DELSTRIGO (Page 3 of 10)

6.2 Postmarketing Experience

The following adverse reactions have been identified during postmarketing experience in patients receiving lamivudine- or TDF-containing regimens. Because postmarketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Lamivudine:

Body as a Whole: redistribution/accumulation of body fat

Endocrine and Metabolic: hyperglycemia

General: Weakness

Hemic and Lymphatic: anemia (including pure red cell aplasia and severe anemias progressing on therapy)

Hepatic and Pancreatic: lactic acidosis and hepatic steatosis, posttreatment exacerbations of hepatitis B

Hypersensitivity: anaphylaxis, urticaria

Musculoskeletal: muscle weakness, CPK elevation, rhabdomyolysis

Skin: alopecia, pruritus

TDF:

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

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

Renal and Urinary Disorders: 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

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 Concomitant Use with Other Antiretroviral Medications

Because DELSTRIGO is a complete regimen for the treatment of HIV-1 infection, co-administration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. Information regarding potential drug-drug interactions with other antiretroviral medications is not provided.

7.2 Effect of Other Drugs on DELSTRIGO

Co-administration of DELSTRIGO with a CYP3A inducer decreases doravirine plasma concentrations, which may reduce DELSTRIGO efficacy [see Contraindications (4), Warnings and Precautions (5.3), and Clinical Pharmacology (12.3)].

Co-administration of DELSTRIGO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine.

Table 6 shows the significant drug interactions with the components of DELSTRIGO. The drug interactions described are based on studies conducted with either DELSTRIGO or the components of DELSTRIGO as individual agents.

Table 6: Drug Interactions with DELSTRIGO *
Concomitant Drug Class: Drug Name Effect on Concentration Clinical Comment
↑ = increase, ↓ = decrease
All other drug-drug interactions shown are anticipated based on the known metabolic and elimination pathways.
*
This table is not all-inclusive
The interaction between doravirine and the concomitant drug was evaluated in a clinical study.
Androgen Receptors
enzalutamide ↓ doravirine Co-administration is contraindicated with enzalutamide.At least a 4-week cessation period is recommended prior to initiation of DELSTRIGO.
Anticonvulsants
carbamazepineoxcarbazepinephenobarbitalphenytoin ↓ doravirine Co-administration is contraindicated with these anticonvulsants. At least a 4-week cessation period is recommended prior to initiation of DELSTRIGO.
Antimycobacterials
rifampin rifapentine ↓ doravirine Co-administration is contraindicated with rifampin or rifapentine. At least a 4-week cessation period is recommended prior to initiation of DELSTRIGO.
rifabutin ↓ doravirine If DELSTRIGO is co-administered with rifabutin, one tablet of doravirine (PIFELTRO) should be taken approximately 12 hours after the dose of DELSTRIGO [see Dosage and Administration (2.4)].
Cytotoxic Agents
mitotane ↓ doravirine Co-administration is contraindicated with mitotane. At least a 4-week cessation period is recommended prior to initiation of DELSTRIGO.
Hepatitis C Antiviral Agents
ledipasvir/sofosbuvirsofosbuvir/velpatasvir ↑ tenofovir Monitor for adverse reactions associated with TDF.
Herbal Products
St. John’s wort ↓ doravirine Co-administration is contraindicated with St. John’s wort. At least a 4-week cessation period is recommended prior to initiation of DELSTRIGO.
Other Agents
sorbitol ↓ lamivudine Co-administration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine-containing medicines.

Co-administration of DELSTRIGO with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of lamivudine, tenofovir, and/or other renally eliminated drugs. Some examples of drugs that are eliminated by active tubular secretion 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 (5.2) and Clinical Pharmacology (12.3)].

No clinically significant changes in concentration were observed for doravirine when co-administered with the following agents: TDF, lamivudine, elbasvir and grazoprevir, ledipasvir and sofosbuvir, ritonavir, ketoconazole, aluminum hydroxide/magnesium hydroxide/simethicone containing antacid, pantoprazole, or methadone [see Clinical Pharmacology (12.3)].

No clinically significant changes in concentration were observed for tenofovir when co-administered with tacrolimus or entecavir [see Clinical Pharmacology (12.3)].

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