Odefsey

/ Janssen

One tablet to be taken once daily with food
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Adults and adolescents (aged 12 years and older with body weight at least 35 kg) infected with human immunodeficiency virus-1 (HIV-1) without known mutations associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, tenofovir or emtricitabine and with a viral load ≤ 100,000 HIV-1 RNA copies/mL.

* Hypersensitivity to the active substances or to any of the excipients.
* This product should not be co-administered with medicinal products that can result in significant decreases in rilpivirine plasma concentrations (due to cytochrome P450 [CYP]3A enzyme induction or gastric pH increase), which may result in loss of therapeutic effect of Odefsey.
See prescribing information for full details

Cardiovascular
At supratherapeutic doses (75 mg once daily and 300 mg once daily), rilpivirine has been associated with prolongation of the QTc interval of the electrocardiogram (ECG). Rilpivirine at the recommended dose of 25 mg once daily is not associated with a clinically relevant effect on QTc. Should be used with caution when co-administered with medicinal products with a known risk of Torsade de Pointes.
Patients co-infected with HIV and hepatitis B or C virus
Patients with chronic hepatitis B or C treated with antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions.
Tenofovir alafenamide is active against hepatitis B virus (HBV). Discontinuation of this medical product therapy in patients co-infected with HIV and HBV may be associated with severe acute exacerbations of hepatitis. Patients co-infected with HIV and HBV who discontinue this medical product should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.
Liver disease
Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities during combination antiretroviral therapy (CART) and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
Weight and metabolic parameters
An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy. Such changes may in part be linked to disease control and lifestyle. For lipids, there is in some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating this to any particular treatment. For monitoring of blood lipids and glucose reference is made to established HIV treatment guidelines. Lipid disorders should be managed as clinically appropriate.
Mitochondrial dysfunction following exposure in utero
Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine. There have been reports of mitochondrial dysfunction in HIV negative infants exposed in utero and/or postnatally to nucleoside analogues; these have predominantly concerned treatment with regimens containing zidovudine. The main adverse reactions reported are haematological disorders (anaemia, neutropenia) and metabolic disorders (hyperlactatemia, hyperlipasemia). These events have often been transitory. Late onset neurological disorders have been reported rarely (hypertonia, convulsion, abnormal behaviour). Whether such neurological disorders are transient or permanent is currently unknown. These findings should be considered for any child exposed in utero to nucleos(t)ide analogues, who present with severe clinical findings of unknown aetiology, particularly neurologic findings. These findings do not affect current national recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV.
Immune Reactivation Syndrome
In HIV infected patients with severe immune deficiency at the time of institution of CART, an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, such reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples include cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis jirovecii pneumonia. Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.
Opportunistic infections
Patients receiving this medical product may continue to develop opportunistic infections and other complications of HIV infection, and therefore should remain under close clinical observation by physicians experienced in the treatment of patients with HIV associated diseases.
Osteonecrosis
Cases of osteonecrosis have been reported particularly in patients with advanced HIV disease and/or long-term exposure to CART. Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.
Nephrotoxicity
Post-marketing cases of renal impairment, including acute renal failure and proximal renal tubulopathy have been reported with tenofovir alafenamide-containing products. A potential risk of nephrotoxicity resulting from chronic exposure to low levels of tenofovir due to dosing with tenofovir alafenamide cannot be excluded. It is recommended that renal function is assessed in all patients prior to, or when initiating, therapy with this medical product and that it is also monitored during therapy in all patients as clinically appropriate. In patients who develop clinically significant decreases in renal function, or evidence of proximal renal tubulopathy, discontinuation should be considered.
Patients with end stage renal disease on chronic haemodialysis
It’s should generally be avoided but may be used with caution in adults with end stage renal disease (estimated CrCl < 15mL/min) on chronic haemodialysis if the potential benefits outweigh the potential risks.
Excipients
This medical product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
See prescribing information for full details.

