Gralise

Gabapentin is a prescription medicine used to treat:

• Pain from damaged nerves (postherpetic pain) that follows healing of shingles (a painful rash that comes after a herpes zoster infection) in adults.
• Partial seizures when taken together with other medicines in adults and children 3 years of age and older.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Do not stop taking gabapentin without first talking to your healthcare provider.

Stopping gabapentin suddenly can cause serious problems.

Gabapentin can cause serious side effects including:

Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:

• thoughts about suicide or dying
• attempts to commit suicide
• new or worse depression
• new or worse anxiety
• feeling agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• other unusual changes in behavior or mood

How you can watch for early symptoms of suicidal thoughts and actions:

• Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
• Keep all follow-up visits with your healthcare provider as scheduled.

Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Do not stop taking gabapentin without first talking to a healthcare provider.

• Stopping gabapentin suddenly can cause serious problems. Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus).

Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.

• skin rash
• hives
• fever
• swollen glands that do not go away
• swelling of your lip and tongue
• yellowing of your skin or of the whites of the eyes
• unusual bruising or bleeding
• severe fatigue or weakness
• unexpected muscle pain
• frequent infections

These symptoms may be the first signs of a serious reaction. A healthcare provider should examine you to decide if you should continue taking gabapentin.

Do not take gabapentin if you are allergic to gabapentin or any of the other ingredients in gabapentin.

Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking gabapentin without first talking with your healthcare provider. Taking gabapentin with alcohol or drugs that cause sleepiness or dizziness may make your sleepiness or dizziness worse.

Do not drive, operate heavy machinery, or do other dangerous activities until you know how gabapentin affects you. Gabapentin can slow your thinking and motor skills.

Tell your healthcare provider if you are pregnant or plan to become pregnant. It is not known if gabapentin can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking gabapentin. You and your healthcare provider will decide if you should take gabapentin while you are pregnant.

• If you become pregnant while taking gabapentin, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. You can enroll in this registry by calling 1-888-233-2334.

• Take gabapentin exactly as prescribed. Your healthcare provider will tell you how much Gabapentin to take.
  • Do not change your dose of gabapentin without talking to your healthcare provider. If you break a tablet in half, the unused half of the tablet should be taken at your next scheduled dose. Half tablets not used within several days of breaking should be thrown away. If taking capsules, always swallow them whole with plenty of water.
• Gabapentin can be taken with or without food. If you take an antacid containing aluminum and magnesium, such as Maalox, Mylanta, Gelusil, Gaviscon, or Di-Gel, you should wait at least 2 hours before taking your next dose of gabapentin.
• If you take too much gabapentin, call your healthcare provider or your local Poison Control Center right away.

• Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking gabapentin without first talking with your healthcare provider. Taking gabapentin with alcohol or drugs that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
• Do not drive, operate heavy machinery, or do other dangerous activities until you know how gabapentin affects you. Gabapentin can slow your thinking and motor skills.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how Gralise affects you.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• This medicine is not the same as gabapentin enacarbil (Horizant™). Do not use in its place. Talk with the doctor.
• A very bad and sometimes deadly reaction has happened with Gralise. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
• Do not stop taking this medicine all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop Gralise, you will want to slowly stop it as ordered by your doctor.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Use with care in children. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Gralise while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Gralise is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration.

The safety and effectiveness of Gralise in patients with epilepsy has not been studied.

Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs), including gabapentin, the active ingredient in Gralise, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed. Table 3 shows absolute and relative risk by indication for all evaluated AEDs.

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing Gralise must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which products containing active components that are AEDs (such as gabapentin, the active component in Gralise) are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Patients, their caregivers, and families should be informed that Gralise contains gabapentin which is also used to treat epilepsy and that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.

Withdrawal of Gabapentin

Gabapentin should be withdrawn gradually. If Gralise is discontinued, this should be done gradually over a minimum of 1 week or longer (at the discretion of the prescriber).

Tumorigenic Potential

In standard preclinical in vivo lifetime carcinogenicity studies, an unexpectedly high incidence of pancreatic acinar adenocarcinomas was identified in male, but not female, rats. The clinical significance of this finding is unknown.

