Community Pharmacy Supply for Hepatitis c pharmaceutical Care Information Pack
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- Administration
- Prescribing Information
- Dosage Modifications / Considerations
- Metabolism
- Contraindicated (10)
- Serious - Use Alternative (2)
Prescribing InformationSofosbuvir is indicated for treatment of chronic hepatitis C infection as a component of a combination antiviral regimen for patients with HCV mono-infection and HCV/HIV-1 co-infection. The treatment regimen and duration are dependent on both viral genotype and patient population
400 mg PO daily plus ribavirin and peginterferon alfa for 12 weeks; may consider Sofosbuvir plus ribavirin for 24 weeks in genotype 1 patients ineligible to receive peg-interferon-based regimen
400 mg PO daily plus ribavirin for 12 weeks
400 mg PO daily plus peginterferon alfa and ribavirin for 12 weeks, may consider Sofosbuvir plus ribavirin for 24 weeks in patients ineligible to receive peg-interferon-based regimen Dosing Considerations Sofosbuvir must not be used as monotherapy; if peginterferon alfa or ribavirin is discontinued for any reason, Sofosbuvir must also be discontinued AdministrationThe film-coated tablet is for oral use. Patients should be instructed to swallow the tablet whole. The film-coated tablet should not be chewed or crushed, due to the bitter taste of the active substance. The tablet should be taken with food if possible although efficacy on an empty stomach is not affected to any clinically significant extent (as per Sovaldi SPC, Gilead 2014) Patients should be instructed that if vomiting occurs within 2 hours of dosing an additional tablet should be taken. If vomiting occurs more than 2 hours after dosing, no further dose is needed. These recommendations are based on the absorption kinetics of Sofosbuvir and GS-331007 suggesting that the majority of the dose is absorbed within 2 hours after dosing. If a dose is missed and it is within 18 hours of the normal time, patients should be instructed to take the tablet as soon as possible and then patients should take the next dose at the usual time. If it is after 18 hours then patients should be instructed to wait and take the next dose at the usual time. Patients should not be instructed to take a double dose. [CLOSE WINDOW]
When Sofosbuvir is used in combination with ribavirin or peginterferon alfa/ribavirin, women of childbearing potential or their male partners must use two effective forms of contraception during the treatment and for a period of time after the treatment as recommended in the Summary of Product Characteristics for ribavirin. Effects on ability to drive and use machines Sofosbuvir has moderate influence on the ability to drive and use machines. Patients should be informed that fatigue and disturbance in attention, dizziness and blurred vision have been reported during treatment with Sofosbuvir in combination with peginterferon alfa and ribavirin. Sofosbuvir has mainly been studied in combination with ribavirin, with or without peginterferon alfa. In this context, no adverse drug reactions specific to Sofosbuvir have been identified. The most common adverse drug reactions occurring in subjects receiving Sofosbuvir and ribavirin or Sofosbuvir, ribavirin and peginterferon alfa were fatigue, headache, nausea and insomnia. Drug interactions Consult www.hep-druginteractions.com for current advice on drug interactions or contact specialist clinical pharmacist. Simeprevir - Protease Inhibitor (Available Sep 14) Similar to telaprevir and boceprevir, simeprevir is a NS3/4A protease inhibitor. Its mechanism of action is similar to other protease inhibitors which are currently approved to treat genotype 1 HCV infection. Simeprevir is highly effective in treating treatment-naive and treatment-experienced patients. In addition to being highly efficacious, simeprevir also appears to be safe with relatively few adverse side effects. The incidence of anaemia and rash appears to be lower compared to telaprevir and boceprevir. Unlike telaprevir and boceprevir, which need to be administered every 8 h with a fatty meal or snack; simeprevir can be taken as once-daily dosing with food. This should theoretically improve patient compliance with HCV therapy. Prescribing InformationDuration of Treatment In all patients, treatment with Simeprevir should be initiated in combination with peginterferon alfa and ribavirin and should be administered for 12 weeks.
