SIROY, Shanayne SOLAIMAN, Alyssa

PATIENT D:
Acetazolamide 250mg
Levodopa/Carbidopa 25/250
Pilocarpine 4%
Reserpine 0.25mg
Diltiazem 30mg
Vitamin B Complex with Vitamin C
Entacapone Tablets
Tolcapone

POSSIBLE DRUG INTERACTIONS
LEVODOPA + DILTIAZEM
Levodopa and diltiazem may have additive effects in lowering your blood pressure. You may experience headache, dizziness, lightheadedness, fainting, and/or changes in pulse or heart rate. These side effects are most likely to be seen at the beginning of treatment, following a dose increase, or when treatment is restarted after an interruption. Let your doctor know if you develop these symptoms and they do not go away after a few days or they become troublesome. Avoid driving or operating hazardous machinery until you know how the medications affect you, and use caution when getting up from a sitting or lying position. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.
MONITOR: The hypotensive effects of levodopa and antihypertensive agents may be additive. Postural hypotension may occur.

MANAGEMENT: Hemodynamic responses should be monitored during coadministration, especially during the first few weeks of therapy. Dose adjustments of the antihypertensive agent may be required. Patients should be advised to notify their physician if they experience dizziness or syncope.

LEVODOPA + ACETAZOLAMIDE
Levodopa and Acetazolamide have additive effects in lowering your blood pressure. You may experience headache, dizziness, lightheadedness, fainting, and/or changes in pulse or heart rate. These side effects are most likely to be seen at the beginning of treatment, following a dose increase, or when treatment is restarted after an interruption.

Let your doctor know if you develop these symptoms and they do not go away after a few days or they become troublesome. Avoid driving or operating hazardous machinery until you know how the medications affect you, and use caution when getting up from a sitting or lying position. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

MONITOR: The hypotensive effects of levodopa and antihypertensive agents may be additive. Postural hypotension may occur.

MANAGEMENT: Hemodynamic responses should be monitored during coadministration, especially during the first few weeks of therapy. Dose adjustments of the antihypertensive agent may be required. Patients should be advised to notify their physician if they experience dizziness or syncope.
References
1. "Product Information. Stalevo 150 (carbidopa/entacapone/levodopa)." Novartis Pharmaceuticals, East Hanover, NJ.

RESERPINE LEVODOPA
Limited data suggest that reserpine may block the antiparkinsonian effects of levodopa. The mechanism is believed to be reserpine-induced depletion of brain dopamine. There is little clinical evidence for this theoretical interaction. In general, however, alternative antihypertensive therapy is recommended for patients in whom levodopa is required.
References
1. Bianchine JR, Sunyapridakul L "Interactions between levodopa and other drugs: significance in the treatment of Parkinson's disease." Drugs 6 (1973): 364-88 2. Cotzias GC, Papavasiliou PS, Gellene R "L-dopa in Parkinson's syndrome." N Engl J Med 281 (1969): 272

DILTIAZEM LEVODOPA

MONITOR: The hypotensive effects of levodopa and antihypertensive agents may be additive. Postural hypotension may occur.

MANAGEMENT: Hemodynamic responses should be monitored during coadministration, especially during the first few weeks of therapy. Dose adjustments of the antihypertensive agent may be required. Patients should be advised to notify their physician if they experience dizziness or syncope.
References
1. "Product Information. Stalevo 150 (carbidopa/entacapone/levodopa)." Novartis Pharmaceuticals, East Hanover, NJ.

LEVODOPA + TOLCAPONE
When COMT inhibitors are administered together with levodopa/carbidopa, they may increase the relative bioavailability (AUC) of levodopa. This is due to a decrease in levodopa clearance resulting in a prolongation of the terminal elimination half-life of levodopa (from approximately 2 hours to 3.5 hours).

In the presence of the decarboxylase inhibitor carbidopa, catechol-O-methyltransferase (COMT) is the major metabolizing enzyme for levodopa. In clinical trials of COMT inhibitors (administered concomitantly with levodopa), patients required a decrease in their daily levodopa dose if their daily dose of levodopa was greater than 600 mg for tolcapone or 800 mg for entacapone or if the patients had moderate or severe dyskinesias before beginning treatment. Although COMT inhibitors are intended for use with along with levodopa/carbidopa, the clinician should be aware that the dose of levodopa may need to be decreased when they are added to the patients drug regimen. This is especially true if the patient is experiencing dyskinesias induced by levodopa. Use with caution with severe dyskinesias or dystonia.
References
1. Dingemanse J, Jorga K, Zurcher G, Schmitt M, Sedek G, Da Prada M, Van Brummelen P "Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa." Br J Clin Pharmacol 40 (1995): 253-62 2. "Product Information. Comtan (entacapone)" Novartis Pharmaceuticals, East Hanover, NJ. 3. Sedek G, Jorga K, Schmitt M, Burns RS, Leese P "Effect of tolcapone on plasma levodopa concentrations after coadministration with levodopa/carbidopa to healthy volunteers." Clin Neuropharmacol 20 (1997): 531-41

