Synarel Side Effects Center

Last updated on RxList: 5/9/2022
Synarel Side Effects Center

What Is Synarel?

Synarel (nafarelin acetate) nasal solution is a man-made form of a protein that is like a hormone and is used to treat precocious puberty in both male and female children. Synarel is also used to treat endometriosis in women who are 18 years of age or older.

What Are Side Effects of Synarel?

Common side effects of Synarel in children include:

The same side effects of Synarel along with:

  • headaches,
  • decreased sexual interest or changes in sexual desire,
  • muscle pain,
  • vaginal dryness,
  • oily skin or acne,
  • increased body odor,
  • dandruff,
  • increase in pubic hair growth,
  • runny nose,
  • light and occasional menstrual bleeding, or
  • changes in breast size may occur in women.

Tell your doctor if you have unlikely but serious side effects of Synarel including:

  • abdominal or lower back pain,
  • bone pain,
  • depression,
  • fast or pounding heartbeat,
  • numbness or tingling of arms or legs, or
  • eye pain.

Dosage for Synarel

For the management of endometriosis, the recommended daily dose of Synarel is 400 µg.

What Drugs, Substances, or Supplements Interact with Synarel?

Synarel may interact with decongestants. Tell your doctor all medications and supplements you use.

Synarel During Pregnancy and Breastfeeding

Do not use Synarel if you are pregnant. This medication can harm a fetus or cause birth defects. Tell your doctor if you become pregnant during treatment. Use a barrier form of birth control (such as a condom or diaphragm with spermicide). Hormonal contraception (such as birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective to prevent pregnancy during treatment. It is unknown if this drug passes into breast milk or if it could harm a nursing baby. Do not breastfeed while using Synarel.

Additional Information

Our Synarel (nafarelin acetate) Nasal Solution 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.

Synarel Consumer Information

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

Call your doctor at once if you have:

  • vaginal spotting or continued menstrual bleeding;
  • pelvic pain or swelling;
  • a seizure; or
  • signs of a pituitary gland problem--sudden headache, confusion, vision changes, vomiting, weak pulse, slowed breathing.

Some children using nafarelin have had new or worsening mental problems. Call your doctor right away if your child has any unusual changes in mood or behavior (anger, aggression, crying, feeling restless or irritable).

Some side effects can be expected during the first month of using nafarelin nasal and are not a reason to stop using the medicine. Tell your doctor if you have any side effect that is ongoing or bothersome.

Common side effects may include:

  • vaginal bleeding, discharge, or dryness;
  • hot flashes;
  • acne;
  • increase or decrease in breast size;
  • runny nose;
  • headaches, muscle pain;
  • mood changes;
  • decreased interest in sex;
  • itchy, red, or flaky rash;
  • increased body odor; or
  • increase in pubic hair growth.

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 Synarel (Nafarelin Acetate for Central Precocious Puberty)

Synarel Professional Information

SIDE EFFECTS

CENTRAL PRECOCIOUS PUBERTY

In clinical trials of 155 pediatric patients, 2.6% reported symptoms suggestive of drug sensitivity, such as shortness of breath, chest pain, urticaria, rash, and pruritus.

In these 155 patients treated for an average of 41 months and as long as 80 months (6.7 years), adverse events most frequently reported (>3% of patients) consisted largely of episodes occurring during the first 6 weeks of treatment as a result of the transient stimulatory action of nafarelin upon the pituitary-gonadal axis:

  • acne (10%)
  • transient breast enlargement (8%)
  • vaginal bleeding (8%)
  • emotional lability (6%) [see WARNINGS]
  • transient increase in pubic hair (5%)
  • body odor (4%)
  • seborrhea (3%)

Hot flashes, common in adult women treated for endometriosis, occurred in only 3% of treated children and were transient. Other adverse events thought to be drug-related, and occurring in >3% of patients were rhinitis (5%) and white or brownish vaginal discharge (3%). Approximately 3% of patients withdrew from clinical trials due to adverse events.

In one male patient with concomitant congenital adrenal hyperplasia, and who had discontinued treatment 8 months previously to resume puberty, adrenal rest tumors were found in the left testis. Relationship to SYNAREL is unlikely.

Regular examinations of the pituitary gland by magnetic resonance imaging (MRI) or computer assisted tomography (CT) of children during long-term nafarelin therapy as well as during the post-treatment period has occasionally revealed changes in the shape and size of the pituitary gland. These changes include asymmetry and enlargement of the pituitary gland, and a pituitary microadenoma has been suspected in a few children. The relationship of these findings to SYNAREL is not known.

Post-Marketing

Pituitary apoplexy: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed, with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

Psychiatric adverse events: Emotional lability, such as crying, irritability, impatience, anger, and aggression has been observed with GnRH agonists [see WARNINGS]; Depression, including rare reports of suicidal ideation and attempt, has been reported f or GnRH agonists in children treated for central precocious puberty. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression.

Central/peripheral nervous adverse events: Convulsion, pseudotumor cerebri (idiopathic intracranial hypertension).

ENDOMETRIOSIS

Clinical Studies

In formal clinical trials of 1509 healthy adult patients, symptoms suggestive of drug sensitivity, such as shortness of breath, chest pain, urticaria, rash and pruritus occurred in 3 patients (approximately 0.2%).

As would be expected with a drug which lowers serum estradiol levels, the most frequently reported adverse reactions were those related to hypoestrogenism.