In clinical trials of gabapentin therapy in epilepsy comprising 2,085 patient-years of exposure in patients over 12 years of age, new tumors were reported in 10 patients, and pre-existing tumors worsened in 11 patients, during or within 2 years after discontinuing the drug. However, no similar patient population untreated with gabapentin was available to provide background tumor incidence and recurrence information for comparison. Therefore, the effect of gabapentin therapy on the incidence of new tumors in humans or on the worsening or recurrence of previously diagnosed tumors is unknown.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan Hypersensitivity, has been reported in patients taking antiepileptic drugs, including Gralise. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved.

It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Gralise should be discontinued if an alternative etiology for the signs or symptoms cannot be established.

Laboratory Tests

Clinical trial data do not indicate that routine monitoring of clinical laboratory procedures is necessary for the safe use of Gralise. The value of monitoring gabapentin blood concentrations has not been established.

Gralise (gabapentin) Tablets are supplied as follows:

300 mg tablets:
Gralise 300 mg tablets are white, oval shaped tablets debossed with "SLV" on one side and "300" on the other side.

NDC 13913-004-19 (Bottle of 90)

600 mg tablets:
Gralise 600 mg tablets are beige, oval shaped tablets debossed with "SLV" on one side and "600" on the other side.
NDC 13913-005-19 (Bottle of 90)

30-Day Starter Pack:
NDC 13913-006-16 (Blister package containing 78 tablets: 9 x 300 mg tablets and 69 x 600 mg tablets)

Storage

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Keep out of reach of children.

• Advise patients that Gralise is not interchangeable with other formulations of gabapentin.
• Advise patients to take Gralise only as prescribed. Gralise may cause dizziness, somnolence, and other signs and symptoms of CNS depression.
• Advise patients not to drive or operate other complex machinery until they have gained sufficient experience on Gralise to gauge whether or not it adversely affects their mental and/or motor performance. Advise patients who require concomitant treatment with morphine to tell their prescriber if they develop signs of CNS depression such as somnolence. If this occurs the dose of Gralise or morphine should be reduced accordingly.
• Advise patients that if they miss a dose of Gralise to take it with food as soon as they remember. If it is almost time for the next dose, just skip the missed dose and take the next dose at the regular time. Do not take two doses at the same time.
• Advise patients that if they take too much Gralise, to call their healthcare provider or poison control center, or go to the nearest emergency room right away.

Medication Guide

Advise patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking Gralise.

Suicidal Thoughts and Behavior

Advise patients, their caregivers, and families that AEDs, including gabapentin, the active ingredient in Gralise, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers [see Warnings and Precautions (5.1)].

Dosing and Administration

Advise patients that Gralise should be taken orally once-daily with the evening meal. Gralise tablets should be swallowed whole. Do not split, crush, or chew the tablets [see Dosage and Administration (2.1)].

Marketed by:
Depomed, Inc.
Newark, CA 94560

Opadry® is a registered trademark of BPSI Holdings, LLC.

© 2015 Depomed, Inc.
GRA-004-C.7 SEP 2015
Issued SEP 2015

U.S. Patents: 7,438,927; 6,340,475; 6,488,962; 6,635,280; 6,723,340; 7,731,989; 8,192,756; 8,252,332; 8,333,992

MEDICATION GUIDE

Gralise® (gra leez')
(gabapentin) Tablets

Read this Medication Guide before you start taking Gralise and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about Gralise, ask your healthcare provider or pharmacist.

What is the most important information I should know about Gralise?

Do not stop taking Gralise without first talking with your healthcare provider. Stopping Gralise suddenly can cause serious problems.

Like other antiepileptic drugs, gabapentin, the active ingredient in Gralise, may cause suicidal thoughts or actions in a very small number of people, about 1 in 500. However, it is not known if Gralise is safe and effective in people with seizure problems (epilepsy). Therefore, Gralise should not be used in place of other gabapentin products.

Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:

• thoughts about suicide or dying
• attempts to commit suicide
• new or worse depression
• new or worse anxiety
• feeling agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• other unusual changes in behavior or mood

How can I watch for early symptoms of suicidal thoughts and actions?

• Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
• Keep all follow-up visits with your healthcare provider as scheduled.
• Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

Do not stop taking Gralise without first talking with your healthcare provider.

• Stopping Gralise suddenly can cause serious problems.

What is Gralise?

Gralise is a prescription medicine used in adults, 18 years and older, to treat:

• pain from damaged nerves (neuropathic pain) that follows healing of shingles (a painful rash that comes after a herpes zoster infection).

It is not known if Gralise is safe and effective in people with seizure problems (epilepsy).

