Updates from FDA
APhA Staff
New Formulations
CABOTEGRAVIR
(Apretude—ViiV Healthcare)
Drug class: HIV-1 integrase strand transfer inhibitor (INSTI).
Indication: Apretude is indicated as pre-exposure prophylaxis (PrEP) for adults and adolescents, weighing at least 35 kg, who are at risk of sexually acquired HIV-1 infection. Apretude is the first long-acting injectable medication that has been approved by FDA for PrEP.
Recommended dosage and administration: Apretude is supplied in single-dose vials containing 600 mg (3 mL) cabotegravir and is only approved for gluteal intramuscular injection. The initial dose is a single injection of 600 mg (3 mL) cabotegravir once monthly for 2 months. After the first 2 doses, the dose continues to be a single 600 mg cabotegravir injection but the frequency changes to every 2 months. Individuals also have the option to do a lead-in with oral cabotegravir for one month prior to starting Apretude (see full prescribing information for lead-in dosing).
Common adverse effects: Injection site reactions, diarrhea, headache, fever, fatigue, nausea, dizziness, flatulence, abdominal pain, vomiting, muscle pain, rash, decreased appetite, somnolence, back pain, and upper respiratory infection.
Black box warning: Risk of drug resistance with unknown HIV-1 infection. All individuals who are initiating therapy must have a negative HIV-1 test immediately prior to initiation of Apretude or oral cabotegravir therapy and prior to each Apretude injection. Therapy must not be initiated if HIV-1 status is unknown. If individual tests positive for HIV-1, appropriate antiretroviral therapy should be initiated.
Other warnings and precautions: Individuals receiving Apretude should receive appropriate counseling on how to reduce the potential for HIV transmission. Liver toxicity is possible and Apretude should be discontinued if liver toxicity is suspected. Depressive disorders have also been reported, if patient experiences depressive symptoms, they should be seen immediately. For full list of warnings and precautions, see package insert.
CLINDAMYCIN PHOSPHATRE
(XACIATO—Daré Bioscience, Inc.)
Drug class: Lincosamide antibacterial.
Indication: Xaciato is indicated for the treatment of bacterial vaginosis in patients 12 years and older.
Recommended dosage and administration: Xaciato is a new formulation of clindamycin phosphate that is supplied as a 2% vaginal gel and is administered as a single-dose regimen for patients with bacterial vaginosis. The 100 mg clindamycin dose is contained within 5 g of Xaciato gel and should be administered intravaginally via a single-use applicator.
Common adverse effects: Vulvovaginal candidiasis and vulvovaginal pain or discomfort.
Warnings and precautions: As with most antibiotics, if severe diarrhea occurs, medication should be discontinued, and patient should be evaluated. Polyurethane condoms should not be used during treatment with or 7 days after treatment with clindamycin to prevent pregnancy or transmission of sexually transmitted diseases/infections. Patients should be counseled to use latex or polyisoprene condoms instead. Patients should also be cautioned against having vaginal intercourse during treatment and for at least 3 days after treatment.
RIVAROXABAN
(Xarelto—Janssen Pharmaceuticals, Inc.)
Drug class: Factor Xa inhibitor.
Indication: As of mid-December 2021, Xarelto received FDA approval for 2 new pediatric indications. The first newly approved indication is the treatment or reduction of recurrent venous thromboembolism (VTE) in pediatric patients from birth to 18 years. The second new indication is as thromboprophylaxis for patients who are 2 years or older with congenital heart disease and have undergone a Fontan procedure.
Also newly approved in December in the United States is an oral suspension dosage form of Xarelto. The suspension, which has been previously approved in the UK, will be available as a product to be reconstituted—once reconstituted, the strength will be 1 mg/1 mL rivaroxaban. The oral suspension will allow for more precise weight-based dosing for pediatric patients.
Recommended dosage and administration: Dosing is based on weight and indication for pediatric patients. Pediatric dosing varies between both indications as does whether to take the dose with or without food. See full prescribing information for in-depth dosing recommendation charts. In general, the oral suspension is recommended for most pediatric dosing—the tablet form should NOT be split to try to achieve correct dose. Once mixed, the oral suspension is good for 60 days and should be stored at room temperature. The suspension should be dispensed in its original container and with the oral syringes that are supplied with it.
