CAPIVASERTIB Drug Interactions: What You Need to Know

INTERACTIONS

• Strong CYP3A Inhibitors : Avoid concomitant use. If concomitant use cannot be avoided, reduce TRUQAP dose. ( 2.5 , 7.1 )
• Moderate CYP3A Inhibitors: Reduce TRUQAP dose. ( 2.5 , 7.1 )
• Strong and Moderate CYP3A Inducers: Avoid concomitant use. ( 7.1 )

7.1 Effects of Other Drugs on TRUQAP Table 6 describes drug interactions where concomitant use of another drug affects TRUQAP.

Table

6: Drug Interactions with TRUQAP Strong CYP3A Inhibitors Clinical Impact

• Capivasertib is a CYP3A substrate. Strong CYP3A inhibitors increase capivasertib exposure [see Clinical Pharmacology (12.3) ], which may increase the risk of TRUQAP adverse reactions. Prevention or Management
• Avoid concomitant use with a strong CYP3A inhibitor. If concomitant use cannot be avoided, reduce the dose of TRUQAP and monitor patients for adverse reactions [see Dosage and Administration (2.5) ] . Moderate CYP3A Inhibitors Clinical Impact
• Capivasertib is a CYP3A substrate. Moderate CYP3A inhibitors increase capivasertib exposure [see Clinical Pharmacology (12.3) ], which may increase the risk of TRUQAP adverse reactions. Prevention or Management
• When concomitantly used with moderate CYP3A inhibitor, reduce the dose of TRUQAP and monitor patients for adverse reactions [see Dosage and Administration (2.5) ] . Strong and Moderate CYP3A Inducers Clinical Impact
• Capivasertib is a CYP3A substrate. Strong and moderate CYP3A inducers decrease capivasertib exposure [see Clinical Pharmacology (12.3) ], which may reduce the effectiveness of TRUQAP. Prevention or Management
• Avoid concomitant use of TRUQAP with strong or moderate CYP3A inducers.

TRUQAP is contraindicated in patients with severe hypersensitivity to TRUQAP or any of its components. Severe hypersensitivity to TRUQAP or any of its components. (4)

AND PRECAUTIONS

• Hyperglycemia: TRUQAP can cause hyperglycemia. Evaluate blood glucose levels prior to starting and at regular intervals during treatment. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. ( 2.2 , 2.4 , 5.1 )
• Diarrhea: TRUQAP caused diarrhea in most patients. Advise patients to increase oral fluids, start antidiarrheal treatment, and consult with a healthcare provider if diarrhea occurs while taking TRUQAP. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. ( 2.4 , 5.2 )
• Cutaneous Adverse Reactions: Monitor for signs and symptoms of cutaneous adverse reactions. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity. ( 2.4 , 5.3 )
• Embryo-Fetal Toxicity: TRUQAP can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. Refer to the Full Prescribing Information of fulvestrant for pregnancy and contraception information. ( 5.4 , 8.1 , 8.3 )

