Concomitant Drug Class:
ANTI GOU T
Ketoconazole increases the plasma concentrations of telaprevir.
Concomitant systemic use of itraconazole or posaconazole with telaprevir
may increase plasma concentration of telaprevir.
Plasma concentrations of itraconazole, ketoconazole, or posaconazole
may be increased in the presence of telaprevir. When co-administration
is required, high doses of itraconazole or ketoconazole (greater than
200 mg/day) are not recommended.
Caution is warranted and clinical monitoring is recommended for
itraconazole, posaconazole and voriconazole.
QT interval prolongation and Torsade de Pointes have been reported
with voriconazole and posaconazole. QT interval prolongation has been
reported with ketoconazole.
Due to multiple enzymes involved with voriconazole metabolism, it is
difficult to predict the interaction with telaprevir. Voriconazole should not
be administered to patients receiving telaprevir unless an assessment of
the benefit/risk ratio justifies its use.
Patients with renal or hepatic impairment should not be given colchicine
colchicine dosage or an interruption of colchicine treatment is
recommended in patients with normal renal or hepatic function.
Treatment of gout flares: co-administration of colchicine in patients
0.6 mg ( 1 tablet) for 1 dose, followed by 0.3 mg (half tablet) 1 hour later.
Not to be repeated before 3 days.
If used for prophylaxis of gout flares: co-administration of colchicine in
patients on telaprevir:
If the original regimen was 0.6 mg twice a day, the regimen should be
adjusted to 0.3 mg once a day.
If the original regimen was 0.6 mg once a day, the regimen should be
adjusted to 0.3 mg once every other day.
Treatment of familial Mediterranean fever (FMF): co-administration of
colchicine in patients on telaprevir:
Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).
Concentrations of telaprevir may be decreased, while rifabutin
concentrations may be increased during co-administration. Telaprevir
may be less effective due to decreased concentrations. The concomitant
use of rifabutin and telaprevir is not recommended.
CALCIUM CHANNEL BLOCKERS
Concomitant use of alprazolam and telaprevir increases exposure to
alprazolam. Clinical monitoring is warranted.
Concomitant use of parenterally administered midazolam with telaprevir
increased exposure to midazolam. Co-administration should be done in
a setting which ensures clinical monitoring and appropriate medical
management in case of respiratory depression and/or prolonged sedation.
Dose reduction for midazolam should be considered, especially if more
than a single dose of midazolam is administered.
Co-administration of oral midazolam with telaprevir is contraindicated.
Exposure to zolpidem was decreased when co-administered with
telaprevir. Clinical monitoring and dose titration of zolpidem is
recommended to achieve the desired clinical response.
Exposure to amlodipine was increased when co-administered with
telaprevir. Caution should be used and dose reduction for amlodipine
should be considered. Clinical monitoring is recommended.
Systemic corticosteroids such as prednisone and methylprednisolone are
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concentrations of these corticosteroids can be increased significantly.
Co-administration of systemic corticosteroids and telaprevir is
ENDOTHELIN RECEP TOR ANTAGONIS T
bosentan bosentan Concentrations of bosentan may be increased when co-administered with
telaprevir. Caution is warranted and clinical monitoring is recommended.
HIV-ANTIVIRAL AGEN TS: HIV-PROTEASE INHIBITORS (PIs)
Concomitant administration of telaprevir and atazanavir/ritonavir resulted
in reduced steady-state telaprevir exposure, while steady-state atazanavir
exposure was increased.
➞ ➞➞ ➞➞ ➞ ➞➞
Concomitant administration of telaprevir and darunavir/ritonavir resulted
in reduced steady-state exposures to telaprevir and darunavir. It is not
recommended to co-administer darunavir/ritonavir and telaprevir.
Concomitant administration of telaprevir and fosamprenavir/ritonavir
resulted in reduced steady-state exposures to telaprevir and amprenavir.
It is not recommended to co-administer fosamprenavir/ritonavir
Concomitant administration of telaprevir and lopinavir/ritonavir resulted in
reduced steady-state telaprevir exposure, while the steady-state exposure
to lopinavir was not affected. It is not recommended to co-administer
lopinavir/ritonavir and telaprevir.
HIV-ANTIVIRAL AGEN TS: REVERSE TRANSCRIPTASE INHIBITORS
Concomitant administration of telaprevir and efavirenz resulted in reduced
steady-state exposures to telaprevir and efavirenz.
Concomitant administration of telaprevir and tenofovir disoproxil fumarate
resulted in increased tenofovir exposure. Increased clinical and laboratory
monitoring are warranted. Tenofovir disoproxil fumarate should be
discontinued in patients who develop tenofovir-associated toxicities.
