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Drug overview for ODEFSEY (emtricitabine/rilpivirine hcl/tenofovir alafenamide fumarate):
Generic name: EMTRICITABINE/RILPIVIRINE HCL/TENOFOVIR ALAFENAMIDE FUMARATE (EM-trye-SYE-ta-been/RIL-pi-VIR-een/ten-OF-oh-vir AL-a-FEN-a-mide)
Drug class: Antiviral-HIV (Antiretroviral) Nonnucleoside RT Inhibitor
Therapeutic class: Anti-Infective Agents
Emtricitabine, an antiretroviral agent, is a human immunodeficiency virus Rilpivirine, an antiretroviral agent, is a human immunodeficiency virus Tenofovir alafenamide fumarate, an antiviral agent, is a nucleotide reverse (HIV) nonnucleoside reverse transcriptase inhibitor (NNRTI). (HIV) nucleoside reverse transcriptase inhibitor (NRTI). transcriptase inhibitor that is active against hepatitis B virus (HBV) and human immunodeficiency virus (HIV).
Tenofovir alafenamide fumarate is available as a single entity for the treatment of chronic hepatitis B virus (HBV) infection in adults and pediatric patients >=6 years of age and weighing >=25 kg with compensated liver disease. Tenofovir alafenamide fumarate is also available in various fixed-combination preparations that contain additional antiretroviral agents; these products are used for the treatment of human immunodeficiency virus (HIV) infection and/or for HIV pre-exposure prophylaxis (PrEP). Refer to separate combination product monographs for information related to the specific uses of these products and the role of tenofovir alafenamide fumarate-containing regimens in the treatment and prevention of HIV infection.
Generic name: EMTRICITABINE/RILPIVIRINE HCL/TENOFOVIR ALAFENAMIDE FUMARATE (EM-trye-SYE-ta-been/RIL-pi-VIR-een/ten-OF-oh-vir AL-a-FEN-a-mide)
Drug class: Antiviral-HIV (Antiretroviral) Nonnucleoside RT Inhibitor
Therapeutic class: Anti-Infective Agents
Emtricitabine, an antiretroviral agent, is a human immunodeficiency virus Rilpivirine, an antiretroviral agent, is a human immunodeficiency virus Tenofovir alafenamide fumarate, an antiviral agent, is a nucleotide reverse (HIV) nonnucleoside reverse transcriptase inhibitor (NNRTI). (HIV) nucleoside reverse transcriptase inhibitor (NRTI). transcriptase inhibitor that is active against hepatitis B virus (HBV) and human immunodeficiency virus (HIV).
Tenofovir alafenamide fumarate is available as a single entity for the treatment of chronic hepatitis B virus (HBV) infection in adults and pediatric patients >=6 years of age and weighing >=25 kg with compensated liver disease. Tenofovir alafenamide fumarate is also available in various fixed-combination preparations that contain additional antiretroviral agents; these products are used for the treatment of human immunodeficiency virus (HIV) infection and/or for HIV pre-exposure prophylaxis (PrEP). Refer to separate combination product monographs for information related to the specific uses of these products and the role of tenofovir alafenamide fumarate-containing regimens in the treatment and prevention of HIV infection.
DRUG IMAGES
ODEFSEY TABLET
The following indications for ODEFSEY (emtricitabine/rilpivirine hcl/tenofovir alafenamide fumarate) have been approved by the FDA:
Indications:
HIV infection
Professional Synonyms:
Human immunodeficiency virus disease
Human immunodeficiency virus infection
Indications:
HIV infection
Professional Synonyms:
Human immunodeficiency virus disease
Human immunodeficiency virus infection
The following dosing information is available for ODEFSEY (emtricitabine/rilpivirine hcl/tenofovir alafenamide fumarate):
Dosage of tenofovir alafenamide fumarate is expressed in terms of tenofovir alafenamide.
Emtricitabine capsules and oral solution are not bioequivalent. Rilpivirine is commercially available as rilpivirine hydrochloride; dosage Bioavailability of the oral solution is 80% relative to that of the is expressed in terms of rilpivirine.
capsule.
If rilpivirine (Edurant(R)) is coadministered with rifabutin, the rilpivirine dosage should be increased to 50 mg once daily. If rifabutin coadministration is halted, the rilpivirine dosage should be decreased to 25 mg once daily.
Reduce dosage in patients with renal impairment; emtricitabine is principally eliminated by the kidney.
Emtricitabine capsules and oral solution are not bioequivalent. Rilpivirine is commercially available as rilpivirine hydrochloride; dosage Bioavailability of the oral solution is 80% relative to that of the is expressed in terms of rilpivirine.
capsule.
If rilpivirine (Edurant(R)) is coadministered with rifabutin, the rilpivirine dosage should be increased to 50 mg once daily. If rifabutin coadministration is halted, the rilpivirine dosage should be decreased to 25 mg once daily.
Reduce dosage in patients with renal impairment; emtricitabine is principally eliminated by the kidney.
Tenofovir alafenamide fumarate is administered orally once daily with food. Store at <30degreesC in the original container; keep container tightly closed. Rilpivirine hydrochloride is available as oral tablets (Edurant(R)) and tablets for oral suspension (Edurant PED(R)); both formulations are administered once daily with a meal.
Rilpivirine tablets should be administered to adults and pediatric patients weighing >=25 kg. Rilpivirine tablets for oral suspension should be administered only to pediatric patients weighing >=14 kg to <25 kg. Rilpivirine oral tablets and tablets for oral suspension have differing pharmacokinetic profiles; therefore, the tablets and tablets for oral suspension should not be substituted on a milligram-per-milligram basis.
Rilpivirine tablets for oral suspension must be dispersed in drinking water and immediately consumed with a meal. If not consumed immediately, the suspension should be discarded and a new dose prepared. Rilpivirine tablets for oral suspension should not be crushed, chewed, or swallowed whole.
In order to properly prepare the tablets for oral suspension for administration, an appropriate number of tablets should be placed in a cup and 5 mL of room temperature drinking water should be added. The cup should be swirled carefully for 1--2 minutes; the oral suspension should begin to have a cloudy appearance. After swirling the cup for 1--2 minutes, the oral suspension may be consumed immediately or the suspension can be further diluted with 5 mL of drinking water, orange juice, or applesauce to assist in administration.
All the medicine within the cup should be consumed immediately; a spoon may be used if needed. If medicine is still present in the cup, another 5 mL of drinking water (or alternative beverage or soft food) may be added to the cup, swirled, and consumed immediately. Food enhances rilpivirine bioavailability.
Systemic exposure is approximately 40 or 50% lower if rilpivirine tablets are administered under fasting conditions or with only a protein-rich nutritional drink, respectively, compared with following a standard meal (533 kcal) or high-caloric meal (928 kcal). Systemic exposure is 31 or 28% lower if rilpivirine tablets for oral suspension are dispersed in drinking water in fasted conditions or after yogurt consumption, respectively, compared with following a meal in adults containing 533 kcal. If a dose of rilpivirine is missed within 12 hours of the time it is usually taken, take the missed dose as soon as possible with a meal.
If a dose of rilpivirine is missed by more than 12 hours, then skip the missed dose and resume the normal dosing schedule. Rilpivirine must be used in conjunction with other antiretrovirals. Single-entity rilpivirine should not be used concomitantly with emtricitabine/rilpivirine/tenofovir alafenamide or cabotegravir/rilpivirine injeciton.
Single-entity rilpivirine should not be used concomitantly with emtricitabine/rilpivirine/tenofovir DF, unless needed for adjustment of rilpivirine dosage (e.g., when the fixed combination is used concomitantly with rifabutin). Store rilpivirine tablets and tablets for oral suspension at 20--25oC; (excursions permitted between 15-30oC). Store tablets in original bottle to protect from light and tablets for oral suspension in original package to protect from moisture.
Emtricitabine is administered orally once daily without regard to meals. Single-entity emtricitabine is commercially available as 200-mg capsules or an oral solution containing 10 mg/mL. Emtricitabine is also commercially available in the following fixed-combination tablets for oral use: emtricitabine/tenofovir DF (Truvada(R)), efavirenz/emtricitabine/tenofovir DF (Atripla(R)), emtricitabine/rilpivirine/tenofovir DF (Complera(R)), elvitegravir/cobicistat/emtricitabine/tenofovir DF (Stribild(R)), elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya(R)), emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey(R)), emtricitabine/tenofovir alafenamide (Descovy(R)), and bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy(R)).
