simeprevir


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Related to simeprevir: daclatasvir, sofosbuvir, telaprevir

simeprevir

(sim-e-pre-vir ),

Olysio

(trade name)

Classification

Therapeutic: antivirals
Pharmacologic: protease inhibitors
Pregnancy Category: C (alone)
Pregnancy Category: X (for combination with ribavarin and peginterferon alfa)

Indications

Treatment of Hepatitis C in combination with other agents (peginterferon alfa and ribavirin) as a total regimen in patients with infection caused by the hepatitis C virus (HCV) genotype 1 (other genotypes may not respond). Not to be used as monotherapy.

Action

Inhibits viral replication; a direct-acting antiviral (DAA).

Therapeutic effects

Clearing of infection with decreased severity and sequelae of HCV.

Pharmacokinetics

Absorption: Well absorbed following oral administration, food increases and delays absorption (blood levels are ↑ in HCV-infected patients as compared to non-HCV-infected patients).
Distribution: Unknown.
Protein Binding: >99.9%.
Metabolism and Excretion: Highly metabolized (primarily by CYP3A), eliminated primarily via biliary excretion, 31% excreted unchanged in feces, <1% in urine.
Half-life: HCV-infected patients—41 hr; HCV-uinfected patients —10–13 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown6–8 hr24 hr

Contraindications/Precautions

Contraindicated in: Moderate-to-severe hepatic impairment (ribavirin and peginterferon alfa contraindication); Any condition in which peginterferon alpha or ribavirin is contraindicated;Concurrent use of moderate or strong inhibitors or inducers of the CYP3A system (may significant changed in blood levels, effectiveness and risk of toxicity/adverse reactions); Obstetric: Pregnant women and men whose female partners are pregnant (ribavirin contraindication).
Use Cautiously in: History of sulfonamide hypersensitivity (cross sensitivity may occur);genetic implication East Asian ancestry (high blood levels, ↑ risk of adverse reactions including rash and photosensitivity);Severe renal impairment/dialysis.

Adverse Reactions/Side Effects

Reflects combination use with peginterferon alfa and ribavirin

Respiratory

  • dyspnea (most frequent)

Gastrointestinal

  • hyperbilirubinemia
  • nausea

Dermatologic

  • photosensitivity (most frequent)
  • pruritus (most frequent)
  • rash (most frequent)

Musculoskeletal

  • myalgia (most frequent)

Interactions

Drug-Drug interaction

Blood levels and the risk of toxicity may be ↑ moderate or strong inhibitors CYP3A including clarithromycin, cobicistat-containing products, darunavir/ritonavir, erythromycin, itraconazole, posiconazole, ritonavir, telithromycin and voriconazole, concurrent use is not recommended. May ↑ levels and risk of toxicity of digoxin due to inhibition of P-gp (blood level monitoring recommended).Blood levels and therapeutic effects may be ↓ by inducers of CYP3A and CYP3A4 including carbamazepine, dexamethasone, efavirenz, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine ; concurrent use is not recommended.Blood levels may be altered (↑ or ↓) by atazanavir, delavirdine, etravirine, fosamprenavir, lopinavir, indinavir, nelfinavir, nevirapine, saquinavir or tipranavir (concurrent use is not recommended). May ↑ blood levels and risk of arrhythmias with cisapride (concurrent use is not recommended). May↑ blood levels and risk of toxicity with amiodarone, amlodipine, atorvastatin (atorvastatin dose should not exceed 40 mg daily), diltiazem, disopyramide, felodipine, flecainide, lovastatin (use lowest effective dose), mexiletine, nicardipine, , nifendipine, nisoldipine, pitavastatin (use lowest effective dose), pravastatin (use lowest effective dose), propafenone, quinidine, rosuvastatin (rosuvastatin dose should not exceed 10 mg daily), simvastatin (use lowest effective dose) and verapamil (clinical and/or blood level monitoring recommended).May alter blood levels of sirolimus (monitor sirolimus levels).May ↑ blood levels and risk of adverse reactions/toxicity of sildenfil, tadalafil and vardenafil (no adjustments needed when used for erectile dysfunction, when sildenafil or tadalafil are used for pulmonary arterial hypertension, use lowest effective dose and monitor clinically). May ↑ blood levels and the risk of sedation with midazolam or triazolam, use cautiously.Blood levels and risk of toxicity may be ↑ bymilk thistle (concurrent use is not recommended).Blood levels and effectiveness may be ↓ by St. John's wort, concurrent use is not recommended.

Route/Dosage

Oral (Adults) 150 mg once daily (with peginterferon alfa and ribavirin) for 12 weeks. Treatment with peginterferon alfa and ribavirin may continue for 12–48 wk depending on virologic response.

