Zokinvy Side Effects Center

Last updated on RxList: 7/21/2021
Zokinvy Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Zokinvy?

Zokinvy (lonafarnib) is a farnesyltransferase inhibitor indicated in patients 12 months of age and older with a body surface area of 0.39 m2 and above to reduce risk of mortality in Hutchinson-Gilford Progeria Syndrome; and for treatment of processing-deficient progeroid laminopathies with either heterozygous LMNA mutation with progerin-like protein accumulation or homozygous or compound heterozygous ZMPSTE24 mutations.

What Are Side Effects of Zokinvy?

Side effects of Zokinvy include:

Dosage for Zokinvy

The starting dose of Zokinvy is 115 mg/m2 twice daily with morning and evening meals. After 4 months, increase to 150 mg/m2 twice daily.

Zokinvy In Children

The safety and effectiveness of Zokinvy for the treatment of HGPS and processing-deficient Progeroid Laminopathies (with either heterozygous LMNA mutation with progerin-like protein accumulation or homozygous or compound heterozygous ZMPSTE24 mutations) have been established in pediatric patients 12 months of age and older.

The safety and effectiveness of Zokinvy in pediatric patients less than 12 months of age have not been established.

What Drugs, Substances, or Supplements Interact with Zokinvy?

Zokinvy may interact with other medicines such as:

  • strong or moderate CYP3A inhibitors or inducers,
  • grapefruit or Seville oranges,
  • CYP2C9 inhibitors,
  • HMG CoA reductase inhibitors ("statins"),
  • Midazolam,
  • other sensitive CYP3A substrates,
  • loperamide,
  • CYP2C19 substrates such as lonafarnib, and
  • P-gp substrates (e.g., digoxin, dabigatran)

Tell your doctor all medications and supplements you use.

Zokinvy During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Zokinvy; it may harm a fetus. Females of reproductive potential are advised to use appropriate effective contraception during treatment with Zokinvy. It is unknown if Zokinvy passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Zokinvy (lonafarnib) Capsules, for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Zokinvy Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • new or worsening vision problems (such as decreased night vision);
  • severe ongoing nausea, vomiting, diarrhea;
  • loss of appetite that causes weight loss;
  • high blood pressure--severe headache, blurred vision, shortness of breath, nosebleeds, pounding in your neck or ears;
  • kidney problems--little or no urination, swelling in your feet or ankles, feeling tired or short of breath;
  • high potassium level--nausea, weakness, tingly feeling, chest pain, irregular heartbeats, loss of movement;
  • low potassium level--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling;
  • low sodium level --headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
  • low calcium level--muscle spasms or contractions, numbness or tingly feeling (around your mouth, or in your fingers and toes); or
  • signs of infection--fever, chills, cough, rash, swelling, diarrhea, pain or burning when you urinate.

Common side effects may include:

  • an electrolyte imbalance (such as low levels of potassium, sodium, or calcium in your blood);
  • infection;
  • increased blood pressure;
  • stomach pain, nausea, vomiting, diarrhea;
  • decreased appetite, weight loss;
  • headache;
  • feeling tired;
  • muscle or joint pain;
  • cold symptoms such as stuffy nose, sneezing, sore throat, cough; or
  • abnormal lab tests;

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Zokinvy (Lonafarnib Capsules)

Zokinvy Professional Information

SIDE EFFECTS

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

A total of 84 subjects were treated with at least one dose of ZOKINVY with or without additional therapy, of which 8 were treated at a dosage of at least 115 mg/m2 twice daily for greater than or equal to 10 years.

The safety profile of ZOKINVY is based on 128 patient-years of treatment exposure (62 patients with HGPS and 1 patient with processing-deficient Progeroid Laminopathy with LMNA heterozygous mutation) and pooled results from two Phase 2 open-label, single-arm trials (n=63: 28 patients from Study 1 and 35 treatment naïve patients from Study 2). In Study 1, ZOKINVY treatment was initiated at 115 mg/m2 twice daily and increased to 150 mg/m2 twice daily after approximately 4 months for a total treatment duration of 24 to 30 months. Treatment naïve patients in Study 2 received ZOKINVY 150 mg/m2 twice daily for up to 36 months. In both studies, ZOKINVY was administered orally via capsules or the capsule contents were mixed with Ora Blend SF or Ora-Plus and administered orally as a suspension.