See the full prescribing information for administration of each of these combination products. Emtricitabine is used in conjunction with other antiretrovirals. Single-entity emtricitabine should not be used concomitantly with any other emtricitabine-containing preparations.
Store capsules at 25degreesC (excursions permitted to 15-30degreesC). Store oral solution at 2-8degreesC. For patient use, store at 25degreesC (excursions permitted to 15-30degreesC); use within 3 months.
Rilpivirine tablets should be administered to adults and pediatric patients weighing >=25 kg. Rilpivirine tablets for oral suspension should be administered only to pediatric patients weighing >=14 kg to <25 kg. Rilpivirine oral tablets and tablets for oral suspension have differing pharmacokinetic profiles; therefore, the tablets and tablets for oral suspension should not be substituted on a milligram-per-milligram basis.
Rilpivirine tablets for oral suspension must be dispersed in drinking water and immediately consumed with a meal. If not consumed immediately, the suspension should be discarded and a new dose prepared. Rilpivirine tablets for oral suspension should not be crushed, chewed, or swallowed whole.
In order to properly prepare the tablets for oral suspension for administration, an appropriate number of tablets should be placed in a cup and 5 mL of room temperature drinking water should be added. The cup should be swirled carefully for 1--2 minutes; the oral suspension should begin to have a cloudy appearance. After swirling the cup for 1--2 minutes, the oral suspension may be consumed immediately or the suspension can be further diluted with 5 mL of drinking water, orange juice, or applesauce to assist in administration.
All the medicine within the cup should be consumed immediately; a spoon may be used if needed. If medicine is still present in the cup, another 5 mL of drinking water (or alternative beverage or soft food) may be added to the cup, swirled, and consumed immediately. Food enhances rilpivirine bioavailability.
Systemic exposure is approximately 40 or 50% lower if rilpivirine tablets are administered under fasting conditions or with only a protein-rich nutritional drink, respectively, compared with following a standard meal (533 kcal) or high-caloric meal (928 kcal). Systemic exposure is 31 or 28% lower if rilpivirine tablets for oral suspension are dispersed in drinking water in fasted conditions or after yogurt consumption, respectively, compared with following a meal in adults containing 533 kcal. If a dose of rilpivirine is missed within 12 hours of the time it is usually taken, take the missed dose as soon as possible with a meal.
If a dose of rilpivirine is missed by more than 12 hours, then skip the missed dose and resume the normal dosing schedule. Rilpivirine must be used in conjunction with other antiretrovirals. Single-entity rilpivirine should not be used concomitantly with emtricitabine/rilpivirine/tenofovir alafenamide or cabotegravir/rilpivirine injeciton.
Single-entity rilpivirine should not be used concomitantly with emtricitabine/rilpivirine/tenofovir DF, unless needed for adjustment of rilpivirine dosage (e.g., when the fixed combination is used concomitantly with rifabutin). Store rilpivirine tablets and tablets for oral suspension at 20--25oC; (excursions permitted between 15-30oC). Store tablets in original bottle to protect from light and tablets for oral suspension in original package to protect from moisture.
Emtricitabine is administered orally once daily without regard to meals. Single-entity emtricitabine is commercially available as 200-mg capsules or an oral solution containing 10 mg/mL. Emtricitabine is also commercially available in the following fixed-combination tablets for oral use: emtricitabine/tenofovir DF (Truvada(R)), efavirenz/emtricitabine/tenofovir DF (Atripla(R)), emtricitabine/rilpivirine/tenofovir DF (Complera(R)), elvitegravir/cobicistat/emtricitabine/tenofovir DF (Stribild(R)), elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya(R)), emtricitabine/rilpivirine/tenofovir alafenamide (Odefsey(R)), emtricitabine/tenofovir alafenamide (Descovy(R)), and bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy(R)).
See the full prescribing information for administration of each of these combination products. Emtricitabine is used in conjunction with other antiretrovirals. Single-entity emtricitabine should not be used concomitantly with any other emtricitabine-containing preparations.
Store capsules at 25degreesC (excursions permitted to 15-30degreesC). Store oral solution at 2-8degreesC. For patient use, store at 25degreesC (excursions permitted to 15-30degreesC); use within 3 months.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| ODEFSEY TABLET | Maintenance | Adults take 1 tablet by oral route once daily |
No generic dosing information available.
The following drug interaction information is available for ODEFSEY (emtricitabine/rilpivirine hcl/tenofovir alafenamide fumarate):
There are 6 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Selected Nephrotoxic Agents/Cidofovir SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Cidofovir is nephrotoxic. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1-3) CLINICAL EFFECTS: Concurrent use of cidofovir with nephrotoxic agents such as adefovir, intravenous aminoglycosides, amphotericin B, foscarnet, intravenous pentamidine, tenofovir, vancomycin, voclosporin and non-steroidal anti-inflammatory agents may result in renal toxicity.(1-3) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The Australian,(1) UK,(2) and US(3) manufacturers of cidofovir state that concurrent administration of potentially nephrotoxic agents such as adefovir, intravenous aminoglycosides, amphotericin B, foscarnet, intravenous pentamidine, tenofovir, vancomycin, voclosporin and non-steroidal anti-inflammatory agents may result in renal toxicity.(1-3) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin. These agents should be discontinued at least 7 days before the administration of cidofovir. DISCUSSION: The safety of cidofovir has not been studied in patients receiving other known potentially nephrotoxic agents. Renal impairment is the major toxicity of cidofovir.(1-3) |
CIDOFOVIR |
| Adefovir/Tenofovir SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: The mechanism involves competition for active tubular secretion sites in the kidney.(1-4) CLINICAL EFFECTS: Concurrent use of adefovir and tenofovir in the treatment of hepatitis B may result in elevated levels of tenofovir or adefovir. PREDISPOSING FACTORS: Renal impairment or use of concurrent renally excreted drugs. PATIENT MANAGEMENT: The US manufacturer of adefovir(1) and the UK(2) and US(3) manufacturers of tenofovir state that adefovir and tenofovir should be not be administered together. DISCUSSION: Tenofovir is eliminated principally by renal tubular secretion and any competitive inhibition of excretion of tenofovir by adefovir increases the likelihood of increased serum concentrations of tenofovir and resultant toxicity.(1-4) |
ADEFOVIR DIPIVOXIL, HEPSERA |
| Rilpivirine/Selected Strong CYP3A4 Inducers SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Apalutamide, barbiturates, carbamazepine, dexamethasone, enzalutamide, eslicarbazepine, fosphenytoin, ivosidenib, lumacaftor, mitotane, natisedine, phenobarbital, phenytoin, primidone, oxcarbazepine, rifampin, rifapentine, and St. John's wort may induce the metabolism of rilpivirine by CYP3A4.(1) CLINICAL EFFECTS: Concurrent or recent use of apalutamide, barbiturates, carbamazepine, dexamethasone, enzalutamide, eslicarbazepine, fosphenytoin, ivosidenib, lumacaftor, mitotane, natisedine, phenobarbital, phenytoin, primidone, oxcarbazepine, rifampin, rifapentine, or St. John's wort may result in decreased levels and effectiveness of rilpivirine, as well as the development of resistance.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of rilpivirine states that concurrent use of CYP3A4 inducers such as apalutamide, barbiturates, carbamazepine, dexamethasone, enzalutamide, eslicarbazepine, fosphenytoin, ivosidenib, lumacaftor, mitotane, natisedine, phenobarbital, phenytoin, primidone, oxcarbazepine, rifampin, rifapentine, or St. John's wort is contraindicated.(1) It may take several weeks after the discontinuation of an enzyme inducer for enzyme activity to return to normal.(1) DISCUSSION: In a study in 16 subjects, rifampin (600 mg daily) decreased the Cmax, AUC, and Cmin of rilpivirine (150 mg daily) by 69%, 80%, and 89%, respectively. There were no significant effects on the Cmax or AUC of rifampin or 25-desacetylrifampin.(1) Strong CYP3A4 inducers linked include: apalutamide, barbiturates, carbamazepine, dexamethasone, encorafenib, enzalutamide, eslicarbazepine, fosphenytoin, ivosidenib, lumacaftor, mitotane, natisedine, phenobarbital, phenytoin, primidone, oxcarbazepine, rifampin, rifapentine, or St. John's wort. |
