Amprenavir

Because amprenavir oral solution contains a large amount of propylene glycol, concurrent use /with alcohol, disulfiram, or metronidazole/ is not recommended.

Although these medications /alprazolam, clorazepate, diazepam, or flurazepam/ have not been specifically studied with amprenavir, amprenavir may increase the serum concentrations of these medications.

Although these medications /amiodarone, lidocaine (systemic), tricyclic antidepressants, or quinidine/ have not been specifically studied with amprenavir, amprenavir may interfere in the metabolism of these medications and cause serious or life threatening adverse events; monitoring of serum concentrations for these medications is recommended if amprenavir is used concurrently.

Although antacids have not been specifically studied with amprenavir, based on data from other protease inhibitors, antacids (and didanosine due to the antacid content present in didanosine formulations) may interfere with the absorption of amprenavir; it is recommended that antacid and didanosine administration be separated from amprenavir administration by at least one hour.

For more Interactions (Complete) data for AMPRENAVIR (21 total), please visit the HSDB record page.

Rapidly absorbed after oral administration in HIV-1-infected patients with a time to peak concentration (T_max) typically between 1 and 2 hours after a single oral dose. The absolute oral bioavailability of amprenavir in humans has not been established.

/HUMAN EXPOSURE STUDIES/ Although these medications /amiodarone, lidocaine (systemic), tricyclic antidepressants, or quinidine/ have not been specifically studied with amprenavir, amprenavir may interfere in the metabolism of these medications and cause serious or life threatening adverse events; monitoring of serum concentrations for these medications is recommended if amprenavir is used concurrently.

/HUMAN EXPOSURE STUDIES/ Although these medications /astemizole, bepridil, cisapride, dihydroergotamine, ergotamine, midazolam, or triazolam/ have not been specifically studied with amprenavir, amprenavir may interfere in the metabolism of these medications and cause serious or life threatening adverse events; concurrent use is not recommended.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Amprenavir

Ambiguous-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies in rats and rabbits at amprenavir exposure levels calculated to be 5-50% of the exposure seen at the recommended human dosage have resulted in adverse effects to fetuses/offspring. In rats (amprenavir given from 15 days before pairing to day 17 of gestation), fetuses/offspring had thymic elongation and incomplete ossification of bones attributed to amprenavir. In rabbits (amprenavir given from days 8-20 of gestation), abortions and an increased incidence of 3 minor skeletal variations resulting from deficient ossification of the femur, humerus trochlea, and humerus occurred and were attributed to amprenavir. In rats (amprenavir given from day 7 of gestation until day 22 of lactation), offspring had reduced body weight (10-20% decrease) at amprenavir exposure levels that were approximately twice that associated with the recommended human dosage; subsequent development of these offspring (including fertility and reproductive performance) was not affected by maternal exposure to amprenavir.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ In fertility studies in male and female rats, there was no evidence that amprenavir impairs mating or fertility in either sex and there was no evidence that the drug affects development or maturation of sperm. The reproductive performance of the F1 generation born to female rats given amprenavir was not different from control animals.

/GENOTOXICITY/ Amprenavir was not mutagenic or genotoxic in several in vitro and in vivo assays, including bacterial mutation, mouse lymphoma, rat micronucleus, and chromosomal aberration assays in human peripheral blood lymphocytes.

The usually recommended dosage of amprenavir oral solution (22.5 mg/kg twice daily) provides a propylene glycol intake of 1650 mg/kg daily; however, an acceptable intake of propylene glycol used as an excipient in pharmaceuticals has not been established to date. Propylene glycol is metabolized in the liver by the alcohol and aldehyde dehydrogenase enzyme pathway, and the possibility exists that young infants, patients with renal or hepatic impairment, and certain patient groups (females, Asians, Native Alaskans, Native Americans) may be at increased risk of propylene glycol-associated adverse effects if they receive amprenavir oral solution because of diminished ability to metabolize propylene glycol /SRP: due to alcohol dehydrogenase polymorphism/.

There is no known specific antidote for amprenavir overdose. It has not been determined whether amprenavir can be removed from the circulation by peritoneal dialysis or hemodialysis. Amprenavir oral solution contains large amounts of propylene glycol, and propylene glycol can be removed by hemodialysis. Monitoring: Amprenavir capsules: Patients should be monitored for signs of toxicity. Amprenavir oral solution: Because of the propylene glycol content, patients should be additionally monitored for signs and symptoms of acid-base abnormalities, with appropriate management. Supportive care: Standard supportive treatment should be provided as necessary. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

Treatment of overdose: To decrease absorption: Patients may benefit from treatment with activated charcoal. Monitoring: Patient's vital signs should be monitored. Supportive care: Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.

Maintain an open airway and assist ventilation if needed. Treat coma, seizures, hypotension or anaphylaxis if they occur. replace fluid losses resulting from gastroenteritis with intravenous crystalloids. Maintain steady urine flow with intravenous fluids to alleviate crystalluria and reverse renal dysfunction. Treat lactic acidosis with judicious doses of sodium bicarbonate and by withdrawal of the offending drug. There are no specific antidotes for these agents. Administer activated charcoal.