LEVODOPA + ENTACAPONE
When COMT inhibitors are administered together with levodopa/carbidopa, they may increase the relative bioavailability (AUC) of levodopa. This is due to a decrease in levodopa clearance resulting in a prolongation of the terminal elimination half-life of levodopa (from approximately 2 hours to 3.5 hours).

In the presence of the decarboxylase inhibitor carbidopa, catechol-O-methyltransferase (COMT) is the major metabolizing enzyme for levodopa. In clinical trials of COMT inhibitors (administered concomitantly with levodopa), patients required a decrease in their daily levodopa dose if their daily dose of levodopa was greater than 600 mg for tolcapone or 800 mg for entacapone or if the patients had moderate or severe dyskinesias before beginning treatment.
Although COMT inhibitors are intended for use with along with levodopa/carbidopa, the clinician should be aware that the dose of levodopa may need to be decreased when they are added to the patients drug regimen. This is especially true if the patient is experiencing dyskinesias induced by levodopa. Use with caution with severe dyskinesias or dystonia.
References
1. Dingemanse J, Jorga K, Zurcher G, Schmitt M, Sedek G, Da Prada M, Van Brummelen P "Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa." Br J Clin Pharmacol 40 (1995): 253-62 2. "Product Information. Comtan (entacapone)" Novartis Pharmaceuticals, East Hanover, NJ. 3. Sedek G, Jorga K, Schmitt M, Burns RS, Leese P "Effect of tolcapone on plasma levodopa concentrations after coadministration with levodopa/carbidopa to healthy volunteers." Clin Neuropharmacol 20 (1997): 531-41

DILTIAZEM + MULTIVITAMINS
MONITOR: Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium. Calcium chloride has been used to manage acute severe verapamil toxicity.

MANAGEMENT: Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.
References
1. Oszko MA, Klutman NE "Use of calcium salts during cardiopulmonary resuscitation for reversing verapamil-associated hypotension." Clin Pharm 6 (1987): 448-9 2. Lipman J, Jardine I, Roos C, Dreosti L "Intravenous calcium chloride as an antidote to verapamil-induced hypotension." Intensive Care Med 8 (1982): 55-7 3. Luscher TF, Noll G, Sturmer T, Huser B, Wenk M "Calcium gluconate in severe verapamil intoxication." N Engl J Med 330 (1994): 718-20

DILTIAZEM + FOOD
MONITOR: Like many CNS-active agents, alcohol can exhibit hypotensive effects. Coadministration with antihypertensive agents including diltiazem may result in additive effects on blood pressure and orthostasis.
MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered diltiazem in some patients. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In a study of ten healthy male volunteers, administration of a single 120 mg oral dose of immediate-release diltiazem in combination with 250 mL of grapefruit juice increased the diltiazem peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 22% and 20%, respectively, compared to administration with water. The time to reach Cmax (Tmax) and the terminal half-life were not affected, and no statistically significant differences in blood pressure and heart rate were observed during administration with grapefruit juice relative to water. In a different study, repeated administration of 200 mL of grapefruit juice at 0, 2, 4, 8 and 12 hours had no significant effect on the Cmax or AUC of a single 120 mg oral dose of diltiazem, but increased its half-life from 4.1 to 5.1 hours. The ratios for the N-demethyl and deacetyl metabolites to diltiazem were also not affected by grapefruit juice. However, because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised that alcohol may potentiate the hypotensive effects of diltiazem, especially during the initiation of therapy and following a dosage increase. Caution should be exercised when rising from a sitting or recumbent position, and patients should notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients who regularly consume grapefruit or grapefruit juice should be monitored for increased adverse effects of diltiazem such as such as headache, irregular heartbeat, edema, unexplained weight gain, and chest pain. Grapefruit and grapefruit juice should be avoided if an interaction is suspected.
References
1. Sigusch H, Henschel L, Kraul H, Merkel U, Hoffmann A "Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects." Pharmazie 49 (1994): 675-9 2. Christensen H, Asberg A, Holmboe AB, Berg KJ "Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers." Eur J Clin Pharmacol 58 (2002): 515-520