Dosage Adjustment or Interruption To prevent treatment failure, the dose of Simeprevir must not be reduced or interrupted. If treatment with Simeprevir is discontinued because of adverse reactions or inadequate on-treatment virologic response, treatment must not be reinitiated. If adverse reactions potentially related to peginterferon alfa and/or ribavirin occur which require dosage adjustment or interruption of either medicine, refer to the instructions outlined in the respective prescribing information for these medicines. Photosensitivity Photosensitivity reactions have been observed with Simeprevir in combination with peginterferon alfa and ribavirin, including serious reactions which resulted in hospitalization. Photosensitivity reactions occurred most frequently in the first 4 weeks of treatment with Simeprevir in combination with peginterferon alfa and ribavirin, but can occur at any time during treatment. Photosensitivity may present as an exaggerated sunburn reaction, usually affecting areas exposed to light (typically the face, "V" area of the neck, extensor surfaces of the forearms, and dorsa of the hands). Manifestations may include burning, erythema, exudation, blistering, and oedema. Use sun protective measures and limit sun exposure during treatment with Simeprevir in combination with peginterferon alfa and ribavirin. Avoid use of tanning devices during treatment with Simeprevir in combination with peginterferon alfa and ribavirin. Discontinuation of Simeprevir should be considered if a photosensitivity reaction occurs but this decision should only by made by a senior member of the Infectious Disease or Gastroenterology prescribing team (contact on call medic out of hours if necessary) and patients should be monitored until the reaction has resolved. Rash Rash has been observed in subjects receiving Simeprevir in combination with peginterferon alfa and ribavirin. Rash occurred most frequently in the first 4 weeks of treatment with Simeprevir in combination with peginterferon alfa and ribavirin, but can occur at any time during treatment. Severe rash and rash requiring discontinuation of Simeprevir have been reported. Most of the rash events in Simeprevir-treated patients were of mild or moderate severity. Patients with mild to moderate rashes should be followed for possible progression of rash, including the development of mucosal signs (e.g., oral lesions, conjunctivitis) or systemic symptoms. If the rash becomes severe, Simeprevir should be discontinued, again only after contact is made with member of the specialist prescribing team. Patients should be monitored until the rash has resolved. Discontinue if inadequate virologic response
Dosage Modifications / Considerations
MetabolismSubstrate: CYP3A (major); CYP2C8 (minor) and CYP2C19 (minor) Inhibits OATP1B1/3 and P-gp transporters Mildly inhibits CYP1A2 and intestinal CYP3A, but does not affect hepatic CYP3A4 activity Consult www.hep-druginteractions.org for safety of concomitant meds Daclatasvir Daclatasvir is an inhibitor of nonstructural protein 5A (NS5A), a multifunctional protein that is an essential component of the HCV replication complex. Daclatasvir inhibits both viral RNA replication and virion assembly Prescribing Information Genotype 1 or 4 with significant fibrosis Daclatasvir + Sofosbuvir for 12 weeks Genotype 1 or 4 with compensated cirrhosis Daclatasvir + Sofosbuvir for 24 weeks (consider adding ribavirin for patients with very advanced liver disease or with other negative prognostic factors) Genotype 3 with compensated cirrhosis and/or treatment experienced Daclatasvir + Sofosbuvir + Ribavirin for 24 weeks can reduce to 12 weeks if less severe fibrosis
The recommended dose of Daklinza is 60 mg once daily, to be taken orally with or without meals. The tablet should be swallowed whole and not crushed or chewed due to the bitter taste of the active ingredients. Dose modification of Daklinza to manage adverse reactions is not recommended. If treatment interruption of components in the regimen is necessary because of adverse reactions, Daklinza must not be given as monotherapy. There are no virologic treatment stopping rules that apply to the combination of Daklinza with sofosbuvir. Missed doses Patients should be instructed that, if they miss a dose of Daklinza, the dose should be taken as soon as possible if remembered within 20 hours of the scheduled dose time. However, if the missed dose is remembered more than 20 hours after the scheduled dose, the dose should be skipped and the next dose taken at the appropriate time. Dose recommendation for concomitant medicines Strong inhibitors of cytochrome P450 enzyme 3A4 (CYP3A4) The dose of Daklinza should be reduced to 30 mg once daily when coadministered with strong inhibitors of CYP3A4. Moderate inducers of CYP3A4 The dose of Daklinza should be increased to 90 mg once daily when coadministered with moderate inducers of CYP3A Contraindications Coadministration with Strong Inducers of cytochrome P450 enzyme3A4 is contraindicated Coadministration with medicinal products that strongly induce cytochrome P450 3A4 (CYP3A4) and P-glycoprotein transporter (P-gp) and may lead to lower exposure and loss of efficacy of Daklinza. These active substances include but are not limited to phenytoin, carbamazepine, oxcarbazepine, phenobarbital, rifampicin, rifabutin, rifapentine, systemic dexamethasone, and the herbal product St John's wort (Hypericum perforatum). Consult www.hep-druginteractions.org for safety of concomitant meds Pregnancy and contraception requirements Daklinza should not be used during pregnancy or in women of childbearing potential not using contraception. Use of highly effective contraception should be continued for 5 weeks after completion of Daklinza therapy. When Daklinza is used in combination with ribavirin, the contraindications and warnings for that medicinal product are applicable. Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin; therefore, extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients (see the Summary of Product Characteristics for ribavirin).