5.1 Hyperglycemia Severe hyperglycemia, including diabetic ketoacidosis and fatal outcomes, can occur in patients treated with TRUQAP. Increased fasting glucose from baseline occurred in 37% of patients treated with TRUQAP, including 11% of patients with Grade 2 (FG &gt; 160 to 250 mg/dL), 2% with Grade 3 (FG &gt; 250 to 500 mg/dL), and 1.1% with Grade 4 (FG &gt; 500 mg/dL) events. The median time to first occurrence of hyperglycemia was 15 days (range: 1 to 367). Dose reduction for hyperglycemia was required in 0.6% of patients and permanent discontinuation was required in 0.6% of patients. Diabetic ketoacidosis occurred in 0.3% of patients and diabetic metabolic decompensation in 0.6% of patients. In CAPItello-291, 12% (43/355) of patients who received TRUQAP had an anti-hyperglycemic medication regimen either initiated or changed during the study, including treatment with insulin in 4.8% (17/355) of patients. The safety of TRUQAP has not been established in patients with Type I diabetes or diabetes requiring insulin. Patients with insulin-dependent diabetes were excluded from CAPItello-291. Before initiating treatment with TRUQAP, test fasting glucose levels (FPG or FBG), HbA1C levels, and optimize fasting glucose. After initiating treatment with TRUQAP, monitor or self-monitor fasting glucose levels on Day 3 or 4 of the dosing week during weeks 1, 2, 4, 6 and 8; then monthly while on treatment with TRUQAP; and as clinically indicated. Monitor HbA1C levels every 3 months during treatment with TRUQAP and as clinically indicated. Patients with a history of well-controlled Type 2 diabetes mellitus may require intensified anti-hyperglycemic treatment and close monitoring of fasting glucose levels. For patients who experience hyperglycemia during treatment with TRUQAP, monitor fasting glucose at least twice weekly, on days on and off TRUQAP, until fasting glucose decreases to baseline levels. During treatment with anti-diabetic medications, monitor fasting glucose at least once a week for 2 months, followed by once every 2 weeks, or as clinically indicated. Consider consultation with a healthcare practitioner with expertise in the treatment of hyperglycemia and initiation of fasting glucose monitoring at home for patients who have risk factors for hyperglycemia or who experience hyperglycemia. Advise patients of the signs and symptoms of hyperglycemia and counsel patients on lifestyle changes. Withhold TRUQAP immediately when ketoacidosis is suspected. If ketoacidosis is confirmed, permanently discontinue TRUQAP. Based on the severity of the hyperglycemia, withhold, reduce dose, or permanently discontinue TRUQAP <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) ]</span> .

5.2 Diarrhea Severe diarrhea associated with dehydration occurred in patients who received TRUQAP. Diarrhea occurred in 72% of patients.

Grade

3 or 4 diarrhea occurred in 9% of patients. The median time to first occurrence was 8 days (range 1 to 519). In the 257 patients with diarrhea, 59% required anti-diarrheal medications to manage symptoms. Dose reductions were required in 8% of patients, and 2% of patients permanently discontinued TRUQAP due to diarrhea. In patients with Grade ≥ 2 diarrhea (n=93) with at least 1 grade improvement (n=89), median time to improvement from the first event was 4 days (range: 1 to 154). Monitor patients for signs and symptoms of diarrhea. Advise patients to increase oral fluids and start antidiarrheal treatment at the first sign of diarrhea while taking TRUQAP. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity [see Dosage and Administration (2.4) ] .

5.3 Cutaneous Adverse Reactions Cutaneous adverse reactions, which can be severe, including erythema multiforme (EM), palmar-plantar erythrodysesthesia, and drug reaction with eosinophilia and systemic symptoms (DRESS), occurred in patients who received TRUQAP. Cutaneous adverse reactions occurred in 58% of patients.

Grade

3 or 4 cutaneous adverse reactions occurred in 17% of patients receiving TRUQAP. EM occurred in 1.7% of patients and DRESS occurred in 0.3% of patients. Dose reduction was required in 7% of patients and 7% of patients permanently discontinued TRUQAP due to cutaneous adverse reactions. The median time to onset of cutaneous adverse reactions was 13 days (range 1 to 575 days). Among the 204 patients with cutaneous adverse reactions, 44% (90/204) required corticosteroid treatment. Of these, 37% (76/204) were treated with topical corticosteroids and 19% (39/204) with systemic corticosteroids. In patients with Grade ≥ 2 cutaneous adverse reaction (n= 116) with at least 1 grade improvement (n=104), median time to improvement from the first event was 12 days (range 2 to 544). Monitor patients for signs and symptoms of cutaneous adverse reactions. Early consultation with a dermatologist is recommended. Withhold, reduce dose, or permanently discontinue TRUQAP based on severity [see Dosage and Administration (2.4) ] .

5.4 Embryo-Fetal Toxicity Based on findings from animals and mechanism of action, TRUQAP can cause fetal harm when administered to a pregnant woman <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.1) ]</span> . In an animal reproduction study, oral administration of capivasertib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality, and reduced fetal weights at maternal exposures 0.7 times the human exposure (AUC) at the recommended dosage of 400 mg twice daily. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TRUQAP and for 1 month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TRUQAP and for 4 months after the last dose <span class="opacity-50 text-xs">[see Use in Specific Populations (8.1 , 8.3) ]</span> . TRUQAP is used in combination with fulvestrant. Refer to the Full Prescribing Information of fulvestrant for pregnancy and contraception information.