(R)-PMPA
(R)-PMPA Uses, Dosage, Side Effects, Food Interaction and all others data.
(R)-PMPA Disoproxil Fumarate, an acyclic nucleotide analogue of adenosine monophosphate, is a pro-drug of (R)-PMPA. It shows activity against hepatitis B virus polymerase and HIV reverse transcriptase after phosphorylation to the active diphosphate form. (R)-PMPA diphosphate inhibits viral polymerase (reverse transcriptase) by directly competing with the natural substrate deoxyribonucleotide and by causing DNA chain termination after its incorporation into viral DNA.
(R)-PMPA has been shown to be highly effective in patients that have never had an antiretroviral therapy and it seemed to have lower toxicity than other antivirals such as stavudine. In phase 3 clinical trials, tenofovir presented a similar efficacy than efavirenz in treatment-naive HIV patients. In hepatitis B infected patients, after one year of tenofovir treatment, the viral DNA levels were undetectable.
| Trade Name | (R)-PMPA |
| Availability | Prescription only |
| Generic | Tenofovir |
| Tenofovir Other Names | (R)-PMPA, Tenofovir, Tenofovir (anh.) |
| Related Drugs | Biktarvy, Truvada, entecavir, ritonavir, zidovudine, abacavir, emtricitabine, lamivudine, Vemlidy, Complera |
| Type | |
| Formula | C9H14N5O4P |
| Weight | Average: 287.2123 Monoisotopic: 287.078340473 |
| Protein binding | Tenofovir is minimally bound to plasma proteins and only about 7.2% of the administered dose is found in the bound state. |
| Groups | Experimental, Investigational |
| Therapeutic Class | Drugs for HIV / Anti-retroviral drugs, Hepatic viral infections (Hepatitis B) |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
This is used for the treatment of:
- Chronic hepatitis B virus infection in adults
- HIV infected adults in combination with other anti retroviral agents
How (R)-PMPA works
Once tenofovir is activated by a bi-phosphorylation it acts as an antiviral acyclic nucleoside phosphonate. It is a potent inhibitor of the viral reverse transcriptase with an inhibitory constant of approximately 0.022 micromolar.
Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase causing chain termination and the inhibition of viral synthesis. All these activities are attained by its competition with deoxyadenosine 5'-triphosphate in the generation of new viral DNA. Once tenofovir is incorporated in the chain, it induces a chain termination which in order inhibits viral replication. The safety of tenofovir relies on its low affinity towards the cellular DNA polymerase including the mitochondrial DNA polymerase gamma.
Dosage
(R)-PMPA dosage
The recommended dose of (R)-PMPA in chronic hepatitis B virus infection in adults 18 years of age and older with adequate renal function is 300 mg once daily with or without food.
Side Effects
The most common side effects are nausea, vomiting, diarrhea and flatulence.
Toxicity
There haven't been reports regarding the LD50 of the parent compound nor the effects of an overdose. However, based on the reports with the derivative that most rapidly transforms into tenofovir, tenofovir disoproxil, it is recommended to monitor overdose patients. As well, it is widely known that tenofovir is efficiently removed by hemodialysis.
Administration of high doses of tenofovir has been reported to produce bone toxicity reported as osteomalacia and reduced bone mineral density and to produce some degree of renal toxicity.
To know more about the carcinogenicity and mutagenic potential of tenofovir, as well as the effect on fertility, please visit the drug entries for the derivatives tenofovir disoproxil and tenofovir alafenamide.
Precaution
Co-administration with other drugs: (R)-PMPA should not be administered concurrently with Emtricitabine & (R)-PMPA combination or Adefovir Dipivoxil.
Lactic Acidosis & Severe Hepatomegaly with Steatosis: Though the risk of occurrence of lactic acidosis is low for (R)-PMPA, treatment should be suspended in any patient who develops lactic acidosis or hepatotoxicity.
Exacerbation of hepatitis after discontinuation of treatment: Discontinuation of (R)-PMPAtherapy may be associated with severe acute exacerbation of hepatitis.
Interaction
Co-administration of (R)-PMPA with anti-retroviral, entecavir, lamivudine, methadone, oral contraceptives, ribavirin and tacrolimus did not result in significant drug interactions. The effects of co-administration of (R)-PMPA with other drugs that are renally eliminated or are known to affect renal function have not been evaluated.
Food Interaction
- Take with food.
[Minor] Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate.
According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state.
However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state.
Food delays the time to reach tenofovir Cmax by approximately 1 hour.
(R)-PMPA disoproxil fumarate may be administered without regard to meals.
(R)-PMPA Drug Interaction
Moderate: ritonavir, darunavirUnknown: aspirin, Allergy , sulfamethoxazole / trimethoprim, venlafaxine, ginkgo, pregabalin, acetaminophen, tramadol, emtricitabine / tenofovir, valproic acid, sildenafil, thiamine, cyanocobalamin, pyridoxine, ascorbic acid, cholecalciferol, phytonadione, zinc sulfate
(R)-PMPA Disease Interaction
Major: hepatitis B, hepatotoxicity, renal dysfunctionModerate: bone toxicityMinor: liver disease
Volume of Distribution
Accumulation of tenofovir in plasma is related to the presence of nephrotoxic effects. It is reported that tenofovir presents a volume of distribution of 0.813 L/kg.
Elimination Route
(R)-PMPA as the active moiety presents a very low bioavailability when orally administered. Hence, the administration of this active agent is required to be under its two prodrug forms, tenofovir disoproxil and tenofovir alafenamide. This reduced absorption is suggested to be related to the presence of two negative charges among its structure. This negative charge limits its cellular penetration, and its passive diffusion across cellular membranes and intestinal mucosa hindering its availability for oral administration.