Sofosbuvir: Nucleotide prodrug that undergoes metabolism to the active uridine analog triphosphate, an inhibitor of HCV NS5B RNA-dependent polymerase; its inhibition, in turn, suppresses viral replication
Harvoni is indicated for the treatment of chronic hepatitis C (CHC) Genotype 1 and 3 in adults (Sofosbuvir/Rbv in Genotype 2 patients) Treatment-naïve G1 with or without cirrhosis: 12 weeks Treatment-experienced G1 without cirrhosis: 12 weeks Treatment-experienced G1 with cirrhosis: 24 weeks Treatment all G3 with or without cirrhosis: 24 weeks Note: 8 weeks can be considered in treatment-naïve G1 patients without cirrhosis who have pretreatment HCV RNA <6 million IU/mL In patients with compensated cirrhosis requiring the addition of ribavirin to their treatment regimen, the daily dose of ribavirin is weight based (< 75 kg = 1,000 mg and ≥ 75 kg = 1,200 mg) and administered orally in two divided doses with food.
In patients with decompensated cirrhosis, ribavirin should be administered at a starting dose of 600 mg given in a divided daily dose. If the starting dose is well-tolerated, the dose can be titrated up to a maximum of 1,000-1,200 mg daily (1,000 mg for patients weighing < 75 kg and 1,200 mg for patients weighing ≥ 75 kg). If the starting dose is not well-tolerated, the dose should be reduced as clinically indicated based on haemoglobin levels. Patients should be instructed that if vomiting occurs Within 5 hours of dosing an additional tablet should be taken. If vomiting occurs more than 5 hours after dosing, no further dose is needed
If a dose is missed and it is within 18 hours of the normal time, patients should be instructed to take the tablet as soon as possible and then patients should take the next dose at the usual time. If it is after 18 hours then patients should be instructed to wait and take the next dose at the usual time. Patients should be instructed not to take a double dose. Coadministration of ledipasvir with acid-reducing agents may decrease ledipasvir solubility, resulting in decreased serum concentrations
Ledipasvir is an in vitro inhibitor of drug transporter P-gp and breast cancer resistance protein (BCRP) and may increase intestinal absorption of co-administered substrates for these transporters. In vitro data indicate that ledipasvir may be a weak inducer of metabolising enzymes such as CYP3A4, CYP2C and UGT1A1. Compounds that are substrates of these enzymes may have decreased plasma concentrations when co-administered with ledipasvir/sofosbuvir. In vitro ledipasvir inhibits intestinal CYP3A4 and UGT1A1. Medicinal products that have a narrow therapeutic range and which are metabolised by these isoenzymes should be used with caution and carefully monitored. Potential for other medicinal products to affect Harvoni Consult www.hep-druginteractions.com for current advice on drug interactions or contact specialist clinical pharmacist. Ledipasvir and sofosbuvir are substrates of drug transporter P-gp and BCRP while GS-331007 is not. Medicinal products that are potent P-gp inducers (e.g. rifampicin, St. John's wort, carbamazepine and phenytoin) may decrease ledipasvir and sofosbuvir plasma concentrations leading to reduced therapeutic effect of ledipasvir/sofosbuvir and should not be used with Harvoni. Co-administration with medicinal products that inhibit P-gp and/or BCRP may increase ledipasvir and sofosbuvir plasma concentrations without increasing GS-331007 plasma concentration; Harvoni may be co-administered with P-gp and/or BCRP inhibitors. Clinically significant medicinal product interactions with ledipasvir/sofosbuvir mediated by CYP450s or UGT1A1 enzymes are not expected
Contraindicated (10) carbamazepine , fosphenytoin , oxcarbazepine , phenobarbital , phenytoin , rifabutin , rifampin , rifapentine , st john's wort, tipranavir will decrease the level or effect of ledipasvir/sofosbuvir by P-glycoprotein (MDR1) efflux transporter. Never use combination. P-gp inducers decrease sofosbuvir levels, and therefore decrease conversion to sofosbuvir's active metabolite (GS-331007) responsible for 90% of pharmacologic effect Serious - Use Alternative (2) rosuvastatin - ledipasvir/sofosbuvir will increase the level or effect of rosuvastatin by unspecified interaction mechanism. Possible serious or life-threatening interaction. Monitor closely. Use alternatives if available. Coadministration not recommended; combination increases rosuvastatin levels which are associated with myopathy, including rhabdomyolysis
