SYMFI (Page 5 of 16)

Tenofovir Disoproxil Fumarate

Immune System Disorders: allergic reaction, including angioedema.

Metabolism and Nutrition Disorders: lactic acidosis, hypokalemia, hypophosphatemia.

Respiratory, Thoracic, and Mediastinal Disorders: dyspnea.

Gastrointestinal Disorders: pancreatitis, increased amylase, abdominal pain.

Renal and Urinary Disorders: renal insufficiency, acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria [see Warnings and Precautions (5.4)].

Hepatobiliary Disorders: hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT).

Skin and Subcutaneous Tissue Disorders: rash.

Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures), muscular weakness, myopathy.

General Disorders and Administration Site Conditions: asthenia.

The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia, hypokalemia, muscular weakness, myopathy, hypophosphatemia.

7 DRUG INTERACTIONS

7.1 Not Recommended with Other Antiretroviral Medications

SYMFI is a complete regimen for the treatment of HIV-1 infection; therefore, it should not be administered with other antiretroviral medications for treatment of HIV-1 infection.

7.2 QT Prolonging Drugs

There is limited information available on the potential for a pharmacodynamic interaction between EFV and drugs that prolong the QTc interval. QTc prolongation has been observed with the use of EFV [see Clinical Pharmacology (12.2)]. Consider alternatives to EFV when coadministered with a drug with a known risk of Torsade de Pointes.

7.3 Drugs Affecting Renal Function

Tenofovir is primarily eliminated by the kidneys [see Clinical Pharmacology (12.3)]. Coadministration of EFV/3TC/TDF with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the coadministered drug. Some examples include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4)]. Drugs that decrease renal function may increase concentrations of tenofovir.

7.4 Cannabinoid Test Interaction

EFV does not bind to cannabinoid receptors. False-positive urine cannabinoid test results have been reported with some screening assays in uninfected and HIV-infected subjects receiving EFV. Confirmation of positive screening tests for cannabinoids by a more specific method is recommended.

7.5 Established and Other Potentially Significant Interactions

EFV has been shown in vivo to induce CYP3A and CYP2B6. Other compounds that are substrates of CYP3A or CYP2B6 may have decreased plasma concentrations when coadministered with EFV.

Drugs that induce CYP3A activity (e.g., phenobarbital, rifampin, rifabutin) would be expected to increase the clearance of EFV resulting in lowered plasma concentrations.

No drug interaction studies have been conducted using SYMFI. However, drug interaction studies have been conducted with the individual components of SYMFI (EFV, 3TC, and TDF) [see Clinical Pharmacology (12.3)].

Drug interactions with EFV are summarized in Table 3 [for pharmacokinetics data see Clinical Pharmacology (12.3, Tables 6 and 7) ]. This table includes potentially significant interactions, but is not all inclusive.

Table 3. Established and Other Potentially Significant Drug Interactions with EFV: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction
This table is not all-inclusive.
*
The interaction between EFV and the drug was evaluated in a clinical study. All other drug interactions shown are predicted.

Concomitant Drug

Class: Drug Name

Effect

Clinical Comment

Anticoagulant:

Warfarin

↑ or ↓ warfarin

Monitor INR and adjust warfarin dosage if necessary.

Anticonvulsants:

Carbamazepine

↓ carbamazepine *

↓ EFV*

There are insufficient data to make a dose recommendation for EFV. Alternative anticonvulsant treatment should be used.

Phenytoin

Phenobarbital

↓ anticonvulsant

↓ EFV

Monitor anticonvulsant plasma levels periodically because of potential for reduction in anticonvulsant and/or EFV plasma levels.

Antidepressants:

Bupropion

↓ bupropion *

Increases in bupropion dosage should be guided by clinical response. Bupropion dose should not exceed the maximum recommended dose.

Sertraline

↓ sertraline *

Increases in sertraline dosage should be guided by clinical response.

Antifungals:

Itraconazole

Ketoconazole

↓ itraconazole *

↓ hydroxyitraconazole *

↓ ketoconazole

Consider alternative antifungal treatment because no dose recommendation for itraconazole or ketoconazole can be made.

