SYMTUZA (darunavir eth/cobicistat/emtricitabine/tenofovir alafenamide)

There are 2 contraindications. Absolute contraindication.

Contraindication List
Lactation
Lactic acidosis

There are 8 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
Disease of liver
Fanconi syndrome
Hypophosphatemia

There are 5 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
Diabetes mellitus
Hemophilia
Hypercholesterolemia
Hypertriglyceridemia

There are 65 severe adverse reactions.

More Frequent	Less Frequent
Depression Gastroenteritis Hyperbilirubinemia Jaundice Scleral icterus Vomiting	Abdominal distension 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 generalized exanthematous pustulosis Acute pancreatitis Acute renal failure Allergic dermatitis Anemia Angioedema Autoimmune hepatitis Avascular necrosis of bone Bradycardia Diabetes mellitus DRESS syndrome Dyspnea Eosinophilia Erythema multiforme Fanconi syndrome Gastritis Graves' disease Guillain-barre syndrome Hepatic failure Hepatitis Hypersensitivity drug reaction Hypokalemia Hypophosphatemia Interstitial nephritis Kidney disease with reduction in glomerular filtration rate (GFr) Kidney stone Lactic acidosis Maculopapular rash Maculopathy Myocarditis Nephrogenic diabetes insipidus Neutropenic disorder Osteomalacia Pancreatitis Pancytopenia Peripheral neuropathy Pneumonia Polymyositis Progressive multifocal leukoencephalopathy Rectal bleeding Renal tubular necrosis Rhabdomyolysis Steatosis of liver Stevens-johnson syndrome Thrombocytopenic disorder Toxic epidermal necrolysis Uveitis

There are 66 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 Hyperlipidemia Insomnia Nausea Pain Pruritus of skin Rhinitis Skin rash Vomiting	Acute bacterial otitis media Anorexia Arthralgia Chest pain Depression Diarrhea Dream disorder Dyspepsia Elevated serum amylase Elevated serum lipase Fatigue Flatulence Headache disorder Hypercholesterolemia Hypertriglyceridemia Insomnia Myalgia Paresthesia Pharyngitis Polyuria Proteinuria Pruritus of skin Sinusitis Skin rash Urticaria Vomiting Weight loss

Rare/Very Rare
Arthralgia Blurred vision Bone pain Crystalluria Dream disorder Dyschromia Fever General weakness Hypercholesterolemia Hyperglycemia Hyperhidrosis Hypertriglyceridemia Lipodystrophy associated with human immunodeficiency virus infection Muscle weakness Myalgia Myopathy Periorbital edema Skin inflammation Upper abdominal pain Urticaria

There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to DRV/c/FTC/TAF during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 800-258-4263. There are insufficient prospective human data on the use of DRV/c/FTC/TAF in pregnant individuals from the APR to inform on a potential drug-associated risk of birth defects and miscarriage.

Available data from the APR show no difference in rate of overall birth defects for darunavir, cobicistat, emtricitabine, and TAF compared with the background rate for major birth defects of 2.7% in a U.S.

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 animal reproduction studies, no adverse developmental effects were observed. DRV/c/FTC/TAF is not recommended for use during pregnancy because of substantially lower exposures of darunavir and cobicistat during the second and third trimesters compared to the post-partum period, as determined in a pharmacokinetic study. Do not initiate DRV/c/FTC/TAF in pregnant individuals. An alternative regimen is recommended for individuals who become pregnant during therapy with DRV/c/FTC/TAF.

Based on published data, emtricitabine has been shown to be present in human milk. There are no data on the presence of darunavir, cobicistat, or TAF in human milk, the effects on the breastfed infant, or the effects on milk production. Darunavir and cobicistat are present in the milk of lactating rats.

Tenofovir has been shown to be present in the milk of lactating rats and rhesus monkeys after administration of TDF. 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. Clinical trials of DRV/c/FTC/TAF included 35 patients >=65 years of age, of which 26 received the fixed combination preparation. No differences in safety or efficacy have been observed between elderly subjects and those <65 years of age. In general, caution should be exercised in the administration and monitoring of DRV/c/FTC/TAF in elderly patients, reflecting the greater frequency of decreased hepatic function and of concomitant disease or other drug therapy.