APTIOM, ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BRAFTOVI, BUPIVACAINE-DEXAMETH-EPINEPHRN, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTALBITAL, BUTALBITAL-ACETAMINOPHEN, BUTALBITAL-ACETAMINOPHEN-CAFFE, BUTALBITAL-ASPIRIN-CAFFEINE, CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DEXABLISS, DEXAMETHASONE, DEXAMETHASONE ACETATE, DEXAMETHASONE ACETATE MICRO, DEXAMETHASONE INTENSOL, DEXAMETHASONE ISONICOTINATE, DEXAMETHASONE MICRONIZED, DEXAMETHASONE SOD PHOS-WATER, DEXAMETHASONE SODIUM PHOSPHATE, DEXAMETHASONE-0.9% NACL, DILANTIN, DILANTIN-125, DMT SUIK, DONNATAL, DOUBLEDEX, EPITOL, EQUETRO, ERLEADA, FIORICET, FIORICET WITH CODEINE, FOSPHENYTOIN SODIUM, HEMADY, LIDOCIDEX-I, LYSODREN, MAS CARE-PAK, MITOTANE, MYSOLINE, ORKAMBI, OXCARBAZEPINE, OXCARBAZEPINE ER, OXTELLAR XR, PENTOBARBITAL SODIUM, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIFTIN, PRIMIDONE, RIFADIN, RIFAMPIN, SEZABY, TAPERDEX, TEGRETOL, TEGRETOL XR, TENCON, TIBSOVO, TRILEPTAL, XTANDI, ZCORT |
| Rilpivirine/Proton Pump Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Rilpivirine requires an acidic medium for absorption. The proton pump inhibitor induced decrease in gastric pH may result in a decrease in rilpivirine absorption.(1) CLINICAL EFFECTS: Concurrent use of a proton pump inhibitor may result in decreased levels and effectiveness of rilpivirine, as well as the development of resistance.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of rilpivirine states that concurrent use of proton pump inhibitors is contraindicated.(1) When substituting antacids for proton pump inhibitors in patients maintained on rilpivirine, administer the antacid at least 2 hours before or 4 hours after rilpivirine.(1) When substituting H2 antagonists for proton pump inhibitors in patients maintained on rilpivirine, administer the H2 antagonist at least 12 hours before or 4 hours after rilpivirine.(1) DISCUSSION: In a study in 16 subjects, omeprazole (20 mg daily) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of rilpivirine (150 mg daily) by 40%, 40%, and 33%, respectively. The Cmax and AUC of omeprazole decreased by 14% and 14%, respectively.(1) In a study in 24 subjects, famotidine (40 mg single dose) administered 12 hours before a single dose of rilpivirine (150 mg) had no significant effect on rilpivirine Cmax or AUC.(1) In a study in 23 subjects, famotidine (40 mg single dose) administered 2 hours before a single dose of rilpivirine (150 mg) decreased the rilpivirine Cmax and AUC by 85% and 76%, respectively.(1) In a study in 24 subjects, famotidine (40 mg single dose) administered 4 hours after a single dose of rilpivirine (150 mg) increased the rilpivirine Cmax and AUC by 21% and 13%, respectively.(1) |
ACIPHEX, ACIPHEX SPRINKLE, DEXILANT, DEXLANSOPRAZOLE DR, ESOMEPRAZOLE MAGNESIUM, ESOMEPRAZOLE SODIUM, KONVOMEP, LANSOPRAZOL-AMOXICIL-CLARITHRO, LANSOPRAZOLE, NAPROXEN-ESOMEPRAZOLE MAG, NEXIUM, OMECLAMOX-PAK, OMEPRAZOLE, OMEPRAZOLE-SODIUM BICARBONATE, PANTOPRAZOLE SODIUM, PANTOPRAZOLE SODIUM-0.9% NACL, PREVACID, PRILOSEC, PROTONIX, PROTONIX IV, RABEPRAZOLE SODIUM, TALICIA, VIMOVO, VOQUEZNA, VOQUEZNA DUAL PAK, VOQUEZNA TRIPLE PAK, YOSPRALA |
| Cobicistat-Elvitegravir/NNRTIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Cobicistat inhibits CYP2D6, CYP3A4, BCRP, OATP1B1 and OATP1B3. Elvitegravir induces CYP2C9. Efavirenz may induce the metabolism of cobicistat via CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of cobicistat-elvitegravir with non-nucleoside reverse transcriptase inhibitors (NNRTIs) may result in altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir, and/or the NNRTI.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The combination product containing cobicistat-elvitegravir-emtricitabine-tenofovir should not be used with non-nucleoside reverse transcriptase inhibitors.(1) DISCUSSION: Concurrent use of cobicistat-elvitegravir with non-nucleoside reverse transcriptase inhibitors may result in altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir, and/or the NNRTI.(1) |
GENVOYA, STRIBILD |
| Selected Nephrotoxic Agents/Bacitracin SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Bacitracin may cause renal failure due to glomerular and tubular necrosis. Concurrent administration of other nephrotoxic agents may result in additive renal toxicity.(1-3) CLINICAL EFFECTS: Concurrent use of bacitracin with other potentially nephrotoxic agents may result in renal toxicity.(1-3) PREDISPOSING FACTORS: Dehydration and high-dose bacitracin may predispose to adverse renal effects.(1) PATIENT MANAGEMENT: Health Canada states that bacitracin is contraindicated in patients with renal impairment, including those taking other nephrotoxic drugs.(1) The Canadian and US manufacturers of bacitracin state that concomitant use of bacitracin with other potentially nephrotoxic agents should be avoided.(2,3) DISCUSSION: Renal impairment is a major toxicity of bacitracin. Cases of nephrotoxicity have been reported when bacitracin was used off-label.(1-3) |
BACITRACIN, BACITRACIN MICRONIZED, BACITRACIN ZINC |
There are 9 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Colistimethate/Selected Nephrotoxic Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Colistimethate can cause nephrotoxicity.(1,2) Concurrent administration of other nephrotoxic agents may result in an increased risk of nephrotoxicity.(1) It is suspected that cephalothin interferes with the excretion of colistimethate resulting in enhanced nephrotoxicity.(2,3) CLINICAL EFFECTS: Concurrent use of colistimethate with other nephrotoxic agents may result in additive nephrotoxic effects. PREDISPOSING FACTORS: Factors predisposing to nephrotoxicity include higher cumulative doses of colistimethate, longer treatment duration, hypovolemia, and critical illness. PATIENT MANAGEMENT: Concurrent use of potentially nephrotoxic agents with colistimethate should be avoided.(1,2) If concurrent use is necessary, it should be undertaken with great caution.(1) DISCUSSION: In a case control study of 42 patients on intravenous colistimethate sodium, NSAIDs were identified as an independent risk factor for nephrotoxicity (OR 40.105, p=0.044).(4) In 4 case reports, patients developed elevated serum creatinine and blood urea nitrogen following concurrent colistimethate and cephalothin (3 patients) or when colistimethate followed cephalothin therapy (1 patient).(3) A literature review found that individual nephrotoxic agents, including aminoglycosides, vancomycin, amphotericin, IV contrast, diuretics, ACE inhibitors, ARBs, NSAIDs, and calcineurin inhibitors, were not consistently associated with additive nephrotoxicity when used with colistimethate. However, when multiple agents (at least 2 additional potential nephrotoxins) were used concurrently, there was a significant correlation to colistimethate nephrotoxicity.(5) |
COLISTIMETHATE, COLISTIMETHATE SODIUM, COLY-MYCIN M PARENTERAL |