In these two studies, a total of 63 patients received ZOKINVY for a median duration of 2.2 years, with approximately 1.9 years at the recommended dose of 150 mg/m2 twice daily. The population was 2 to 17 years old, with a similar proportion of males (33 [52%] patients) and females (30 [48%] patients). Most patients had classic HGPS (60 [95%] patients) compared to non-classic HGPS (2 [3%] patients) and 1 (2%) patient had Progeroid Laminopathy with LMNA heterozygous mutation.

Table 3 summarizes adverse reactions reported in the clinical trials. The most common adverse reactions (≥25%) in the clinical trials were vomiting, diarrhea, infection, nausea, decreased appetite, fatigue, upper respiratory tract infection, abdominal pain, musculoskeletal pain, electrolyte abnormalities, decreased weight, headache, myelosuppression, increased aspartate aminotransferase, decreased blood bicarbonate, cough, hypertension, and increased alanine aminotransferase.

Table 3: Adverse Reactions in ≥5% of Patients in Study 1 and Treatment-Naïve Patients in Study 2 Receiving ZOKINVY

Adverse ReactionsZOKINVY
n=63, n (%)
Gastrointestinal disorders
Vomiting57 (90%)
Diarrhea51 (81%)
Nausea35 (56%)
Abdominal pain130 (48%)
Constipation14 (22%)
Flatulence4 (6%)
General disorders and administration site conditions
Fatigue32 (51%)
Pyrexia9 (14%)
Infections and infestations
Infection249 (78%)
Upper respiratory tract infection332 (51%)
Rhinitis12 (19%)
Investigations
Decreased appetite (anorexia)33 (53%)
Electrolyte abnormalities427 (43%)
Weight decreased23 (37%)
Myelosuppression522 (35%)
Increased aspartate aminotransferase22 (35%)
Decreased blood bicarbonate21 (33%)
Hypertension18 (29%)
Increased alanine aminotransferase17 (27%)
Dehydration3 (5%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain630 (48%)
Nervous system disorders
Headache23 (37%)
Cerebral ischemia77 (11%)
Ophthalmic
Ocular changes815 (24%)
Psychiatric disorders
Depressed mood3 (5%)
Respiratory, thoracic and mediastinal disorders
Cough21 (33%)
Epistaxis13 (21%)
Skin and Subcutaneous Tissue Disorders
Rash7 (11%)
Pruritus5 (8%)
Mucositi5 (8%)
1 Abdominal pain includes stomach pain and abdominal pain.
2 Infection includes abdominal infection, candidiasis, chicken pox, Clostridium difficile colitis, colitis, croup, dengue fever, flu syndrome, flu-like symptoms, fungal infection, gastroenteritis, gastrointestinal infection, Helicobacter pylori infection, infection, infection viral, influenza, nail infection, otitis media, parotitis, perirectal abscess, pneumonia, small intestine infection, submandibular lymphadenitis, tonsillitis, viral infection.
3 Upper respiratory infection includes bronchial infection, bronchitis, sinus infection, and upper respiratory infection.
4 Electrolyte abnormalities includes hypermagnesemia, hypokalemia, hyperkalemia, hyponatremia, hypercalcemia, hyperphosphatemia, hypocalcemia, and hypernatremia.
5 Myelosuppression includes absolute neutrophil count decreased, low total white blood cells, lymphopenia, decreased hemoglobin, and hematocrit low.
6 Musculoskeletal pain includes arthritis, back pain, bone pain, foot pain, intercostal pain, joint pain, knee pain, leg pain, musculoskeletal pain, pain in ankle/extremity/ fingers/hip/leg/limb/lower limbs/left arm, shoulder pain, unilateral leg pain. Excludes musculoskeletal pain for abdomen.
7 Cerebral ischemia includes cerebral ischemia, central nervous system hemorrhage, and ischemia cerebrovascular.
8 Ocular changes include visual acuity change, corneal clouding, conjunctivitis, watering eyes, keratitis.

