Tenofovir - Indications, Pharmacology, Warnings, and Precautions

Overview:

Tenofovir is an efficacious medicine that can deal with a specific infection called hepatitis B virus (HBV) infection, which is a disease evoked by hepatitis B virus, particularly impairing the liver. Tenofovir has gained authorization from the drug regulatory body of the United States, the Food and Drug Administration (FDA), to be prescribed for patients with hepatitis B virus infection. Though Tenofovir got marketing approval in the year 2001, its indication was restricted to human immunodeficiency virus infection (virus infection that wrecks the immune system). Later, in 2008, the FDA extended the applicability of Tenofovir for hepatitis B virus infection after evaluating the potency and safety aspects concerning the use of Tenofovir in hepatitis B virus-infected patients.

Drug Group:

Tenofovir falls under the nucleoside reverse transcriptase inhibitor drug class, encompassing a distinctive antiviral drug category. Antiviral drugs, as the name suggests, curb the progression of various viral infections. It can dramatically decline the virus load in the blood, thereby collapsing the manifestation and disease advancements.

Available Doses and Dosage Forms:

• Dosage Forms: Tenofovir is marketed in two distinct dosage forms - oral powder and pill. Both the dosage forms are intended to be taken by mouth. There are two different pharmacological forms of Tenofovir: one is Tenofovir Disoproxil Fumarate, and the other one is Tenofovir Alafenamide. However, the proportion of active Tenofovir differs in both forms.

• Available Doses: The powder form is a 40 milligram (mg) concentration of Tenofovir Disoproxil Fumarate in one gram of powder. The pill forms are marketed in four doses - 150, 200, 250, and 300 mg. The concerned doctor dictates the dose and dosage form, considering the patient's parameters, like body weight, condition for which the medicine is advised, and general health profile.

For Patients:

What Is HBV Infection?

HBV infection is a peculiar form of liver condition, which is triggered by the hepatitis B virus. It is a catchy infection where the virus particles can gain access to a healthy body upon exposure to their body fluids. Therefore, one-to-one transmission can also happen through sexual contact with a person who is already carrying these virus particles. Hence, it is categorized under sexually transmitted diseases (STDs). The hepatitis B virus particularly strikes the liver, impairing and disrupting its functions. Unnaturally darker urine, stools that resemble clay, stomach upset, diarrhea, and belly pain are some of the frequently reported manifestations associated with HBV infection. In addition, the affected person may experience general weakness, joint pain, fever, and skin yellowing. However, the condition often remains without obvious manifestations, particularly in the pediatric population, which holds up the diagnosis process. The HBV infection either follows a short-term or a long-term course. The long-term course often necessitates therapeutic intervention using appropriate antiviral medicines.

How Does Tenofovir Work?

As a potent antiviral agent, Tenofovir elicits its action by depreciating the proportion of active viral particles in the blood. It checks the cloning of viruses by impeding one of the indispensable enzymes for the virus’ multiplication. The enzyme reverse transcriptase enables the virus to easily convert its genetic material into human-like genetic material and incorporate it into human cells. This completely wrecks the viral replication process and brings appreciable collapses in the active virus count. However, Tenofovir is incapable of establishing a complete cure and resolution of HBV infection.

What Is the Dosage of Tenofovir?

The doctor dictates the dosage of Tenofovir, considering the patient's body weight. For a body weight of not less than 10 kilograms, the recommended drug-body weight proportion should be eight milligrams of Tenofovir Disoproxil Fumarate for every kilogram of body weight daily. For body weight not less than 35 kilograms, a daily dosage of 300 milligrams is advised. The dosage form of Tenofovir is often determined after discussing it with the patient. Powder form makes it easier for administration to babies and children who are unable and hesitant to take up pill form.

How Effective Is Tenofovir?

Tenofovir is reported to be highly efficacious in bringing down the blood’s virus load. More than 90 percent depreciation in the virus count is elicited in patients who underwent one year of Tenofovir therapy. However, it is not a curative therapy and cannot check either disease spread or liver complications that accompany HBV infection. Prolonged therapy using Tenofovir often results in better outcomes than short-term therapy.

