SOVALDY AND OLYSIO MEDS SAME DOSAGE FOR ALL?

[FRED220]

I read this question in another site and it made me think. The dosage for Sovaldi (400) and Olysio (150)  is the same for all, other meds like Riva can/are adjusted. A male at 260 lbs takes the same dosage as a female at 120 lbs, I would think the female would have more in her system because of her size and have more sides and/or better results. Whats the science behind same dosage fits all?    

[HectorSF]

"Whats the science behind same dosage fits all?  "

As with all with all FDA approved medicines/drugs studies (also called trials) are done to learn how long a drug is effective in the human body (how many times a day the medicine needs to be taken) and also to determine the most effective dosage of a drug.

NOTE: Sovaldi and Olysio (which are DAAs) vs. Ribavirin (an antiviral drug) work differently and are processed differently in the body so there is no correlation between the dosing of these very different drugs.

* Ribavirin
Mechanism of Action
The mechanism by which ribavirin contributes to its antiviral efficacy in the clinic is not fully understood. Ribavirin has direct antiviral activity in tissue culture against many RNA viruses (such as HCV). Ribavirin increases the mutation frequency in the genomes of several RNA viruses and ribavirin triphosphate inhibits HCV polymerase in a biochemical reaction.
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I will use trial data from Sovaldi studies to show how the one pill a day was determined and how the 400 mg dose was determined,

All of this information and my quotes are from...

Sofosbuvir
For Treatment of Chronic Hepatitis C Infection
Antiviral Drugs Advisory Committee Meeting
Briefing Document
25 October 2013
NDA 204671

5.2.4. Sofosbuvir (Sovaldi) Pharmacokinetics after Single- and Multiple-Dose Administration in Healthy Subjects

"SOF, a nucleotide analog prodrug, undergoes intrahepatic sequential metabolism to form the long-lived active nucleoside triphosphate analog, GS-461203, that makes SOF suitable for once-daily administration.
SOF and GS-331007 exhibited similar PK upon single- and multiple-dose administration with minimal accumulation of SOF or GS-331007. Dose linearity of SOF using the PK data from a single therapeutic (400 mg) and supratherapeutic (1200 mg) doses of SOF in fasted healthy subjects and from a single dose of SOF (200 mg) in fasted healthy subjects indicated
that near-dose linearity was observed for SOF AUCinf and Cmax, and GS-331007 AUCinf; GS- 331007 Cmax showed modestly less than dose proportional increases."
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5.3.1. Dose Response Relationship with Efficacy Evaluated as On-Treatment Suppression of HCV RNA
....
"In Phase 1 and 2 clinical studies, pharmacokinetic/pharmacodynamic (PK/PD) relationships for efficacy were examined under two treatment paradigms in patients with genotype 1 HCV infection: SOF/GS-9851 monotherapy (GS-9851 50, 100, 200 and 400 mg once daily with
placebo control and SOF 400 mg once daily) and SOF+Peg-IFN+RBV combination therapy (SOF+Peg-IFN+RBV 100, 200, and 400 mg once daily with Peg-IFN+RBV control). Change from baseline in HCV RNA (log10 IU/mL) was evaluated after 3 days of monotherapy and
SOF+Peg-IFN+RBV therapy."

"In the SOF+Peg-IFN+RBV combination therapy paradigm, exposure-virologic response relationships between GS-331007 AUCtau and HCV RNA reduction after three days of treatment is in good agreement with the model predictions from the monotherapy paradigm, with the model predicting 88% of maximal response at the 400 mg dose."

"Collectively, data from dose-ranging studies as either monotherapy or combination therapy with Peg-IFN+RBV reveal exposure response relationships that support the 400-mg dose of SOF. These data are further supported by the observation of universal on-treatment viral suppression lack of on-treatment virologic breakthrough and no development of drug
resistance in the Phase 3 program."

Take care.
Hector

[hrsepwrguy]

Gender,Body Weight, Body Mass Index

No dose adjustment is necessary based on gender, body weight or body mass index. These characteristics have no clinically meaningful relevant effect on the pharmacokinetics of simeprevir based on a population pharmacokinetic analysis of HCV-infected subjects treated with
OLYSIO

http://www.olysio.com/shared/product/olysio/prescribing-information.pdf

[hrsepwrguy]

Sofosbuvir Advisory Committee. October 25, 2013.

Clinical Pharmacology in Special Populations

No CYP450 hepatic metabolism

No dose adjustment in hepatic impairment

No dose adjustment if creatinine clearance >30 mL/min

No impact of HCV patient characteristics
on exposure – No impact of BMI, age, sex, race, or cirrhosis
on pharmacokinetics

http://www.fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/antiviraldrugsadvisorycommittee/ucm375286.pdf

"Only the chemists know for sure :-)"

[Sarah1949]

Come to think of it, perhaps that's why men have less sides.

[FRED220]

I agree only the chemist could answer the question but I would think it would cost them less money to produce one item for all instead a couple. It would cost more money for research and approval, I think...

[Sarah1949]

Or the larger are being under-dosed. :)

[flyinlynn]

Well if you think about it how many medicines are dose adjusted by the size of the patient.

Aspirin take 2 and call me in the morning (well except if you have cirrhosis) does that mean the meds are more effective for smaller people or are all smaller people getting over dosed.

I think it is more because ribavirin is so toxic they want to ensure smaller people dont get too much of it.

Only the chemists know for sure :-)

[patra_]

My husband and I have discusses this very thing w/Sovaldi and these new drugs coming out.

Don't have an answer for you, but agree that is a very valid question.  

Anyone know?     Pat