telaprevir

(tel-a-pre-vir) telaprevir,

Incivek

(trade name)

Classification

Therapeutic: antivirals
Pharmacologic: protease inhibitors
Pregnancy Category: B (telaprevir)
Pregnancy Category: X (with peginterferon and ribavirin)

Indications

genetic implication Treatment of chronic hepatitis C (genotype 1) infection in combination with peginterferon alfa and ribavirin in adult patients with compensated liver disease who are previously untreated or who have failed previous treatment with interferon and ribavirin.

Action

Acts as an inhibitor of viral protease resulting in direct antiviral effect; effect is additive with other antivirals.

Therapeutic effects

Decreased progression of hepatic damage and improved virologic response.

Pharmacokinetics

Absorption: Well absorbed following oral administration; food, especially fat enhances absorption.Distribution: Unknown.Metabolism and Excretion: Extensively metabolized by the liver, primarily by the CYP3A4 enzyme system; metabolites mostly eliminated in feces, 1% excreted in urine.Half-life: 9–11 hr (steady state).

Time/action profile (blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4–5 hr	8–12 hr

Contraindications/Precautions

Contraindicated in: Concurrent use of alfuzosin, rifampin, ergot derivatives, St. John's wort, lovastatin, simvastatin, pimozide, sildenafil (Revatio), tadalafil (Adcirca), midazolam (PO), triazolam, carbamazepine, phenobarbital, or phenytoin; Obstetric: Avoid using in pregnant patients and in male patients whose partners are pregnant (due to concurrent use with ribavirin); Lactation: Avoid breast feeding.Use Cautiously in: Concurrent infection with HIV or Hepatitis B (safety and efficacy not established);Decompensated cirrhosis (safety and effectiveness not established for Child-Pugh score ≥ 7 [Class B and C]);Solid organ transplantation (safety and effectiveness not established); Pediatric: Safety and effectiveness not established.

Adverse Reactions/Side Effects

Central nervous system

fatigue (most frequent)

Gastrointestinal

diarrhea (most frequent)
nausea (most frequent)
anorectal discomfort/pruritus
dysgeusia
hemorrhoids

Dermatologic

drug rash with eosinophilia and systemic symptoms (life-threatening)
stevens-johnson syndrome (life-threatening)
toxic epidermal necrolysis (life-threatening)
rash (most frequent)
prutitus

Genitourinary

acute renal failure

Hematologic

anemia

Interactions

Drug-Drug interaction

↑ blood levels and risk of toxicity from ergot derivatives (dihydroergotamine, ergotamine, methylergonovine, ergonovine ), lovastatin, midazolam (PO), pimozide, sildenafil (Revatio), tadalafil (Adcirca)simvastatin, alfuzosin, or triazolam ; concurrent use is contraindicated.Rifampin, carbamzepine, phenobarbital, and phenytoin may ↓ blood levels; concurrent use contraindicated.↑ blood levels and risk of toxicity with amiodarone, flecainide, lidocaine (systemic), propafenone, and quinidine ; concurrent use should be undertaken with caution and clinical monitoring.↑ digoxin levels; use lowest dose, monitor levels, titrate to desired effect.Concurrent use with clarithromycin, erythromycin, or telithromycin may ↑ levels of anti-infectives and telaprevir; may also ↑ risk of torsade de pointes.May ↑ or ↓ effects of warfarin ; monitor INR.May ↓ levels and effectiveness of escitalopram.May ↑ levels and risk of toxicity with trazodone ; dose ↓ may be warranted.Levels are ↑ by ketoconazole and may be ↑ by posaconazole or itraconazole.↑ levels of ketoconazole, posaconazole, and itraconazole ; daily dose of ketoconazole or itraconazole should not exceed 200 mg.↑ risk of QTc prolongation and arrhythmias with ketoconazole, posaconazole, and voriconazole ; because of variable effects on voriconazole concurrent use should be avoided unless benefits outweigh risks of combined therepy.↑ levels and risk of toxicity with colchicine ; avoid concurrent use in patients with hepatic or renal impairment. If used for gout flares initial dose is 0.6 mg followed by 0.3 mg one hour later, not to be repeated in less than three days. For prophylaxis of gout flares if initial regimen was 0.6 mg twice daily, ↓ to 0.3 mg once daily; if initial regimen was 0.6 mg once daily, ↓ dose to 0.3 mg once every other day. For Familial Mediterranean Fever maximum dose should not exceed 0.6 mg/day (or 0.3 mg twice daily).Rifabutin may ↓ telaprevir levels while telaprevir may ↑ rifabutin levels; concurrent use is not recommended.↑ levels and risk of excess sedation with alprazolam.↓ levels and effect of zolpidem ; dosage adjustments may be necessary.↑ levels and effects of calcium channel blockers including amlodipine, diltiazem, felodipine, nicardipine, nifedipine, nisoldipine, and verapamil ; clinical monitoring is recommended.↑ levels of systemic corticosteroids including prednisone and methylprednisolone and the inhaled corticosteroidsfluticasone and budenoside ; concurrent use is not recommended.Systemic dexamethasone ↓ levels and effectiveness; use cautiously/consider alternatives.↑ levels of bosentan use cautiously and monitor clinically.Levels are ↓ by concurrent atazanavir/ritonavir, ↑atazanivir levels.↓ levels of telaprevir and darunavir when used concurrently with darunavir/ritonavir ; avoid if possible.Concurrent use with fosamprenavir/ritonavir ↓ levels of fosampernavir and telaprevir and should be avoided.Concurrent use with lopinavir/ritonavir ↓ levels and should be avoided.Concurrent use with efavirenz ↓ levels of efavirenz and telaprevir.↑ levels of tenofovir ; dosage ↓ may be necessary.↓ levels of ethinyl estradiol may ↓ contraceptive effectiveness, additional contraception recommended; when used for estrogen replacement, monitor for deficiency.↑ levels of cyclosporine, sirolimus, and tacrolimus and risk of associated toxicities; dose reduction/increased interval are required.↓ levels of methadone; dosage adjustments may be needed during maintenance treatment.↑ levels of sildenafil, tadalafil, and vardenafil ; for erectile dysfunction sildenafil dose should not exceed a single 25 mg dose in 48 hr, tadalafil should not exceed 10 mg in 72 hour and vardenafil should not exceed 2.5 mg in 72 hr. Concurrrent use with vardenafil may ↑ risk of adverse cardiovascular effects.↑ risk of myopathy with atorvastatin ; avoid concurrent use.May ↑ levels of fluvastatin, pitavastatin, pravastatin, and rosuvastatin May ↑ repaglinide levelsMay ↑ alfentanil and fentanyl levels; monitor for respiratory depressionSt. John's wort may ↓ levels and efficacy; concurrent use is contraindicated.

