Astagraf XL Side Effects: What to Expect and When to Call Your Doctor

Astagraf XL (tacrolimus extended-release capsules) carries an FDA Boxed Warning -- the most serious category of drug warning -- about the risk of serious infections, malignancies, and increased mortality in certain patient groups. Understanding what side effects are expected and which ones require immediate attention is critical for kidney transplant patients and their caregivers.

This guide covers what to expect, what to watch for, and when to call your transplant team.

FDA Boxed Warning for Astagraf XL

Astagraf XL's boxed warning covers three critical risks:

1. Increased risk of serious infections and malignancies: Astagraf XL suppresses your immune system, which can increase the risk of serious infections (including life-threatening ones) and certain cancers, especially lymphoma and skin cancer.
2. Increased mortality in female liver transplant patients: In a liver transplant trial, mortality at 12 months was higher among female patients on Astagraf XL. Astagraf XL is NOT approved for liver transplantation.
3. Medication errors from non-interchangeability: Substitution with other tacrolimus formulations without physician supervision has caused graft rejection and serious harm.

Common Side Effects of Astagraf XL

These side effects are reported frequently in kidney transplant patients taking Astagraf XL:

• Kidney problems (nephrotoxicity): Very common; your transplant team will monitor kidney function regularly
• High blood pressure (hypertension): Monitor blood pressure regularly; may require medication
• New-onset diabetes after transplant (NODAT): Tacrolimus can cause high blood sugar; African-American and Hispanic patients are at higher risk
• Tremor: Shaking or trembling hands are common, especially at higher blood levels
• Diarrhea, nausea, and stomach upset: Gastrointestinal effects are common; taking the medication on an empty stomach may help
• Headache
• Insomnia (difficulty sleeping)
• Hyperkalemia (high potassium): Can cause muscle weakness or heart rhythm problems; regularly monitored through blood tests
• Anemia

Serious Side Effects That Require Urgent Medical Attention

Call your transplant team immediately or go to the emergency room if you experience:

• Signs of infection: Fever, chills, unusual fatigue, cough, painful urination, or skin sores -- infections can become life-threatening quickly in immunosuppressed patients
• Signs of kidney rejection: Decreased urine output, weight gain, swelling in legs/ankles, or pain over the transplant site
• Neurological symptoms: Severe headache, seizures, confusion, vision changes, or weakness in limbs (possible signs of PRES -- posterior reversible encephalopathy syndrome)
• Heart rhythm changes: Tacrolimus can prolong the QT interval, potentially causing dangerous heart rhythms (Torsades de pointes)
• Signs of new or worsening cancer: New lumps, unusual skin changes (especially on sun-exposed areas), swollen lymph nodes
• Extreme fatigue or pale skin: May indicate pure red cell aplasia (rare but serious)

Special Considerations for High-Risk Patients

Some patients face additional risk factors with Astagraf XL:

• African-American and Hispanic patients are at increased risk for new-onset diabetes after transplant with Astagraf XL
• Patients with congenital long QT syndrome should not take Astagraf XL due to the risk of further QT prolongation
• Patients with pre-existing kidney disease need particularly careful monitoring of kidney function and tacrolimus levels

Important Safety Tips

• Avoid grapefruit and grapefruit juice -- they increase tacrolimus blood levels
• Avoid alcohol -- it causes Astagraf XL to release too quickly, increasing side effects
• Avoid live vaccines (such as MMR, varicella, live flu vaccine) while on Astagraf XL
• Use sunscreen and protective clothing -- increased skin cancer risk requires sun protection

For more on drug interactions that can make side effects worse, see our article on Astagraf XL drug interactions.