It is not known if Gralise is safe and effective in children under 18 years of age with postherpetic pain.

Gralise is not interchangeable with other gabapentin products.

Who should not take Gralise?

Do not take Gralise if you are allergic to gabapentin or any of the ingredients in Gralise. See the end of this Medication Guide for a complete list of ingredients in Gralise.

What should I tell my healthcare provider before taking Gralise?

Before taking Gralise, tell your healthcare provider if you:

• have or have had depression, mood problems or suicidal thoughts or behavior
• have seizures
• have kidney problems or get kidney dialysis
• are pregnant or plan to become pregnant. It is not known if Gralise can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking Gralise. You and your healthcare provider will decide if you should take Gralise while you are pregnant.
  • If you become pregnant while taking Gralise, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiepileptic drugs, including gabapentin, the active ingredient in Gralise, during pregnancy. You can enroll in this registry by calling 1-888-233-2334.
• are breastfeeding or plan to breastfeed. Gralise can pass into your breast milk. You and your healthcare provider should decide how you will feed your baby while you take Gralise.

Tell your healthcare provider about all the medicines you take including prescription and non-prescription medicines, vitamins or herbal supplements.

Taking Gralise with certain other medicines can cause side effects or affect how well they work. Do not start or stop other medicines without talking to your healthcare provider.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I take Gralise?

• Take Gralise exactly as prescribed. Your healthcare provider will tell you how much Gralise to take and when to take it. Take Gralise at the same time each day.
• Do not change your dose or stop taking Gralise without talking with your healthcare provider. If you stop taking Gralise suddenly, you may experience side effects. Talk with your healthcare provider about how to stop Gralise slowly.
• Take Gralise with food one time each day with your evening meal.
• Take Gralise tablets whole. Do not split, crush, or chew Gralise tablets before swallowing.
• Your healthcare provider may change your dose of Gralise. Do not change your dose of Gralise without talking to your healthcare provider.
• If you miss a dose, take it as soon as you remember with food. If it is almost time for your next dose, just skip the missed dose. Take the next dose at your regular time. Do not take two doses at the same time.
• If you take too much Gralise, call your healthcare provider or poison control center, or go to the nearest emergency room right away.
• If you are taking an antacid containing aluminum hydroxide and magnesium hydroxide, it is recommended that Gralise be taken at least 2 hours following administration of the antacid.

What should I avoid while taking Gralise?

• Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking Gralise without first talking to your healthcare provider. Taking Gralise with alcohol or medicines that cause sleepiness or dizziness may make your sleepiness or dizziness worse.
• Do not operate heavy machines or do other dangerous activities until you know how Gralise affects you. Gralise can slow your thinking and motor skills.

What are the possible side effects of Gralise?

The most common side effect of Gralise is:

• dizziness

Tell your healthcare provider about any side effect that bothers you or that does not go away.

These are not all the possible side effects of Gralise. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at

1-800-FDA-1088.

How should I store Gralise?

Store Gralise at 59°F to 86°F (15°C to 30°C)

• Keep Gralise and all medicines out of the reach of children.

General information about the safe and effective use of Gralise

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Gralise for a condition for which it was not prescribed. Do not give Gralise to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about Gralise. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Gralise that is written for health professionals.

For more information about Gralise, call 1-866-458-6389.

What are the ingredients in Gralise?

Active ingredient: gabapentin

Inactive ingredients:
300 mg tablet: copovidone, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene oxide, and Opadry® II white. Opadry® II white contains polyvinyl alcohol, titanium dioxide, talc, polyethylene glycol 3350, and lecithin (soya).
600 mg tablet: copovidone, hypromellose, magnesium stearate, polyethylene oxide, and Opadry® II beige. Opadry® II beige contains polyvinyl alcohol, titanium dioxide, talc, polyethylene glycol 3350, iron oxide yellow, and iron oxide red.

Marketed by:
Depomed, Inc.
Newark, CA 94560

Opadry® is a registered trademark of BPSI Holdings, LLC.

© 2015 Depomed, Inc.
GRA-004-C.7 SEP 2015
Issued SEP 2015

This Medication Guide has been approved by the U.S. Food and Drug Administration.