Intravenous tenofovir has been shown to produce a maximum plasma concentration of 2500 ng/ml with an AUC of 4800 ng.h/ml.
Half Life
The reported half-life of tenofovir is of 32 hours.
Clearance
The clearance of tenofovir is highly dependent on the patient renal stage and hence the clearance rate in patients with renal impairment is reported to be of 134 ml/min while in patients with normal function the clearance rate can be of 210 ml/min.
Elimination Route
(R)-PMPA is eliminated in the urine by tubular secretion and glomerular filtration. The elimination of this compound is driven by the activity of the human organic anion transporters 1 and 3 and its secretion is mainly ruled by the activity of the multidrug resistance-associated protein 4.
Pregnancy & Breastfeeding use
Pregnancy: Pregnancy category B. It should be used during pregnancy only if clearly needed.
Lactation: It is not known whether it is excreted in human milk. Mothers should be instructed not to breast feed if they are taking (R)-PMPA.
Contraindication
(R)-PMPA is contraindicated in patients with known hypersensitivity to (R)-PMPA or any component of the product.
Special Warning
Pediatric use: Safety and effectiveness of (R)-PMPA in pediatric patients below the age of 18 years have not been established.Geriatrics use: Clinical studies of (R)-PMPA did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. But care should be taken in dose selection, and it may be useful to monitor renal function.Renal Impairment: Haemodialysis patients: 300 mg once every 7 days or after a cumulative total of 12 hr of dialysis.
- CrCl (10-29 mL/min): 300 mg 72-96 hrly.
- CrCl (30-49 mL/min): 300 mg 48 hrly.
Hepatic impairment
: No dose adjustment is required in patients with hepatic impairment.
Acute Overdose
There is no experience of (R)-PMPA overdose reported in patients
Storage Condition
Store in a cool and dry place, protected from light and moisture. Keep the medicine out of the reach of children.
Innovators Monograph
You find simplified version here (R)-PMPA
(R)-PMPA contains Tenofovir see full prescribing information from innovator (R)-PMPA Monograph, (R)-PMPA MSDS, (R)-PMPA FDA label
FAQ
What is (R)-PMPA used for?
(R)-PMPA is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children 2 years of age and older.(R)-PMPA is also used to treat chronic (long term) HBV in adults and children 2 years of age and older weighing 22 pounds (10 kilograms) or more.
How safe is (R)-PMPA?
Possessing potent and sustainable antiviral efficacy, has been reported to be efficacious and safe for patients with multidrug-resistant HBV infection as a rescue therapy.
What are common side effects of (R)-PMPA?
(R)-PMPA may cause side effects are include:
- diarrhea
- headache
- depression
- rash
- itching
- fever
- difficulty falling asleep or staying asleep
- gas
- weight loss
How should (R)-PMPA be used?
(R)-PMPA comes as a tablet and as an oral powder to take by mouth. The tablet is usually taken with or without food once daily. The powder is usually taken with food once daily.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it.If it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
Is (R)-PMPA safe during pregnancy?
(R)-PMPA is safe for pregnant women living with HIV when compared to other antiretroviral treatment (ART) regimes, despite concerns in the past that it could lead to adverse pregnancy outcomes.
Is (R)-PMPA safe during breastfeeding?
(R)-PMPA are safe for breastfeeding women, according to a new review of the evidence.
Can I drink alcohol with (R)-PMPA?
Avoid drinking alcohol. It may increase your risk of liver damage. Using this medicine will not prevent your disease from spreading.
How long can you take (R)-PMPA?
Continue to take (R)-PMPA regularly for as long as your doctor tells you to, even if you feel well. This is to keep your immune system healthy.
Does (R)-PMPA make gain weight?
Most weight gain is modest and occurs in the first year after switching, a review of 12 large clinical trials shows.
Does (R)-PMPA cause hair loss?
Not identify hair loss as a potential side-effect of the (R)-PMPA. In most of the women, the hair loss became apparent between two to four months after switching from the older formula of (R)-PMPA.
How long does (R)-PMPA stay in my body?
(R)-PMPA may longer up to 3 weeks in body.
Can I take (R)-PMPA in the morning?
Many people who have found that (R)-PMPA is best to take it before going to bed. This is because the side effects include feeling drowsy or dizzy. HIV treatment works best if you take it every day, ideally at the same time each day.
Does (R)-PMPA weaken the immune system?
(R)-PMPA affects your immune system, which may cause certain side effects (even weeks or months after you've taken this medicine).
Can I take (R)-PMPA on an empty stomach?
Take with or without food.Best taken with food, but can be taken on an empty stomach.
What happens when I stop taking (R)-PMPA?
If you stop taking (R)-PMPA even for a short time, or skip doses, the virus may become resistant to medications and may be harder to treat.
Can (R)-PMPA treat Covid?
(R)-PMPA was associated with an 83% relative risk reduction of contracting severe COVID-19.
Does (R)-PMPA cause lipodystrophy?
(R)-PMPA is not associated with fat wasting lipoatrophy.
Does (R)-PMPA cause itching?
A very serious allergic reaction to this drug is rare.but may (R)-PMPA can causes itching.
Can I overdose on (R)-PMPA?
If (R)-PMPA is administered by a healthcare provider in a medical setting,it is unlikely that an overdose will occur. If overdose is suspected, seek emergency medical attention.
