Updates from FDA
APhA Staff
New drugs
VUTRISIRAN
(Amvuttra—Alnylam Pharmaceuticals)
Drug class: Vutrisiran is a transthyretin-directed small interfering RNA.
Indication: Amvuttra is indicated for the treatment of hereditary transthyretin-mediated amyloidosis–associated polyneuropathy in adults.
Recommended dosage and administration: The recommended dosage of Amvuttra is 25 mg administered subcutaneously once every 3 months. Amvuttra should be administered by a health care professional.
If a dose is missed, it should be administered as soon as possible, and dosing should resume every 3 months from the most recent dose. The syringe should be warmed to room temperature for 30 minutes prior to injection. The solution should be inspected for discoloration and particulate matter prior to administration.
Amvuttra should be injected into the abdomen, thighs, or upper arms. Once the injection site has been cleaned, the needle cap should be pulled straight off of the syringe. The skin should be pinched, and the needle should be inserted into the pinched skin at a 45–90 degree angle. Push the plunger rod as far as it will go to administer the dose. Immediately dispose of the used syringe into a sharps container.
Common adverse effects: The most commonly reported adverse effects with Amvuttra use include arthralgia, dyspnea, and decreased vitamin A levels.
Warnings and precautions: Because treatment with Amvuttra can lead to a decrease in serum levels of vitamin A, supplementation at the recommended daily allowance is recommended. If ocular symptoms suggestive of vitamin A deficiency occur, patients should be referred to an ophthalmologist.
New dosage form
ROFLUMILAST
(Zoryve—Arcutis Biotherapeutics)
Drug class: Roflumilast is a phosphodiesterase 4 inhibitor.
Indication: Zoryve is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in patients 12 years or older.
Recommended dosage and administration: Zoryve should be applied to affected areas once daily and rubbed in completely. Hands should be washed after application unless the hands are the area being treated. Zoryve is only to be used topically and is not for ophthalmic, oral, or intravaginal use.
Common adverse effects: The most commonly reported adverse effects in patients treated with Zoryve include diarrhea, headache, insomnia, nausea, application site pain, upper respiratory tract infection, and UTI.
Warnings and precautions: Zoryve should not be used in patients with moderate to severe liver impairment. Coadministration of Zoryve with systemic CYP3A4 inhibitors, dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously, or oral contraceptives containing gestodene and ethinyl estradiol may increase systemic exposure to Roflumilast and increase the chance of adverse effects. Zoryve should not be used during labor and delivery.
ZONISAMIDE
(Zonisade—Azurity Pharmaceuticals)
Drug class: Zonisamide is an anticonvulsant that is thought to act on sodium and calcium channels. The exact mechanism of action is unknown.
Indication: Zonisade is indicated as adjunctive therapy for the treatment of partial-onset seizures in adults and pediatric patients 16 years and older.
Recommended dosage and administration: The recommended initial dose of Zonisade is 100 mg daily. The dosage may be increased by 100 mg daily every 2 weeks, based on clinical response and tolerability, to 400 mg daily. Patients who require further reduction of seizures and tolerate 400 mg daily well may be titrated up to a maximum dosage of 600 mg daily. Zonisade is administered orally and can be taken without regard to food.
Common adverse effects: The most common adverse effects in patients treated with Zonisade include somnolence, anorexia, dizziness, ataxia, agitation, irritability, and difficulty with memory and/or concentration.
Warnings and precautions: Zonisade is contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or zonisamide.
Discontinuation should occur at the first sign of rash unless clearly not drug-related. Aplastic anemia and agranulocytosis has been reported with use of Zonisade. Multiorgan hypersensitivity has also occurred.
In pediatric patients, use of zonisamide has been associated with oligohidrosis, sometimes resulting in heat stroke and hospitalization.
If acute myopia or secondary angle closure glaucoma occurs, Zonisade should be discontinued. Patients being treated with Zonisade should be monitored for suicidal behavior or ideation.
Baseline and periodic measurement of serum bicarbonate is recommended as metabolic acidosis may occur. If this does occur, consider dose reduction or discontinuation.
Zonisade should never be stopped suddenly as withdrawal could cause seizures.