HORMONAL CON TRACEPTIVES/ESTROGEN
Exposure to ethinyl estradiol was decreased when co-administered with
telaprevir. Two effective non-hormonal methods of contraception should
be used during treatment with telaprevir.
Patients using estrogens as hormone replacement therapy should be
clinically monitored for signs of estrogen deficiency.
Concomitant Drug Class:
Effect on concentration
of INCIVEK or
Plasma concentrations of cyclosporine and tacrolimus are markedly
increased when co-administered with telaprevir. Plasma concentration of
sirolimus may be increased when co-administered with telaprevir, though
this has not been studied. Significant dose reductions and prolongation of
the dosing interval of the immunosuppressant to achieve the desired blood
levels should be anticipated. Close monitoring of the immunosuppressant
blood levels, and frequent assessments of renal function and
immunosuppressant-related side effects are recommended when
co-administered with telaprevir. Tacrolimus may prolong the QT interval.
The use of telaprevir in organ transplant patients has not been studied.
INHALED BE TA AGONIST
Concentrations of salmeterol may be increased when co-administered
with telaprevir. Concurrent administration of salmeterol and telaprevir
is not recommended. The combination may result in increased risk of
cardiovascular adverse events associated with salmeterol, including QT
prolongation, palpitations and sinus tachycardia.
Concentrations of methadone were reduced when co-administered with
telaprevir. No adjustment of methadone dose is required when initiating
co-administration of telaprevir. However, clinical monitoring is
recommended as the dose of methadone during maintenance therapy
may need to be adjusted in some patients.
PDE 5 INHIBITORS
PDE 5 inhibitors Concentrations of PDE5 inhibitors may be increased when co-
administered with telaprevir. For the treatment of erectile dysfunction,
sildenafil at a single dose not exceeding 25 mg in 48 hours, vardenafil
at a single dose not exceeding 2. 5 mg dose in 72 hours, or tadalafil at
a single dose not exceeding 10 mg dose in 72 hours can be used with
increased monitoring for PDE5 inhibitor-associated adverse events.
QT interval prolongation has been reported with vardenafil. Caution is
warranted and clinical monitoring is recommended.
Co-administration of sildenafil and telaprevir in the treatment of pulmonary
arterial hypertension is contraindicated.
Co-administration of tadalafil and telaprevir in the treatment of pulmonary
arterial hypertension is not recommended.
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of the change in PK.
In addition to the drugs included in the table above, the interaction between INCIVEK and the following drug was evaluated in clinical
studies and no dose adjustment is needed for either drug: esomeprozole.
USE IN SPECIFIC POPULATIONS
Because INCIVEK must be used in combination with ribavirin and peginterferon alfa, the contraindications and warnings
applicable to those drugs are applicable to combination treatment. Extreme care must be taken to avoid pregnancy in female
patients and in female partners of male patients.
INCIVEK/Peginterferon Alfa/Ribavirin Combination Treatment
Pregnancy Category X: ;"OJNBM; TUVEJFT;IB WF; TIPXO;UIBU;SJCB WJSJO;DBVTF T;CJSUI;EFGFDU T;BOE;PS;GFUBM;EFBUI T;XIJMF;QFHJOUFSGFSPO;BMGB;J T;
abortifacient. See the prescribing information for ribavirin.
Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin; and therefore ribavirin
is contraindicated in women who are pregnant and in the male partners of women who are pregnant (see also ribavirin prescribing
information). Interferons have abortifacient effects in animals and should be assumed to have abortifacient potential in humans (see
peginterferon alfa prescribing information).
Extreme caution must be taken to avoid pregnancy in female patients and female partners of male patients while taking this combination.
Women of childbearing potential and their male partners should not receive ribavirin unless they are using effective contraception (two
reliable forms) during treatment with ribavirin and for 6 months after treatment. Systemic hormonal contraceptives may not be as effective
in women while taking INCIVEK. Therefore, two alternative effective methods of contraception, including intrauterine devices and barrier
methods, should be used in women during treatment with INCIVEK and concomitant ribavirin.
A Ribavirin Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies in female patients and
female partners of male patients exposed to ribavirin during treatment and for 6 months follo wing cessation of treatment. Health
care providers and patients are encouraged to report such cases by calling 1-800-593-2214.