| Selected Nephrotoxic Agents/Foscarnet SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Foscarnet is nephrotoxic. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1) Concurrent intravenous pentamidine may also result in hypocalcemia.(1) CLINICAL EFFECTS: Concurrent use of foscarnet with nephrotoxic agents such as acyclovir, adefovir, intravenous aminoglycosides, amphotericin B, cyclosporine, methotrexate, non-steroidal anti-inflammatory agents, intravenous pentamidine, tacrolimus, tenofovir, vancomycin and voclosporin may result in renal toxicity.(1) Other nephrotoxic agents include capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, and streptozocin. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of foscarnet state that concurrent administration of potentially nephrotoxic agents such as acyclovir, intravenous aminoglycosides, amphotericin B, cyclosporine, methotrexate, tacrolimus, and intravenous pentamidine should be avoided.(1) Other nephrotoxic agents include adefovir, capreomycin, cisplatin, gallium nitrate, high-dose methotrexate, non-steroidal anti-inflammatory agents, streptozocin, tenofovir, vancomycin and voclosporin. If concurrent therapy is warranted, monitor renal function closely. In patients receiving concurrent foscarnet and pentamidine, also monitor serum calcium levels and instruct patients to report severe muscle spasms, mental/mood changes, and/or seizures.(1) DISCUSSION: The safety of foscarnet has not been studied in patients receiving other known potentially nephrotoxic agents. Renal impairment is the major toxicity of foscarnet.(1) |
FOSCARNET SODIUM, FOSCAVIR |
| Oral Rilpivirine/Rifabutin SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Rifabutin may induce the metabolism of rilpivirine by CYP3A4.(1) CLINICAL EFFECTS: Concurrent or recent use of rifabutin may result in decreased levels and effectiveness of rilpivirine, as well as the development of resistance.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of oral rilpivirine states that concurrent use of CYP3A4 inducers such as rifabutin warrants dose adjustment. When administering rifabutin with oral rilpivirine, increase the dose of rilpivirine to 50 mg once daily. When rifabutin co-administration is stopped, the rilpivirine dose should be decreased to 25 mg once daily. It may take several weeks after the discontinuation of an enzyme inducer for enzyme activity to return to normal.(1) DISCUSSION: In a study in 18 subjects, rifabutin (300 mg daily) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of rilpivirine (25 mg orally daily) by 31%, 42%, and 48%, respectively.(1) A study in 18 subjects compared rilpivirine administered alone (25 mg orally daily) to coadministration with rifabutin (300 mg daily) and rilpivirine (50 mg orally daily). A significant difference was not found with the Cmax (1.43), AUC (1.16), or Cmin (0.93) of rilpivirine. (1) |
RIFABUTIN, TALICIA |
| Orlistat/Selected Antiretrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. Orlistat may reduce the absorption of lipophilic antiretroviral HIV drugs by retention in the gastrointestinal tract or reduced gastrointestinal tract transit time. CLINICAL EFFECTS: The concurrent administration of orlistat and atazanavir, efavirenz, emtricitabine, maraviroc, ritonavir, or tenofovir may result in a decrease in the levels and clinical effects of the antiretroviral, including loss of virological control.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: HIV RNA levels should be frequently monitored in patients taking orlistat while being treated for HIV infection. If there is a confirmed increase in HIV viral load, orlistat should be discontinued.(1) DISCUSSION: Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with lipophilic antiretroviral drugs.(1) There are three case reports of patients having an increased HIV viral load after taking orlistat concomitantly with their HIV therapy.(2-4) Antiretrovirals included in this monograph are atazanavir, efavirenz, emtricitabine, maraviroc, ritonavir, and tenofovir. |
ORLISTAT, XENICAL |
| Deoxycytidine Kinase Substrates/Cladribine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine may inhibit the intracellular phosphorylation of cladribine by deoxycytidine kinase (dCK). CLINICAL EFFECTS: Concurrent administration of clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine, or zalcitabine with cladribine may result in decreased clinical efficacy of cladribine. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of lamivudine states that the concurrent use of lamivudine and cladribine is not recommended.(1) The manufacturer of cladribine states that concurrent use of compounds that require activation by intracellular phosphorylation should be avoided.(2) DISCUSSION: Cladribine undergoes a series of phosphorylations to its active metabolites. In a case report, a patient on lamivudine who received cladribine concurrently did not experience a decrease in his lymphocyte count. After discontinuation of lamivudine and readministration of cladribine, his lymphocytes dropped as expected.(3) It is expected that other compounds phosphorylated by dCK would also decrease cladribine's efficacy.(4) Compounds phosphorylated by dCK include: clofarabine, cytarabine, emtricitabine, fludarabine, gemcitabine, lamivudine, molnupiravir, nelarabine and zalcitabine. |
CLADRIBINE, MAVENCLAD |
| Betibeglogene Autotemcel/Anti-Retrovirals; Hydroxyurea SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Betibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. Hydroxyurea may interfere with hematopoietic stem cell (HSC) mobilization of CD34+ cells.(1) CLINICAL EFFECTS: Use of hydroxyurea before mobilization may result in unsuccessful stem cell mobilization. Use of antiretrovirals before mobilization and apheresis may interfere with the production of betibeglogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals and hydroxyurea for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications and hydroxyurea may interfere with the manufacturing of betibeglogene autotemcel therapy.(1) |
ZYNTEGLO |
| Elivaldogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Elivaldogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of elivaldogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of elivaldogene autotemcel therapy.(1) |
SKYSONA |
| Lovotibeglogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lovotibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of lovotibeglogene autotemcel.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed.(1) There are some long-acting antiretroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.(1) DISCUSSION: Antiretroviral medications may interfere with the manufacturing of lovotibeglogene autotemcel therapy.(1) |
LYFGENIA |
| Atidarsagene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Atidarsagene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of atidarsagene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization (or the expected duration of time needed for elimination of the medication) until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of atidarsagene autotemcel therapy.(1) |
LENMELDY |
There are 5 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Tenofovir/Selected Nephrotoxic Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tenofovir and other nephrotoxic agents may result in additive or synergistic effects on renal function and increase nephrotoxicity risk.(1) CLINICAL EFFECTS: Concurrent use of tenofovir and other nephrotoxic agents may result in renal toxicity and acute renal failure.(1) Reports of acute renal failure and Fanconi syndrome have been reported with tenofovir use.(2,3) However, this has been reported in 3 case reports and the renal failure may have been complicated by other pre-existing conditions.(2) PREDISPOSING FACTORS: Pre-existing renal dysfunction, long duration of use, low body weight, concomitant use of drugs that may increase tenofovir levels may increase the risk of nephrotoxicity.(1) PATIENT MANAGEMENT: The US prescribing information for tenofovir recommends avoiding concurrent or recent use of a nephrotoxic agent.(3) Evaluate renal function prior to initiation of concurrent therapy and continue renal function monitoring during therapy. Dose adjustments may be required for impaired renal function. Tenofovir should be avoided with high-dose or multiple NSAIDs. Alternatives to NSAIDs should be considered in patients at risk for renal dysfunction.(3) Patients receiving concurrent NSAIDs with tenofovir should be monitored for possible renal toxicity.(1,2) The dosing interval should be adjusted in patients with a baseline creatinine clearance of less than 50 ml/min.(1-3) DISCUSSION: From March 18, 2003 to December 1, 2005, Health Canada received 10 reports of nephrotoxic reactions with tenofovir. Three of these occurred following the addition of a NSAID to tenofovir therapy. In the first report, a patient maintained on tenofovir for 29 months developed acute renal failure and acute tubular necrosis requiring dialysis 5 days after beginning indomethacin (100 mg rectally twice daily). In the second report, a patient maintained on tenofovir for 7 months developed acute renal failure and acute tubular necrosis after taking 90 tablets of naproxen (375 mg) over 2 months. The patient died. In the third report, a patient maintained on tenofovir for over a year developed acute renal failure and nephrotic syndrome after 2 months of valdecoxib (20 mg daily) therapy. Symptoms subsided following discontinuation of valdecoxib.(1) |