Posaconazole

↓ posaconazole *

Avoid concomitant use unless the benefit outweighs the risks.

Anti-infective:

Clarithromycin

↓ clarithromycin *

↑ 14-OH metabolite *

Consider alternatives to macrolide antibiotics because of the risk of QT interval prolongation.

Antimycobacterial:

Rifabutin

↓ rifabutin *

Increase daily dose of rifabutin by 50%. Consider doubling the rifabutin dose in regimens where rifabutin is given 2 or 3 times a week.

Rifampin

↓ EFV *

Increase EFV total daily dose to 800 mg once daily when coadministered with rifampin to patients weighing 50 kg or more.

Antimalarials:

Artemether/lumefantrine

↓ artemether *

↓ dihydroartemisinin *

↓ lumefantrine *

Consider alternatives to artemether/lumefantrine because of the risk of QT interval prolongation [see Warnings and Precautions (5.16)].

Atovaquone/

proguanil

↓ atovaquone

↓ proguanil

Concomitant administration is not recommended.

Calcium channel blockers:

Diltiazem

↓ diltiazem *

↓ desacetyl diltiazem *

↓ N-monodesmethyldiltiazem *

Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem).

Others (e.g., felodipine,

nicardipine, nifedipine,

verapamil)

↓ calcium channel blocker

When coadministered with EFV, dosage adjustment of calcium channel blocker may be needed and should be guided by clinical response (refer to the full prescribing information for the calcium channel blocker).

HMG-CoA reductase

inhibitors:

Atorvastatin

Pravastatin

Simvastatin

↓ atorvastatin *

↓ pravastatin *

↓ simvastatin *

Plasma concentrations of atorvastatin, pravastatin, and simvastatin decreased. Consult the full prescribing information for the HMG-CoA reductase inhibitor for guidance on individualizing the dose.

Hepatitis C antiviral agents:

Boceprevir

↓ boceprevir *

Concomitant administration of boceprevir is not recommended.

Elbasvir/Grazoprevir

↓ elbasvir

↓ grazoprevir

Coadministration of EFV with elbasvir/grazoprevir is contraindicated [see Contraindications (4)] because it may lead to loss of virologic response to elbasvir/grazoprevir.

Pibrentasvir/Glecaprevir

↓ pibrentasvir

↓ glecaprevir

Coadministration of EFV is not recommended because it may lead to reduced therapeutic effect of pibrentasvir/glecaprevir.

Simeprevir

↓ simeprevir *

↔ EFV

Concomitant administration of simeprevir is not recommended.

Velpatasvir/Sofosbuvir

↓ velpatasvir

Coadministration of EFV and sofosbuvir/velpatasvir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir.

Velpatasvir/Sofosbuvir/Voxilaprevir

↓ velpatasvir

↓ voxilaprevir

Coadministration of EFV and sofosbuvir/velpatasvir/voxilaprevir is not recommended because it may result in loss of therapeutic effect of sofosbuvir/velpatasvir/voxilaprevir.

Ledipasvir/Sofosbuvir

↑ TDF

Monitor for adverse reactions associated with TDF.

Hepatitis B antiviral agents

Adefovir dipivoxil

Concomitant administration of adefovir dipivoxil is not recommended.

Hormonal contraceptives:

Oral Ethinyl estradiol/ Norgestimate

↓ active metabolites of norgestimate *

A reliable method of barrier contraception should be used in addition to hormonal contraceptives.

Implant Etonogestrel

↓ etonogestrel

A reliable method of barrier contraception should be used in addition to hormonal contraceptives. Decreased exposure of etonogestrel may be expected. There have been postmarketing reports of contraceptive failure with etonogestrel in EFV-exposed patients.

Immunosuppressants: Cyclosporine, tacrolimus,

sirolimus, and others metabolized by CYP3A

↓ immunosuppressant

Dose adjustments of the immunosuppressant may be required. Close monitoring of immunosuppressant concentrations for at least 2 weeks (until stable concentrations are reached) is recommended when starting or stopping treatment with EFV.

Narcotic analgesic:

Methadone

↓ methadone *

Monitor for signs of methadone withdrawal and increase methadone dose if required to alleviate withdrawal symptoms.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.