analogs, anabolic steroids, fibrates, monoamine oxidase
inhibitors (MAOIs, including linezolid), salicylates, selective serotonin reuptake inhibitors (SSRIs),
sulfonamides, disopyramide, propoxyphene, quinidine, quinine, and ginseng. These drugs may increase the
risk of hypoglycemia by enhancing insulin sensitivity (ACE inhibitors, ARBs, fibrates, ginseng); stimulating
insulin secretion (salicylates, disopyramide, pentoxifylline, propoxyphene, quinidine, quinine, MAOIs,
ginseng); increasing peripheral glucose utilization (SSRIs, insulin-like growth factor); inhibiting
gluconeogenesis (SSRIs, MAOIs, insulin-like growth factor); slowing the rate of gastric emptying (amylin
analogs); and/or suppressing postprandial glucagon secretion (amylin analogs). Clinical hypoglycemia has
been reported during use of some of these agents alone or with insulin and/or insulin secretagogues. Use
of SSRIs has also been associated with loss of awareness of hypoglycemia in isolated cases.

MANAGEMENT: Close monitoring for the development of hypoglycemia is recommended if these drugs are
coadministered with insulin, particularly in patients with advanced age and/or renal impairment. The insulin
dosage may require adjustment if an interaction is suspected. Patients should be apprised of the signs and
symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness,
sweating, palpitations), how to treat it, and to contact their physician if it occurs. Patients should be
observed for loss of glycemic control when these drugs are withdrawn.

References
1. "Product Information. Apidra (insulin glulisine)." Aventis Pharmaceuticals, Bridgewater, NJ.

2. Abad S, Moachon L, Blanche P, Bavoux F, Sicard D, Salmon-Ceron D "Possible interaction between glicazide, fluconazole and sulfamethoxazole resulting in
severe hypoglycaemia." Br J Clin Pharmacol 52 (2001): 456-7

3. Daubresse JC, Daigneux D, Bruwier M, Luyckx A, Lefebvre PJ "Clofibrate and diabetes control in patients treated with oral hypoglycaemic agents." Br J Clin
Pharmacol 7 (1979): 599-603

View all 75 references

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Moderate
ramipril  insulin aspart
Applies to: ramipril, insulin aspart
MONITOR: The hypoglycemic effect of insulin may be potentiated by certain drugs, including ACE inhibitors,
angiotensin receptor blockers (ARBs), amylin analogs, anabolic steroids, fibrates, monoamine oxidase
inhibitors (MAOIs, including linezolid), salicylates, selective serotonin reuptake inhibitors (SSRIs),
sulfonamides, disopyramide, propoxyphene, quinidine, quinine, and ginseng. These drugs may increase the
risk of hypoglycemia by enhancing insulin sensitivity (ACE inhibitors, ARBs, fibrates, ginseng); stimulating
insulin secretion (salicylates, disopyramide, pentoxifylline, propoxyphene, quinidine, quinine, MAOIs,
ginseng); increasing peripheral glucose utilization (SSRIs, insulin-like growth factor); inhibiting
gluconeogenesis (SSRIs, MAOIs, insulin-like growth factor); slowing the rate of gastric emptying (amylin
analogs); and/or suppressing postprandial glucagon secretion (amylin analogs). Clinical hypoglycemia has
been reported during use of some of these agents alone or with insulin and/or insulin secretagogues. Use
of SSRIs has also been associated with loss of awareness of hypoglycemia in isolated cases.
MANAGEMENT: Close monitoring for the development of hypoglycemia is recommended if these drugs are
coadministered with insulin, particularly in patients with advanced age and/or renal impairment. The insulin
dosage may require adjustment if an interaction is suspected. Patients should be apprised of the signs and
symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness,
sweating, palpitations), how to treat it, and to contact their physician if it occurs. Patients should be
observed for loss of glycemic control when these drugs are withdrawn.