Common adverse effects: The most reported adverse effects from clinical trials in pediatric patients were bleeding, vomiting, cough, and gastroenteritis.
Black box warning: Discontinuing Xarelto prematurely may lead to an increased risk of thrombotic events. Epidural or spinal hematomas have been reported in patients who were taking Xarelto and underwent neuraxial anesthesia or a spinal puncture.
Other warnings and precautions: Xarelto was not studied and is not recommended for use in patients younger than 6 months who were born at less than 37 weeks of gestation, have received less than 10 days of oral feeding, or have a body weight less than 2.6 kg.
GLYCOPYRROLATE
(Dartisla ODT—Edenbridge Pharmaceuticals, LLC)
Drug class: Anticholinergic.
Indication: Dartisla ODT is indicated as an adjunct therapy to help relieve peptic ulcer symptoms. The package insert notes that it is not indicated for and should not be used as monotherapy for a peptic ulcer.
Recommended dosage and administration: Dartisla ODT is supplied as a 1.7 mg orally disintegrating tablet. It should be disintegrated on top of the tongue and given 2 to 3 times per day on an empty stomach (1 hour prior to eating or 2 hours after eating). Refer to package insert for recommendations on switching patients to Dartisla ODT if they are taking another dosage form of glycopyrrolate for peptic ulcer.
Common adverse effects: The most commonly reported adverse effects relate to the anticholinergic properties of the medication which may include dry mouth, blurred vision, constipation, urinary retention, drowsiness, decreased sweating, and an increased heart rate.
Warnings and precautions: Glycopyrrolate may increase intraocular pressure and lead to precipitation of acute angle glaucoma. Patients are at an increased risk of adverse GI reactions due to decreased GI mobility caused by the medication.
New Combination Medication
FINASTERIDE/TADALAFIL
(Entadfi—Veru Inc.)
Drug class: Finasteride is a 5 a-reductase inhibitor; tadalafil is a phosphodiesterase 5 (PDE5) inhibitor.
Indication: Entadfi is indicated as a treatment option for men with an enlarged prostate experiencing signs and symptoms of benign prostatic hyperplasia.
Recommended dosage and administration: Entadfi is an oral capsule that contains 5 mg finasteride and 5 mg tadalafil. One capsule should be taken by mouth once daily at approximately the same time each day and should be taken on an empty stomach. Entadfi should only be taken for up to 26 weeks.
Common adverse effects: Adverse effects associated with finasteride include impotence, decreased libido, breast enlargement, breast tenderness, and rash. Adverse effects associated with tadalafil include headache, dyspepsia, back pain, muscle pain, nasal congestion, and flushing.
Warnings and precautions: The use of organic nitrates with Entadfi is contraindicated due to risk of severe hypotension. Concomitant use with alpha blockers, antihypertensive medications, alcohol, or strong CYP3A4 inhibitors may increase the risk of symptomatic hypotension. See full prescribing details for entire list of warnings and precautions. ■
FDA issues EUAs for COVID-19 oral antivirals
In late December 2021, FDA issued an EUA for two oral antiviral medications to treat patients with mild to moderate COVID-19. Neither medication is authorized for pre- or post-exposure prophylaxis, nor should they be used to treat patients with severe COVID-19, including patients who have been hospitalized. Both medications require prescriptions and should be started as soon as possible after a COVID-19 diagnosis and within 5 days of symptom onset.
Paxlovid, manufactured by Pfizer, is supplied as nirmatrelvir 150 mg and ritonavir 100 mg tablets. Paxlovid is dosed as two nirmatrelvir tablets and one ritonavir tablet by mouth, twice daily, for 5 days. Nirmatrelvir inhibits SARS-CoV-2 replication, while ritonavir works by slowing the breakdown of nirmatrelvir. Paxlovid is authorized for use in patients 12 years and older who weigh at least 40 kg and have received a positive COVID-19 diagnosis.
Molnupiravir, manufactured by Merck, is supplied as a 200 mg oral capsule. It is dosed as 4 capsules by mouth, twice daily, for 5 days. Molnupiravir works by introducing errors into the SARS-CoV-2 genetic code. It is only authorized for patients 18 years and older because it may also inhibit bone and cartilage growth.
For more information about Paxlovid or molnupiravir, see the EUA FDA fact sheets for health care providers.
Also in this issue: COVID-19 antivirals compared.