In clinical studies, fatigue and headache were more common in patients treated with ledipasvir/sofosbuvir compared to placebo. When ledipasvir/sofosbuvir was studied with ribavirin, the most frequent adverse drug reactions to ledipasvir/sofosbuvir + ribavirin combination therapy were consistent with the known safety profile of ribavirin, without increasing the frequency or severity of the expected adverse drug reactions. Viekirax plus Exviera Each Viekirax tablet contains 12.5mg of ombitasvir, 75mg of paritaprevir and 50mg Ritonavir The usual dose is Two tablets daily with food. Each Exviera tablet contains 250mg dasabuvir. The usual dose is one tablet twice daily (morning and evening) Prescribing Information Genotype 1b without cirrhosis Viekirax plus Exviera for 12 weeks Genotype 1b with compensated cirrhosis Viekirax plus Exviera for 12 weeks Genotype 1a without cirrhosis Viekirax plus Exviera plus ribavirin for 12 weeks Genotype 1a with compensated cirrhosis Viekirax plus Exviera plus ribavirin for 24 weeks See summary of product characteristics www.medicines.org.uk for further details Missed doses If a dose of Viekirax is missed and more than 12 hours have passed then the patient should just wait until the next dose is due and take that as normal. If a dose of Exviera is missed and more than 6 hours have passed then the patient should wait until the next dose is due and take that. Interaction with other medication Use of Ethinylestradiol containing products is contraindicated with Viekirax. Medications which are cleared via CYP3A4 as their main elimination pathway may have increased levels when administered with Viekirax which could lead to serious adverse effects. Medications which induce CYP3A enzymes may lead to increased metabolism of Viekirax and subsequent treatment failure. Please check www.hep-druginteractions.org for potential interactions with co prescribed medication. Pregnancy When Viekirax and Exviera are used in combination with Ribavirin the contraception requirements pertaining to Ribavirin must be followed.
Community Supply of HCV Medication Fife NHS Board has a commitment to deliver on the Scottish Government’s policy initiative “Shifting the Balance of Care”. The policy guidelines require improvements to health and social care services that improve the health and well-being of the population. In particular, changes are required so that the work of secondary care and primary care becomes more integrated and that care becomes located around community-based services. The development of new medicines, like those for HCV, has meant that many treatments have become available that transform previously fatal or debilitating diseases into conditions that a patient may manage successfully for many years. Realising the investment in the patient’s health requires that health services commit to normalising the patient’s experience of care as much as possible, through integration with standard primary-care services. To achieve these aims for patients with HCV in Fife the multidisciplinary hospital team led by the prescribing consultants will identify patients that fit the current guidelines for appropriate prescribing of the high cost HCV agent. A start date will be agreed at pre- treatment visit (usually in 3-4 weeks time) and the hospital clinical pharmacist will then make arrangements with the patient (via Clinical Nurse Specialists) for which community pharmacy they will attend. They will ensure prescription is legal and liaise with community pharmacist to allow seamless supply chain and cover of any issues that may arise. The community pharmacist will provide suitable information and advice to the patient to enable them to take their medicines accurately and appropriately and to manage any adverse effects that they may experience. The community pharmacist’s first port of call will be the clinical nurse specialists during working hours if there are supply or compliance issues. They will in turn, if deemed appropriate, contact a member of the clinical team. A member of the hospital pharmacy team will contact community pharmacies on a weekly basis to check compliance of patients on treatment and feed back any issues to prescribing consultant. Reproduced with permission from NHS Greater Glasgow and Clyde Yüklə 236 Kb. Dostları ilə paylaş:
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