Route/Dosage

Oral (Adults) 1125 mg twice daily, duration of treatment depends on virologic response.

Availability

Tablets: 375 mg

Nursing implications

Nursing assessment

Monitor symptoms of hepatitis during therapy.
Assess for skin reactions (rash, fever, edema, mucosal erosions or ulcerations, red or inflamed eyes). Monitor patient with mild to moderate rash for progression. If rash becomes severe or systemic symptoms occur, discontinue telaprevir. If no improvement after 7 days, discontinue sequentially or simultaneously peginterferon alfa and ribavirin. Do not restart telaprevir if discontinued due to rash.
Lab Test Considerations: Monitor HCV-RNA levels at Treatment Weeks 4 and 12 to determine effectiveness of therapy.
- Monitor hemoglobin prior to and at least at weeks 2, 4, 8, and 12 during telaprevir combination therapy. Ribavirin dose should be reduced according to guidelines to manage anemia. If ribavirin dose reductions are inadequate, consider discontinuing telaprevir. If ribavirin is permanently discontinued for anemia, telaprevir must be discontinued. Ribavirin may be restarted according to guidelines. Telaprevir dose must not be reduced and must not be restarted if discontinued.
- Monitor CBC with differential, electrolytes, serum creatinine, uric acid, hepatic enzymes, bilirubin, and TSH prior to and at Treatment Weeks 2, 4, 8, and 12, and as clinically appropriate. May cause ↓ lymphocyte counts, ↓ platelet counts, ↑ serum bilirubin and ↑ uric acid levels.

Potential Nursing Diagnoses

Risk for infection (Indications, Side Effects)

Implementation

Oral: Administer 2 times daily, 10–14 hrs apart, with food (not low fat). Swallow tablets whole; do not break, crush, dissolve, or chew.

Patient/Family Teaching

Instruct patient to take telaprevir as directed, with peginterferon alfa and ribavirin. If peginterferon alfa and ribaviron are discontinued for any reason, telaprevir must be discontinued. Do not discontinue without discussing with health care professional. If a dose is missed and it is within 6 hrs of when its usually taken, take as soon as possible; if more than 6 hrs from the time usually taken, skip dose and resume normal dosing schedule. Advise patient to read the Medication Guide prior to starting therapy and with each Rx refill in case of changes.
Advise patient that fat content of the meal or snack is essential for absorption of telaprevir. Food should be eaten within 30 min prior to each dose. Examples of food include a bagel with cream cheese, 1/2 cup nuts, 3 tbsp peanut butter, 1 cup ice cream, 2 ounces American or cheddar cheese, 2 ounces of potato chips, or 1/2 cup trail mix.
Inform patient of importance of keeping hydrated by drinking fluids. Signs and symptoms of dehydration include increased thirst, dry mouth, decreased urine frequency or volume, and dark colored urine. Notify health care professional if these symptoms occur or if severe vomiting or diarrhea occur.
Advise patient to notify health care professional promptly of any skin changes or itching or signs and symptoms of anemia (tiredness, weakness, shortness of breath, dizziness). Do not stop telaprevir due to rash unless instructed by health care professional.
Inform patient that telaprevir may not reduce the risk of transmission of HCV to others; precautions should be taken.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
Inform female patients of the importance of simultaneously using two reliable non-hormonal forms of contraception, unless abstinence is the chosen method, during therapy and for 6 mo post-therapy. Hormonal contraceptives may not be reliable during and for up to 2 wks following discontinuation of telaprevir therapy. Advise pregnant women and men whose female partners are pregnant to avoid this therapy due to birth defects and fetal death with ribavirin. Encourage pregnant patients or partners to register with Ribavirin Pregnancy Registry by calling 1-800-593-2214.

Evaluation/Desired Outcomes

Decreased progression of hepatic damage and improved virologic response.
- Therapy is discontinued if HCV-RNA levels are ≥1000 IU/mL at Treatment Week 4 or 12 or confirmed detectable HCV-RNA levels at Treatment Week 24.