References
1. "Product Information. Apidra (insulin glulisine)." Aventis Pharmaceuticals, Bridgewater, NJ.

2. Abad S, Moachon L, Blanche P, Bavoux F, Sicard D, Salmon-Ceron D "Possible interaction between glicazide, fluconazole and sulfamethoxazole resulting in
severe hypoglycaemia." Br J Clin Pharmacol 52 (2001): 456-7

3. Daubresse JC, Daigneux D, Bruwier M, Luyckx A, Lefebvre PJ "Clofibrate and diabetes control in patients treated with oral hypoglycaemic agents." Br J Clin
Pharmacol 7 (1979): 599-603

View all 75 references

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No other interactions were found between your selected drugs. This does not necessarily mean no other
interactions exist. Always consult your healthcare provider.

Drug and food interactions

Moderate
ramipril  food
Applies to: ramipril
GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients
who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using
a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-
aldosterone-angiotensin (RAA) system.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid
moderately high or high potassium dietary intake. Particular attention should be paid to the potassium
content of salt substitutes.

References
1. "Product Information. Vasotec (enalapril)." Merck & Co, Inc, West Point, PA.

2. Good CB, McDermott L "Diet and serum potassium in patients on ACE inhibitors." JAMA 274 (1995): 538

3. Ray K, Dorman S, Watson R "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life
threatening interaction." J Hum Hypertens 13 (1999): 717-20

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Moderate atorvastatin  food

Applies to: atorvastatin
GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of
atorvastatin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the
gut wall by certain compounds present in grapefruit. When a single 40 mg dose of atorvastatin was
coadministered with 240 mL of grapefruit juice, atorvastatin peak plasma concentration (Cmax) and
systemic exposure (AUC) increased by 16% and 37%, respectively. Greater increases in Cmax (up to 71%)
and/or AUC (up to 2.5 fold) have been reported with excessive consumption of grapefruit juice (>=750 mL
to 1.2 liters per day). Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma is associated
with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness
associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been
reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal
failure secondary to myoglobinuria and may result in death.

ADJUST DOSING INTERVAL: Fibres such as oat bran and pectin may diminish the pharmacologic effects of
HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract.

MANAGEMENT: Patients receiving therapy with atorvastatin should limit their consumption of grapefruit
juice to no more than 1 liter per day. Patients should be advised to promptly report any unexplained muscle
pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine.
Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous
exercise or if myopathy is otherwise suspected or diagnosed. In addition, patients should either refrain from
the use of oat bran and pectin or, if concurrent use cannot be avoided, to separate the administration times
by at least 2 to 4 hours.

References
1. Richter WO, Jacob BG, Schwandt P "Interaction between fibre and lovastatin." Lancet 338 (1991): 706

2. "Product Information. Lipitor (atorvastatin)." Parke-Davis, Morris Plains, NJ.

3. McMillan K "Considerations in the formulary selection of hydroxymethylglutaryl coenzyme a reductase inhibitors." Am J Health Syst Pharm 53 (1996): 2206-
14

View all 7 references

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Moderate
cilostazol  food
Applies to: cilostazol
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of cilostazol. The proposed
mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain
compounds present in grapefruits. The extent and clinical significance are unknown. Moreover,
pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a
high degree of interpatient variability.

MANAGEMENT: Until more information is available, the manufacturer recommends avoiding consumption
of grapefruit juice during cilostazol therapy. Orange juice is not expected to interact with cilostazol.

References
1. "Product Information. Pletal (cilostazol)." Otsuka American Pharmaceuticals, Rockville, MD.

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the
recommended therapeutic duplication maximum.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific
individual is difficult to determine. Always consult your healthcare provider before starting or stopping
any medication.

Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the
benefit.

Moderate Moderately clinically significant. Usually avoid combinations; use it only under special
circumstances.

Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative
drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.

Unknown No interaction information available.

Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your
personal circumstances.