In controlled studies comparing SYNAREL (400 μg/day) and danazol (600 or 800 mg/day), adverse reactions most frequently reported and thought to be drug-related are shown in the figure below:

ADVERSE EVENTS DURING 6 MONTHS TREATMENT WITH SYNAREL®  400 µg/DAY VS DANAZOL 600 OR 800 mg/DAY

ADVERSE EVENTS DURING 6 MONTHS TREATMENT WITH SYNAREL®  400 µg/DAY VS DANAZOL 600 OR 800 mg/DAY - Illustration

In addition, less than 1% of patients experienced paresthesia, palpitations, chloasma, maculopapular rash, eye pain, asthenia, lactation, breast engorgement, and arthralgia.

Changes In Bone Density

After six months of treatment with SYNAREL, vertebral trabecular bone density and total vertebral bone mass, measured by quantitative computed tomography (QCT), decreased by an average of 8.7% and 4.3%, respectively, compared to pretreatment levels. There was partial recovery of bone density in the post-treatment period; the average trabecular bone density and total bone mass were 4.9% and 3.3% less than the pretreatment levels, respectively. Total vertebral bone mass, measured by dual photon absorptiometry (DPA), decreased by a mean of 5.9% at the end of treatment.

After six months treatment with SYNAREL, bone mass as measured by dual x-ray bone densitometry (DEXA), decreased 3.2%. Mean total vertebral mass, re-examined by DEXA six months after completion of treatment, was 1.4% below pretreatment. There was little, if any, decrease in the mineral content in compact bone of the distal radius and second metacarpal. Use of SYNAREL for longer than the recommended six months or in the presence of other known risk factors for decreased bone mineral content may cause additional bone loss.

Changes In Laboratory Values During Treatment

Plasma enzymes. During clinical trials with SYNAREL, regular laboratory monitoring revealed that SGOT and SGPT levels were more than twice the upper limit of normal in only one patient each. There was no other clinical or laboratory evidence of abnormal liver function and levels returned to normal in both patients after treatment was stopped.

Lipids. At enrollment, 9% of the patients in the group taking SYNAREL 400 μg/day and 2% of the patients in the danazol group had total cholesterol values above 250 mg/dL. These patients also had cholesterol values above 250 mg/dL at the end of treatment.

Of those patients whose pretreatment cholesterol values were below 250 mg/dL, 6% in the group treated with SYNAREL and 18% in the danazol group, had post-treatment values above 250 mg/dL.

The mean (± SEM) pretreatment values for total cholesterol from all patients were 191.8 (4.3) mg/dL in the group treated with SYNAREL and 193.1 (4.6) mg/dL in the danazol group. At the end of treatment, the mean values for total cholesterol from all patients were 204.5 (4.8) mg/dL in the group treated with SYNAREL and 207.7 (5.1) mg/dL in the danazol group. These increases from the pretreatment values were statistically significant (p<0.05) in both groups.

Triglycerides were increased above the upper limit of 150 mg/dL in 12% of the patients who received SYNAREL and in 7% of the patients who received danazol.

At the end of treatment, no patients receiving SYNAREL had abnormally low HDL cholesterol fractions (less than 30 mg/dL) compared with 43% of patients receiving danazol. None of the patients receiving SYNAREL had abnormally high LDL cholesterol fractions (greater than 190 mg/dL) compared with 15% of those receiving danazol. There was no increase in the LDL/HDL ratio in patients receiving SYNAREL, but there was approximately a 2-fold increase in the LDL/HDL ratio in patients receiving danazol.

Other changes. In comparative studies, the following changes were seen in approximately 10% to 15% of patients. Treatment with SYNAREL was associated with elevations of plasma phosphorus and eosinophil counts, and decreases in serum calcium and WBC counts. Danazol therapy was associated with an increase of hematocrit and WBC.

Post-Marketing

Pituitary apoplexy: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed, with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

Cardiovascular adverse events: Cases of serious venous and arterial thromboembolism have been reported, including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, and transient ischemic attack. Although a temporal relationship was reported in some cases, most cases were confounded by risk factors or concomitant medication use. It is unknown if there is a causal association between the use of GnRH analogs and these events.

Central/peripheral nervous adverse events: Convulsion.

Hepatic adverse events: Rarely reported serious liver injury.

Reproductive system adverse events: Cases of ovarian hyperstimulation syndrome have been reported with Synarel monotherapy when used for Assisted Reproductive

Technology which is not an approved indication.

DRUG INTERACTIONS

CENTRAL PRECOCIOUS PUBERTY

No pharmacokinetic-based drug-drug interaction studies have been conducted with SYNAREL. However, because nafarelin acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes, and the drug is only about 80% bound to plasma proteins at 4°C, drug interactions would not be expected to occur.

ENDOMETRIOSIS

No pharmacokinetic-based drug-drug interaction studies have been conducted with SYNAREL. However, because nafarelin acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes, and the drug is only about 80% bound to plasma proteins at 4°C, drug interactions would not be expected to occur.

Drug/Laboratory Test Interactions

Administration of SYNAREL in therapeutic doses results in suppression of the pituitarygonadal system. Normal function is usually restored within 4 to 8 weeks after treatment is discontinued. Therefore, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and up to 4 to 8 weeks after discontinuation of therapy with SYNAREL may be misleading.

Read the entire FDA prescribing information for Synarel (Nafarelin Acetate for Central Precocious Puberty)

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

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