AKYNZEO 300mg Capsules (Hard Gelatin)

What is AKYNZEO 300mg

AKYNZEO is an oral fixed‑dose combination capsule containing 300 mg netupitant (a selective neurokinin‑1 [NK₁] receptor antagonist) and 0.5 mg palonosetron hydrochloride (a potent 5‑HT₃ receptor antagonist). Marketed as a single‑use antiemetic, it comes in a hard gelatin capsule contained in a blister pack.

• Indication: Alongside dexamethasone, AKYNZEO is authorized for the prevention of both acute (within 24 h) and delayed (1–5 days) chemotherapy‑induced nausea and vomiting (CINV) in adults receiving highly or moderately emetogenic chemotherapy :contentReference[oaicite:1]{index=1}.
• Formulation: A single capsule ensures patient convenience, combining two complementary agents in one dose.
• Beneficial for: Patients undergoing cisplatin-based regimens, anthracycline/cyclophosphamide protocols, or any CINV-prone therapies where maximal prophylaxis is advised :contentReference[oaicite:2]{index=2}.
• Regulatory approval: Approved by the FDA in October 2014 (capsules) and EU in 2015. Its IV fosnetupitant/palonosetron version launched in 2018 :contentReference[oaicite:3]{index=3}.
• Mechanism synergy: The NK₁ antagonist largely controls delayed symptoms; the 5‑HT₃ blocker covers the acute phase, making the combo more effective than single agents :contentReference[oaicite:4]{index=4}.
• Once-per-cycle dosing: One capsule is taken ~1 hour prior to chemotherapy, reducing pill burden and improving adherence :contentReference[oaicite:5]{index=5}.

How to use AKYNZEO 300mg

To achieve optimal antiemetic prophylaxis with AKYNZEO, follow this patient-friendly protocol:

• Timing: Take one capsule orally approximately 1 hour before starting chemotherapy, with or without food :contentReference[oaicite:6]{index=6}.
• Adjunct therapy: Concurrent dexamethasone enhances efficacy. Dosage depends on chemotherapy emetogenicity (see Dosage section) :contentReference[oaicite:7]{index=7}.
• Capsule integrity: Swallow whole—do not crush, chew, or open the capsule to preserve drug combination :contentReference[oaicite:8]{index=8}.
• Monitoring: Observe for signs of nausea, vomiting, headache, or constipation. Most adverse events are mild and manageable :contentReference[oaicite:9]{index=9}.
• Repeat dosing: Administer once per chemotherapy cycle unless otherwise guided by your oncology team. No daily repetition :contentReference[oaicite:10]{index=10}.
• Missed dose: If chemotherapy hasn’t started, take immediately; if chemotherapy has started, skip and resume at next cycle.
• Patient counseling: Inform about possible side effects like headache and constipation. Encourage hydration, eyeglasses for glare, and reporting severe or unusual symptoms.

Mode of Action AKYNZEO 300mg

AKYNZEO's antiemetic effect arises from the pharmacodynamic synergy between its active components:

• Netupitant (NK₁ antagonist): Blocks substance P from binding NK₁ receptors in the brainstem (e.g., nucleus tractus solitarius, area postrema). This disrupts delayed-phase vomiting pathways, lasting over 80 hours with >90% receptor occupancy :contentReference[oaicite:11]{index=11}.
• Palonosetron (5‑HT₃ antagonist): Blocks serotonin at peripheral and central 5‑HT₃ receptors, preventing acute chemotherapy-triggered emesis. It has high affinity and long half-life (~40–50 hours) :contentReference[oaicite:12]{index=12}.
• Combined effect: Palonosetron covers the acute phase (0–24 h post-chemo), while netupitant prevents delayed symptoms (24–120 h) :contentReference[oaicite:13]{index=13}.
• Pharmacokinetics: Both agents are orally bioavailable; palonosetron has ~97% bioavailability, reaching peak within 5 hours, and netupitant is metabolized mainly by CYP3A4 with a long elimination half-life of ~88 hours :contentReference[oaicite:14]{index=14}.
• Synergy vs monotherapy: Combining NK₁ and 5‑HT₃ blockade shows superior prevention across both acute and delayed phases compared to either alone :contentReference[oaicite:15]{index=15}.