ABELCET, ACYCLOVIR, ACYCLOVIR SODIUM, ACYCLOVIR SODIUM-0.9% NACL, AFINITOR, AFINITOR DISPERZ, AMBISOME, AMIKACIN SULFATE, AMPHOTERICIN B, AMPHOTERICIN B LIPOSOME, ANAPROX DS, ANJESO, ARTHROTEC 50, ARTHROTEC 75, ASTAGRAF XL, BROMFENAC SODIUM, BUPIVACAINE-KETOROLAC-KETAMINE, CALDOLOR, CAMBIA, CELEBREX, CELECOXIB, CISPLATIN, COMBOGESIC, COMBOGESIC IV, CONSENSI, COXANTO, CYCLOSPORINE, CYCLOSPORINE MODIFIED, DAYPRO, DICLOFENAC, DICLOFENAC POTASSIUM, DICLOFENAC SODIUM, DICLOFENAC SODIUM ER, DICLOFENAC SODIUM MICRONIZED, DICLOFENAC SODIUM-MISOPROSTOL, EC-NAPROSYN, ELYXYB, ENVARSUS XR, ETODOLAC, ETODOLAC ER, EVEROLIMUS, FELDENE, FENOPROFEN CALCIUM, FENOPRON, FLURBIPROFEN, FYARRO, GANCICLOVIR SODIUM, GENGRAF, GENTAMICIN SULFATE, GENTAMICIN SULFATE IN NS, HYDROCODONE-IBUPROFEN, IBU, IBUPAK, IBUPROFEN, IBUPROFEN LYSINE, IBUPROFEN-FAMOTIDINE, INDOCIN, INDOMETHACIN, INDOMETHACIN ER, INFLAMMACIN, INFLATHERM(DICLOFENAC-MENTHOL), KANAMYCIN SULFATE, KEMOPLAT, KETOPROFEN, KETOPROFEN MICRONIZED, KETOROLAC TROMETHAMINE, KIPROFEN, LODINE, LOFENA, LUPKYNIS, LURBIPR, MECLOFENAMATE SODIUM, MEFENAMIC ACID, MELOXICAM, METHOTREXATE, METHOTREXATE SODIUM, NABUMETONE, NABUMETONE MICRONIZED, NALFON, NAPRELAN, NAPROSYN, NAPROTIN, NAPROXEN, NAPROXEN SODIUM, NAPROXEN SODIUM CR, NAPROXEN SODIUM ER, NAPROXEN-ESOMEPRAZOLE MAG, NEOMYCIN SULFATE, NEOPROFEN, NEORAL, OXAPROZIN, PENTAM 300, PENTAMIDINE ISETHIONATE, PHENYLBUTAZONE, PIROXICAM, PROGRAF, R.E.C.K.(ROPIV-EPI-CLON-KETOR), RELAFEN DS, ROPIVACAINE-CLONIDINE-KETOROLC, ROPIVACAINE-KETOROLAC-KETAMINE, SANDIMMUNE, SIROLIMUS, SPRIX, STREPTOMYCIN SULFATE, SULINDAC, SUMATRIPTAN SUCC-NAPROXEN SOD, SYMBRAVO, TACROLIMUS, TACROLIMUS XL, TEMSIROLIMUS, TOBRAMYCIN, TOBRAMYCIN SULFATE, TOLECTIN 600, TOLMETIN SODIUM, TORISEL, TORONOVA II SUIK, TORONOVA SUIK, TORPENZ, TOXICOLOGY SALIVA COLLECTION, TRESNI, TREXIMET, VALACYCLOVIR, VALACYCLOVIR HCL, VALCYTE, VALGANCICLOVIR HCL, VALTREX, VANCOMYCIN, VANCOMYCIN HCL, VANCOMYCIN HCL-0.9% NACL, VANCOMYCIN HCL-D5W, VIMOVO, VIVLODEX, ZIPSOR, ZORTRESS, ZORVOLEX, ZOVIRAX, ZYNRELEF |
| Rilpivirine/Antacids; H2 Antagonists SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Rilpivirine requires an acidic medium for absorption. Antacid or H2 antagonist induced decrease in gastric pH may result in a decrease in rilpivirine absorption.(1) CLINICAL EFFECTS: Simultaneous administration of an antacid or a H2 antagonist may result in decreased levels and effectiveness of rilpivirine, as well as the development of resistance.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: In patients maintained on rilpivirine, administer antacids at least 2 hours before or 4 hours after rilpivirine.(1) In patients maintained on rilpivirine, administer H2 antagonists at least 12 hours before or 4 hours after rilpivirine.(1) Concurrent use of proton pump inhibitors with rilpivirine is contraindicated.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: In a study in 16 subjects, omeprazole (20 mg daily) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of rilpivirine (150 mg daily) by 40%, 40%, and 33%, respectively. The Cmax and AUC of omeprazole decreased by 14% and 14%, respectively.(1) In a study in 24 subjects, famotidine (40 mg single dose) administered 12 hours before a single dose of rilpivirine (150 mg) had no significant effect on rilpivirine Cmax or AUC.(1) In a study in 23 subjects, famotidine (40 mg single dose) administered 2 hours before a single dose of rilpivirine (150 mg) decreased the rilpivirine Cmax and AUC by 85% and 76%, respectively.(1) In a study in 24 subjects, famotidine (40 mg single dose) administered 4 hours after a single dose of rilpivirine (150 mg) increased the rilpivirine Cmax and AUC by 21% and 13%, respectively.(1) |
ALUMINUM HYDROXIDE, CIMETIDINE, FAMOTIDINE, GAVILYTE-C, GAVILYTE-G, GAVILYTE-N, GOLYTELY, IBUPROFEN-FAMOTIDINE, KONVOMEP, NIZATIDINE, OMEPRAZOLE-SODIUM BICARBONATE, PEG 3350-ELECTROLYTE, PEG-3350 AND ELECTROLYTES, PEPCID, SODIUM BICARBONATE, VAXCHORA BUFFER COMPONENT |
| Cobicistat; Ritonavir/Tenofovir Alafenamide (> 10 mg) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tenofovir alafenamide (AF) is a substrate of P-glycoprotein (P-gp) and BCRP, which may be inhibited by cobicistat or ritonavir.(1-6) Ritonavir coadministered with tipranavir has a net inductive effect on P-gp.(7) CLINICAL EFFECTS: Cobicistat or ritonavir in combination with tenofovir alafenamide (AF) may increase the concentration of tenofovir AF and the risk of renal or other toxicities in some patients.(1-6,8-9) Ritonavir-boosted tipranavir may decrease the levels of tenofovir AF.(4-6,8) PREDISPOSING FACTORS: Patients with baseline impairment of renal function and/or receiving commitant nephrotoxic agents are at increased risk of renal-related adverse events.(1-6,8-9) PATIENT MANAGEMENT: Regulatory agencies in different countries differ with regard to recommendations for the coadministration of cobicistat or ritonavir and tenofovir alafenamide (AF). The US National Institute of Health HIV guidelines state that no dose adjustment is necessary when using tenofovir AF 25 mg concurrently with cobicistat or ritonavir boosted atazanavir, darunavir, or lopinavir.(8) The US manufacturer of emtricitabine-tenofovir AF states that there are no clinically significant interactions with cobicistat or ritonavir boosted atazanavir, darunavir, or lopinavir. Coadministration with tipranavir-ritonavir is not recommended.(4,8) Note that other countries have different recommendations. The Canadian and European manufacturers of emtricitabine-tenofovir alafenamide that that the dose of tenofovir alafenamide should be 10 mg when coadministered with cobicistat or ritonavir boosted atazanavir, darunavir, or lopinavir. Coadministration with tipranavir-ritonavir is not recommended. There are no data to make recommendations for use of tenofovir AF with other protease inhibitors.(5-6) In patients receiving concurrent therapy, check glucose and urine protein at baseline and routinely monitor CrCl, urine glucose, urine protein, and serum phosphorus. Discontinue concurrent therapy if CrCL decreases below 30 ml/min.(4-6) DISCUSSION: In clinical trials, cobicistat 150 mg daily increased the area-under-curve (AUC) and maximal concentration (Cmax) of tenofovir alafenamide (AF) by 2.65-fold and 2.83-fold, respectively. Atazanavir 300 mg daily with ritonavir 100 mg daily increased the AUC and Cmax of tenofovir AF by 1.91-fold and 1.77-fold, respectively, whereas cobicistat-boosted atazanavir caused 1.75-fold and 1.8-fold increases in tenofovir AF AUC and Cmax. Darunavir 800 mg daily with cobicistat 150 mg daily did not affect the pharmacokinetics of tenofovir AF, but increased tenofovir AUC and Cmax by 3.24-fold and 3.16-fold, respectively. Similarly, darunavir 800 mg daily with ritonavir 100 mg daily did not affect the levels of tenofovir AF, but increased AUC and Cmax of tenofovir by 2.05-fold and 2.42-fold, respectively. Lopinavir 800 mg daily with ritonavir 200 mg daily increased AUC and Cmax of tenofovir AF by 1.47-fold and 2.19-fold, respectively.(4,6) Renal toxicity, including proximal renal tubulopathy and Fanconi syndrome, has been documented with coadministration of cobicistat with tenofovir disoproxil fumarate (DF) but not tenofovir alafenamide (AF). Monitoring of renal function is prudent and discontinuation is recommended when CrCl decreases below 30 ml/min to avoid renal impairment.(1-6,8-9) In a phase 3 trial of tenofovir AF versus tenofovir DF coformulated with elvitegravir, cobicistat, and emtricitabine, at 48 weeks patients in the tenofovir AF group had significantly smaller mean serum creatinine increases(0.08 vs 0.12 mg/dL; p<0.0001) and significantly less proteinuria (median % change -3 vs 20; p<0.0001).(9) Tenofovir AF strengths less than or equal to 10 mg are excluded from this interaction. In a pre-approval drug-drug interaction study, concurrent cobicistat (150 mg daily) increased tenofovir AF exposure (area-under-curve, AUC) 2.5-fold. Due to this interaction, the tenofovir AF strength in the cobicistat-elvitegravir-emtricitabine-tenofovir AF combination product was reduced from the originally proposed 25 mg to 10 mg.(10) |