PRINCIPAL DISPLAY PANEL - 90 ct, 300 mg Tablets

NDC 13913-004-19

90 Tablets
ONCE-DAILY
Gralise®
(gabapentin) tablets
300 mg
Do not use Gralise interchangeably with other gabapentin products
ATTENTION: Distribute required medication guide to each patient
Depomed®

PRINCIPAL DISPLAY PANEL - 600 mg Tablets

NDC 13913-005-19

90 Tablets
ONCE-DAILY
Gralise®
(gabapentin) tablets
600 mg
Do not use Gralise interchangeably with other gabapentin products
Distribute required medication guide to each patient
Depomed®

PRINCIPAL DISPLAY PANEL - 30-Day Starter Pack

NDC 13913-006-16

9 x 300 mg tablets • 69 x 600 mg tablets
ONCE-DAILY
Gralise®
(gabapentin) tablets
STARTER PACK
This 30-day starter pack of Gralise® includes the following:
Nine 300 mg tablets
Sixty-nine 600 mg tablets
Medication Guide enclosed.
Do not use Gralise interchangeably with other gabapentin products
Rx ONLY
Dosage and Administration: See prescribing information.
Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].
Keep out of reach of children.
Depomed®

Gralise is a prescription medicine used in adults, 18 years and older, to treat pain from damaged nerves (neuropathic pain) that follows healing of shingles (a painful rash that comes after a herpes zoster infection).

It is not known if Gralise is safe and effective in people with seizure problems (epilepsy).

It is not known if Gralise is safe and effective in children under 18 years of age with postherpetic pain.

Gralise is not interchangeable with other gabapentin products.

Store Gralise at 59°F to 86°F (15°C to 30°C)

Keep Gralise and all medicines out of the reach of children.

Applies to gabapentin: oral capsule, oral solution, oral suspension, oral tablet

Along with its needed effects, gabapentin (the active ingredient contained in Gralise) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking gabapentin:

• Clumsiness or unsteadiness
• continuous, uncontrolled, back-and-forth, or rolling eye movements

• Aggressive behavior or other behavior problems
• anxiety
• concentration problems and change in school performance
• crying
• depression
• false sense of well-being
• hyperactivity or increase in body movements
• rapidly changing moods
• reacting too quickly, too emotional, or overreacting
• restlessness
• suspiciousness or distrust

• Black, tarry stools
• chest pain
• chills
• cough
• depression, irritability, or other mood or mental changes
• fever
• loss of memory
• pain or swelling in the arms or legs
• painful or difficult urination
• shortness of breath
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• unusual bleeding or bruising
• unusual tiredness or weakness

• Abdominal or stomach pain
• blistering, peeling, or loosening of the skin
• clay-colored stools
• coma
• confusion
• convulsions
• dark urine
• decreased urine output
• diarrhea
• dizziness
• fast or irregular heartbeat
• headache
• increased thirst
• itching or skin rash
• joint pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of appetite
• muscle ache or pain
• nausea
• red skin lesions, often with a purple center
• red, irritated eyes
• unpleasant breath odor
• vomiting of blood
• yellow eyes or skin

Some side effects of gabapentin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Blurred vision
• cold or flu-like symptoms
• delusions
• dementia
• hoarseness
• lack or loss of strength
• lower back or side pain
• swelling of the hands, feet, or lower legs
• trembling or shaking

• Accidental injury
• appetite increased
• back pain
• bloated or full feeling
• body aches or pain
• burning, dry, or itching eyes
• change in vision
• change in walking and balance
• clumsiness or unsteadiness
• congestion
• constipation
• cough producing mucus
• decrease in sexual desire or ability
• difficulty with breathing
• dryness of the mouth or throat
• earache
• excess air or gas in the stomach or intestines
• excessive tearing
• eye discharge
• feeling faint, dizzy, or lightheadedness
• feeling of warmth or heat
• flushed, dry skin
• flushing or redness of the skin, especially on the face and neck
• frequent urination
• fruit-like breath odor
• impaired vision
• incoordination
• increased hunger
• increased sensitivity to pain
• increased sensitivity to touch
• increased thirst
• indigestion
• noise in the ears
• pain, redness, rash, swelling, or bleeding where the skin is rubbed off
• passing gas
• redness or swelling in the ear
• redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
• runny nose
• sneezing
• sweating
• tender, swollen glands in the neck
• tightness in the chest
• tingling in the hands and feet
• trouble sleeping
• trouble swallowing
• trouble thinking
• twitching
• unexplained weight loss
• voice changes
• vomiting
• weakness or loss of strength
• weight gain