What Are the Things to Inform the Doctor Before Taking the Drug?

The success of every treatment therapy necessitates proper patient-doctor interaction. The doctor should be informed about certain things beforehand to prevent unwanted outcomes. Some of the critical data that need to be shared with the doctor include the following:

• Prior allergy encounters the patient had with Tenofovir or other medicines about the same class of Tenofovir need to be discussed with the concerned doctor so that necessary changes in the medicine choice can be made to ensure safety.

• The doctor should be provided with a comprehensive medical history of the patient, which gives a thorough idea concerning the patient's general health. Existing kidney, liver, or bone issues need to be paid attention to before proceeding with Tenofovir therapy.

• It is imperative to give a detailed drug history, which enables the doctor to look for possible drug-to-drug associations. The drug history should encompass all the medicines, whether over-the-counter, herbal, dietary supplements or topical.

• The doctor should be made aware of the lactating and pregnancy status of the patient. There are specific guidelines that need to be adhered to while initiating therapy using Tenofovir during conception. Similarly, the potential hazards concerning Tenofovir therapy during pregnancy and lactation need to be assessed. Informing the doctors beforehand aids in bringing in appropriate alterations for the drug choice and dosage. In case the patient conceives while undergoing Tenofovir therapy, it needs to be discussed with the doctor right away.

How Is Tenofovir Administered?

Tenofovir is marketed under various brand names in powder and pill forms. Both these forms need to be introduced orally. The pill is advised to be taken with a glass of water, while the oral powder form requires a medium for the introduction. Soft foods like yogurt, apple puree, or baby food are the frequently preferred medium into which the Tenofovir oral powder needs to be blended. Liquids cannot dissolve the Tenofovir powder particle and hence are not preferred for incorporating the oral powder form of Tenofovir. The measuring scoops are provided in powder form, in which a single flat scoop accounts for one gram of powder.

What Are the Side Effects of Tenofovir?

There are a set of adverse reactions that may accompany Tenofovir therapy. Some of the widely reported side effects that are precipitated upon Tenofovir therapy include the following:

• Headache, stomach issues like indigestion, diarrhea, heartburn (flaming sensation in the chest), and collapse in body weight are some of the less significant side effects.

• In addition, depression (extreme grief), skin rashes, prickling sensation, trouble sleeping, and fever are also encountered during Tenofovir therapy.

• Bone pain, frequent fractures, stomach pain, puffy legs, dizziness, disorganized and racing heartbeat, altered breathing rate, diminishing urination, and extremities (arms and legs) turning out blue are some of the alarming side effects that often demand medical attention.

Dietary Considerations:

No specific dietary guidelines need to be considered during Tenofovir therapy. The patient can adhere to a healthy diet during the therapy. However, certain studies have revealed that taking Tenofovir after a fatty meal enhances the availability of the drug molecules in the circulation and subsequent hike in the drug’s concentration. For certain patients, the concerned medical professionals may advise specific dietary restrictions by considering the patient’s health status and the presence of concurrent diseases. In such cases, it is imperative to follow the instructions without fail.

Missed Dose:

Tenofovir must be taken only once a day, preferably at a specified time regularly. But occasionally, the patient may fail to recall the dosage time and miss out on the dose. In such cases, the patient can administer the dose once they become aware of the overlooked dose. If the patient recalls the next day at the time of the subsequent dose, they need to inform the concerned doctor as an abrupt break in Tenofovir can bring in adverse effects in the body.

Overdose:

Administering Tenofovir in excess doses, typically more than the prescribed dose, can bring in overdose issues. It can impair the functioning of vital organs, like kidneys. Therefore, upon exposure to an overdose of Tenofovir, immediate medical attention needs to be sought.

Storage:

Twenty-five degrees Celsius (77 degrees Fahrenheit) is the ideal storage temperature for both pill and powder forms of Tenofovir. However, the storage temperature range of 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit) is reported to be safe for Tenofovir. It is made available in small medicine bottles and must be stored within the bottle until the time of intake. After taking the medicine, ensure that the bottle is tightly shut.

