Tenofovir Drug Interactions

- Nov 30, 2017 -

Tenofovir Drug Interactions

Concurrent with tenofovir disoproxil fumarate, the mean serum concentration (Cmax) and plasma area under the curve (AUC) of deshydroxyanhydretic sustained release or enteric formulations (Videx, VidexEC) were significantly increased high. The mechanism of this interaction is not clear. Higher concentrations of creatinine may lead to adverse events associated with dehydroxy-creatinine, including pancreatitis and nephropathy. A decrease in CD4 cell counts was observed in patients receiving tenofovir disoproxil fumarate and 400 mg daily of dehydroxy-creatinine. In adults weighing> 60 kg, the dose of dehydroxyanhydrides should be reduced to 250 mg when used in combination with tenofovir disoproxil fumarate. In patients weighing <60 kg, there is no data available for dose adjustments for dehydroxyanhydrides. When administered in combination, tenofovir disoproxil fumarate and dehydroxy-creatinine enteric solvent can be taken after fasting or after eating light food (<400 kcal, 20% fat). The dehydroxy-creatinine extended-release tablets and tenofovir disoproxil fumarate should be co-administered in the fasting state. Care should be taken when taking tenofovir disoproxil fumarate in combination with dehydroxy-creatinine, and patients receiving combination therapy should be closely monitored for adverse events associated with dehydroxy-creatinine. In patients with adverse events associated with dehydroxyanisation, dehydroxyanhydrides should be discontinued. [1] 

Since tenofovir is mainly cleared through the kidneys, tenofovir disoproxil fumarate in combination with drugs that lead to reduced renal function or competing with active tubule clearance can increase the serum concentration of tenofovir High and / or other renal clearance of drugs increased concentration. Such drugs include, but are not limited to, adefovir, cidofovir, aciclovir, valacyclovir, ganciclovir, and valganciclovir.

Higher concentrations of tenofovir are likely to lead to tenofovir disoproxil fumarate-related adverse events, including kidney disease.

Atazanavir and lopinavir / ritonavir may increase tenofovir concentrations. The mechanism of this interaction is not clear. Patients receiving atazanavir, lopinavir / ritonavir, and tenofovir dipivoxil fumarate should monitor adverse events associated with tenofovir dipivoxil fumarate. Tenofovir disoproxil fumarate should be discontinued in patients who develop an adverse event associated with tenofovir disoproxil fumarate.

Tenofovir disoproxil fumarate reduced AUC and Cmin of atazanavir. In combination with tenofovir disoproxil fumarate, it is recommended that atazanavir 300 mg be given concurrently with ritonavir 100 mg. If there is no ritonavir, atazanavir should not be given in combination with tenofovir disoproxil fumarate.

Bone effect

During the 144 weeks of study 903, bone mineral density (BMD) in the lumbar spine and hip was found to decline from baseline in both treatment groups studied. At week 144, tenofovir disoproxil fumarate + lamivudine was compared with patients receiving stavudine + lamivudine + efavirenz (-1.0% ± 4.6) Patients treated with efavirenz had a significantly higher mean percentage decrease in lumbar bone mineral density relative to baseline (-2.2% ± 3.9). Hip bone mineral density changes were similar between the two treatment groups (-2.8% ± 3.5 for tenofovir disoproxil fumarate and -2.4% ± 4.5 for stavudine). In both treatment groups, the decline in bone mineral density occurred mostly in the first 24-48 weeks of the study and then down to the 144th week, with the decline remaining stable. 28% of patients receiving tenofovir disoproxil fumarate and 21% of patients receiving stavudine had a loss of bone mineral density of at least 5% of the lumbar spine or hip bone Mineral density loss of at least 7%. Four patients with tenofovir disoproxil fumarate and six patients with stavudine reported clinically relevant fractures (except for fingers and toes). In addition, biochemical markers of bone metabolism (serum-specific alkaline phosphatase, serum calcitonin, serum carboxy-terminal peptide, urine Amino-terminal peptide) was significantly increased, suggesting increased bone turnover. Serum parathyroid hormone levels and 1,25 vitamin D levels were also higher in the tenofovir disoproxil fumarate group. With the exception of bone-specific alkaline phosphatase, these changes remain within the normal range. The impact of changes in bone mineral density and biochemical markers associated with tenofovir dipivoxil fumarate on long-term bone health and future fracture risk remains unknown. [1] 

Cases of osteomalacia (associated with proximal tubular lesions) associated with tenofovir disoproxil fumarate have been reported.

In HIV-infected patients at risk for pathological fractures or osteosclerosis, bone monitoring should be considered. Although studies have not been conducted on the effects of calcium and vitamin D supplementation, such supplementation may be of benefit to all patients. If suspected bone abnormalities, should be appropriate consultation.

Fat redistribution

In patients receiving antiretroviral therapy, body fat redistribution / build-up has been observed to include central obesity, increased back fat (buffalo dorsal), thinner skin, thinner face, enlarged chest, and Cushing's face. The mechanisms and long-term consequences of these phenomena are tentatively unknown. Causal relationship has not been established.

Immune Reconstitution Syndrome

Among patients who received combined antiretroviral therapy, including tenofovir disoproxil fumarate, had reported immune reconstitution syndrome. In the early stages of combination antiretroviral therapy, patients with immune system responses may have the potential for intractable or residual opportunistic infections such as Mycobacterium aureus infection, cytomegalovirus, pneumocystis pneumonia (PCP) Tuberculosis) have an inflammatory reaction, which is necessary for further evaluation and treatment.

Pregnant and lactating women medication

American pregnancy grading class B:

Reproductive studies were conducted in rats and rabbits, with doses up to 14 and 19 times higher by body surface area, respectively. The results showed no evidence of fertility or fetal injury due to tenofovir. However, no adequate and well-controlled studies have been conducted in pregnant women. Because animal reproductive studies do not always predict human response, tenofovir disoproxil fumarate should not be used during pregnancy unless it is needed.

Breastfeeding mothers: The Centers for Disease Control and Prevention recommends that HIV-infected mothers not breastfeed their babies to avoid the risk of transmitting HIV after birth. Studies conducted in rats demonstrate that Tenofovir is secreted in milk. It is unclear whether there is any secretion of norfovir in human milk. Because HIV transmission and serious adverse reactions are likely to occur in breastfeeding infants, mothers should be asked not to breastfeed if they are receiving tenofovir disoproxil fumarate.

Children's medication

Safety and efficacy have not been established in patients younger than 18 years of age.

Elderly medication

Clinical studies of tenofovir disoproxil fumarate Not enrolled a sufficient number of subjects 65 years of age or older to determine whether their response differed from that of younger subjects. In general, elderly patients choose the dose should be cautious, remember that their liver, kidney, heart function decline, concurrent disease or are using other drugs to increase the chance of treatment.