telaprevir


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Related to telaprevir: sofosbuvir

telaprevir

(tel-a-pre-vir) ,

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)

ROUTEONSETPEAKDURATION
POunknown4–5 hr8–12 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.
References in periodicals archive ?
In addition, four approved hepatitis C antivirals--simeprevir, telaprevir, boceprevir, and sofosbuvir--may cause photosensitivity, Dr.
Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial.
Telaprevir was administered with a fat supplement by directly observed therapy.
A reanalysis of boceprevir and telaprevir clinical trials by the FDA's Harrington and others revealed that HCV RNA measures reported as detectable/BLOQ were common during treatment and tended to peak in their frequency before or near key RGT decision timepoints.
Even so, "Up to 13% of boceprevir-treated veterans and 24% of telaprevir-treated veterans would have been excluded from the phase III trials [of these therapies] based on hematologic exclusion criteria used in the telaprevir trials," Dr.
telaprevir with peginterferon alfa-2a plus ribavirin for 8 weeks, then placebo with peginterferon alfa-2a plus ribavirin for 4 weeks, followed by 12 to 36 weeks of peginterferon alfa-2a plus ribavirin using the HCV RNA criteria applied to Group 1 (Group 2)
Treatment for the hepatitis C viral (HCV) infection may take half as long now as the 48 weeks that the therapy required in the past, and may result in a much higher cure rate, according to a recent study on the effectiveness of the medication telaprevir.
Release date- 22072011 - Beerse, Belgium,- Tibotec Virco-Virology BVBA, one of the Janssen Pharmaceutical Companies announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the approval of telaprevir, a direct acting antiviral (DAA) for the treatment of chronic genotype-1 hepatitis C virus (HCV), in combination with pegylated-interferon and ribavirin (current standard of care).
Now major studies show that adding a new drug - either Vertex Pharmaceuticals' telaprevir or Merck & Co.
Vertex Pharmaceuticals Inc's (Cambridge MA) high-profile experimental hepatitis C drug telaprevir cured 65% of patients who had previously failed to be cured by current standard drugs, according to data from a pivotal late-stage clinical trial.
Vertex continues to make important advancements across the business as we prepare to submit a New Drug Application for telaprevir in the second half of 2010.
London, Apr 9 (ANI): Telaprevir, a protease inhibitor, combined with standard hepatitis C treatment, cures a significantly higher number of difficult-to-treat patients than standard treatment alone, a new study has found.