For Doctors:

Indications:

• Chronic HBV infection (pediatric patients over two years and adult patients).

• Human immunodeficiency virus type-1 infection (pediatric patients over two years and adult patients).

Dose:

The Tenofovir dose for HBV infection is largely based on the patient’s body weight. It is generally not advised for babies with weight below 10 kilograms.

• Minimum of 10 Kilograms of Body Weight: For patients who weigh a minimum of 10 kilograms and prefer to have the powder form, the recommended daily dose is eight milligrams for each kilogram of body weight.

• Minimum of 17 Kilograms of Body Weight: The daily dose of Tenofovir pill form is recommended to be eight milligrams for every single kilogram of body weight.

• Minimum of 35 Kilograms of Body Weight: A daily dose of 300 milligrams is the preferred drug dosage.

Dosing Considerations:

Before the Tenofovir therapy commences, it is essential to establish the confirmed diagnosis of the HBV infection using specific diagnostic strategies. The dosage frequency of Tenofovir needs to be altered and modified when indicated for a patient with compromised renal functions. The adjustment must be executed after considering the patient’s creatinine clearance rate. However, no extension in the dosage frequency is advised for patients with mildly disrupted renal functions precipitating creatinine clearance rate in the range of 50 to 80 milliliters per minute. The lesser the creatinine clearance rate, the more the dosage interval suggested not to overburden the failing kidneys.

What Are the Pharmacological Aspects of Tenofovir?

• Mechanism of Action: Tenofovir works to depreciate the viral load as an antiviral medicine of the drug class nucleoside reverse transcriptase inhibitor. The hepatitis B virus possesses a ribonucleic acid (RNA) genetic structure. Virus particles cannot carry out replication without the assistance of human cells. It needs to be incorporated into the human genetic structure, which is deoxyribonucleic acid (DNA). The viral RNA must be structurally modified into DNA form to facilitate the incorporation. This conversion is denoted as reverse transcription, mediated by the reverse transcriptase enzyme. Tenofovir actively impedes the reverse transcriptase enzyme's activities, thereby hindering virus replication. The virus load elicits a tremendous fall, disrupting the HBV infection's progression.

• Pharmacodynamics: Tenofovir’s influence over the virus replication affects the immune response. It offers the body’s immune mechanism an opportunity to defend against viral intrusion. In the presence of an appreciable viral load, the immune response gets stamped out, and only when the viral load diminishes does it become capable of eliciting its defensive properties.

• Pharmacokinetics: Following oral intake, Tenofovir is quickly uptaken from the stomach. Both the pharmacological forms of Tenofovir are inert. After getting absorbed, the inactive form will be transfigured into the Tenofovir diphosphate structure, which is the functional form of Tenofovir. Unlike other drug molecules, tenofovir exhibits minimal binding to plasma proteins and circulates in the bloodstream as free drug molecules. Tenofovir’s volume of distribution is estimated to be around 0.813 milliliters per kilogram (mL/kg). These drug molecules get metabolized and broken down in the kidneys. The urinary route is the primary pathway for the elimination of Tenofovir from one’s body.

Toxicity:

Clinical toxicology study reports of Tenofovir’s carcinogenic and mutagenic properties failed to point out any such association in the therapeutic dosage level. However, certain scientific discussions signaled Tenofovir’s ability to alter genetic sequencing at appreciably higher dosages. Limited toxicology assessments on humans restrict the depth of data available concerning these parameters.

Clinical Studies:

Randomized, case-control clinical studies were conducted to gauge potency and safety aspects of Tenofovir for individuals with hepatitis B infection. However, the studies revealed that Tenofovir cannot interrupt the liver complications that are often flagged in association with HBV infections. Concomitant decompensated liver disease in patients detected with hepatitis B virus infection enhances kidney impairments. Studies also analyzed the depreciation in bone density following Tenofovir therapy against a placebo. They were reported to have accelerated bone density depreciation in the subjects compared to the placebo groups.