Gastrointestinal Adverse Reactions

As noted in Table 3, gastrointestinal adverse reactions were the most frequently reported adverse reactions. Of the 57 patients who experienced vomiting, 30 (53%) patients had mild vomiting (defined as no intervention required), 26 (46%) patients had moderate vomiting (defined as outpatient intravenous hydration; medical intervention required), and 1 (2%) patient had severe vomiting (defined as tube feeding, total parental nutrition, or hospitalization indicated). Of the 35 patients who experienced nausea, 34 (97%) patients had mild nausea (defined as loss of appetite without alteration in eating habits) and 1 (3%) patient had moderate nausea (defined as oral intake decreased without significant weight loss, dehydration, or malnutrition). During the first four months of treatment in Study 1, 19 (68%) patients had vomiting and 10 (36%) patients had nausea. By the end of therapy, 4 (14%) patients who were still on ZOKINVY required antiemetics or anti-nauseants. A total of 4 patients discontinued ZOKINVY, mostly due to nausea or vomiting.

Of the 51 patients who experienced diarrhea, the majority of patients (approximately 92%) experienced mild or moderate diarrhea; 38 (75%) patients reported mild diarrhea (defined as an increase of less than 4 stools per day over baseline) and 9 (18%) patients reported moderate diarrhea (defined as an increase of 4 to 6 stools per day over baseline; limiting instrumental activities of daily living). Four (8%) patients reported severe diarrhea (defined as an increase of seven or more stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self-care activities of daily living). During the first four months of treatment in Study 1, 23 (82%) patients had diarrhea; by the end of therapy, 3 (11%) patients had diarrhea. Twelve (43%) patients were treated with loperamide.

Alanine Aminotransferase And Aspartate Aminotransferase Elevations

Increased alanine aminotransferase was commonly reported (17 [27%] patients). Of the 17 patients with increased alanine aminotransferase, 14 (82%) patients had mild increases (defined as greater than upper limit of normal (ULN) to 3.0 times ULN if baseline was normal; 1.5 to 3.0 times ULN if baseline was abnormal), 1 (6%) patient had moderate increases (defined as greater than 3.0 to 5.0 times ULN if baseline was normal or abnormal), and 2 (12%) patients had severe increases (defined as greater than 5.0 to 20.0 times ULN if baseline was normal or abnormal). Increased aspartate aminotransferase was also commonly reported (22 [35%] patients). Of the 22 patients with increased aspartate aminotransferase, 21 (95%) patients had mild increases (defined as greater than ULN to 3.0 times ULN if baseline was normal; 1.5 to 3.0 times ULN if baseline was abnormal) and 1 (5%) patient had a severe increase (defined as greater than 5.0 to 20.0 times ULN if baseline was normal or abnormal). One patient with alanine and aspartate aminotransferase elevations also experienced hypertriglyceridemia and hyperglycemia resulting in discontinuation of ZOKINVY.

Hypertension

Increases in blood pressure have been documented in patients treated with ZOKINVY. At baseline 22 (35%) patients had either a systolic blood pressure or a diastolic blood pressure or both above the 95th percentile. Over the course of the trials, 18 (29%) patients had hypertension based on systolic blood pressure or diastolic blood pressure measurements above the 95th percentile on 3 or more occasions. Five (8%) patients who were normotensive at baseline had either systolic blood pressure or diastolic blood pressure above the 95th percentile at the end of treatment.

Read the entire FDA prescribing information for Zokinvy (Lonafarnib Capsules)

© Zokinvy Patient Information is supplied by Cerner Multum, Inc. and Zokinvy Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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