People with reproductive potential should be advised to use an effective method of contraception during treatment with Zonisade and for one month after discontinuation as fetal harm may occur.
TADALAFIL
(Tadliq—Ajanta Pharma USA)
Drug class: Tadalafil is a phosphodiesterase 5 inhibitor.
Indication: Tadliq is indicated for the treatment of pulmonary arterial hypertension to improve exercise ability.
Recommended dosage and administration: The recommended dose of Tadliq is 40 mg (10 mL) once daily without regard to food. In patients with mild or moderate renal impairment, initial dosing should be 20 mg (5 mL) daily and titrated to 40 mg daily as tolerated.
Patients with mild or moderate hepatic impairment should be initiated at a dose of 20 mg daily and titrated as tolerated.
In patients receiving ritonavir for at least one week, Tadliq should be initiated at 20 mg daily and titrated to 40 mg daily as tolerated. Use of Tadliq should be avoided during the initiation of ritonavir. Stop Tadliq at least 24 hours prior to starting ritonavir. Tadliq may be restarted at 20 mg daily after at least one week of ritonavir therapy and titrated to 40 mg daily as tolerated.
Common adverse effects: The most commonly reported adverse reaction in patients being treated with Tadliq is headache.
Warnings and precautions: Tadliq should be avoided in patients with severe renal or hepatic impairment.
Use of Tadliq is contraindicated in patients on concomitant organic nitrate or guanylate cyclase stimulator therapy or those who have a history of known hypersensitivity reaction to Tadliq, Adcirca (Eli Lilly), or Cialis (Eli Lilly).
Use of Tadliq is not recommended in those with pulmonary veno-occlusive disease. Sudden loss of vision due to nonarteritic ischemic optic neuropathy and hearing impairment have been reported.
Avoid use with concomitant phosphodiesterase 5 inhibitors. Patients should seek emergency treatment if an erection lasts > 4 hours.
DROSPIRENONE
(Drospirenone—Exeltis USA)
Drug class: Drospirenone is a progestin-only oral contraceptive.
Indication: Drospirenone is indicated for use in people of reproductive potential to prevent pregnancy.
Recommended dosage and administration: Drospirenone is dosed as one chewable tablet taken daily for 28 days. It should be chewed and not swallowed whole. One active chewable tablet is taken daily for 24 days and one inert chewable tablet daily during the following 4 days.
Common adverse effects: The most common adverse effects with Drospirenone use are acne, menorrhagia, headache, breast pain, weight gain, dysmenorrhea, nausea, vaginal hemorrhage, decreased libido, breast tenderness, and irregular menstruation.
Warnings and precautions: Hyperkalemia may occur. Therapy should be discontinued if a thromboembolic event occurs. It is unknown if Drospirenone use may cause a clinically relevant loss of bone mineral density. Discontinue use if jaundice or disturbances in liver function occur. Be alert to the possibility of ectopic pregnancy.
Patients with diabetes may be at higher risk of hyperglycemia. Bleeding irregularities and amenorrhea may occur.
Concomitant use of drugs that induce CYP3A4 may decrease the effectiveness of Drospirenone chewable tablets or increase breakthrough bleeding. Discontinue use if pregnancy occurs. ■
Levemir label change
In early July 2022, FDA made several changes regarding safety to the label for Levemir (Novo Nordisk). One of these changes includes a new subsection that describes how changes in insulin regimens may affect glycemic control. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to cause hyperglycemia. Additionally, a sudden change in injection site to an unaffected area has been reported to result in hypoglycemia. The new label also notes that symptomatic awareness of hypoglycemia may be decreased in patients with diabetic neuropathy or those being treated with drugs that block the sympathetic nervous system, such as beta-blockers.
Additionally, human data from an open-label clinical trial in pregnant females is now included. Participants were treated with either Levemir or NPH insulin, and both groups received preprandial insulin aspart administration. Rates of preeclampsia observed in the study were comparable to expected rates for pregnancies complicated by diabetes. No differences in pregnancy outcomes, rates of severe hypoglycemia, or rates of severe hyperglycemia were seen between the treatment arms. Levemir was detected in the infant cord blood at levels above the lower level of quantification in about a quarter of infants.