EVOTAZ, KALETRA, LOPINAVIR-RITONAVIR, NORVIR, PREZCOBIX, RITONAVIR, TYBOST |
| Selected Nephrotoxic Agents/Immune Globulin IV (IGIV) SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Immune Globulin Intravenous (IGIV) products, particularly those containing sucrose, can cause renal dysfunction, acute renal failure, osmotic nephrosis, and/or death. Concurrent administration of other nephrotoxic agents may result in additive or synergistic effects on renal function.(1-4) CLINICAL EFFECTS: Concurrent use of Immune Globulin Intravenous (IGIV) products with nephrotoxic agents such as adefovir, intravenous aminoglycosides, amphotericin B, non-steroidal anti-inflammatory agents, tenofovir, and vancomycin may result in renal toxicity.(1-4) Other nephrotoxic agents include capreomycin, gallium nitrate, and streptozocin. PREDISPOSING FACTORS: Patients at risk of acute renal failure include those with any degree of pre-existing renal insufficiency, diabetes mellitus, advanced age (above 65 years of age), volume depletion, sepsis, paraproteinemia, or receiving known nephrotoxic drugs.(1-4) Renal dysfunction and acute renal failure occur more commonly in patients receiving IGIV products containing sucrose.(3-4) PATIENT MANAGEMENT: For patients at risk of renal dysfunction or renal failure, the US manufacturers of Immune Globulin Intravenous (IGIV) products recommends administration at the minimum dose and infusion rate practicable; ensure adequate hydration in patients before administration; and monitor renal function and urine output with assessment of blood urea nitrogen (BUN) and serum creatinine before initial infusion and at regular intervals during therapy.(1-3) Concurrent administration of potentially nephrotoxic agents should be avoided.(1) Review prescribing information for IGIV product to be administered for sucrose content. If concurrent therapy is warranted, monitor renal function closely. In high risk patients, consider selecting an IGIV product that does not contain sucrose. DISCUSSION: The safety of Immune Globulin Intravenous (IGIV) has not been studied in patients receiving other known potentially nephrotoxic agents. Renal impairment is a major toxicity of IGIV products.(1-3) A review of the FDA renal adverse events (RAEs) (i.e. acute renal failure or insufficiency) from June 1985 to November 1998 identified 120 reports worldwide associated with IGIV administration. In the US, the FDA received 88 reports of cases with clinical and/or laboratory findings consistent with RAE (i.e. increased serum creatinine, oliguria, and acute renal failure). Patient cases involved a median age of 60.5 years and 55% were male. Of the 54 patients who developed acute renal failure, 65% were greater than 65 years, 56% had diabetes, and 26% had prior renal insufficiency; 59% had one, 35% had two, and 6% had three of these conditions. Upon review of the IGIV product received, 90% of cases received sucrose-containing IGIV products with the remaining patients receiving either maltose- or glucose-containing products. Approximately 40% of affected patients required dialysis and RAE may have contributed to death in 15% of patients.(4) |
ALYGLO, BIVIGAM, CUTAQUIG, CUVITRU, FLEBOGAMMA DIF, GAMMAGARD LIQUID, GAMMAGARD S-D, GAMMAKED, GAMMAPLEX, GAMUNEX-C, HIZENTRA, HYQVIA, HYQVIA IG COMPONENT, OCTAGAM, PANZYGA, PRIVIGEN, XEMBIFY |
| Rilpivirine/Tecovirimat SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tecovirimat may induce the metabolism of rilpivirine by CYP3A4.(1-4) CLINICAL EFFECTS: Concurrent or recent use of tecovirimat may result in decreased levels and effectiveness of rilpivirine, as well as the development of resistance.(1-4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of rilpivirine with tecovirimat should be approached with caution. Consider increasing rilpivirine to 50 mg daily during treatment with tecovirimat and for approximately 2 weeks after the end of treatment.(1-4) DISCUSSION: In a study in 18 subjects, rifabutin (300 mg daily), a moderate CYP3A4 inducer, decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of rilpivirine (25 mg orally daily) by 31%, 42%, and 48%, respectively.(1) A study in 18 subjects compared rilpivirine administered alone (25 mg orally daily) to coadministration with rifabutin (300 mg daily) and rilpivirine (50 mg orally daily). A significant difference was not found with the Cmax (1.43), AUC (1.16), or Cmin (0.93) of rilpivirine.(1) In a pharmacokinetic study, tecovirimat decreased the Cmax and AUC of midazolam by 39% and 32%, respectively.(2-3) |
TPOXX (NATIONAL STOCKPILE) |
The following contraindication information is available for ODEFSEY (emtricitabine/rilpivirine hcl/tenofovir alafenamide fumarate):
Drug contraindication overview.
*None. *Known hypersensitivity to the drug or any ingredient in the formulation. *Concomitant use of rilpivirine with drugs that induce cytochrome P-450 isoenzyme 3A (CYP3A) or drugs that elevate gastric pH is contraindicated since substantially decreased plasma rilpivirine concentrations may occur and may result in loss of virologic response and development of resistance to rilpivirine and/or class resistance to HIV NNRTIs.
*None. *Known hypersensitivity to the drug or any ingredient in the formulation. *Concomitant use of rilpivirine with drugs that induce cytochrome P-450 isoenzyme 3A (CYP3A) or drugs that elevate gastric pH is contraindicated since substantially decreased plasma rilpivirine concentrations may occur and may result in loss of virologic response and development of resistance to rilpivirine and/or class resistance to HIV NNRTIs.
There are 2 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Lactation |
| Lactic acidosis |
There are 10 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Acute renal failure |
| Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min |
| Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Depression |
| Disease of liver |
| Fanconi syndrome |
| Hypophosphatemia |
| Suicidal ideation |
There are 4 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Chronic hepatitis B |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Viral hepatitis |
The following adverse reaction information is available for ODEFSEY (emtricitabine/rilpivirine hcl/tenofovir alafenamide fumarate):
Adverse reaction overview.
The most common adverse effect (incidence >=10%, all grades) is headache. The most common adverse reactions experienced in at least 10% of adult patients with HIV-1 treated with emtricitabine include headache, GI effects (diarrhea, nausea), fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis. Adverse effects reported in pediatric patients 3 months of age or older receiving emtricitabine in clinical studies have been similar to those in adults, with the exception of a higher frequency of hyperpigmentation. Adverse effects of at least moderate to severe intensity reported in 2% or more of patients in clinical trials include depressive disorders, insomnia, headache, and rash.