Availability

Capsules: 150 mg

Nursing implications

Nursing assessment

  • Monitor for signs and symptoms of chronic hepatitis C.
  • Assess for rash, especially during first 4 wk of therapy. Monitor mild to moderate rashes for progression, including mucosal signs (oral lesions, conjunctivitis). If rash becomes severe, discontinue simeprevir and monitor until rash resolved.
  • Lab Test Considerations: Use a sensitive assay with a lower limit of quantification of at least 25 IU/mL for monitoring HCV RNA levels during treatment. In treatment wk 4, if HCV RNA ≥25 IU/mL, discontinue simeprevir, peginterferon alfa, and ribavirin. In treatment wk 12, if HCV RNA ≥25 IU/mL,, discontinue peginterferon alfa and ribavirin; simeprevir is completed at wk 12. In treatment wk 24, if HCV RNA ≥25 IU/mL,discontinue peginterferon alfa and ribavirin.
    • A negative pregnancy test must be obtained immediately before beginning therapy and monthly thereafter.
    • May cause ↑ alkaline phosphatase and bilirubin.

Potential Nursing Diagnoses

Risk for infection (Indications)

Implementation

  • Must be administered in conjunction with ribavirin and peginterferon alfa. If ribavirin and peginterferon alfa are discontinued, simeprevir must be discontinued. If simeprevir is discontinued due to adverse reactions or inadequate response, do not restart simprevir.
  • Oral: Administer once daily with food.

Patient/Family Teaching

  • Instruct patient to take simeprevir with ribavirin and pegainterferon alfa as directed. Take missed doses within 12 hr with food or skip dose and take next scheduled dose; do not double doses. Advise patient to read Patient Information before starting and with each refill in case of changes.
  • Caution patient to wear sunscreen and protective clothing and avoid tanning devices to prevent photosensitivity reaction.
  • Advise patient to notify health care professional if rash or photosensitivity reaction (burning, redness, swelling or blisters on skin; mouth sores or ulcers; red or inflamed eyes like pink eye or conjunctivitis) occurs.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. Johns Wort.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. Johns Wort.
  • Advise female patients and male patients with female partners who are pregnant or may become pregnant to use effective contraception due to risks for birth defects and fetal death and avoid breastfeeding. Women and male partners must use 2 forms of non-hormonal contraception during and for at least 6 mo after discontinuation of therapy. Advise women who become pregnant to enroll in the Ribavirin Pregnancy Registry by calling 1-800-593-2214.

Evaluation/Desired Outcomes

  • Decreased severity and sequelae of HCV following treatment with simeprevir, ribavirin, and peginterferon alfa for 12 wk.
    • Patients who are treatment-naïve and prior relapser, including those with cirrhosis, should receive an additional 12 wk of peginterferon alfa and ribavirin for a total of 24 wk.
    • Prior non-responders should receive an additional 36 wk of peginterferon alfa and ribavirin for a total of 48 wk.
References in periodicals archive ?
Ongoing studies focus on the investigation of the NS3/4A protease inhibitor simeprevir in a number of different treatment combinations and HCV patient populations, including those who are difficult to cure.
Lawitz added that this trial provided a glimpse into the outcomes of sofosbuvir and simeprevir for treatment of hepatitis C and both drugs were approved by the FDA but were not yet approved together for this treatment.
12) These guidelines also recommend interferon (1) plus ribavirin and sofosbuvir or simeprevir for retreatment of HCV genotype 1 infection after failure of PEG/RBV, and (2) plus ribavirin and sofosbuvir for retreatment of HCV genotype 4, 5, or 6 infection after failure of PEG/RBV.
However, when used alone, the animal data suggest that sofosbuvir was low risk, whereas simeprevir might have a higher risk.
Once-daily all-oral simeprevir and sofosbuvir with or without ribavirin was generally well tolerated.
New medicinal products for the treatment of chronic hepatitis C: Simeprevir, Daclatasvir, Sofosbuvir, Dasabuvir, Ledipasvir and Sofosbuvir, Ombitasvir and Paritaprevir and Ritonavir.
There have been nine postmarketing reports of symptomatic bradycardia in patients who were taking amiodarone with Harvoni; amiodarone with Sovaldi plus another hepatitis C antiviral drug, simeprevir (Olysio); or amiodarone with an investigational hepatitis C antiviral drug, daclatasvir.
In a review posted online Tuesday, the FDA reported that J&J's drug simeprevir has a slightly higher cure rate than currently available treatments, though it also caused rashes and sunburn in some patients.
Medivir AB (STO:MVIR-B) today announced first interim results from the cohort 1 of a Phase IIa study of the investigational protease inhibitor simeprevir (TMC435) administered once daily with Gilead's investigational nucleotide inhibitor sofosbuvir (GS-7977) with and without ribavirin for 12 and 24 weeks in genotype 1 prior null-responder hepatitis C patients with mild to moderate fibrosis (METAVIR F0-2).
5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg and 8 mg/kg or placebo; (ii) a multiple-ascending dose study in which healthy volunteer subjects received a monthly single subcutaneous dose for four months of RG-101 or placebo; (iii) a single-dose drug-drug interaction study in which healthy volunteer subjects received a single subcutaneous dose of RG-101 in combination with simeprevir (OLYSIO(TM)), an approved direct acting antiviral; and (iv) a single-dose study in which HCV patients received either a single subcutaneous dose of RG-101 or placebo at two doses, 2 mg/kg of RG-101 (the first dose cohort) or 4 mg/kg of RG-101 (the second dose cohort), to assess the safety and viral load reduction.
The FDA approved sofosbuvir and another new drug for hepatitis C, simeprevir (Olysio), in late 2013.
o Phase III trials of simeprevir or telaprevir in combination with pegylated interferon and ribavirin began.