What Are the Contraindications of Tenofovir?

Tenofovir therapy is not advisable for patients with a known hypersensitivity towards the medicine containing Tenofovir. Exaggerated reactivity to any of the medicines belonging to the nucleoside reverse transcriptase inhibitor drug class mandates caution and scrutiny. Even in the suspected allergic cases, the therapy must be held up until the allergic response is ruled out. Allergy to any components included in the Tenofovir pill and powder form restricts the therapy, as it carries the risk of aggravated allergic response.

Warnings and Precautions:

• Worsening of Infection Upon Abrupt Drug Withdrawal: Tenofovir therapy always bears the risk of withdrawal aggravation. Upon withdrawal of the therapy, it precipitates exacerbation, manifesting severe symptoms. Therefore, the patient should be under surveillance post-termination of Tenofovir therapy. The exacerbation can be precipitated even months after the actual drug withdrawal, and it mandates an extended monitoring period.

• Impaired Kidney Functioning: Fanconi syndrome and acute kidney failure cases are also reported following long-term therapy using Tenofovir. The therapy can progressively hamper kidney functioning. Therefore, the functional status of the kidneys needs to be assessed before commencing the Tenofovir therapy. Periodic valuation of the kidney functioning by checking parameters like creatinine clearance rate aids in tracking any approaching impairments. In addition, when Tenofovir is advised for patients with pre-existing kidney issues, appropriate alterations in the dosing frequency need to be exercised.

• Resistance Development: When administered as a single drug regimen, Tenofovir enhances the susceptibility to acquiring resistance to the human immunodeficiency (HIV) type 1 virus. Therefore, to check inadvertent resistance development, the presence of HIV infection needs to be ruled out in HBV-infected patients. The concurrent existence of both infections necessitates combination therapy encompassing multiple antiretroviral drugs.

• Diminishing Bone Density: Tenofovir can reduce bone density when administered over an extended period. It enhances the susceptibility to osteopenia and osteomalacia and makes individuals vulnerable to fractures.

• Hepatomegaly: Tenofovir can bring in hepatomegaly or lactic acidosis when employed for a significant treatment duration. So, the patient must be vigilant about the early manifestations associated with hepatomegaly.

What Are the Drug Interactions of Tenofovir?

Tenofovir, when administered in conjunction with other drugs, can bring in unwanted and undesirable effects due to drug-drug associations. These interactions may often alter the potency and even the drug’s concentration. Some of the widely encountered drug interactions of Tenofovir include the following:

• Simultaneous administration of Tenofovir with other antiviral medicines, like Acyclovir and Ganciclovir, that share the common elimination pathway often tends to enhance the proportion of both medicines in the blood.

• Certain nonsteroidal anti-inflammatory drugs and aminoglycosides also exaggerate the drug concentration when coupled with Tenofovir.

• Concurrent intake of Tenofovir with drugs that deplete kidney function also potentiates the Tenofovir’s concentration.

Specific Considerations:

• During Pregnancy: Pregnancy does not flag any contraindication for Tenofovir therapy, as there is no supporting evidence concerning fetal harm and inborn defects. However, any drug administration during conception needs to be discussed with the doctor to look for possible adverse effects and risks.

• During Lactation: Studies have identified Tenofovir’s presence in breast milk upon maternal Tenofovir therapy. However, only restricted information is available concerning the impact it can have on the breastfed baby.

• Pediatric Population: Tenofovir’s efficacy has been proven for pediatric populations over two years of age. Nevertheless, there is still no clarity on the therapeutic applicability of Tenofovir in the pediatric population under the age of two. Therefore, it is generally not advised for babies who fall below 10 kilograms of body weight.

• Geriatric Population: Appropriate dose alterations need to be exercised when Tenofovir is advised for the elderly population, as they are more susceptible to underlying kidney or liver issues. However, Tenofovir’s therapeutic effects on the senior population are analogous to those in younger adults.