AKYNZEO 300mg Interactions AKYNZEO 300mg

AKYNZEO’s dual agents have notable drug‑drug interaction profiles:

• CYP3A4 inhibition by netupitant: Inhibits CYP3A4, elevating exposure to drugs metabolized by this enzyme—e.g., dexamethasone, etoposide, docetaxel, midazolam, some hormonal contraceptives, erythromycin :contentReference[oaicite:16]{index=16}.
• Dexamethasone adjustment: Lower dexamethasone doses may be required due to increased exposure from netupitant co-administration :contentReference[oaicite:17]{index=17}.
• QT prolongation risk: Palonosetron may further prolong QT in patients taking drugs like sotalol, thioridazine, moxifloxacin, dolasetron – monitor ECG when used together :contentReference[oaicite:18]{index=18}.
• Serotonergic agents: Rare cases of serotonin syndrome have been reported when used with SSRIs/SNRIs due to palonosetron’s serotonergic effects :contentReference[oaicite:19]{index=19}.
• CYP3A4 inducers: Rifampin and barbiturates may reduce netupitant/palonosetron exposure; avoid or adjust dosing accordingly :contentReference[oaicite:20]{index=20}.
• Other chemo agents: Monitor carefully when combined with CYP3A4 substrates like taxanes and etoposide due to potential increased toxicity :contentReference[oaicite:21]{index=21}.

Dosage of AKYNZEO 300mg

The dosing protocol for AKYNZEO is aligned with standard antiemetic regimens:

• Adult dose: One capsule (300 mg netupitant / 0.5 mg palonosetron) taken orally ~1 hour before emetogenic chemotherapy cycle begins :contentReference[oaicite:22]{index=22}.
• High emetogenic chemo (HEC): Co-administer dexamethasone 12 mg PO 30 minutes before chemo, then 8 mg daily on days 2–4 :contentReference[oaicite:23]{index=23}.
• Moderate emetogenic chemo (MEC): Dexamethasone 12 mg PO on day 1; no steroid required days 2–4 :contentReference[oaicite:24]{index=24}.
• Renal impairment: No adjustment for mild/moderate; avoid in CrCl <30 mL/min or ESRD :contentReference[oaicite:25]{index=25}.
• Hepatic impairment: Use with caution in mild/moderate; avoid in severe hepatic dysfunction (Child-Pugh ≥9) :contentReference[oaicite:26]{index=26}.
• Pediatrics: Safety/efficacy not established in <18 years; reserved for clinical trials :contentReference[oaicite:27]{index=27}.
• Geriatrics: Use caution due to potential altered hepatic/renal function and polypharmacy :contentReference[oaicite:28]{index=28}.

Possible side effects of AKYNZEO 300mg

Common and serious adverse effects occur with AKYNZEO. Early recognition and management are essential:

• Common (≥1%): Headache (7–9%), asthenia/weakness (7–8%), fatigue (5–7%), constipation, dyspepsia, and skin redness :contentReference[oaicite:29]{index=29}.
• Serious but rare: Hypersensitivity including anaphylaxis related to palonosetron; serotonin syndrome in patients on serotonergic drugs :contentReference[oaicite:30]{index=30}.
• Cardiac effects: Palonosetron may cause QT prolongation; monitor ECG especially if combined with QT‑prolonging drugs :contentReference[oaicite:31]{index=31}.
• Liver enzyme elevation: Transaminases or bilirubin increases >3× ULN seen in some patients, though generally asymptomatic :contentReference[oaicite:32]{index=32}.
• Gastrointestinal: Nausea, vomiting (rare), abdominal discomfort, diarrhea :contentReference[oaicite:33]{index=33}.
• General: Dizziness, somnolence, mild rash, flushing, or mouth dryness. Monitor and manage with supportive care.

AKYNZEO 300mg Contraindications AKYNZEO 300mg

According to the FDA label, there are no absolute contraindications listed for AKYNZEO capsules. However, precautions and contraindications exist in certain contexts:

• Hypersensitivity: Known allergy to netupitant, palonosetron, or any capsule excipients—reports of anaphylaxis with palonosetron :contentReference[oaicite:34]{index=34}.
• Concurrent QT drugs: Use caution when co-administered with medications prolonging QT interval (e.g., sotalol, thioridazine); consider ECG monitoring :contentReference[oaicite:35]{index=35}.
• Severe hepatic impairment: Avoid in patients with Child‑Pugh ≥9 due to altered metabolism and exposure :contentReference[oaicite:36]{index=36}.
• End-stage renal disease: Avoid use in CrCl <30 mL/min/ESRD; insufficient safety data :contentReference[oaicite:37]{index=37}.
• Pregnancy & lactation: Pregnancy category B3 in AU; use only if benefits outweigh risks. Unknown if excreted in breast milk—cadre decisions advised :contentReference[oaicite:38]{index=38}.

Storage of AKYNZEO 300mg

• Storage conditions: Keep at controlled room temperature (20–25 °C / 68–77 °F). Allowed short excursions to 15–30 °C (59–86 °F) :contentReference[oaicite:39]{index=39}.
• Packaging: Store in original blister packs to maintain capsule integrity and dryness.
• Light & humidity: Protect from moisture and direct sunlight, which may degrade gelatin capsule.
• Keep sealed: Only open right before use; discard any damaged or broken capsules.
• Expiry: Discard expired capsules; avoid using beyond printed date.
• Child-safety: Keep out of reach of children to prevent accidental ingestion.
• Disposal: Dispose unused capsules per local drug waste regulations.