The most frequently reported adverse reactions in clinical studies of treatment-naïve patients taking emtricitabine + tenofovir alafenamide in combination with elvitegravir + cobicistat were nausea (11%), diarrhoea (7%), and headache (6%). The most frequently reported adverse reactions in clinical studies of treatment-naïve patients taking rilpivirine hydrochloride in combination with emtricitabine + tenofovir disoproxil fumarate were nausea (9%), dizziness (8%), abnormal dreams (8%), headache (6%), diarrhoea (5%) and insomnia (5%).
Very common: increased total cholesterol, increased LDL-cholesterol, insomnia, headache, dizziness, nausea, increased pancreatic amylase, and increased transaminases (AST and/or ALT).
Common: decreased white blood cell count1, decreased haemoglobin1, decreased platelet count, decreased appetite, increased triglycerides, depression, abnormal dreams, sleep disorders, depressed mood, somnolence, abdominal pain, vomiting, increased lipase, abdominal discomfort, dry mouth, flatulence, diarrhea, increased bilirubin, rash, fatigue.
See prescribing information for full details.

Emtricitabine
Co-administration of emtricitabine with medicinal products that are eliminated by active tubular secretion may increase concentrations of emtricitabine, and/or the co-administered medicinal product. Medicinal products that decrease renal function may increase concentrations of emtricitabine.
Rilpivirine
Rilpivirine is primarily metabolised by CYP3A. Medicinal products that induce or inhibit CYP3A may thus affect the clearance of rilpivirine.
Tenofovir alafenamide
Tenofovir alafenamide is transported by P-gp and breast cancer resistance protein (BCRP). Medicinal products that affect P-gp and BCRP activity may lead to changes in tenofovir alafenamide absorption. Medicinal products that induce P-gp activity (e.g., rifampicin, rifabutin, carbamazepine, and phenobarbital) are expected to decrease the absorption of tenofovir alafenamide, resulting in decreased plasma concentration of tenofovir alafenamide, which may lead to loss of therapeutic effect of this medical product and development of resistance. Co-administration of this medical product with other medicinal products that inhibit P-gp and BCRP activity (e.g., ketoconazole, fluconazole, itraconazole, posaconazole, voriconazole, ciclosporin) is expected to increase the absorption and plasma concentration of tenofovir alafenamide.
Concomitant use contraindicated
Co-administration of this medical product and medicinal products that induce CYP3A has been observed to decrease the plasma concentrations of rilpivirine which could potentially lead to loss of virologic response to this product and possible resistance to rilpivirine and to the NNRTI class.
Co-administration of this medical product with proton pump inhibitors has been observed to decrease the plasma concentrations of rilpivirine (due to an increase in gastric pH) which could potentially lead to loss of virologic response to this product and possible resistance to rilpivirine and to the NNRTI class.
Concomitant use where caution is recommended
QT prolonging medicinal products
This product should be used with caution when co-administered with a medicinal product with a known risk of Torsade de Pointes.
See prescribing information for full details.

Pregnancy: There is a limited amount of data (less than 300 pregnancy outcomes) from the use of tenofovir alafenamide in pregnant women A moderate amount of data on pregnant women (between 300-1,000 pregnancy outcomes) indicate no malformative or foetal/neonatal toxicity of rilpivirine. Lower exposures of rilpivirine were observed during pregnancy; therefore viral load should be monitored closely. A large amount of data on pregnant women (more than 1,000 exposed outcomes) indicate no malformative nor foetal/neonatal toxicity associated with emtricitabine.
Lactation: Emtricitabine is excreted in human milk. It is not known whether rilpivirine or tenofovir alafenamide are excreted in human milk. In animal studies it has been shown that tenofovir is excreted in milk. Rilpivirine is excreted in the milk of rats.
There is insufficient information on the effects of all the components of this medical product in newborns/infants.
Because of the potential for adverse reactions in breastfed infants, women should be instructed not to breast-feed if they are receiving this product.
In order to avoid transmission of HIV to the infant it is recommended that women living with HIV do not breast-feed their infants.

If overdose occurs the patient must be monitored for evidence of toxicity (see section 4.8), and standard supportive treatment applied as necessary including observation of the clinical status of the patient and monitoring of vital signs and ECG (QT interval).
There is no specific antidote for overdose with this medical product. Up to 30% of the emtricitabine dose can be removed by haemodialysis. Tenofovir is efficiently removed by haemodialysis with an extraction coefficient of approximately 54%. It is not known whether emtricitabine or tenofovir can be removed by peritoneal dialysis. Since rilpivirine is highly protein bound, dialysis is unlikely to result in significant removal of the active substance. Further management should be as clinically indicated or as recommended by the national poisons center, where available

may have minor influence on the ability to drive and use machines. Patients should be informed that fatigue, dizziness and somnolence have been reported during treatment