Understanding Tenofovir and Its Importance
Tenofovir is a nucleotide reverse transcriptase inhibitor (NtRTI) used in the treatment of HIV and chronic hepatitis B virus (HBV) infection. It works by blocking the replication of these viruses within the body. Tenofovir is available in two main forms: tenofovir disoproxil fumarate (TDF) and the newer tenofovir alafenamide (TAF). TAF is known to be associated with fewer bone and kidney toxicities compared to TDF. Despite its effectiveness, tenofovir must be taken with care, as interactions with other substances can compromise its efficacy or increase the risk of adverse reactions, particularly kidney or liver damage. This guide highlights the most significant interactions to be aware of.
Medications to Avoid or Use with Caution
Drug interactions with tenofovir primarily involve medications that can affect the kidneys, alter drug metabolism, or have overlapping toxicities. Always inform your healthcare provider about all medications you are taking, including over-the-counter drugs, to prevent dangerous interactions.
Nephrotoxic Drugs
Because tenofovir is primarily eliminated through the kidneys, combining it with other drugs that can harm the kidneys increases the risk of renal injury. This can lead to serious conditions like Fanconi syndrome or acute kidney failure.
- NSAIDs (Nonsteroidal Anti-inflammatory Drugs): Chronic, high-dose use of NSAIDs like ibuprofen, naproxen, and aspirin should be avoided or used with great caution. Regular monitoring of kidney function is recommended if co-administration is necessary.
- Certain Antivirals: Other antiviral agents that are also eliminated by the kidneys can compete with tenofovir for excretion. Examples include acyclovir, valacyclovir, ganciclovir, valganciclovir, cidofovir, and adefovir. Co-administration with adefovir is generally contraindicated.
- Aminoglycoside Antibiotics: Drugs such as gentamicin and amikacin can increase the nephrotoxic effects of tenofovir.
- Certain Antibiotics: Prolonged courses of vancomycin in combination with tenofovir have been reported to cause renal failure.
Protease Inhibitors (PIs) and Other Antiretrovirals
Certain HIV protease inhibitors (PIs), especially when pharmacologically boosted with ritonavir or cobicistat, can alter tenofovir's concentration in the blood. These changes are more significant with TDF, increasing the risk of tenofovir-related toxicity. Cobicistat can also reduce renal clearance and should be used cautiously.
- Atazanavir/Ritonavir and Darunavir/Ritonavir: These boosted PIs can lead to increased tenofovir plasma concentrations, amplifying the risk of kidney problems, particularly with TDF.
- Ledipasvir/Sofosbuvir (Hepatitis C treatment): This combination is contraindicated with TDF when used alongside a boosted PI due to increased risk of tenofovir nephrotoxicity.
Potent Enzyme Inducers
Strong inducers of enzymes like P-glycoprotein (P-gp) can significantly decrease the concentration of tenofovir alafenamide (TAF) in the blood, potentially leading to treatment failure.
- Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, and phenytoin should not be co-administered with TAF.
- Antimycobacterials: Rifampin, rifabutin, and rifapentine can decrease TAF concentrations and should be avoided or monitored closely.
- Herbal Product: St. John's wort is a potent enzyme inducer that drastically reduces tenofovir levels and is not recommended.
Herbal Supplements and OTC Products
Several non-prescription and herbal products can interfere with tenofovir. Patients should always discuss these with their doctor or pharmacist before use.
- St. John's Wort: As mentioned, this supplement can reduce tenofovir effectiveness by decreasing its concentration.
- Supplements with Cations: Over-the-counter supplements or antacids containing polyvalent cations like magnesium, calcium, aluminum, or iron can reduce the absorption and effectiveness of some tenofovir-containing regimens, particularly those including integrase inhibitors.
- Other Supplements: Some forms of Ginkgo biloba and Garlic oil may also cause problematic interactions with antivirals.
Alcohol Consumption
While moderate alcohol consumption may not have a direct, severe interaction with tenofovir disoproxil fumarate (TDF), excessive alcohol use poses a significant risk, especially for those on tenofovir alafenamide (TAF).
- Liver Function: Alcohol can worsen existing liver problems, an important consideration for patients with chronic HBV or HIV.
- TAF Metabolism: A study showed that alcohol can negatively impact the efficacy and worsen liver steatosis associated with TAF. It decreases the formation of the active tenofovir diphosphate and enhances lipid retention in liver cells.
Tenofovir Disoproxil Fumarate (TDF) vs. Tenofovir Alafenamide (TAF)
| Interaction Type | Tenofovir Disoproxil Fumarate (TDF) | Tenofovir Alafenamide (TAF) |
|---|---|---|
| Nephrotoxic Drugs (e.g., NSAIDs, Acyclovir) | Increased risk of nephrotoxicity due to competition for renal tubular excretion. | Still requires caution due to potential increased risk, but generally less kidney toxicity than TDF. |
| Protease Inhibitors (Boosted) | Some (e.g., Atazanavir/r) increase tenofovir plasma levels, raising kidney toxicity risk. | Generally associated with fewer renal issues when used with boosters due to lower plasma tenofovir levels. |
| Potent P-gp Inducers (e.g., Rifampin, St. John's Wort) | Interactions are less understood, but co-administration is generally not recommended due to safety concerns. | Avoid due to significantly decreased TAF concentrations, risking treatment failure. |
| Alcohol | Avoid or limit to mitigate potential liver damage. | Avoid or limit as it can decrease efficacy and worsen liver steatosis. |
Conclusion
Managing drug interactions is a critical component of tenofovir therapy. The list of substances to avoid or use with caution includes a variety of medications, especially those that impact kidney function, and potent enzyme inducers like certain anticonvulsants and St. John's wort. The emergence of TAF has provided an option with a safer renal profile, but it is not immune to interactions, particularly with P-gp inducers. Always consult your healthcare provider before starting any new medication, supplement, or herbal product while on tenofovir to ensure your treatment remains both safe and effective. Active patient-provider communication is the best strategy for preventing complications related to drug interactions.
HIVinfo, National Institutes of Health