The most common adverse effect (incidence >=10%, all grades) is headache. The most common adverse reactions experienced in at least 10% of adult patients with HIV-1 treated with emtricitabine include headache, GI effects (diarrhea, nausea), fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis. Adverse effects reported in pediatric patients 3 months of age or older receiving emtricitabine in clinical studies have been similar to those in adults, with the exception of a higher frequency of hyperpigmentation. Adverse effects of at least moderate to severe intensity reported in 2% or more of patients in clinical trials include depressive disorders, insomnia, headache, and rash.
There are 50 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Depression Gastroenteritis Vomiting |
Anemia Bullous dermatitis Hypercholesterolemia Increased alanine transaminase Increased aspartate transaminase Maculopapular rash Osteopenia Peripheral neuropathy Pneumonia Urticaria |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Acute renal failure Angioedema Autoimmune hepatitis Biliary calculus Blistering skin Bronchospastic pulmonary disease Cholecystitis Conjunctivitis DRESS syndrome Dyspnea Eosinophilia Facial edema Fanconi syndrome Glomerulonephritis Graves' disease Guillain-barre syndrome Hepatitis Hypersensitivity drug reaction Hypokalemia Hypophosphatemia Interstitial nephritis Kidney disease with reduction in glomerular filtration rate (GFr) Kidney stone Lactic acidosis Nephrogenic diabetes insipidus Nephrotic syndrome Osteomalacia Pancreatitis Peripheral neuropathy Pneumonia Polymyositis Renal tubular necrosis Rhabdomyolysis Steatosis of liver Suicidal Suicidal ideation |
There are 60 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute abdominal pain Back pain Cough Diarrhea Dizziness Dream disorder Dyspepsia Fatigue Fever General weakness Headache disorder Injection site sequelae Insomnia Musculoskeletal pain Nausea Pain Pruritus of skin Rhinitis Skin rash |
Acute bacterial otitis media Anorexia Arthralgia Chest pain Diarrhea Dizziness Dream disorder Dyspepsia Elevated serum amylase Elevated serum lipase Fatigue Fever Flatulence Insomnia Myalgia Nausea Paresthesia Pharyngitis Polyuria Proteinuria Sinusitis Skin rash Vomiting Weight loss |
| Rare/Very Rare |
|---|
|
Acute abdominal pain Agitation Anorexia Depression Drowsy Drug fever Dyschromia Hyperhidrosis Hypertriglyceridemia Muscle weakness Myopathy Oral hypoesthesia Sleep disorder Stomatitis Symptoms of anxiety Urticaria Weight gain |
The following precautions are available for ODEFSEY (emtricitabine/rilpivirine hcl/tenofovir alafenamide fumarate):
The steady-state pharmacokinetics, safety, and efficacy of tenofovir alafenamide for the treatment of chronic HBV infection have been established in pediatric patients 6 to <18 years of age and weighing >=25 kg. No clinically meaningful differences in pharmacokinetics or safety were observed in comparison to adults. Safety and efficacy of tenofovir alafenamide have not been established in pediatric patients with chronic HBV infection <6 years of age or weighing <25 kg.
Safety and efficacy of emtricitabine have been established for treatment of HIV-1 infection in children 3 months of age and older. The pharmacokinetics and safety of emtricitabine were evaluated in a dose-finding study in 20 neonates born to HIV-infected mothers. These neonates received zidovudine prophylaxis for 6 weeks.
In addition, these neonates received 2 short courses of emtricitabine (3 mg/kg daily for 4 days per course) during the first 12 weeks of life. This dosage was not associated with any safety issues. Systemic exposure (AUC) in infants 0-3 months of age receiving emtricitabine 3 mg/kg daily was similar to that reported in children 3 months to 17 years of age receiving emtricitabine 6 mg/kg daily.
All neonates were HIV-1 negative at the end of the study (6 months postpartum); the efficacy of emtricitabine for the prevention or treatment of HIV was not determined. Safety and efficacy of rilpivirine tablets (Edurant(R)) and tablets for oral suspension (Edurant PED(R)) have been established for the treatment of HIV-1 infection in treatment-naive pediatric patients >=2 years of age and weighing >=14 kg. The use of rilpivirine in this patient population is supported by the results of 3 trials (i.e., Trial TMC278-C213, Trial TMC278HTX2002, MOCHA trial).
The single arm, open-label, phase 2, TMC278-C213 trial involved 2 cohorts of treatment-naive HIV-1 infected pediatric patients. Cohort 1 assessed the efficacy, safety, and pharmacokinetics of rilpivirine tablets in 36 pediatric patients (12 to <18 years of age and weighing >=32 kg). Cohort 2 assessed the safety, tolerability, antiviral activity, and pharmacokinetics of rilpivirine tablets and tablets for oral suspension weight-adjusted doses in 18 pediatric patients (6 to <12 years of age and weighing >=17 kg).
The single-arm, open-label, phase 2, TMC278HTX2002 trial assessed the safety, tolerability, antiviral activity, and pharmacokinetics of rilpivirine tablets and tablets for oral suspension weight-adjusted doses in 26 pediatric patients (2 to <12 years of age and weighing >=16 kg). In the ongoing MOCHA trial, the safety, tolerability, and pharmacokinetics of oral/injectable cabotegravir and oral/injectable rilpivirine are being evaluated. Rilpivirine tablets for oral suspension (Edurant PED(R)) are not recommended for use in pediatric patients <2 years of age or weighing <14 kg.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Safety and efficacy of emtricitabine have been established for treatment of HIV-1 infection in children 3 months of age and older. The pharmacokinetics and safety of emtricitabine were evaluated in a dose-finding study in 20 neonates born to HIV-infected mothers. These neonates received zidovudine prophylaxis for 6 weeks.
In addition, these neonates received 2 short courses of emtricitabine (3 mg/kg daily for 4 days per course) during the first 12 weeks of life. This dosage was not associated with any safety issues. Systemic exposure (AUC) in infants 0-3 months of age receiving emtricitabine 3 mg/kg daily was similar to that reported in children 3 months to 17 years of age receiving emtricitabine 6 mg/kg daily.
All neonates were HIV-1 negative at the end of the study (6 months postpartum); the efficacy of emtricitabine for the prevention or treatment of HIV was not determined. Safety and efficacy of rilpivirine tablets (Edurant(R)) and tablets for oral suspension (Edurant PED(R)) have been established for the treatment of HIV-1 infection in treatment-naive pediatric patients >=2 years of age and weighing >=14 kg. The use of rilpivirine in this patient population is supported by the results of 3 trials (i.e., Trial TMC278-C213, Trial TMC278HTX2002, MOCHA trial).
The single arm, open-label, phase 2, TMC278-C213 trial involved 2 cohorts of treatment-naive HIV-1 infected pediatric patients. Cohort 1 assessed the efficacy, safety, and pharmacokinetics of rilpivirine tablets in 36 pediatric patients (12 to <18 years of age and weighing >=32 kg). Cohort 2 assessed the safety, tolerability, antiviral activity, and pharmacokinetics of rilpivirine tablets and tablets for oral suspension weight-adjusted doses in 18 pediatric patients (6 to <12 years of age and weighing >=17 kg).
The single-arm, open-label, phase 2, TMC278HTX2002 trial assessed the safety, tolerability, antiviral activity, and pharmacokinetics of rilpivirine tablets and tablets for oral suspension weight-adjusted doses in 26 pediatric patients (2 to <12 years of age and weighing >=16 kg). In the ongoing MOCHA trial, the safety, tolerability, and pharmacokinetics of oral/injectable cabotegravir and oral/injectable rilpivirine are being evaluated. Rilpivirine tablets for oral suspension (Edurant PED(R)) are not recommended for use in pediatric patients <2 years of age or weighing <14 kg.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to tenofovir alafenamide during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263. Data from the APR of >1330 exposures to tenofovir alafenamide-containing regimens showed that the prevalence of birth defects in live births was 3.9%
and 4.8% following first and second/third trimester exposure, respectively. The rate of miscarriage is not reported in the APR.
The overall risk of birth defects for tenofovir alafenamide was not markedly different compared to the background rate for major birth defects of 2.7% in the United States reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Use of the MACDP population as the comparator group has several limitations; the MACDP is not disease-specific, assesses populations from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks' gestation.
