Entecavir (entecavir)

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Entecavir is administered orally (as tablets or oral solution).

Because the presence of food in the GI tract may decrease the rate and extent of absorption, entecavir should be administered on an empty stomach at least 2 hours before or 2 hours after meals.

Administer the oral solution using the supplied oral dosing spoon according to the patient instructions provided by the manufacturer. The oral solution contains 0.05 mg of entecavir per mL; do not dilute or mix the solution with water or any other liquid. Refer to the full prescribing information for specific instructions for administration of the oral solution.

Store entecavir tablets and oral solution at 25oC (excursions permitted between 15-30oC); the tablets should be stored in a tightly-closed container. Store both the tablets and the oral solution in the outer carton to protect from light. After opening, the oral solution can be used up to the expiration date on the bottle.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Selected Antiviral Agents/Cladribine Oral

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Antiviral agents may inhibit the intracellular phosphorylation of cladribine by competitive inhibition of intracellular kinases.(1-4)

CLINICAL EFFECTS: Concurrent administration of antiviral agents with cladribine may result in decreased clinical efficacy of cladribine.(1-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of cladribine states that concurrent use of compounds that require activation by intracellular phosphorylation is not recommended.(1)

DISCUSSION: Cladribine undergoes a series of phosphorylations to its active metabolites.(1) Compounds phosphorylated by kinases linked to this monograph include: acyclovir, entecavir, ganciclovir, tenofovir, valacyclovir, and valganciclovir.

There are no moderate interactions for this drug.

None.

There are no contraindication contraindications for this drug.

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Lactic acidosis
• Steatosis of liver

• Drug resistance to anti-retroviral therapy
• Kidney disease with likely reduction in glomerular filtration rate (GFr)

The most common adverse effects (>=3%, all severity grades) in adults were headache, fatigue, dizziness, and nausea. Adverse effects observed in pediatric patients were consistent with those observed in adults.

More Frequent

• Abnormal hepatic function tests
• Hematuria
• Lactic acidosis

Less Frequent

• Glycosuria
• Hyperbilirubinemia

Rare or Very Rare

• Anaphylaxis
• Hepatomegaly
• Hyperglycemia
• Steatosis of liver
• Thrombocytopenic disorder

More Frequent

• Alopecia
• Dizziness
• Drowsy
• Fatigue
• Headache disorder
• Nausea
• Skin rash

Less Frequent

• Acute abdominal pain
• Diarrhea
• Dysgeusia
• Vomiting

Rare or Very Rare

• Dyspepsia
• Insomnia

No enhanced messaging available.

Safety and efficacy of were evaluated in clinical trials of pediatric patients >=2 years of age with HBeAg-positive chronic HBV infection and compensated liver disease.

Steady-state pharmacokinetics of entecavir were evaluated in pediatric patients 2 to <18 years of age with compensated liver disease. Entecavir exposures in nucleoside inhibitor-naive children receiving the oral solution in a dosage of 0.015 mg/kg (<=0.5 mg) once daily were similar to exposures observed in adults receiving a 0.5-mg tablet once daily. Exposures in lamivudine-experienced children receiving the oral solution in a dosage of 0.03 mg/kg (<=1 mg) once daily were similar to exposures observed in adults receiving a 1-mg tablet once daily.

There are limited data available on the use of entecavir in lamivudine-experienced pediatric patients; use entecavir in these patients only if potential benefits justify potential risks. Since some pediatric patients may require long-term or lifetime management of chronic active HBV infection, consider the impact of entecavir use on future treatment options.

Safety and efficacy of entecavir have not been established in pediatric patients <2 years of age; entecavir has not been evaluated in these patients since treatment of HBV is rarely required in this age group.

A pregnancy exposure registry (the Antiretroviral Pregnancy Registry (APR)) monitors maternal-fetal outcomes of pregnant women exposed to entecavir; clinicians are encouraged to enroll patients in the registry by calling 800-258-4263.

Prospective data from the APR are insufficient to adequately evaluate the risk of birth defects, miscarriage, or adverse maternal or fetal outcomes. The limited number of entecavir exposures reported to the APR is not sufficient to inform a risk assessment in comparison to a reference population. The rate of miscarriage is not reported in the APR.

In animal reproduction studies, there was no evidence of developmental toxicities in rats or rabbits at systemic entecavir exposures approximately 28 or 212 times, respectively, human exposures achieved at the maximum recommended human dose (MRHD) of 1 mg daily. In a pre/postnatal development study, no adverse effects on the offspring were observed when entecavir (<=30 mg/kg per day) was administered orally to pregnant rats from gestation day 6 to lactation/post-partum day 20, resulting in exposures >94 times those in humans at the MRHD.

It is not known whether entecavir is distributed into human milk, affects human milk production, or has effects on the breastfed infant. Entecavir was present in milk when administered to lactating rats.

Consider the benefits of breastfeeding and the importance of entecavir to the mother along with the potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

Select dosage of entecavir for geriatric patients with caution due to possible age-related decreases in renal function; monitoring renal function also may be helpful.

Clinical studies did not include sufficient numbers of patients >=65 years of age to determine whether they respond differently to entecavir than younger adults.

Entecavir is substantially excreted by the kidneys, and the risk of entecavir-induced toxicity may be increased in patients with impaired renal function. The area under the plasma concentration-time curve (AUC) of entecavir is increased compared with younger adults, possibly as the result of age-related changes in renal function. Since geriatric patients may be more likely to have decreased renal function, select dosage with caution; it also may be useful to monitor renal function in geriatric patients.