DARUNAVIR (darunavir)

There are 1 contraindications. Absolute contraindication.

Contraindication List
Lactation

There are 1 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Disease of liver

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
Diabetes mellitus
Hemophilia
Hypercholesterolemia
Hypertriglyceridemia

There are 33 severe adverse reactions.

More Frequent	Less Frequent
None.	Abdominal distension Increased alanine transaminase Increased aspartate transaminase

Rare/Very Rare

Abnormal hepatic function tests Acute generalized exanthematous pustulosis Acute pancreatitis Allergic dermatitis Anemia Angioedema Autoimmune hepatitis Avascular necrosis of bone Bradycardia Diabetes mellitus DRESS syndrome Eosinophilia Erythema multiforme Gastritis Graves' disease Hepatic failure Hepatitis Hypersensitivity drug reaction Maculopapular rash Maculopathy Myocarditis Neutropenic disorder Pancytopenia Polymyositis Progressive multifocal leukoencephalopathy Rectal bleeding Stevens-johnson syndrome Thrombocytopenic disorder Toxic epidermal necrolysis Uveitis

There are 27 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Diarrhea Headache disorder Hyperlipidemia Nausea Skin rash Vomiting	Anorexia Dyspepsia Fatigue Flatulence Pruritus of skin Urticaria

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

The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in females exposed to darunavir 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 ritonavir-boosted darunavir 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.

It is not known whether darunavir or ritonavir is distributed into human milk; darunavir is distributed into milk in rats. 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.

Experience in those 65 years of age and older is insufficient to determine whether they respond differently to ritonavir-boosteddarunavir than younger adults. Appropriate caution should be exercised in administration and monitoring because of age-related decreases in hepatic function and potential for concomitant disease and drug therapy. Pharmacokinetics of darunavir do not differ substantially over an age range of 18-75 years of age.