In animal studies, there was no evidence of impaired fertility or harm to the fetus. Adverse developmental effects were not observed when tenofovir alafenamide was administered during organogenesis to rats or rabbits in dosages that resulted in exposures equal to or 51 times higher, respectively, than human exposures reported with the recommended daily dosage of tenofovir alafenamide. The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to emtricitabine during pregnancy.
Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.APRegistry.com.
Based on prospective reports to the APR, the overall risk of birth defects among live births with first-trimester exposure to emtricitabine was 2.4%, and 2.3% with second/third trimester exposure, compared to the background rate for major birth defects of 2.7%
in the United States reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Limitations of using an external comparator (i.e., MACDP) include differences in populations and methodology, and confounding due to the underlying disease. The rate of miscarriage for individual drugs is not reported in the APR.
Additional observational data have not shown an increase in major malformations with emtricitabine exposure in pregnancy. The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to rilpivirine during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com/.
The overall risk of birth defects with first-trimester exposure for rilpivirine was not markedly different compared to the background rate for major birth defects of 2.7% in the United States reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Limitations of using an external comparator (the MACDP) includes differences in populations and methodology, and confounding due to the underlying disease.
The rate of miscarriage is not reported in the APR. In a small study of 19 HIV-1 infected women on a rilpivirine-based regimen, protein binding was similar during the second and third trimesters and the postpartum period; however, total exposure of rilpivirine was approximately 30-40% lower during pregnancy when compared to the postpartum period. Of the 12 virologically suppressed patients at baseline (<50 copies/mL), virologic suppression with a rilpivirine-based regimen was maintained through the third trimester in 10 patients, and was well-tolerated.
Among 10 infants born to HIV-1 infected women, all were HIV-1 negative at delivery and for 16 weeks post-partum. All infants received prophylactic zidovudine treatment at delivery. Animal data have shown no increases in embryo-fetal toxicity at rilpivirine exposures 15-70 times the equivalent human exposure. Monitor viral load closely in pregnant women; lower rilpivirine exposures have been observed in pregnant individuals.
and 4.8% following first and second/third trimester exposure, respectively. The rate of miscarriage is not reported in the APR.
The overall risk of birth defects for tenofovir alafenamide was not markedly different compared to the background rate for major birth defects of 2.7% in the United States reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Use of the MACDP population as the comparator group has several limitations; the MACDP is not disease-specific, assesses populations from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks' gestation.
In animal studies, there was no evidence of impaired fertility or harm to the fetus. Adverse developmental effects were not observed when tenofovir alafenamide was administered during organogenesis to rats or rabbits in dosages that resulted in exposures equal to or 51 times higher, respectively, than human exposures reported with the recommended daily dosage of tenofovir alafenamide. The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to emtricitabine during pregnancy.
Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.APRegistry.com.
Based on prospective reports to the APR, the overall risk of birth defects among live births with first-trimester exposure to emtricitabine was 2.4%, and 2.3% with second/third trimester exposure, compared to the background rate for major birth defects of 2.7%
in the United States reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Limitations of using an external comparator (i.e., MACDP) include differences in populations and methodology, and confounding due to the underlying disease. The rate of miscarriage for individual drugs is not reported in the APR.
Additional observational data have not shown an increase in major malformations with emtricitabine exposure in pregnancy. The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to rilpivirine during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com/.
The overall risk of birth defects with first-trimester exposure for rilpivirine was not markedly different compared to the background rate for major birth defects of 2.7% in the United States reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Limitations of using an external comparator (the MACDP) includes differences in populations and methodology, and confounding due to the underlying disease.
The rate of miscarriage is not reported in the APR. In a small study of 19 HIV-1 infected women on a rilpivirine-based regimen, protein binding was similar during the second and third trimesters and the postpartum period; however, total exposure of rilpivirine was approximately 30-40% lower during pregnancy when compared to the postpartum period. Of the 12 virologically suppressed patients at baseline (<50 copies/mL), virologic suppression with a rilpivirine-based regimen was maintained through the third trimester in 10 patients, and was well-tolerated.
Among 10 infants born to HIV-1 infected women, all were HIV-1 negative at delivery and for 16 weeks post-partum. All infants received prophylactic zidovudine treatment at delivery. Animal data have shown no increases in embryo-fetal toxicity at rilpivirine exposures 15-70 times the equivalent human exposure. Monitor viral load closely in pregnant women; lower rilpivirine exposures have been observed in pregnant individuals.
Published data report the presence of tenofovir alafenamide and tenofovir in human milk; however, these data have not documented adverse effects of tenofovir alafenamide in the breastfed child. It is unknown if tenofovir alafenamide affects milk production. Consider the benefits of breast-feeding and the importance of tenofovir alafenamide to the mother along with the potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.
Based on published data, emtricitabine is distributed into human milk. It is not known whether emtricitabine affects milk production or has effects on the breast-fed infant. The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding.
The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk.
Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery. Based on limited data, rilpivirine is present in human milk; however, there are no data on the effects of rilpivirine on the breast-fed infant or on milk production. The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding.
The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
Based on published data, emtricitabine is distributed into human milk. It is not known whether emtricitabine affects milk production or has effects on the breast-fed infant. The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding.
The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk.
Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery. Based on limited data, rilpivirine is present in human milk; however, there are no data on the effects of rilpivirine on the breast-fed infant or on milk production. The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding.
The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
The manufacturer makes no specific dosage recommendations for geriatric patients. Consult the product labeling of commercially available fixed-combination products containing rilpivirine for specific dosage adjustments of each component in geriatric patients. In clinical trials of tenofovir alafenamide, no clinically significant differences in safety or efficacy were observed between patients >=65 years of age and patients 18 to <65 years of age.
Experience in those 65 years of age or older is insufficient to determine whether they respond differently to emtricitabine than younger adults. Dosage should be selected with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy. Experience in those 65 years of age and older is insufficient to determine whether they respond differently to rilpivirine than younger adults. Dosage should be selected with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.
Experience in those 65 years of age or older is insufficient to determine whether they respond differently to emtricitabine than younger adults. Dosage should be selected with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy. Experience in those 65 years of age and older is insufficient to determine whether they respond differently to rilpivirine than younger adults. Dosage should be selected with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.
The following prioritized warning is available for ODEFSEY (emtricitabine/rilpivirine hcl/tenofovir alafenamide fumarate):
WARNING: If you have hepatitis B infection, your hepatitis symptoms may get worse or become very serious if you stop taking this medication. Talk with your doctor before stopping this medication. Your doctor will monitor liver tests for several months after you stop emtricitabine/rilpivirine/tenofovir alafenamide. Tell your doctor right away if you have symptoms of worsening liver problems.
WARNING: If you have hepatitis B infection, your hepatitis symptoms may get worse or become very serious if you stop taking this medication. Talk with your doctor before stopping this medication. Your doctor will monitor liver tests for several months after you stop emtricitabine/rilpivirine/tenofovir alafenamide. Tell your doctor right away if you have symptoms of worsening liver problems.
The following icd codes are available for ODEFSEY (emtricitabine/rilpivirine hcl/tenofovir alafenamide fumarate)'s list of indications:
| HIV infection | |
| B20 | Human immunodeficiency virus [HIv] disease |
| B97.35 | Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere |
| O98.7 | Human immunodeficiency virus [HIv] disease complicating pregnancy, childbirth and the puerperium |
| O98.71 | Human immunodeficiency virus [HIv] disease complicating pregnancy |
| O98.711 | Human immunodeficiency virus [HIv] disease complicating pregnancy, first trimester |
| O98.712 | Human immunodeficiency virus [HIv] disease complicating pregnancy, second trimester |
| O98.713 | Human immunodeficiency virus [HIv] disease complicating pregnancy, third trimester |
| O98.719 | Human immunodeficiency virus [HIv] disease complicating pregnancy, unspecified trimester |
| O98.72 | Human immunodeficiency virus [HIv] disease complicating childbirth |
| O98.73 | Human immunodeficiency virus [HIv] disease complicating the puerperium |
| Z21 | Asymptomatic human immunodeficiency virus [HIv] infection status |
Formulary Reference Tool