Drug Interactions between Capital with Codeine Suspension and Razadyne ER

Ask your doctor before using acetaminophen together with ethanol. This can cause serious side effects that affect your liver. Call your doctor immediately if you experience a fever, chills, joint pain or swelling, excessive tiredness or weakness, unusual bleeding or bruising, skin rash or itching, loss of appetite, nausea, vomiting, or yellowing of the skin or the whites of your eyes. If your doctor does prescribe these medications together, you may need a dose adjustment or special tests to safely take both medications. 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.

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ADJUST DOSING INTERVAL: The administration of galantamine with food and adequate fluid intake may reduce the impact of nausea, vomiting, diarrhea, anorexia, and weight loss that are commonly associated with acetylcholinesterase inhibitors (AChEIs). According to product labeling, the administration of food with various galantamine formulations (e.g., liquid, immediate-release tablets, modified/extended-release capsules) has no significant effect on the systemic absorption (AUC) of galantamine. While the presence of food has been shown to delay the rate of absorption (Tmax) and reduce peak concentration (Cmax), these changes are unlikely to be clinically significant. For example, when galantamine modified release was given after food, Tmax increased by approximately 30 minutes. Similarly, in 24 healthy elderly subjects, the presence of food with galantamine immediate release tablets (12 mg twice a day) delayed the Tmax by 1.5 hours and decreased the Cmax by about 25% without affecting the AUC.

MONITOR: Grapefruit and grapefruit juice may increase the plasma concentrations of galantamine, which is partially metabolized by the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported with both moderate and potent CYP450 3A4 inhibitors. When study subjects (n=16) received the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 4 days) with galantamine (4 mg twice daily for 8 days), the systemic exposure (AUC) of galantamine increased by 30%. However, when study subjects (n=16) received the moderate CYP450 3A4 inhibitor erythromycin (500 mg 4 times daily for 4 days) with galantamine (4 mg twice daily for 6 days), the AUC of galantamine only increased by 10%. In general, the effects of grapefruit products are concentration-, dose-, and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. While the clinical significance of this interaction is unknown, increased exposure to galantamine may lead to AChEI related adverse effects such as vagotonic effects on the heart rate (e.g., bradycardia and heart block), neurologic side effects (e.g., seizure activity), respiratory distress, bladder outflow obstruction, dizziness or syncope, nausea, vomiting and/or diarrhea.

MANAGEMENT: According to product labeling, galantamine should be administered with food and adequate fluid intake to reduce the impact of cholinergic-related gastrointestinal adverse effects (e.g., nausea, vomiting, diarrhea, anorexia, and weight loss). Caution and closer monitoring for AChEI related adverse effects may advisable if galantamine is used in combination with grapefruit and/or grapefruit juice. Modified and/or extended-release formulations must also be swallowed whole and not crushed, chewed, or divided.

Do not use alcohol or medications that contain alcohol while you are receiving treatment with codeine. This may increase nervous system side effects such as drowsiness, dizziness, lightheadedness, difficulty concentrating, and impairment in thinking and judgment. In severe cases, low blood pressure, respiratory distress, fainting, coma, or even death may occur. With certain long-acting formulations of narcotic pain medication, consumption of alcohol may also cause rapid release of the drug, resulting in high blood levels that may be potentially lethal. Talk to your doctor or pharmacist if you have questions on how to take this or other medications you are prescribed. Do not use more than the recommended dose of codeine, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medication without first talking to your doctor.

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