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Sprycel (Dasatinib) - Drug Interactions, Contraindications, Overdosage, etc



Drugs That May Increase Dasatinib Plasma Concentrations

CYP3A4 Inhibitors: Dasatinib is a CYP3A4 substrate. In a study of 18 patients with solid tumors, 20-mg SPRYCEL once daily coadministered with 200 mg of ketoconazole twice daily increased the dasatinib Cmax and AUC by four- and five-fold, respectively. Concomitant use of SPRYCEL and drugs that inhibit CYP3A4 may increase exposure to dasatinib and should be avoided. In patients receiving treatment with SPRYCEL, close monitoring for toxicity and a SPRYCEL dose reduction should be considered if systemic administration of a potent CYP3A4 inhibitor cannot be avoided [see Dosage and Administration ].

Drugs That May Decrease Dasatinib Plasma Concentrations

CYP3A4 Inducers: When a single morning dose of SPRYCEL was administered following 8 days of continuous evening administration of 600 mg of rifampin, a potent CYP3A4 inducer, the mean Cmax and AUC of dasatinib were decreased by 81% and 82%, respectively. Alternative agents with less enzyme induction potential should be considered. If SPRYCEL must be administered with a CYP3A4 inducer, a dose increase in SPRYCEL should be considered [see Dosage and Administration ].

Antacids: Nonclinical data demonstrate that the solubility of dasatinib is pH dependent. In a study of 24 healthy subjects, administration of 30 mL of aluminum hydroxide/magnesium hydroxide 2 hours prior to a single 50-mg dose of SPRYCEL was associated with no relevant change in dasatinib AUC; however, the dasatinib Cmax increased 26%. When 30 mL of aluminum hydroxide/magnesium hydroxide was administered to the same subjects concomitantly with a 50-mg dose of SPRYCEL, a 55% reduction in dasatinib AUC and a 58% reduction in Cmax were observed. Simultaneous administration of SPRYCEL with antacids should be avoided. If antacid therapy is needed, the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of SPRYCEL.

H2 Antagonists/Proton Pump Inhibitors: Long-term suppression of gastric acid secretion by H2 antagonists or proton pump inhibitors (eg, famotidine and omeprazole) is likely to reduce dasatinib exposure. In a study of 24 healthy subjects, administration of a single 50-mg dose of SPRYCEL 10 hours following famotidine reduced the AUC and Cmax of dasatinib by 61% and 63%, respectively. In a study of 14 healthy subjects, administration of a single 100-mg dose of SPRYCEL 22 hours following a 40-mg omeprazole dose at steady state reduced the AUC and Cmax of dasatinib by 43% and 42%, respectively. The concomitant use of H2 antagonists or proton pump inhibitors with SPRYCEL is not recommended. The use of antacids (at least 2 hours prior to or 2 hours after the dose of SPRYCEL) should be considered in place of H2 antagonists or proton pump inhibitors in patients receiving SPRYCEL therapy.

Drugs That May Have Their Plasma Concentration Altered By Dasatinib

CYP3A4 Substrates: Single-dose data from a study of 54 healthy subjects indicate that the mean Cmax and AUC of simvastatin, a CYP3A4 substrate, were increased by 37% and 20%, respectively, when simvastatin was administered in combination with a single 100-mg dose of SPRYCEL. Therefore, CYP3A4 substrates known to have a narrow therapeutic index such as alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids (ergotamine, dihydroergotamine) should be administered with caution in patients receiving SPRYCEL.


Experience with overdose of SPRYCEL in clinical studies is limited to isolated cases. Overdosage of 280 mg per day for 1 week was reported in two patients and both developed severe myelosuppression and bleeding. Since SPRYCEL is associated with severe myelosuppression [see Warnings and Precautions and Adverse Reactions ], patients who ingested more than the recommended dosage should be closely monitored for myelosuppression and given appropriate supportive treatment.

Acute overdose in animals was associated with cardiotoxicity. Evidence of cardiotoxicity included ventricular necrosis and valvular/ventricular/atrial hemorrhage at single doses ≥100 mg/kg (600 mg/m2) in rodents. There was a tendency for increased systolic and diastolic blood pressure in monkeys at single doses ≥10 mg/kg (120 mg/m2).




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  2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999, http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html.
  3. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. (2006) 63:1172–1193.
  4. Polovich M, White JM, Kelleher LO (eds). 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd ed). Pittsburgh, PA: Oncology Nursing Society.

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