INCIVEK (telaprevir) Tablets
Pregnancy Category B: Telaprevir treatment alone in mice and rats did not result in harm to the fetus. The highest doses tested produced
exposures equal to 1.84- and 0.60-fold the exposures in humans at the recommended clinical dose, respectively. Telaprevir treatment alone
0.17-fold the human exposures at the recommended clinical dose. Potential effects on sperm (e.g., decreased motile sperm and increased
non-motile sperm count) were observed in a rat fertility study at exposures 0.30-fold the human exposures at the recommended clinical
percent of nonviable conceptuses per litter. These effects are likely associated with testicular toxicity in male but contributions of the female
cannot be ruled out. There are, however, no adequate and well-controlled studies in pregnant women.
Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. Extreme care must be
taken to avoid pregnancy in female patients and in female partners of male patients—both during treatment and for 6 months after the
completion of all treatment. INCIVEK combination treatment should not be started unless a female patient has a negative pregnancy test
immediately prior to initiation of treatment. Pregnancy testing should occur monthly during INCIVEK combination treatment and for 6 months
after all treatment has ended. Pregnancy testing in non-pregnant female partners is recommended before INCIVEK combination therapy,
every month during INCIVEK combination therapy, and for 6 months after ribavirin therapy has ended.
Hormonal contraceptives may be continued but may not be reliable during INCIVEK dosing and for up to two weeks following cessation of
INCIVEK. During this time, female patients of childbearing potential should use 2 effective non-hormonal methods of contraception. Examples
Two weeks after completion of INCIVEK treatment, hormonal contraceptives are again appropriate as one of the 2 required effective methods
PG;CJSUI;DPOUSPM;;IPXFWFS;; TQFDJGJD;QSFTDSJCJOH;JOGPSNBUJPO;SFDPNNFOEBUJPOT; TIPVME; CF; GPMMPXFE;GPS;UIF;DPOUSBDFQUJWFT;; 3FGFS;BMTP;UP;UIF;
prescribing information for ribavirin.
It is not known whether telaprevir is excreted in human breast milk. When administered to lactating rats, levels of telaprevir were higher in
rat pup body weight gain was similar in offspring from telaprevir-treated and control dams. Because of the potential for adverse reactions in
nursing infants, nursing must be discontinued prior to initiation of treatment. See also the prescribing information for ribavirin.
The safety, efficacy and pharmacokinetic profile of INCIVEK in pediatric patients have not been established.
Clinical studies of INCIVEK did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently
from younger patients. In general, caution should be exercised in the administration and monitoring of INCIVEK in geriatric patients reflecting
the greater frequency of decreased hepatic function, and of concomitant disease or other drug therapy.
INCIVEK is not recommended for use in patients with moderate or severe hepatic impairment (Child-Pugh B or C, score greater than or equal
to 7) because no pharmacokinetic or safety data are available regarding the use of INCIVEK in HCV-infected patients with moderate or severe
hepatic impairment, and appropriate doses have not been established. No dose adjustment of INCIVEK is necessary for patients with mild
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co-administered with INCIVEK.
No dose adjustment is necessary for INCIVEK in HCV-infected patients with mild, moderate or severe renal impairment. INCIVEK has not been
studied in HCV-infected patients with CrCl less than or equal to 50 mL/min.
The pharmacokinetics of telaprevir were assessed after administration of a single dose of 750 mg to HCV-negative subjects with severe renal
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The safety and efficacy of INCIVEK have not been established in patients co-infected with HCV/HIV or HCV/HBV.
Solid Organ Transplantation
The safety and efficacy of INCIVEK have not been established in solid organ transplant patients.
The highest documented dose administered is 1875 mg every 8 hours for 4 days in healthy subjects with INCIVEK alone. In that study, the
following common adverse events were reported more frequently with the 1875 mg q8h regimen compared to the 750 mg q8h regimen:
nausea, headache, diarrhea, decreased appetite, dysgeusia, and vomiting. No specific antidote is available for overdose with INCIVEK.
Treatment of overdose with INCIVEK consists of general supportive measures including monitoring of vital signs and observation of the
clinical status of the patient. In the event of an overdose, it is reasonable to employ the standard supportive measures, such as, removing
unabsorbed material from the gastrointestinal tract, employing clinical monitoring (including obtaining an electrocardiogram), and instituting
supportive therapy if required. It is not known whether telaprevir is dialyzable by peritoneal or hemodialysis.
Vertex Pharmaceuticals Incorporated
U. S. Patent No. 7,820,671
©2011 Vertex Pharmaceuticals Incorporated
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Pharmaceuticals Incorporated. The brands listed are the registered trademarks of their respective owners and are not trademarks of Vertex